Name

Mechanism

Furosemide
1. Block active transport of ions in the
Ascending Loop of Henle by
blocking the luminal Na-K-2Cl
cotransporter.
2. This leads to less reabsorption of
Ca2+ and Mg2+.
3. Leads to equal proportional loss
of water and sodium, so NO effect
on plasma osmolality.
Torsemide

Name

Mechanism

Hydrochlorothiazide
(HCTZ)

1. Inhibit the distal tubule Na/Cl

co-transporter
2. Lose more sodium than water, so
the plasma osmolality decreases.
3. Results in slightly lower Na+
concentration in the plasma, which
allows arteriolar smooth muscle to
relax.

Chlorthalidone

Name
Indapamide

Mechanism
Weak blockade of Na+
reabsorption in the proximal
tubule

Metolazone

Name

Weak blockade of Na+

reabsorption in the proximal
tubule

Mechanism

Spironolactone
Aldosterone Antagonist in the
principal cells of the Collecting
Tubule
Eplerenone

Amiloride
Traimterene

Inhibit luminal Na+ transport in

principal cells of the Collecting
Tubule

CA
Name

Mechanism

Acetazolamide

Name

1. Inhibit conversion of H+ and

HCO3- to/from CO2 and H20.
2. Diminish reabsorption of HCO3and Na+.
3. Net effect is reduced HCO3- going
back into the blood, and less H+
available in the nephron.

Mechanism

Mannitol

1. Non-electrolytes, but highly polar

(Confined to ECF; Don't enter cells)
2. Freely filterable at the glomerulus
3. Not reabsorbed
4. Provide a higher solute load in the
nephron
-Increased osmotic pressure in the
nephron decreases water reabsorption
-Leads to more water loss than
Na+ loss
5. Poorly absorbed, so given
parenterally (IV)

LOOP DIURETICS
Clinical Uses

1. ***Emergency and Chronic tx of Edematous

states***, even with low GFR (Loops are actively
secreted into the lumen)
A. Cardiac (MI, CHF)
B. Pulmonary
C. Hepatic (Ascites secondary to cirrhosis; Tx
improves morbidity, but not mortality)
D. Renal failure
2. Hypercalcemia (Used as a temporary measure)
3. Hypertension (Only when not responsive to
Thiazides)
4. Hyperkalemia
5. Anion Poisoning (Fluoride, Iodide, and Bromide)

THIAZIDE DIURETICS
Clinical Uses

1. Hypertension
a. Should get a 10-15mmHg fall in pressure
b. Reduce blood volume (Volume returns to near
normal over 6-8 weeks, but antihypertensive effect
remains)
c. Reduce vascular resistance by relaxation of
arterioles (Na+ increases vessel stiffness, so
reducing Na+ relaxes arterioles)
d. Reduce responsiveness of arterioles to NE (also
because of lower Na+)
e. Combat sodium retention (Many antihypertensives promote Na+ retention, particularly
the vasodilators and alpha-blockers)
f. Potentiate effects of other antihypertensive
drugs when used in combination
g. Used in Blacks (and Non-Blacks) Under 60
2. Diabetes Insipidus
a. Thiazides decrease urine output by about 50%
in these patients
3. Non-emergency edematous states (Cyclical
edema with menstruation)
4. Hypercalciuria
a. Volume contraction caused by the thiazide
diuretics stimulates proximal tubule reabsorption of
Ca2+

THIAZIDE-LIKE DIURETICS
Clinical Uses
When loop diuretics fail, the addition of one of these
agents with the loop diuretic may again produce
diuresis.

When loop diuretics fail, the addition of one of these

agents with the loop diuretic may again produce
diuresis.

POTASSIUM-SPARING DIURETICS
Clinical Uses

1. Heart failure
2. Prevent K+ loss by other diuretics
-Counteract this side-effect of thiazides and loops
-Hyperaldosteroneism syndromes (rare
occurrence)

CARBONIC ANHYDRASE INHIBITORS (CAIs; "-zolam

Clinical Uses

1. ***GLAUCOMA***
-Decreases production of aqueous humor
-Given topically, so it does not gain access to
systemic circulation in high enough dose to effect
the kidneys.
2. Alkalization of the urine
-Useful in nephrolithiasis, caused by uric acid
and cystine stones, both of which are poorly
soluble in acidic pH.
-Cystinuria is rare (pH has to be raised to 7.5 to
avoid)
-Uric acid stones are more common (pH only has
to be raised to 6-6.5)
-In either condition, too aggressive aliklization of
urine promotes Ca2+ stones.
3. Mountain Sickness (Above 9,000 ft)
-CSF is formed in part because bicarb is secreted
from blood into CSF space, and water follows
-CAIs reduce brain edema in part by CSF
mechanism and in part by causing a systemic
metabolic acidosis (Stimulates deep breathing to
compensate)
-Best tx is to move to low altitude and gradual
acclimation
-If CAIs used, must be given prophylactically
4. Epilepsy
-Tolerance develops quickly
-Typically used in emergency settings for 1-2 days

OSMOTIC DIURETICS
Clinical Uses

1. Prophylaxis of renal failure

2. Decrease the pressure and volume of intraocular
fluid and CSF
-Emergent tx of life-threatening increased
ICP
3. Hemodialysis

LOOP DIURETICS
Side Effects

Contraindications

Excessive fluid and electrolyte loss:

1. Hypokalemia
-Watch out for CHF patients on Digoxin.
-K+ is lost in the collecting tubule, not the loop or the
distal tubule
2. Hypokalemic Metabolic Alkalosis
3. Hyperuricemia
-Hypovolemia enhances reabsorption of urate at
1. Sulfa allergy
proximal tubule.
2. PMHx/FHx of Gout
4. Hypomagnesemia
-Loss of Mg2+ is usually more profound than loss of
calcium (PTH acts to increase Ca2+ reabsorption in
distal tubules, but Mg2+ has no such site)
5. Ototoxicity
-Usually reversible
-Watch out for patients taking aminoglycosides
6. HYPOVOLEMIA

THIAZIDE DIURETICS
Side Effects

Contraindications

1. When the dose is kept low, side-effects are usually

not a problem.
2. Hypokalemia
3. Hypokalemic Metabolic Alkalosis
4. Hyperuricemia
a. Can produce gout attack in patients with a
history or family history of gout.
b. Without such a history, they almost never cause
gout.
5. Hyponatremia with or without Hypovolemia
(Usually without)
a. Water loss is non-ADH dependent
b. Common in elderly and frail patients
c. Causes weakness (seizures occur in severe
hyponatremia)
d. Watch for this in patients who have been stable on
Thiazides, but who for some reason (i.e. viral illness)
suddenly decrease their salt intake.
Sulfa allergy
e. Dizziness and lightheadedness in the first
few days of use (initial response to lowering of
plasma Na+ with subsequent adaptation).
6. Hyperlipidemia (5-15mg/dL)
a. But no increase in morbidity or mortality
7. Hyperglycemia
a. Decrease insulin secretion (May reveal latent DM)
b. Usually clinically important only at high dose
c. Usually reversible with correction of hypokalemia
d. Avoiding this effect is often why another
antihypertensive is added to patient's regimen when a
thiazide is already being used to maximum reasonable
dose.
8. Allergic reactions (Sulfa)
a. Contraindicated in Sulfa allergy
9. ERECTILE DYSFUNCTION (Impotence)
-Frequency is even greater than with Beta-blockers

HIAZIDE-LIKE DIURETICS
Side Effects

Contraindications

SSIUM-SPARING DIURETICS
Side Effects

Contraindications

1. Hyperkalemia
-Especially with ACEI's, NSAIDS, and Beta-blockers
-Most common when co-administered with K+
supplement
2. Anti-androgen effect
-Gynecomastia (Typically irreversible)
-Impotence
-Steroid structure leads to competitive inhibition of
androgen receptors
-Stronger with Spironolactone
1.
2.
3.
4.

GI (Nausea/Vomiting)
Dizziness
Leg cramps ("Charlie-horse")
Nephrolthiasis (Triamterene)

DRASE INHIBITORS (CAIs; "-zolamide")

Side Effects

Contraindications

1. Metabolic acidosis
-Secondary to reduced plasma bicarbonate
2. Hypokalemia
3. Renal stones (Calcium-containing stones)
4. Hypersensitivity reactions (rare)
-Rash
-Fever
-Bone marrow suppression

Sulfa allergy

OSMOTIC DIURETICS
Side Effects

Contraindications

1. Transient volume expansion of ECF volume;

Hyponatremia
-Can result in volume overload in the vascular tree,
with cardiac failure and/or pulmonary edema.
2. Headaches, Nausea/Vomiting
3. Long-term:
-Hypernatremia
-Dehydration

Do NOT use these

agents in patients
with diminished
cardiac capacity.

Notes
1. Standard drug of this
class
2. Loops can increase
fractional Na+ excretion
to 20-25% of glomerular
filtrate and diminish
interstitial fluid
osmolality (countercurrent mechanism).

Once daily dosing

Notes

Drug Interactions

1. Aminoglycosides
-Ototoxicity
2. Digitalis
(Digoxin/Digitoxin)
-Enhanced efficacy of
digitalis, but enhanced
likelihood of arrhythmias.
3. Sulfonylureas used for DM
Type II
-Hyperglycemia
4. Lithium (Used for bipolar
disorder)
-Na+ is preferentially
excreted
5. NSAIDs
-NSAIDs can blunt the
diuretic response by reducing
glomerular filtration
6. Thiazides
-Diuretic synergism

Drug Interactions

1. Slow onset; Longlasting

2. Less efficacious than
loop diuretics, but
capable of fluid and
electrolyte disturbances
3. Elderly and Blacks
respond well

Notes

Drug Interactions

Notes

Drug Interactions

Not very efficacious

diuretics by themselves

Notes

Drug Interactions

Do NOT use Carbonic

Anhydrase Inhibitors in
poisoning with Aspirin (an
organic acid) to try to speed
Not very useful diuretics
excretion.
because tolerance
-Instead, use HCO3- to
develops in days (Rapid
alkalize the urine
refractoriness)
-Use of a CAI will add to the
acidemia caused by the
organic acid, which is
deleterious

Notes

Drug Interactions

Name

Mechanism

Hydrochlorothiazide
(HCTZ)

1. Inhibit the distal tubule Na/Cl co-transporter

2. Lose more sodium than water, so the plasma
osmolality decreases.
3. Results in slightly lower Na+ concentration in
the plasam, which allows arteriolar smooth
muscle to relax.

Chlorthalidone

Name

Mechanism

Amlodipine (All end 1. L-type calcium channel blocker

a. The "ipine"s are more vascular selective.
in "ipine")
b. Verapamil and Diltiazem are relatively
selective for cardiac tissue.
2. Decrease Calcium influx into smooth muscle,
resulting in smooth muscle relaxation
3. Tend to see more artery and arteriolar
dilation than venous dilation, which is important
for lowering BP without causing intolerable
Verapamil/Diltiazem
orthostatic hypotension.

ANGIO
Name

Mechanism

Captopril

Enalapril

1. Block conversion of Angiotensin I to

Angiotensin II by inhibiting Angiotensin
Converting Enzyme (ACE).
2. Decreases Angiotensin II-mediated release
of Aldosterone.
3. Decreases breakdown of Bradykinin
a. Bradykinin is a tissue irritant and vasodilator
b. ACE is also the same enzyme as Kininase II,
which inactivates Bradykinin
4. Decreases overly active SNS
a. MInimal reflex tachycardia
5. Decreases preload and afterload
a. Decreases BP
6. All (except Lisinopril) are Pro-drugs and are
converted to the active agents in the liver

a. MInimal reflex tachycardia

5. Decreases preload and afterload
a. Decreases BP
6. All (except Lisinopril) are Pro-drugs and are
converted to the active agents in the liver

Lisinopril

A
Name

Mechanism

Candesartan
Valsartan
Losartan

1. Block AT1 subtype of the Angiotensin (AT) II

receptors
a. This receptor mediates many of the Angiotensin
II effects, including:
i. Constriction of vascular smooth muscle
ii. Release of Aldosterone
iii. CNS activation of sympathetic discharge
iv. Enhanced responsiveness of vascular smooth
muscle to sympathetic activation
2. ARBs do NOT elevate Bradykinin

Name
Labetalol
Clevidipine &
Nicardipine

Mechanism
Both alpha and beta blocker
Calcium channel blockers

Nitroprusside

Donates Nitric Oxide (NO)

a. Direct smooth muscle relaxant/Vasodilator
b. Very short half-life

Fenoldopam

1. Very short-acting Dopamine D1 partial agonist

2. May have some alpha receptor blocking
effects (decreased BP with blood flow
maintained to kidneys) that are important for
hypertensive emergencies in patients with chronic
kidney disease.

Name

Mechanism

Converted in sympathetic nerve terminals to

alpha-methylnorepinephrine, which is an alphaMethyl-DOPA
2 agonist.
(Alpha Methyldopa)
a. In the brainstem, stimulation of alpha-2
receptors results in reduction of sympathetic
tone, with resultant reduction in BP.

Name

Mechanism

Magnesium

Name

Mechanism

Aliskiren (Tekturna)

Name

Propranolol

Metoprolol

Atenolol

Name

Blocks renin receptors

a. Decreases the conversion of
Angiotensinogen to Angiotensin I

Mechanism

1. Critical event is likely the block of renin release

by blocking the beta-1 receptor.
2. Decreases cardiac contractility
3. Decreases heart rate (HR)
4. Decreases cardiac output (CO)
5. In the absence of reflexes, these effects lead to
decreased BP.
a. In reality, if CO falls, sympathetic tone is
increased.
b. In the presence of a beta-blocker sympathetic
activation doesn't do much to cardiac function.
c. However, through alpha-receptors, peripheral
resistance increases
6. Peripheral resistance
a. Block of Beta-2 can lead to increased BP
(usually does not)
b. Block of renin release leads to a decrease
in peripheral resistance (usual effect).
i. Renin release is under the control of cAMP
(Predominant control is exerted by sodium
concentration)
ii. High Sodium inhibits renin release
(Adenosine stimulates Gi second message)
iii. Low Sodium increases cAMP production
through a prostaglandin mechanism.
iv. Lesser control is exerted by Beta-1
receptor stimulation, which stimulates cAMP
production.

Mechanism

Prazosin

Terazosin &
Doxazosin

Name

Clonidine

1. Block post-synaptic alpha-1 receptors

2. Decrease sympathetic nervous system
effect on vasculature
3. Decreases preload and afterload
a. Decreases BP

Mechanism
1. CNS-Active, Alpha-2 Agonist
a. In the periphery, alpha-2 receptor is an
autoreceptor on norepinephrine nerve
terminals, and when stimulated, it decreases
release of norepinephrine.
b. In the CNS, stimulation of alpha-2 receptors in
the brainstem decreases the responsiveness of
the sympathetic system.
c. The brainstem is the main site of action as an
anti-hypertensive.
2. Part of the effect may be via Imidazoline
receptors in the brainstem.

Converted in sympathetic nerve terminals to

alpha-methylnorepinephrine, which is an alphaMethyl-DOPA
2 agonist.
(Alpha Methyldopa)
a. In the brainstem, stimulation of alpha-2
receptors results in reduction of sympathetic
tone, with resultant reduction in BP.

Name
Nitric Oxide (NO)

Mechanism
Direct-acting vasodilator

Isosorbide Dinitrate Nitric Oxide (NO) Donor

Hydralazine

Arterial dilator (Likely a NO donor)

THIAZIDE DIURETICS
Clinical Uses

1. Hypertension
a. Should get a 10-15mmHg fall in pressure
b. Reduce blood volume (Volume returns to near normal
over 6-8 weeks, but antihypertensive effect remains)
c. Reduce vascular resistance by relaxation of arterioles
(Na+ increases vessel stiffness, so reducing Na+ relaxes
arterioles)
d. Reduce responsiveness of arterioles to NE (also
because of lower Na+)
e. Combat sodium retention (Many anti-hypertensives
promote Na+ retention, particularly the vasodilators and
alpha-blockers)
f. Potentiate effects of other antihypertensive
drugs when used in combination
g. Used in Blacks (and Non-Blacks) Under 60
2. Diabetes Insipidus
a. Thiazides decrease urine output by about 50% in
these patients
3. Non-emergency edematous states (Cyclical edema
with menstruation)
4. Hypercalciuria
a. Volume contraction caused by the thiazide diuretics
stimulates proximal tubule reabsorption of Ca2+

CALCIUM CHANNEL BLOCKERS (CCBs; "-ipine")

Clinical Uses

Hypertension
a. Used in Blacks (and Non-Blacks) Under 60

1. Cardiac problems (Particularly Diltiazem)

2. Hypertension
a. Can be used for HTN, but are usually not
b. Used in Blacks (and Non-Blacks) Under 60

ANGIOTENSIN CONVERTING ENZYME INHIBITORS (ACE-Is; "

Clinical Uses

1. Essential Hypertension (HTN)

a. Used in Non-Blacks Under 60
2. Particularly effective in high plasma renin
a. Blacks often have a low plasma renin, so these drugs
do not work well in that population
3. Diabetes Mellitus
a. Reduces proteinuria
4. Renal Insufficiency
5. Congestive Heart Failure (CHF)
a. Decreases mortality
b. Used for this effect even in the absece of HTN
6. Blacks and Elderly may not respond well

a. Decreases mortality
b. Used for this effect even in the absece of HTN
6. Blacks and Elderly may not respond well

ANGIOTENSIN RECEPTOR BLOCKERS (ARBs; "sartans"

Clinical Uses

1. Hypertension
a. First-choice agents for Non-Black, Under 60
population

TREATMENT OF EMERGENT HYPERTENSION

Clinical Uses

Emergent Hypertension
a. High BP (>180/120) with end-organ damage (i.e.
retinal hemorrhage)
b. Pressure must be reduced quickly
c. Want agents that are very short-acting and given
IV, so if BP is unintentionally reduced too much, stopping
administration allows pressure to rise quickly.

HYPERTENSION PREDATING PREGNANCY

Clinical Uses

1. Used in pregnant women

2. Hypertension
a. Not a particularly efficacious antihypertensive
b. Often HTN will not be adequately controlled

TREATMENT OF PREECLAMPSIA
Clinical Uses
Preeclampsia
a. The sudden emergence of hypertension during
pregnancy.
b. In the worst forms, Eclampsia, the hypertension is so
severe the CNS is grossly affected.
c. Even in preeclampsia, seizures are possible.

RENIN ANTAGONISTS
Clinical Uses

Hypertension
a. Effects are comparable to ACE-Is or ARBs
b. No documented efficacy for improving
morbidity/mortality

BETA-BLOCKERS ("olol")
Clinical Uses

1. Hypertension
2. Used for preventing arrhythmias
a. Especially after Myocardial Infarction (MI)
3. Improve mortality in heart failure

ALPHA-1 ANTAGONISTS ("zosin")

Clinical Uses

1. Hypertension
a. Not first-line drugs
b. Use in combination with other classes
2. Benign Prostatic Hypertrophy (BPH)

CNS-ACTIVE, ALPHA-2 AGONISTS

Clinical Uses

1. Used in treatment of emergency hypertensive

states, particularly those with a large sympathetic
component.
2. Useful in opioid withdrawal
a. Calms sympathetic component of the withdrawal
b. Only used for short period, so termination is not
associated with hypertensive crisis.

1. Used in pregnant women

2. Hypertension
a. Not a particularly efficacious antihypertensive
b. Often HTN will not be adequately controlled

DIRECT-ACTING VASODILATORS
Clinical Uses
1. Angina
2. Pulmonary Edema
3. Hypertension
1. Isosorbide Dinitrate and Hydralazine are used in
combination in some heart failure patients to improve
morbidity and mortality
2. Hypertension

E DIURETICS
Side Effects

1.
2.
3.
4.

When the dose is kept low, side-effects are usually not a problem.
Hypokalemia
Hypokalemic Metabolic Alkalosis
Hyperuricemia
a. Can produce gout attack in patients with a history or family
history of gout.
b. Without such a history, they almost never cause gout.
5. Hyponatremia with or without Hypovolemia (Usually without)
a. Water loss is non-ADH dependent
b. Common in elderly and frail patients
c. Causes weakness (seizures occur in severe hyponatremia)
d. Watch for this in patients who have been stable on Thiazides, but
who for some reason (i.e. viral illness) suddenly decrease their salt
intake.
e. Dizziness and lightheadedness in the first few days of use
(initial response to lowering of plasma Na+ with subsequent
adaptation).
6. Hyperlipidemia (5-15mg/dL)
a. But no increase in morbidity or mortality
7. Hyperglycemia
a. Decrease insulin secretion (May reveal latent DM)
b. Usually clinically important only at high dose
c. Usually reversible with correction of hypokalemia
d. Avoiding this effect is often why another antihypertensive is
added to patient's regimen when a thiazide is already being used to
maximum reasonable dose.
8. Allergic reactions (Sulfa)
a. Contraindicated in Sulfa allergy
9. ERECTILE DYSFUNCTION (Impotence)
-Frequency is even greater than with Beta-blockers

LOCKERS (CCBs; "-ipine")

Side Effects

1. Relatively low incidence of side-effects

2. Headache, Flushing, and other orthostatic problems
3. Grapefruit can block metabolism

NZYME INHIBITORS (ACE-Is; "-pril")

Side Effects

1. ***Cough***
a. Caused by elevated bradykinin in the lungs
b. Dry, non-productive
c. Irritating
d. Dose-related, but seen in the therapeutic range
e. Not seen with ARBs, which do not elevate bradykinin
2. First-dose hypotension
a. Especially if hypovolemic
b. Relatively common if a full dose is given
c. Work dose up gradually
3. Skin rashes
a. Captopril seems worse than others because it contains an SH
group, which has a greater propensity for allergy
4. Acute renal failure in renal artery stenosis
a. Since renin levels are high in renal artery stenosis, ACE-Is will
further dilate the efferent arteriole, resulting in even less pressure in the
glomerulus.
b. Significant danger of acute renal failure because pressure in the
capsule is too low to cause filtration.
5. Angioneurotic edema (Angioedema)
a. Rapid swelling of dermal tissue
b. If in the upper respiratory tract, such as the tongue, it can be lifethreatening.
c. Typically occurs within the first week of therapy, often with first
dose
d. IgG reaction
e. NOT IgE immune-mediated (NOT anaphylaxis)
6. Hyperkalemia

a. Rapid swelling of dermal tissue

b. If in the upper respiratory tract, such as the tongue, it can be lifethreatening.
c. Typically occurs within the first week of therapy, often with first
dose
d. IgG reaction
e. NOT IgE immune-mediated (NOT anaphylaxis)
6. Hyperkalemia
a. Possible especially if combined with other drugs that increases K+
7. Contraindicated in Pregnancy
a. Number of profound fetal problems in 2nd and 3rd trimesters:
i. Fetal malformation
ii. Hypotension
iii. Renal failure

BLOCKERS (ARBs; "sartans")

Side Effects

1. Incidence of ARB side-effects is low

a. ARBs are least problematic of all antihypertensives from a
compliance standpoint because of lesser side-effect profiles than other
agents
2. ARBs do NOT elevate bradykinin, therefore:
a. Do NOT cause cough
b. Have significantly less chance of producing Angioedema
3. Blunt the hypokalemia caused by diuretics
a. Decreases aldosterone release
4. Minimal orthostatic hypotension
5. Minimal reflex activation of sympathetic nervous system
6. No effect on triglycerides or cholesterol
7. Hyperkalemia
8. Acute renal failure in renal artery stenosis
9. First-dose hypotension
a. Same propensity as ACE-Is
10. Contraindicated in pregnancy
a. During 2nd and 3rd trimesters
b. If pregnancy occurs while on these drugs, no diverse effects
occur if the drugs are dicontinued early on.
c. Toxic to the developing kidneys (Nephrotoxicity)

ERGENT HYPERTENSION
Side Effects
Avoid in typical contraindication patients (i.e. asthmatics)

Converted to Thiocyanate and Cyanide

a. Both are toxic, so duration of use of agent has to be relatively brief.
b. Consequently, caused a decline in popularity

REDATING PREGNANCY
Side Effects

1. Various side-effects
2. ***Rebound hypertension***
a. If the drug is discontinued too rapidly
3. Sleepiness/tiredness

OF PREECLAMPSIA
Side Effects

NTAGONISTS
Side Effects

Contraindicated in pregnancy

CKERS ("olol")
Side Effects

1. This class of medicines has decreased dramatically in popularity with

increasing evidence that they are:
a. Not as efficacious as other antihypertensives in improving
mortality/morbidity
b. Implicated in causing Type 2 Diabetes
2. Impotence (CNS mediated)
3. Depression (CNS mediated)
4. AV Block
5. Severe bradycardia
6. ***Bronchospasm and respiratory distress in

asthma and COPD***

a. Class toxicity
7. Exacerbation of acute CHF and pulmonary edema
8. Delay of receovery from hypoglycemia
9. Hypertriglyceridemia
a. Decreased HDL cholesterol

AGONISTS ("zosin")
Side Effects

1. Increased risk for aggravating or causing CHF

2. First-dose hypotension
a. Can be severe
3. Salt and water retention
a. Must use diuretic
4. ***Orthostatic hypotension***
a. Including chronic fatigue and light-headedness

ALPHA-2 AGONISTS
Side Effects

1. Not first-line because of side-effects and

***withdrawal/rebound HTN***
a. Sudden discontinuation can lead to a hypetensive crisis.
b. When used short-term, withdrawal HTN is not an issue
2. CNS:
a. Drowsiness
b. Dry mouth
c. Depression

1. Various side-effects
2. ***Rebound hypertension***
a. If the drug is discontinued too rapidly
3. Sleepiness/tiredness

NG VASODILATORS
Side Effects

1. Hypotension
2. Orthostatic Hypotension

Notes

1. Slow onset; Long-lasting

2. Less efficacious than loop diuretics, but capable of
fluid and electrolyte disturbances
3. Elderly and Blacks respond well

Notes

Blacks respond well

Notes

1. Twice per day dosing

2. More allergy issues
3. Although the prototype, is now much less
frequently prescribed

1. No SH groups
a. Less allergy than Captopril

1. Once daily dosing

2. Not a pro-drug

Notes
1. Candesartan:
a. Shorter acting than other ARBs
b. Multiple daily dosing is undesirable
2. Many authorities would prefer ACE-Is or ARBs in
Diabetes.
a. They more selectively reduce pressure in the
glomeruli
b. They dilate the efferent arteriole, thus reducing
pressure in the capsule.
c. This should provide better protection against
diabetes-induced damage of the capsule.
3. Whether Black or not, ACE-Is and ARBs are
the starting drugs for patients with
Hypertension and Chronic Kidney Disease.
a. Prolongs kidney function
b. Most patients with HTN and CKD require
more than one antihypertensive.
c. Many patients also require a diuretic.
d. In chronic renal failure, Thiazides are not
efficacious enough as diuretics; have to use loop
diuretics.
4. ***Don't combine ACE-Is and ARBs***
a. Causes profound hyperkalemia
b. Act through similar mechanisms, so their
mechanisms basically cancel each other out.

Notes
Very short duration of action
Very short-acting (1-2 minutes)

Notes
1. All antihypertensives cross the placenta.
2. Many are known to be teratogenic.
a. ACE-Is, ARBs, and Anti-Renin agents are
contraindicated.
3. Choices are usually:
a. Calcium Channel Blockers (CCBs)
b. Methyl-DOPA (Alpha Methyldopa)
c. Beta-blockers

Notes
1. Magnesium is the drug of choice to prevent
eclampsia.
2. From a treatment standpoint, this condition tends
to occur later in pregnancies, so first therapy is
delivery, if possible.
3. Because the fetus is more developed, a variety of
drug therapies are available.
a. ACE-Is and ARBs are still contraindicated.

Notes

Notes

1. Non-selective beta-blocker
2. Prototype agent of this class
3. Advantages:
a. Cheap
b. Efficacious
c. Extensive history

1. Prototype of beta-1 selective blocker

2. Short half-life limits utility

1. Beta-1 selective blocker

2. Longer half-life than Metoprolol
a. Permits less frequent dosing
3. One of the least effective in terms of
morbidity/mortality in stroke prevention.

Notes

1. Prototype
2. Short-acting

More popular if an alpha-blocker must be used

Notes

1. All antihypertensives cross the placenta.

2. Many are known to be teratogenic.
a. ACE-Is, ARBs, and Anti-Renin agents are
contraindicated.
3. Choices are usually:
a. Calcium Channel Blockers (CCBs)
b. Methyl-DOPA (Alpha Methyldopa)
c. Beta-blockers

Notes
Although effective in reducing BP, side-effects
generally limit prescription.
1. Long-acting
2. Orally active

Name

Alirocumab
(Praluent)

Ezetimibe (Zetia)

Name

Lovastatin
(Mevacor)

Name

Gemfibrozil
(Lopid) &
Fenofibrate

Niacin

Omega-3 Fatty
Acids (Fish Oils)

LD
Mechanism
1. PCSK9 inhibitor
a. PCSK9 is a protein that binds to and causes degradation of the liver receptor
for low density lipoprotein (LDLR).
b. PCSK9 results in less binding of LDL-C to LDLR, so the amount of plasma
LDL-C increases.
c. PCSK9 inhibitor increases hepatic LDLR, resulting in markedly reduced
LDL-C.
1. Inhibits cholesterol absorption
2. Phytol receptor blocker
a. Blocks cholesterol uptake from diet to any degree desired
b. Inhibits absorption of phytosterols and cholesterol by acting on
intestinal wall receptors
3. Excreted with the bile and acts at the brush border of the small
intestine to inhibit the uptake of dietary and biliary cholesterol into the
enterocytes.
a. Unlike bile acid binders, this drug does NOT decrease absorption of
other fatty substances.
b. Well tolerated
4. No inhibition of cholesterol synthesis in the liver.
5. No increase in bile acid secretion.

Mechanism

1. HMG-CoA reductase inhibitors

a. Decreases hepatic cholesterol synthesis
2. Leads to increased synthesis of LDL receptors in the liver (Because the
liver attempts to get more cholesterol from the plasma)
a. Results in reduction of circulating LDL-C and total cholesterol
b. Small decrease in triglycerides
c. Small increase in HDL cholesterol
3. Anti-inflammatory, particularly in the vasculature
4. Reduce the vascular reactivity of the lumen, thus decreasing the
propensity for clots
a. C-reactive protein (CRP) is reduced.
5. Reduce the likelihood of plaque rupture
6. Inhibit Q10 (Ubiquinone)
a. Causes Rhabdomyolysis

F
Mechanism

1. Decreases triglycerides
2. Increases activity of lipoprotein lipase
a. Cleaves free fatty acids from triglycerides more readily
b. Promotes delivery of triglycerides to adipose tissue
3. Decreases VLDL formation in the liver
a. Modest reduction in LDL (May increase in some patients)
b. Rise in HDL

Raises HDL

LDL-C LOWERING AGENTS

Clinical Uses
1. Decrease plasma LDL-C beyond that produced by
increasing the dose of a statin
2. Approved for additional LDL-C lowering or for a rare genetic
condition in which PCSK9 is overactive.

1. Decrease plasma LDL-C

a. Decreases cholesterol absorption approximately 50%
b. Does NOT modify triglyceride absorption
2. When added to statin therapy, decreases LDL-C substantially
3. Ezetimibe improves outcomes when added to statins in
doses that dramatically reduces LDL-C.

STATINS
Clinical Uses

1. Improves morbidity/mortality in established CV disease

a. Post-MI
b. Post-stroke
2. ***Hypercholesterolemia***
3. Elevated cholesterol of all types
a. Particularly effective at lowering levels of LDL.
b. If the primary problem is too much cholesterol, Statins are
good choices.

FIBRIC ACID DERIVATIVES

Clinical Uses

1. In grossly elevated triglycerides, these drugs are important

for protecting against pancreatitis
2. Hypertriglyceridemia in which VLDL or IDL is elevated
a. Follow VLDL. If it is elevated, Gemfibrozil is a candidate
drug.
b. If LDL is elevated, but VLDL is not elevated, do NOT
use this drug.

1. Mainly reduces triglycerides

-No evidence that triglyceride reduction by itself improves CV
morbidity/mortality
2. LDL cholesterol increases slightly

Side Effects

1. Relatively benign side-effects

2. Reversible change in liver function
3. Like statins, if pushed too aggresively with dose, may see myalgia/rhabdomyolysis
phenomena.

Side Effects

1. Frequency of toxicities is generally low, and most are reversible on discontinuation of the
drug.
2. Hyperglycemia and increased HbA1c.
3. Cognitive impairment in the elderly
a. Usually mild and reversible
4. Hepatic damage
a. Frequent (1-2%)
b. Elevated serum hepatic enzymes occur, with the possibility of hepatitis; incidence,
however, is relatively low
c. Contraindicated in hepatic disease
5. Peripheral neuropathies
a. Reversible upon discontinuation of drug
6. Most frequent untoward effect is ***Myalgia*** (1-5%- Muscle pan is common on these

agents), ***Myopathy*** (<1%), and ***Rhabdomyolysis*** (rare)

a. Monitor for myopathy more carefully when combining with fibrate drugs (5% incidence
with this combination), which can cause the same toxicity. These toxicities occur more
frequently with this combination.
b. In rhabdomyolysis, myoglobin dumped from striated muscle may cause AKI.
7. Lovastatin and Simvastatin cross the BBB and may cause sleep disturbances.
8. Anything that competes for liver metabolism (CYP3A4) of these drugs can increase their
plasma concentrations, which has been associated with muscle problems:
a. Erythromycin
b. Verapamil, Diltiazem (Observe caution)
c. Grapefruit juice (Current recommendation is no more than one, 6 oz glass of grapefruit
juice per week for patients taking Lovastatin, Simvastatin, or Atorvastatin)
9. Contraindicated in pregnancy
a. Cholesterol is needed for formation of cell walls in the fetus.
b. Teratogenicity has not been proven.

Side Effects
1. Low incidence
2. GI problems
3. Liver enzyme abnormalities
a. Usually transient
4. Myositis
a. Myopathy and Rhabdomyolysis are reported when combined with HMG-CoA
reductase inhibitors
b. Increased myopathy risk at least 10-fold when combined with a Statin
5. ***Gallstones***
a. Increased biliary excretion
b. Do NOT use in patients with gallbladder problems

Name

Mechanism

Aspirin (ASA)

1. Irreversible inhibitor of COX (Binds

covalently)
2. Recovery of COX from ASA inhibition in
most tissues is by synthesis of new
enzyme.
3. Platelets cannot synthesize new COX
(due to lack of nucleus), so inhibition
with ASA is irreversible.
4. Low doses of ASA irreversibly inhibit
COX and platelet aggregation for the
life of the platelet (8-11 days).
5. Importance of Low Dose:
a. Although there is a small effect to
decrease Prostacyclin synthesis, endothelial
cells make new Prostacyclin.
b. All of this works well with low dose
ASA. WIth high dose ASA or full doses of
other NSAIDs, both TXA2 AND Prostacyclin
production are significantly decreased, and
the selective antiplatelet effects are lost.

Clopidogrel
(Plavix)

Prasugrel
(Effient)
Ticagrelor
(Brilinta)

1. Irreversibly blocks P2Y12 site of the

ADP receptor
a. Leads to irreversible blockade of
ADP receptor on the platelet cell
membrane
b. The ADP receptor is the binding site for
IIb/IIIa cross-linking
Allosterically, reversibly blocks ADP
receptor activation at the PY12 site

Dipyridamole

Abciximab
Tirofiban &
Eptifibatide

Name

1. Inhibits adenosine metabolism

a. Adenosine is a vasodilator
b. Adenosine also appears to counteract
the effect of ADP to aggregate
platelets
2. Inhibits phosphodiesterase
a. Increases intracellular cGMP in
smooth muscle, which causes
vasodilation
1. IIb/IIIa inhibitor
a. Prevents fibrinogen binding to
glycoprotein GP IIb/IIIa
b. Inhibits platelet aggregation

Mechanism

Heparin

1. Binds to and activates antithrombin

III.
a. The Heparin-Antithrombin III
complex binds to and inactivates
factors including:
i. Thrombin (IIa)
ii. IXa
iii. Xa
iv. XIa
v. XIIa
vi. Becvause so many factors are
inhibited (2a and 9-12a), anticoagulant
effects are variable between patients, so
monitoring of clotting time must be
performed.
2. Prolongs the aPTT
a. Activated Partial Thromboplastin Time
(aPTT) is a measure of clotting due to the
intrinsic and common pathway

LMWH
(Enoxaparin,
Dalteparin,
Ardeparin,
Danaparoid)

1. Much more selective for Factor Xa

2. Reduced number of factors affected
a. Simpler kinetics
b. Clotting tests usually not required

Warfarin

1. Inhibits Vitamin K epoxide reductase

2. Inhibits Vitamin K-dependent posttranslational modification of clotting
factors:
a. Thrombin (II)
b. VII
c. X
d. Proteins C and S
3. Without addition of the gamma
carboxyglutamic acid residue, the clotting
factors cannot bind Calcium and are
inactive.

Warfarin

Rivaroxaban
(Xarelto)

Dabigatran
(Pradaxa)

Name

factors:
a. Thrombin (II)
b. VII
c. X
d. Proteins C and S
3. Without addition of the gamma
carboxyglutamic acid residue, the clotting
factors cannot bind Calcium and are
inactive.

Competitive Factor Xa inhibitor

Competitive Factor IIa (Thrombin)

inhibitor
-Through different binding sites, it is able
to inactivate both free and fibrinbound thrombin

Mechanism

tPA
(Recombinant
Tissue
Plasminogen
Activator, rtPA,
Alteplase,
Activase)

Reteplase

1. Normal fibrinolysis:
a. Clots are dissolved by the action of
the protease Plasmin
b. Plasmin is formed from inactive
Plasminogen by tissue Plasminogen
Activator (tPA)
c. Produces fibrinolysis
d. Fibrinolysis is controlled by fast
clearance of tPA by a circulating inhibitor of
tPA
2. Objective of Thrombolytic Therapy:
a. Dissolve pathological blood clots by
injecting a fibrinolytic enzyme or an
activator of endogenous fibrinolysis without
uncontrolled bleeding.

ANTIPLATELETS (ARTERIAL)
Clinical Uses

1. Low dose ASA together with diet and exercise is

useful for the treatment of:
a. MI
b. Secondary prevention of MI and stroke
c. Coronary Artery Disease (CAD)
d. Unstable angina
e. Peripheral vascular disease
2. Reduction in thromboembolic complications in
patients with:
a. Artificial heart valves
b. Hemodialysis
c. Coronary bypass grafts
3. Very little, if any, efficacy in venous clotting
4. In the same low doses effective in antiplatelet
activity, ASA is also effective in reducing the
occurrence and metastasis of cancer (reduced at
least 1/3).
5. ASA and Plavix are frequently used in
combination in high risk situations, like:
a. Stents
b. Acute Coronary Syndrome

Acute coronary syndrome

1. When combined with ASA, significantly improves

outcomes for stroke prevention over ASA alone
a. Due to Dipyridamole's vasodilation and ASA's
antiplatelet
2. Secondary prevention for stroke and MI
associated with sclerotic disease

Antithrombotic during angioplasty when given

with ASA and Heparin
1. Used in conjunction with ASA and Clopidogrel
for great anti-platelet activity
2. Acute Coronary Syndrome

ANTICOAGULANTS (VENOUS)
Clinical Uses

1.
2.
3.
4.
5.

Inhibit growth of thrombus or embolus

Prophylaxis of postoperative thrombosis
MI and Unstable Angina
DVT and PE
Extra-corporal uses
a. For in vitro anticoagulation (Hep-Lock solution) to
clear IV lines, Hemodialysis, or Heart-lung machine.
6. DIC
7. TIA
a. Probably effective, but very risky
b. Not used if stroke is in progress
8. Heparin is used when rapid onset of anticoagulant
is required
a. Small doses
-Prevent thromboembolism
b. Medium doses
-Prevent propagation of thrombus
c. Large doses
-Inhibit established PE
9. If prolonged anticoagulation is necessary, then
heparin therapy is overlapped with and replaced
with oral anticoagulant (Warfarin or Dabigatran)

Prophylaxis of DVT associated with hip, knee, and

abdominal surgery

1. ***Overlap

with Heparin/LMWH
therapy to avoid long delay in onset
of Warfarin action when switching
from Heparin/LMWH to Warfarin***
2.
3.
4.
5.
6.

DVT (Deep Vein Thrombosis) prophylaxis

PE (Pulmonary Embolism)
A-Fib (Atrial Fibrillation)
Rheumatic Heart Disease
Mechanical and prosthetic heart valves

of Warfarin action when switching

from Heparin/LMWH to Warfarin***
2.
3.
4.
5.
6.

DVT (Deep Vein Thrombosis) prophylaxis

PE (Pulmonary Embolism)
A-Fib (Atrial Fibrillation)
Rheumatic Heart Disease
Mechanical and prosthetic heart valves

1. Stroke prophylaxis secondary to A-Fib

2. DVT and PE prophylaxis

1. Strokes in those at high risk (HTN, etc.)

2. Thrombus prevention following surgery for
hip or knee replacement
3. DVT and PE recurrence

THROMBOLYTIC/FIBRINOLYTIC AGEN
Clinical Uses

1. Acute MI (if catheterization is not possible)

2. PE
a. Life-threatening only
b. First choice therapy is anticoagulant to keep the
thrombus from growing
3. DVT
a. Usual therapy is anticoagulant to keep the
thrombus from growing
4. Ischemic stroke
a. Special circumstances only:
i. CT scan to determine this is NOT a hemorrhagic
stroke
ii. Must be given shortly after the embolic stroke

ANTIPLATELETS (ARTERIAL)
Side Effects

1. ***Reye's Syndrome*** is a rare, but often fatal, consequence

of infection with chicken pox, varicella, and influenza viruses.
a. Liver damage and encephalopathy
b. The use of Salicylates in children or adolescents with chicken pox
or influenza is contraindicated.
c. All NSAIDs in children are a second choice to Acetaminophen
because of this issue.
2. Patients with nasal polyps in combination with asthma are particularly
prone to show significant allergy to ASA.
a. Can progress from hives, nasal secretion, and edema to severe dyspnea,
hypotension, and shock.
b. Hypersensitivity to ASA is a caution to other NSAIDs.
3. GI Bleeding, GI Pain, and GI Ulcers
a. Low dose minimizes untoward effects

1. Benign
2. GI upset
3. Dizziness and Headache
a. Common untoward effects with vasodilation
b. Relatively low frequency

Significantly bleeding potential

ANTICOAGULANTS (VENOUS)
Side Effects

1. ***Hemorrhage***
a. Inadvertent overdose
b. Undiagnosed disease site
2. Hematoma at site of injection
3. Thrombocytopenia (Heparin-induced thrombocytopenia; HIT)
a. Platelet-factor 4 is released by activated platlets to block the anticoagulant effects of Heparin.
b. The closer to the clot, the greater the concentration of this factor, which
tends to promote clotting within an appropriate area.
c. These antigen-antibody complexes bind to Fc receptors on adjacent
platelets, causing:
i. Aggregation
ii. Platelet activation
iii. Paradoxical thrombosis
d. Occurs in about 5-7 days after starting treatment.
4. Hyperkalemia due to Aldosterone antagonist
a. Watch for patients on ACE-Is, ARBs, Potassium-sparing diuretics, and
Potassium supplements.
5. Contraindications:
a. Any site of active or potential bleeding
b. Severe HTN or known vascular aneurysm
c. Recent surgery of head, eye, or spinal cord
d. Head trauma
e. Lumbar puncture or regional anesthetic block
f. Tuberculosis
g. Visceral carcinoma
h. GI ulcers
6. Less common side effects:
a. Platelet aggregation
b. Acute Hypersensitivity
c. Alopecia
d. Osteoporosis
e. Priapism

Much less potential for thrombocytopenia

1. ***Hemorrhage***
2. Anorexia, nausea, vomiting, and diarrhea
3. Drug-drug interactions:
a. Warfarin is a classic exaple for many types of drug-drug interaction
b. Inhibition or acceleration of Warfarin metabolism
c. Displacement from plasma protein binding sites (Albumin)
d. Interference with mechanism of action
e. Interference with absorption
4. Skin necrosis
a. Rare
b. Result of extensive microvascular thrombosis within subcutaneous
fat (stasis).
c. Caused by depletion of Protein C and/or Protein S
d. Usually occurs within 3-6 days of initiating therapy with painful
discoloration of breast, buttocks, thigh, or penis
e. Lesions progress to frank necrosis with black eschar
5. Contraindications:
a. Pregnant patients: Congenital abnormalities
b. Unreliable/Uncompliant patient
c. Any recent bleeding
d. Recent head, eye, brain, or spinal cord injury
e. Severe HTN or known vascular aneurysm

4. Skin necrosis
a. Rare
b. Result of extensive microvascular thrombosis within subcutaneous
fat (stasis).
c. Caused by depletion of Protein C and/or Protein S
d. Usually occurs within 3-6 days of initiating therapy with painful
discoloration of breast, buttocks, thigh, or penis
e. Lesions progress to frank necrosis with black eschar
5. Contraindications:
a. Pregnant patients: Congenital abnormalities
b. Unreliable/Uncompliant patient
c. Any recent bleeding
d. Recent head, eye, brain, or spinal cord injury
e. Severe HTN or known vascular aneurysm

***Bleeding***

1. Generally well-tolerated
2. ***Bleeding***
a. As compared to Heparin and Warfarin, no test is available to monitor the
extent of reduced clotting when these agents are used.
b. Occurs in about 10% of patients

ROMBOLYTIC/FIBRINOLYTIC AGENTS
Side Effects

***Hemorrhage***

Notes

1. Generic; OTC
2. Prototype drug
3. Salicylic Acid derivative

1. Prodrug
a. Metabolized in the liver by Cytochrome CYP2, which is
not a frequent target for drug interactions
2. Slow onset (2 hours)
3. Same indications as ASA, but marginally better outcomes
4. Costs more than ASA
1. Prodrug
a. Metabolized in the liver by Cytochrome CYP3A/4

1. Monoclonal chimeric antibody

2. Greater antiplatelet activity than ASA or Clopidogrel

Notes

1. Routes of Administration:
a. Continuous IV
-Often preceded by IV bolus
b. Subcutaneous Minidose
-Post-surgery prophylaxis
c. NOT given IM
-Hematoma potential
d. NOT given Orally
-Too polar to cross into plasma
2. Pharmacokinetics:
a. Onset:
i. IV Bolus- Immediate anticoagulant
ii. SC- Begins in 20-30 minutes
iii. Continuous IV infusion- 2-3 hour delay, unless an
initial bolus injection is administered
b. Termination:
-Metabolized in the liver or excreted unchanged
3. Negatively charged polysaccharide
4. In the native extracted form, it is unfractionated.
5. Treatment of Heparin Overdose:
a. Stop administration
b. Protamine Sulfate
i. Binds to and inactivates Heparin
ii. Must be given slowly IV
c. Infusion of fresh-frozen plasma

1. Low Molecular Weight Heparin (LMWH) are the smaller, active

fragments separated from reagular Heparin.
2. Longer duration than regular Heparin
3. Less frequent dosing than regular Heparin

1. Route of Administration:
a. Only given orally
2. Out-patient
a. Noncompliant and unreliable patients are NOT good
candidates for Warfarin therapy
3. Pharmacokinetics:
a. Onset:
i. Considerably delayed (36-72 hours)
ii. Pre-existing clotting factors are slowly cleared from the
blood
b. Duration:
i. Prolonged
ii. Proportional to the elimination half-life (~25-60 hours)
c. Distribution:
i. Rapid and complete absorption
ii. Highly fat soluble
iii. 99% bound to plasma albumin (Tremendous potential
for drug interactions)
d. Termination:
i. Delayed (2-5 days)
ii. Long elimination half-life (Liver and kidney)
iii. New, active clotting factor must be synthesized
4. Therapeutic Use:
a. Initial doses followed by maintenance dose and are adjusted
according to PT time (INR)
b. Determine PT time (INR):
i. Prior to starting therapy
ii. Daily until response stablized
iii. Weekly until maintenance dose established
c. Warfarin is often administered concurrently with Heparin until
target INR is achieved, and then the patient is maintained on
Warfarin
5. INR (Interntional Normalization Ratio)
a. Used to standardize PT times between different batches of
Thromboplastin and between different laboratories
b. 1 is normal clotting time
c. 2 is twice as long as normal
6. Treatment of Warfarin (Warfarin Antidote):
a. "Routine" Warfarin Overdose:
i. Hold Warfarin and give Vitamin K replacement
ii. Often continued for several days (even with adequate
Vitamin K present, the body has to synthesize clotting
components)
b. "Superwarfarin" Toxicity (Intentional- Suicide attempt;
Unintentional- Confusion, drug displacement, etc.)
i. Fresh frozen plasma
ii. Packed RBCs
iii. Vitamin K

iii. New, active clotting factor must be synthesized

4. Therapeutic Use:
a. Initial doses followed by maintenance dose and are adjusted
according to PT time (INR)
b. Determine PT time (INR):
i. Prior to starting therapy
ii. Daily until response stablized
iii. Weekly until maintenance dose established
c. Warfarin is often administered concurrently with Heparin until
target INR is achieved, and then the patient is maintained on
Warfarin
5. INR (Interntional Normalization Ratio)
a. Used to standardize PT times between different batches of
Thromboplastin and between different laboratories
b. 1 is normal clotting time
c. 2 is twice as long as normal
6. Treatment of Warfarin (Warfarin Antidote):
a. "Routine" Warfarin Overdose:
i. Hold Warfarin and give Vitamin K replacement
ii. Often continued for several days (even with adequate
Vitamin K present, the body has to synthesize clotting
components)
b. "Superwarfarin" Toxicity (Intentional- Suicide attempt;
Unintentional- Confusion, drug displacement, etc.)
i. Fresh frozen plasma
ii. Packed RBCs
iii. Vitamin K

1. Oral anticoagulant
2. Once daily dosing
3. Predictable pharmacokinetics and limited number of targets in
the clotting cascade, so clotting time does not need to be
monitored.
4. Treatment:
a. No approved treatment for Rivaroxaban overdose
1. Orally active anticoagulant
2. Once daily dosing
3. Treatment:
a. Idarucizumab (Praxibind)
i. Antibody fragment against Dabigatran
ii. Approved for uncontrolled bleeding when
Dabigatran is involved
iii. Adverse reaction comparable to placebo

Notes

1. tPA produced by genetic engineering

2. Half life is 3 minutes
3. Route of Administration:
a. IV Bolus first
b. Followed by IV infusion

1. A shorter, genetically engineered form of tPA

2. Diffuses more freely into clot than Alteplase
3. Does not bind Fibrin as readily
a. Thus not bound to the surface of the thrombus as extensively
as Alteplase
4. Permits more targeting of thrombus
a. Less bleeding potential

Name

Mechanism

NSAIDs

All NSAIDs (except Aspirin):

a. REVERSIBLY inhibit Cyclooxygenase (COX),
both Types 1 and 2
b. Block Prostaglandin (PGE2) formation.
c. Inhibit activation and function of
inflammatory cells (May stabilize lysosomal
membranes and inhibit phagocytosis). Much less
efficacious than corticosteroids in this regard.

NSAIDs

Name

a. REVERSIBLY inhibit Cyclooxygenase (COX),

both Types 1 and 2
b. Block Prostaglandin (PGE2) formation.
c. Inhibit activation and function of
inflammatory cells (May stabilize lysosomal
membranes and inhibit phagocytosis). Much less
efficacious than corticosteroids in this regard.

Mechanism

Aspirin (ASA)

1. Irreversible inhibitor of COX (Binds covalently)

2. Recovery of COX from ASA inhibition in most
tissues is by synthesis of new enzyme.
3. Platelets cannot synthesize new COX (due to
lack of nucleus), so inhibition with ASA is
irreversible.
4. Low doses of ASA irreversibly inhibit COX
and platelet aggregation for the life of the
platelet (8-11 days).
5. Importance of Low Dose:
a. Although there is a small effect to decrease
Prostacyclin synthesis, endothelial cells make new
Prostacyclin.
b. All of this works well with low dose ASA. WIth
high dose ASA or full doses of other NSAIDs, both
TXA2 AND Prostacyclin production are significantly
decreased, and the selective antiplatelet effects are
lost.

Indomethacin
(Indocin)

Ketorolac (Toradol)

All NSAIDs (except Aspirin):

a. REVERSIBLY inhibit Cyclooxygenase (COX),
both Types 1 and 2
b. Block Prostaglandin (PGE2) formation
(PGE2 keeps the ductus arteriosus open following
birth).
c. Inhibit activation and function of
inflammatory cells (May stabilize lysosomal
membranes and inhibit phagocytosis). Much less
efficacious than corticosteroids in this regard.

Name

Mechanism

Celecoxib (Celebrex) Selective for COX-2

Name

Acetaminophen
(Tylenol)

Mechanism

Not proven, but best evidence is that it is

metabolized in the brain to a COX inhibitor; thus, the
CNS effects (analgesia, antipyretic) are seen, but no
peripheral anti-inflammatory activity.

GENERAL PROPERTIES OF NSAIDs

Clinical Uses

1. Analgesia
a. PGE2 sensitizes pain nerve endings to the actions of
bradykinin, histamine, and substance P.
b. Mild analgesics, effective against pain of low-tomoderate intensity.
c. NSAIDs can be superior to intermediate efficacy opioids
for relief of some forms of post-operative pain,
particularly when pain is associated with inflammation.
d. Efficacy of pain relief by NSAIDs is lower than with
high-efficacy opioids (NSAIDs + Opioids provide greater
pain relief than intermediate opioids alone).
e. NSAIDs do NOT produce opioids effects of:
a. Respiratory depression
b. Development of physical tolerance/dependence or
use for abuse
c. Production of constipation
2. Antipyretic Effects
a. Temperature control center in the hypothalamus
regulates body temperature
b. Pyrogens (cytokines) from lymphocytes lead to higher
temperature set point (i.e. fever).
c. Heat generation (metabolism) increases and heat loss
(vasodilation) decreases.
d. NSAIDs effectively suppress this response.
3. Anti-Inflammatory Effects
-PGE2 and PGI2 cause vasodilation and are important
mediators of localized erythema and edema in
inflammation.

a. Respiratory depression
b. Development of physical tolerance/dependence or
use for abuse
c. Production of constipation
2. Antipyretic Effects
a. Temperature control center in the hypothalamus
regulates body temperature
b. Pyrogens (cytokines) from lymphocytes lead to higher
temperature set point (i.e. fever).
c. Heat generation (metabolism) increases and heat loss
(vasodilation) decreases.
d. NSAIDs effectively suppress this response.
3. Anti-Inflammatory Effects
-PGE2 and PGI2 cause vasodilation and are important
mediators of localized erythema and edema in
inflammation.

NON-SELECTIVE COX INHIBITORS

Clinical Uses

1. Low dose ASA together with diet and exercise is useful

for the treatment of:
a. MI
b. Secondary prevention of MI and stroke
c. Coronary Artery Disease (CAD)
d. Unstable angina
e. Peripheral vascular disease
2. Reduction in thromboembolic complications in
patients with:
a. Artificial heart valves
b. Hemodialysis
c. Coronary bypass grafts
3. Very little, if any, efficacy in venous clotting
4. In the same low doses effective in antiplatelet activity,
ASA is also effective in reducing the occurrence and
metastasis of cancer (reduced at least 1/3).
5. ASA and Plavix are frequently used in combination
in high risk situations, like:
a. Stents
b. Acute Coronary Syndrome
Indomethacin is the NSAID often used to stimulate
closure of the patent ductus arteriosus.
1. Used for post-operative pain as an alternative to
opioids.
2. Pain and Fever: Symptomatic relief for pain of low to
moderate intensity.
a. HA
b. Dysmenorrhea
c. Arthralgia
d. Myalgia
e. Neuralgia
f. Arthritis
3. Anti-inflammatory agent:
a. Rheumatoid Arthritis (RA)
b. Osteoarthritis (OA)
c. Gout and Crystal Arthritis
d. Systemic Lupus Erythematosus (SLE)
e. Seronegative Spondyloarthropathy
f. Arthralgia
g. Myalgia
h. Bursitis, Tendonitis

SELECTIVE COX-2 INHIBITORS

Clinical Uses
Originally approved for:
a. Dysmenorrhea
b. Osteoarthritis (OA)
c. Rheumatoid Arthritis (RA)
d. Acute post-operative pain

NON-NSAID ANTIPYRETIC/ANALGESIC
Clinical Uses

1. Analgesic and antipyretic effects equal to common

NSAIDs
2. Very weak anti-inflammatory activity (Thus, NOT an
NSAID)
3. Useful analgesic, antipyretic for children and those with
contraindication to ASA.

ERTIES OF NSAIDs
Side Effects

1. GI Irritation Effects (As a salicylic acid derivative, ASA does this more so than
most other NSAIDs):
a. Epigastric distress
b. Nausea
c. Vomiting
d. Microhemorrhage (Doesn't cause gross blood in vomit/Hematemesis)
e. Ulceration
f. Anemia
2. Effects on the Kidney:
a. Little effect in normal subjects
b. In situations where there are high levels of circulating vasoconstrictors
(i.e. compensated CHF, Chronic renal disease), NSAIDs can reduce the renal
blood flow, precipitating acute kidney injury (AKI).
c. Retention of sodium and water. Reduced effectiveness of hypertensive
regimens.
d. NSAIDs and COX-2s should be used with caution in patients with:
i. Reduced renal function
ii. Heart failure
iii. Liver dysfunction
iv. Patients on ACE inhibitors or diuretics, especially elderly patients
3. Overt Toxicity:
a. Increased risk of serious CV events (Class effect: Both selective and nonselective NSAIDs increase risk)
b. Salicylism- Mild Intoxication
i. Nausea
ii. Vomiting
iii. Tinnitus
iv. Hyperventilation
v. HA
vi. Mental confusion
vii. Dizziness
c. Overdose- Acute medical emergency (Children especially vulnerable)
i. Fever
ii. Dehydration
iii. Delirium
iv. Hallucination
v. Convulsions
vi. Coma
vii. Respiratory and Metabolic Acidosis
viii. Death
4. Adverse Effects during Pregnancy
-Avoid use during third trimester unless absolutely necessary
a. Low birth weight
b. Increased perinatal mortality
c. Anemia
d. Antepartum and Postpartum hemorrhage

a. Increased risk of serious CV events (Class effect: Both selective and nonselective NSAIDs increase risk)
b. Salicylism- Mild Intoxication
i. Nausea
ii. Vomiting
iii. Tinnitus
iv. Hyperventilation
v. HA
vi. Mental confusion
vii. Dizziness
c. Overdose- Acute medical emergency (Children especially vulnerable)
i. Fever
ii. Dehydration
iii. Delirium
iv. Hallucination
v. Convulsions
vi. Coma
vii. Respiratory and Metabolic Acidosis
viii. Death
4. Adverse Effects during Pregnancy
-Avoid use during third trimester unless absolutely necessary
a. Low birth weight
b. Increased perinatal mortality
c. Anemia
d. Antepartum and Postpartum hemorrhage
e. Prolonged gestation
f. Premature closure of ductus arteriosus

E COX INHIBITORS
Side Effects

1. ***Reye's Syndrome*** is a rare, but often fatal, consequence of

infection with chicken pox, varicella, and influenza viruses.
a. Liver damage and encephalopathy
b. The use of Salicylates in children or adolescents with chicken pox or
influenza is contraindicated.
c. All NSAIDs in children are a second choice to Acetaminophen because of
this issue.
2. Patients with nasal polyps in combination with asthma are particularly prone
to show significant allergy to ASA.
a. Can progress from hives, nasal secretion, and edema to severe dyspnea,
hypotension, and shock.
b. Hypersensitivity to ASA is a caution to other NSAIDs.
3. GI Bleeding, GI Pain, and GI Ulcers
a. Low dose minimizes untoward effects

High rates of GI bleeds prevent the drug from being used chronically in arthritis
(Has to be used episodically).

1. NOT for use in obstetrics because of enhanced bleeding risk.

2. Unlike opioids, it is NOT associated with tolerance, withdrawal effects, or
respiratory depression.
3. Bleeding (Particularly the GI tract, with ulcer formation and aggravation)
4. Kidney (Particularly important in uncontrolled HTN)

OX-2 INHIBITORS
Side Effects
1 By leaving COX-1 unaffected, a number of benefits are available:
a. Significantly fewer GI ulcers (but by endoscopy, decreased GI bleeding with
Celecoxib is still unproven).
b. Does not impact platelets and bleeding time.
2. Contraindicated in ASA allergy and 3rd trimester pregnancy

PYRETIC/ANALGESIC
Side Effects

1.Well tolerated; lacks GI and platelet side effects

2. NOT associated with Reyes Syndrome
3. Toxicity:
a. Acetaminophen does not have the GI bleeding toxicity seen with NSAIDs.
However, a toxic metabolite of Acetaminophen is generated in the liver.
b. Toxicity is seen with large overdose (usually suicide attempts),
although there is increasing interest in whether even small doses of Acetaminophen
cause some damage to the liver.
c. FDA moved to reduce dose available over the counter, which has greatly
reduced the frequency of this toxicity.

Notes

1. COX-1 is constitutively active

and is present in most tissues.
2. COX-2 is induced by cytokines
and other inflammatory mediators.
3. Advantages of other NSAIDs vs ASA:
a. More potent
b. More efficacious
c. Cause less GI irritation or other
side effects
d. Have longer duration of action,
so taken less frequently

and other inflammatory mediators.

3. Advantages of other NSAIDs vs ASA:
a. More potent
b. More efficacious
c. Cause less GI irritation or other
side effects
d. Have longer duration of action,
so taken less frequently

Notes

1. Generic; OTC
2. Prototype drug
3. Salicylic Acid derivative

Indomethacin is the most efficacious

of the NSAIDs.

1. Most efficacious NSAID

analgesic. Efficacy approaches high
efficacy opioid in some conditions.
2. Weaker anti-inflammatory effect.
3. Can be used orally, IM, or IV (One
of only a few NSAIDs that can be given
parenterally).

Notes

Notes
1. A non-narcotic analgesic
2. Mechanism of Acetaminophen
Toxicity:
a. Depletion of Glutathione
b. Major Pathways: Sulfation and
Glucuronidation
c. Minor Pathways: Particularly in
overdose, Glutathione can be
depleted, and hepatic damage occurs.
3. Treatment of Acetaminophen
Overdose:
a. Glutathione does not cross cell
membranes readily.
b. N-acetylcysteine substitutes for
glutathione, and this compound can be
administered to treat toxicity.

GENERA
Name

Mechanism

Opioids

1. Endorphins
a. Usually associated with ***mu*** receptor
activation
b. Derived from Prepro-opiomelanocortin (POMC)
i. Gives met-enkephalin, beta-endorphin, ACTH, etc.
2. Enkephalins
a. Usually associated with ***delta/mu*** receptor
activation
b. Methionine (met-enkephalin) and Leucine (leuenkephalin) containing pentapeptides
c. Derived from Preproenkephalin
i. 6 copies of met-enkephalin and 1 copy of leuenkephalin
3. Dynorphins
a. Usually associated with ***kappa*** receptor
activation
b. Derived from Prodynorphin
i. Dynorphin A and B
4. Endogenous Peptide Activity:
a. Mu- Endorphins > Enkephalins > Dynorphins
b. Kappa- Dynorphins >> All others

Opioids

Name

a. Usually associated with ***delta/mu*** receptor

activation
b. Methionine (met-enkephalin) and Leucine (leuenkephalin) containing pentapeptides
c. Derived from Preproenkephalin
i. 6 copies of met-enkephalin and 1 copy of leuenkephalin
3. Dynorphins
a. Usually associated with ***kappa*** receptor
activation
b. Derived from Prodynorphin
i. Dynorphin A and B
4. Endogenous Peptide Activity:
a. Mu- Endorphins > Enkephalins > Dynorphins
b. Kappa- Dynorphins >> All others

Mechanism

Morphine

1. Binds to all opioid receptor subtypes

2. Highest affinity is for Mu receptors
3. Low oral:parenteral ratio
a. Morphine is highly polar, hence it is both slowly
and incompletely absorbed after oral
administration.
b. Both factors are important in its lower potency by
the oral route

Meperidine
(Demerol)

Shorter elimination half-life, so more frequent

dosing required

Methadone
(Dolophine)

1. Very long elimination half-life (approx. 24 hours)

2. Blocks NMDA receptors and monoamine
reuptake pumps (a typical antidepressant mechanism)

Fentanyl
(Sublimaze;
Duragesic)

1. Fentanyl and Sufentanil are the most lipid soluble,

highest potency agents.
2. Very low doses are required
3. Effective by transdermal patch (Good alternative for
vomiting patients)

Name

Mechanism

Butorphanol
(Stadol)

Relatively pure kappa agonist

Nalbuphine
(Nubain)

1. Relatively intermediate to high efficacy kappa

agonist
2. Also a mu antagonist

Name

Mechanism

Hydrocodone

Intermediate to high efficacy (Particularly after oral

administration)

Oxycodone
(Percodan;
Percocet;
OxyContin)

Intermediate to high efficacy (Particularly after oral

administration)

Pentazocine
(Talwin)

Moderate Kappa agonist with either very weak partial

agonist or pure antagonist actions at Mu receptors

Name

Mechanism

Buprenorphine
(Buprenex)

1. Long duration of action

2. Slow to dissociate from Mu receptors

Codeine

1. Codeine is a pro-drug.
2. The analgesic effects of the drug come from the slow
conversion of Codeine to Morphine by
demethylation via cytochrome CYP2D6

Name

Mechanism

Tramadol

1. Weak Mu agonist
a. Metabolite is a somewhat more efficacious Mu
agonist than the parent compound
2. CNS Serotonin Releaser
a. In pain management programs, drugs that block
serotonin re-uptake (Older antidepresants) are often the
cornerstones of therapy
3. Norepinephrine re-uptake inhibitor
4. Several other actions as well (NOT an NSAID)

Name
Naloxone (Narcan)

Mechanism
1. Short acting
2. Not absorbed orally, so main use is parenterally

Naltrexone (ReVia; 1. Long acting

Depade; Trexan) 2. Oral route only (Not given parenterally)

Name

Mechanism

Dextromethorphan Non-opioid available OTC

Name
Docusate
Mineral Oil

Mechanism
Facilitates water and fat entering the stool
By coating the stool, holds water inside

Name
Mechanism
Methylnaltrexone
Peripherally active opioid antagonist
(Relistor)

GENERAL PROPERTIES OF OPIOID ANALGESICS AND ANTAGON

Clinical Uses

1. Indicated for moderate to severe pain where

opioid use is to be continuous
a. Typically prescribed post-surgery on
outpatient basis.
b. Not for intermittent or PRN use
c. Mu agents are usually NOT for
immediate post-op use following major
surgery (first 12-24 hours after surgery)
i. Kappa agents are often used in this
period
ii. Then Mu agents are introduced once
respiration is documented to be stable
2. All opioids are efficacious cough
suppressants
a. The ceiling on abuse liability has resulted in
Codeine usually selected as the first agent
of the opioid drugs that is prescribed if OTC meds
are ineffective

c. Mu agents are usually NOT for

immediate post-op use following major
surgery (first 12-24 hours after surgery)
i. Kappa agents are often used in this
period
ii. Then Mu agents are introduced once
respiration is documented to be stable
2. All opioids are efficacious cough
suppressants
a. The ceiling on abuse liability has resulted in
Codeine usually selected as the first agent
of the opioid drugs that is prescribed if OTC meds
are ineffective

HIGH EFFICACY MU OPIOIDS

Clinical Uses

Prototypic opioid analgesic

Significant use when analgesia of relatively

short duration (<3 days) is required (such as
during pregnancy delivery).
1. Often more efficacious than Morphine in
difficult to treat pain
2. Used in opioid-abuse treatment programs
Used in surgery, particularly cardiovascular
surgery, to obtain analgesia with minimal
cardiodepressant effects.

HIGH EFFICACY KAPPA OPIOIDS

Clinical Uses
1. Post-surgery control of pain
2. Women show a greater analgesic response
to Butorphanol than do men.
Post-surgery, when patients are having
respiratory depression, this drug is often used to
remove the respiratory depression effects
of mu agonists given prior to (or during)
surgery, while maintaining analgesia.

OPIOIDS WITH INTERMEDIATE EFFICACY

Clinical Uses

1. Often used outpatient when pain relief is

needed that is greater than can be obtained
with Hydrocodone

Developed as an oral analgesic with limited

abuse potential

OPIOIDS WITH LOW EFFICACY

Clinical Uses
Ideal drug for preventing access to the
receptor by high efficacy compounds (Used in
narcotic treatment programs for this effect).

Often the opioid of choice for cough

a. As with most opioids, cough suppression
appears to be by action at Mu receptors

MISCELLANEOUS MU AGENTS
Clinical Uses

1. Efficacy is good against pain into the

moderate to moderately severe range (Pain
relieving efficacy is nearly equivalent to that of
Hydrocodone)
2. Neuropathic pain
3. Often a choice for outpatient therapy
(Particularly if there is any concern about a
patient engaging in non-medical use of
opioids).

OPIOID ANTAGONISTS
Clinical Uses
Useful for opioid overdose (Coma,
Respiratory depression, and Miosis)
1. Opioid treatment programs
a. Poorly tolerated by patients
2. Adjuvant in alcohol treatment
a. Decreases craving

COUGH SUPPRESSORS
Clinical Uses
Cough

STOOL SOFTENING AGENTS

Clinical Uses
Offsetting opioid-induced constipation

PERIPHERALLY ACTIVE OPIOID ANTAGONIST

Clinical Uses
Offsetting opioid-induced constipation

OPIOID ANALGESICS AND ANTAGONISTS

Side Effects

1. Opioid Receptor Subtypes:

a. Mu receptors (Important for most of the classical effects described for opioids):
i. Analgesia (The greater the efficacy against pain, the greater the abuse
potential)
A. Best with severe, constant pain
B. Not as effective with sharp, intermittent pain
C. Although dulled, pain is still perceived (Reaction to pain is diminished)
ii. Respiratory depression (Cause of death in overdose due to decreased response
of brainstem to CO2)
iii. Euphoria
iv. Physiological dependence
v. Miosis (Pinpoint pupils)
vi. Constipation
A. Reduced GI mobility secondary to increased tone due to effects both in the CNS
and the local enteric nervous system
B. Sometimes described as a spasm (not a coordinated contraction)
C. Treat with Stool Softeners, NOT Fiber.
vii. ***NO TOLERANCE TO MIOSIS OR CONSTIPATION***
b. Delta receptors:
i. May be more associated with euphoria than mu receptors
c. Kappa receptors:
i. ***Dysphoria***
ii. Analgesia
iii. Sedation
iv. Vasodilation (Morphine is the most efficacious for this effect)
v. Increased urinary output
vi. Less respiratory depression and miosis than mu agonists
vii. Psychotomimetic responses (Disoriented or depersonalized feelings)
viii. Less involvement in abuse potential and physical dependence
2. Opioid Tolerance:
a. Occurs even with the lowest therapeutic doses and increases as dose and duration
of treatment increase
b. Tolerance, with cross-tolerance, can develop to all opioid agonists (If you become
tolerant to one Mu agonist, you can be cross-tolerant to all Mu agonists)
c. Rate of development varies among agents, but generally develops faster with more
potent drugs and/or higher doses
d. Starts with first dose, but doesn't become clinically relevant for 2-3 weeks
(at normal therapeutic doses)
e. There is specificity of tolerance development:
i. ***No or very little tolerance to miosis and

constipation***
ii. Tolerance to other effects develops essentially in parallel (equal degree to
sedation, respiratory depression, etc.)
f. Tolerance can be profound (as great as 35-fold)
3. Opioid Dependence:
a. Accompanies tolerance development

ii. Analgesia
iii. Sedation
iv. Vasodilation (Morphine is the most efficacious for this effect)
v. Increased urinary output
vi. Less respiratory depression and miosis than mu agonists
vii. Psychotomimetic responses (Disoriented or depersonalized feelings)
viii. Less involvement in abuse potential and physical dependence
2. Opioid Tolerance:
a. Occurs even with the lowest therapeutic doses and increases as dose and duration
of treatment increase
b. Tolerance, with cross-tolerance, can develop to all opioid agonists (If you become
tolerant to one Mu agonist, you can be cross-tolerant to all Mu agonists)
c. Rate of development varies among agents, but generally develops faster with more
potent drugs and/or higher doses
d. Starts with first dose, but doesn't become clinically relevant for 2-3 weeks
(at normal therapeutic doses)
e. There is specificity of tolerance development:
i. ***No or very little tolerance to miosis and

constipation***
ii. Tolerance to other effects develops essentially in parallel (equal degree to
sedation, respiratory depression, etc.)
f. Tolerance can be profound (as great as 35-fold)
3. Opioid Dependence:
a. Accompanies tolerance development
b. May include both physical and psychological dependence
c. Withdrawal syndrome is seen upon cessation of drug use or upon treatment
with opioid antagonists or mixed agonist/antagonists (Precipitated withdrawal)
d. Withdrawal is extremely unpleasant, but for patients in even relatively normal health,
it should never be life-threatening
4. Opioid Overdose:
a. Primary Triad:
i. ***Lethargy or Coma***
ii. ***Respiratory

Depression***
iii. ***Miosis (Pinpoint Pupils)***
b. Secondary:
i. Hypotension
ii. Hypothermia with cold or clammy skin
iii. Pulmonary edema
iv. Convulsions (Primarily in children)
v. Dilated pupils (Caused by hypoxia, but this is a very near death event; usually
see miosis)

FFICACY MU OPIOIDS
Side Effects

High efficacy for:

a. Analgesia
b. Respiratory depression
c. Dependence

Metabolite (Normeperidine) can cause Seizures if the drug is taken for significant
periods

Highly lipid soluble opioids when given I.V. quickly can cause truncal rigidity

ICACY KAPPA OPIOIDS

Side Effects
1. Kappa agonists have a limited role in pain management because
dysphoria/psychotomimetic effects increase in parallel with pain relief.
2. Less potential for respiratory depression than mu agonists
3. ***Dysphoria***

***Dysphoria***

H INTERMEDIATE EFFICACY
Side Effects
Schedule II (High abuse potential) drug

Attempts to Limit Oxycodone Abuse:

-Matrix:
a. Intended to prevent parenteral abuse
b. Still in use with high dose formulations of Oxycodone (OxyContin)
c. Permits sustained drug effects, without loss of efficacy at end of dosing
interval, but:
i. Most abuse is oral
ii. Abusers crush the matrix (New formulations make it extremely difficult to get the
drug out of the matrix in this fashion)

WITH LOW EFFICACY

Side Effects
Difficult to reverse respiratory depression
1. Ceiling on analgesia effect is not limited by efficacy
a. Rather, at high doses, Codeine is an agonist at non-Mu receptors that mediate
psychotomimetic effects that are unpleasant
b. This may limit the abuse potential of this agent, but it also limits the efficacy.
2. CYP2D6 is missing in 5-10% of Caucasians
a. Failure to perform demethylation reactions results in unexpectedly high levels
of the parent drugs
b. In the case of Codeine, results in no efficacy as an analgesic (Codeine has no
efficacy at Mu receptors until converted to Morphine) and increased likelihood of
psychotomimetic effects.

LANEOUS MU AGENTS
Side Effects

1. High doses can cause seizures (Most frequently seen as a consequence of misuse)
2. Physical dependence/withdrawal of the opioid type, but relatively minor in intensity
3. Very little respiratory depression on its own, but enhances that effect in other
respiratory depressants (i.e. alcohol)
4. It has so few typical Mu agonist effects that it is a DEA Schedule IV agent

OID ANTAGONISTS
Side Effects
Precipitates withdrawal syndrome in chonic users of opioids

GH SUPPRESSORS
Side Effects
Overdose can cause respiratory depression

SOFTENING AGENTS
Side Effects

Chronic use may decrease fat-soluble vitamins (A, D, E, & K), which can be treated
with vitamin supplements

ACTIVE OPIOID ANTAGONIST

Side Effects
Can precipitate withdrawal because the activity of Methylnaltrexone is not entirely
confined to the periphery

Drug Interactions

1. The addition of NSAIDs to an

opioid give much better analgesia
than the same dose of either agent
alone.
2. Combination of NSAIDs has been
used with good success for all
opioids that are NOT classified as
high efficacy
a. NSAIDs do not add much to the
pain relief of a drug like Morphine
b. However, NSAIDs enhance the
efficacy of drugs like Hydrocodone
3. Weak partial agonist act as
antagonists when given with a full
agonist
-Antagonist Proterties:
i. Block the effects of full
agonists
ii. Precipitate withdrawal
symptoms in individuals physically
dependent on Mu agonists
4. Opioid Overdose Treatment:
a. Administer opioid antagonist
(Naloxone is DOC)
b. Support of respiration and other
vital functions
c. Identify the most likely drug
d. If determined that other drugs
were also ingested, treat for the
overdose of these drugs accordingly

efficacy of drugs like Hydrocodone

3. Weak partial agonist act as
antagonists when given with a full
agonist
-Antagonist Proterties:
i. Block the effects of full
agonists
ii. Precipitate withdrawal
symptoms in individuals physically
dependent on Mu agonists
4. Opioid Overdose Treatment:
a. Administer opioid antagonist
(Naloxone is DOC)
b. Support of respiration and other
vital functions
c. Identify the most likely drug
d. If determined that other drugs
were also ingested, treat for the
overdose of these drugs accordingly

Drug Interactions

Drug Interactions

Drug Interactions
Efficacy is enhanced by adding
Aspirin or Acetaminophen (Vicodin;
Lortab)

High abuse potential when

combined with an anti-histamine

Drug Interactions
Not readily reversible by an opioid
antagonist

Drug Interactions
Many patients are on SerotoninSelective Reuptake Inhibitors
(SSRIs) for the treatment of depression
and/or anxiety. Because Tramadol
increases the release of Serotonin, the
potential exists for provocation of
***Serotonin Syndrome***:
a. Tremor and perhaps clonus
b. Hyperreflexia
c. ***Hyperpyresis***
(Elevated temperature can be deadly)

Drug Interactions
Reverses the action or blocks the
action of agonists

Drug Interactions
When used with opioids, this drug
increases the cough suppressant
effects of the opioid.

Drug Interactions
***Do NOT treat opioid-induced
constipation with Fiber***

Drug Interactions
***Do NOT treat opioid-induced
constipation with Fiber***