RICHARD DUNHAM

CHOLINERGIC DRUGS
Drug type Drug Mechanism Clinical Use Side Effects
Muscarinic receptors bind acetylcholine (ACh). Receptors M1-M5 not important to know but M2/4 are inhibitory
CHOLINERGIC These are direct acting agonists (do not require nerve inervation).
AGONIST Methacholinel -Agonist of muscarine CV -Salivation, Miosis,
receptor (M>N) -Lowers BP & HR Lacrimation, Urination,
(Muscarinic)
-Slows conduction thru AV node Defacation, Sweating, -
-Only used in dx of bronchial Bronchoconstriction,
reactivity Bradychardia
NOTE: Sweating is the only
Sympathetic action here
*Relaxation of blood vessel
BP reflex HR
Carbechol -Direct stimulant of RARE USE THERAPEUTICALLY same
muscarine & nicotinic Eye
receptor -Potent & long duration
-NOT degraded by ACh- -Relieve glaucoma
esterase -After cataract surgery
Bethanechol -Muscarinic only GU same
-Not degraded by ACh- -Stimulate atonic bladder (urinate)
esterase GI
-Increase motility
-Esophageal reflux relief
-Post-op ileus tx

Pilocarpine -3’ amine, partial agonist at ** Intraocular pressure in open -Aggravates ulcers
M receptor angle glaucoma tx (DOC before
-Crosses the BBB timolol)
-Closed angle glaucoma (used w/
other drugs)
-Xerostomia tx – post radiation tx
etc.
-Selective for sweat, salivary,
lacrimal, bronchial glands & iris
smooth muscle (weak effects on GI
smmoth muscle and heart)
Cevimeline M1 & M3 agonist Tx of Sjogren syndrome Similar to pilocarpine
AChE- AChE Inhbitors are indirect acting cholinomimetics (requires nerve innervation for effects so no effect on blood
INHIBITORS vessels). Since ACh is released onto nicotinic (N) and muscarinic (M) receptors. You would see nicotinic sitmulation (unlike
bethanecol) and muscarinic stimulation. Increasing ACh in the synapse would compete away competetive muscarinic
antagonists (e.g. atropine overdose) and competetive nicotinic antatonists (curare). IF you have desensitized muscle
receptors causing paralysis, should you use an agonist to stimulate? If you use an agonist, it will only make it worse by
further desensitization. Should you use an antagonist? No, the efficacy of a blocker is zero.
Edrophonium -Similar to neostigmine, -Used in dx of myasthenia gravis -Generalized ACh stimulation
duration of 2-10 min -MG tests: better =MG crisis Cholinergic crisis – antidote is
worse= cholinergic crisis Atropine
Physostigmine -Indirect acting 3’ amine -GI/GU motility -CNS convulsion (@dose)
-Periphery & INTO CNS -Miosis (constriction) -Paralysis of skeletal muscle
(lipid sol) -Tx of Glaucoma (ocular pressure) (too much ACh)
-Antidote for OD of muscarinic -Potentially fatal arrhythmias
-Reversible inhibition of antagonists (Atropine, from AV block
ACh-esterase phenothiazine, TCA) -Aggravation of asthma

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 Neostigmine -Reversibly inhibits ACh-
esterase
-4’ amine; does NOT into
CNS
-Orally active
Pyridostigmine Same as neostigmine
Ambenonium
Demecarium Same as neostigmine
Organophosphates “Irreversible” & lipid
DFP/Echothiphaate soluble (CNS effects)
Slow Reversible Covalently binds to ACh-
Malathion, esterase
parathion, soman, -Nerve gas & insecticides
tabun, sarin
-These compounds
phosphorylate the esteratic
site on AChE at serine
hydroxyl groups
Tacrine -Only used for the CNS
Donepezil muscarinic effects ACh
Rivastigmine in brain
Galantamine
Given Orally
OXIMES Pralidoxime Binds to ACh-esterasee
(2-PAM) inhibitor to pull it from
enzyme (breaks P-bond)
(NO CNS effects)
DAM
DAM has CNS effects
Antimuscarinic drugs are always contraindicated in patients with benign prostatic hypertrophy because of aggravation of
CHOLINERGIC
symptoms. They are also contraindicated in glaucoma because of the mydriasis and cycloplegia effects of the drug. Blocking
ANTAGONIST
ciliary muscle contraction blocks the outflow of vitreous humor, may lead to blindness.
Atropine Competitive antagonist to
muscarinic receptor
Effects (in order of dose):
 All secretions shut down
 Mydriasis, cycloplegia
 Hyperthermia (w/
resulting vasodilation)
 Tachycardia
 Sedation
 Urinary retention &
constipation
 Behavioral excitation &
hallucination
Scopolamine -Competitive blocker of
muscarin receptors
-Greater action in CNS,
longer duration
-Stimulates GI/GU motility
-Tx for myasthenia gravis (b/c no
CNS effects & long life)
-Antidote for tubocurarine
Tx. Myasthenia gravis
Tx. glaucoma
-Glaucoma only in very very dilute
solutions
-Tounge Fasiculations
Antidote  Pralidoxime &
ATROPINE
*CHRONIC toxicity is different
from acute toxicity, and causes
demyelination motor/sensory
impairment (think of a farmer)
Symptomatic Tx of Alzheimer’s
Antidote for acute
organophosphate exposure
NOT chronic exposure
-Must use oxime before aging
(aging for serine is 2-3 min)
Eye
-Cycloplegic & myadriatic (near
accommodation/dilation)
-Antispasmodic in GI/GU
-Antidote for organophosphates
-Tx of incontinence (must use
doses, & would see many SE, so
not really used)
-Antisecretory for surgery
-Tx ulcer (stops secretion of H+)
Anesthetic – decreases secretions
-Tx of parkinsons
DOC- Motion Sickness
(prophylactic)
-Potentially fatal arrhythmias
from AV block
-aggravation of asthma
-NO Pupil constriction
CNS
-Excessive muscarinic/
nicotinic effects: confusion,
ataxia, slurred speech, loss of
reflexes, sweating, salivation,
convulsions, coma, respiratory
paralysis, death
-Organophosphates (except
echothiophate) are
distributed to all parts of the
body including the CNS
-Many side effects of Ach in
periphery on M and N
receptors (unwanted effects)
-N receptor paralysis
(desensitized muscle) may
cause respiratory paralysis of
diaphragm
-AV block in elderly
-Only effective in short time
period after AchE conversion.
New nerve gases have very
short window of opportunity.
*DAM not available in USA
Low dose:
-Bradycardia
-Sedation
Higher doses
-Tachycardia (may 
ventricular arrhythmias)
-CNS hyperexcitation
-Delerium
-Hallucinations
-Seizures
-Dry mouth (no salivation)
-Blurred vision (Pupil dilation +
loss of accommodation)
-Flushing of skin
-Hot (no sweat i.e. no
thermoregulation)
CI: glaucoma, BPH
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 Tropicamide Competitive antagonist to Eye exam -SE only last a few hours
muscarinic receptor -Cycloplegic& myadriatic
-Topical use
Ipatropium Competitive antagonist to -Anti-asthmatic, esp. in COPD Generally considered safer
Tiotropium muscarinic receptor w/ vagal componenets & elderly than giving a -agonist for
Thiotropium -Does not change mucous patients asthma b/c the agonist will
viscosity, overal mucous -DOC in bronchospasms definitely have an effect
volume associated w/ -blockers in drugs elsewhere, antaonist has no
-Thio = inhalant w/ much used in asthmatics efficacy
longer half life
Pirenzepine Selective M1 receptor Ulcer tx Central effects not seen
antagonist
Benztropine -Penetrates CNS Parkinson’s Disease (central
Trihexyphenidyl effects)…will Tx the tremor &
rigidity (caused by too much ACh)

CHOLINERGIC ANTAGOINIST (Classified by structure)

3’ Amines Atropine
Scopolamine
Pirenzepine
Flavoxate
Oxybutynin
Tolterodine
Oxybutynin Anticholinergic, Tx of hyper-reflexic bladder
antispasmotic
Homatropine -Opthamology (preferred to
Cyclopentolate atropine b/c shorter duration)
Tropicamide
Benztropine -enter CNS -Tx parkinsonism
mesylate -Tx extrapyramidal effects of
antipsychotic drugs
Trihexyphenidyl
hydrocholoride
Dicyclomine -Tx irritable bowel syndrome
Solifenacin Selective M3 receptor -Tx overactive bladder
Darifenacin antagonist
4’ Amines Ipratropium
Tiotropium
Methscopolamine
Trospium
Propantheline -Antispasmodic, rhinitis, urinary -Neuromuscular blocking b/c
incontinence, Tx of ulcers nicotinic effects (high doses)
Glycopyrrolate -used orally to inhibit GI motility
-used parenterally to prevent
bradycardia during surgical
procedures

GANGLIONIC & NEUROMUSCULAR DRUGS

Class Drug Mechanism Clincal Use Side Effects

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 Ganglionic The effects of ganglionic blockers will cause the dominant system (symp or para) at the tissue to be blocked.
blockers  Arterioles (symp)  vasodilatoin; veins (Symp) dilation, venous return, CO
 Heart (para) tachycardia. Does the tachycardia result from excess sympathetics after blocking parasympathetic?
No, all autonomic output is blocked. The intrinsic heart rate is faster than normal heart rate. If you put this person on
a treadmill, will their HR ? No, all autonomic output blocked.
 Iris (para) mydriasis. So is this do to excess sympathetic tone on the iris? No, it is because the normal tone is
dilated (think of a person in a coma). If you flashed a pin light in the eye, would you see miosis? No, fixed pupils.
 Ciliary muscle (para) cycloplegia
 GI tract (para) tone and motility, constipation; Bladder (para)urinary retention
 Salivary glands (para) xerostomia; Sweat glands (symp)  anhydrosis
These are important (only on board exams) for preventing baroreceptor reflex changes in heart rate orthostatic hypotension
Trimetaphan (given -Short-acting blocker -Reduces HTN & -All effects listed above
IV) prevents reflex
tachycardia
-Good for treating a
HTN patient w/ acute
aortic dissecting
Mecamylamine (given 2’ amine, so better absorption from GI Same as trimetaphan -WILL cross BBB (unlike
orally) trimetaphan)
-SE: sedation, tremor,
choreiform movements & mental
aberrations
Tetraethyl- 1st ganglionic blocker No longer used
ammoniium (TEA) very short acting
4’ ammonium
Hexamethonium 4’ ammonium Experimental only,
hypertension
Decamethonium Neuromuscular depolarizing blocking
agent
Ganglionic Tetramethyl- Stimulation is not followed by Experimental only
stimulants ammonium ganglionic blockade

Dimethylphenyl
piperazinium
Varenicline Partial agonist at N receptor -used to stop smoking
Ganglionic & Nicotine -Preferentially stimulate Nn Higher doses cause ganglionic
NMJ stimulants Lobeline (ganglionic) block
-3’ amines
NM BLOCKERS The nicotinic receptors have 2yd structures. ACh binds to the  subunit, thus 2 ACh must bind to a receptor for activation.
There are no cardiac or smooth muscle side effects because those tissues do not have the receptors. Make sure to add a CNS
depressant so that patient does not remember.
Tubocurarine Low dose: Competitive blocker by -Flaccid paralysis – 30- *Low dose action can be
binding nicotinic Receptor 60 min overcome by increasing [Ach]
NONdepolarizing (AChE inhib)
-Progressive paralysis (face,
High dose: block ion channels of end limbs, respiratory muscles
plate must intubate
-NO effects on cardiac & SM
-NO CNS effects (non-
responding, but still aware)
Mivacurium Very short duration, metabolized by -Emergency -Not short duration in slow
plasma cholinesterases (genotypically metabolizer (could antagonize
determined) long duration w/ AChE-I)
Atracurium Ester hydrolysis, Hofmann elimination; -Safe in hepatic or -HR/BP changes
Onset – 2-3min; moderate duration; renal impairment (b/c -Bronchospasm
Rapid recovery not metab) -Laudanosine toxicity
-Not metab spontaneous inactivation -Not used seizures
to laudanosine

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 CisAtracurium 1 of 10 stereoisomers -People like it -No CV or Autonomic SE
Hofmann Elimination -Predictable elimination
Stable BP w/ dosing
Onset in 2-3min Moderate duration
Pancuronium
Vecuronium
Rocuronium
Succinylcholine -Nicotinic receptor agonist (analog of -Initial fasciculations -Malignant hyperthermia (due
AChhas efficacy) -Short acting: to excessive release of Ca from
-DEPOLARIZING, noncompetitive deactivated by butyryl the SR) Tx = dantrolene (blocks
-IV b/c very short duration ChE in serum release of Ca from SR)
-Rapidly hydrolyzed by -Useful for rapid -NO ganglionic block unless in
pseudocholinesterase endotracheal intubation doses
and during ECT -No antidotes b/c AChE-I would
Two phases: worsen b/c no breakdown, and
1. Phase I: depolarization, agonist would only worsen depol
fasciculation, prolong block
depolarization, flaccid paralysis CI: atypical
2. Phase II: desensitization (thus no pseudocholinesterase,
impulses through) hyperkalemia (risk of prolonged
depolarization of tissue)

NM Blockers Short acting Intermediate acting Long Acting AE: autonomic effects, some
NON-depolarizing Mivacurium Atracurium Tubocurarine (pancuronium) block M
Cisatracurium Metocurine receptors;
Rocuronium* Doxacurium Histamine Release-
(*Steroid derivatives) Vecuronium* Pancuronium* tubocurarine and metocurine;
Pipecuronium* and possibly with atracurium
and mivacurium
Neuromuscular Blockers:
Two Types:

I. Non-depolarizing-Competitively inhibits the NMJ receptors by binding without

activation of pre and postsynaptic sites. These cannot enter CNS due the charge of
the ammonium ions.

a. Presynaptic inhibition- Release of Ach diminishes and contraction “fades”

b. Postsynaptic inhibition- Blocks Ach at receptor. This is a competitive block

therefore increased Ach can reverse this.

II. Depolarizing-Competitive agonist that binds to and activates the NMJ receptor but
inactivates it by keeping the ion channel open (IE the receptor is prevented from
cycling back to it’s closed state).

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 ADRENERGIC DRUGS
Beta-receptors are usually more sensitive to activators. So, beta responses are dominant at low doses. At higher doses, the alpha responses
will predominate. (pp=pulse pressure, later)
1
 Radial muscle of eye mydriasis
 Arterioles & veins vasoconstriction
 Liver glycogenolysis
 Kidney renin
2
 Autoregulation (presynaptic inhibition)
 Pancreas insulin (remember that insulin is regulated by cAMP, that’s why it can’t be 1 receptor mediated, which causes Ca++)
 Platelets aggregation (since platelets are not innervated, this effect is caused by circulating epinephrine)
1
 Heart contractility, HR, conduction velocity
 Kidney renin
 2 (mostly not innervated)
 Vasodilation
 Uterus Relaxation
 Liver gluconeogenesis, glycogenolysis,  lipolysis (& in adipose)
 Skeletal muscle glycogenolysis (for muscle contraction)
 Pancreas insulin secretion (if you are running away from the alligator, you have to be able to use the glucose) lipoprotein lipase
 Lung bronchodilation
Drug type Drug Mechanism Clinical Use Side Effects
Epinephrine (1, 1, 2) DOC – bronchospasm & -CNS – anxiety, fear, tension,
*Note: only epinephrine interacts w/ 2 anaphylaxis (2) h/a, tremor
receptors -Glaucoma – pressure via -Cerebral hemorrhage via
-Since  receptors are more sensivitve, these vasoconstriction of ciliary blood BP
effects would be seen at low dose epinephrine vessels -Pulmonary edema
-Duration of local anesthetics
LOW dose: (like isoproterenol) via vasoconstriction (1) to limit -Cardiac arrhythmia – esp. in
 1: HR, SV, CO, pp abs & distribution digitalis pt.
 2: TPR, BP, pp -Tx cardiac arrest
Slightly lower BP, systolic BP, diastolic BP
HINTS (Is it Epi or NE):
MEDIUM dose: 2 effects = epi
 1: HR, SV, CO, pp If bronchodilate = Epi
 2:TPR, BP, pp If prevent premature labor= Epi
 1: TPR, BP If metabolic effects = Epi
So, maintains BP, while CO & perfusion
pressure **At dose epinephrine: if give
an 1 blocker, only have 1, 2
HIGH dose: (like NE) effects and the previous
 1: TPR, BP, potential reflex HR hypertension (1)  hypotension
 1: HR, SV, CO, pp b/c unmasked 2 = EPINEPHRINE
 2:TPR, BP REVERSAL
 BP, vasoconstrict & in shock this would *Clinically, if titrating doses of
perfusion more hypoxia, infarction, necrosis epi into emergency patient in
HR via reflex perfusion even more shock, and pt goes into
hypertension, giving 1 blocker
can be lifesaving
Norepinephrine (1, 1) Shock –powerful vasoconstrictor
-Less pulmonary action than w/ epi -Not good enough for
NE can NEVER drop BP (no 2 activty) bronchodilation

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 AGONIST These will cause a decrease in blood pressure (2) and an increase in heart rate (1). Pulse pressure also increases.
nonselective Isoproterenol 2 > 1 >>>a -Tx bronchospasms (bronchodilat) -Flushing (vasodilat) (2)
-Tx heart block & -HR arrhythmias (1)
bradyarrhythmias (by conduct)
Decreases peripheral resistance -Discontinued from due to
b/c no association w/ alpha deaths from CV involvement
receptor
1 AGONIST Dobutamine B1 selective agonist -Tx acute CHF  CO w/ little Use w/ caution in A-fib
(1 > 2) change in HR
-Shock/resucitation – increases Dobutamine - Tx
force more than rate NORMOTENSIVE
*Chronic CHF would have
desensitization of those Dopamine – Tx
receptors, so cannot use dobutam HYPOTENSIVE
2 AGONISTS These will cause a decrease in blood pressure (2) and a reflexive increase in heart rate (causing palpitations). These
are not anti-inflammatory, so you would need to address the inflammatory effects if you were treating asthma. Common
Short acting (4hrs) complaints of those using 2 agonists are anxiety & insomnia (think that 2 is part of fight/fright, so CNS stimulating).
Albuterol Also, 2 prepares muscles for fight/flight (glycogenolysis, perfusion), so may see muscle tremors. Glucose levels
Levabuterol would also increase because liver gluconeogenesis and glycogenolysis are stimulated. So don’t give to diabetics.
Pirbuterol Metaproterenol -Little effect on heart -Acute Bronchodilator – asthma 2-Muscle tremor,
Terbutaline -Resistant to COMT -Relaxes uterus to prevent restlessness, death rate in
Metaproterenol methylation/degradation childbirth asthmatics
1- tachycardia, arrhythmia,
Long acting (>12hr) pulmonary edema in
Salmeterol pregnancy, high dose
Formoterol continuous use hypokalemia
Terbutaline -More selective for 2 than SAME
Albuterol metaproterenol -Prevent premature labor (give IV
albuterol)
Salmeterol -Slow PK, onset in 30-45min -Only used for prophylaxis, may
nighttime attacks
Ritodrine Same -Primarily against premature labor -Hyperglycemia in mother &
reactive hypoglycemia in
newborn
-Risky – CV effects
Blocking 2 may precipitate (not cause) bronchospasms and vasospastic diseases. Also, since 2 increases lipolysis,
1/2 BLOCKER
glycogenolysis, then with a blocker you may expect hyperlipidemia and fasting hypoglycemia. 2 typically increase
nonselective
insulin, so blocking insulin release would not cause fasting hypoglycemia (insulin has little role between meals), but
rather it would cause HYPERglycemia after a meal, when insulin is required for glucose uptake. So obviously, B-
blockers would always be bad to diabetics (epinephrine’s effects are good via 1 and 2 to help alert to hypoglycemia, &
if blocked they would not know they are hypoglycemic)
Propanolol Don’t give B-blockers: MAJOR USE: -CI in acute CHF b/c cannot
1. Diabetics -Essential Hypertension, give drug to CO
2. CHF arrhythmia, -Rebound tachycardia if
3. Asthmatics -Migraines – blocks catechlamine suddenly removed
induced vasodilation in brain CNS depressive!!!!
-Anxiety CI: ASTHMA
-Hypethyroidism – decrese -Exercise intolerance – can’t
sympathetic stimulation & blocks increase CO
periphera conversin of T4 to T3 -Decreased HR
-Angina pectoris – reduction of -Exacerbate CHF
O2 requirement of heart -Conduction slowing
-MI-reinfarct protection -Incease TAGS (LDL)
-Glaucoma -Sexual dysfxn
-Delays response to
hypoglycemics
-Arrhythmics

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 Naldol Longer acting pure
antagonist
-No CNS involvement
Timolol Glaucoma – reduced ciliary -Watch for systemic effects
epithelial humour production -Sedating
Pindolol Partial agonist (have No effect on blood lipids
intrinsic symp activity) (due to ISA)
Sotalol K+ channel blocker & B- -Antiarrhythmic (class III)
blocker
In the heart, 1 block would case a decrease in CO, SV, and HR. In the kidney, 1 block would allow 1 predominance,
1 BLOCKER
leading to a suppressed rennin release. In general, a drop in blood pressure would cause a reflex tachycardia (1) and in
a few days an increase in rennin (1). Both of these effects are blocked. 1 blocker also decreases aqueous humor
production. Blockers A  M are 1 selective, NZ are nonselective
Atenolol Anti hypertension/ sympathetic Atenolol does not cause
cardiac overstimulation sedation (too water soluble
-Pt. on antidepressants w/ HTN, to cross BBB)
atenolol good b/c no sedation
Acebutolol Partial agonist (have No effect on blood lipids
intrinsic symp activity) (due to ISA)
-Sedating
Esmolol -Very short t1/2 -Use in ill pt.s where risk of
hypotension or heart failure is
great
-If they start to die, fine…. just
stop giving the med
Metaprolol Used in pregnancy
1/2 BLOCKER Labetalol 1/2 BLOCKER Hypertension – peripheral Orthostatic hypotension
nonselective & Carvediolol nonselective & vasodilator. Decrease BP w/o Dizziness
1 Blocker 1 Blocker altering TAG or glucose
concentration
-Antihypertensive w/o reflex
tachycardia
DA Dopamine Precursor ofr NE Tx of shock –CO (1 on heart), -Same SE as sympathetics
DA > 1 > 1 enhances perfusion to renal (D1), -DA metabolized (MOA or
splanchnic & coronary arteries COMT) HVA Nausea,
*DA = NE w/out the OH -But at DA TPR (bad) hypertension, arrhythmia
group aggravating the ischemic/necrosis
potential and possible reflex HR
*Think about DA w/ 1 blocker!
1 AGONISTS Phenylephrine 1 > 2 Tx of mydriasis & hypotension
Methoxamine -Slow metabolism w/ little -Nasal decongestant
Metaraminol CNS penetratin -Eye drops –  redness via
-Likely to be used topically vasoconstriction
to cuase vasoconstriction -End paroxysmal atrial
tachycardia (via vagal reflex)
Midorine 1 agonist Tx of postural hypotension
Prodrug desglymidodrine
In gerneral, antagonists have zero efficacy. so blocking  does not CAUSE vasodilation. Blocking  prevents
vasoconstriction. Lowering blood pressure can cause reflex tachycardias (via 1), but you can block with B-blockers.

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 Phenoxybenzamine -IRREVERSIBLY blocks 1 Decrease BP Only mechanism to overcome
 BLOCKER
& 2 (slightly 1 selective) -Tx for pheochromocytoma- is by making new adreno-
nonselective
induced hypertension. recptors, which takes approx
-Also blocks H1, muscarinic -Dx of pheochromocytoma 24 hrs
& 5HT receptors, & inhibits -Frostbite -MPR reflex tachycardia
NE reuptake -Clonidine w/drawal -Reflex CO from blocked
-Raynaud’s phenomena 2 1 system overrides
-Preoperative tx to help control -Postural hypotension, nasal
hypertension & sweating stuffiness, nausea, vomiting
-Ejaculation problems
(shooting blanks)
Phentolamine Nonselective, REVERSIBLE -Same as Phenox but reversible -Can trigger arrhythmias and
-Blocks 1 & 2 -Prevention of dermal necrosis anginal pain
-Blocks 5HT after the inadvertent
-Agonist at muscarinic, H1, extravasation ofNE CI: patients w/ coronary
H2 receptors perfusion
1 BLOCKER Prazosin Highly 1 selective Decreases BP w/ no reflex Orthostatic hypotension (u’ll
tachycardia get suPRAZed when u stand
Antihypertensive up)
-Vertigo
-Nasal congestion
-Drowsiness
Terazosin 1 selective Tx of BPH-associated urinary
retention
-Relaxes SM of prostate
Tamsulosin -1a selective antagonist Tx BPH  Incidence of orthostatic
(GU sm musc) hypotension
The effect of an 2 agonist is never immediate because enzyme activity (tyrosine hydroxylase) is changed by
2 AGONIST
decreased synthesis. So, these are not likely to have effects on the blood pressure tracings seen on board exams. You
may see a transient hypertension initially.
Clonidine -Decreases central NE -Tx of mild hypertension Sedation
-Minimize sx from w/d from -Orthostatic hypotension
opiates, cigarettes & BDZ’s w/d sx include hi BP, h/a,
-Rx’s heroin’s anti-adrenergic tremors, sweating,
effects tachycardia
CNS
-Decreases sympathetic activity
Methyldopa Prodrug
2 BLOCKER Yohimbine Increased release of NE, -Erectile dysfunction Replaced by PDE 5 inhibitors
stimulating cardiac 1 & -Reverse Clonidine effects
vascular 1
Since these drugs are indirect, the de-inervated tissues will be nonresponsive. Indirect acting agonists will displace
INDIRECT
norepinephrine from mobile pool. Drug interactions include MOA-a inhibitors.
ACTING
1. MOA-a breaks down catecholamines (ACh, NE, serotonin), but NOT dopamine
AGONISTS
2. MOA-b breaks down dopamine
Tyramine -Released from cheese and red wine, normally oral bioavailability CI: MAO-a inibitors
is limited by MOA-a metabolism of tyramine in the gut & liver.
With MOA-a inhibition, there is bioavailability
Amphetamine -Promote NE release (DA, Used to be used for ADHD CI: MAO-a inibitors
Ritaline 5HT release also)
-CNS target
Ephedrine -Same as above -Included in many cold medicines CI: MAO-a inibitors
-CNS is side effect
REUPTAKE Reserpine -Prevents cytosolic -Reduces reuptake of NE -Side effects limited by
INHIBITORS reuptake of NE into vesicles -Effective, cheap using low dose (Depression)
antihypertensive

9
 Cocaine Block reuptake of NE -Used socially
-Amplifies any adrenergic
neurotransmission
peripheral or central

GLAUCOMA
There are two types of glaucoma. The angel refers to the irido-corneal angel, where the aqueous humor drains
1. Open Angel glaucoma – degenerative changes in the canal of Schlemm to drain causes slowly increasing pressure, pressing the back of the
eye. GOAL: decrease production of aqueous humor by blocking 1
2. Closed Angel glaucoma – the angel is narrowed. It could be because the iris is obstructing the canal of Schlemm, or it could be from genetics.
A drug that causes constriction of the radial muscle may cause a mechanical blockage of the canal (1 agonist drugs). GOAL: stretch the iris
via miosis, or constrict the ciliary muscles to allow the iris to bow backwards and allow drainage
Class Drug Mechanism Clincal Use Side Effects
Cholinomimetic Pilocarpine M agonist DOC for emergency closed
angel or open angel glaucoma
Echothiophate AChE inhibitor (organophosphate) Same, longer duration
-Blocker Timolol Block actions of NE at ciliary
nonselective epithelium and  aqueous humor
formation
Carbonic anhydrase
inhibitor

AUTOCOIDS
Class Drug Mechanism Clinical Use Side Effects

Histamine H1 receptor:
(H1) BLOCKER  Gq coupled
Found on the endothelium Ca NO synthesis diffuses to smooth muscle relaxation
 Increases capillary permeability (associated w/ contraction of endothelial cells)
 Found on bronchioles bronchoconstriction
 Increases activation of peripheral nociceptors (PAIN & pruritus)
 Involved in inflammatory and allegic reactions
 Via Gi coupling, will decrease AV nodal conduction
H2 receptor:
Gs coupled (cAMP)
In stomach, causes increased gastric acid secretion from parietal cells ulcers
In the heart, causes increased SA nodal conduction
Also found on mast cells & in the CNS

10
 Diphenhydramine -Competetive blockers at -Allergic rhinitis/urticaria -Sedation, antimuscarinic,
Chlorpheniramine H1 receptors -Motion sickness antagonize serotonin
Hydroxyzine (scopolamine is better) -Dry mouth
Meclizine 1st Generation -Sedation (side effect) -Drug induced parkinson’s
Promethazine -Also antagonize ACh, -Sleep induction Potentiates effects of other CNS
NE, Serotonin in CNS -Parkinson’s disease (b/c depressants (alcohol etc)
**Not used in antimuscarinic) Loss of appetite, nausea, distress,
bronchospasm** -Diphyd – also good local constipation or diarrhea
anesthetic that reverses
effect of phenothiazines
Fexofenadine -Competetive blockers at Allergic rhinitis (daytime PVC’s – tachycardia
Larotidine H1 receptors benefits) “non sedative” Prolonged QT interval
Terfenadine* Liver dysfxn
Astemizole* 2nd generation Substrates for P-glycoprotein
(*Taken off market)
-No sedation (do NOT transp.
cross BBB)
Histamine Cimetidine -Inhibit gastric acid -Gastric ulcer Mainly Cimetidine:
(H2) secretion -Zollinger-ellison syndrome -Inhibits P450**
BLOCKER -See GI drugs -GERD (PPI are better) Anti-androgenic Gynecomastia,
-Hiatal hernia low sperm count, galactorrhea
Ranitidine -Do NOT inhibit P450 -Same -VERY safe drugs
Famotidine -Longer acting -Headache, dizzy, diarrhea,
Nizatidine Less side effects than cimetidine
Serotonin Methysergide -Congener of LSD which -Migraine – prophylactically -Toxic effects limit use
antagonist antagonizes 5-HT Carcinoid sndrome -Leads to fatal pulmonary/cardiac
Nonselective receptor fibrosis if used chronically
HT2 BLOCKER HT2 (a-c):
 Gq coupled IP3/DAG
 In CNS excitatory
 In PERIPHERY  vasodilation, GI contraction, bronchial contraction, uterine SM contract, platelet aggregation
Cyproheptidine -Also blocks H1 -Post gastric dumping Sedating due to H1 Block
syndrome
-Vasospastic disease- trials
-May be used as
antihistamine
-Allergic rhinitis, vasomotor
rhinitis
-Tx of smooth muscle
manifest of carcinoid synd.
Olanzapine Blocks HT-2a receptors in -Tx of schizophrenia
CNS (atypical antipsychotic)
Ketanserin -Highly selective Hypertension – trials
-Also blocks 1 receptors Vasospastic disease – trials
HT3 BLOCKER HT3:
 Found in area postrema, peripheral sensory and enteric nerves
 Opens ion channels (only 5HT ion channel)
Ondansetron Adjunct in cancer
Granisetron chemotherapy:
Palonosetron -Anti-emetic
Dolasetron -Prevents nausea/vomiting
(esp from cisplatin)
(“setron”)
HT4 HT4:
AGONIST  Coupled through Gs cAMP
 Found in GI SM
Cisapride HT4 agonist in GI Tx constipation in IBS Serious cardiac effects, no longer
Tegaserod prokinetic GERD? used in USA
Metoclopramide HT4 agonist in GI Prokinetic (aka constipation)

11
HT1 HT1 (a-f):
AGONIST  Usually coupled through Gi cAMP (sometimes Gs coupled)
 Found in CNS
Busipirone HT-1a partial agonist, Anxiolytic Non-addicting
DA2, HT2 blocker No cross tolerance w/ alcohol
Sumatriptan HT1d agonist Migraine acute tx (b/c -Tingling/flushing @ injection site
(“triptan”) vasoconstriction effect) -Chest tightness, angina in CAD
Cost -CI patients at risk for coronary
-More effective than ergots heart disease b/c of the drug’s
(ergonovine, vasoconstriction
methylergonivine, ergotamine
–used in postpartum
bleeding)

SSRI Fluoxetime Inhibits reuptake of 5HT Depression Weight loss

(Prozac)  5HT levels Insomnia
Flushing, sweating
GI disturbances
Ergot Ergotamine Partial agonist at  and Tx of acute migraine -GI distress
Alkaloids 5HT-2 receptors in the attacks -Prolonged vasoconstriction
vasculature & maybe CNS ischemia & gangrene, abortion
near term
dihydroergotamine Bind -adrenoceptors, Tx of acute migraine Avoid over use (rebound migraine)
dopamine recpt, 5-HT attacks
Bromocriptine Tx of hyperprolactinemia
Cabergoline (Cabergoline more potent)
Ergonovine Same -Tx of postpartum
maleate IM -Uterine SM hemorrhage (usually use
contractioncan stimulate oxytocin)
labor -Diagnosis of variant angina
-Causes constriction of by inducing coronary
vascular smooth muscle by vasospasm
stimulating both adrenergic
and serotonergic receptors

Adenosine Adenosine Inhibits all excitable cells Paroxysmal Supraventricular -Receptors through out body
-Esp. AV node tachycardia -Anginal pain – vasodilation
-Involved in autoregulation -DOC after failure of -Asystole (watch dose)
valsalva type maneuvers --Luckily short acting drug
-Diagnostic & curative -Contraindicated in pt. on
Adenosine stress test – for dipyridamol – potentiates affects
those unable to jump on the (theophylline is antidote)
stairmaster
Adenosine Methylxanthines -Intereferes w/ Ca++ CNS Stimulant Anxiety, agitation
Antagonists (Theophylline, binding by SR HR & CO Insomnia
caffeine, -Inhibits -CVS: catecholamine release,
theobromine) phosphodiesterase Arrhythmias
prevents cAMP & cGMP

12
 Theophylline -Bronchodilation via Asthma –(controversial) -Many PK drug interactions
inhibition of PDE cAMP -CVS: catecholamine release,
& also by antagonism of Arrhythmias
adenosine (a
bronchoconstrictor)
-Induction of histone
deacetylases to suppress
inflammatory gene
expression
-Promotes corticoid action
Adenosine Dipyramidole -Blocks adensine reuptake -Tx angina pectoris Do not give adenosine while on
agonists -i.e. increases levels -Inhibit emboli from this drug b/c pt. may arrest
-Vasodilator (increases prosthetic valve
cAMP)
Prostaglandins Misoprostol PGE1 analog – mucosal -GI protection from NSAID- -Diarrhea, cramping abdominal
resistance to injury induce ulcers only in high risk pain
-Inhibits secretion of HCl patients b/c of high adverse -Stimulates uterine contractions
in stomach & inhibit SE and need for multiple
gastric acid & gastrin dosing (give PPI instead) CI: pregnancy
secretion -Opens Ductus arteriosus
-Ripen cervix before
induction of labor
-Used w/ methotrexate (or
mifepristone) in terminating
pregnancy in 1st trimester
Alprostadil PGE1 -Keeps open ductus
Given IV arteriosus
-Male impotence (old use)
Dinoprostone PGE2 causes uterine -Ripen cervix before
contraction induction of labor w/
oxytocin
Epoprostenol Analog of PGI2 -Used in severe pulmonary
peripheral, pulmonary & hypertension
coronary resistance -Prevents platelet
aggregation in dialysis
Latanoprost PGF2 (aqueous humor -Glaucoma
Bimatoprost production)
Travoprost
Unoprostone
Leukotriene Zileuton Inhibits 5-lipoxygenase Asthma Tx
inhibitor (inhibits leuktn snth) -Cold, NSAID, exercise
induced
Zafirlukast Blocks receptor for LTD4 Same
Montelukast
Corticosteroid Inhalants: Inhibit phospholipase A2 ASTHMA Inhalants: Local- oral/esophageal
Beclomethasone *Inhalants: tx of asthma candidiasis, hoarseness; Systemic-
Budesonide (mild-moderate), decrease minor AE b/c little bioavailability
Fluticasone hyperreactivity, improve
epithelial function;
Systemic: *Oral: used w/ long acting 2
Prednisone agonist (and theophylline) in
Dexamethasone severe persistent asthma

13
 Cortisol Same -Tx of adrenal crises -Na retention, EC volume
Prednisone -Immunosuppres, antinflamm expansion, hypokalemia, alkalosis
Triamcinolone -Withdraw drug slowly -Preterm labor to stimulate -Iatrogenic cushings
Betamethasone fetal lung maturation -Osteoporosis
Dexamethasone *Avoid in diabetics -GI acid & pepsin release
plasma glucose *Lack of cortisol associated -Glaucoma, cataracts (via
(Listed in w/ hypotension b/c sorbitol)
increasing potency) *Avoid in CHF b/c Na permissive effects -Wound healing, infections
retention DRUG toxicities:
-Cardiac glycosidehypokalemia
-Loop diuretics, thiazides K
loss
-NSAIDs – peptic ulcers,  GI
bleed
-ACE-I - risk of blood dyscrasias
-Chloroquine/mefloquine- risk of
myopathy, cardiomyopathy
-Anticholinergics - intraoc Pres
Aldosterone Stimulates -Fludro= also has some anti-
Fludrocortisone mineralocorticoid R inflamm
Cortisol Metyrapone Blocks 11-OH, inhibit -Diagnose adrenal
Blocker synthesis of adrenal deficiencies
steroids (Cortisol) -Tx Cushings
Mast cell Cromolyn Inhibit early/late mast cell Topical aerosol for Cough & airway irritation
stabilizers Nedocromil histamine release prophylaxis in asthma CI: acute episodes
(prevents degranulation)
Anti-IgE Omalizumab Inhibits IgE binding to Tx asthma
antibodies FceR
Mucolytic Acetylcysteine Disrupts S-S bonds in -Asthma (Facilitate -Mechanical airway irritation, GI
mucoproteins expectoration) disturbances
CAUTION: in severe asthma or
gastric ulcer patients (mucous is
protective)
Progestin Mifepristone Blocks glucocorticoid & -Abortion (esp. when given w/ Uterine bleeding, malaise, GI, skin
Antagonist progestin recptrs PGE1 or PGF or misoprostol) rashes
-Give during mid-luteal -Postcoital contraception CI: ectopic preg; COPD,
phase when progesterone (w/in 72 hours) renal/hepatic dysfunction, adrenal
is normally high -Interferes w/ failure, steroid therapy
glucocorticoid for Cushing
syndrome
-Tx of progesterone dep
meningiomas

NSAIDS
Drug Mechanism Clinical Use Side Effects

14
 Nonselective Aspirin Irreversible acetylation of -Analgesia– not visceral pain, -GI bleed
COX Inhibitor COX prevents sensitization of pain -Risk of gout, competes w/
-Prevents formation of receptrs to mechanical & chemical excretion/reabs of uric acid
PGE, TXA2, Prostacyclin stimuli (blocks PGE2) -Reyes syndrome
-Deacetylation  salicylate -Reduce fever -Liver toxicity
OTHERS: which is anti-inflammatory -Reduce inflammation -Acute Interstitial Nephritis –
Azapropazone** -Analgesic at low doses and -Anti-platelet coagulation (more type 1 HS rxn acute renal
Carprofen anti-inflamm at doses later) failure
Diclofenac (45mg/kg/day) - Survival post-MI -Analgesic Nephropathy renal
Diflunisal PK: Elimination follows 1st -Some evidence that aspirin papillary necrosis aftr many yrs
Etodolac order kinetics at low doses incidence of colon cancer -Bronchoconstriction (b/c blocked
(half life=3.5 hr); 0 order
Fenoprofen -------- COX  leukotrienes)
Flurbiprofen* kinetics at doses -Salicylism (at chronic doses)–
Overdose stimulate resp centr
Ibuprofen reversible tinnitus, dizziness, h/a,
hyperventilation Respiratory
Indomethacin confusion
alkalosis
Ketoprofen* -PGE2 (normally renal vasodilator
Metabolic acidosis
Ketorolac that maintains renal perfusion)
1. Salicylates are a weak acids
Meclofenamate can Na and water retention
2.Impairs renal function
Mefenamic acid -PGI2 (normal renal vasodil) may
accumult of sulfuric and
Nabumetone  hyperkalemia, acute renal
phosphor acid
Naproxen failure
3.Uncoupled oxidat phosph
Oxaprozin BT (antiplatelet at low dose)
CO2 product glycolysis
Phenylbutazone PT (anticoagulant at high dose)
glycogenolysis, gluconeo,
Piroxicam* lipolysis, FA ox ketones
Sulindac Overdose tx --- fluid, glucose,
4.Inhibited dehydrogenases in
Tenoxicam HCO3-, K+, cooling, diuresis
Krebs cycle lactic acidosis
Tiaprofen (enhance renal excretion by
*Patient presents w/ mixed resp
Tolmetin alkaline urine – CAI), lavage,
alk & metab acid but after
charcoal
doses/prolonged exposure
depress medullaresp paralysis
*High risk of GI side effects
resp acidosis mixed acidosis
resp & met (bicarb, Pco2)
Ibuprofen -Same potency as aspirin Inflammatory diseases GI disturbances
-hi analgesia & antipyretic Dysmenorrhea Tinnitus
properties Rashes
-Reversible inhibition of H/a
cyclo-oxygenase Interstitial nephritis
Naproxen Longer-acting derivative of
ibuprofen
Indomethacin More potent cyclo- Serious hematologic rxns
Closes ductus arteriosis
oxygenase inhibitor
-No bleeding time Only effective in Hodgkin’s fever Aplastic anemia
Ankylosing spondylitis Acute renal failure
N/V h/a
Gouty arthritis Acute pancreatitis
Pre-term uterine-contraction
reduction
Phenylbutazone No longer used Bad SE (aplastic anemia)

Tolmetin Long t ½ More potent than aspirin <than aspirin

Piroxicam
Sulindac Pro-drug (hepatic Gouty arthritis Agranulocytosis
activation) Pre-term labor
Decreases adenomas w/ FAP
RA/Osteoarthritis
Ankylosing spondylitis
Keterolac Injectible form Same as other NSAIDS
Post-op pain –visceral
Like opiates w/o CNS side
effets Allergic conjunctivitis

15
 COX-2 Celecoxib -Coxibs used primarily for -Fewer GI SE than nonselective
Selective inflammatory disorders COX inhibitors
Inhibitor -Renal toxicities similar to
nonselective COX inhib
-HS rxns (it is a sulfonamide)
-COX-1 not blocked  plateltes
make TXA2 thrombotic state
Rofecoxib Withdrawn from US market Associated w/ thrombotic events
Valdecoxib
Etoricoxib 2nd generation, highest Not approved in US
select,
Meloxicam Preferentially inhibits COX-
2, but not as selective as
coxibs
Non-NSAID Accetominophen NO anti-inflammatory Analgesia -Does not affect uric acid levels
NO antiplatlet Fever -Hepatotoxic @ doses
-Weak COX-1,2 inibitor in Good for pt. on probenecid &
peripheral tissues uricosuric for gout b/c no X- ANTIDOTE: Acetylcystein is
-May inhibits COX-3 in CNS tolerence antidote (sometimes cimetidine)
Phenacetin Toxic prodrug is metabolized Still available in some countries
to acetaminophen

16
 GI Drugs

Drug Mechanism Clinical Use Side Effects

H2 Receptor Cimetidine MOA: Blocks gastric mucosal -Tx of Zollinger-Ellison -Many drug interactions
Antagonist histamine (H2) receptor syndrome -Decrease hepatic blood flow
gastric acid production (by -Tx GERD -Inhibit P450
90%) & decrease pepsin -Tx peptic ulcers & prevent -Anti-androgenic effects
formation recurrence (gynecomastia in males and
-Must take before eating -Prophylaxis in ICU against galactorrhea)
stress ulcers -Infertility, libido
PK: usually given PO, in -Preoperative prevents -Skin rash
emergencies give IV aspiration pneumonia -Immunosuppression
-Tx of Tylenol O.D. -IV dose hallucination,
-Hiatal hernia delirium, restlessness,
dizziness, somnolence
-Absorption of weak acids
CI: pregnancy
Ranitidine More potent than cimetidine, same -No anti-androgen effects
Famotidine longer duration -No CNS effects
Nizatidine -No P450 inhibition
-Absorption of weak acids
Muscarinic Prienzepine -Selective M3 receptor -Adjuncts to histamine receptor -Same as atropine
Antagonists blocker blocker tx -Dryness of mouth, blurred
-Atropine-like compound have -Tx peptic ulcer vision, tachycardia, urinary
only small ability to decrease -Not currently used retention, constipatin (higher
gastric acid doses)
-Little ability to cross CNS -More side effects than benefit
Dicyclomine -Inhibits vagal stimulation of -Tx of IBS same
acid secretion
PROTON Omeprazole -Prodrugsulfenamide DOC Z-E Syndrome (or MEN) -Very safe at low doses
PUMP L MOA: Covalently DOC peptic ulcers -H/a, dizzy, nausea
INHIBITOR a (irreversibly) binds H/K -Tx histamine resistant ulcers -Abdominal Pain
S (PPI) n ATPase on mucosal side of -Tx GERD -Long term use may be
s parietal cell suppresses H+ -H. pylori infection carcinogenic due to hi gastrin
o secretion (18hrs); they -Tx of hemorrhagic ulcers levels
p support platelet aggregation -Tx systemic mastocytosis -Hyperplasia of oxyntic mucosal
r maintain clot integrity (mast cells histamine) cells
a PK: effects in 1 hour -Absorption of weak acids
z H. pylori triple therapy (7-14 -Acid environment is required
o days): for absorption of Ketoconazole/
l PPI + Clarithromycin + itraconazole (impairs abs)
e Amoxicillin
Esomeprazole PPI + Clarithromycin +
Pantoprazole Metronidazole (give if penicillin
Rabeprazole allergic)
PPI + Tetracycline +
Metronidazole + bismuth
subsalicylate
*But continue PPI or H2-R block
for 4-6 weeks
MUCOSAL Misoprostol PGE1 receptor agonist -Prevent NSAID-induced ulcer -Diarrhea
PROTECTIVE inhibits basal & stimulated only in high risk patients b/c of -Uterine contraction
AGENTS gastric acid secrtion (Gi high adverse SE and need for -Abdominal pain
cAMP) multiple dosing (give PPI
-Enhances mucosal barrier by instead) CI: pregnancy
increasing mucus & NaHCO3 -Abortiion w/ (MTX)

17
 Sucralfate -At pH < 4 extensive -GI ulcers & erosions No major side effects
polymyerizationsticky gel -Stimulate PGE production -Alterss bioavailability of other
adheres strongly to base -Promotes healing (increase drugs
of ulcer crater (physical cell#) -“Large Pill” compliance
barrier ( -Constipation
-Coats for >5 hrs CI: other anti-ulcer meds (b/c
this drug needs an acid pH)
Bismuth e.g. peptobismol -Said to have some antibacterial
-Not a prodrug action against H. pylori 
-Forms into white precipitate combined w/ metronidazole +
at pH <3.5 coats ulcer tetracyclines
crater & acts as a diffusion
barrier to H+/pepsin
ANTACIDS The carbonanates will alkalinize (remember carbonate is an endogenous buffer). The hydroxides work as a bze to
neutralize the acid. Antacids will increase oral absorption of weak bases (e.g. quinidine), decrease oral absorption of
weak acid (e.g. warfarin), and decrease absorption of tetracyclines (via chelation).
Na-bicarbonate Immediate onset -ANTACIDS Symptomatic -Belching
-Short duration (not curative) relief of -GAS!!!
-May increase gastric pH to dyspepsia associated w/ GERD, -Alkalosis
alkaline level which increases gastritis, peptic ulcers -Sodium retention
HCl secretion
Ca Carbonate Rapid onset -Same -Nephrolithiasis
-Think: carbonates alkalinize -Can be given as an adjuvant in -Hypercalcemia
osteoporosis -Alkalosis
-Gastric acid rebound
-Dense stools (constipation)
-chleated by tetracylcines
Mg hydroxide Mg(OH)2 – milk of magnesia Same -Osmotic diarrhea
Relatively insoluble (poorly -Hypermagnesemia
abs)  slows removal from -Belching
stomach -Abs of digoxin & tetracyclins
-Gastric acid rebound
Mgloss of DTR & respiratory
paralysis
Al3+ Hydroxide Least potent Used in combo w/ other antacids -Reacts w/ HCl AlCl3
Think: hydroxides neutralize constipation
-Long term use hypophosphat
-NO Gastric acid rebound
PRO-EMETIC Ipecac Stimulate CTZ/gastric Tx of accidental poisonings
Apomorphine mucosal irritation
ANTI- The sources of afferent input to the Chemotactic Trigger Zone (CTZ):
EMETIC 1. CTZ has D2 receptors, 5HT-3 receptors, neurokinin1 (NK1) receptors, and opiod receptors stimuli = emesis
2. Vestibular system (CN VIII) motion sickness  emesis
3. Irritation of the pharynx, innervated by the vagus (CN X) gag reflex (note: vagus = muscarinic R)
4. Vagal and spinal afferent nerves from the GI tract are rich in 5HT-3 receptors  irritation of GI mucosa from
chemo, radiation, or distention release of serotoninvagus stimulationemesis
5. CNS psychological  emesis (e.g. vomiting prior to chemo)
Ondansetron 5HT-3 receptor blocker - Tx nausea/vomiting Well tolerated & very safe
5HT-3 Recptor Granisetron centrally at CTZ and -H/a, dizziness, constipation,
blockers Dolasetron peripherally at GI Diarrhea
Palonosetron PK: PO, IV; Palonnewer
drug, more specific for -Small prolongation of QT
5HT-3 & longer ½ life (40 interval
hrs)
-Others have short ½ life
(4-9hrs)
-Hepatic metabolism
Dexamethasone Unknown mechanism for -Enhance efficacy of 5HT-3
Methylprednisolone antiemesis recptr blockers

18
Corticosteroids Aprepitant NK1 receptor blocker (this -Used w/ 5HT-3 blocker for -Fatigue, dizziness, diarrhea
is the receptor to prevention of acut/delayed n/v -Metab by CPY3A4 & would
NK1 Recptor
substance P) inhibit other drugs from metab
Blocker
Dopamine receptors (D1) are also found on the lower esophageal shpincter, causing it to contract better
Phenothiazines -Blocks DA receptors in Cisplatin induced N/V Sedation
D2 receptor Prochlorperazine chemoreceptor zone Poisons & visceral afferent pain Extrapyramidal dyskinesias
Blocker Promethazine -Blocks muscarinic (dystonias)
receptors
-Antihistamine sedation
Metoclopramide D2-receptor blocker -Anti-emetic -Fatigue
HT3-receptor blocker -GERD -Insomnia
HT4-receptor agonist -Uremia -Hyperprolactinemia, infertility
-ACh agonist w/in GI -Diabetic gastroperesis -Extrapyramidal symptoms
GI motility (dystonias, restlessness,
parkinsonian)
Diphenhydramine -Antihistamine (Blocks H1) Motion sickness Sedation
See antihistamines Allergic rhinits/urticaria Don’t give w/ other CNS
H1 blocker Sedation depressants
Dimenhydrinate -Antihistamine (Blocks H1) Motion sickness (inner ear) Sedation
M -Blocks muscarinic receptrs Vestibular inflammation
ec (Remember 1st generation
liz H1 blockers)
in
M blocker e
Hyoscine -Antimuscarinic
Scopolamine
Canabanoid Nabilone Canabanoids (THC) -Tx n/v associated w/ chemo Hi abuse potential
Dronabinol Unknown mechanism -Tx wasting syndrome in AIDs & Drowsiness
-Works in higher centers in certain cancers Ataxia
brain -Tx glaucoma Inability to concentrate
Disorientation
Dronabinol not really used Anxiety
b/c bioavailability Psychosis
Laughter (that horrible stuff….)
Lorazepam Benzodiazepinesreduce
Diazepam anticipatory vomiting
PROKINETIC Cisapride -Release Ach in myenteric -Tx GERD -Long QT syndrome
plexus -Tx diabetic gastroparesis (predisposes to arrhythmias w/
-Muscle tone in the erythromycin or ketoconazole)
esophageal sphincter -Diarrhea
-Gastric empyting in
people w/ diabetic
gastroparesis
Metoclopramide See above See above See above
The prokinetic is via
muscarinic activity
LAXATIVES Bran BULK FORMING AGENTS -Tx Constipation Virtually safe & effective
Agar -Pre-op or pre-radiological exam
Methylcellulose -Indigestible, hydrophilic, -Maintain insulin control -If not taken w/ H2O, then may
Psyllium absorb water form bulky -Cholesterol cause obstruction/impaction
geldistends colon, -Colon cancer risk -Dehydration, electrolyte
promotes peristalsis imbalance
-Cramping, constipation

19
 Lactulose OSMOTIC LAXATIVE
Sorbitol Soluble, non-abs salts 
Mg oxide hold water in stool by
osmosis
-Lactulose also a substrate
for gut bacteria lactic
acid pH of gut (NH3
NH4+, now not absorbed
from gut)
Polyethylene Glycol OSMOTIC LAXATIVE
(P Nonabs sugar w/ other
E saltsno signif fluid or
G) electrolyte shifts
Docusate STOOL SOFTENER
-Soften stool, permitting
water and lipids to
penetrate
Mineral oil STOOL SOFTENER
Lubricates fecal material,
retarding water absorption
Caster oil STIMULANT LAXATIVES
Bisacodyl -Induce bowel movement
Phenolphthalein
(E
x-
La
x)
Aloe STIMULANT LAXATIVES
Senna Occur naturally in plants
Cascara
ANTI- Diphenoxylate OPIATE w/ little CNS
DIARRHEAL action
-Produces bowel relaxation
& peristalsis
-Onset in 1hr
-Atropine is added to
discourage abuse. Atrope is
an antispasmodic & would
help in the constipating
Loperamide OPIATE, much lower abuse
(Imodium) potential b/c ability to
cross CNS
Hyoscyamine Block ACh receptors to
Dicyclomine decrease parasympathetic
tone & motility of GI tract
-Antispasmodic action
-Tx constipation
-Tx systemic encephalopathy
-Tx IBS-constipation (lac/sorb)
-Don’t use -Mg oxide for long
time in renal disease b/c hyper-
Mg
-Flatulence & gas & cramping w/
lactulose
-Preop GI cleaning
-IBS-constipation
NO bowel cramps
-Tx painful defecation or
constipation
-Prevent/Tx fecal impaction in
young children and debilitated
-Used for constipat of morphine
Caster oilpotent (seldom used)
Ex-lax removed from market
(carcinogenic)
Produce bowel movement in 6-12
hrs
-General diarrhea
-AIDS associated diarrhea
-Tx IBS-diarrhea
-Much more effective on GI
-Tx IBS-diarrhea
-Over the counter
Diarrhea
-Nutritional def of calories,
vitamins, & minerals
CI: bowel obstruction,
undiagnosed acute abdomen
*Stimulants avoided in
pregnancy
-May develop cathartic colon?
Fluid/electrolyte deficit
Allergic rxn
Turns urine/feces pink
Chronic use brown
pigmentation of the colon
(melanosis coli)
-May turn urine red?
-Habit forming
-Not too addicting b/c they are
relatively insoluble
-Promotes ulcer formation
-Antimuscdry skin, dry mouth,
tachycardia, arrhythmias
CI: don’t give to kids
Only produce the atropine-like
side effects @ hi doses
20
 Bismuth- Coats intestinal epithelium H. pylori diarrhea
su & irritation
bs
ali
cy
la
te
(P
ep
to
Bi
s
m
ol)
Octreotide -Somatostatin derivative -Tx diarrhea associat w/
(Somatostn normally used in metastatic carcinoid &
Tx acromegallyinhib GH) VIPomas

Sulfasalazine Have anti-inflamm effect -Used in ulcerative colitis &

crohn’s disease
Infliximab Monoclonal antibody to TNF -Tx IBS & RA

Tegaserod Selective 5HT-4 agonist Relieve Irritable Bowel

Syndrome – constipation
Alosetron Selective 5HT-3 blocker Relieve Irritable Bowel
Cilansetron Syndrome – diarrhea
SSRIs Serotonergic effect Would seem to help IBS
Kaolin Adsorbants absorb water
Pectin to form better stools

GOUT
Acute Colchicine Binds to tubulin microtubul Acute attach of gout
episodes polymerization, LTB4,  (rarely used anwymore,
give NSAIDS)
Prophylaxis Allopurinol Prodrug converted by Prevents the synthesis GI distress, peripheral neuropathy
xanthine oxidase inhibit the -Rash, vasculitis
enzmze purine metab -Stone formation
uric acid -Inhibits 6-mercaptopurine
Probenecid Inhibits PCT reabsorption of -Do urinanalysis, and if -Crystallization if high excretion of
uric acid see high concentration of uric acid
uric acid crystals (do -Inhibits the secrtion of many acidic
NOT use probenecid , drugs (e.g. penicillins,
give allopurinol if patient cephalosporins)
is a high excretor)

Duretics
“Diuretic should be interpreted as “loss of salt”, not lose of fluids. Many of these drugs have sulfa allergies associated with
them. A quick screening is that many white wines have sulfites in them, so ask if patient can drink white wines.
21
 Class Drug Mechanisms Side Effects
Clincal Use

Carbonic Intracellular carbonic anhydrase generates H+ and HCO3-. The H+ leaves via the NHE. The H+ combines with
anhydrase filtered HC03 to form H2C03, which is broken down by luminal membrane CA into water and CO2 (both
inhibitor permeable).
Acetazolamide -Related to -Short term tx of -Bicarbonaturia
Dorzolamide dichlorphenamide glaucoma aqueous hum -Hyperchloremic
(“-zolamide”) (dorzol topical, acetazol in -ACIDOSIS
MOA: emergency) -HYPOKALEMIA
1. H+ formed in PCT by CA -Urinary alkalinisation -Renal stones (b/c
(Carb Anhydrase blocked) excretion of weak acids bicarb in urine, Ca++,
2. Na+/H+ antiport (NHE) (e.g. ASA Overdose) Phophate precipitate)
3. Na & bicarb in lumen -CSF production -Sulfa allergies
4. Diuresis -Tx of metabolic alkalosis
-Acute mountain sickness CI – cirrhosis  NH4+
-K+ secretion distally in (altitude hypervent usually trapped in acidic
exchange for Na resp alk, which is compens urine but reversed on
-Cl b/c Na absorbed in by metab acidosis; also drug alkaliniztion  hepatic
DCT via NCCT prevents hypoxic vasoconstr encephalopathy (NH4+)
ACIDazolamide = ACIDosis in lungedema)
Osmotic Mannitol -Excreted in glomerular -Acute diuresis -H/a, n/v
diuretic filtrate w/in 30 min -Maintain tubular flow/flush -Acute hypovolemia
-Mannitol is not debris -Dehydration,
reabsorbed Retains H2O -Intracranial/intraocular hypernatremia
in tubule pressure (mannitol 1st causes
*Work on entire tubule, but -Tx of Rhabdomyolysis fluid retention in
considered to have greatest vascular b/for kidney
action at PCT b/c PCT = preload = bad)
most active CI: anuric states, CHF
Loop diuretic Furosemide -Duration 2-3 hours -Tx acute pulmonary -Ototoxic  esp. w/
Bumetanide -Given IV, instant onset edema aminoglycoside
Torsemide -Direct effects on blood -Fored diuresis esp. in acute -Hypokalemic
flow (renal/ pulmonary) renal failure -ALKALOSIS
-Tx anion overdose -HYPOCALCEMIA
1. Block NKCC of TAL -Tx hypercalcemia, -Hypomagnesemia
2. Intracell K in TAL hyperkalemia -Hyperuricemia (loops =
3. Back diffusion of K into -Tx of HTN weak acids, which would
lumen compete w/ uric acid for
4. Lose (+) lumen potential HTN, CHF – 2nd line tx secrtion)
5. Mg, Ca reabsporption (thiazides #1) -Nephritis
6. Reabsorption of Na+
7.  Diuresis -Patient w/ sulpha allergies Drug interactions: digoxin
use ethacrynic acid (NOT (from the hypo-Mg)
*Loops = potent vasodilators furosemide)
by prostaglandins (prostag CI: GOUT,
blocked by NSAIDS)
Ethacrynic acid -Pt w/ sulfa allergies NO sulfa allergy
OTOTOXIC!!!!!!
Thiazide There is a basolateral Na/Ca pump (Na in, Ca out). So if the NCCT blocked, then there is less Na inside the cell,
so more will be pumped in via the Na/Ca (thus, more Ca exported into blood). The only way the Ca gets into the
tubule cell is via a Ca channel, which is PTH regulated. The effect of hypercalcemia has never proven beneficial
for osteoporosis because the calcium entery can only occur if PTH is there (which is only stimulated by low Ca).
There is NO change in blood/urine Ca or phosphate in osteoporosis anyways.

22
 Hydrochlorothiazide -Excreted by organic acid -HTN Hypokalemic metabolic
secretory system -CHF alkalosis
1. Block NCCT in DCT -Tx of kidney stones (if Ca Hyperglycemia*
2. Luminal Na & Cl stones) due to idiopathic Hyperlipidemia *
3. Diuresis hypercalciuria Ca does not Hyperuricemia
*Hypocalcemia (+) PTH, (Gs build up in renal tubule HYPERCALCEMIA
coupled) phorylates lumen -DOC in nephrogenic ALKALOSIS
Ca+ channel to Ca uptake diabetes insipidus loss of *From insulin release
Na at DCL will cause (K channel open
*Thiazides = potent Na/water at CD hyperpol of islets)
vasodilators via ATP dep-K+ -Avoid use in diabetics or
channel opening (remember *Note “thio” means sulfur in hyperlipidemias
minoxidil or dizoxide) the drug (think sulfa Drug interactions: digoxin
allergy) (toxicity from
electrolyte disturb)
Sulfa-Allergies
Indapamide Same Same No hyperlipidemia
Metolazone Similar to thiazides BUT unlike thiazides, also
effective at GFR < 30mL
K+ sparing K+ sparing diuretics will not enhance diuresis much because they act at the very end of the system, after most
of Na reabsorption has already occurred. Aldosterone inserts ENaC into the luminal membrane, causing passive
Na diffusion on luminal side. For each Na coming in, a K+ leaves the cell into the urine.
Triamterene Triamterene hepatic -Adjunct to K+ wasting HYPERKALEMIA esp w/
Amiloride metab & renal excretion diuretics B-blockers, ACE-I
Amiloride only renal -Lithium induced DI -ACIDOSIS
excretion
Triamterene – acute renal
*Block Na/K or Na/H failure (+indomethacin),
antiporters in principle cells kidney stones
of CD
Spironolactone Aldosterone receptor -Adjunct to K+ wasting -Same
antagonist diuretics -Antiandrogen: Female
-Only used in aldosterone hirsuitism, male
states (remember blockers gynecomastia
have zero efficacy) so no
effect in Addison’s disease
(b/c no aldosterone)
Eplerenone Aldosterone receptor Same -Same
antagonist (Kidney specific) -NO antiandrogen
Natriuretic Nesirtide 1. Activates guanylyl -CHF
peptide cyclasevascular SM B-type natriuretic peptide
relaxation in cardiac ventricles
2.tubular Na reabs & GFR released b/c of distension

UTERINE DRUGS
Drug type Drug Mechanism Clinical Use Side Effects
Mifeprestone -PGE-1 analog -Induction of labor upto 7wk.s Uterine bleeding, malaise,
(RU 486) -The morning after (72 hr) rash

CI: ectopic, COPD,

renal/hepatic, adrenal
failure, steroid therapy
PGE2/PGF2a Cause uterine contractions Induce abortion/labor -GI-nausea, vomiting,
Topical – ripen cervix diarrhea
-Hypotension-PGE2

23
 -Hyperthermia
-Bronchospasm

CI: asthma, COPD, CAVD

Oxytocin -Milk ejection -Lactation – nasal spray Rare
-Contraction in gravid uterus – -Induce/maintain labor
efficacy increases near term Antidote: fenoterol CI:
-Weak antidiuretic -Control hemorrhage -Fetal distress
(contraction) -Premature
-Test fetoplacental circulatory -Cephalopelvic
reserve misproportion
-
Engonovine -a-adrenergic, dopaminergic, DOC: induce p.p. contraction N/ abd pain
serotoninergic (hemorrhage control) H/a
-Lo dose – contract gravid uterus -Prophylaxis Dizziness
(promote labor/stop -Uterine atony (prolonged Tinnitus
hemorrhage) labor/big uterus) Hypertension
Bradycardia
Dyspnea
Toxicity
Ergotism – necrosis of
extremities
MI
Convulsions
Tocolytics Tocolytics inhibit uterine contraction.
Ritodrine B2 agonist-high cAMP to relax -Prevention of premature labor -Maternal tachycardia
smooth muscle of the uterus -Relaxes SM in uterus/resp. -h/a, vertigo
-3-6 hr. onset tract -Constipation
-Fetal tachycardia
Tocolytic indication: uterine -Hypoglycemia in fetus
bleeding, cramping (<20wk.), CI:
premature labor w/ dilation (36 -
wk.)
Mg++ sulfate -Prolonged distribution in deep -Tx pre-eclampsia seizure -Bradycardia, delayed AV
compartments -Hypomagnesemia – prevent fetal conduction
-Similar efficacy to B- hypotrophy -Hypotension
sympathomimetics -Adjunct tx of MI -Must monitor, BP, fetal
-Mg++ antagonizes Ca++ -Osmotic laxative HR, reflexes
-Antacid
Ca++ gluconate - antidote
Toxicity: ECG changes  resp.
depression  loss of corneal CI:
reflex -Renal failure,
myasthenia, AV block,
before delivery

ANTIHYPERTENSIVE DRUGS
Any drug that lowers blood pressure will cause a reflex tachycardia. Over a few days, the kideys will retain fluids via rennin secretion, which
may lead to edema. These side effects must be addressed when trying to treat hypertension. Also, any of the drugs affecting the
sympathetics will causes CNS depression and as well as many parasympathetic side effects.
Drug type Drug Mechanism Clinical Use Side Effects

24
Diuretics Thiazides See diuretic section -1st line against -Hyper-GLUC
hypertension -Hypokalemia – add K+ sparing if this is
-CHF –shows the greatest a problem
effect to dec. ventricular
hypertrophy, morbidity, and
mortality
-GFR < 30mL use
Metolazone
Loop & K Sparing See diuretic section -K+- sparing is 2nd line
-GFR < 30mL use loops
Presynaptic Reserpine Destroys vesicles CO, -Not used clinically anymore Denervation of sympathetics
blocking TPR (b/c NE in -60-80%  nasal congestion
periphery) (inhibit -Hypersecretion
VMAT?) -Bronchoconstriction
GI secretion, incontinence
-Mental depression, may promote
suicide
-Parkinsonism, ulcers
Guanethidine Accumulated into nerve Drug interactions: TCA or cocaine
ending by reuptake pump, (TCA block reuptake pump block
binds vesicles, preventing action of guanethedine)
release of NE from -Diarrhea, edema
vesicles
Stimulation of 2 causes a decrease of sympathetics outflow. This means there is a decrease TPR (symp on 1) and
2 AGONIST also a decrease HR (less NE on 1). No reflex tachycardias.
Clonidine Central acting -2nd line tx for HTN -Dry mouth
-CO -Tx withdrawl symptoms in -Sedation
- Peripheral resistance alcohol/heroin/benzodiazepi -Orthostatic Hypotension
w/ maintanence of renal en -Bradycardia
blood flow -Alcoholic delirium -AV block
-Relaxation of veins -Postmenopausal syndrome -Would never see rebound tachycardia
-Refractory diarrhea b/c sympath outflow
-w/drawal symptoms: Rebound
(High BP, headache, tremor, sweathing,
tachycardia)

Methyldopa -Similar to clonidine -Tx of HTN in pregnancy -Coombs test (+) receptors become
-Centrally acting b/c highly protein pound antigenic when bound to methyldopa
-ProdrugmethylNE (b/c similar to endogenous compnds)
-Perfusion pressure of kidney
renin  edema, so give w/ diuretic
Drug interactions: TCA (block re-
uptake, NE)
1 BLOCKER Prazosin -Competitively bocks a1 -Mild HTN -1st-dose Phenomenon weakness &
(t½ 3-4hr) receptors w/out a reflex -Low TPR syncope w/in 1hr. after 1st dose.
tachycardia -Low BP by relaxing arterial -Postural hypotension
Terazosin -No effect on A2 and venous smooth muscle -Dizziness, h/a
(t½ 12hr) -HTN -Reflex tachycardia
*Good effect on lipid -BPH -Tests for antinuclear factor (ANF)
Doxazosin profile: LDL & HDL may turn (+)
(t½ 22hr) -Urinary incontinence under strain
b/c relaxed sphincters
-BLOCKER Propanolol -LDL, TAGs, & HDL -Do not use in asthma, CI of nonselective BB: pregnancy,
Atenolol COPD, CHF, SA or AV node IDDM, (Blocks sympathetic response
Metoprolol abnormalities to hypoglycemia therefore pt could
Pindolol drop dead due to hypoglycemia with no
Esmolol symptoms)
Labetol
Carvedilol *-Blockers also suppres renin

25
VASODILATORS These drugs work by the Nitric Oxide (NO) pathway
(Direct acting) Hydralazine TPR via arteriole -Use in moderate to severe -Edema
dilation HTN Reflex tachycardia
-Blacks respond well -Drug induced SLE-like syndrome
Nitroprusside TPR via dilation of -Use in HTN emergencies -Cyanide toxicity (coadministered
BOTH arterioles & (only use acutely, 12-24h) thiosulfate)
venules
These drugs act by opening potassium channels, causing hyperpolarization of smooth muscle and dilation.
Minoxidil -Opens K-channels -Tx of SEVERE HTN Hyperglycemia (insulin release)
arteriolar vasodilation -Topical minoxidil used to
-NO? Tx baldness
Diazoxide -Given IV HTN emergencies -Hyperglycemia (from insulin)
-Opens K channels
arteriolar vasodilation
Ca Channel Blockers CCBs block the L-type of Ca channel (found in Heart & blood vessels). All CCBs vasodilate arterioles, but not all go into
the heart and decrease CO. All CCBs will be used for angina and hypertension treatment.
Verapamil Cause CO & vasodilate -Antiarrhythmic due to -No reflex tachycardia
Diltiazem arterioles nodal conductivity -Constipation (Verapamil)
-Verapamil most potent
on heart.
“--dipines” Vasodilate (especially -Hypotension reflex tachycardia
coronary)  TPR -Gingival hyperplasia (remember…
-very little effect on AV phenytoin & cyclosporin)
conduction
Fast onset/short Long acting, slow onset Long acting &  vascular  potency:
Verapamil Amlodipine selectivity: Isradipine
Diltiazem Felodipine Nisoldipine
Nifedipine
Diuretics Thiazides See diuretic section -1st line for HTN -Hyper-GLUC
-CHF –shows the greatest -Hypokalemia – add K+ sparing if this is
effect to ventricular a problem
hypertrophy, morbidity, and
mortality
-GFR < 30mL use
Metolazone
Loop & K Sparing See diuretic section -K+- sparing is 2nd line
-GFR < 30mL use loops
Angiotensin-II (AT-II) has two receptors, AT-1 and AT-2. The AT-1 receptors are found on blood vessels and are sitmulated through Gq
coupling, causing vasoconstriction. AT-1 receptors are also found the zona glomerulosa of the adrenal cortex and their stimulation results in
aldosterone secretion. The vasoconstriction raises TPR and increases the blood pressure back to normal. Angiotensin II causes EFFERENT
vasoconstriction at renal arterioles. Aldosterone causes the DCT or collecting duct to retain Na and water. These drugs will not need the
coadministration of diuretics
ACE-I Captopril See CHF -Protective of diabetic -Dry cough (bradykinin)
-Blocks formation of AT- nephropathy -Hyperkalemia (due to aldosterone)
II, -CHF -Angioedema
-Acute renal failure in renal art sten
ARB Losartan AT-1 receptor antagonist Same No cough
*NOT approved for CHF
Pulmonary Hypertension may result from left heart failure or may be a consequence of fibrousing diseases of the lungs. Conversely, it may be
a consequence of shunts, or it may simply be idiopathic.
ET-A BLOCKER Bosentan Endothelin (ET-1) is a Tx of pulmonary HTN CI: pregnancy (Teratogenic)
powerful vasoconstrictor
through ET-A and ET-B
receptors
-Bosentan blocks ET-A
receptors
PGI2 analogs Epoprostenol Anolog of prostacyclin Tx of pulmonary HTN CI: pregnancy (promotes aborption &
(PGI2), contraction of myometrium)
-Given via infusion pump

26
PDE-5 inhibitor Sildenafil Inhibit PDE-5 cGMP CI: nitrates
pulmon artery vasodilat

What if HTN and a comorbidity?

Angina Beta blocker, CCB
Diabetes ACE-I, ARB (avoid B-blocker + thiazide hyperglycemia)
Heart Failure ACE-I, ARB (or B-blocker)
Post-MI Beta blocker
BPH Alpha blocker
Dyslipidemia Alpha blockers, CCB, ACE-I, ARB (basically avoid B-blockers & thiazides)

ANGINA
Angina is an ischemic heart disease. There are two basic categories: angina of exertion (coronary atherosclerosis) and Prinzmetal angina
(vasospastic). Angina and heart attack only differ at the histological level. In heart attack, the tissue has infracted and died. Effective
treatment of angina must address the development of atherosclerosis. Risk factors for angina: hypertension, diabetes, hyperlipidemia, and
smoking. Vasospastic angina does not typically involve hyperlipidemias.
The strategy of treatment:
1. Increase oxygen delivery to the heart by dilation of the coronaies. This should reduce vasospasms. (Nitrates and CCBs)
2. Decrease oxygen requirement of the heart by TPR, CO, or both (Nitrates, CCBs, and Beta blockers)
Drug type Drug Mechanism Clinical Use Side Effects
B-blockers Propranolol -Decrease severity/freq of -Cardioprotective post-MI CI: vasospastic angina
Atenolol exertional angina (keep on for 2-3 yr.s)
Metoprolol -Ineffective in unstable Remember other CI:
-(-) Inotropic effect Angina associated w/: -Astham/COPD
-(-) Chronotropic effect -Exertional -CHF
-Decreased sys BP w/ exercise -Diabetes
NET EFFECT: decrease heart
O2 demand
Ca Channel blockers Nifedipine Binds serum proteins -DOC for vasospastic angina Dihydropyradines
(dihydropyridine) -Hepatic metabolism, renal (Nifedipine) -Dizzy, h/a, flush, digital
secretion dyasthesia, peripheral edema,
Verapamil -Blocks L-type Ca++ receptors – All CCBs can be used for constipation, reflex tachy
Diltiazem cardiopressant & vasodilation angina, only nifed for vasosp
-Decrease afterload Verapamil, diltiazem –
- risk of MI in HTN patient bradycardia, slow SA & AV
Nitrates In an endothelial cell, there is Nitric Oxide synthase, which is turned on by phosphorylating reactions when bradykinin,
serotonin, and ACh bind. Nitric Oxide synthase will produce NO, which will diffuse into the vascular smooth muscle.
Nitric Oxide will stimulate the production of cGMP leading to dephosphorylation of the myosin light chain (i.e.
relaxation). Nitroglycerin (R-O-N=O) require cellular cysteine to be metabolized to a nitrosothiol, which will donote
NO. Note: people with angina may have atherosclerosis and diabetes, both of which may decrease penile function. A
side effect of nitrates also causes some dysfunction, BUT sildenafil is contraindicated.
*Review the mechanism of smooth muscle contraction and relaxation and drugs affecting them (Kaplan 2008 p.109).
VERY complicated

27
 Nitroglycerin -Relax coronary arteries
-Venodilate  preload of
heart less contractility needed
 less work done by heart
*(Some arteriolar dilation at
doses)
-Decreased myocardial demand
PK: Buccal, IV, transdermal,
sublingual
-Decrease preload
Isosorbide PK: only PO, extended release
dinitrate
(& mononitrate)
Amyl Nitrites Extremely volatile at room temp
-Tx of acute angina
Chronic management of
angina (preventive)
No longer used for angina
-Tx of CN- poisoning
-Flush, headache (vasodilat)
-Orthostatic hypotension
-Doses arterial vasodil
reflex tachy & edema
-Methemoglobinemia
-Tachphylaxis (repeated
use uses sulfhydryl groups)
-Dizziness, weakness,
cerebral ischemia
CI: Sildenafil
(cardiovascular toxicity)
Methemoglobinemia
Abuse

CONGESTIVE HEART FAILURE

DIURETICS Loops Tx CHFassociated backward
failure & pulmonary edema
Spirinolactone Improves survival Remodeling in CHF
ANF analog Nesiritide Recombinant ANF (recombinant human Tx acutely decompensated CHF
B-type natriuretic peptide (rh BNP)
cGMP vasodilation
ACE-inhibitors Captopril -Renal elmination -1st line drug—Hypertension -Hypotension
-Angiotensin II Antagonist -CHF – decrease sudden death, -Dry cough/bronchospasm
-Decreased vasoconstriction, NE, progression, morbidity, (bradykinin)
aldosterone -MI – if started in preinfarct -Angioedema
 Bradykinin  vasodilation period -Hyperkalemia
-No, Reflex tachy, no change in CO, No -Progressive renal disease -Proteinuria
Na/H2O retention -Dysgeusia (taste)
 sympathetic tone -Less efficacious in Black -Hypercalcemia
Vasodilates venous blood vessels to Patients. CI – renal artery stenosis, renal
decreased pre-load and aterioles to failure, pregnancy fetal
lower TPR. Decreased Na/fluid -1st DOC-first line of choice in hypoperfusino oligohydramnios),
retention the Rx of CHF w/ diuretics hx of angioedema (COPD)
Toxicity – hypotension w/o
tachycardia
Interactions: NSAID (bradykinin
pthway), K+ spare/waste diuretic,
digoxin, lithium levels
Enalapril -Enalapril is prodrug (hepatic -More potent than captopril,
(enalaprilat) conversion) slower onset, longer action
Fosinopril -Enalaprilat – IV for HPT emergency
Moexipril -Fosinopril, moexipril – only hepatic
INOTROPES Diuretics are often on board in a patient with CHF. All diuretics will distrurb electrolytes. All diuretics (except K+ sparing) will
decrease K+, which increases digoxin toxicity. Loop diuretics can cause hypomagnesemia. Thiazides may cause hyper-Ca. Low Mg and
high Ca cause increased contractility, which may precipitate arrhythmias if on digoxin.

28
 Digitalis Inhibits cardiac Na/K ATPase -CHF -Arrhythmia (any type)
(Digoxin) intracell Na+, Na/Ca exchange -Tx arrythmias: supraventricul -GI distress: anorexia, vomiting,
intracell CaCa release from SR tachycardia ( AV conduction) diarrhea (abs of nutrients follows
contraction force *Do NOT use in Wolf Parkinson Na+ gradient, which is now blocked)
White syndrome -Neurologic- seizures (also due to
Indirect effect: Na+ block), “digitalis delirium”
-Inhibits neuronal Na/K ATPase Non-indicated (headache, fatigue, neuralgia,
results in vagal and sympath -Myocarditis, cor pulmonale hallucinations, and mental sx)
stimulation -Uncontrolled HTN -Visual disturbances  halo’s,
-Decrease AV conduction (prolong -Bradyarrhythmias particularly everything yellow
ERP) -Gynecomastia – rare
Tx of Digoxin toxicity:
*Long half life need loading dose - or withdraw drug Precipitating factors for toxicity
-Monitor dig & K+ levels, EKG -Hypokalemia
ECG -Correct electrolyte -Hypo Mg++, or hyper Ca++
Atria- P changes -Arrhythmias lidocaine -Quinidine & verapamil displace
AV – PR prolonged (heart is more depol than digoxin from binding sites
Ventricles – short QT, depressed ST, normal, & lidocain binds depol), -Sympathomimetics may
T contractility arrythmias
-Mg++, K+(take to normal hi), -Resp. disease – increase digoxin
 Morbidity but no effect on -Temporary pacemaker response
mortality -Digitalis Ab ->65, skinny, fever
-Acid base imbalance
Amrinone (AKA Phosphodiesterase inhibitorscAMP -Like coffee it relaxes vascular Milrinone has actually shown to
inamrinone) which Ca current contractility… and bronchial smooth muscle have an mortality
(Remember that NE on 1 causes -Never actually proved beneficial
Milrinone cAMP)
Dopamine Sympathomimetics cAMP PKA -Acute CHF b/c chronic CHF See autonomics
Dobutamine phosphorylates Ca-channelsCa  recepters are desensitized -Use with caution in atrial fib.
current into heart contractility. -Shock
Also has some vasodilating effects -BP up with perfusion to
Kidneys,
ARB (AT-II Losartan Like ACE-I: decrease -Hypertension NO COUGH b/c there is no
Receptr Blckr) vasoconstriction, NE release, levels of bradykinin
aldosterone secretion -It may be fetotoxic

Unlike ACE-I: no affect on

degradation of bradykinin

Antiarrhythmic Drugs
NOTE: these are some of the harder arrhythmias to understand:
 Atrial tachycardias are divided into those originating from the node and those that do not. If it comes from the node,
use B-blocker or CCB to slow nodal conduction. If not from the node, use something that slows AV nodal conduction
(e.g. adensine). Atrial tachycardias not from the SA node (but at other sites in atria) can be caused by CAD, COPD,
increased catecholamines, alcohol and digoxin.
 Supraventricular tachycardias (PSVT) refer to those SVT that have a sudden almost immediate onset. A person
experiencing PSVT may see their heart rate go from 90 to 180 beats per minute instantaneously. Because sinus
tachycardias have a gradual (i.e. non-immediate) onset, they are excluded from the PSVT category. PSVTs are usually
AV nodal reentrant tachycardias.
 AV nodal reentrant tachycardia (AVNRT) is also sometimes referred to as a junctional reciprocating tachycardia. It
involves a reentry circuit forming just next to or within the AV node itself. The circuit most often involves two tiny
pathways one faster than the other, within the AV node. Because the AV node is immediately between the atria and
the ventricle the re-entry circuit often stimulates both, meaning that a retrogradely conducted p-wave is buried

29
 within or occurs just after the regular, narrow QRS complexes.
 Atrioventricular reentrant tachycardia also results from a reentry circuit, although one physically much larger than
the AVNRT. One portion of the circuit is usually the AV node, and the other, an abnormal accessory pathway from the
atria to the ventricle (e.g. Wolff-Parkinson-White syndrome with the Bundle of Kent).
Class Drug Mechanism
Na+ CHANNEL
BLOCKERS
Ia Quinidine -Binds to open, activated
Na-channels to prevent Na
influx & prolong APD
(prolong phase 0)
-Block K+ channel (prolong
AP & ERP)
-Antimuscarinic– (low doses)
paradoxical AV conduction
b/c  sympathetic control
- Blocker (high
concentration) hypotens
reflex tachycardia (arrhth)
*Quinidine = weak base, &
antacids abs toxcity
*ANY DRUG prolonging
depolarization will be a risk
for torsade d’pointes (this
includes all anti-M drugs)
Procainamide Similar to Quinidine
Dysopyramide -Ischemic tissue is more
depolarized than normal
tissue & closer to threshold
-Prolongs the refractory
period
-Block active Na+ channel
-Less antimuscarinic
-1 block? (Kaplan says no)
-Acetylated  (NAPA)
(blocks K+ channels)
Ib Lidocaine -Block inactive/refractory
Na+ channels & shorten
APD (phase 0) due to
block “window” Na current
-Inactive channels more
likely to be found in
ischemic tissue (since partly
depolarized) drug
preferentially goes to
ischemic tissue
EXTENSIVE 1ST PASS
METABOLISM due to
metabolism by amidases
(So only given IV)
Indications Adverse Effects
*Tx of Atrial fib, need Toxicity
prior digitalization -Cinchonism (blurred vision,
(digoxin slows AV nodal ringing in ears, headache,
conduction counteracting altered color perception, nausea,
the antimuscarinic vomiting, diarrheaall referr
effects of quinidine) to the drug’s autonomic effects)
-Contractility
-Supraventricular -Proarrhthmic: block M symp
arrhythmia control of heart HR
-DOC for Chronic
Ventricular Tachycardia ***Toxicity, wide QRS***
-Wide QRS (b/c anti-M & more
-Depress automaticity cells depolarized at a period of
(ectopic pacemakers) time)
-Depress conduction & -Long QT & changed T
excitability (esp. -Prolong PR intervaltorsade
depolarized tissue) d’pointes
-Antimalarial Drug interactions: hyperkalemia,
quinidine displace digoxin from
tissue binding sites
Procainamide – 2nd line Procainamide
acute MI-associated -Drug induced SLE
vent. Arrhythmias -Agranulocytosis,
(lidocaine – 1st) -Antimuscarinic: aggravate
glaucoma, urinary retention
-Mental confusion/ psychosis
Disopyramide
-Negative inotropy,
-Cardiac failure w/o existing
myocardial dysfxn
-Atropine-like systemic AE
Suppression of arrhyth -Exacerbation of arrhythmia
assosociated w/ -SA stands still in pt. w/ MI
depolarization: -CNS toxicity @ high dose
-DOC Post-MI
-Open heart surgery Interactions
-Digoxin toxicity -Agents enterfering w/ hepatic
-CNS toxicity perfusion or P450-
-DOC for ventricular
tachycardia & fibrillation Least cardiotoxic
after cardio-conversion
-Not for long-term
prophylactic post MI
*Not useful in atrial
arrhythmias
30
 Tocainamide Similar to lidocaine Same as lidocaine -Frequent @ therapeutic dose
Mexilitine Orally active (used in -Neurologic: N, tremor, blurred
chronic dosing) vision
-Allergic: rash, fever,
agranulocytosis
Phenytoin
Ic Flecainide -Acts on ALL Na channels -Life threatening *MOST pro-arrhythmogenic
Propafenone conformations refractory ventricular (15% of patients die)
Moricizine -NO effect on APD arrhythmias ONLY -Visual disturbances
-NO ANS effects -Use only orally for atrial -Increases mortality post-MI tx
-Slow dissociation from Na+ arrhythmias of PVC
channel in recovery -Pretreat w/AVN blocker
II -BLOCKERS: They are used to control supraventricular tachychardias like atrial fib and atrial flutter. Their
mode of action is on NODAL tisussue.
Propranolol Decrease Phase 4 -Recovery from MI  Hypotension
Acebutol (1) -Depresses SA-node freq  prevent sudden death Aggravation of CHF
Esmolol (1) sinus bradycardia (post -MI prophylaxis) Asystole
Satolol (1,2) - Automaticity of purkinje Propanolol= very lipid soluble 
- Conduction AV-node -Control SVT & A-fib CNS depression
-Negative ionotrope the (b/c class II affects
reason -blockers are good nodal tissue, the atrial CI – diabetes, vasospastic
prophylaxis post-MI, beats must go thru AV) disorders (e.g asthma,
prevent heart working too -Exercise/stress induced prinzmetal angina)
hard vent. Arrhythmias
-Suppress ectopic -Ischemic HD/ angina
ventricular depolarization -In ICU give esmolol
-Hemodynamic activity (short t ½ IV)
Metoprolol DOC in pregnancy
III K+ BLOCKERS: Used only with life threatening ventricular arrhythmias (i.e. wide QRS) that don’t respond well
to class I, but all of this is debatable and changes often.
Amiodarone -Blocks K+ channels APD -CHF w/ <30% EF -Pulmonary Fibrosis up to 45%
-Low dose for atrial fib of pts
-Blocks Na-channels (Ia) -Supraventricular -Photosensitivity
Arrhythmia -“Grey man syndrome”
-Mostly effects -IV for acute ventricular -Blue skin discolor (“smurf
purkinje/ventricular (long tachycardia skin”) b/c of iodine rxn w/
plateau) -Anti-anginal starches in skin
t½ = 30-120 days steady -Corneal depositis
state @ 8-10mo (use *Amiodarone is a class Ia, -Hepatotoxicity
loading doses) II, III, IV, so no -Hyperthyroidism
matter what arrhythmia QT (but Torsade rare)
“iod” in amiodarone means it it should have an effect
has iodine Drug interaction – digoxin,
warfarin, quinidine, theophylline
Ibutilide Used for emergencies QT (risk of Torsade)
CI: if K or QT
Sotalol Prolongs repol (phase 3) Tx/prophylaxis severe -Postural Hypotension
Nonselective 1-blocker ventricular arrhythmias -Proarrhythmic
(class II) esp those not responding -Torsades des pointes
-Renal excretion to class Ib -CNS depression
(unchanged) -Atrial arrhythmias *Before starting sotolol, must
hospitalz for 72 hrs & make sure
patient not a fast responder
IV Ca+ CHANNEL BLOCKERS: The main clinical use will be that of supraventricular tachycardias (like B-blockers).
Their mode of action is on NODAL tissue (the depolarization in nodal tissue is due to Ca entry).

31
 Verapamil -Blocks L-type Ca++
Diltiazem channels
Bepridil -Lg effect on AV conduction
due to phase O of nodal
conduction (also some
effect on phase 4)
DOC in atrial -Well tolerated
fibrillation/flutter -Constipation
-AV block (esp w/ added AV
-Re-entry SVT block of B-block & digoxin)
-SVT -Verapamil displaces digoxin
-Ischemic heart disease from tissue binding sitesmore
& HTN dig toxicity
-Negative inotropic effect

-CI: depressed cardiac function.

Other These are not classified as antiarrhythmics, but they have a role in management.
Adenosine Adenosine receptors in
heart nodal tissue are Gi
coupled (cAMP)SA/AV
nodal conduction
-Enhance K+ conductance
-Inhibits cAMP-mediated
influx  hyperpolarization
(esp. AV node)
-Degraded in seconds by
adenosine deaminase
Atropine Muscarinic antagonist
Magnesium -Functional Ca++ antagonist
-K+ channel block
Treatment of Torsades des pointes:
 Correct hypokalemia
 Correct hypomagnesemia
 Discontinue drugs that prolong the QT interval
 Attempt to shorten APD with drugs (e.g. isoproterenol) or electrical pacing
-DOC for Tx of -Flushing
paroxysmal ventricular -Bronchoconstriction (Gq)
tachycardia (90% dyspnea
effective)  stops heart
for a second -A-fib, V-fib
-Potent vasodilator
-Emergency management -Adenosine is antagonized by
theophyline (so theophyline
would  nodal conduction)
Brady-arrhythmias to
vagal tone
Tx for torsades des
pointes
-Tx for digitalis induced
arrhythmia
-prophylaxis for
arrhythmias in acute MI
Drugs causing Torsades:
 K+ channel blockers (class
IA & III)
 Antipsychotics
(thioridazine)
 TCA’s

Things u shouldn’t do

Disease Contraindicated Reason

COPD, asthma B-blockers Induction of bronchospasm
ACE-I Induction of cough, use AT1
Bradycardia Clonidine Aggravation, risk of Adams-Stokes
B-blocker syndrome
Verapamil/diltiazem
Diabetes Thiazides Reduced glucose tolerance
B-blockers Blunt sx of hypoglycemia
Gout Thiazides Reduced excrfetion of uric acid
CAD Hydralazine Provocation of angina (reflex
Prazosin tachycardia)
Minoxidil
Peripheral artery occlusive disease B-blockers Aggravation/manifestation
CHF Ca++ antagonist Negative inotrope
B-blockers
Renal failure Amiloride, Triamterene May cause hyperkalemia
Spironolactone
ACE-I Plasma concentration up, side effects
32
 CHF
Sx/problem Approach
Fatigue Rest, + intotrope
Edema Salt restriction
Diuretic
Digitalis (+ inotropre)
Dyspnea Diuretic (thiazide, loop)
Congestion Nitrovasodilator
Poor cardiac + Inotrope, digitalis
contractility
 preload/afterload ACE-I
Ang-block
Ven-vasodilators
Cardiac tissue ACE-I
remodeling Ang-block
B-block
Spironolactone
Irreversible heart Transplant
failure

33
 ANTIBIOTIC CLASSIFICATION
Cell wall damage/syntheisis Penicillin
inhibited Cephalosporins
Monobactams
Bacitracin
Vancomycin
Cycloserine
Cytoplasmic membrane damage Polymyxins
or sythesis inhibited Polyene antibiotics
Inhibit synthesis/metabolism Quinolones (DNA Gyrase)
of nucleic acids Rifmapin
Nitrofuranotoin
Nitroimidazoles
Inhibit protein synthesis 30S
Tetracyclines
Spectinomycin
Aminoglycosides (e.g. Neomycin)

50S
Macrolides (e.g. Chloramphenicol, Erythromycin)
Clindamycin
Modify energy metabolism Sulfonamide
Trimethoprim
Dapsone
Nucleic acid analogs Zidovudine
Ganciclovir
Vidarabine
Acyclovir

ANTIBIOTICS
General principles:
For seriously ill patients, use bactericidal drugs because their immune system cannot clear the organism
For drugs that act by concentration dependent killing (aminoglycosides, fluoroquinolones, and carbapenems), once daily dosing can achieve the
high levels.
For drugs that act by time dependent killing (B-lactams, glycopeptides, macrolides, clindamycin, and linezolid), treatment should be via
continuous infusion or multiple daily dosing.
Note: bacteriostatic vs. bacteriocidal is a little outdated, but listed anyways. Many bacteriostatic become bacteriocidal at higher doses
Class Drug Mechanism Clincal Use Side Effects

34
 SULFONAMIDES Sulfonamides were the 1st drugs used to cure or prevent systemic infections, but since the penicillins they have become less
useful. Sulfonamides are derivates of PABA. They are bacteriostatic. Sulfonamides are acetylated by the liver (actually
become less water soluble) and then excreted by the kidneys. Drink a lot of water to avoid renal stones. Sulfonamdies inhibit
RAPIDLY dihydropteroate synthase. Generally, sulphonamides are DOC for PCP infections of AIDS. Sulfonamides inhibit gram (+) and (-),
AB nocardia, chlamydia, and some protozoa. Ricketsiae are NOT inhibited but are actually stiulated in their growth.
SO
RB PABA(Dihydropteroate synthase) DIHYDROFOLIC ACID (dihydrofolate reductase) THF  purines/DNA
ED:
Dont give sulphonamides to neonates (no conjugating rxns) & the drugs will displace bilirubin from albumin. Sulphonamides are
used for E. coli and are soluble enough to cross BBB  but don’t give for neonatal E. coli meningitis.
Sulfisoxazole -Short acting (4-8h), rapidly -Nocardia (immunocompromised) -Hypersensitivity
absorbed Pneumonia/brain abcess (Stevens-johnson)
-Trachoma -Crystalluria, hematuria
-Lympphogranuloma venereum -Hemolytic anemia (in G6PD
Short acting -Tx of UTI (sulfisoxazole + def)
phenazopyridein) -Kernicterus
-1st line Tx against Toxoplasma -High protein binding
(sulfisoxazole + pyrimethamine) displacement of drugs from
binding sites (warfarin,
tolbutamide)
-Phototoxicity
-Drug interaction (292
lippencott)
Sulfadiazine -Short acting, rapidly Above
absorbed - Tx of toxoplasma (sulfadiazine +
pyrimethamine)
Sulfamethoxoazole -Intermediate acting (12- Above + resp. infection in combo
(SM 18h) -Neisseria
X) -Gram (–)
Intermediate
SMX + trimethroprim = BACTRIM’s spectrum:
Bactrim for UTI/resp. tract -DOC & prophylaxis of
Pneumocystis carini
-DOC for nocardia
-Toxoplasma
- Complicated UTI
-TB (part of tx)
Sulfadoxine -Long acting (7-9 days) Prophylaxis for malaria
-Used w/ pyrimethamine
Sulfasalazine -In the GI broken down to -Tx IBD & RA -Reversible infertility
Long 5-aminosalicylate (anti- Derivatives of 5-ASA: -Crystalluria (esp at acid pH)
inflam) & sulfapyridine 1. Pentasa – controlled relase
POORLY ABSORBED formulation delivering to entire
POORLY absorbed GI tract including small bowel
2. Asacol – delayed delivery to
terminal ileum & beyond
3. Olsalazine – new prodrug, coupled
5-ASA split by intestinal bacteria
4. Rowasa – Rectal enema and
suppositories, used for
proctosigmoiditis
Sulfacetamide -Opthalmic infxns (e.g. trachoma)

Mafenide Carbonic anhydrase -Burns (topical) use for short -Irritation

SPECIAL USES Inhibitor period & only localized area -Pain
-Acidosis (w/ extensive use)
Silver sulfadiazine -Prevents infection of burnt -Well tolerated (minimal SE)
surfaces and chronic ulcers -Rash, itch, allergy

35
 Trimethoprim Inhibits DHF reductase in Used w/ sulfamethoxazole BMS & enterocolitis
bacteria -Megaloblastic anemia
TMP-SMX oral -PCP, most community acquired
MRSA, toxoplasma
Pyrimethamine Inhibits DHF reductase in BMS & enterocolitis
protozoa
FLUORO- Inhibit replication by inhibiting topoisomerase II & IV (block A subunit of DNA gyrase). DNA gyrase normally introduces
QU negative supercoiles. Quinolones enter cells easily via porins and are used to treat INTRACELLULAR pathogens (e.g. legionella
IN or mycoplasma). Good against S.pneumo + atypicals so, great for pneumonia
OL -Fe and Ca limit absorption due -UTI -Articular damage (children)
ON to chelation –Gram (–)’s -Tendonitis/tendon rupture
ES -STD’s/PID -Photosensitivity
-Cutaneous, soft tissue (except -GI irritation
nalidixic acid) & bone infections -Rash
(osteomyelitis) -Convlsions, N/V
-Respiratory –) except nalidixic -All quiniolones QT interval
acid) -May cause increase
-Bacterial enteritis intracranial pressure in kids
-Diarrhea - [plasma] of theophylline
CI: pregnancy, kids
Nalixic acid Narrow spectrum UTI
Norfloxacin
Ciprofloxacin -Pseudomonas assoc. w/ cystic
Ofloxacin fibrosis
-Enterobacteriacea & other
gram (–) bacilli
-Synergistic w/ penicillins
-Acute diarrrheal enteric
pathogens (grm – rods)
-Gonorrhea (2nd line after
ceftriaxone)
-UTI’s comp/uncomp
Lomefloxacin -More gram (+)
-Some strains of MRSA &
enterococci
-Fewer gram (-)
Moxifloxacin -Broadest spectrum *Elminated via biliary -Moxiflox risk of long QT
-Anaerobes
OTHERS Methenamine -Liberates formaldehyde w/ UTI -Gastritis
man urinary pH <5.5 -Chemical cystitis
dela -No affect at alkaline pH -Hematuria
te -Metabolite caustic to bugs in -Painful/frequent micturition
(Methenamine + urinary system. -DO NOT GIVE W/
mandelic acid) SULFONAMIDES – insoluble
complex (crystaluria)
Nitrofurantoin -Bacteriostatic UTI’s – E. Coli -Interstitial pulmon fibrosis
-U/k mechanism (reactive -Hemolytic anemia G6PD
intermediates damage DNA) def.
-Turns urine brown -Peripheral neuritis
-Cholestatic jaundice
-GI irritation
Phenazopyridine -Used along w/ urinary -Urinary analgesic (takes care of -Red/Orange urine
antiseptics burning piss) -Overdosage can produce
-No antibacterial effects methemaglobinemia

36
 CELL WALL Penicillins are BACTERICIDAL drugs that inhibit cell wall synthesis. They bind to penicillin binding proteins (PBP), which
IN inhibits transpeptidase enzymes (responsible for the linking/cross linking of peptidoglycans). This causes the activation of
HI autolytic enzymes. Penicillins are effective against actively growing microbes, but ineffective against microbes that do not
BI have a cell wall (e.g. mycoplasma). Betalactamase enzymes are bacterial enzymes that break the betalactam ring. Penicillins
TO cause TIME DEPENDENT killing, where drug is directly related to the time above MIC. B-lactams are synergistic with
RS aminoglycosides.

PENICILLINS Generally, all penicillins are water soluble (exceptions: nafcillin, ampicillin), thus renal excretion and need dose reduction in
renal disease. Tubular secretion can be blocked by probenecid so that high concentrations can be achieved. Aquired
resistance to penicillins by plasmid transfer has become a serious problem. Most of the penicillins are incompletely absorbed
after oral administration, and they reach the intestine in sufficient amounts to affect the composition of the intestinal
flora. However, amoxicillin is almost completely absorbed. So, amoxicillin is NOT appropriate therapy for the treatment of
(for example) shigella or salmonella derived enteritis. Also, penetration for penicillins is generally good, although no
penetration into the CNS, unless inflammation has opened pores in the BBB.

Penicillin G -Acid labile, so give IV or IM Serious life threatening disease Jarisch Herxheimer rxn
(Benzyl penicillin) -SHORT DURATION ACTIVE AGAINST:
-Poor CNS effects (unless -Strep pneumo (although
meningitis) resistance)
-90% excreted by renal -Strep pyogenes
1st generation secretion, 10% by glomerular -Strep viridans
-Bacillus anthracis
-Corynebacterium diptheriae
-Syphillus (1’ and 2’)
-Neisseria gonorrhoeae
-Neisseria meningitides
-Clostridium perfringens
Penicillin V Given PO b/c acid stable Prophylaxis/mild infections -Not used for Tx of
bacteremia b/c of its
minimum bactericidal
concentration
Procaine penicillin Slo abs. Lasts 12-24 hr.s Gonococcal infections
Benzathine penicillin Abs. Very slow lasts 2 wk.s
Usually suppository form
Cloxacillin Penicillinase resistant -Very narrow spectrum Interstitial nephritis
Oxacillin -Tx penicillinase producing Staph (Methicillin)
Nafcillin Nafcillin is elimited primarily via
Dicloxacillin the biliary route. “Naf for Staph”
2nd generation Methicillin
Amoxicillin -Commonly given w/ Beta -Broad spectrum -Pt. w/ mono will develop
Ampicillin lactamase inhibitors (sulbactam (Similar spectrum to penicillin G, rash when given Ampicillin
& clavulinic acid) but includes some gram -) -Inactivation a problem b/c
-Widely used in Tx of of plasmid mediated
3rd generation Not water soluble respiratory diseases penicilliniase (typically E.coli
-Amoxicillin is completely and H.influenza)
absorbed from GI, so don’t tx GI
infections
Active against:
-Ecoli
-H.influenza
-Proteus
-Salmonella typhi
DOC for Listeria (Ampicillin)
Piperacillin -Tx Pseudomonas infxn Carbenicillin & Ticarcillin
Mezlocillin -Effective against many gram (-), causes platelet dysfxn
Carbenicillin but NOT Klebsiella
Azlocillin (constituative penicillinase)…add
4th generation Ticarcillin clavulanic acid

37
 Most cephalosporins are eliminated through the kidney (a few exceptions). Cephalosporins have ADVERSE EFFECTS:
been divided into 4 generations. As the generations progress, there is: -Cross sensitivity w/
5th generation   Gram (+) coverage penicillin in 10%
 Gram (-) coverage -Cefamandole, cefotetan,
  CNS penetration cefoperazone cause
CEPHALOSPORINS   Resistance to -lactamase hypoprothrombinemia
(inhibit Vit K dep factors)
Cephalosporins are INEFFECTIVE against LAME: & disulfiram-like rxn (due
L= Listeria monocytogenes to MTT side chain (“azol”)
A= Atypicals (mycoplasma, legionella, C. pneumonia) -Nephrotoxicity (doses)
M= MRSA -Hemolytic anemia (rare)
E= Enterococci
PARENTERAL Water soluble Don’t cross -Good activity against gram (+)
Cefazolin into CSF -Modest activity against Gram (-)
Cephalothin
Cephapirin Active against PEcK:
Cephradine *Note: ”ph” in name = 1st Proteus
1st generation generation E. Coli
ORAL Klebsiella
Cephalexin Cefazolin – long half life, used Moraxella
Cefadroxil in surgery prophylaxis
Cephadrine
PARENTERAL gram (-), gram (+) Active against HEN-PEcKS
Cefamandole* -H. influenza
Cefotetan None enter CSF EXCEPT: -Enterobacter aerogenes
Cefonicid -Cefuroxime -Neisseria
Cefuroxime sodium -Cefaclor -Proteus mirabilis
Cefoxitin -E. coli
2nd generation Ceforanide *Eliminated via biliary (for pts -Klebsiella
w/ renal problems) -Strep pneumo & pyogenes
ORAL -Tx B. fragilis (Cefoxitin, but has
Cefaclor little activity against H. influenza)
Cefuroxime axetil
PARENTERAL *Eliminated via biliary (for pts -Often used w/ a macrolide to cover -All penetrate CNS
Cefoperazone* w/ renal problems), i.e. NOT atypicals in community aquired EXCEPT cefoperazone
Ceftriaxone* water soluble pneumonia (does not cross enough to
Ceftazidime -DOC for Gonorrhea (IM fight meningitis)
Cefotaxime CNS cefotAXime, Ceftriaxone single dose)
Ceftizoxime ceftriAXone -DOC in meningitis (Cefotaxime,
Moxalactam --Think of an AX to the head Ceftriaxone)
that chops meningitis. - Tx B. fragilis (Cetizoxime)
ORAL -Ceftazidime has pseudomonas
3rd generation Cefiximne coverage
Cefepine -Extended spetrum -Tx gram (–) resistant bacilli to
- Stability to beta- 3rd generation cephalo’s
lactamases -Effective against pseudomonas

4th Generation

38
OTHER CELL WALL Cycloserine -Structural analog of D- -Tx TB resistant to streptomycin, -Psychoses
SY alanine competitively isoniazid, PAS -Delirium
NT inhibits conversion of L- -Atypical mycobacterium (MAC, -Confusion
HE alanine to D-form and linkage kansasii) often sensitive -H/a
SI (stage 1 of cell wall synth) -2nd line in TB & CNS nocardia -Convulsions
S (1st= sulfa) -Tremors
IN Bacitracin Inhibitor of the isoprenyl -Topical use only (ointment & drops) -Toxic for systemic use
HI phosphate (stage 2 of cell wall -Tx furunculosis, impetigo, -Nephrotoxicity
BI synth) pyoderma, carbuncle, abscesses
TO -Tx suppurative/infected corneal
RS ulcers
Vancomycin -Inhibits transglycosylase by -Tx MRSA (IV Vanco) -Must be given slowly!!
interfering w/ D-alanyl-D- -Tx Enterococci -Red man syndrome (type-
alanine cell wall precursor -Backup for C. difficile 1 HS causing vasodilation
units (stage 3 of cell wall (pseudomembranous colitis) give from histamine i.e.
synth) Flagyl 1st extreme flushing)
-SERIOUS staph infections -Pain, chills, rash, fever
-Does NOT enter CNS -Hypotension
-Water soluble Resistance: -Nephrotoxic
1. Cytoplasmic protein that reduces
-Systemic effects only when the access of the drug to the FONT
given IV site of its action Flushing
-Oral form is not absorbed 2. VRE use D-alanyl-D-lactate Ototoxic
from GI as a precursor Nephrotoxic
Resistant VRSA & VRE give Thrombophlebitis
Daptomycin &/or quinopristin/
dafopristin & linezolid
Teicoplanin -Inhibits bacterial cell wall -Similar spectrum to Vanco
synthesis -Tx MRSA & E. Fecalis
Aztreonam MOA: same as penicillins; Tx of gram (-) rods only (give IV) No cross-allergenicity w/
resistant to -lactamases penicillins or cephalosporin
Carbapenems are resistant to -lactamases, active against most gram (-) and (+) including anaerobes (except MRSA and VRE).
They are NOT active against intracellular bacteria. They have a structure very similar to the penicillins, but they have sulfur
in the structure. Carbapenems are thus far the only antibiotic capable of inhibiting the L,D-Transpeptidases. They are
administered IV in the hospital for SEVERE infections.
Imipenem Cilastatin is not an antibiotic Seizures (50% of pts)
(+ Cilastatin) but a peptidase inhibitor that
protects imipenem from renal
Monobactam breakdown
Ertapenem
Meropenem
Carbapenems Doripenem
MEMBRANE Polymyxin B -Competively replace Mg++ and
INHIBITORS Polymyxin E Ca++ from negatively charged
P groups on membrane lipids
disrupts cell membrane

PROTEIN SYNTHESIS INHIBITORS

39
AMINOGLYCOSIDE Aminoglycosides are bactericidal, accumulated intracellularly via an oxygen-dependent uptake (do not work against
anaerobics). Use aminoglycosides to kill GRAM NEGATIVE RODS.
 Concentration dependent killing & are bacteriocidal.
 Inhibit the formation of initiation complex (30S)
 Water-soluble (no surprise w/ glycoside, ie sugar), and they are excreted unchanged in the urine thus,
[aminoglycoside] in renal disease
 Synergistic with -lactams
 Poorly absorbed from the GI tract.
 Limited penetration into CSF
 Ototoxicity (esp when used w/ loop diuretics) & nephrotoxicity (esp when used w/ cephalosporins). Other side effects
include: 1) neuromuscular blockade from inhibiting the release of ACh (reverse w/ infusion of calcium gluconate or
neostigmine) and 2) contact dermatitis. Toxcity may be enhanced by loop diuretics
 There is some partial cross-resistance among them. The main mode of resistance is the production of conjugating
enzymes.
Streptomycin -Not very effective against gram (-) -Optic nerve dysfunction
-Tx of TB (chronic use)
-Tx of Enterococcal infections
(Penicillin G + streptomycin)
-DOC for bubonic plague &
tularemia
Neomycin Used topically (very toxic); Adjunct in hepatic encephalopathy -Contact dermatitis
can be used orally sometimes to kill off gut bacteria systemic -Found over the counter in
not absorbed to kill gut ammonia the triple antibiotic
flora ointment (e.g. Neosporin)

Amikacin -Resistant to aminoglycoside -Pseudomonas coverage

inactivating enzymes
Netilmicin -Resistant to aminoglycoside
inactivating enzymes
Tobramycin
Gentamicin
Daptomycin Distinct MOA, disrupts
multiple aspects of bacterial
cell membrane function &
appears to bind to the
membrane & cause rapid
depolarization loss of
membrane potential 
inhibition of protein, DNA and
RNA synthesis, bacterial
cell death
Spectinomycin
-Reserved for organisms resistant
to other aminoglycosides
-Pseudomonas coverage
- NEVER use for respiratory
-Skin and soft tissue infections
caused by Gram (+) infections
-Staph aureus bacteraemia and
right-sided S. aureus endocarditis.
-Binds avidly to pulmonary
surfactant, and therefore cannot be
used in the treatment of pneumonia.
-Good against mutidrug resistant
staph (e.g. MRSA)
Tx of resistant gonococcal infection

40
TETRACYLCINE -Broad spectrum (same spectrum as macrolide)
-Bacteriostatic
-30s at A site prevents elongation
-Impaired abs w/ milk & food
-Chelation w/ cations
-Concentrate in liver, spleen, skin, teeth
-Gram + resistant
-Gonococci/meningococci respond
-Resistance b/c of of pumping drug out of cell
-Binds Ca in body in teeth and bone (so don’t give kids)
-DON’T GIVE W/ PENICILLIN
Doxycycline -Lipid sol biliary excretion
(Good for renal problems)
-Good penetration into tissues
-No food interruption
Minocycline -Water sol distributes in
body fluids ( in saliva/tears)
-Enters CSF w/o inflamed
meninges
-No food interruption
Demeclocycline
Tigecycline Derivatve of minocylcine
Chloramphenicol -Lipid soluble
-Broad spectrum, binds 50S
-Inhibits peptide bond
formation
-Inhibit peptidyl transferase
-Inhibits CYP 450
MACROLIDES Macrolides inhibit protein synthesis by blocking transloctation (50S). They inhibit CYP450. They are probably safe in
pregnancy, and may cause reversible deafness at high doses. Since macrolides are bacteriostatic and are used in HIV patients,
you must use huge doses pay attention to the side effects. Resistance is usually by the production of methyltransferases.
Macrolides increase serum concentrations of theophyllines & oral contraceptives.
Erythromycin -Metabolized by liver &
excreted in bile
Azithromycin -Metabolized by liver &
excreted in bile
-DOES NOT inhibit CYP450
Clarithromycin
Clindamycin -NOT a macrolide, same MOA
-Distributes to bone & stays
VACUUM THe Bed Room
-Vibrio cholerae
-Acne (propionibacter)
-Chlamydia
-Ureaplasma Urealyticum
-Mycoplasma (erythromycin also
DOC)
-Tularemia
-H. pylori
-Borellia burgdorferi
-Rickettsia
*Cannot be used for bone
infections
-Tx traveler’s diarrhea from
ETEC
-Good CNS penetration
-DOC for Lyme’s disease
-DOC for prostatitis
-Tx of asymptomatic
meningococcal carrier state
(rifampin same use)
-Tx nocardiosis (better combined
w/ sulfonamides)
Tx of SIADH
Active against gram (-) and (+),
anaerobes, chlamydiae,
mycobacteria, MRSA, VRE
-Meningitis (H. influenzae, N.
meningitides, S. pneumo) used in -Gray baby syndrome (baby
babies in past before vaccinat
-Backup for Salmonella typhi, B.
fragilis, Rickettsia
-DOC for Rickettsia in pregnancy
or in child
-Gram (+), not MRSA
-Atypicals
-Legionella
-Campylobacter
-Similar spectrum, more active in
respiratory infections
-Best macrolide to use in pregnant
-Mycobacterium avium
Activity against M. avium &
H.pylori
-Gram (+) (except enterococcus)
-Some ANAEROBES
-Fanconi-like syndrome
-GI irritaton
-Pain & phlebitis
-Hepatotoxic (esp in
pregnant)
-Photosensitivity
-Superinfection
-Hypersensitivity
-Brown mottled teeth (Ca
binding)
-Leucocytosis, thromboct
purpura
CI: pregnant,& kids (<8yrs)
Photosenstivity:
-Sulfonamides
-Quinolones
-Tetracycline
-Vestibular toxicity (balance
not hearing, reversible)
-Food does not interfere w/
abs & poor Ca++ chelation
-Vestibular toxicity
-Food does not interfere w/
abs & poor Ca++ chelation
Photosensitivity (also seen w/
sulphonamides, quinolones)
Diabetes insipidus
-Don’t use in kidney
infections
-Aplastic anemia
lacks UDP glucuronly trans)
-Superinfection
-Hypersensitivity
-Very toxic, not used often
-GI distress (from
stimulating motilin receptors)
-Erythromycin estolate
cholestasis & obstructive
jaundice
-GI distress (from
stimulating motilin receptors)
LEAST GI distressing
-1st known drug associated w/
pseudomembranous colitis
41
 active
-Does not cross CNS,
eliminated via biliary
Linezolid Inhibits the formation of the
initiation complex (50S)
-No cross resistance w/ other
protein synthesis inhibit
STREPTOGRAMINS Quinupristin + -Given together 30:70
Dalfopristin -Binds 50S preventing AA
incorporation at A site
-Osteomyelitis
-Tx VRSA & VRE (enterococcus -BMS (platelets)
faecium NOT faecalis) & other
drug resistant Gram (+) cocci
-VRSA
-VRE (enterococus faecium AND
fecalis)

Disulfiram-like Effects
Metronidazole Tx of MRSA
Cefamandole ORAL:
Cefoperazone -TMP/SMX
Cefotetan -Clindamycin
Chlorpropamide Linezolid
Doxycycline

OTHER:
Daptomycin
Vancomycin
Tigecycline

HIV ANTIVIRALS
Class Drug Mechanism Clinical Use Side Effects
NRTI Nucleoside Reverse Transcriptase Inhibitors (NRTIs) are components of most combination drug regimens. Commonly two NRTIs are
used together with a protease inhibitor. They all lack a 3’ OH group, and once phosphorylated by cellular enzymes they are
incorporated into viral DNA by reverse transcriptase. They inhibit elongation because cannot form a phosphodiester bond. The NRTIs
are mostly renally excreted. Also, do not give the same nucleoside analogue. All the drugs put on the market after AZT are less
BMS.
HAART = 2 NRTIs + PPI
Zidovudine The 1st drug for HIV infection -Tx and prophylaxis of HIV -BMS (esp at doses)
(AZT) lots of different resistances -Headache  don’t forget the added
Resistance: toxicities from taking an antiinflamm (e.g.
MOA: thymine analogue, requires -Mutations in the genes aspirin)
triphosphorylation to be activated that code for RT -Hematotoxicity (dose limit) may
PK: well abs PO (less w/ food), require blood transfusion on starting tx
crosses CNS, ½ life (1 hrs), -Myalgia and myopathy (don’t take aspirin
intracell ½ life (3 hrs) family drugs kidney toxicity)
-Peripheral neuropathy
Rare, but potentially fatal lactic acidosis

Drug Interact:
-Azole antifungals, cimetidine inhibit
CYP450s AZT (worse toxicity)
-Indomethacin & probenecid they
affect renal clearance
-TMP-SMX additive BMS (used in
pneumocystis carini)
-Rifampin (induces P450) AZT
-Stavudine & rivavirin activated by the
same pathways

42
 Abacavir -Analog of guanosine
PK: NOT renally excreted, but
metab by alcohol dehydrogenase
and glucuronyl transferase
Didanosine (DDI) Inosine analogue (precursor for
guanosine/adenosine) ddATP in
cell
PK: Abs best in fasting state or
w/ antacid, crosses CNS (less
than AZT)
Lamivudine (3TC) MOA: Cytosine analog that
terminates synthesis of proviral
DNA chain & inhibits HIV & HBV
RT (does not affect mito DNA
synth or BM precursor cells
Emtricitabine -Fluoro-derivative of analog of
3TC
-Taken once a day
Stavudine (D4T) AZT analogue (thymidine alalog)
binds same site
-Strong inhibitor of  and y DNA
polymerases
PK: completely abs PO not
affected by food, crosses CNS
Zalcitabine 1st cytosine analog developed, but
(DDC) removed from the market b/c of
toxicity
Tenofovir MOA: nucleoTIDE (AMP) analog
PK: take w/ food, long half life
once daily dosing
NNRTI Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) are highly selective, noncompetitive inhibitors of HIV-1 RT do not
require metabolic activation. They inhibit reverse transcriptase at a different site from the NRTIs. Since they can be added to
the NRTIs, they are synergistic with NRTIs. They lack cross-resistance with NRTIs. These drugs have cross-resistance WITHIN
the NNRTI class, drug interactions, and a high incidence of hypersensitivity rxns. These drugs are NOT myelosuppressive.
Nevirapine PK: well abs PO (not affected by
(NVP) food), crosses to CNS, excreted in
the urine as metabolites (CYP3A4 +
CYP2B6)
Resistance:
-May be cross-resistance
w/ strains resistant to AZT
& 3TC
-Tx of HIV
-Acitive in hepatitis B
-Never used alone too
weak (should not be used w/
other cytosine analogs
Resistance:
-Mutation at viral codon 184
(but restores sensitivity to
AZT & tenofovir)
-Inhibits HIV and HBV RT
Tx HIV
Tx HIV
Tx HIV
Used in combination
with other antiretroviral in women w/ CD4 < 250, male CD4 < 400)
drugs for HIV-1 tx in
adults and children
Resistance:
-Target site is HIV-1
specific, not essential to warfarin
enzyme rapid resist
GI, h/a, dizziness
5% hypersensitivity rxn (1 or more: rash,
GI, malaise, respiratory distress)
0sensitized individuals should never be
rechallenged (can be genetically screened)
Greater affinity for mito DNA
polymerase peripheral neuropathy,
lipoatrophy, pancreatitis (…remember
valproate)
-Less BMS than AZT
CI: Zalcitabine, stavudine (similar
toxicities)
-Least toxic of NRTIs (least potent)
-Few significant SE
-Does not affect CYP450s, no significant
interactions w/ other drugs
-Diarrhea, h/a, rash
-Hyperpigmentation of the soles/palms
-Lactic acidosis, fatty liver, hepatomegally
Greater affinity for mito DNA
polymerase peripheral neuropathy,
pancreatitis, lipoatrophy
-Less BMS than AZT
-DO NOT USE W/ AZT
-Peripheral neuropathy (dose limiting)
-GI distress
-Pancreatitis, neutropenia, rash
CI: Didanosine (similar toxicities)
GI (n/v/d, flatulence)
CI: only NRTI w/ sig drug interactions
(DDI, no longer recommended combined
use & atazanavirso  by boosting w/
ritonavir)
-Potential severe hepatotoxicity (don’t use
CI: induces CYP3A4 metab of PI’s (no
dosage adjust needed), oral
contraceptives, ketoconazole, methadone,
metronidazole, quinidine, theophyline,
43
 Efavirenz (EFV) Preferred NNRTI -Mostly CNS (50%) dizziness, h/a, vivid
PK: bioavail w/ fatty meal; well dreams, loss of concentrationresolves
distrib after PO, 99% plasma after few weeks
albumin bound, half life -Rash (25%)
(>40hrs)once-a-day dosing
CI: Pregnancy; potent inducer of CYP450
Delavirdine
Adefovir Does not require phosphorylation
Protease Aspartate protease (pol gene encoded) is a viral enzyme that cleaves precursor polypeptides in HIV buds to form the proteins of the
Inhibitors mature virus core. The enzyme contains a dipeptide structure not seen in mammalian proteins (important for selectivity). PIs bind to
this dipeptide, inhibiting the enzyme. Resistance occurs via specific point mutations in the pol gene, such that there is not complete
cross-resistance b/w different PIs. Since PIs have nothing to do with DNA replication, they will NOT cause BMSthus, good for
adding these drugs to the regimen!. Since they have a different MOA, they can only be synergistic with those drugs blocking
replication. Most have poor bioavailablity. However, the biggest problem is the inhibition of CYP450s. They also cause disorded lipid
and carbohydrate metabolism.
Saquinavir Given w/ low dose RTV; high fat meals H/A, fatigue, nausea, GI
enhance absorption CI: drugs that enhance metabolism
Half life = 7-12 hours (e.g. rifampin, rifabutin, nevirapine)
Indinavir Given w/ RTV to increase absorption, -Nephrolithiasis
permit twice daily dosing -Hyperbilirubinemia
-Least protein bound, absorption decreaed -Fat redistribuation
when taken w/ meals -GI distress
-Half life = 1.8hours -Thrombocytopenia
-Inhibition of CYP3A4
CI: dosage should be reduced w/
hepatic insufficiency
Ritonavir PK enhancer/ booster of other PI’s -GI distress
-Potent inhibitor of CYP3A4 -Asthenia & circumoral paresthesias
-Half life = 3-5 hours -Major drug interactions: induces
CYP 1A2 & inhibit the major P450s
(3A4 & 2D6) thus limited use
Nelfinavir (NFV) Canot be boosted y RTV; metabol by several Diarrhea (controlled by loperamide),
CYPS; major metabolite (CYP2C19) has nausea, flatulence
antiviral activity equal to parent compound
-half life = 5h CI: can inhibit metabolism of other
drugs
Fosamprenavir Given w/ RTV; prodrug amprenavir H/A, fatigue, nausea, vomiting,
(fAPV) paresthesias
CI: can inhibit metab of other drugs
Lopinavir (LPVr) One of the preferred PIs; given with RTV GI, hypertriglyceridemia, insulin
-Poor intrinsic bioavailability resistance
-half life =1.8 hours CI: enzyme inducers (avoid St Johns
Wort), Oral solution contains EtOH
(ovoid disulfiram or metroniadazole)
Atazanavir ATV + RTV = only once daily preferred PI; -Competitive inhibitor of glucuronyl
(ATZ) structurally unrelated to other PIs; well transferase (benign hyperbilirubinemia
absorbed orally (increased by food) + jaundice)
-Highly protein bound (86%) -Prolongs PR intervale + slows HR
-Half life = 7h CI: Metabolized by & inhibits
CYP3A4, proton pump inhibitors;
administration must by more than
12h apart from H2 blockers &
antacids
Tipranavir (TPV) Inhibits HIV protease resistant to other Same as other PIs + severe and fatal
PIs hepatitis
-Twice daily w/ RTV -Fatal/nonfatal intracranial
-Well absorbed when taken with food; half hemorrhags
life = 6h
CI:Inducer of CYP 450

44
 Darunavir Inhibits HIV protease resistant to other Same as other PIs + RASH
PIs; well absorbed when taken w/ food
Half life = 15 h (w/ RTV) CI: metabolized by & inhibits
CYP3A4
VIRAL Enfurvitide -Fusion inhibitor; structurally resembles -Use for tx- -Injection-related (3% discontinue)
ATTACHMENT gp41 experienced adults w/ $$$ (estimated at $20,000)
MOA: Binds gp41 (recognizes chemokine evidence of HIV
receptrs) and inhibits fusion of HIV-1 to replication
CD4+
(note: gp120  recognizes CD4+)
-Has to be administered parenterally (twice
daily subQ injections)
VIRAL ENTRY Maraviroc Blocks CCR5 coreceptor that works w/ -Well tolerated
gp41 to facilitate HIV entry through cell
membrane (only CCR5 expressing virus can
be treated w/ maraviroc
INTEGRASE Raltegravir Specifically inhibts final step in integration -Give w/ other Well tolerated
INHIBITOR (RAL) of viral DNA into host cell DNA retrovirals for tx- Nausea, h/a
-Half life = 9h twice daily dose experienced patients Diarrha
-Metabol via UGT1A1-mediated w/ evidenc of viral
glucuronidation no interactions w/ replication
CYP450 inducers, inhibitors

OTHER ANTIVIRALS
Respiratory Virus Oseltamivir -Inhibits viral neuraminidase by acting as -Effective against both -GI discomfot & vomiting, so take
infections Zanamivir a sialic aicd analog Influenza A and B the drug w/ food (oselt)
-Does not interfere w/ the immune -Prevent infection (if -Airway irritation (zana)
response to influenza A given prior to exposure)
-Oseltamivir (oral) -Modest effect if given CI: severe reactive asthma (zana)
-Zanamivir (inhaled/nasal spray) w/in first 24-48h of
onset
Blocks the viral membrane matrix protein (M2), which functions as a channel for H+ (required for fusion of viral membrane w/ host
cell membrane). Does not impair immune response to Influenza A vaccine. Viral Uncoating Inhibitors
Amantadine PK: Distributes well and penetrates CNS; -Tx & prevention of -Livedo reticularis
NOT extensively metabolized, but Influenza A infxns -Nose/throat irrriation
excreted in urine & may accumulate in -Atropine-like SE
renal failure -Parkinson’s
-Also antimuscarinic action
Rimantadine Does NOT cross CNS; extensively
metabolized by liver; metabolites and
drug eliminated by kidney
Ribavirin Synthetic guanosine analog Effective against a broad Dose-dependent transient anemia
phoshorylat then inhibits IMP spectrum of RNA and (hematotoxic)
dehydrogenase as a triphosphate DNA viruses (RSV, -Upper airway irritation
inhibits viral mRNA capping Influenza A & B, Lassa
fever, Hanta viruses) CI: Pregnancy
-Adjunct to  INF in HCV
Palivizumab Monoclonal antibody against RSV -Given in premature
infants before start of
RSV season if <12mo old
Anti-Herpes Acyclovir Guanosine analog that is 1st phosphorylated -Tx HSV-1,2 & VZV -Will NOT cause BMS
Drugs by viral thimidine kinase incorporates -Minor SE w/ oral use
into DNA & causes chain termination Resistance: change or -Crystaluria
absence (TK- strains) in
the thymidine kinase -Cannot be used for CMV b/c
virus lacks thymidine kinase
Valacyclovir Prodrug acyclovir; longer half life than
acyclovir and more bioavail

45
 Pencyclovir Acivated by viral thymidine kinase &
inhibits DNA pol, but does not cause chain
termination
Famcyclovir Prodrugpencyclovir -Gential herpes & herpes
-Given Orally zoster
Docosanol Aliphatic alcohol that inhibits fusion -Shortens healing time
between HSV envelope and plasma
membranes, preventing viral entry &
subsequent replication
-Used toppically
Ganciclovir Guanine derivative that is -Prophylaxis & Tx of Dose limiting BMS (a problem with
phosphorGTP inhibits DNA pol of CMV CMV retinitis and over those already immunosuppressed)
and HSV & causes chain termination; CMV infections
usually given IV; penetrates into CNS
-Any kinase can turn on ganciclovir
Valganciclovir
Foscarnet Not an antimetabolite; but still inhibits -CMV Dose-limiting nephrotoxicity with
DNA & RNA pol. Requires an IV infusion -HSV resistant strains acute tubular necrosis, electrolyte
pump (so must be hospitalized) (e.g. TK- strains) imbalance with hypocalcemia
(tremors & seizures)
-NOT hematotoxic (so no BMS)
-Avoid pentamidine IV (used for
pneumocystis when bactrim not
working also nephrotoxicity)
HEPATITIS

CHEMOTHERAPY
Drug type Drug Mechanism Clinical Use Side Effects
Drugs that are cell cycle specific are more effective against actively growing tumors with high growth fractions (leukemias, lymphomas).
ANTI- Cell cycle specific (S phase) are easy to recognize because typically they have some type of nucleotide analog.
METABOLI 5-Fluorouracil MOA: 5-FU 5’ FUMP5- -Topical for basal cell -BMS, alopecia, anorexia, n/v/d
TES FUDP 5-FdUMP, which cancer and -Severe ulceration of oral & GI
1. Pyrimidine inhibits thymidylate keratoses mucosa
Antagonists synthetase (dUMPdTMP) -Tx slowly growing solid -Hand/foot syndrome
PK: IV, topical; rapidly metab tumors (e.g. (erythmatous desquamation of
in liver, lug, kidneyfluoro-- colorectal, breast, palms & soles after extended
alanine (urine) + CO2 (exhaled) ovarian, pancreatic, infusions)
-Elevated levels of gastric)
dihydropyrimidine
dehydrogenase (DPD) = 5-FU *Usually given w/
breakdown Leucovorin
effectiveness of
5-FU

46
 Capecitabine MOA: Oral prodrug5-FU,
but the final step is thymidine
phosphorylase (found in
tumors)TUMOR SPECIFIC
PK: PO, well absorbed
Cytarabine Analog of 2’deoxy-cytidine
(ara-C) (arabinose instead of ribose)
MOA: Ara-c enters
cellphosph by deoxycytidine
kinase & other kinases ara-
CTP (cytotoxic) inhibits
DNA polymerase
Inhibits DNA elongation
PK: not effective orally
(deaminated in intestine,
liver); does NOT go into CNS
Gemcitabine MOA: Analog of
deoxycytidine
(deoxycytidine kinase) 2’,2’-
difluorodeoxycytidine
triphosphate, which:
Inhibits DNA synth
Inhibits ribonucleotide
reductase
PK: IV, eaminated to non-toxic
metaboliteurine
6-Mercaptopurine MOA: 6-MP  6-thioinosinic
2. Purine (6-MP) acid (TIMP, a thio analog of
Antagonists hypoxanthine) by HGPRT,
which adds a ribose-P:
Blocks 1st step of de novo
purine ring biosynth (via
glutamine phosphoribosyl
pyrophasphate
amidotransferase)
Blocks IMP AMP & XMP
TIMPTGMP to inhibit
RNA
PK: PO, erratic abs; metab in
liver 6-methyl-MP or to
thiouric acid via xanthine
oxidase)
Cladribine -Similar rxns to fludarabine
-Incorporated At 3’ end of
DNAblocks elongation
-Also, blocks DNA repair and
inhibits ribonucleotide reducts
PK: single continuous 7-day
infusion; well distributes &
into CNS
-Metastatic breast cancer
(resistant to 1st line)
-Colorectal cancer
-AML 1st line (Cytarabine +
6-TG +
daunorubicin)
Locally advanced or
metastatic
adenocarcinoma of
pancreas (1st line)
-Non small cell lung cancer
-Acute lymphocytic
leukemia (ALL)
-Immunosuppression
Resistance:
1. Inability to
biotransform 6-MP to
the corresponding
nucelodite b/c of
HGPRT (e.g. lesch
nyhan syndrome)
2. Dephos
3.  Metab of the drug to
thiouric acid
-Hairy cell leukemia
-Non-hodgkin lymphoma
Similar to 5-FU
-GI toxicity
-Carefully used in patients w/
renal or hepatic impairment
CI: pregnancy, lactation,
patients on coumarin
anticoagulants or phenytoin
-N/V/D
-Severe BMS
-Hepatic dysfunction
-High doses or IT injection
leukoencephalopathy
BMS (dose limited)
-N/V, alopecia, rash, flu-like
syndrome
-Transient elevation of serum
transaminases, proteinuria,
hematuria
-BMS
-Hepatotox (jaundice, necrosis)
-
When taking Allopurinol (inhibits
xanthine oxidase) reduce 6-MP
dose by 75% to avoid toxicities
Severe BMS
Fever
Peripheral neuropathy
Teratogenic
47
 Fludarabine 5’ phosphate of 2-
fluoroadenine arabinoside
MOA: prodrug loses Phos 2-
F-araA taken into cells &
phosph incorporated into
DNA & RNA (S-phase)
PK: IV (if oralintest bacter
split off the sugar toxic)
Pentostatin MOA: potent inhibitor of
adenosine deaminase (ADA)
Blocks DNA synth
Blocks ribnucleotide
reductase
6-Thioguanine 6-TG TGMP (6-thioguanylic
(6-TG) acid) via HGPRTTGDP
TGTP:
Blocks purine synth
Blocks phosphorylation of
GMPGDP
TGTP incorporated into
DNA, blocking cell cycle
PK: PO, abs erratic &
incomplete
Methotrexate MOA: Folate analogue
enters cell via active
transpor inhibits DHF
3. Folate reductase (S phase)
antagonists
Antidote = Leucovorin
rescue (N5, N10-methylene
FH4 DHFR not needed) b/c
healthy cells pick up the
folate better than the
cancer cells (can give before
MTX)
Pemetrexed -Folate analogue, transported
into cell same as MTX
-Inhibits DHFR &
thymidylate synthase
-CLL* -BMS (dose limiting)
-Hairy cell leukemia -Diarrhea, n/v
-Indolent Non-Hodgk Lymph -Fever
-Edema,
*May replace chlorambucil -Severe neuro toxicity
-Progressive encephalopathy,
blindess & death at doses
-Hairy Cell Leukemia (good BMS
at causing complete GI symptoms
remission) Skin rashes
-CLL, CML, promyelocytic Abnormal liver function results
leukemia cutaneous Immunosuppression (long lasting)
T cell lymphoma, Renal/neuro complications
non-Hodgkin (doses)
lymphoma,
Langerhans cell
histiocytosis CI: given w/ fludarabine 
-No sig affect on solid severe/fatal pulmonary toxicity
tumors or multiple
myeloma
-AML (6-TG + BMS (dose dependent)
Daunorubicin + Liver toxicity
Cytarabine)
*Breakdown via thiopurine
*Not recommended for methyltransferase (TPMT), must
maintainance screen patients before therapy
therapy or (3% of whites/blacks have a
continuous for long homozygous deletion of TPMT)
term (liver tox) *Can give w/ Allopurinal w/out
dose b/c 6-TG requires
deamination before it is
metabolize by xanthine oxidase
(so if XO is inhib, already
inactiv)
-ALL -Diarrhea, n/v, stomatitis, rash,
-Burkitt’s lymphoma erythema, urticaria, alopecia
-Breast cancer -Crystalluria
-Choriocarcinoma -Long use liver cirrhosis
-Head and neck carcinomas -Pulmonary toxicity (rare)
-RA, psoriasis -Neurotoxicity
--Abortion when used w/ -BMS,
misoprostol in 3rd CI: pregnancy
term
-Mesthelioma (+ cisplatin) -BMS
-Second line therapy of non- -Skin rash, mucositis, diarrhea,
small cell lung cancer fatigue
48
ANTI-TUMOR Bleomycin G2 phose
ANTIBIOT Copper/Fe chelating
ICS (CCS) Complexes w/ Fe and O2
Dna strand breaks
PK: bleomycin inactivating
enzyme is high in some
tissues (liver, spleen), low in
others (lung, skin)
Anthracycline Doxorubicin MOA: effective in S & G2
phases
Inibits topoisomerase II
Intercalation into DNA
inhibition of synth & DNA
strand breaks
Bind to cellular membranes,
altering the fluidity/ion
transport
Generation of semiquinone
& oxygen free radicals
(cardiotoxicity) by CYP450
PK: IV, metab by liver
Anthracycline Daunorubicin Same
Idarubicin
Mitoxantrone MOA: resembles
anthracycline ring binds
DNA strand breaks
synth inhbiited
Plicamycin MOA: plasma calcium thu
actions on osteoclasts indep
of action on tumors
ANTI-TUMOR Dactinomycin MOA:
ANTIBIOT (Actinomycin D)  Intercalates into double
ICS (CCNS) helix stable complex
Also blocks RNA
polymerase elongation &
causes strand breaks
Mitomycin MOA: Generates alkylating
agents (via reduction) that
cross link DNA
-Targets hypoxic tumor stem
cells (as environment is more
conducive to reduction)
EPIPODO- Etoposide Cell cycle specific
PHYLLOTO MOA: inibit late S-G2
XINS phase; inhibits
topoisomerase II
PK: water insoluble
Teniposide -Same as etoposide
-Semisynthetic derivative of
podophyllotoxin (mayapple
root)
Microtubule inhibitors are effective because the mitotic spindle is part of the cytoskeleton and is essential for equal
partitioning of DNA. These compounds are NATURAL products that are cell cycle specific (CCS) at the M phase.
-Testicular cancers
(Bleomycin +
etoposide + cisplatin
or vinblastine)
-Squamous cell carcinomas
-Lymphomas
Broad spectrum:
-Hematologic malignancies
-Solid tumors (e.g. lung,
ovarian, breat)
*One of the most widely used
-Tx AML
-Advanced, hormone
refractory prostate
cancer
-Low grade non-Hodgkin’s
lymphoma
-Breast cancer
-AML
-Testicular cancer
-Hypercalcemia associated
w/ neoplasms
-Wilm’s tumor (Surgury +
Dactinomycin +
vincristine)
-Gestationl choriocarcinoma
(Dactinomycin +
MTX)
-Squamous cell cancer of
the anus (Mitomycin
+ 5-FU + radiation)
-Squamous cell carcinomas
-Pancreatic cancer
-Superficial bladder cancer
(intravesical tx)
-Germ cell cancer (testicul)
-Gastic cancer
-Lung cancer
-Lymphomas
ALL
-Pulmonary fibrosis
-Pneumonitis
-Mucocutaneous rxns (blisters)
-Alopecia
-Hypersensitivity
-BMS IS RARE
-Irreversible cardiotxicity
dilated cardiomyopathy (co-
admin w/ iron chelator
dextrazone to toxicity)
-Transient BMS, stomatitis, GI
disturbances
-Severe Alopecia
-Increased skin pigmentation
*Drugs are dark red veins may
become visible and red urine
*Extravasation of drug is a
serious proglem tissue necrosis
Same
-BMS (dose limiting)
-Blue discoloration of
fingernails, sclera & urine
-Mild nausea, vomiting, mucositis,
alopecia
Highly toxic, older drug
-BMS (dose limiting)
-Stomatitis, n/v/d, alopecia
-Sensitizes to radiation
-Hemolytic Uremic Syndrome
Leukopenia (dose limiting)
Note: “topo” = topoisomerase
Leukopenia (dose limiting)
49
MICROTUBULE Paclitaxel -From European Yew
INHIBITO -Stabilize microtubules
RS: PK: IV (not into CNS)
TAXANES
Docetaxel -Same as paclitaxel
-Semisynthetic
Vinblastine -Block microtubule
synthprevents cell prolif
PK: rapid cytotoxicity
VINCA
ALKALOID
S Vincristine Same
Vinrelbine Same
CAMPTOTHECINS Irinotecan -Semisynthetic
-Inhibit topoisomerase I
Topotecan Same as Irinotecan
ALKYLATING Alkylating agents are Cell Cycle Non-Specific (CCNS) and do not differentiate b/w cycling and resting cells, although
AGENTS they are most toxic to rapidly dividing cells. In addition to being cytotoxic, they are mutagenic and carcinogenic and can
lead to 2’ malignacies, such as acute leukemia.
Mechlorethamine -Alkylation of N7 Guanine on -Lymphatic cancers (mainly
both strands of DNA
(“bifunctional agent”)
-Cross-linkage between
chains & depurination
strand breaks, miscoding
mutations
PK: very unstable, must be
made just before using;
powerful blistering agent
(vesicant) so give IV
Cyclophosphamide -Similar to mustard agents
Pro-Drug hydroxylation
via CYP450 breaks
down into
phosphoramide
mustard + acrolein
(acroleinhem cy)
-Phosph mustard rxn w/ DNA
is cytotoxic, attaks
DNA at N7 guanine
PK: Oral (unlike most
alkylating agents)
Ifosfamide Similar to cyclophosphamide
Nitrosureas
-Ovarian cancer
-Metastatic breast cancer
-Non small cell lung cancer
(Paclitaxel +
cisplatin)
-Metastatic testicular
cancer (Bleomycin +
Cisplatin +
Vinblastine)
-Lymphomas
-ALL
-Wilm’s tumor
-Ewing’s sarcoma
-Lymphomas
Non-small cell lung cancer
-Colon or rectal cancer (1st
line) (Irinotecan +
5-FU + leucovorin)
-Ovarian Cancer (when
primary therapy
fails)
used for Hodgkin’s)
-Solid tumors
-Developed as a nitrogen
mustard during WWII
-Many cancers (e.g. Burkitt’s,
breast)
-Nephrotic syndrome
-Intractable RA
-Neutropenia
-Hypersensitivity (premedicate
w/ dexamethasone +
diphenhydramine)
CI: patients w/ cardiac disease
-Fewer SE than paclitaxel
-Neutropenia
CI: patients w/ cardiac disease
BMS (dose limiting)
GI, alopecia
Peripheral neuropathy
Granulocytopenia (dlose limiting)
-BMS (dose limiting)
-Thrombocytopenia
-Anemia
Same
-Severe n/v (can premedicate w/
dexamethasone)
-Severe BMS
-Latent viral infxn
-Extravasation is serious (give
sodium thiosulfite to inactivate
drug)
-BMS
-Mucositis
-HEMORHAGIC CYSTITIS 
Antidote = mesna
-Hepatotoxicity (dose)
-Veno-oclusive disease of the
liver
-Amenorrhea, testicular atrophy,
sterility
-Neurotoxicity  probably
related to the metabolite,
chloroacetaldehyde
50
 Carmustine MOA: Alkylation that inhibits Brain tumors (glioblastoma -Delayed hematopoietic
Lomustine replication, RNA, protein multiforme) depression
synthesis, target dividing -Aplastic BM (prolonged use)
cells -Renal toxicity
PK: crosses CNS -Pulmonary fibrosis
Carmustine = IV
Nitrosureas Lomustine = oral
Streptozocin MOA: Alkylation that inhibits Insulinomas -Diabetogenic
replication, RNA, protein -Minimal BM toxicity
synthesis, target dividing
cells
-Specifically toxic to -cells
of pancreas
Dacarbazine Prodrug MTIC via CYP450 Melanoma -BMS, n/v
forms methylcarbonium -Hepatotoxicity
ions that attack nucleophilic Hepatic vascular occlusion
gropus, cytotoxic by DNA
methylation
PK: IV
Temozolomide MOA: prodrugMTIC (NOT -Resistant gliomas -BMS
via CYP450) forms methyl- -Anaplastic astrocytomas -n/v
carbonium ions that attack
nucleophilic groups, cytotoxic
via DNA methylatation
-Also inhibits DNA repair
enzyme 06-guanine DNA
alkyltransferase
PK: PO, crosses CNS (but to
lesser extent than
carm/lomustine)
Melphalan -Bifunctional alkylating agent -Multiple myeloma Hematologic toxicities
PK: PO -GI upset
Chlorambucil CLL -Leukemogenic
Busulfan CML -BMS & pulmonary fibrosis in old
-Leukemogenic
HORMONAL Glucocorticoids: Bind to receptor to induce -Induce remission in ALL -Immunosuppresion
AGENTS: Dexamethazone production of specific -Lymphomas -Hyperglycemia
Prednisone proteins -Cataracts
Glucocorticoids Hydrocortisone -Glaucoma
-Osteoporosis
-Mood changes
SERMs interact at estrogen receptors but have different effects on different tissues. Tamoxifen is an estrogen
antagonist in breast cancer tissue, but can cause endometrial hyperplasia by acting as a partial agonist in the uterus
Tamoxifen Estrogen antagonist (SERM) -Estrogen receptor positive -Similar to estrogen (hot
Selective Estrogen  binds to estrogen breast cancer flashes, n/v, rash, vaginal
Receptor recepotors depletes *Note: estrogen competes w/ bleeding)
Modulators (SERM) estrogen, estrogen receptrs, tamoxifen, use w/ a GnRH -Hypercalcemia
& growth factors analog (e.g. leuprolide) in -Endometrial cancer
premenopausal
Toremifene SERM, Similar to tamoxifen -Advanced breast cancer
(postmenopausal)
-Prophylaxis in high risk
women
AIs block aromatase in liver, fat, muscle, skin and breast tissue. Peripheral aromatization is an important estrogen
source postmenopausally

51
Aromatase Aminoglutethemide -AI Metastatic breast cancer *Newer AI’s developed due to
inhibitors (AI’s) -Inhibits adrenal synth of SE
pregnenolone (precursor of  Usually taken w/
estrogen) hydrocortisone
-Inhibits hydrocortisone
synth compensatory
ACTH overrides drug
Exemestane -Steroidal AI Breast cancer -Hot flashes, n/v
-Metab by CYP450 -Androgenic SE (acne, hair
changes)
Anastrozole -Non-steroidal AI -Breast cancer (2nd line to -Do not predispose to
Letrosole -More potent & selective tamoxifen) endometrial cancer
than aminoglutethemdie Do not need to be given w/ -Do not have androgenic SE
hydrocortisone
Prostate cancer is dependent upon hormonal stimulation with androgens
Leuprolide GnRH agonist androgens Prostate cancer -Impotence
Anti-Androgens & estrogens (castration level) -Hot flashes
PK: sustained release prep, -Tumor flare (minimal compared
SC, depot IM to estrogen tx)
Goserelin GnRH agonist Prostate cancer Same
PK: IM
Flutamide Synthetic, non-steroidal Prostate cancer Liver failure
antiandrogen  competes w/ -Since it blocks inhibitory
natural hormone for recetpor effects of testosterone on
binding, preventing GnRH LH, testosterone,
translocation to nucleus it is always given w/
PK: PO leuprolide or goserelin
Nilutamide Same Prostate cancer Visual problems

Ethinyl estradiol Synthetic estrogens Block Postatic cancer Thromboemboli, MI, strokes,
Diethylstilbesterol production of LH *Replaced by GnRH (SE) hypercalcemia, gynecomastia,
androgen synthesis in impotence
testes
Other
Megesterol- -Progestins Breast
Acetate *Replaced by AIs Endometrial cancer
PLATINUM Cisplatin -Similar to alkylating agents, -Solid tumors (e.g. -Severe persistent vomiting
COORDINATION bind to DNA cross links testicular cancer) (Cisplatin (1hr-5days) (use ondansetron)
COMPLEXES inhibit synthesis + Bleomycin + etoposide) -Nephrotoxicity (dose limiting)
-Cell cycle nonspecific tx w/ amifostine, also requires
(CCNS) -Ovarian cancer aggressive hydration
(Cyclophosphamide + -Hypomagnesemia
PK: IV, intraperitoneally for Cisplatin) -Hypocalcemia
ovarian cancer -Ototoxicity, tinnitus
-Bladder cancer -NO BMS
-Neurotoxicity (deafness)
Carboplatin Same -When patients cannot be -Mild n/v
vigorously hydrated -NO nephrotox
-Switch to carboplatin when -NO ototoxicity
nephrotox on cisplatin -NO neurotox
-BMS (dose limiting)
Oxaliplatin Same Advanced Colorectal Cancer
MONOCLONAL Trastuzumab Binds to HER2 sites in Breast cancer CHF, fever, chills, h/a, dizziness,
ANTIBODIES breast cancer tissue n/v
Rituximab Binds to CD20 antigen on B -Posttransplant lymphoma -Hypotension, bronchospasm,
cells -CLL -Angioedema
PK: infuse slowly (fast can be -Cardiac arrythmias,
fatal) -Tumor lysis syndrome
Bevacizumab Inhibits angiogenesis Bevacizumab + 5-FU 
colorectal cancer

52
 Cetuximab Targets EGF & interferes w/
cancer cell growth
Gemtuzumab-
ozogamicin
Alemtuzumab
I131-tositumonab
SIGNAL Imatinib Deregulates BCR-ABL
TRANSDUCTION kinase prevents tyrosine
INHIBITORS phosph inhibits proliferat
Gefitinib Targets EGF
Bortezomid Proteasome inhibitor,
induces growth inhibition &
apoptosis
Sunitinib Inhibits VEGFR-1, VEGFR-2,
PDGFR
Sorafenib Inhibits B-RAF, VEGFR-1,
VEGFR-2, PDGFR
Vatalanaib Inhibits VEGFR-1, VEGFR-2
Thalidomide -Immunomodulatory drug
-Inhibits angiogenesis,
stimulates T-cells
Lenalidomide Analogue of thalidomide
Procarbazine Undergoes oxidative rxn
cytotoxic
L-Asparaginase Breaks down asparagine
(tumor cells cannot
synthesize asparagine)
INTERFERONS Interferon 2
Interferon 2
Hydroxyurea Urea analog inhibits
ribonucleotide reductase
inhibit DNA synth
-S phase
Tretinoin All trans-retinoic acid
(tretinoin) induces remission
through induction of terminal
differentiation, in which
leukemic promyelocytes lose
ability to proliferate
Arsenic Trioxide Induces differentation &
apoptosis
Colorectal cancer
AML
B-cell CLL
Relapsed non-Hodgkin’s
lymphoma
-CML in blast crisis
-GI stromal tumor
Non-small cell lung cancer
(when other therapy fails)
Hodgkin’s disease
*Inhibits MOA avoid
tyramine
-ALL (L-asparginase +
Vincristine + prednisone)
-Hiary cell Leukemia
-CML
-Aids relatd Kaposi sarcoma
-Hiary cell Leukemia
-CML
-Aids relatd Kaposi sarcoma
-Follicular lymphoma
-CML
-Tx of blast crisis of AML
-Adjunct therapy w/
radiation for head + neck ca
(Also synth of HbFuse fo
tx of sickle cell)
-Acute promyelocytic
leukmia
-Acute promyelocytic
leukemia (induces remission
in those w/ the t(15:17)
Difficulty breathing, low BP,
interstitial lung disease, rash,
fever, constipation
-Fluid retention, edema
-Hepatotoxicity
-Thrombocytopenia
-N/V
Acne, nausea, diarrhea,
interstitial lung disease (rare)
Few adverse SE
-BMS, n/v/d
-Neurotoxic
-Mutagenic & teratogenic
-BMS (dose limiting)
-Mucositis, diarrhea, h/a,
lethargy
-Maculopapular rash
Vitamin A toxicity (h/a, fever,
dry skin & mucous membranes,
skin rash, pruritis,
conjunctivitis), CNS toxicity,
weight gain
-Teratogenic
-Fatigue
-QT elongation
-Arrthymias
Teratogenic
53
 Immunosuppression
Immune activation cascade SIGNALS:
1. T-cell triggering at CD3-APC
2. Co-stimulation (CD80/86 of APC engage CD28 on T cell)
 Signals 1 and 2 activate several intracellular signal transduction pathways, one of which is the
calcium-calcineurin pathway, which is targeted by cyclosporine and tacrolimus
3. Stimulus for T cell proliferation: IL-2 binds to CD25 (aka IL-2 receptor) on the surface of other T
cells to activate mammalian target of rapamycin (mTOR)
Drug type Drug Mechanism Clinical Use Side Effects
CORTICOSTEROID Prednisone MOA: unclear, but Tcells -Suppress acute rejection of -Diabetes
Methylprednisolon affected most organ allografts -Hypercholesterolemia
-Tx chronic GVHD -Cataracts
-Tx autoimmune conditions -Osteoporosis
-Hypertension
ANTIMETABOLITE Azathioprine Pro-drug interacts w/ sulfhydral -Immunosuppression after N/V,
(OLD) compounds (e.g. transplantation Skin rash
glutathione)  6- -Inflammatory bowel disease Hypersensitivity rxn
mercaptopurinethioino *Antimetabolites usually used BMS
sinic acid w/ corticosteroids + calcineurin Gi irritation
(immunosupprssive inhibitors (CsA, TAC)
nucleotide) *Little effect suppressing a CI: pregnancy
-Lymphocytes mostly affected chronic immune response *Allopurinol significantly
by cytotoxicity due to their *Has been replaced by MMF metab of azathioprine
rapid proliferation & dependence
on de novo synthesis of purines
Methotrexate MOA: Unknown -Tx rheumatoid arthritis, Hepatic fibrosis/cirrhosis
Particularly active against psoriasis (not BM suppression)
lymphoid cells -Prevent GVHD Abortion w/ misoprostol
-See cancer chemotherapy (PGE1 analog)
-Antinflamm but not cytotoxic
ANTIMETABOLITE Mycophenolate- MOA: inhibit purine synth; -Heart, liver, kidney transplant -Diarrhea, n/v,
(NEW) mofetil MMFmycophenolic acid (MPA), -Abdominal pain
(MMF) a potent reversible inhib of IMP -Leucopenia
dehydrogenase (block the de -Anemia
novo formation of GMP b/c
lymphocytes lack the salvage CI: pregnancy
pathway)
PK: extensively bound to albumin,
long ½ life (14-18days);
-Prodrugactive metabolite
-Antacids absorption
Leflunomide -Blocks dihydroorotateorotate Rheumatoid Arthritis CI: pregnancy
(drug inhibits dihydroorotate
dehydrogenase)
ALKYLATING Cyclophosphamide -2nd line to azothioprine -Tx disorders of humoral Leukopenia
AGENTS -Hi dose  tolerance to new immunity (SLE) Cardiotoxicity
antigen Alopecia
PK: PO, Prodrug hydroxylatd- Autoimmune Risk of bladder cancer
intermedactive phosphoramide -RBC hemolysis, Ab RBC b/c of mutagenicity
mustard & acrolein (phos must dyscrasia, BM suppression (acrolein)
cytotoxic) BM transplant @ hi doses BM suppression
-Hemorrhagic cystitis
(antidote = mesna)

-Doesn’t cause side

effects of steroids/anti
ca drugs

54
CYTOKINE Cyclosporin A -Complexes w/ cyclophilin (an
INHIBITOR (CsA) immunophilin) binds calcineurin
S inhibits dephos of NFATc
NFATc cannot enter nucleus to
promote rxns for cytokine synth
 IL-2 synthesis
PK: PO or IV, metab by CYP3A4
Tacrolimus (TAC) MOA: same as CsA (but binds
immunophilin-FKBP-12
instead)
-Higher potency & fewer side
effects than CsA
PK: PO or IV, oral abs variable,
abs  w/ fatty meal, long half
life, metab by CYP3A4
Sirolimus/ MOA: forms complex w/ FKBP-
Rapamycin 12binds MTOR (serine-
(SRL) threonine kinase)block
progression of activated T cells
from G1S phase inhibit cell
proliferatinhibit cell response
to IL2 (NOT IL-2 synthesis)
PK: Oral only, Abs w/ fatty
meal, long ½ life, metab by
CYP3A4,
*SRL  [CsA], so don’t give at
same time (separate 1-2 hrs)
TNF Inhibitors Etanercept TNF-receptor dimmer binds
both TNF and TNF
Infliximab Ab against TNF
Adalimumab IgG1 against TNF
IL-1 Inhibitors Anakinra Recombinant form of IL-1ra
(receptor antagonist)
ANTIBODIES Antithymocyte- Rxn against T-cell precursors
Globulins (thymocytes); polyclonal
(ATG) PK: IV (very slow infusion, 1-
2wk), half life 3-9 days
Note: Muro murine Muromonab-CD3 Monoclonal antibody against
antibodies (OKT3) CD3 of mature T-cell
-Depletes Tcells for 48 hrs
PK: IV
-Organ transplants -Nephrotoxicity
-Severe RA (alternative to -Hepatotoxic
methotrexate) -Viral infection common
-Recalcitrant psoriasis not (CMV, herpes)
responding to other therapies -Hypertension,
*Most effective w/ -Hyperlipidemia
cortisteroids + antimetabolite -Hyperkalemia, tremor
-Glucose intolerance
-Gum hyperplasia
-Hirsutism
-Lymphomas
-Liver, kidney transplants (give -Similar to Cyclosporin A
w/ corticostrds &/or (NO gingival hyperplasia,
antimetab) NO hirsutism)
-Ointment prep for mod-severe -Nephrotox, neurotox
atopic dermatitis more common than CsA
*Preferred to CsA b/c doses -Post transplant insulin
of corticosteroids required dependent diabetes (esp
Black & Hispanic patients)
-Avoid use w/ NSAID –
interferes w/ renal blood
flow
-Prevent reject of renal -CsA + SRL more
transplnt nephrotoxic than CsA
-SRL + CsA + corticosteroids -Nausea, diarrhea, h/a
(allows lower doses) -Leucopenia
-SRL-coated stents inhibit -Thrombocytopenia
restenosis of blood vessels -Impaired wound healing
(endothelial cell proliferation) (esp diabetics & obese
problem for transplantng)
-Hyperlipidemia
-RA Risk of reactivating
-Chron’s disease latent TB must screen
-Psoriasis
*Will improve symptoms but not
reverse pathophys
-RA Neutropenia
-Modest effects on pain, Susceptibility to
swelling, but bony erosions infeciton
-Give at time of transplant to Chills
prevent early allograph Fever
rejection Leukopenia
-Tx severe rejection episodes of Thrombocytopenia
corticosteroid resist acute Infections
reject Skin rashes
-Acute reject of renal allograph -Anaphylactic rxns
-Corticosteroid resist acute -Cytokine storm (initial
allograft reject (heart, liver) binding of OKT3
-Depletes T-cells from donor BM activation of Tcell)
prior to transplant *Prevent cyto storm w/
methylprednisolone+
diphenhydramine +
acetaminophen
55
Note: Chimeric Basiliximab Monoclonal anti-IL-2 receptor -Acute rejection of renal Well tolerated
antibodies Daclizuma (Anti-CD25) transplant (give w/ CsA +
“xi” b PK: IV, Corticosteroids)
Dacilizumab: long ½ life
(20days); give 5 doses (1@ 24hr
before, 4@14 day intervals)
*Basiliximab ½ life only 7 days,
only 2 doses given (1@ 2hrs
prior, 1@4days after
Alemtuzumab Monoclonal Anti-CD52 (depletes -Refractory B-cell CLL -Cytokine storm
Note: Humanized T cells -Neutropenia
antibodies  -Anemia
“zu” -Pancytopenia (rare)
Alefacept Anti-CD2 (inhibits T cells) Chronic plaque psoriasis CI: HIV patients (drug
depletes CD4, CD8 cells
Note: anything  risk of infection)
binding to a Abataccept Anti-B7 (down regulates Tcells) Rheumatoid Arthritis -Exacerbations of
receptor  bronchitis
ends in -Risk of infection
“cept” Efalizumab Anti-LFA-1 (limits Tcell Chronic plaque psoriasis Immune-mediated
adhesion, activation, & migration) thrombocytopenia
-Hemolytic anemia
risk of infection
STEROIDS Prednisone CANCER: Lymphomas Adrenal suppression
General anti-lymphocytic effect DOC for: Growth inhibition
-Triggers apoptosis -ITP Decreased muscle tone
IMMUNOSUPPRESSION: -Autoimmune hemolytic anemia Osteoporosis
Toxic to some T-cell lines -Acute glomerulonephritis Cushing’s syndrome
-Suppress immunity & inhibits G vs. H disease Immune suppression
production of mediators
-Ameliorate drug
toxicity/inflammation

ANTIHYPERLIPIDEMIC DRUGS
Hypercholesterolemia is associated with atherosclerosis. Liver synthesizes cholesterol-esters and package with TAGs to make a VLDL (B-100).
Loss of TAG via lipoprotein lipase (requires C2) from the VLDL produces IDL (mainly Chol-ester). The IDL collects more chol-esters from HDL.
The IDL becomes LDL. HDL picks up extra cholesterol from tissues (via LCAT & A2).
Drug type Drug Mechanism Clinical Use Side Effects

56
 STATIN Lovastatin ALL statins -Tx for hypercholesterolemia Grapefruit juice inhibits CYP450
Simvastatin 1. Inhibit HMG CoA (LDL-c) 3A4 aggravating statin toxicity
Atorvastatin reductase block -Tx for hypertrigleridemias (esp. rhabdomyolysis
cholesterol synthesis mixed LDL, TAG
Liver cholesterol, diseases) ALL STATINS:
LDL-R expression -Myalgia check CK regularly
Plasma LDL Rule of 6’s = 2x dose of statin  -Rhabdomyolysis (risk w/
2. VLDL synthesis  6% cholesterol (use drug gemfibrozil) relased myoglobin
triglyceridemia combos instead) ATN kidney failure (give
mannitolenhance mg excret)
-PK: metabolized on P450 -Hepatotoxicity (check liver function
3A4 tests)
Fluvastatin PK: metabolized by -Same *Don’t give to homozyogos familial
alternative P450’s hypercholest.  No LDL recptrs
Pravastatin PK: NOT metabolized by -Same CI: pregnancy, breast feeding, active
Rosuvastatin P450’s -Good for people on other drugs liver disease, & may cause problems in
kids
Niacin Niacin -Inhibits lipolysis in adipose -Increases HDL -Cutaneous Flush (b/c of
(Nicotinic Acid) tissue TAG prostaglandins tx w/ aspirin)
Vitamin B3 synthesis requird for -Hepatotoxicity (fatty liver b/c liver
VLDL Blocks is forced to keep its fat)
synthesis of VLDL -Impaired insulin sensitivity
-Myopathy (if given w/ statinjust
HDL, VLDL, LDL monitor closely)
ApoA1 Clearnce (HDL) -Pruritius
-Acute gouty attack
Fibrates Fenofibrate Activate PPAR activates Tx of hypertriglyceridemia -Mild GI (less common w/ fenofibr)
Gemfibrozil lipoprotein lipase -Gall stones (risk b/c more free
FA uptake fatty acids being excreted)
plasma TAG -Myositis (renal patients at risk)
-More breakdown of VLDL can cause
VLDL, IDL production of LDL in some
Modest LDL
HDL in most Drug interacts: compete w/ warfarin
for plasma binding sites
CI: Statins; safety in pregnancy not
known
Bile acid Cholestyramine Prevents reabsorption of -Tx of hypercholesterolemia (esp. -Steatorrhea, constipation,
Seq Colestipol bile acid synthsis in young and pregnant bloating, flatulence, nausea
uest Colesvelam uses cholest.  women) -Malabsorption of fat sol vitamins &
rant LDL-Recpt LDL -DOC for type IIa/b oral lipid soluble drugs (digoxin,
clearance hyperlipidemias warfain, & thiazides)
-Tx of pruritus (only -Colesvelam has fewer GI SE
-IF LDL the liver tries to Cholestyramine) caused by -VLDL & TAG
make more VLDL and accumulation of bile acid in
TAG synthesis hyper-TAG patients w/ biliary CI: hypertriglyceridemia
obstruction (e.g. in
pancreatic cancer)
Cholesterol Ezetimibe -Inhibits uptake of dietary -Hypercholesterolemia (when -Diarrhea, abdominal pain
Abs Plant sterols cholesterol by statin CI) -Used w/ statins -Headache
orpt blocking transporter -Rash & angioedema (rare)
ion (NPC1L1 receptr) in
Inhi GI  forces liver to CI: Breast feeding
bito synth more
rs cholesterol LDL
-Inhibit VLDL prodct LDL
PK: metabolized in SI & liver
w/ biliary & renal
exretion

57
 Omega 3-FA TAG biosynthesis & FA -Used if TAG >500mg/dL
(fish oils) oxidation

BLOOD DISORDERS
Drug Mechanism Clinical Use Side Effects
THROMBOLYTIC Streptokinase -Acts on both bound & free - IV in short term emergency -Excessive bleeding, possible
AGENTS plasminogen plasmin not clot management of coronary intracerebral hemorrhage
specific deplete circulating thrombus in MI, DVT, PE -Hypersensitivity rxns &
fibrinogen, & factors V, VIII -EARLY ADMINISTRATION!! hypotension
-used in situations angioplasty is -antigenic, s trep antibodies
not readily available may activity
Antidote: aminocaproic &
tranexainic acids
Urokinase Human kidney cells Same
Generates plasmin
Alteplase (tPA) Recombinant Same, but also used in ischemic -No allergy problems b/c
Reteplase -Clot specific, acting mainly on fibrin stroke human recombinant
Tenecteplase bound plasminogen plasmin -Very $$ ($500/dose)

Anistreplase
ANTI- Block Aspirin -Irreversible acetylation of COX -Prophylactic treatment of
COX -Inhibits TXA2 (normally TXA2 transient cerebral ischemia
PLATELET
platelets to degranulate & aggregate) -Incidence of recurrent-MI
-Increases bleeding time -Mortality in post-MI
-Vascular COX is less sensitive to
aspirin than platelet COX
Block Clopidogrel -ADP Receptor Blocker - Ischemic events in patients Clopifewer SE(preferred)
ADP-R Ticlopidine -Irreversible inhibitors of P2Y12 (ADP with ischemic stroke, MI, or -Hemorrhage, leucopenia,
receptor subtype on platelet peripheral vascular disease thrombocytopenic purpura
surface)interfering w/ aggregation (alternative to aspirin) (making aspirin safer)
and activation by preventing ADP- -Used as antiplatetlet (instead
induced expression of platelet GP2b/3a of aspirin) if patient also has
gastric ulceration
Block Dipyridamole -Phosphodiesterase inhibitor cAMP -Little effect by self
PDE (Percantin (which platelet sensitivity to - Dipyridamole + warfarin
e) activating stimuli) prevent thromboemboli in
patients w/ artificial valves
-and block uptake of adenosine (acts at -Prophlaxis tx in angina
A2 receptors to activate platelet -Coronary vasodilator
adenylyl cyclase)??? -Aspirin + dipyridamole (extend
release) 2’ prophylaxis of
cerebrovascular disease

58
 Cilostazol -Phosphodiesterase inhibitor
-Promotes vasodiation and inhibition
of platelet aggregation
Block Abciximab -Monoclonal antibody against human
GPIIb GP IIb/IIIa receptor
/IIIa
- platelet aggregation by preventing
the cross linking rxn
Eptifibatide -cyclic peptide reversible antagonist
of GP IIb/IIIa receptor
Tirofiban -Nonpeptide reversible antagonist of
GP IIb/IIIa receptor
ANTICOAGULANT Heparin Renal excretion
Structure: large polysaccharide, water
soluble
-Kinetics: give parenterally (IV, SC),
hepatic & RES elimination; no placental
access, half life = 2 hrs
-Mechanism: binds antithrombin III
 serine protease-inhibiting activity
fast inactivation of IIa, IXa, Xa, XIa,
XIIa (binding of heparin to ATIII
allows it to rapidly inhibt thrombin
except that already bound to fibrin);
works on active form of factors,
inactivating intrinsic/common pathway
(i.e. works in plasma & works fast)
LMWH inhibit activated factor X but
have less effect on thrombin (II)
than UFH
Monitoring: PTT (no LMWH monitor)
Enoxaparin LMWH
(Lovenox)
Danaparoid -Mainly inhibits factor Xa, less
inhibition of thrombin
-LMWH-like from porcine gut mucosa
-Contains heparin sulfate, dermatan
sulfate, chondroitin sulfate
Fondaparinux -Factor Xa inhibitor
-Synthetic pentasaccharide, binds
antithrombin III which leads to
inhibiting of Xa;
-Once daily SC injection
Direct Factor Xa Rivaroxaban Direct Factor Xa inhibitor
Inhibitors Apixaban Direct Factor Xa inhibitor
Lepirudin Direct Thrombin Inhibitors (DTIs)
Desirudin -Recombinant forms of hirudin (from
Direct Thrombin Bivalirudin leech)
Inhibitors Argatroban -Directly bind to active site of
thrombin (independent of AT-III, thus
can reach and inactivate fibrin-bound
thrombin in thrombi)
-Monitored by PTT, given parenterally
Dabigatran Direct Thrombin Inhibitor
(pradaxa)
-Tx of intermittent claudication
-Acute coronary syndromes
-Post-angioplasty
-Acute coronary syndromes
-Post-angioplasty
-Acute coronary syndromes
-Post-angioplasty
-Good for emergency situations
-DOC for anticoagulation in
pregnancy
DOC for unstable Angina
DOC for MI
-Prophylaxis of deep vein
thrombosis in hip replacement
surgery
-Tx of HIT
-Prevention & tx of DVT
Bivalirudin + aspirin tx of
unstable angina when undergoing
percutaneous transluminal
coronary angioplasty (PTCA)
-Bleeding  1st sign
-Hypersensitivity rxns
-High doses AT-III
(sequestration) inactivat
of coagul factthrombosis
-Heparin induced
thrombocytopenia (HIT)
type II (antibodies to
complex of heparin and a
platelet protein, Platelet
Factor 4) platelet
aggregation & degranulation
discontinue heparin & give
a DTI or fondaparinux
-LMWH have longer half
lives, less thrombocytopenia
Antagonist: Protamine
sulfate chemical
antagonism, fast
-Less immunogenic, safer in
hypersens rxns to heparin
-No antidote
59
 Warfarin Structure: small, lipid soluble
(coumarins -Kinetics: lipid soluble ORAL, 98%
) protein bound, half life = 30+ hours;
placenta access, slow hepatic metab
-Mechanism: inhibits Vit K epoxide
Dicumarol reductase prevents -carboxy
liver synthesis of vit. K-dep. clotting
factors (II, VII, IX, X, protein C); No
effect on factors already present (i.e.
works on inactive forms of clot factors
in liver), effect takes 8-12 hours,
inhibit extrinsic/common pathway
Monitoring: PT (need close monitoring)
Antagonist: Vit K (slow onset), fresh
flozen plasma
Phytonadione Cofactor for synthesis of clotting
(Vit K) factors
Prophylaxis use
Drug interactions:
-Inhibitors of P450’s warfarin
activity (cimetidine macrolide,
azole antifungal)
-Inducers of P450’s: warfarin
activity (barbituates,
carbamazine, rifampin)
-Warfarin is an acidic molecule
abs by cholestyramine
-Displacement from plasma
proteins by other drugs free
fraction anticoagulat
Give for all coagulopathy as
adjuctive.
-Hemorrhage
-Bleeding of fetus
-Petechiae
-Adrenal insufficiency
-Low Therapeutic index
-Protein C deficiency
procoagulant effect in 1st
few days & thus requires
heparinization of patient
always before warfarin
Cutaneous necrosis (b/c
protein C)
CI: pregnancy
CI: Synthetic analogs
Hemolysis – G6PD
Kernicterus – newborn
(hyperbilirubinemia)

Deficiency
-decrease prothrombin/
clotting factors
-ecchymoses, bleeding
PRO-CLOTTING VIII Hemophilia A
IX From dried human plasma Hemophilia B (Christmas)
Has several Vit. K-dep. factors
Cryo-
precipitate
FFP
PCC Trivalent:

Quad-valent:
Plasminogen Tranexamic Inhibit conversion of plasminogen to
Activation Inhibitors acid plasmin
Aminocaproic Same Post-tPA, urokinase,
acid streptokinase
i.e. bleeding due to fibrinolysis
Thrombin Clots fibrinogen Topical hemostat (capillary
bleeding)
OTHER Protamine Heparin antagonist Anaphylaxis in some
sulfate From fish sperm vasectomy patients

ANTIPROTOZOALS
Drug Mechanism Clincal Use Side Effects
MALARIA Liver forms of malaria are common in plasmodium vivax and ovale.

60
 Chloroquine MOA: Drug is concentrated in
organism’s food vacuolein the food
vacule, the organism digets the host’s
Hbrelease of toxic hemeorganism
protects itself by polymerizing the
heme to hemozoinBUT chloroquine
binds to heme, preventing its
polymerization to hemozin pH,
heme = oxidative damage to
membranedeath of parasite and cell
PK: given PO rapidly, completely abs;
concentrates in erythrocytes, liver,
spleen, kidney, lung, crosses CNS
BLOOD SCHIZONTICIDE
(Erythrocytic phase)
-Gametocidal except for falciparum
Primaquine 8-aminoquinolone
-Liver phase of infxn
-Extensive metabolism (oxidation/
demethylation)
TISSUE SCHIZONTICIDE
Gametocidal
Pyrimethamine ANTIFOLATES!
Proguanil -Pyrimeth, proguan cycloguanil
Sulfadoxine* inhibits DHF reductase of parasite (at
Dapsone* low concentrations)
*Oral route, urinary elimination
Blood schizonticide & sporontocide-(in
mosquito’s gut)
Quinine -MOA: unknown…interfere w/ heme
polymerization death of erythrocytic
form of parasite? Prevent DNA strand
separation?
-Quinidine can be used in place of
quinine
BLOOD SCHIZONTICDE
Mefloquine -MOA: unknown
-PK: Long half life (6 days)b/c of
enterohepatic circulaiton; ONLY given
orally b/c IM causes irritation; highly
protein bound; 20% excreted
unchanged,
BLOOD SCHIZONTICDE
Amiodaquine Similar to cloroquine
BLOOD SCHIZONTICDE
-DOC for Tx of all malaria
(except resistant falciparum)
-Chloroquine + primaquine
Prophylaxis for all malaria
-Chloroquine + primaquine Tx
of persistent liver stage
-Chloroquine + emetine
Amebic liver abcess
-Collagen disorders/autoimmune
like lupus & RA due to the anti-
inflammatory effect
-Chloroquine resistant species
can expel the drug via a
membrane P-glycoprotein pump
Safe in pregnancy if traveling
-Tx exoerythrocytic forms of
recurring malarias (P. vivax and
ovale)
-Proguanil + Atorvaquone
(malarone) prophylxis of
resist falciparum
-Pyrimethamine + sulfadoxine
(fansidar) prophylaxis in
chloroquine sensitive regions
-Reserved for the serious
infections (IV dose)
-Tx chloroquine-resistant
falciparum (1st line therapy)
-Relieve leg cramps
-Myotonia congenital
-Sclerosing agent
-Quinine + doxycycline or
clindamycin or pyrimethamine
 limits toxicity & shortens
therapy
-1st line for prophylaxis (Use
doxycline instead??)
-Tx for chloroquine resist
falciparum (alternative)
-Safe for pregnancies if
traveling to chloroquine-
resistant areas
-Not available on USA market
Often used b/c of low cost,
limited toxicity, and sometimes
effective against falciparum
Amiodaquine + artesunatetx
falciparum (as an alternative)
Very well tolerated even w/
long use
1. Short term – GI
disturbance
2. Long-term – SIGHT,
HEARING DAMAGE
Toxicity: dizziness, blurred
vision, retinal damage,
headache, diarrhea, GI
irritation, epigastric pain,
exfoliative dermatitis, rarely
myocardia depression
*Long term high dose for
rheumatologic disease
irreversible ototoxicity,
retinopathy, myopathy,
neuropathy
*Causes EKG changes (b/c
quinidine like effect)
CI: psoriasis, porphyria
-GI irritation, H/A
-Agranulocytosis
-Pruritis
-Methemaglobinemia
-Hemolysis in G6PD def.
(primaquine is a cell oxidant)
-Pyrimethamine
megaloblastic anemia (tx w/
leucovorin)
-GI distress
-Sulfas crystalluria,
hemolysis, Steven-Johnson
syndrome
-Cinchonism (h/a, tinnitus,
vertigo blurred vision, GI
distress)
-Cardiac conduction
disturbances & hypotension w/
overdose
- Black water fever,
(intravascular hemolysis)
-Hemolysis in G6PD patients
-Avoid in psoriasis
CI: pregnancy (X)
-Cardiac conduction
abnormalities
-Avoid in psychiatric disorders
& seizures
-Neurological abnormalities
(people becoming vegetables)
-Agranulocytosis
-Aplastic anemia
-Hepatotoxicity
-Photosensitivity
-Dermatitis
-GI disturbances, H/A
61
 Halofantrine MOA: unknown
-Effective in erythrocytic phases
Doxycycline ANTIBIOTIC
Often used w/ quinine
Artemether MOA: metabolized in food vacuole
Artesunate PK: short half life (thus, not good
prophylaxis), lipid soluble
BLOOD SCHIZONTICDE
Atorvaquone -Inhibits electron transport/ATP
synthesis;
AMEBIASIS
(Drug choice DEPENDS ON CLINCIAL PRESENTATION)
Asymptomatic Intestinal Amebic Colitis metronidazole + luminal amebicide
infection  give luminal
amebicide TC + erythromycin (alternative) for moderate colitis
Dehydroemetine or emetine (alternative) for severe
infection, but usually avoided due to toxicities
Metronidazole MOA: prodrug bioactivation
AMEBIASIS Tinidazole (pyruvate:oxidoreducase – present in E. histolytica
anerobic bacteria)  forms a
cytotoxic product which binds to
protein and DNAkills parasite
PK: PO, parenteral
*It is elminated via hepatic
metabolism. Thus, any P450
drug
TISSUE AMEBICIDAL
Emetine MOA: Blocks ribosomal movement
Dehydroemetine inhibting protein synthesis
Only given to hospital patients
Narrow therapeutic range
PK: subcutaneously or IM,
concentrated in liver, spleen,
kidney heart; eliminated through
kidney
TISSUE AMEBICIAL
Diloxanide- MOA: unknown
furoate PK Oralhydrolyzed in gut
diloxanide (amebicidal) & furoate
(abs from the gut, conjugated in
liver & excreted in urine)
-Oral, 90% absorbed, conjugated
in liver, urine excretion
LUMINAL AMEBICDE
-Tx all malarias (even resistant) -Cardiotoxicity long QT
-Not available in USA, but -Embryotoxicity
approved by FDA -Limited use b/c of irregular
abs & cardiotoxicity
Prophylaxis for chloroquine-
resistant & mefloquine-
resistant falcip
-Tx multi-drug resistant Nausea, vomiting, diarrhea
falciparum (acts very rapidly)
-Only drugs reliably effective Very $$, limited availability
against quinine resistant strains (Not available in USA)
No resistance seen
Extraintestinal Infection metronidazole + luminal
amebicide
*10 day course of metronidazole cures 95% of
uncomplicated liver abscesses (can follow w/ choloroquine)
-DOC for all tissue infxns from -Seizures
-Ataxia
-DOC for Tx giardiasis -Disulfiram-like effects
-DOC for Tx urogenital -N/V, diarrhea
trichomoniasistx both partnr -Dry mouth/stomatitis
-Gardnerella vaginalis -Insomnia
-Anaerobic infxn “below the -Weakness
diaphragm” esp B. fragilis & -Potentiates coumarin drugs
C. difficile (DOC for -Urethral burning
Pseudomembranous colitis) -Metallic taste
-Acute ulcerative gingivitis
Safety in pregnancy not
-Cancrum oris
established,
-Ulcerative colitis
teratogenic/
-Cutaneous leishmania
carcinogenic in
-Decubitis ulcers
animals
-Alternative for Tx H. pylori
(metronidazole + TC + PPI/H2X)
-Severe intestinal & extra- VERY TOXIC
intestinal amebiasis Heartcloudy swelling &
*Almost completely replaced by necrosis, hypotension, CHF,
metronidazole arrhythmia, retrosternal pain
-Urticaria/ pruritic eruption
-Balantidium coli -N/V, diarrhea
-Fasciiola hepatica -Muscular weakness, pain,
-Pargonimus westermani abscess @ injxn site
-Fatigue, h/a, dizziness
DOC asymptomatic carriers Mild, mainly GI
of cysts -N/V, abdominal cramps
-Tx moderate/severe -Esophagitis
intestinal amebiasis -Dry mouth
*Kills amebiasis in 80-90% of -Pruritus
patients w/ single course of -Urticaria
therapy -Proteinuria
62
 Iodoquinol MOA: unknown -Alternate for tx asymptomatic Infrequent SE:
carriers -Diarrhea, anorexia, N/V
LUMINAL AMEBICDE -Alternate for Tx mild to High dosessystemic:
severe intestinal amebiasis -Nephrotoxicity
-Optic atrophy
-Peripheral neuropathy
-Thyroid enlargement
-Agranulocytosis
CI: thyroid, renal disease
Paramomycin LUMINAL AMEBICDE -Some efficacy against
cryptosporidiosis in AIDs
Tetracycline MOA: eliminates normal intestinal *Ineffective used alone CI: children under 8yrs &
flora (ameba’s main food source) pregnancy
-Chelates Ca, Mg, Al forms into non-
absorbable compounds
Chloroquine Tissue amebicidal Used in combo for hepatic absc See malaria
TRYPANOSOMIASIS Nifurtimox Tx of trypanosma cruzi (Chagas
disease)
Arsenicals Tx of African trypanosma
(rhondiense, gambiense)
LEISHMANIASIS Stibogluconate
TOXOPLASMOSIS Pyrimethamine +
sulfadiazine
GIARDIASIS Metronidazole
PNEUMOCYSTOSIS TMP-SMX DOC
Pentamidine Backups CI: foscarnet
Atovaquone Interferes w/ electron transport Backups Very toxic

ANITHELMINTHS
Typically, the treatment will be one large dose. So, the side effects generally are mild or not an issue.
FOR Mebendazole -Inhibits microtubule synthesis
NEMATODES -Depletes helminth energy stores
(“roundworms”) by decreasing glucose uptake
-Affected parasites are expelled w/
feces
-Rapid metabolization, reduced abs
w/ high fat meal
Thiabendazole -Inhibits microtubules synthesis
Larvicidal & ovicidal
Inactivated by liver hydroxylation
-Excreted urine/liver
DOC: Nematodes GI irritation
1. Whip worm (trichuris
trichuria); prolapsed Use w/ caution: in cirrhosis, in
rectum children under 2yrs
2. Pin worm (enterobius
vermicularis) CI: pregnancy
3. Hookworms (Necator
americanus & Ancyclostoma
duodenale)
4. Roundworm (Ascaris
lumbricoides)
1. Threadworm TOXIC
(strongyloides)alternat -CNS distorbances, n/v,
to ivermectin dizziness, anorexia
2. Trichinella (early stages) - Rarely, Steven-Johnson
3. Cutaneous larva migrans syndrome, erythema
(Ancyclostoma caninum, A. multiforme, fatalities
braziliense) alternative
to ivermectin CI: pregnancy, kidney/liver
*Much more toxic than other disease
benzimidazoles/ivermectin, so
other drugs are preferred

63
 Ivermectin MOA: GABA agonist, chloride influx
is enhanced hyperpolarization
paralysis of worm
PK: doesn’t cross BBB
Diethylcarbamazine MOA: not known
PK: Take after meals
Pyrantel-pamoate Depolarizing NM block spastic
paralysis of worm expelled from
GI tract
PK: poorly abs orally, exerts effects
in GI
Doxycylcine -Tetracycline
MOA: indirectly acting by killing
Wolbachia (intracell symbiont of
filarial parasites)
FOR Praziquantel MOA: permeability of cell
TREMATODES membrane to Ca paralysis of
(flukes) parasite
PK: rapidly abs orally, goes into CSF,
short ½ life
Bithionol MOA: inihibit helminth’s electron
transport chain
-Not available in USA
FOR CESTODES Albendazole MOA: Similar to mebendazole
(tapeworm)
PK: erratically absorbed after PO,
abs enhanced by high fat meal; rapid
first pass
*Give on empty stomach for luminal
parasites
*Give w/ fatty meal for use against
tissue parasites
Niclosamide -Salicylamide derivate
MOA: Inhibits parasit mitochondrial
anaerobic phosphorylation of ADP in
-Lethal for cestode’s scolex &
segments of cestodes, but not
against ova present in segments
-Give laxative prior purge bowl of
all dead segments to prevent
digestion and liberation of the ova,
which could lead to cysticercosis.
DOC:
1. Onchocerca volvulus
2. Strongloidiasis
-Tx scabies, lice, cutaneous
larva migrans w/ external use
DOC:
1. Lymphatic filariasis
2. Loa loa
3. Tropical eosinophilia
*Replaced by ivermectin for tx
of onchocerca
Broad spectrum antihelmintic
-Tx pinworm & Ascaris
(roundworm)
-Moderately effective for Tx
of hookworm
Tx Wuchereria bancrofti
-Also onchocerca
DOC:
1. ALL schistosomiasis
2. Most trematodes
3. Most Cestode
*Cysticercosis albendazole
preferred but prazi has similar
efficacy
DOC for Tx of fasciolia
hepatica (sheep liver fluke)
-Tx pulmonary paragonimas
westermani (alternate)
DOC:
1. Neurocystercosis (Taenia
solium) controversial
2. Hydatid disease
(Echinococcus)
3. Pinworm
Also: Hookworm, strongyloides,
trichuris
*Glucocorticoids usually given
gefore therapy to SE from
dying cysticerci
2nd line Tx of most cestodes
-T. Solium (followed by purge)
-T. saginata
-Diphyllobothrium (fish tape
worm, B12 def)
NO longer used in USA
-Mazotti rxn: killing of
microfilaria (oncocerca)
fever, h/a, dizziness,
somnolence, hypotension if
severe, given corticoids
CI: pregnancy, patients w/
meningitis
Lacks serious toxicity
Mild: n/v, diarrhea
-Drowsiness, dizziness,
malaise, anorexia, GI upset
-Not recommended in
pregnancy
CI: ocular cysticercosis
worm would blow up in
eyeblindness (tx surgical)
Drug interact phenytoin,
dexamethasone,
carbamazepine, cimetidine
(prazi b/c inhibit P450s)
Common/mild, can be severe
-Diarrhea, abdominal cramps,
anorexia, n/v, dizziness, h/a,
skin rashes
-Few SE w/ 1-3 day use
-Long term use (hydatid
disease)GI distress, h/a,
fever, fatigue, alopecia,
pancytopenia
-Neurocyster tx
inflammatory responses
*Follow blood count & liver
enzyms for long therapy
CI: pregnancy, kids <2yrs
Nausea
Abd pain
Pruruitis
Fever
*Avoid alcohol w/in 1 day of
Tx
64
 ANTIFUNGALS
Drug Mechanism
SUBCUTANEOUS Amphotericin B MOA: Binds ergosterol pores in
& SYSTEMIC membrane (increases permeability)
INFECTIONS -Low therapeutic index
-Fungicidal or fungistatic depending
on organism
PK: Slow IV infusion; extensively
bound to plasma proteins; little
goes into CSF give intrathecal in
meningitis (no inflamm effect on
meninges)
-Poorly absorbed from the GI, so
oral effective only on fngi within
the lumen of the tract (not
systemic)
-Half life is > 2 weeks
-Hepatic impairment, renal
impairment, and dialysis have little
impact on drug concentrations
Amphotec® New lipid formulations
Abelcet®
AmBisome®
Flucytosine MOA: Pro-Drug(fungal cytosine
deaminase) 5-fluorouracil (5-FU)
1. 5-FU5fdUMPinhibits
thymidylate synthase
inhibits DNA synthesis
2. 5-FUFUTP
incorporates into RNA
inhibit protein synthesis
PK: well absorb orally, enters CSF
Azoles
Imidazoles have two nitrogens on azol ring (ketoconazole, miconazole, clotrimazole). Triazoles have three nitrogens on the azol
ring (intraconazole, fluconazole, voriconazole, posaconazole). They all block 14-sterol demethylase(CYP 450)block
demethylation of lanosterol to ergosterol (blocks ergosterol synth). Generally, the imidazoles are less specific than the
triazoles. Effective orally & will have problems with absorption. Absorption is decreased by food and antacids. Resistance via
pumps.
Clincal Use
Broad spectrum
-DOC –for life threatening
systemic mycoses
(Candida, Histoplasma,
Cocidioides, Blastomyces,
Aspergillus, cryptococcus)
-Fungal mening (Intrathecal)
-GI mycosis (Oral)
-Tx of mucormycosis
Resistance:
-Fungi w/ low ergosterol in
their membranes
Used for those who cannot
tolerate Amphotericin B
-Tx systemic mycoses &
Cryptococcus meningitis
(Flucytosine + Ampho B)
-Tx Chromoblastomycosis
(Flucytosine + itraconazole)
-Synergistic (Ampho B
flucytosine penetrance)
Side Effects
“Amphoterrible”
Cumulative toxicity:
-Nephrotoxic (dose
dependent) tubular acidosis,
GFR, anemia
-Neurologic (intrathec neural
damage/seizures)
-Anemia (from EPO)
Infusion releated:
-Fever, chills, vomiting, h/a,
hypotension (sometime K+)
-Histamine release
-Alleviated partly by pre-tx w/
NSAIDs, antihistamines
Nephrotoxicity
-$$$
5-FU is an antineoplastic, so
would see those side effects,
which ar significant b/c tx
lasts 6-9 months
-BM depression (dose-
depend)
-Hepatic dysfunction
-GI disturbances
-Severe enterocolitis
*Flucytosine NOT used along
b/c synthesis of cytosine
resistance
65
 Ketoconazole -Less selective for fungalP450
than newer azoles)
-Disrupts membrane,
permeability
-Also inhibits gonadal/adrenal
steroid synthesis
PK: PO only; azoles = weak
acids abs w/ food or
antacids, (e.g. give w/ coke),
DOES NOT ENTER CNS
Itraconazole PK: PO, metab in liver
(CYP3A4) major metabolite
also antifungal
-Strong inhibitor of CYP3A4
-Does NOT enter CSF
Fluconazole -Enters CSF
-Slow metabolism, renal
excretion
-No endocrine side effects
-High oral bioavailability, wide
therapeutic index, NOT
dependent on gastric acidity
-Poorly metabolized
Voriconazole PK: PO, IV preps; metabolized
by multiple CYP450’s
-Goes into CSF
Posaconazole PK: Oral only, CYP3A4 inhibitor
-Administer w/ full meal
Echinocandins
-Goes into CSF
Caspofungin MOA: inhibit (1,3) glucan
Micafungin synthesisinterfere w/ fungal
Anidulafungin cell wall synthesis cell lysis
PK: only IV, not CYP450’s
CUTANEOUS Terbinafine Inhibits squalene epoxidase
INFECTIONS synthesesis of ergosterol in
dermatophytes
PK: PO, but for topical fungal
infxn; deposited in skin, nails,
fat; long ½ life (200-400hrs)
-Does NOT affect CYP450
-Rarely used to Tx systemic
mycoses b/c narrow spectrum &
adverse effects replaced by
itraconazole
-Active against Histo, Blasto,
Candida, and Coccidiodies, but not
aspergillus species.
-Still used for Tx of
mucocutaneous candidiasis
-Tx Cushings Syndrome,
Testicular Ca (anti-androgen)
Resistance seen esp in protracted
therapy w/ advanced HIV infxn
Broad spectrum
-Azole of choice (DOC) for Tx:
1. Blastomycosis
2. Sporotrichosis
3. Paracoccidiomycosis
4. AIDs-Histoplasmosis
-Broad spectrum
-Azole of choice for Tx of
systemic funal infxn less toxic
than amphoB and distributes to CNS
-Tx & prophyalxis (azole of
choice, DOC?)
1. Cryptococal meningitis
2. Candidiasis
3. Coccidoides
-Prophylactic in bone marrow
transplants & AIDs
Broad spectrum
Tx serious infections from
scedosporium, apiospermum,
fusarium species
-DOC invasive aspergillosis (seems
to have replaced ampho B)
-Broad spectrum, similar to
itraconazole
-Tx Mucor and other zygomycetes
-Tx Aspergillus & Candida (2nd line
after ampho B
DOC for dermatophytoses (esp
onychomycoses)
-Tx candida
-N/V, anorexia
-Allergic rash
-Inhibits steroid synthesis
cortisol, testosterone
Antiandrogen effects
libido, gynecomastia
-Liver dysfxn (rare)
-Nephrotoxic
INHIBTS CYP450’s  Many
drug interactions
CI: pregnancy
-N/V, rash, hypokalemia, h/a,
edema, hypertension
Least toxic azole
-NO endocrine effects
-Least effect of all azoles
on hepatic microsomal
enzymes
*Many drug interactions b/c
metab by multiple P450’s
-Transiet visual
disturbances, resolves in
30min-1hr (>30% of users)
-Fever, rash, nausea,
phlebitis, flushing (histamine
release)
-GI disturbances, h/a, rash
-Taste & visual disturbances
(rare)
-Possilbe hepatotoxicity
66
 Griseofulvin -Accumulates in keratin Tx Dermatophytes only (Replaced -Barbiturates absorption
containing tissues (keratin is in by terbinafine) -Hepatotoxic  metab of
hair, skin, nails) Disrupts -Microsporum warfarin, contraceptives
mitotic spindlesinhibits fungal -Epidermophyton -H/a post-discontinuation
mitosis -Trichophyton -Peripheral neuritis
PK: PO, but for topical fungal -Teratogenic /carcinogenic
infxn active, must given w/ -Can be given IV to tx Candidas if -Potentiates effects of
fatty meal, allergic to ampho B alcohol
-Induces CYP450 (so avoid
-Tx for 6-12mo w/ history of porphyrias)
Nystatin (topical) MOA: Similar to Ampho B Candidiasis Rare SE
-Not well-absorbed from GI -Vaginal –Lack of absorption
-Too toxic for IV -Skin -N/V
-Never used parenterally, only -Oral for topical tx of GI fungi
given PO (thrush)
Micoconazole MOA: same as ketoconazole -DOC – topical Tx of candida Rare SE
Clotrimazole Topical only -Micoconpotent inhib of
Butoconazole warfarin metabolism
Terconazole

OPIOD ANALGESICS
Headaches or mild/moderate pain is usually treated with an NSAID. Neurogenic pain responds best to anticonvulsants, TCA, or SSRI. However, for
severe or chroinic malignant pain, opiods are the drug of choice. Opiods interact with  (mu),  (kappa), and  (delta) receptors. The analgesic
properties are mainly mediated by the  receptors, but the with  receptors in the dorsal horn also contribute. The enkephalins interact more
selectively with the  receptors in the periphery. All the opiod receptors are Gi protein linked (cAMP). The respiratory depression of opiods is due
to suppression of the respiratory drive in response to high CO2 (opiods do NOT affect respiratory drive in response to low O2). The distribution of
receptors:
1.Brainstem receptors influence respiration, cough, nausea, vomiting, blood pressure, papillary diameter, and control of stomach secretions
2.Medial Thalamus receptors mediate deep pain that is poorly localized and emotionally influenced
3.Spinal cord Receptors in the substantia gelantinosa receive incoming sensory information, leading to the attenuation of painful afferent
stimuli.
4.Hypothalamus receptors affect neuroendocrine function
5.Limbic system greatest concentration of opiate receptors in the limbic system is in the amygdala. These do not exert analgesic action, but
may influene mood.
6.Periphery  Opiods bind to peripheral sensory nerve fibers and their terminals. As in the CNS, they inhibit calcium-dependent release of
excitatory proinflammatory substances (e.g. substance P) from these nerve endings.
 Longitudinal smooth muscle tends to relax
 Circular smooth muscle tends to constrict
7.Immune cells have a role in nociception (response to painful stimuli)

Tolerance is pharacodynamic (aka functional) because of a change in receptor sensitivity to drugs. Opiate receptors are Gi coupled, and tolerance
causes an cAMP production, escaping effects of opiates. Tolerance occurs in all CNS effects, but there is no tolerance in peripheral effects such as
miosis and constipation. Dependence is both physical and psychological.
Withdrawl syndrome (physical) yawning, lacrimation, rhinorrhea, salivation, t anxiety, sweating, goose bumps, muscle cramps, spasms, CNS originating
pain (mostly b/c excessive sympathetic response) (clonidine can be given for many symptoms, but the pain management must be centrally acting,
methadone is used because of its longer half life). Withdrawl lasts several weeks and is very PAINFUL. Withdrawl is also psychological, and craving
may be seen.

67
Why are opiods contraindicated in pregnancy? They are lipid soluble and would cross the placenta into the baby, causing respiratory depression. Most
likely the baby would be stillborn. Don’t forget that the baby cannat do glucuronidation. (Exception, you can give meperidine, not glucuronidated).
Class Drug Mechanism Clincal Use Side Effects
STRONG These drugs show a high affinity for  receptors and varying affinities for the other receptors.
AGONIST Morphine MOA: -Analgesia -Respiratory depression (most
-Act at CNS receptors -Tx diarrhea common cause of death in OD)
hyperpolarize nerve inhibit -Relief of cough (codeine or -Pin point pupils (morphine excites
firing dextromethorphan used now) the Edinger-Westphal nucleus of the
-Acts at k recptors in Lamina I/II -Tx acute pulmonary edema oculomotor nerve  parasymp to
of the dorsal horn release of eye)
substance P (modulates pain -Emesis (morphine directly stimulates
percept) the CTZ)
-Inhibits the release of many -GI symptoms ( circular SM tone,
excitatory transmitters from longitudinal SM relax constipat,
noceceptive nerves cramping, biliary pressure,
-No major cardiovasc effects
-Inhibits release of GnRH, CRH, -Histamine releaseurticaria,
LH, FSH, ACTH, -endorphin sweating, vasodilation, & sometimes
-GH, prolactin, ADH (causes bronchoconstrict
urinary retention) -Hormonal (can urinary retention,
but inhibit voiding, so may need a
PK: abs slow, erratic; significant catheter)
1st pass in liver, only small amount -Labor – may prolong the 2nd stage of
crosses CNS, duration of 3-5hrs labor b/c uterine contractions
-Liver conjugation morphine- -Enhances cerebral and spinal
6-glucuronide (100X more potent) ischemia
-Little effect on the heart

Drug interact: depressant actions

enhanced by phenothiazines, MOA-I,
TCA. Low doses of amphetamine or
hydroxyzine enhance analgesia
Caution: renal dysfunction
metabolite build uprespiratory
dysfunction
CI: Asthmatics, pregnancy (no
glucuronidation in newborn death
Meperidine -Antimuscarinic -Analgesia -NO miosis (pupil dilation)
MOA: 1. Biliary colic -Tachycardia
-IVDilates blood vessels, 2. Analgesia in pregnancy -NO GI/GU/gallbladder spasm
including cerebral vessels CSF (Baby’s have CYP450s, -Seizures (from serotonin)
pressure but main potential SE is -Respiratory depression similar to
-Contracts SM (lesser extent still respiratory morphine
than morphine) depression) -Antimuscarinic (e.g. dry mouth)
PK: short acting; metabolized by
CYP450normeperidine (SSRI) Drug interactions: SSRI (too much
Duration of 2-4hrs serotonin)
Methadone Causes less euphoria -Withdrawl maintenenance of -Biliary pressure
PK: PO good abs, longer duration opiate addicts -Constipation
(25hrs), -Physical dependence
Fentanyl PK: IV, epideral, intrathecal, rapid -Anesthesia -Respiratory depression
onset, short duration (15- -Tx of cancer patients w/ CI: fentanyl patch in the
30min) but half life terminal breathrough pain who are management of acute & postop pain
(9hrs); tolerant to opiods (Fentanyl (due to hypoventilation)
100X potent as morphine; metab patch used in chronic pain
by CYP3A4 managemnt)

Transdermal half life (17hrs)

68
 Alfentanil An ultra-short acting (5-10 min) -Analgesia Stronger respiratory depression than
derivative of fentanyl, but less fentanyl
potent
Sufentanil A more potent (5-10X) derivative -Heart surgury
of fentanyl
Remifentanil The shortest acting opiod w/ -Anesthesia
rapid offset, even after prolonged
infuss
Carfentanil Derivative of fentanyl, but -Veterinary medicine to
10,000X more potent immobilize large animals
(e.g.elephants)
Heroin Produced by diacetylation of morphine 3x more potent and lipid -Not used clinically in USA
solubility crosses CNS exaggerated euphoria -Used in the UK
Heroin is converted to morphine in body, but lasts half as long -most abused
Oxycodone -Semisynthetic morphine Tx. Severe pain -Abuse death
derivative
MIXED Nalbuphine k Agonist spinal cord analgesia, -Little abuse potential
AGONIST- Pentazocine dysphoria (as opposed to
ANTAGONIST euphoria)
 Antagonist precipitate
withdrawl
PARTIAL Partial agonists can precipitate withdrawl if the patient is taking a full agonist (e.g. heroin or methadone). The ceiling effect is
AGONIST seen with the partial agonists. At some point after continuing to up the dose, there is no further analgesic effect, only further
side effects. However, if you were using a full agonist (e.g. morphine) you cannot saturate the receptors and can continue to
increase dosing with increasing analgesia
Codeine Lower doses antitussive w/ -Cough suppressant (replaced by -Rarely produces dependence
little analgesic dextromethorphan)
-Analgesia (due to conversion to
morphine)
-Used w/ NSAIDS
Tramadol MOA: unknown, partial agonist?? Ceiling effect for respiratory
-Centrally acting, binds  depression
receptors
-Weakly inhibts reuptake of
serotonin & NE
Buprenorphine -Partial agonist at  receptors -Opiate detox less severe -Little sedation
-Antagonist at k recptors withdrawl symptom compared to -Little respiratory depression
PK: sublingual, parenteral, long methadone (ceiling effect)
half life (37hrs), OD hard to
reverse b/c high binding affinity
ANTAGONIST Naloxone PK: IV, PO; duration (60-100min) -Reversal for respiratory depression (IV)…can give for a relative
Competitive antagonist at at , overdose and the patient can walk out of the room…will drift back into
k,  receptors intox like an hour later
Naltrexone Much longer acting (48hrs), PO -Craving for alcohol (PO)
-Tx of opiate addiction (PO) for “painless withdrawl”rich kid put
on general anesthesia and muscle relaxants and given naltrexone to
mediate the biochemical withdrawl within 48 hours instead of a week…
and without seizures.
Alvimopan Peripherally acting antagonist at -Relief constipation from analgesic
 receptors, basically the “anti- therapy w/ chronic tx w/ opiods
loperamide
ANTIDIARRHEA Loperamide Peripheral opiate receptor Tx diarrhea
L agonist, not abs stays in the gut
Tinctura opii Basically pure opium -Given if loperamide isn’t enough, so
this would stimulate all the opiate
receptors
ANTITUSSIVE Dextrometorphane -no analgesia Tx of cough
Levopropoxyphene
Codeine

69
 Other Apomorphine -Dopaminergic agonist (D1,
D2) centrally acting
-Morphine derivative, but does
not contain morphine or bind to 
receptors
-Adjunct tx of Parkinsons
-Powerful emetic (Used to be used
for intoxications to cause emesis,
now used in torture)
-Alternative medicine, tx of
addiction, “vomiting therapy” for 2-
3weeks…low relapse rates

ANTIMYCOBACTERIALS

1st line for TB The treatment of TB is always multiple drugs, at minimum two drugs (both bacteriocidal). Most of these drugs will be used for
6mo-1yr for tx. Treatment is divided into two phases. The intensive phase lasts 2 months, and the Continuation phase is the
final four months of treatment. For example, the intial short course therapy for TB includes rifampin, isoniazid,
pyrazinamide, and ethambutol (RIPE) for 2 months. Then isoniazid and rifampin are given for the next 4 months.
Isoniazid and Rifampin will cure 95-98% in 9 mo. The other drugs are added to shorten duration of treatment.
Isoniazid (INH) MOA: INH = prodrug, needs -DOC in latent TB -Peripheral neuritis (20%)
bacterial catalase (KatG) to be Given 1 yr for PPD+ kids from B6 exretion (give B6),
turned on inhibits synthesis of (<3yr) restlessness, muscle
mycolic acid & cell wall effective -Prophylaxis: twitching, insomnia
against intracell and extracellular 1. Immunosuppressed -Hepatotoxicity (<2%) in
organisms 2. Infants of highly infx elderly due to conversion of
PK: well abs (not w/ antacids), Goes parents (used for 6 weeks) INH in the liver to hydrazine
into CNS 3. Close contacts of active TB (toxic metabolit) take
-INH is acetylated (genetic *INH is specific for TB, baseline hepatic enzyme level
variable), excreted through renal effective against intracellular -Sideroblastic anemia (no B6
bacteria  used in transaminase rxn
*INH is the most potent of TB to detox amino groups from
drugs, but never given alone. Resistance: INH)
-Deletion of KatG gene -SLE in slow acetylators
*Bactericidal for rapidly growing, -Deletion of inhA (codes for
but bacteriostatic for bacilli in the “target” low Resistance) Drug Interact:
stationary phase; -Inhibits phenytoin &
warfarin metab
-MAO-I tyramine rxn
Rifampin MOA: Inhibits RNA polymerase -Broader spectrum; -Hepatitis
(Rifabutin) (by inhibiting rho factor) -Rifabutin = DOC for TB -Rash, n/v
(Rifapentine) -Bactericidal against intracell & infected HIV patients b/c less -Induces many P450’s
extracell mycobacterial strains interaction w/ HAART drugs, (elimination of steroid Oral
(and other gram +/-) also better aginst MAC contracept)
-Enhances effect of -Red-orange metabolites
-Rifapentine- longer half life, amphotericin B in systemic (desmethyl?) all biological
permits weekly dosing; fungal infexn fluid turns red
-Tx of Brucellosis (Doxy + -Flu-like syndrome
Rifampin) -Take baseline hepatic
*Resistance via change in enzymes & CBC count
enzyme

70
 Ethambutol Inhibits synthesis of -Bacteriostatic, specific for TB Dose-dep retrobulbar (optic)
arabinogalactan (cell wall and M. kansasii neuritis visual acuity and
component) red/green discrimination
-Restistance: mutation of emb (Don’t give kids <5)
gene -Interferes w/ excretion of
uric acid
-Establish baseline visual
acuity and color vision
Streptomcin -May be included as 2nd line, see -One of the first drugs used to Deafness, vestibular
aminoglycosides tx TB, dysfunction, nephrotoxicity
Pyrazinamide MOA: unknown, but metabolically -Bactericidal to actively Hepatitis, polyarthralgia,
activated by bacteria (pncA dividing TB myalgia, rash, hyperuricemia,
gene) strains lacking the photosensitivity, porphyrin
bioactivating enzyme are resistanc Resistance  lack of pncA gene synthesis (porphyria)
-Take baseline hepatic
enzymes and uric acid
2nd line for TB The 2nd line drugs are either less effective, more toxic, or have not been studied as extensively. They are useful in patients who
cannot tolerate the first line drugs or who are infected with mycobacteria that are reistant to the 1 st line agents.
Capreomycin Inhibits protein synthesis -Reserved for tx of multidrug -Nephrotoxicity
resistant TB -Ototoxicity
Ethionamide Structural analog of Capreomycin, -Gastric irritation
but different MOA -Hepatotoxicity
MOA: inhibits acetylation of -Peripheral neuropathies
isoniazid -Optic neuritis
-Mental disturub, impotence
Cycloserine Bacteriostatic, inhibits bacterial -CNS disturbances
cell wall synthesis involving D- (psychosis)
alanine (alanine racemase) -Peripheral neuropathy
CI: Epileptic patients
Para-Amino- -Blocks dinhdropteroate -Alternative for ethabutol in -Hypersensitivity rxns
Salicylic Acid (PAS) synthase) kids < 5 yrs -Renal, thyroid, liver
-Does not go into CNS dysfunctions
Ciprofloxacin Fluoroquinolones Tx of multidrug resistant TB &
Ofloxacin some atypical strains
Sparfloxacin
Azithromycin Macrolides, use doses -Azithgood prophylactic for
Clarithromycin M. avium in AIDs
Azithromycin – long ½ life (4 days) -Part of the regimen that
Clarithromycin – short ½ life includes ethambutol and
rifabutin
-Tx of M. avium intracellulare
LEPROSY DRUGS Mycobacterium leprae (leprosy) does not grow on artificial media (obligate intracellular). Droplets from sneezes and nasal
mucosa are heavily infected. M. Leprae shows a predilection for peripheral nerves, skin, and mucosa of upper respiratory tract,
and it appears to grow in cooler areas of the body. Severeity depends on host immunity. Primary resistance is due to acquiring
infection from patients harboring resistant organisms. Secondary resistance develops during treatment from noncompliant or
subtherapeutic dosing.
TUBERCULOUS LEPROSY: Rifampin + Dapsone (for 6 months)
LEPROMATOUS LEPROSY: Rifampin + Dapsone + clofazimine (for 12 months)
Dapsone -Structurally & MOA like to -DOC for leprosy (daspone + -Hemolysis (esp in G6PD)
sulfonamides & inhibits folate rifampin) -Methemoglobinemia
synthesis -Tx pnuemocystis jiroveci -Peripheral neuropathy
-Short acting pneumonia -Drug induced SLE
-Bacteriostatic for M. leprae -Lepra Rxn Erythemia
nodosum leprosum (like
Jarisch Herxheimer rxn)
tx w/ clofazimine
Acedapsone Repository from of dapsone; longer
duration

71
 Clofazimine -Structurally related to dapsone, -Tx of dapsone-resist leprosy
but no cross resistance -Tx of Lepra Rxn
-Tx of leprosy in those not
tolerating dapsone
Amithiozone -Alternative to dapsone
-Used in combination
-Eosinophilic enteritis, GI
irritation
-Skin discoloration (red-
brown)

Disease Modifying Anti-Rheumatid Drugs (DMARD)

Rheumatoid arthritis appears to be an autoimmune disease driven primaryily by activated T cells (IL-1, TNF). NSAIDS offer mainly symptomatic relief.
They reduce inflammation and the pain it causes and often preserve function, but they have little effect on the progression of bone and cartilage
destruction. . The DMARDs have the potential to reduce or prevent joint damage, but the effects of therapy may take 6 weeks to 6 months to become
evident. You can start the patient on an NSAID in this window period. Combination therapy generally more effective: give weekly MTX and add other
agents (note: leflunomide + MTX increases the risk of hepatotoxicity, so monitor closely; Anakinra & TNF inhibitors increase the risk of neutropenia
and infections, so don’t use)
Class Drug Mechanism Clincal Use Side Effects
Methotrexate MOA: competitively inhibits AICAR -DOC for Tx of RA -Nausea
transformylase (the last step in de -Mucosal ulcers
novo purine synthesisIMP), causes -Hepatotoxicity (dose related)
AICAR levels which inhbits ADA -Hypersensitivty (rare)
andd AMP deaminase (no degradation -Pseudolymphomatous rxn
of AMPIMP). AMP is extracell (rare)
converted to adenosine by the ecto-
5’nucleotidase Antidote = leucovorin
-Adenosine is a potent anti- (toxicity)
inflammatory mediator (acts on A2b
receptors)suppresses NFkB
activation induced by TNF
Gold -IM formulations contain 50% -Used infrequently b/c of
Aurothiomalate elemental -gold; PO contain 29% gold toxicity
(IM) MOA: gold salts taken up by
Aurothioglucose macrophages and suppress
(IM) phaocytosis and lysosomal enzyme
Auranofin(PO) activity
CYTOTOXIC Chlorambucil -Probably phenylacetic acid mustard
AGENTS: (a metabolite) cross links
Alkylating agents DNApreventing cell replication
Cyclophosphamide -Phosphoramide mustard cross links -PO for tx of RA (not -Infertility (dose limiting)
DNAprevents cell replication effective IV) -BMS
-Suppresses T/B cell function by 30- -Tx SLE -Hemorrhagic cystitis
40%
Antimetabolites Azathioprine Purine antimetabolite 6- -BMS
MPsuppresses B/T cell function -GI disturbances
-Xanthine oxidase degrades it 6- -infexns & malignancies
thiouric acid prior to excretion via -Dose if given w/ allopurinol
urine
Leflunomide -Undergoes rpaid conversion to active -Patients not responding to -Diarrhea & elevation of liver
metabolite A77-1726inhibits MTX, give MTX + enzymes
dihydroorotate dehydrogenase de leflunomide
novo orate synth UMP p53
translocates to nucleus
-Lymphocytes arrested in G1 phase

72
 Mycophenolate See immunosuppress; IMP
mofetil dehydrogenase inhibitor (isoform 2,
the one expressed in lymphocytes)
IMMUNOPHILIN Cyclosporine MOA: see immunosuppress; also
LIGANDS increases expression of TGF-B, a
potent inhibitor of IL-2 stimulated T
cell proliferation and generation of
CTL lymphs
ANTIMALARIAL Chloroquine MOA: mechanism of anti-inflamm -Often used as adjuvants to -Irreversible retinal damage
DRUGS Hydrochloroquine unclear NSAIDs (never gonna see the malaria
-Often given to those who comin’) less w/
have not responded hydrochloroquine
optimally to salicylates and
NSAIDS
D-penicillamine Analog of AA cysteine -Tx RA (after use of gold -Dermatologic problems
MOA: unknown salts has failed but before -Nephritis
use of corticosteroids) -Aplastic anemia
Sulfasalzine drug 5-aminosalicylic (5-ASA) + -Tx ulcerative colitis -Rash
sulfapyridine; metabolized by GI -Tx RA (5-ASA) -Dizziness, n/v & h/a
bacteria -Tx juvenil arthritis -Occasionally leukopenia
-TX ankylosing spondylitis
ANTI-CYTOKINE Adalimumab Human IgG1 anti-TNF antibody
DRUGS binds TNF-prevents interaction
w/ p55 & p75 cell surface
receptors downregulation of
macrophage & T cell function
Infliximab Chimeric monoclonal antibody that -Tx RA, ankylosing -B/c it is a chimeric therapy,
binds w/ affinity/specificity to spondylitis, Crohn’s disease, can  formation of human
TNF psoriatic arthritis antichimeric antibodies
-Given IV (HACA) give MTX to 
prevalence
-ANA antibodies & anti-double
stranded DNA found, but only
very rarely drug induce SLE
Etanercept Recombinant fusion receptor; has two -Injection site reactions
soluble TNF p75 receptor moieties erythema, local pain, swelling,
linked to the Fc portion of human itching (20-40% of patients)
IgG1 binds TNF and also inhibits -ANA antibodies & anti-double
lymphotoxin- stranded DNA found, but not
“cept” = receptor analog documented SLE
ANTI-INTERLEUKIN Anakinra IL-1 receptor antagonist
DRUGS
INHIBITORS OF Abatacept -Fusion protein composed of an
COSTIMULATION immunoglobulin fused to the extracell
domain of CTLA-4 (can bind B7)
-Inhibits activation of T-cells
Rituximab -Chimeric monoclonal antibody -Targets CD20 positive B
-Anti-CD20 lymphocytes
GLUCOCORTICOIDS -Inhibit phospholipase A2 -Can slow down the -Fractures, infections,
-Also selectively inhibit expression of appearance of new bone cataracts
COX-2 erosions -Diabetes, hypertension,
-Alleviate pain (intra- accelerated atherosclerotic
articular glucocort) heart disease

73
 ANTI-DIABETIC DRUGS
Class Drug Mechanism Clincal Use Side Effects
INSULIN Insulins may be in suspensions, the thicker the suspension (i.e more complexing agent), the slower the kinetic. Insulin will be
ANALOGS used to treat type 1 DM, life-threatening hyperkalemias, and stress induced hyperglycemia.
Lispro Not suspension, IV solution
Rapid Acting Onset: 0.3-0.5h
Peak effect: 1-2h
Duration: 3-4h
Aspart Rapid & short acting
Glulisine

Regular Insulin Not suspension, IV solution

Short Acting (Regular Humulin) Onset: 0.5-1h
Peak effect: 2-4h
Duration: 5-7h
Short acting, soluble, crystalline zinc insulin, usually given SC
Lente Suspension (30% semilente, 70% ultralente), given only SC
Intermediate Onset: 2-4h
acting Peak effect: 8-12h
Duration: 18-24h
Semilente Insulin Amorphous precipitate of insulin with zinc ion in acetate buffer;
suspension not suitable for IV (only SC)
Neutral protamine -Suspension of crystalline zinc insuoin combined at neutral pH
Hagedorn (NPH) with protamine (positively charged polypeptide) (only given SC)
(AKA isophane insulin
suspension)
Ultralente Suspension -Used to have a baseline
Long Acting
Onset: 3-4h insulin level in a diabetic
Peak effect: 8-16h (LONG ACTING) patient
Duration: 18-24h
Glargine LONG ACTING
Detemir LONG ACTING
ORAL Tachyphylaxis is a term describing a rapid decrease in response to the drug after repeated doses over a short period of time.
SECRETOGOGUES This may be due to change in drug metabolism, progression of B cell failure, change in dietary compliance, misdiagnosis of slow
onset type 1 DM. Most of these patients will eventually require insulin. Since some of these drugs are cleared by liver or
kidney, drug interactions will cause hypoglycemia. Cimetidine (inhibit p450) for the liver metab or acetylacetates (kidney).
Long term administration of oral secretogogues reduces serum glucagon levels, which may contribute to the hypoglycemic effect
of the drugs.
SULFONYLUREAS MOA: Block (bind SUR1 subunit) the -Used in Type 2 -Hypoglycemia
ATP-dep K+ channels on B-cells (like diabetics -Weight gain
ATP)  insulin release, glucagon -Hypersensitivity (possible cross-
release, insulin receptor sensitivity allergy w/ sulfonamides
-Tachyphylaxis
Drug interactions:
-Mainly w/ first generation
drugs hypoglycemia w/
1st generation cimetidine insulin, salicylates,
Sulfonylureas sulfonamides
Tobutamide -Short duration of action, rapidly Appropriate in renal
metabolized by the liver dysfunction
-Safest sulfonylurea
for use in elderly
diabetics

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 Chlorpropamide Long acting, slowly metabolized by -SIADH (drug potentiates action
the liver of ADH)
-Transient hematologic toxicity
(leucopenia, thrombocytopenia)
-Disulfiram rxns
CI: elderly patients
Acetohexamide Active metabolites, cleared by kidney
dose in renal dysfunction
Second generation sulfonlyreas have increased potency by weight compared to the first generation. They have decreased side
2nd generation effects and are more expensive. They should be used with caution in patients with cardiovascular disease.
Sulfonylureas Glipizide Shortest half life (2-4h), metaboliz -Safe to use in elderly CI: hepatic impairment & renal
by liver (little hypoglycemia) insufficiency
-Absoption delayed w/ food (take
30min before breakfast)
Glyburide Metabolized in liver, longer acting -Causes hypoglycemia in 20-30%
CI: hepatic impairment & renal
insufficiency
Glimepiride Long duration & most potent once -Hypoglycemia in only 2-4%
daily dosing & improves compliance;
metabolized by liver
-Sometimes called 3rd generation
Repaglinide MOA: like sulfonlyureas, stimulate -Postprandial glucose -Do not use w/ sulfonlyureas
insulin release by binding to SUR1 and regulators (b/c so rapid) -No sulfur in the structure
Meglitinide analogs inhibiting ATP-dep K+ channel -Used in Type 2
PK: rapid onset (peak at 1hr), short diabetics w/ sulfa Drugs interactions:
duration (5-8hr), metab by CYP3A4 allergy -Drugs that inhibit CYP3A4
-Take just before each meal enhance glucose lowering effect
*Not as effective as sulfonlyureas in -Drugs that induce CYP3A4 lower
reducing FPG and HbA1c levels effects
Nateglinide -Newer drug, SAME as repaglinide SAME SAME
-Also partially restores initial insulin -Safe in patients w/
release in response to glucose (lost in renal function
type 2 DM -In contrast to other
-Cleared by CYP2C9 and 3A4 oral secretogogues, dose
-Duration is less than 4 hrs titration not required
INSULIN Two classes of agents, the biguanides and thiazolidinediones, improve insulin action. These agents lower blood sugar by improving
SENSITIZERS target cell response to insulin (thus require insulin for action) without increasing pancreatic insulin secretion. These drugs are
euglycemic
Biguanides Metformin MOA: Inhibits hepatic -Newly diagnosed Type -Risk for hypoglycemia is very low
gluconeogenesis hepatic glucose 2 DM (1st line) -GI distress (anorexia, n/v/d)
output; also slows intestinal abs of -Tx of polycystic ovary -Small risk of potentially fatal
sugars & improves peripheral glucose disease lactic acidosis (impairment of
uptake & utilization -Decreases body weight liver gluconeoblocks liver
-NOT metabolized, excreted as an -Only hypoglycemia metabolism of lactic acid)
active compound by kidneys agent shown to -Absorption of B12 (long term
-Hyperlipidemia (LDL & VLDL) macrovascular events use) annually screen B12 levels
cholesterol &HDL, (plasma TAGs by in Type 2 DM
15-20%) CI: Renal or hepatic disease,
*Equivalent efficacy to sulfonylureas alcoholism, acute MI, severe
in FPG and HBA1c infection, or diabetic
ketoacidosis due to risk of
lactic acidosis
Thiazolidinediones have “thio” in the name, noting that they have sulfur in their structure and may cause hypersensitivity. Since
Thiazolidinediones another thiazolidinedione (troglitazone) was withdrawn from the market because of hepatic toxicity, liver function enzymes are
routinely monitored.

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 Pioglitazone MOA: ligand of PPARy, a nuclear Mortality & -Hepatotoxicity (watch liver enz)
receptor (promotes glucose macrovascular events -Less hypoglycemia than
uptake/use, modulates synthesis of sulfonylureas
lipid hormones or cytokines, -Prevention of Type 2 -Weight gain
adiponectin?, adiopcyte production diabetes -Fluid retention (presents as mild
& secretion of FA) insulin anemia w/ peripheral edema)
sensitivity/resistance in adipose
tissue, liver, & skeletal muscle Drug interactions: oral
-Also has PPAR- effects contraceptives
-Metabolized by 2C8 & 3A4 to active -CI: pregnancy, heart failure, liver
metabolites disease
Rosiglitazone Ligand of PPARy, less TAG effects Same, but no significant drug
-Metabolized mainly by 2C8 and 2C9 interactions
to active metabolites
-GLUCOSIDASE Acarbose Competitive e inhibitors of the Used as monotherapy in -Gas, diarrhea, abdominal pain
INHIBITOR intestinal  glucosidases type 2 DM or in -Hypoglycemia if combined w/
postprandial hyperglycemia combinations sulphonureas must tx w/ glucose
Miglitol Same effects, different structure, (dextrose) NOT sucrose
much more potent (breakdown blocked
CI: renal impairment or IBD
DPP-4 INHIBITOR Sitagliptin Inhibitor of dipeptidyl peptidase-4 -Potentiation of glucose
(DPP-4), the enzyme that degrades mediated insulin
GLP-1 and other GLP-1-like secretion, suppression
of postprandial glucagon
INCRETIN Exenatide Synthetic analog of GLP-1 N/V/D
ANALOG
AMYLIN ANALOG Pramlintide Amyli is a small polypeptide released by the -cells of pancreas at
the same time as insulin. Amylin is also deficient in diabetics. It
slows gastric emptying and promotes satiety glucose in
blood. It is used as an ajunct in both type 1 & 2 DM

HYPOTHALAMIC & PITUITARY

Drugs that mimic or block the effects of hypothalamic and pituitary hormones have three primary applications:
1.Replacement therapy for hormone deficiency states
2.Antagonists for diseases that result from excess production of pituitary hormones
3.Diagnostic tools for identifying endocrine abnormalities
Class Drug Mechanism Clincal Use Side Effects
GROWTH GH (somatotropin) secretion varies throughout life. Secretion is high in childhood, reaches maximum levels during adolexcence &
HORMONE (GH) decreases as the age advances. Amplitude of GH secretory pulses is maximal at night, shortly after the onset of deep sleep. GH
release is stimulated by 5HT, clonidine, & HYPOGLYCEMIA. GH release is suppressed by IGF-1, free fatty acids, &
hyperglycemia
Somatropin Recombinant human GH -Tx of GH-dep growth retardation KIDS:
Somatrem (rhGH) (symmetrical pituitary dwarfism) -Intracranial hypertension
PK: given SC or IM 3X/week, -Improves muscle or bone strength (rare)
onset=2-4h, duration =36h -Tx AIDs associated wasting -Scoliosis from rapid growth
syndrome -Hypothyroidism
-Tx of growth failure in Prader Willi ADULTS:
Syndrome -Tend to have more AE
-Tx of Turner syndrome (increase -Peripheral edema, myalgias,
height) arthralgias (esp hands/wrist)
CI: patients w/ malignancies

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 Mecasermin Recombinant IGF-1 (& IGF -Tx of GH insensitivity (Laron -Hypoglycemia (eat a snack
binding protein-3) dwarfism) 20min before or after drug)
-GH deficiency & anti-GH antibodies
GH ANTAGONIST Octreotide Somatostatin analog (45X -Tx small GH-secreting ademonas Very $$$
Lanreotide more potent in inhibiting GH, (whichgigantism/acromegally) -Gall stones & pancreatitis w/
2X potent in inhibiting insulin -Tx many hormone secreting long term use
secretion) reduces GH tumors (e.g. Carcinoid syndrome, -n/v/d, abdominal cramps,
product gastrinoma, glucagonoma) flatulence, steatorrhea
-Long duration
Bromocriptine Dopamine receptor agonist Tx acromegally
reduces GH production
Pegvisomant Prevents GH from activating Tx acromegally
its receptor
GHRH Sermorelin GHRH analog -Used to test for GH secretion
-Stimulate GH (for short people)
GONADOTROPINS are used to induce ovulation in women with anovulation due to hypogonadotropic hypogonadism, polycystic ovarian syndrome,
obesity, & other causes. Because of the high cost of gonadotropins and the need for close monitoring during their administration, gonadotropins are
generally reserved for anovulatory women who fail to respond to other less complicated forms of treatment (e.g. clomiphene, AI, metformin). The two
most serious complications in women treated with gonadotropins and hCG are the ovarian hyperstimulation syndrome (0.5% of pateints ovarian
enlargement, ascites, hydrothorax, hypovolemia, sometimes shock) and multiple pregnancies (risk at 15-20%).
Menotropins (hMG) Extracted from the urine of -Used in hypogonadal states of men
postmenopausal women (FSH- & women
like and LH-like & hCG?)
FSH Urofolitropin Purified preparation of human -Stimulates gametogenesis & follicle
(uFSH) FSH extraceted from the development in women &
urine of post-menopuasal spermatogenesis in men
women -Tx infertility
-Tx hypogonadotropic hypogonadism
& associated oligospermia
Folitropin alfa Recombinant forms of FSH
Folitropin beta (rFSH), shorter half life than
ones from urine
LH LH is a major stimulant of gonadal steroid production. It regulates follicular development and ovulation. No pure preparation of
LH is available for use. Drugs may produce ovarian hyperstimulation or familial ovarian hyperstimulation, causing multiple
pregnancies (Rx. Ganirelix)
Lutropin Recombinant hman LH (rLH), -Stimulates follicular development in
given SC, half life of 10h infertile women w/ profound LH def
(Lutropin + Folitropin alfa)
hCG -Purified hCG from the urine -Used in infertility
-LH agonist
Choriogonadotropin Recombinant hCG (rhCG)
alfa
GnRH Leuprolide -Given in pulsatile doses, Long acting agonists -Gonadotroph suppression
Histrelin resembling physiological -Tx prostate cancer does not occur immediately
cycling -Endometriosis (tx up to 6mo) (transient flare up initially)
-Continuous dosing would LH -Precocious puberty -Less likely than gonadotropins
& FSH -Uterine leiomyoma (tx 3-6mo) to cause multiple pregnancies
-First 7-10 days causes “flare” & ovarian hyperstimulation
& afterwards suppresses Pulsatile: syndrome
PK: injected once daily -Amenorrhea, infertility
Goserelin PK: depot injection 1x/mo -Cryptorchism
Nafarelin PK: Nasal spray, longer lasting

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 GnRH Ganirelix When gonadotropins are used -Used in controlled ovarian -These produce an immediate
ANTAGONIST Cetrorelix to stimulate follicle develop hyperstimulation until the effect (as opposed to GnRH
risk of premature endogenous apprapriate follicular maturation has agonists), so don’t need to use
surge in LH b/c of rapidly occurred, then drug discontinued until day 6-7 of cycle
changing hormones the LH -Lower risk of ovarian
surge could prematurely hyperstimulation syndrome
stimulate ovulation -Adherence is critical b/c
effects reverse very quickly
Abarelix Palliative prostate cancer
PROLACTIN Prolactin is responsible for lactation (milk production). Hyperprolactinemia inhibits GnRH release causing hypogonadism and
infertility. Also seen with high prolactin levels are amenorrhea, galactorrhea in women, & loss of libido & infertility in men.
Prolactin -No therapeutic value
PROLACTIN Bromocriptine Dopamine agonist, affinity -Suppresses prolactin release -Light headedness, h/a, nausea
ANTAGONIST Cabergoline for D2 receptor -Shrink pituitary prolactin secretg -Orthostatic hypotension
Pergolide -Bromocriptine ½ life = 7h tumors & restore ovulation in many -Fatigue
-Pergolide ½ life = 20h -Acromegally -Psychiatric manifestations
-Cabergoline ½ life = 65h -Erythromelalgia (rare)
CORTISOL is bound to plasma Corticosteroid binding globulin (CBG), an 2 globulin synthesized by the liver that binds about 90% of the circulating
hormone. The remainder is free (5-10%) or loosely bound to albumin (5%). CBG is in pregnancy due to estrogen and hypothyroidism
CRH CRH CRH stimulates the release of -CRH can be used in the diagnosis of
ACTH from the anterior pituit ACTH secretion by pituitary
adenoma, adrenal & ectopic tumors
ACTH ACTH -Only used in diagnostic purposes in
adrenal insufficiency
Cosyntropin Synthetic analog of ACTH -DOC in infantile spasms
Tetracosactide

Signs of hyperthyroidism: 1) Marie’s sign- tremors of the body or extremity seen especially in outstretched hands, 2) Dalrymaple sign– staring look, 3)
Ballet sign– loss of voluntary movements of the eye, 4) Stellwag’s sign– infrequent blinking.

Steps in synthesis of THYROID hormones:

1.TSH stimulates the thyroid to uptake Iodide (I-) via the sodium/iodide symporter (NIS). This can be inhibited by thiocyanate (SCN-),
pertechnetate and perchlorate & radioactive iodide.
2.Oxidation to iodine (I2) by thyroid peroxidase at the apical membrane. Thyroidal peroxidase is transiently blocked by high levels of
intrathyroidal iodide and blocked more persistently by thioamide drugs
3.Then tyrosine residues on the thyroglobulin molecule are rapidly iodinated to form MIT & DIT in a process called iodide organification (occurs
in the colloid)…blocked by thioamide drugs
4.Condensation of two DITs produces T4 (still attached to thyroglobulin)…blocked by thioamide drugs.
5.Thyroglobulin is endocytosed back into the cell
6.T3 & T4 are cleaved from thyroglobulin via the lysosome and secreted into the plasma. Inhibited by Ipodate
7.Peripheral deiodination of T4 produces T3. Deiodination may occur in the inner ring, producing rT3, which is metabolically inactive. Amiodarone,
iodinated contrast media, B-blockers, corticosteroids, severe illness, or starvation inhibit the 5’ deiodinase necessary for the conversion
of T4 to T3, resulting in low T3 and high rT3 in the serum.

Goitrogenic: cabbage (contain thiocyanate), sulfodimethoxine, & cassave (contains carbohydrates and thiocyanate)

Severeal drugs may provoke autoimmune or destructive inflammatory thyroiditis hypothyroidism:

1.Amiodarone, structurally similar to thyroid hormone
2.Lithium, increased levels in thyroid gland inhibit release of hormones
3.Interferon Alfa & interleukin-2
TRH Protirelin -TRH stimulates TSH and -Test the anterior pituitary’s
prolactin secretion ability to secrete TSH
THYROID T3 & T4 T3 is fast acting, has short -Tx Myxedema -T4 sensitizes myocardium to the
HORMONES half life and more $$$ effects of sympathetics
Arrhythmias
-Thyrotoxicosis
-Osteoporosis?
-Borderline adrenal insuff
patient adrenal insufficiency

78
 THIOAMIDES Methimazole -Block thyroid peroxidase
-Block iodination of tyrosine
residue on TG
-Block coupling rxns
-Methimazole does not
inhibit conversion from T4 to
T3 (& antagonizes PTU)
-Methimazole is 10X as
potent as PTU
PK: given 1x/day, PO
Propylthiouracil Same, but also blocks
5’deiodinase in peripheral
tissue
PK: given 3x/day, PO
IODIDES Wolff-Chaikoff effect - large doses of iodides initially causes hypothyroidism for 10-14 days, but they the effect “escapes”
and thyroid hormone production resumes.
Iodine/Iodide salts -Inhibit organification
-Block hormone release
-The size & vascularity of
the hyperplastic gland
*Do NOT use alone b/c gland
will escape from iodide block
in 2-8 wksmay exacerbate
thyrotoxicosis
Lugols solution A mixture of iodine &
potassium iodide
Saturated solution Potassium iodide
ANION K+ Perchlorate Competitive block of iodide
INHIBITORS Pertechnetate uptake
Thiocyanate *Effects can be overcome by
large doses of iodides, so
effectiveness is somewhat
unpredictable
Iodinated Contrast Diatrizoate MOA: Rapidly inhibit
Media converstion of T4T3
PK: PO
Ipodate MOA: same, may also inhibit
hormone release from
thyroid gland
Iohexol MOA: same
PK: PO, IV
RADIOACTIVE 131-Iodine Emits  rays that destroy
IODINE thyroid after a few weeks
B-Blockers Esmolol Improve symptoms, but do
not alter thyroid hormone
levels
ANDROGENS
-Tx of thyrotoxicosis
(preferred drug b/c less serious
SE)
*Note, since the synthesis rather
than the release of hormones is
affected, the onset of these
agents is slow, often requiring 3-4
weeks before stores of T4 are
depleted.
-Tx of thyrotoxicosis
-Preferable in pregnancy
-Preferred in thyroid storm due
to ability to block T4 to T3
-Used prior to introduction of
thioamides in 1940’s, now rarely
used as sole therapy
-Improvement in thyrotoxic in 2-
7d (valuable in thyroid storm)
- Useful in preoperative prep
-Thyrotoxic crisis (Iodides +
PTU + B-blockers)
-Patients w/ iodide induced
hyperthyroidism
*Rarely used today b/c of SE
-Tx of hyperthyroidism (offlabel
use)
same
-Only isotope used in Tx of
thyrotoxicosis
-Tx of refractory Grave’s disease
-Tx tachycardia, tremors,
sweating from thyrotoxicosis
-Nausea, GI distress
-Altered sense of taste or smell
(only methim)
-Maculopapular pruritic rash
-Arthralgia
Rare:
-Agranulocytosis
-Hepatotoxicity
-Vasculitis (manifests as lupus)
-Cross placental barrier and are
concentrated by the fetal thyroid
(Category D in preg risk of fetal
hypothyroidism
-Same AE as Meth, but is more
highly protein boundless cross
placenta, so preferable in
pregnancy
-More serous AE
-Hypoprothrombinemia
-Jodbase-dow phenomenon
(hyperthyroidism in susceptible
people)
-Intraglandular stores of iodine
(may delay onset of thioamide tx or
prevent use of radioactive iodine)
-Avoid chronic use in preg (fetal
goiter)
-Iodide intoxication (iodism)
-Anaphylactoid rxn (angioedem)
-Brassy taste, burning of
teeth/gums
-Enlargement of parotid and
maxillary glands
Aplastic anemia
Relatively nontoxic
No risk of cancer
NO pain
Hypothyroidism
CI: pregnancy, nursing
79
 Oxandrolone Synthetic androgens -Replacement therapy in -Over-masculinization
Stanozolol hypogonadism, osteoporosis, and -Hirsutism (in women)
Fluoxymesterone could be used in growth -Depression of menses
Oxymetholone stimulation (muscle mass, RBC) -Acne
Nandrolone -Clitoral enlargment
Phenpropionate -Rarely causes hepatic adenomas
and carcinomas
-Cholestatic jaundice & prostatic
hypertrophy
-Premature closure of epiphysis
-May lead to dependence
CI: pregnancy
ANDROGEN Leuprolide GnRH analog @ continuous -Tx of prostatic cancer
ANTAGONIST Gonadorelin dose
Flutamide Receptor inhibitors -Tx of hirsuitism (cypro or
Cyproterone spironolac)
Spironolactone
Ketoconazole Steroid synthesis inhibitors -Tx of Cushing’s disease
Metyrapone Synthesis inhibitor (blocks
11-hydroxylation)
Finasteride 5- reductase inhibitor -Tx of benign prostatic
reduces production of DHT hyperplasia
Mifepristone Blocks Glucocorticoid & -Abortion
progestin receptors
ESTROGENS Estradiol is the major natural estrogen. Conjugated equine estrogen is purified from pregnant mare’s urine. The most common
synthetic froms are ethinyl estradiol and mestranol. Diethylstilbestrol is a nonsteroidal estrogen.
ESTROGEN Regulates growth & -Tx of hypogonadism in girls -Hypertension
maturation of reprod -Oral Contraceptive Pills (+ -Thromboembolism
tract Progestins) -Hepatic adenoma
Stimulates endomet growth -Postmenopausal HRT -Breast & endometrial cancer
Bone resorption & -Tx prostate cancer, acne, -Procoagulant (ATIII, & @
maintain normal structure dysmenorrheal, DUB dosesfactors II, VII, IX, X)
of the skin & blood -Endometrial hyperplasia, breast
vessels tenderness, migraine,
Thyroxin binding globulin cholestastasis
HDL and TAG levels CI: Hx of thromboembol,
LDL levels Pregnancy, Liver disease, Breast
Promotes coagulation cancer
Estradiol
Conjugated
estrogen
Ethinyl estradiol
Quinestrol
Clomiphene -Estrogen antagonist Multiple births, ovarian
(hypothal & anterior pit) enlargment, hot flashes, visual
-Estrogen Agonist (ovary) disturbances
PROGESTIN Progestin is normally not used, only the synthetic compounds. Progesterone is a progestin, but also androgenic and
antiestrogenic.
Medroxyprogestero
ne acetate
Norethindrone
Norethindrone
acetate
Desogestrel -NO androgenic effects
-NO anti-estrogenic effects
PROGESTIN Mifepristone
INHIBITOR (RU 486)
Other Danazol Partial agonist at -Used to tx endometriosis (anti- -Weight gain
progesterone, glucocorticoid proliferative effect by negative -Edema
80
 and androgen receptors feedback) -Acne
-HDL levels
Oxytocin Synthesized in 1. A uterine stimulant, used to -Hypertensive epidosdes (b/c of
(Pitocin) paraventricular nuclei of the induce or enhance labor contraction of blood vessels)
(Syntocinon) hypothalamus 2. Contracts myoepithelial cells of -Uterine rupture
breast & cuase milk letdown
3. Can control postpartal and
postabortal bleeding
ADH ANALOGS ADH is Synthesized in the supraoptic nuclei of the hypothalamus. Adverse effects generally include: hypertension, headache,
abdominal cramps, and nausea. Too much ADH think SIADH  hyponatremia, dizziness, volume contraction
ADH Receptors:
1. V1 in the arterioles vasoconstriction
2. V2 insertion of aquaporin channels in kidney
Desmopressin -Synthetic, long acting ADH -Tx diabetes insipidus from No effect on V1, so will not
analog at V2 only, not V1 surgery or trauma or cranial affect blood pressure (no
-Nasal spray radiotherapy for lymphocytic hypertension)
leukemia
Vasopressin Boosts factor VIII -Used in mild to moderate
hemophilia
-Used in bleeding from varices,
prior to definitive tx of portal
hypertension
PTH Teriparatide PTH analog, use once daily -Promotes osteoblastic activity
-Continuous PTH promotes new bone formation
osteoclastic activity

Calcium Salts Ca chloride IV preparations -Used in severe cases of -Peripheral vasodilation

Ca gluconate hypocalcemia -Transient tingling
-Cardiac arrhythmias (if rapid
infusion)
Ca carbonate Oral preparations -Preventive measures against
Ca citrate osteoporosis
Ca phosphate -Tx mild cases of hypocalcemia
Ca Lactate
Vitamin D Calcitriol Active form of Vit D Used in: -Vascular calcification
Cholecalciferol Vitamin D3 -Osteoporosis -Nephrocalcinosis
Ergocalciferol Vitamin D2 -Chronic renal failure -Soft tissue calcification
Calcifediol 25-(OH) Vit D -Nutritional rickets -HYPERCALCEMIA (typically
asymptomatic)
Bisphosphonates Etidronate (IV, PO) Inhibit osteoclastic activity -Tx malignancy associated -Erosive esophagitis (alendronate)
Pamidronate (IV) by disrupting mevalonate hypercalcemia -GI distress (gas)
Alendronate pathway ( osteoclast H+ -Tx paget’s disease of bone
ATPase) -Tx osteoporosis (esp -Osteomalacia if taken > 12 mo
“-dronate” -Reduce resorption and helps corticosteroid induced) (etidronate & pamidronate)
formation of hydroxyapatite
-Structural analog of
pyrophosphate Patient should stand for 30 min
-Very poorly absorbed (<1%) afterwards (reflux = caustic to
after oral administration, so esophagus)
must be given in fasting
state with

MULTIPLE SCLEROSIS
Class Drug Mechanism Clincal Use Side Effects

IFN B-1a Flu-like symptoms,

81
 transamonitis
Betaseron
Glatiramer Ac

Class Drug Mechanism Clincal Use Side Effects

ANTICONVULSANTS
Class Drug Mechanism Clincal Use Side Effects
General principles:
1.Select AED that is most efficacious for seizure type
2.Consider other comorbidities that may also be treated w/ AED (e.g depression, headache) or other special considerations (pregnancy)
3.Consider side effect profile
a. Inducers vs. inhibitors
b. There is decreased efficacy of oral contraceptives via induction of cytochrome P450. A person with seizures may want to avoid
pregnancy since many of the drugs cannot be taken, but remind patients that oral contraceptives are metabolized quicker
potentially causing an unwanted pregnancy.
c. Safe for pregnancy: f
4.Consider conviencence and dosing
5.Consider cost

The mechanisms of action:

1.Decrease axonal conduction by preventing Na influx through fast Na channels (blocks the propagation of seizures, does not prevent)
2.Increasing inhibitory tone by facilitation of GABA-mediated hyperpolarization
3.Decrease the excitatory effects of glutamate
4.Decrease the presynaptic Ca influx through type T channels in the thalamic neurons

Inducers: Phenytoin, carbamazepine, oxcarbazepine, phenobarbitol

Inhibitors: valporic acid

Approach to Status Epilepictus:

1st generation Carbamazepine Same as phenytoin Same -CNS depression

-CYP450 inducer -DOC for trigeminal -Exfoliative dermatitis (SJS)
neuralgia -Osteomalacia (Vit D)
-ADH secretion
-Megaloblastic anemia (folate)
-Aplastic anemia rare
-Teratogenic (cleft lip/palate/
spina bifida)
-Hyponatremia
-Hepatotoxicity
-Arrhythmia
Clonazepam
Clorazepate

82
 Diazepam
Ethosuximide Blocks T-type Ca channels mainly in DOC for Absence Blood toxicities
thalamus seizures
Phenobarbitol Act POSTsynaptically Block Sedation
glutamate receptors (and also help Dizziness
GABA) Impaired ognitive function
Hyperactivity
Rash
BM suppression
Hepatotoxicity
Frozen shoulder
Dupuytren contracture
Reduced libido
Phenytoin Blocks axonal Na channels in their -Blocks the propagation of -Induction of CYP 450
inactivated state seizures -CNS depression
-Non-linear kinetics ([blood] faster -Tx of any seizure except -Gingival hyperplasia (…
than expected) absence seizures remember dihydropyridines)
-Zero order elimination kinetics -Hirsutism
-Osteomalacia (Vit D)
-Megaloblastic anemia (folate)
-Aplastic anemia (check CBCs)
-Teratogenic (cleft lip/palate)
-Neuoropathy
-Cerebellar degeneration
-Lupus
-Lymphadenopathy
Primidone
Valproate -Like phenytoin (block Na channel) -Any seizure state (even -Inhibits CYP 450
-Inhibits GABA transaminase (blocks absence seizure) -Hepatotoxicity
degradation of GABA GABA) -Tx of mania in bipolar -Thrombocytopenia
-Block T-Type Ca Channels (thalamus) -Tx of migraines -Pancreatitis (rare)
-Alopecia
-Teratogenic (spina bifida)
2nd Generation Felbamate -Block Na channels -Hepatotoxicity
-Block glutamate receptor (NMDA) -Aplastic anemia
Gabapentin
Lamotrigine -Block Na channels -SJS rashes
-Block glutamate receptor (AMPA)
Lacosamide
Lamotrigine
Levetiracetam
Oxcarbazepine CYP450 inducer -Drowsiness
-Dizziness
-Diplopia
-Rash
-nausea
-Hyponatremia
-Lymphadenopathy
-Hepatotoxicity
Pregabalin
Rufinamide
Tiagabine Act PREsynaptically, inhibit
reuptake of GABA
Topiramate Act POSTsynaptically Block
glutamate receptors (and also help
GABA)
Viagabatrin Act PREsynaptically, inhibit
degradation of GABA (inhibits
GABA aminotransferase)

83
 Zonisamide Same as phenytoin

3rd generation

SEIZURE DOC
Partial seizure (simple or complex) Valproate, phenytoin,
carbamazepine
General-tonic clonic Valproate, phenytoin,
carbamazepine
General- Absence Ethosuximide
Status epilepticus Lorazepam (IV), diazepam,
phenytoin, or fosphenytoin

NEUROTRANSMITTER RECEPTOR EFFECT AGONIST ANTAGONIST

GABA GABA-A INHIBITORY: When two molecules of GABA Muscimol Picrotoxin
bind receptor, the ion gate is opened and influx Bucuculline
of Cl. Found throughout CNS, generates fast
IPSP
GABA-B INHIBITORY: GABA binds receptor and elicits
action through AC pathway (cAMP levels +
opens a K+ channel so that K+ flows out of the
cell hyperpolarization + closes Ca channel) 
slow IPSP
Glutamate NMDA STIMULATORY: When Glutamate + glycine Amantadine
(cofactor) bind NMDA receptor, the ion gate Memantine
opens with influx of Na and Ca and efflux of K. Ketamine
Stimulatory. A voltage dependent membrane PCP
depolarization is also required to open the gate Dizocilpine
b/c NMDA is plugged by extracellular Mg.
AMPA STIMULATORY: When Glutamate bind AMPA
receptor, the ion gate opens with influx of Na
and Ca and efflux of K. May play a role in
excitotoxicity in neuronal cell death
Glycine Glycine INHIBITORY: Glycine binds receptors found in
Receptors spinal cord causing ion channel to open and influx
of Cl
Dopamine D1 STIMULATORY: dopamine binds D1 receptor Pergolide
activates AC pathway (cAMP) and PLc pathway
(IP3 + DAG). Found in the CNS
D2 INHIBITORY: dopamine binds D2 receptor Bromocriptine
AC pathway (cAMP + opens K channel so efflux Pergolide
of K)  hyperpolarization Pramipexole
Ropinirole
Histamine H1 PLC pathway
H2 AC pathway Diphenhydramine
Cimetidine

84
 GENERAL ANESTHETICS
The stages of anesthesia (1-4):
1.Stage of analgesia: The patient initially experiences analgesia without amnesia. Later in Stage I, both analgesia and amnesia are produced
2.Stage of excitement: During this stage, the patient often appears to be delirious and may vocalize but is definitely amnesic. Respiration is
irregular both in volume and rate, and retching and vomiting may occur if the patient is stimulated. For these reasons, efforts mre made to
limit the duration and severity of this stage, which ends with the reestablishment of regular breathing.
3.Stage of surgical anesthesia: This stage begins with the recurrence of regular respiration and extends to complete cessation of spontaneous
respiration (apnea). The most reliable indication that stage III has been achieved is loss of responsiveness to noxious stimuli and
reestablishment of a regular respiratory pattern.
4.Stage of medullary depression: This deep stage of anesthesia includes severe depression of the vasomotor center in the medulla, as well as the
respiratory center. Without circulatory and respiratory support, death rapidly ensues.

Class Drug Mechanism Clincal Use Side Effects

IV ANESTHETICS Many IV drugs have an onset of anesthetic action faster than the most rapid inhaled agents (desflurane, sevoflurane).
Adjunctive use of potent opiods (fentanyl) contributes cardiovascular stability, enhanced sedation, and profound perioperative
analgesia. Benzodiazepines have a slower onset and slower recovery than the barbiturates or propofol and are rarely used for
induction of anesthesia. However, preanesthetic administration of benzodiazepines can be used to provide anxiolysis, sedation,
and amnesia when used in conjunction with other anesthetic agents
Hypnotics Propofol Short acting hypnotic -Induction & -Patients feel better in the
(Diprivan) -Alkylphenol/10% lipid (made from mantainance anesthesia immediate post-op b/c post-op n/v
”milk of amnesia” soy/egg) (most popular) -Cardiovas/resp depression
MOA: GABA & NMDA -DOC for ambulatory -Hypertriglyceridemia
surgery -Severe acidosis in kids w/
PK: half life = 15-20min; rapid -Given w/ adjuvant respiratory infection
hepatic clearance (10x faster than antimicrobials (infections Drug of abuse
thiopental) from bacterial -Burning at injection site (90%) b/c
Blood pressure during induction contamination of drug is a direct irritant to blood
through peripheral arterial emulsion) vessel (pain if lipids in emulsion)
resistance -Antiemetic Cerebral metabolic rate
Cerebral blood flow,  ICP
Etomidate -Short acting hypnotic Cardiovascular stability -Less Cardiovas/resp depression
-Imidazole (only dextro isomer w/ (NO histamine release)
anesthetic properties) -Burning at injection site
MOA: GABA? -Cerebral metab rate
Half life = 3-6 min; hepatic -Cerebral blood flow
clearance -ICP
-Myoclonic jerks
-Inhibition of adrenocortical
synthesis (8-24h)
-Proemetic
Ketamine -Moderately rapid action hypnotic -Bronchodilator -Oral secretions
(“Special K”) -Dissociative anesthetic -Good in elderly w/ CV -Night terrors
-Acrylcyclohexilamine (PCP-like, S- disase -CVS stable (slight stimulant), slight
isomer >>>> R) -Induction BP
MOA: NMDA -ICP, cerebral blood flow,
PK: Half life = 5 min; liver clearance cerebral metabolic rate
(hepatic active metabolite 30%- -Seizure activation
norketamine) -Emergent delirium, hallucinations
(emergent rxns impair recovery)
CI: intracranial surgery
Barbiturate Barbiturates reduce hepatic blood flow and glomerular filtration rate, but these drugs produce no adverse effects on hepatic or
renal function. Barbiturates can exacerbate acute intermittent porphyria by inducing the production of hepatic ALA synthase.

85
 Thiopental -Moderate duration thiobarbituarte -Tx seizure -People complain of “hangover”
-Rapid onset and rapid recovery -Given when operating on -Cardiovas/resp depression
(bolus dose); slow recovery following aortic arch to lower -Cerebral metab rate (55% w/
infusion cerebral meatab rate isoelectric EEG)
-Rapidly diffuses out of brain & is while blood flow is -Bronchoconstriction (histamine)
redistributed to muscle/fat stopped -Precipitation & porphyria
MOA: GABA agonist -Standard induction
Half life = 11min; hepatic clearance, agent CI: porphyrias
long elmination time -Used on patients w/
-30% dose in elderly cerebral swelling (b/c no
ICP from drug)
Methohexital Short duration oxybarbiturate -Used for ECT sedation -Mild cardiovas/resp depression
MOA: GABA (poor antiseizure med) -Can Cerebral metab rate (55%
PK: half life = 4 min, hepatic -Neurosurg ablation of w/ isoelectric EEGbut doesn’t
clearance (faster than thiopental) sezure foci (b/c drug can change the seizure threshold)
cause central excitatory -Hiccoughing
activity) Non-malignant hypertherm trigger
Opiods Fentanyl -Analgesia -Significant depression of
Hydromorphone -Blunt sympathetics hypercarbic respiratory drive
Benzodiazepines are primarily used as premediation before anesthesia b/c of sedative, anxiolytic, amnestic properties.
Benzodiazepines Compared with the IV barbiturates, benzodiazepines produce a slower onset of central nervous system depressant effects
which reach a plateau at a depth of sedation that is inadequate for surgical anesthesia
Midazolam PK: more rapid, shorter elimination -Used in balanced -AMNESIA
half life (2-4h); steep dose response anesthesia & conscious Flumazenil reversal available
curve; sedation, cardiovascular
-Water soluble stability
-DOC for parenteral
admin
Lorazepam Not water soluble
Diazepam Not water soluble
Dexmedetomidate -2 agonist (central > peripheral) -Atypical sedative -Little RR effects
PK: half life = 6min, but  w/ renal & (cardiac surgical -Twilight state
2 Agonist hepatic dysfunction indication, ICU & OR -Hypertension & bradycardia
use)’ -Low BP & bradycardia
-Used for people on
drugs?

86
 INHALED Volatile anesthetic = liquid at room temp, but evaporate easily (Halothane, Isoflurane, Desflurane, Enflurane, Sevoflurane)
ANESTHETICS
Uptake & Distribution of Inhaled anesthetics
1. Solubility – The blood:gas partition coefficient is a useful index of solubility and defines the relative affinity of an
anesthetic for the blood compared with that of inspired gas. So, low coefficients mean a relatively insoluble drug in the
blood (desflurane, nitrous oxide). When an anesthetic with low blood solubility diffuses from the lung into the arterial blood,
relatively few molecules are required to raise its partial pressure, and so arterial tension rises rapidly. If high arterial
tensions are reached rapidly, then there is a rapid equilibration with the brain and a fast onset of action. Conversely, for
anesthetics with moderate to high solubility (halothane, isoflurane), more molecules dissolve before partial pressure changes
significantly.
2. Anesthetic concentration in the inspired air – has direct effects on both the maximum tension that can be achieved in the
alveoli and the rate of increase in its tension in arterial blood. Increases in the inspired anesthetic concentration increase
the rate of induction of anesthesia by increasing the rate of transfer into the blood.
3. Pulmonary ventilation – the rate of rise of anesthetic gas tension in arterial blood is directly dependent on both the rate
and depth of ventilation (magnitude of effect related to the blood:gas partition coefficient). An increase in pulmonary
ventilation is accompanied by only a slight increase in arterial tension of an anesthetic with low blood solubility or low
coefficient but can significantly increase tension of agents with moderate to high blood solubility. THUS, hyperventilation
increases the speed of induction of anesthesia with inhaled anesthetics that would normally have a slow onset.
4. Pulmonary blood flow – An increase in pulmonary blood flow (ie increased CO) slows the rate of rise in arterial tension,
particularly for those anesthetics with moderate to high blood solubility. Increased pulmonary blood flow exposes a larger
volume of blood to the anesthetic. In persons with circulatory shock, the combined effects of decreased cardiac output
(resulting in decreased pulmonary flow) and increased ventilation will accelerate induction of anesthesia with halothane.
5. AV concentration gradient – dependent mainly on uptake of the anesthetic by the tissues

EFFECTS OF INHALED ANESTHETICS

 All inhaled anesthetics tend to increase right atrial pressure in a dose-related fashion, which reflects depression of
myocardial function. (Enflurane, Halothane more so)
 Inhaled anesthetics decrease the metabolic rate of the brain.
 The more soluble volatile agents increase cerebral blood flow because they decrease cerebral vascular resistance.
The increase in cerebral blood flow (thus ICP) is not wanted in patients who already have increased intracranial
pressure. At low concentrations, all of the halogenated agents increase cerebral blood fow, but at higher
concentrations, the increase in cerebral blood flow is less with the more insoluble agents.
 All volatile anesthetics are respiratory depressants and also depress mucociliary function in the airway. Prolonged
anesthesia may lead to pooling of mucus and then result in atelactasis and postoperative respiratory infections.
 Solubility: Halothane > Enflurane > Isoflurane > Nitrous Oxide
 Nitrous oxide has little effect on uterine muscle, but the halogenated anesthetics are potent uterine muscle relaxants
(concentration dependent)
 Minimum Alveolar Concentration (MAC) = concentration (as a % of inspired gas) to prevent movement in 50% of
people to a surgical incision
 Malignant Hyperthermia – hypermetabolic state in muscle tissue & dysfunctional Ryr1 receptor; seen in 1:15000 kids &
1 in 40000 adults; triggers include inhalation anesthetics and succinylcholine. The signs of MH include increased
ETCO2, trunk or total body rigidity, masseter spasm or trismus, tachycardia, tachypnea, acidosis, increased
temperature may be a late sign
Nitrous oxide PK; true gas, not metab (no -May be a better inducer -B12 inactivation
(“Laughing gas”) hetapotox), sweet smelling for those w/ CV disease -Spontaneous abortions
LOW SOLUBILITY than halothane -PostOperative Nausea Vomiting
-MAC = 104, low potency (30%)
-Cerebral metab rate -Minimal CV effects
-Least likely to cerebral blood flow
Note: of inhaled anesthetics
Nitric Oxide = NO -Expanding gas (75% N20 for 10 min
Nitrous Oxide = N2O = 2X size of pneumothorax b/c N20 is
20X more soluble than N2?)
-Diffusional hypoxia

87
 Desflurane Fluorinated methyl ethyl ether
-Isoflurane w/ a F- instead of Cl-
PK:
MAC = 6.1, low potency
LOW SOLUBILITY
-MAP in direct proportion to their
alveolar concentration due to 
systemic vascular resistance
Sevoflurane Fluorinated methyl isopropyl ethyl
PK: degraded by contact with the
carbond dioxide absorbent in
anesthesia machines to vinyl ether
called “Compound A”
MAC = 2.1, medium potency
LOW SOLUBILITY
-MAP in direct proportion to their
alveolar concentration due to 
systemic vascular resistance
-Bronchodilation
Isoflurane -Halogenated methyl ethyl ether
-MAC = 1.2, medium potency
Medium solubility
-MAP in direct proportion to their
alveolar concentration due to 
systemic vascular resistance
-Depressant effect on the EEG
Enflurane Halogenated methyl ethyl ether
-MAP in direct proportion to their
alveolar concentration due to CO
-Depressant effect on the EEG
Halothane Halogenated ethane
PK: 40% metab by liver (highest),
-HIGH SOLUBILITY
-MAP in direct proportion to their
alveolar concentration due to CO
(bradycardia w/ kids)
MAC = 0.75, High potency
-Depressant effect on the EEG
-Bronchodilation
-Pleasant smell
Methoxyflurane 70% metab by liver release
fluoride ions nephrotox
HIGH SOLUBILITY
Xenon Inert gas, “ideal agent”
MAC: High 70
VERY INSOLUBLE
SEDATIVE-HYPNOTIC-ANXIOLYTIC
GABA-A receptor activation opens Cl- channels. GABA-B receptors allow K+ effux. Both receptors cause hyperpolarization. Benzodiazepines and
barbiturates act only on the GABA-A receptors. Benzodiazepines use the y (gamma) binding site. Barbiturates bind at the  site.
-Ambulatory patients -Expensive
(rapid anesthesia, rapid -Caustic smell (too much too quickly
off) causes bronchospasms/coughing &
sympathomimetic SE)
-Carbon Monoxide production
-Little hepatitis risk
-Low volatility  need special
vaporizer
Cardiac stable: -[Compound A] renal damage
-Ischemic preconditioning -Expensive
(via K-ATP channels) -NO hepatitis risk
-Pediatric anesthesia
-Ambulatory patients
(rapid anesthesia, rapid
off)
-Mainstay anesthetic -Respiratory depression
-Possible coronary steal
Cardiac stable:
-Ischemic preconditioning
(via K-ATP channels,  w/
sulfonylurea &
hyperglycemia)
-precursor to Isoflurane -Mild generalized muscle twitching
(myoclonic) @ doses
-Respiratory depression
-Seizures
-Renal complications
-One of the most widely -Halothane hepatitis (cumulative, so
used internationally, not if used halothane in past, risk)
used in the USA -Intracranial pressure (ICP)
-Cheap -Sensitizes the myocardium to
-Still used in pediatric circulating catecholamines
anesthesia (being (epinephrine) may cause ventricular
replaced by sevoflurane) arrhythmias
-Malignant hyperthermia (give
dantrolene)
-Nephrotoxicity
-VERY slow onset and recovery
-CV stable EXTREMELY EXPENSIVE
-non-smelly
88
 Class Drug Mechanism Clincal Use Side Effects
Benzodiazepines Benzodiazepines are used in insomnia, anxiety, and as anticonvulsants. Benzodiazepines potentiate the action of GABA. They
have zero efficacy. Most of the benzodiazepines are very similar and really only differ in their pharmacokinetics. These drugs
are liver metabolized to active compounds (except for oxazepam, temazepam, and lorazepam). Because of all the active
metabolites, half-life of the drug does not correspond to duration of action. The onset of action is related to the relative
degree of lipid solubility. BZs that are highly lipid soluble (midazolam, triazolam, diazepam, flurazepam) have a more rapid
onset of action. Longer acting drugs will be used for anxiety, while the short acting will be used for insomnia. Just a few points
to remember…Do not treat pain with a benzodiazepine & benzodiazepines are NOT antipsychotics.
Midazolam Ultra-short acting (3-8h) -Use for uncomfortable -Drowsiness, sedation, confus
Triazolam procedures (Preop sedation, -Ataxis (vertigo, slurr speech)
Anesthesia) -Resp depression (very dose)
Temazepam Short acting, No active metabolites Sleep disorder -Amnesia (retrograde &
Oxazepam Anxiety (oxazepam) anterograde)
Alprazolam Short duration of action Anxiety, panic attacks, -Floppy infant syndrome if taken
(Xanex) phobias in the perinatal period
Lorazepam Short-medium duration (10-20h) Anxiety, preop sedation, - Libido
IV, no active metabolites status epilepticus (IV) -Enhanced sedation w/ many other
Diazepam -Very long duration (1-3 days) due to Anxiety, preop sedation, drugs
many active metabolites muscle relaxation, withdrawl
-Given IV states Long term:
-Sleep disturbances (REM is
Clonazepam Very long duration (1-3 days) Tx of epilepsy suppressed)
-Withdrawl syndrome (rebound
insomnia, anxiety)
Flurazaepam Short onset, long duration Acute Tx of insominia risk of falls in elderly
Flumazenil BZ receptor antagonist (BZ-1 & BZ- -Reverse the CNS -Will NOT reverse CNS
2) depressant effect of BZ depression of barbiturates or
overdose alcohols
Barbiturates Barbiturates increase the duration of Cl channel opening (allow GABA to stay on there longer), but they also have GAGAmimetic
activity at high doses. Barbiturates also inhbit complex 1 of the electron transport chain. Barbiturates are general inducers of
CYP450. Barbiturates induce metabolism of most lipid-soluble drugs, such as oral contraceptives, carbamazepine, phenytoin,
warfarin, ect.
Thiopental Ultra-short acting; extremely lipid Induce anesthesia (IV) -Sulfa allergies (thiopent)
soluble (half life = 3-10h) -Withdrawl (anxiety, agitation,
Pentobarbital Half life = 15-50 hours ER management of seizures life threatening seizures)
Phenobarbital Long acting (half life = 80-120 h) Tx seizures CI: porphyrias
Non-BZ drugs Zolpidem These are NOT benzodiazepines. They do not share the benzodiazepine stucture, but they bind to the
Zaleplon BZ-1 receptor specifically
BZ-1 receptor agonist Tx of insomnia -Less tolerance & abuse potential
-OD reversed by flumazenil
Buspirone No effect on GABA, Used for generalized anxiety -Nonsedative anxiolytic (as
5HT-1a portial agonist (modulates disorders opposed to BZ)
serotonin transmission) -Pupillary constriction
-Takes 1-2 weeks to have an effect -Nervousness, restlessness,
dysphoria, tachycardia

LOCAL ANESTHETICS
Class Drug Mechanism Clincal Use Side Effects

89
 DOPAMINE: Parkinson’s & Psychosis
Dopamine receptors are classifed into D1 and D2:
 D1Gs coupled
 D2Gi coupled. These receptors are the most sensitive (by about 1000x compared to D1)
o D2A = nigrostriatal pathway (cell bodies in substantia nigra project to the striatum, where they release DA, which inhibits
GABAergic neurons. In Parkinson disease, the loss of DA neurons in this tract leads to excessive ACh activity  extrapyramidal
dysfunction)
o D2C= mesolimbic pathway (cell bodies in the midbrain project to the cerebrocortical and limbic structures  functions include
regulation of affect, reinforcement (addiction), cognitive functions, and sensory perception. Psychotic disorders and addition are
partly explained by DA in these pathways… and drugs that DA functions reinforcemtn and at high doses may cause psychoses
o Tuberoinfundibular (Cell bodies in hypothalamus project to anterior pituitary and release DA prolactin
o Chemotactic trigger zone (activation of DA receptors  emesis
Class Drug Mechanism Clincal Use Side Effects
DA PRECURSORS Levodopa Prodrugdopamine: via aromatic -Symptomatic relief -Dyskinesias
amino acid decarboxlase (aka dopa -“On-off” effects
decarboxylase) in periphery & CNS -Psychosis
-Take on an empty stomach, don’t -In the periphery/GI tract n/v
take w/ B6 (DA metabolism) cardiac arrhythmias, hypotension,
-Response after 3-5yrs (tolerance flushing
+ sensitization) CI: history of melanoma, concomitant
use of MOA inhibitor
Carbidopa Inhibits DOPA decarboxylase -Blocks peripheral L-dopa + carbidopa:
CNS availability of L-dopa effects of L-dopa -Brown urine & saliva
-Does not cross into CNS -Always give L-dopa + CI: B6 (Breakdown of L-dopa),
carbidopa psychotic patients, glaucoma,
antipsychotics
COMT Increased L-DOPA causes a compensatory increase in COMT degradation of dopamine to 3-O-methyldopa, which competes w/ L-
INHIBITORS DOPA for active transport into CNS (decreasing L-DOPA in brain). 3-O-methyldopa is a partial agonist. So, in the presence of a
full agonist, it acts like an antagonist
Tolcapone COMT inhibitor, crosses into CNS -Use when other -Fulminating hepatic necrosis
therapies fail
Entacapone COMT inhibitor, acts only in -Largely replaced
periphery tolcapone
DA AGONIST Bromocriptine Ergot derivative No longer available in -Dyskinesias
USA -Psychosis
-Pulmonary & retroperitoneal fibrosis
Pergolide
Pramipexole Depends on good renal function
Apomorphine Injectible -Acute management of -Powerful emetic drug
“off phenomenon”
Ropinirole Not an ergot derivative Tx. of parkinsons Lower incidence of postural
hypotension, dyskinesia, vomiting and
hallucination, unlike most DA agonists
Rotigotine Available in transdermal
formulation (once a day)
ANTI- Benztropine Tremor and rigidity but have -Many side effects similar to atropine
MUSCARINIC Trihexyphenidyl little effect on bradykinesia CI: glaucoma, prostatic hyperplasia,
Diphenhydramine pyloric stenosis
MAO-B MAO-A breaks down NE and serotonin. MOA-B breaks down dopamine. Since MAO-B does not interfere with tyramine
INHIBITORS breakdown there is no “cheese” effect.

90
 Selegiline Inhibitor of MAO-B (not MAO-A -Insomnia
at recommended doses) -Severe HTN (@ doses)
-Selegiline is metabolized in body
to amphetamine
Rasagiline -Irreversible inhibitor of MAO-B
-5X more potent than selegiline
-Not metabolized to amphetamine
OTHERS Amantadine -MORE effective than -Antiviral Livedo Reticularis (skin mottling,
anticholinergics against rigidity & -Tx of parkinson’s purplic meshwork of blood vessels
bradykinesia generally around ankles)

PSYCHOSIS
Schizophrenia is a mixture of positive and negative symptoms. To fight the positive symptoms, you need a depressant, but that would worsen the
negative symptoms. Also, to fight the negative symptoms you need an antidepressant (i.e. stimulant), which would worsen the positive symptoms. The
main mechanism by which drugs will fight psychosis is by a blockade of dopamine D2 receptors and block of 5HT-2 receptors.
If you block dopamine, side effects may include:
1.Acute EPS from acute block of DA in the nigrostriatal
a. Presents like a pseudoparkinsonism, dystonia, akathisia
b. Management: antimuscarinics
2.Chronic EPS (aka tardive dyskinesia) from chronic block of DA receptors in the nigrostriatal, which may be irreversible
a. The brain may either upregulate the number or sensitivity of DA receptors, and the little DA around will cause hyperkinetic
movements
b. Management: discontinue drug (may cause a tremendous epidosde of psychosis) & switch to an atypical psychotic
3.Dysphoria, making compliance an issue
4.Endocrine dysfunction
a. Temperature regulation
b. prolactin
c. Eating (weight gain)
5.Antimuscarinic effects (tachycardia, seizure threshold)
6.-blocking (hypotension)
TYPICAL Chlorpromazine Ocular deposits in the lens
ANTIPSYCHOTICS Sedation
Thioridazine Such a strong antimuscarinic that -Little EPS
(Phenothiazines) it autotreats its EPS effects -Quinidine toxicity
-Strong  block -Retinal deposits
-Low potency Sedation
Fluphenazine High potency
Can give as depot form
(Butyrophenones) Haloperidol Can give as depot form -Most likely cause of neuroleptic
malignant syndrome and TD
-EPS
ATYPICAL Atypicals lack the tardive dyskinesias side effects. The newer antipsychotics also block the 5HT2 receptors, which are found
ANTIPSYCHOTICS presynaptically  increased release and synthesis of serotonin. This will address the negative symptoms of schizophrenia.
Clozapine -Block D2C receptors (found 5-10% of pts suffer agranulocytosis
mesolimbic, mesocortical) (need weekly blood testing)
-Blocks 5HT-2
-Moderate antimuscarinic
-Strong -blocker
Olanzapine -Block D2C receptor (not as well)
-Blocks 5HT-2
Risperidone Some tardive dyskinesia
Aripiprazole Partial agonist at D2 receptors -Not for severe psychosis
Blocks 5HT-2 b/c of ceiling effect

DEPRESSION
91
 Class Drug Mechanism Clincal Use Side Effects
TCA TCA have a number of SE:
1.Anti-cholinergic
2.Anti-adrenergic
3.Anti-histaminic
4.Other
Amitriptyline Tertiary amines block the reuptake of -Major depression COMA, CONVULSIONS,
Imipramine 5-HT > NE -Phobia CARDIOTOXICITY (the 3 C’s)
-OCD -Prevent antihypertensive action of
-Neuropathic pain 2 agonist & guanethidine
Nortriptyline Secondary amines block the re-uptake CI: MAO-I + TCA (if switching
Desipramine of NE > 5-HT b/w give washout period of 2-3
weeks

SSRI Fluoxetine Selectively block serotonin reuptake -Major depression -Sexual dysfunction (anorgasmisa)
Fluvoxamine -Bulimia
Sertraline -Anxiety disorder Withdrawl: (“finish”)
Paroxetine F = flu-like symptoms
Citalopram I = insomnia
Escitalopram N = nausea
I = imbalance
S = sensory stuff (e.g. itchy teeth)
H = headache/hyperarousal
SNRI Duloxetine 5HT & NE reuptake inhibitor at all
relevant doses
MAO-I Phenelzine Irreversible, nonselective inhibitor of “Cheese effect” (HTN crisis)
Tranylcypromine MAOs -Serotonin syndrome (if SSRI +
MOA-I
Molobemide Reversible, selelctive for MAO-A
OTHER Bupropion Weak reuptake blocker of DA and -Smoking cessation Minimal sexual SE (b/c does not
NE -WAS an antidepress enhance 5HT)
Mirtazapine 2 antagonist NE -HTN, tachycardia
-Weight gain
Trazodone 5HT by interfering w/ metabolism Antidepressant Cardiac arrhthmias
-Metabolized  serotonin agonist -Priapism
- Block
Venlafaxine Non-selective reuptake blocker devoid
of ANS sideffects (like a TCA, but no
SE)

BIPOLAR & ADHD

Rapid cycling Bipolar – at least 4 epidosdes of mood disturbances within the last 12 months
Class Drug Mechanism Clincal Use Side Effects
Lithium -Prevent the recycling of PIP2 -DOC for Bipolar -Tremor & life threatening
Ca seizures (dose depend)
-Inhibit cAMP signaling -Hypothyroidism w/ goiter
-Therapeutic index = 1-2 -For Toxicity (give amiloride) -Nephrogenic Diabetes Insipidus
-Lithium “looks like” Na+ -Chronic doses of diuretics
will clearance of lithium
Valproate Rapid cycling
Carbamezepine Pure and mixed mania

Methylphenidate Amphetamine derivative (a

releaser)

92
 Atomoxetine Selective NE reuptake inhibitor

Class Drug Mechanism Clincal Use Side Effects

Class Drug Mechanism Clincal Use Side Effects

93