I.

Adrenergic & Cholinergic:

TABLAS DE RESUMEN BIEN IMPORTANTE!!!
M3 receptor in Blood vessels is SYMPATHETIC

Predominant tones in ANS:

Arterioles Sympathetic (adrenergic)
o Ganglionic Block: Vasodilation
Veins Sympathetic
o Ganglionic Block: Hypotension, Venidilation

Heart (inotropic/Force) Sympathetic

o Ganglionic Block: Force contraction

Heart (chronotropic/HR (ANS)) Parasympathetic

o Ganglionic Block: Tachycardia
EYE Parasympathetic
o Ganglionic Block: Mydriasis
Cilary Muscle Parasymp
o Ganglionic Block: Cycloplegia
Bladder Parasympathetic
o Ganglionic Block: Retention
GI Parasympathetic
o Constipation, motility
Sweat Sympathetic (Cholinergic)
o Ganglionic Block: Anhidrosis

Adrenergic Agonist and Antagonist:

- methyl-tyr inhibe la formacion de L-DOPA inhibiendo tyrosine hydroxylase
o Norepinephrine Synthesis: TyrosineDOPADopamineNorepinephrine

1, 1, 2, 3 localization POST-SYNAPTICA
2 PRE SYNAPTIC (autoreceptor, acoplado negativamente a AdenylCyclase)

Guanethidine, Reserpine Inhibit el release de NE (como si no existiera)

o DEPLETES CATECHOLAMIES, so they are nerve released

Dexmedtomidine: Prominent sedative effects used in anesthesia

o 2 Agonist

Pherntermine NE reuptake (para bajar de peso)

o Familia de Amphtemamine

1 Antagonist: IP3/DAG
o Phento-Lamine (non-selective)
 o Phenoxy-Benzamine (non-selective)
o Pra, Doxa, Tera-zonzin: Benign prostatic hyperplasia,
o Blocking a1 te va dar Orthostatic hypertension
Das un agonista para mejorarlo
Cloplomazine (anti-psychotic con propiedades -antagonist)

1 Agonist: IP3
o PhenylEphrine- pupillary dilator (+ Tropicamide) @ radial muscle,
Vasoconstriction (for epistaxis), Nasal decongestion
MYDRIATIC
IV for short term maintenance of BP in Acute Hypotension
Intranasal for vasoconstriction as decongestant
o Methoxamine,
o MirdorineOrthostatic hypotension

Ephedrine Indirect agonist releasing stored catecholamine

Used in Nasal congestion, Urinary Incontinence, Hypotension

2 Agonist: cAMP
o Clonidine: inhibes el RELASE de catecholamine (Tx: Glaucoma)
Inhibe a nivel central
HYPERTENSION
o Oxymetzoline
o Tizanidine Muscle Relaxant
o Apraclonidine and Brimodine agonista del 2-receptor used in Galucoa
Aqueous secretion

2 Antagonist: cAMP Betaxolol

o Rwawolscine, Yohimbine, Tolazoline
o Yohambine ANTAGONISTA de a2 Receptor
Dysfunction erectile
anxiety

Non-selective Antagonist: LABETALOL, Phentolamine

Beta receptors cAMP

B1 Agonist:
o DOBUTAMINE ( lo usas no quieres bloquiar el Corazon pq tiene CHF y lo quieres estimular)
 Cardiogenic shock, Heart failure
o Receptor 1 produce humor aqueous y 2 disminuye la produccion de humor aqueous

1 Antagonist: cAMP
o Acebutol (partial agonist), Atenolol, Betaxalol, Esmolol, Metoprolol
Bueno para un pte con asthma se lo das para no tocar el B2
o 1 Antagonist: -olol from A-M

2 Agonist: @lungs (cAMP y relaja musculo liso)

o Albuetrol, Terbutaline, Metoproterenol
o VASODILATACION
o RELAJAR el musculo liso en Aborto

B2- Antagonist Butoxamine

o No clinical value

B3 LYPOLISIS!

NON-SELECTIVE -Agonist
o Iso-Proterenol (activa B1 y B2)

NON-SELECTIVE -ANTAgonist:
o Nadolol
o Pindolol (partial agonist)
o Propranolol
Profilaxis for migraines, SOCIAL PHOBIA
o Timolol
o Hyperthryroidism, Arrhytmia, Angina, Hypertension
o Non-Selective go from N to Z

/ Antagonist Mixto: Labetalol, Cavediol (modified suffix instead of -OLOL)

o Crisis hypertensiva
o Clavedilol- tiene un efecto antioxidante

Mixed Alpha and Beta Agonist:

Norepinephrine: 1=2; 1>>2
Epinephrine: 1=2; 1=2 [Epinephrine Reversal]
o 1 es el mas fuerte para BP
o si bloqueo el 1, ahora epinephrine va a 1 (HR) y 2 vasodilatacion

Dopamine: D1=D2>>>>
D1: Vasodilatation de la AFERENTE RENAL
o Fenoldopam (D1>B1>>1)
 o urine output (diuresis)
o CAUTION!!! si lo dejas pegado puedes el activar 1 y contractile force y eventualmente activar
receptor va a Resistencia y podria inducir un arrhythmia
D2: Bromocriptine

1 and 2 contribute to the formation of GLUCOSE (GLYCOGENOLYSIS)

o PANCREAS: =insulin secretion; =Glucagon
o LIVER: =Glycogenolysis
o SKEELTAL Mu: = Glycogenolysis

Adrenergic AGONISTS:

Lacrimal system: Both sympathetic and Parasympathetic go in same direction

o 1 y M3 producen SECRECION
THE EYE!!!

Intraocular Pressure by:

o 2 receptor activation
o Ciliary VASCULAR 1 receptor activation (vasoconstriction)
o 2 receptor block, improving ovescleral outflow

Glaucoma:

Muscarinic antagonists or sympathetic 1 agonists (both of which can dilate

the pupil) exacerbate glaucoma, by reducing drainage of the aqueous humor

Timolol, Betaxolol B-blocker

o DRUG OF CHOICE for OPEN Angle Glaucoma (timolol)
o Betaxolol B1 Antagonist
o Mechanism: aqueous secretion
o Cartolol

Apraclonidine and Brimodine Selective 2 Agonist

o Mechanism: Aqueous secretion and outflow

Epinephrine, Dpivefrin = outflow aqueous

o Dipivefrin Epinephrine Prodrug
2 receptor (aquous humor)
2 (improves uveoscleral outflow)
Grupo pivalil q se rompen cuando entran al ojo y se convierte en epinephrine

ADRENERGIC MECHANISM REDUCES AQUOUS HUMOR FORMATION!!!

o CHOLINERGIC MECHANISM (Pilcarpine, Carbachol) Drainage of Aqueous humor

 LatanaprostActivation of pros tanoid preceptors that imporves uvescleral output
o PG72 Analogue (Prostaglandin)
o No se si sea relevante para este examen

Conjuntival Descongestant:
o Phenyleprhine (1agonist)
o Oxymetazoline, Zylometazline alpha 2 agonist, Longer acting

Angle Closure Glaucoma Test:

o Phenyleprhine (1agonist) + Tropicamida (muscarinic Antagonist): si en 1hr IOP 8mmHg
es positive para ANGULO CERRADO
Tropicamida: Least Potent Mydriatic/ Cyclopegic, Muscarinic ANTAGONIST
o HydroxyAmphetamine + tropicamide is another alternative

Examination (dilation of pupil) Phenyleprhine (1agonist) + Tropicamida

Anisocoria Cocaine/ Amphetamine

Horner Syndrome: MIOSIS, PTOSIS, and ANHYDROSIS

o Step 1: Si tiene anisocoria y le das COCAINA debe relajarse, pero cuando esta fallida el efecto
no se produce, pero la normal se dilate
Permits identification of the affected eye

o Step 2: Hydroxy- amphetamine or Tyrosine (Paredrine test): se da1%

hydroxy-amphetamine y si observo que la q estaba danada se DILATA quiere decir que la
neurona esta synthetizando catecholaminas y que el musculo esta bien pero la neurona
PRE-SYNAPTICA esta mala
hydroxy-amphetamine release of catecholamines
Si NO dilata, la POSTGANGLIONICA esta fallida

HEART:
Norepinephrine (1=2; 1>>2): MAP
o Vasopresive/hypertensive
o PVR (vasoconstriction via 1) and HR (reflex bradicardia)
o
Epinephrine (2>1; 1=2): slight MAP
o Reverse effect (1 y 2 son los mas relevates)
o PVR (vasodilation/B2)
o HR (Chronotripism/inotropism (1))
o MAP en ALTAS DOSIS
 Isoproterenol (B1=B2): MAP
o PVR (2)- vasodilatacion masivo
o HR (1)
o Tx: Electrophysiologc evaluation of Tachyarrhythmias

Tx for Hypostensive State: The GOAL is to perfusion

o Ephedrine (Indirect agonist)
o Midodrine (1)
o Dobutamine (1)
o Dopamine (renal blood flow)
o Epinephrine

Local Anesthesia: Goal is to bloodflow

o Cocaine
o Note: NEVER give -blocker if cocaine intoxication is suspected bc can lead to unopposed 1
application and EXTREEME HYPERTENSION
o EpinephrineVasoconstriction (1)

Paroxysmal Atrial Tachycardia PhenylEphrine (1 vagal discharge)

The increase in PVR will result in a VAGAL DISCHARGE (bradicardia)
o Intranasal congestion
o IV Hypotension

Postoperative Hypertension:
Fenoldopam (D1)
o Promotes NATRIURESIS
Clonidine (Central 2)

Congestive Heart Failure:

Dobutamine (1>2, )
Cardiac stress testing

Nasal decongestant Ephedrine

Goal is to blood flow
Improves Urinary Incontinence
Improves Hypotension

Narcolepsy, Obesity, ADHD Amphetamines

Reuptake inhibitor, releases stored catecholamines
Genitourinary Smooth Mu***:
o 2 Relaxes Bladder wall and UTERUS (use 2 agonist for abortive delivery)
o 1 CONTRACTS the Sphincter/Uterus and induces EJACULATION

Abortion: 2 agonists
Ritodrine/Tertbutalin
Albutrerol
Metoproterenol
o Uterine smooth mu relaxation

Benign Prostatic Hyperplasia:

Tamsulosin: SELECTIVE 1 ANTAGONIST w less sides effects (Hypotension) new drug
Prazozin

CNS: indirect acting drug can cross the BBB

Substance abuse (craving):
CLONIDINE (2 agonist)

CENTRAL Sympatholytics 2 AGONISTS :

-Methyldopa
Guanfacine
Guanabenzine

Narcoplepsy:
Amphetamines

Suppress appetite:
o Phentermine** (inhibit reuptake de catecholamine, se parece a amphetamine)

ADHD Methypheydate (Ritalin)

Anaphylaxis:
EPINEPHRINE: 2>1;2=1
o BronchospasmB2
o Angioedema a1
o Mucous congestiona1
o Cadiovascular collapseB1
o Mast cell release B2
o B2 receptor inhibits histamine release from inflammatory cells
Others:
Dexmedelomide 2 agonist w SEDATIVE effects; used in ANESTHESIA

Tiazidine 2 Muscle Relaxant

Drug interactions and Adrenoreceptor Agonist Toxicity:

Wine and Cheese effect (tyramine) w MAO HYPERTENSIVE CIRSIS
o AD + TYRAMINE (tyramine es como dar NOREPINEPHRINE)
o AD + Sympathimimethics

Drug interactions:
Also avoid OPIATES (Meperidine) cough secretions, cold remedies, Nose , Laxatives
SSRI
Methyphenidate (RITALIN; amphetamine-like)
Cocaine
L-DOPA

Adrenergic ANTAGONIST
Most common toxicity in 1 AntagonistORTHOSTATIC HYPOTENSION
Phenoxybenzamine IRREVERSIBLE 1- Antagonist
o Tx Pheochromocytoma
o Preoperatively to prevent Catecholamine (hypertensive) crisis
o Toxicity: Orthostatic Hypotension and Reflex tachycardia
Yohombine-antagonist (fue remplazado)
o Impotencia and erectile disfuntion
o induce panic attack

Propranolol, Nadolol Non-selective B-blockers

o ProparanololShort half-life
o Nadolol Long half-life
o Variceal Bleeding: Hepatic venous pressure gradient and portal hypertension

Butoxamide no clinical value, causes asthma

Penbutolol, Pindolol Partial Agonists

 Prazosin, Terazosin, Doxazosin for Hypertension, Urinary Retention in BPH
o 1 blocker

B-Blockers:

1 receptor mediates the RELEASE of RENIN

Inhibits Supraventricular Tachycardia

B1-Selective antagonist (Maldonado)

o Acebutol (B1 partial agonist)
o Alprenolol (B1 partial agonist)
o Atenolol (antagonist)
o Metoprolol (1 selective @LOW doses)
o (olol from A-M)

B2 selective Antagonist: BUTOxamine (no clinical value)

Non-selective Antagonist (B1=B2):

o Nadolol
o Pindolol (partial)
o Timolol
o Propranolol
 o (-from N to Z)

Glaucoma:
Timolol (non-selective B-blocker)
Betoxolol (1 antagonist)
Mechanism: aqueous humor

Geniturinary:
BPH Tamsulosin, Alfuzosin, Silsodin: NEW zosins for BPH
o Prazosin, Terazonsin, Doxazosin also for BPH
o TamsulosinSelective 11A antagonist

Erectil dysfunction** Phentyolamine (non-selective)+ Papverine

Hypertensive Crisis/EMERGENCY** LABETOLOL (Mixed /)

Hypertension 1 selective, nonselective and Mixed

Prophylaxis for MIGRAINE:

Propranolol,
Metoprolol, Nadolol, Atenolol

Esmolol rapid and short acing B-blocker (es el de media vida mas corta de todos)
Rapid control of BP and Arrhythmias
THYROTOXICOSIS
Setting of SURGERY

Methyrosine Tyrosine Hydroxylase Inhibitor

Lo utilizas cuando NO quieres catecholaminas como en PHEOCRHOMOCYTOMA
o Pheochromocytoma (Methyrosine, Phenoxybenzamine)
Phenoxybenzamine is first line

II. CHOLINERGICS AGONIST and ANTAGONIST

 Adrenal medulla Receptor Nicotinico (Sympathetic con ACh)
Sweat Glands Sympathetic w ACh
Vasos sanguines NO hay PARASYMPATETIC pero hay M3 (release NO for Vasodilation)
M1 Nerves (including Myenteric)
M2 Heart, Nerves, Smooth mu
M3 Glands, Smooth mu, Endothlelium, SECRETION!!! Bronchonstriction!!
o Eye Miosis
o Human Lacrimal Glnads

EYE:
Mydriatics/ Cycloplegics Muscarinic Antagonist
o Mydriatics Adrenergic Agonists
o Note: the most effective mydriatics are the MUSCARINIC R ANTAGONIST due to the
predominance Parasympathetic tone in the eye (Cycloplegia and Mydriasis mediated by
M3)
Acute Angle-Closure Glaucoma:
Pilocarpine in emergency situations

Primary Angle Glaucoma:

Timolol Drug of choice
 Pilocarpine is the Cholinergic drug of choice
o promote outflow/drainage of aqueous humor
o Lowers Iris Capture
o 3ry amine (Central)
o Binds only to Muscainic recptors
o Potent stimulator of sweat, tears, saliva used to dx Cystic Fibrosis
o Partial agonist
o SJOGRENs SYNDROME

Cevimeline:** Selective agonist of M3 (parecido a Pilocarpine)

o De los pocos cholinergicos selectivos

Carbachol 4ry Amine (do NOT crosses BBB)

o Non-Selective MAChR Agonist and Nicotinic agonist
o Full agonist
o Outflow/ drainage of aqueous humor (Constrict pupuil and relieves IOC in OPEN
glaucoma)
o Lowers Iris Captures
Mechanism (Pilocarpine, Carbachol) Drainage of Aqueous Humor (activation of
muscarinic receptors and smooth mu (circular & longitudinal) improves uveoscleral outflow

AChE Inhibitors (ACh) in Gluacoma:

Reversible Physostigmine (no longer used)
Irreversible Demecarium(4ry), Echotiophate (4ry)
SE: Can cause Retinal detachment and Cataratogenic potential

Adverse effects of MIOTIC AGENTS:

Lens curvature
Induced myopia
Potential pupillary block
Night vision
Opacities
TEARING and DETACHMENT Cholinesterase inhibitors
Contraindication: AChEI and Pilocarpine!!
Genitourinary:
Betanechol (4ry) MUSCARINIC AGONIST
o Reflux esophagitis, Ileus, Megacolon
Si das ACh solo se degrada en un instante
BETANECHOL es mas resistente a la Cholinesterase
4ry pq quieres que el efecto sea PERISPHERALMENTE
o For Post-operative Urinary Retention
o Close Lower Esophageal Sphincter (promueve vaciaje y aumenta el sphincter)
Prokinetic,isatypeofdrugwhichenhancesgastrointestinalmotility
o SE: Abdominal Pain, Diarrhea (estimula ACh, no es raro)

Cholynesterase inhibitors Amplify both NICOTINIC and MUSCARINIC Action of ACh

Indirect acting agents (AChE inhibitors) do NOT typically cause VASODILATION bc endothelial
receptors are NOT innervated and does NOT release ACh!! They have Mucarinic receptors that
resistance by NO

Edrophonium/Neostigmine (both 4ry): CHOLINESTERASE INHIBITORS

o Edrophonium an ALCOHOL (Short half life)
Dx of Mysasthenia Gravis

o Neostigmine:
like Edrophonium w LONGER Half life
A CARBAMATE, 4ry (no BBB crossing)
Reflux esophagitis, Ileus, Megacolon, Reversal of neuromuscular junction
block (Postoperative)
Se utilizan mas para un CHALLENGE del Ileo a ver como se comporta

Pyridostingmine (4ry) (AChE inhibitor;ACh )

o A CARBAMATE
o Drug of choice for Myasthenia Gravis
 o Reversal of Non-depolarizing Blockade (Pyridostigmine/Neostigmine)
Does NOT cross BBB

PHYsostigmeine (3ry) (AChE inhibitor; ACh, CARBAMATE)

Drug of choice for detoxification of Anti-Muscarinic (atropine-like) drugs
ATROPINEMuscarinic antagonist (used for Bradycardia and Eye)
Amanita muscarie
Note: Atropine-like drugs (anitmuscarinic) should be avoided in ELDERLY
bc can precipitate DEMENTIA

Xerostomia: Pilcarpine, Cevimeline

o Ayuda a estimular la secrecion de SALIVA
o Le puedes dar un shot de PILOCARPINA y si la glandula esta functional, debe producer
sudoracion
o Cevimeline: Selective agonist of M3 (parecido a Pilocarpine)
o De los pocos cholinergicos selectivos

Dementia:
o Tacrine: 1st AChEI available; Hepatoxic
o DonazepilAChE inhibitor drug of choice w NO hepatoxicity and 1 day dosing
Galantamines, Rivastigminete AChEI of choice for Dementia
o Dont give NSAIDS w ACHEI (will upset GI)
o Memantine NMDA Antagoinst for moderate to severe Alzehmiers

Arrhythmias:
o Supraventricular and Paroxysmal Tachycardia: Edrophonium (4ry) and/or
Phenylephrine (CHECK)
ACh will promote BRADYCARDIA
Atropine & Physozztigmine Cruzza BBB!!

Succinyl-choline (NICOTINIC) Skeletal muscle Relaxant

o Depolarizing blocker; agonist that causes depolarizing Neuromuscular BLOCK resulting in
paralysis
o Used to facilitate intubation and other procedures of very short duration
o Toxicity: abdominal pressure, Arrhythmias, POSTOPERATIVE MUSCLE PAIN

Varenicline (Chantix)Exclusively for Smoking cessation

o SELECTIVE PARTIAL AGONIST 42 NICOTINIC receptors

Toxicity of Muscarinic Agonist:

o Hypotension
o Nausea, Vomiting
o Diarrhea
 o Sweating
o Bronchoconstriction
o URESIS
o CNS
Tx: ATROPINE (muscarinic Antagonist)

Tx: Organophosphate intoxicationAtropine (competitive inhibitor; ACh)+ Pralidoxime

(regenerates AChE)
o IRREVERSIBLE
o Pralidoxime is a CHOLINESTERASE REGENERATOR that binds w high affinity to the
phousphorous atom of insecticides.
o Malathion
o Parathion
o Sarin
o Mushroom (Amanita Muscaria)
o Pts can die form Respiratory failure due to neuromuscular paralysis or CNS depression

Muscarinic Antagonist:
ATROPINE: (Muscarinic Antagonist; ACh; NON-SELECTIVE)
o Eye: Pupil dilation, Cycloplegia
o Airway: Secretions
o Stomach: acid secretion
o Gut: Motility
o Bladder: Urgency in cystitis
o Heart: Tachycardia (Atropine is used to treat BRADICARIDA by ACh levels)
Long onset of action: 45-120 min

Imipramine (TCA) Anti-muscarinic

***Ipratropium:
4ry amine (stays in the LUNGS)
Clinical use: ASTHMA/BRONCHITIS

Mydriatics/ Cycloplegics
Cyclopentolate (muscarinic antagonist) and Atropine are the preferred dugs for producing
CYCLOPEGIA in CHILDREN
Cycloplegia:Preventsaccommodationoftheeyetodifferentdistances(permits
detectionofhyperopias)
o SE: Mydriatics are hazardous in CLOSED-angle glaucoma
Pupil dilation and paralysis of the ciliary muscle reduce the drainage of aqueous
humor
Anti-muscarinic and -1 agonist are detrimental in glaucoma
Flushing, Fever, Tachycardia, Constipation, Enuresis, Delirium
Management is mild toxicity discontinuation of drug
Management in severe toxicity Physostigmine
Emetics:
Emetic Agonists Dopamine, Serotonin, ACh, Histamine
o D2 Receptor, 5HT3, M1 Receptors
o Area postrema (fenestrated capillaries)
o

Emetic Antagonist:
o Chlorpromazine, Metoclopramine Dopamine
Phenergan (Promazine)agente antiemetic
CAUTION!!
*****Trimethobenamide (TiganR) nombre parecido a PhenerGAN (tiGAN)
pero son agents MISCELLANOUS, no es como Phenergan pero por el nombre trajo
 el problema pq se dio como agente anti-emetico
o Can cause RYE SYNDROME!!!!
o Ondasteron 5HT
o ScopolamineACh
o Meclizine, Deiphenhydramine Hisatmine
o Estos son los mismos que causan diarrheas!!

Drugs causing Diarrhea:

o Prokinetics:
Metoclopramide (Dopamine Antagonist)
Beanechol (selective Muscarinic R Agonist)
Cisapride (Serotonin drug that motility in GI)
o Parasympathomimetics (substancethatstimulatestheparasympatheticnervoussystem)
CholinergicsandAChEinhibitors
o SSRI
o B-blockers
o L-Dopa
o Mg+ salts, Antacids

Drugs causing Constipation:

o Al++ salts, Antacids
o Anti-cholinergic
o Ca+ channel blockers
o Opiates, Sympathomimetics

Dr. Maldonado

B. Drugs for HYPERTENSION:

HYPERTENSION: BP >140/90mmHg (20/10)
o Treatments: Diuretics, Sympathoplegics, Vasodilators, Angiotensin Antagonits
BP Goal pts w RENAL disease and DIABETS 130/80 mmHg
BP goal in ALL Pts Less 140/90mmHg
o Includes the ELDERLY
Lifelong modifications: Na (<2g/day), 3 servings of Fruit, Vegetables daily, Whole grains, BMI<30,
alcohol (<7 drinks/week males and <5 drinks females)
Systolic BP >140mmHg is an important CARDIOVASCULAR RIKS
Pre-hypertension: 120-139 / 80-80
o NO Hypertension drug indicated
 Tx for Uncomplicated Hypertension Thiazide diuretics (alone or combined)
Prehypertension: 120-139 / 80-80
o NO Hypertension drug indicated
o most pts require 2 or more drugs

HYPERTENSION: BP >140/90mmHg (20/10)

o Stage 1: 140-159/90-99
o Stage 2: 160-179/ 100-109
o Stage 3: >180/110

Treatments requirements:
o Stage 1: 140-159/90-99 Treat w Thiazide diuretics (mild)
o Stage 2: Sys>160 or Dys >100 Treat w 2-drug combination (for example Thiazide and
ACEI or blockers)

Tx for Chronic Hypertension in PREGNANCY: Hypertensive Moms Love Netflix

o Hydralazine (diuretics)
o Methyldopa (most WIDELY USED) ***
o Labetalol (mixed / ANTAGONIST) PREFERED*
o Nefidipime (Ca channel blocker)
o Note: ACE inhibitors, and Angiotensin II R-blockers are CONTRAINDICATED
-Blockers are NOT recommended in EALRY pregnancy
Stepped treatment in Hypertension:
o 1. Lifetime measures 2. Diuretics 3. Sympathoplegics (-blockers, -blokers, etc)
4. Vasodilators (Hydralazine, Minixodil, NitroPrusside, Diazoxide) 5. ACE inhibitors
o polypharmacy if Monotherapy is unsusscesfull

o Elderly Respond better to Diuretics and -blockers

Close monitoring for Cognition deficits w METHYLDOPA; Postrual Hypotension
(Prazozin)
o BlacksRespond better to Diuretics (1st line) and Ca Channel blockers

o DiabeticsACE inhibitors, -Antagonist, Ca+ antagonist (few adverse effects on CARBS

metabolism)
ACE inhibitors/ARB are protective against Diabetic Nephropathy
B-blockers are contraindicated bc they will induce a HYPOGLYCEMIC state
 o Hyperlipidemic**: LOW DOSE of DIURETICS have little effect on Cholesterol and TG
-blockers LDL, HDL ratio
Ca channel blocker, AG II Receptor block, ACE little effect on LIPIDS

Hypertensive Emergencies:
o Systolic>210 and Diastolic >150
o Diastolic >130 w Vascular Damage (MALIGNAT HYPERTENSION)
o Hypertension + complications such: Cardiac Failure, Stroke, Dissecting Aneurysm
o Tx (@ ICU): Lower BP 25% maintaining diastolic BP NO LESS than 100-110mmHg (prevent
cerebral hypofusion)
o PARENTERAL Antihypertensive drugs are used to BP RAPIDLY in few hrs: NO ORAL
drugs
Niroprusside IMMEDIATE EFFECT
Diazoxide
Combination w DIURETICS and -blockers if necessary

1. DIURETICS: Thiazides and Loops

o Most important DIURETICS in tx of Hypertension
o MILD Hypertension Thiazides (Hydrochloothiazide)**
Orally
o MODERATE-SEVERE Loop Diuretic (Furosemide) **
Orally or Parenteral
o Minimal compensatory Response
o SE: HyperGLU HYPOKALEMIA, HyperGlycemia, HyperLipidemia, HyperUricemia

2. SYMPATHOPLEGIC DRUGS:
CNS Active agents:
o 2 Agonist (Clonidine, Methyldopa)- recuerda que solo los los 2 agonist son CENTRALES
pq estan en la PRESYNAPTIC
Sympathetic OUTFLOW (CO and Vascular Resistance)
o SE Clonidine: REBOUND HYPERTENSION (BP resulting from loss of drug therapy),
SEDATION, Salt Retention
 o SE Methyldopa: Hematologic Immunotoxicity/ Hemolytic Anemia
Cognition deficits in elderly

Ganglionic Blocking drugs: Hexamethonium, Trimethphan

o EXTREMELY POWERFUL BP but SEVRE SIDE EFFECT
Parasympathetic: Constipation, Urinary retention, Blurred vision
Symp: SEXUAL DYSFUNCTION, Orthostatic hypotension
Nerve Terminal blockers:
o Reserpine: DEPLETES Adrenergic nerve terminal of NE
SE: Enters the CNS Behavioral Depression
(PSYCHIATRIC DEPRESION, not used in depressed pts)
Reserpine has a RESERVATION in the CNS
Used in LOW doses w other agents

o Guantidine: DEPLETES + BLOCKS NE stores

Do NOT enter CNS
SE: SEXUAL DYSFUNCTION + Orthostatic Hypotension
Rarely used

Adrenoreceptor Blockers:
o Prazosin (1 blocker) PVR and Venous Return
SE: Orthostatic Hypotension
o Phentolamine/Phenoxybenzamine (non-selective)NO VALUE IN CHRONIC
HYPERTENSION
Compensatory response in tachycardia (bc BP)

o -Blockers: among the most Heavily used Antihypertensive

Cardiac Output first and then after a few days Vascular Resistance
B-blockers CO (blocking 1) and Renin (1)
Se usan mucho en MONOTERAPIA y en combinacions
SE: slight LDL and TG (no se lo des a diabeticos)
3. Vasodilators: se usan mas para Severe/Chronic Hypertension

A. Hydralazine/ Minoxidil
ORAL administration
Used in CHRONIC Treatment
ARTERIOLES>>> VEINS

o Hydralazine:
SE LUPUS (uncommon at doses <200mg/dl)
o Minoxidil:
For SEVERE HYPERTENSION
creer pelo
Potassium Channel Opener (Hyperpolarizes and relaxes vascular smooth
muscle)
SE: Hisurism, Pericardial Abnormalities

B. Nitroprusside + Diazoxide: Used in HYPERTENSIVE EMERGENCIES

PARENTERAL administration

Nitroprusside: SHORT and RAPID ACTING by releasing NO

o SE: CYANIDE accumulation, Hypotension, Tachycardia

Diazoxide: Given in BOLUSES and takes several HOURS of duration

o Similar to Minoxidil, it Opens POTASIUM channels
o SE: HYPERGLYCEMIA, Salt and Water Retention

o Ca Channel Blockers: Ditiazem, Verpamil, Nifedimde

Suitable for CHRONIC use in Hypertension
Nifedipinemost potent VASODILATOR of the 3 and
HEART RATE (Vessels>>>Heart)
 4. Angiotensin Antagonists:
o Beneficial in HEART FAILURE and DIABETES
a. ACE inhibitors (CAPTOPRIL) Angiotensin II and Bradykinin
i. ReninAngiotensin I----X----- Angiotensin II
ii. SE: COUGH, TETRATOGENIC, Renal damage

b. Angiotensin II Receptor Blockers (LORSARTAN):

i. Inhibits Angiotensin II at its RECEPTOR
ii. SE: Tetratogenic, Renal toxicity, K+ retention (aldosterone), NO COUGH

C. Drugs for Heart Failure:

o More responsive to INOTROPIC drugs (force of contraction)
o Diuretics + ACE inhibitors are 1st line drugs in CHRONIC HF
o Cuando hay HF (CO), unfavorable compensatory responses (Sympathetic discharge and Na
Retention) occurs DANGEROUS

o Treatment goals:
o 1. Treat the CAUSE of HF (hypertension)
o 2. Treat the HF itself (esto es basicamente el ppt)
Contractility (+ inotropics); Na retention (ACE inhibitors, Diuretics,);
arteriolar and venous resistance (Vasodilators, ACE inhibitors); Exercise
tolerance

Note: Casi todos pueden dar arrhythmia except:

ACE-I, Vasodilators (although vasodilators can cause reflex Tachycardia)

1. Improve contractility (+ Inotropics): Digoxin, B-agonist, PDE inhibitors (Milrinone, Amirinone)

o Digoxin: (Chronic CHF)
o Inhibits Na/K+ ATPase leading to an in Intracellular Ca
Cardiac output (inotropic), HR (chronotropic)
Puede producer arrhythmia
PARASYMPATHETIC (Stimulates vagal output to SA node rate and conduction
through AV node) This prolongs REFRACTORY PERIOD (harder for extracelluar
Ca to get in)
[Useful in ATRIAL Arryhtmias]
SYMPATHETIC: In Toxic concentration
Half life: 40 Hrs excreted by the KIDENYY!!!!
Toxic Plasma concentration: >2ng/mL
Digitoxin: Rarely used, HALF-LIFE of 7 days; toxic concentration of >35 ng/ml
o SE: ARRHYTMIAS, GI disturbances, Yellow or Blurred vision, Halos, flashing lights
o K+ Interactions: (Digoxin competes w K)
HYPOKALEMIA the effects and causes toxicity w LOWER dose
Diuretics cause HypoKalemia, concurrent use w risk of Toxicity
HYPERKALEMIA Digoxin effects
o Drug interaction:
QUINIDINE (Ia; Malaria): plasma levels of DIGOXIN; acts similar to hypokalemia
CHOLESTYRAMINE (tx for Cholesterol): Digoxin effects

o Tx for Arrhytmia (toxicity) caused by DigoxinLidocaine, Phenytoin (IB class drugs)

Alternatives: Digoxin Antibodies, Hemoperfusion, induce Hyperkalemic state
o Tx for BRADYCARDIA (toxicity) caused by Digoxin ATROPINE (ACh)

o B1 selective Agonists: Dobutamine/ Dopamine:

o Contractility and CO
o Renal Blood flow dopamine
o INEFECTIVE in chronic use bc of DOWN REGULATION of receptors
Long-term may worsen Myocardial function

o MilrinONE and AmriONE: Phosphodiesterase Inhibitors (PDE)

o cAMP bc inhibits PDE Isoenzyme 3 (degredes cAMP)
 o cAMP Cardiac Intracellular Calcium & Vasodilation
o Drug combination the further cAMP DOBUTAMINE

o Clinical use: IV adm for Short Term, SEVERE REFRACTORY CHF

Do NOT use in Chronic HF (morbidity and mortality)
o SE: very common, Liver Enzymes, Thrombocytopenia,
Arrhytmias

2. Na Retention: (Diuretics, ACE inhibitors)

o DIURETICS:
o Preload, Peripheral and Pulmonary Edema
o FUROSEMIDE (loop)Immediate reduction of Pulmonary
congestion
SEVERE EDEMA
Acute or Chornic
o Thiazide: MILD CHRONIC HF
o Spirolactone: Long-term benefits in CHRONIC HF
(aldosterone)
o SE: Hypokalemia, HyperGLUC, VENTRICULAR ARRYTHMIAS

o ACE inhibitors:
o Diuretics + ACE inhibitors are 1st line drugs in CHRONIC HF
o Angiotensin Receptor antagonist have the SAME effect

3. Vasodilators:
- Venodilators Oral Nitrates (preload); Nitroprusside (systemic Vascular resistance)
o ACUTE SEVERE CHF; IV administration only
o Tx: Pt w Continuing Hypertension after MI
o SE: Cyanide accumulation
- Veno and Arterial dilators ACE inhibitors (filling pressure)

- Arterial dilatorsHydralazine (NO), MinoXidil (K channel opener) [CO]

D. Treatment for Ischemic Heart Disease:

Determinants of Cardiac O2 requirement:
Preload: Blood vol and Venous tone (venas traen la sangre) controlled by SYMPTATHETIC
[Vasodilators]
Afterload: Arterial Blood Pressure depends on PVR (determined by SYMPATHETIC and ARTERIOLES)
Heart Rate:
o Systolic Blood Pressure and Heart Rate is a measure of CARDIAC WORK and therefore O2
requirement
 Cardiac Contractility: maintained by SYMPATHETIC

Control of CORONARY BLOOD FLOW:

Flow= Arterial Pressure/ Resistance
Under normal conditions, the single MOST IMPORTANT determinant of Coronary Blood Flow is
Myocardial Metabolic Activity
o Flow can 5-fold in EXERCISE

Major Metabolic Determination of Coronary Blood Flow:

Heart Rate
Wall tension (stress on ventricular during systole)
Myocardial contractility
Systemic Arterial Pressure

ANGINA: goal is to correct the imbalance between O2 supply and demand (BP, HR, ForceVenous
Return or by Improving Coronary Flow)
Angina caused when O2 demand increase EFFORT ANGINA
Angina caused when Coronary Artery Reversibly Constricts VARIANT ANGNIA
Unstable Angina Treated as a MEDICAL EMERGENCY
Stable anginalast 2-10 minutes, rarely over 15 min

O2 Demand:
o Arterial pressure
o Heart Rate
o Wall Tension
o Contractility
O2 Supply:
o Coronary Arterial Relaxation

Tx in Classic Angina: Goal is reduction of myocardia O2 consumption (MVO2) by: End

Diastolic vol, BP, HR, Contractility (

o 1. Nitrates & Nitrites:

Vasodilation by NO in Vascular smooth mucGMP and smooth mu relaxation
(VENODILATORS)
Dilate VEINS>>arteries; preload
Short Acting Drugs:
Isosorbide dinitrate (sublingual)> Sublingual Nitroglycerin >Amyl nitrite
(inhalant)
Isosorbide dinitrate (sublingual) can also account for long acting w higher dose
Long Acting:
ORAL Nitroglycerin> Isosorbide dinitratre
 Nitrites and Nitrates act byO2 demand (PRELOAD)
Effects on Coronary Blood Flow:*****
NO INCREASE in Total Coronary Blood flow
Redistribution of blood flow across the heart wall

Restore endocardial blood flow in Atherosclerotic Coronary Arteries important

in the treatment of CORONARY VASOSPASM

Nitroglycerin (Benefits):
Left Ventricular End Diastolic Pressure (preload)=O2 demand
Subendocardial Blood flow= Oxygen Supply
Epicardial Coronary VASODILATION= Relief of coronary Vasospasm
(Printzmetal)
Arterial pressure, Ejection time

Nitroglycerin (Harmful/Side Effects):

Reflex Tachycardia=O2 demand
Diastolic Perfusion due to Tachycardia= Myocardial Perfusion
o Fase diastolica es cuando las coronarias se llenan de sangre
Pharmacokinetics:
Metabolized by Hepatic Nitrate Reductase
o if ORALLY GIVEN, <10% of the drug is available
Sublingual: RAPID, onset of action within 2 Minutes (declines within 1 hr)
Ointment (topical) application: Effects within 60 minutes (persist up to 6
hrs)

Toxicity & Tachyphylaxis*****:

Nitroglycerin Facial Flushing
Orthostatic Hypotension
Baroreflex-Mediated TACHYCARDIA
Throbbing Headache from Cerebral Arterial Vasodilation

NOTE: Combination with SILDENAFIL:

o Synergistic Relaxation of Vascular Smooth muscle HYPOTENSION and
HYPOPERFUSION
Tolerance can develop
MONDAY DISEASE people who are exposed to nitroglycerin in their work are
and during the week they develop a kind of tolerance. Then after the weekend
where they have no contact with nitro they go back to work, and the nitro effect
comes. Since they are not used to it anymore the body has a contrareaction:
Tachycardia, dDizziness and Deadache

o 2. Calcium Channel Blockers: Block Voltage Dependent Ca Channels

 Act on BOTH, Vascular Smooth Mu and Cardiac Cells
Peripheral VASODILATION and Reduction of cardiac work

To a lesser extent on Bronchial, GI and Uterine smooth mu

Muscle Contractility
Used fro prophylaxis of effort or variant angina, but have little ore benefit in Acute
Coronary Syndrome
In vasospastic angina they prevent coronary vasospasm

Prototypes: Dr. Veras DILated the Ca2+ channel to buy a kNIFE

Verapamil
Diltiazem
Nifedipine

Effects on Myocardial O2 Demand:

o Nifedipine: More POTENT VASODILATOR,
O2 demand (by Afterload) strongest effect in
vasculature
Verapamil has the strongest effect in Heart
SE: can cause Reflex Tachycardia (by Systemic Arterial Pressure)

Pharmacokinetics:x
o All 3 drugs absorbed after ORAL Administration
o Verapamil**Extensively metabolized by FIRST PASS METABOLISM in the
Liver

o TOXICITIES:
Excessive Vasodilation
Negative Inotropy
Depression of SINUS PACE MAKER RATE (Ca is the ion in depolarization in
pacemaker cells)
Depression of AV Nodal Conduction (Ca is the ion in depolarization in
pacemaker cells)

o Drug Interactions:
CAUTION w -Antagonist, can induce severe Depression of Ventricular
function and AV block

o 3. -Blockers: (Cause, both negative Inotropic, Chronitropic effect)

Competitively inhibit the effects of NEURONALLY released or Circulating
Catecholamine on the -receptor
Mycocardial Metabolic Demand (primarily during Active or
 Excitement)
Heart Rate and Contractility (resulting in O2 Consumption)
o B1 block: HR

B1-Selective antagonist: (A-M)

o Acebutol (B1 partial agonist)
o Alprenolol (B1 partial agonist)
o Atenolol (antagonist)
o Metoprolol (1 selective @LOW doses)
o PROPRANOLOL (non-selective) lipid SOLUBLE, mental depressant

o Side Effects and Problems:

SINUS BRADICARDIA
Bronchospasm in asthmatic patients (block 2 receptors)

Mental Depression (lipid soluble, particularly PROPRANOLOL)

Augmentation of hypoglycemic effect of insulin (blockade of Beta 2 receptors may

inhibit the catecholamine-induced glycogenolysis and thereby augment insulin induced
hypoglycemic effects) INSULIN (HYPOGLYCEMIA)
B-block in pancreas: glucagon
-block in Liver and skeletal muscle: Glycogenolysis

Fatigue or lethargy (either from CNS effects or exaggerated decrease in Cardiac

Output)

STABLE Ischemic Heard Disease:*******

Pts w CHRONIC Anginal Symptoms: Stepwise addition of -blockers, Calcium Chanel Antagonist,
LONG-Acting Nitrates should be provided

Treatment Approach for Stable Angina:

SUBLINGUAL Nitroglycerin- drug of choice to terminate ACUTE Episodes of Angina or Prophylaxis
before activities known to induce anginal symptoms

Antiplatelet Therapy: ASPIRIN should be given to all pts unless contraindication

o Clopidogrel is the best alternative otherwise

B-Blockers1st line in pts w PRIOR history of Myocardia Infarction

o They risk of future event
o Contraindication: Severe bradicardia, AV-Block, Sick Sinus Syndrome, Unstable Left Ventricular
 failure, Asthmatics

Ca Channel Blockersadded when Anginal symptoms are NOT controlled w B-blcockers

o 1st line in pt w B-block contraindication:
o Severe bradicardia, AV-Block, Sick Sinus Syndrome, Unstable Left Ventricular failure,
Athmatics
o VERAPAMIL/DILTIAZEM should be used w caution when combined w B-blockers

Long-Acting Nitrates (non-sublingual) pt whose Anginal symptoms was NOT controlled w B-blocker or
Calcium blocker
o Ensure Nitrite free period to avoid TOLERANCE
o Avoid SILDENAFIL (Phosphodiesterase 5 Inhibitor)

Drug of choice for Pinzmetal Variant Angina Ca Channel blocker, Nitrates

Pt w Non-Invasive test revealing High Risk Ischemic Heart DiseaseCoronary Revascularization

Unstable Angina:

Unstable: walking 1 flight of stairs or 2 Blocks on even ground; increasing in severity or requiring
markedly less provocation in pts w previous angina

Treatment approach for Unstable Angina:

o Finding of ST-segment ELEVATION should prompt tx w Fibrinolytics or Percutaneous Coronary

Intervention (PCI) w 10 minutes
o Morphine, IV nitrates, O2should be given to alleviate pain
o Aspirin (or Clipidogrel/Prasugrel) should also be continued

o Tx for SUSPECTED Non-ST elevation Acute Coronary Syndrome (ACS) IV Unfractioned

Heparin or Subcutaneous Low-molecular Weigh Heparin (LMWH)

o Cases of Persistent Ischemic Pain or High Risk pts Glycoprotein IIb/IIIa Inhibitor

o INITIAL treatment for pts w Non-ST elevation ACS -blockers (in first 24 hors)
o Note: Pt should not have signs of Heart failure, Cardiogenic Shock, Athma, heart
block
o I.V. B-block Recommended in EMERGENCY SETTING (Oral tx is sufficient in other cases)
o Target HR w B-Block 50-60 BPM

Calcium Channel blocker (Non-Dihydropyridine/act on heart) Anginal symptoms are NOT controlled w
B-blockers and there is no Left Ventricular Dysfunction
 o Do NOT give Nifedipine (Dihydropyridine) in pt w Coronary Artery Diseae

Metroprolol (b-blocker) Reduces recurrent Angina and Myocardial infraction at 48 hors compared w
Nifidinpine in pts w Unstable angina

Statins recommended to all NON-STEMI ACS pts

E. Antiarrhytmic Durgs:
Torsades de Pointes: Important bc is often induced by Antiarrhytmic and other drugs that change
the shape action potential and PROLONG QT interval
o Associated w Long QT Syndrome: heritable abnormal prolongation of the QT interval caused
by mutations in the IK or INa
o Most common antiarrhythmic causing Torsades de Points Ia (Quinidine, Procainamide,
Disopyramide) and III (Amiodarone, Bretylium, Amiodarone, Ibutilde, Sotalol)
INa: dominates upstroke (phase 0) and is the most important determinant of Conduction Velocity

Abnormal Automaticity: Occur in Atrial and Ventricular tissue that does not normally carry
automaticity Sinus Tachycardia, Atrial Tachycardia

Triggered Rhythms: impulses are triggered by a previous normal impulse

o EADduring Repolarization phase
Associated w abnormally prolonged Action Potential
o DAD after the Action Potential has ended
Typically the result of Ca2+ overload (Ischemia, Reperfusion, Digitalis intoxication
(this are conditions in which Ca is in the cell)

Group 1: Sodium Channel Blockers

Local Anesthetic actions and SLOW the upstroke of Na-dependent action potentials and prolong
QRS
The OPEN and INACTIVATE state is when most susceptible to drugs the channels are
Blocked Na channels in abnormal tissue more EFFECTIVELY than channels in normal tissue
o Use dependent/State dependent: selectively depress tissue that is frequently depolarizing
(during a fast tachycardia; or tissue that is relatively depolarized during REST like Ischemia)
Cardiac toxicity: Hyperkalemia in the 3 groups
 Group 1A: Procainamide, Quinidine, Disopyramide
o Quinidine: clearance of DIGOXIN and may serum concentration of the Glycoside
Phase 0 and Phase 4 Na currents and additionally IK current on Phase 3
Clinical use: ATRIAL and VENTRICULAS Arrhythmia
Prolongs Action potential (APD) and Effective Repolarizing Potential (ERP)
QRS and QT duration
Anti-muscarinic effects; in HIGH doses can result in excessive VENTRICULAR RATE
(sympathetic action)
Overdose: SA or AV Block
Alpha Blocker properties: can cause vasoDilation and induced reflex Tachycardia
Administration: ORAL (80% bound to plasma)
Metabolized in LIVER (T1/2= 6Hrs)

SE: Precipitate Torsades de Points, Nauseas, vomiting, Diarrhea

o Procainamide:
Clinical use: ATRIAL and VENTRICULAS Arrhythmia
Oral, IV, Intramuscular administration (3ways of adm pq se elemina en el kidney)
Eliminated by KIDNEY after N-acetylation
Peak plasma concentration after 50 minutes
SE: may cause Hypersensitivity reversible syndrome similar to LUPUS
o Overdose: Treat w Sodium Lactate and pressory sympathomimetics

Group 1B: Id Buy Lindas Phine Mexican Tacos [Lidocaine, Phenytoin, Mexilentine, Tocainide]
Lidocaine:
o Clinical use: ACUTE Ventricular Arrhythmias related to Ischemia (post MI)
 Prefer Depolarized Purkinje or Ventricular tissue
Digitalis Induced Arrhrymias
o Block Pacemaker Na current in Phase 4
o Inhibit the Small inward Na current (WEAK) during Plateau of Ventricular and Purkinje
cells
Note: Minimal effect on Na+ currant of phase 0
o The have NO change in ECG!
o ACTION POTENTIAL
o Little or no EFFFECT on ERP
o SELECTIVELY affect ISCHEMIC or Depolarized Purkinje and Ventricular tissue (Ventricular
Arrhythmia) Block Activated/Inactivated states
Ex: Used after MI
o Has NO interaction w AUTONOMIC SYSTEM (no effect on BLOOD PRESSURE)
o Metabolized by LIVER Exclusively by Intramuscular or IV routes
o Side effects: Paresthesis, Tremor, Light-headness

Group 1C: I See you LOst FLying the ENterprise (Lorceine, Flecainid, Encainide)
Flecainide
o Clinical use: ONLY Refractory Ventricular Tachycardia
o POTENT and SELECTIVE-FAST Na-channel inhibitors
o Pro-arrhythmic - Restricted use in Persistent arrhythmia that fail to respond to other drugs
o Inhibits Phase 0
Vmax and Conduction Velocity
o No change in VENTRICULAR Action Potential or QT interval
o QRS:
o SE: Pro-arrhythmic effect (Encainide/Flecainide)

Group 2 Antiarrhythmic (-blockers): Propranolol and Esmolol

Remember: -Blockers work in the FUNNY CURRENT of PACEMAKERS cells (Na, Ca ions)
AV NODE is most SUCEPTIBLE PR interval:
Clinical use: Prevent Atrial Arrhythmias from sympathetic stimulation
o Slow Ventricular rate in ATRIAL FLUTTER
cAMPNa and Ca currents and suppression of abnormal pacemakers
REFRACTORY PERIOD of Both SA and AV NODES
Side Effects: Exacerbate Asthma; Glucose, CNS, Cholesterol effects

Group 3 (Potassium Ik Channel blocker): AIBS [Amoidarone, Ibutilide, Bretylium, Sotalol]

Hallmark is Prolongation of AP duration (repolarization)
Prolongation results in Effective Refractory Period (Purkinje and Ventricular cells)
Clinical use:
o Use ONLY in Treatment of Refractory Post-Myocardial Infarction Arrhythmias
Recommended for LIFE THREATHNING Arrhythmias that FAIL to respond to Group 1
A/B****
 Prevents PREMATURE BEATS
the ability of the heart to respond to Rapid Tachycardia
EKG: QT (except BRETYLIUM)
Administration: ORAL, IM
Side effects: Prevent the release of K; SEVERE HYPOTENSION

Group 4 (Calcium L-type Channel Blockers): Verapimil*, Diltiazem

the INWARD Ca during AP and Phase 4
Clinical use: Conduction of the AV NodePrevent VENTRICULAR Tachycardia in response to
Atrial Flutter (esta prolongando el paso del AV a los ventriculos)
o Prevent Reentry rhythms
o Effective for AV node arrhythmias (Nodal Tachycardias)
Nifedipine (NOT USEFUL) as antiarrhythmic bc they Arterial pressure enough to evoke a
compensatory sympathetic discharge to the heart

EKG: Conduction velocity,ERP, PR segment

Contraindications: do NOT use in ptes w Preexisting Left Ventricular Dysfuntion
Side effects: CONSTIPATION

Adenosine:
Slows the conduction of the AV node (Hyperpolarizes the AV node and Ca current)
Clinical use: Drug of Choice for AV Nodal Arrhythmias
SE: Flushing, hypotension (uncommon)

F. Hyperlipidemias:
Hypercholesterolemia:
o Among other risks are Diabetes, Excess body weight mainly in ABDOMINAL AREA,
HYPOTHYROIDISM, Nephrotic Syndrome, Cholestasis Liver disease
o TC, LDL, TG, APOB Lipoprotein A in concentration >90th percentile
o HDL, Apo (A)<10%

o LOW HDL- associated w Smoking and ABDOMINAL OBESITY w Insulin resistance,

Hypertriglyceridemia, Smoking, Genetic diseases such as: ApoA-I or Lecithin-cholesterol
Acyltrransferase (LCAT) deficiency
o Tx: Dietary changes and lifestyle modification
Statin therapy, Nicotinic Acid, Bile Acid sequestrants, Cholesterol
Absorption inhibitors (Ezemibe)
Statins, Eztimbe, Naiacin more effective LDL cholesterol
Fibric acid, niacin, Marine omega 3Fattty acid more effective lowering TG ad VLDL and
HDL
o Being OLDER than 55 yrs in MALES and 45 FEMALES risk for HYPERCHLESTEROLEMIA
o DIABETES: Risk for HyperCholesterolemia and CHD
 o Obesity: BMI> 25Kg/m2 and Waist Circumference >40 inches (male) or 35 (females)
o Alcohol increases TG ad VLDP

Treatment Approach:
o Aerobic exercise + Diet showed reductions on LDL but no increase in HDL compared w Controls or
Diet alone
Pts w AVG of LOW Cardiovascular risk, can be allowed 3 to 6 month of lifestyle modification before
considering Lipid-lowering drugs
o Still controversial
o 2-3 follow-up visits over 2-3 months should be arranged to assess motivation and adherence
o Drugs are used when lifestyle changes are NOT effective
Diet:
o Intake of Total Fat between 25% -35% of total body calories
o Saturated Fat <7% of total body calories
o Trans Fat <1% of total body calories
o Cholesterol <300mg/day
o Diet rich in SOLUBLE FIBER have shown to LDL-Cholesterol

1. Statins: Loavstatin, Simvastatin, Rosuvastatin, Fluvastatin

o Inhibit HMG CoA reductase; UP-Regulations of LDL-R,
o Drug of choice in following (Statins + Lifestyle Modification):
A. <2 cardiac risk factors and LDL> 190 mg/dl
B. >2 Cardiac risk factors and LDL<130 mg/dl
C. Coronary Heart Disease and LDL <100mg/dl
CHD risk: clinical manifestations of non-coronary forms of atherosclerotic
disease, such as peripheral arterial disease, abdominal aortic aneurysm,
carotid artery disease (e.g., transient ischemic attacks (TIA), Stroke of Carotid
origin, or >50% obstruction of a carotid artery), Diabetes, or in the presence of 2
cardiac risk factors.

o Decrease LDL levels, Cardiovascular morbidity, Total Mortality

o For every 1mmol/L (39mg/dL) reduction in LDL:
12% reduction in Total Mortality
17% reduction in Stroke
21% reduction in cardiovascular events

o Main Functions: Inhibit HMG-CoA Reductase, stimulate up regulation of LDL-R to

cholesterol levels in blood
Modest TG
Small effect in HDL
o Most potent pharcologic agents for CHOLESTEROL contained in LDL
o Adverse effects:
Liver enzyme elevations (ALT, AST)
Myosisitis
Rhabdomyolisis
 Creatine phosphkikase (CPK) levels can be elevated bc of myopathy and rhabdomylosis

Muscle toxicity w/out enzyme elevation (when used w drugs that INHIBIT Cyt P450
3A4
MACROLIDES, AZOLE Antifungales, CYCLOSPORINE

Note: Statins such as (-INS): LOVASTATIN, SIMVASTATIN, ROSUVASTATIN,

GLUVASTATIN may DIGOXIN LEVELS and potentiate WARFARIN effects

2. Nicotinic Acid:
AKA: Vitamin B3, Niacin, Vitamin PP
Effective in HDL
Lowering LDL/VLDL
TG
Effect is dose dependent!
o HDL: 1g/day (Cholesterol/HDL ration should be less than 3)
o LDL doses exceeding 1-2 g/day
Adverse Effects:
o COMMON (especially w the Shorter-acting Crystalline form)
o Flushing (80%)
o Pruritus
o Paresthesias
o Nauseas

o Hepatocellular enzymes/ FULMINANT HEPATITIS

o Induction of INSULIN RESISTANCE
o Precipitation of Gout
o Homocysteine levels
o HYPOTENSION in pts treated w VASODILATORS

After 6 weeks of treatment:

o Check LIPIDS, GLUCOSE, LIVER FUNCTION TESTS (LFT), URIC ACID

Niacin/Laparopiprant: novel formulation of EXTENDED-RELEASE NIACIN in association w

Laropiprinat
o Flusing by aprox 60%
o Effects on LIPIDS are similar to HIGH-dose Extended Release Niacin (ldl)
o AVAILABLE in EUROPE, New ZELAND
Laropiprant: Selective PROSTGLANDING D(2) Receptor-1 Antagonist

3. Bile Acid Sequestrants: (Colestiramine and Colesevelam)

Effective in pts w MILD to MODERATE elevation of LDL cholesterol
Used in conjunction of STATINS and NICOTINC ACID (NIACIN) Synergistic
o NO se usan solos, siempre en combinaciones !!
 Prevent reabsorption of BILE ACIDS (90% of bile are extracted)
o Decrease in Cholesterol rich Bile acids leads to LOWERING of INTREHEPATIC Cholesterol and
an UP-REGULATION of LDL-RECEPTORS stimulates further in cholesterol

Adverse effects: these drugs impair emulsification, digestion, absorbtion of fats

o GI Tract-related: Nausea, Bloating, Cramping, hepatic Transaminase
o (this side effects can be very limiting
o Absorption of other drugs impairment to avoid, take drugs 1 hr BEFORE or 4 hrs AFTER
Bile acid sequestrants

o CONTRAIDICTION!!! In pts w TG>500mg/dL

4. Ezetimibe:
Effective in patients with MILD to MODERATE elevations of LDL-cholesterol
Mechanism: Impairs dietary and biliary cholesterol absorption at the intestinal brush border by
interaction with specific receptors and, in contrast to bile acid resins, has Systemic exposure (que
se pueden usar como MONOTERAPIA)
When used ALONE LDL reductions of 15% to 20% have been reported
Although not yet determined whether Ezetimibe-Statin is clinically superior to statin alone,
the combination may be useful in patients unable to tolerate higher doses of statins but in
whom further LDL-lowering is warranted

Ezetimibe is a novel cholesterol absorption inhibitor that blocks the translocation of dietary and biliary cholesterol from
the gastrointestinal lumen into the intracellular space of jejunal enterocytes. Ezetimibe undergoes enterohepatic
recirculation with minimal systemic exposure and not does not adversely impact the pharmacokinetic profile of statins.
Ezetimibe significantly reduces serum LDL-C. It is safe when used as monotherapy or when used in combination
with statins.
Ezetimibe is indicated in the management of hyperlipidemia, familial hypercholesterolemia, and sitosterolemia and
significantly increases the percentage of patients able to reach their lipid-lowering goals

Ezetimbide + Bile Acid Sequestrant (Colestiramein/Colesevalm) or Nicotinic acid:

Patients with high risk of coronary heart disease,
(SEVERE HYPERCHOLESTEROLEMIA)
Side effects: Can increase risk of HEPATIC TOXICITY when combined w STATINS

5. Fibrates: (Gemfirbozil)
Fibrates (Fenofibrate)+ Statins ONLY in the presence of MIXED DYSLIPIDEMIA (to
Cholesterol and TG)*******
Fenofibrate is the drug of CHOICE to use w STATIN
NEVER use GEMFIRBZIL (fibrate) w STATIN******

Mechanism: interact e PPAR- (receptor in Lipid transcription metabolism)

Lipoprotein Lipase synthesis (TG in lipoproteins and releases FA)
e PPAR- Target of the Fibrate drugs and omeg 3 FA
INSULIN LLP synthesis (DM type 1 (low insulin), TG accumulate in circulation
 contributing to ARTHEROSCLEROSIS)
They promote HDL
Little effect on LDL
SE: Severe risk of RHABDOMYOLISIS in uncontrolled combinations of Fibrates and Statins
Nausea,
Skin rashes (GEMFIBROZIL)
Gallstones

HyperTriglyceridemia: (Normal TG<150 mg/dl)

TG>200 mg/dl (High TG levels)
Risk for Acute Pancreatitis when fasting levels are >500mg/dL
Chylomicrnemia present w TG >1000 mg/dl
o Chylomicronemia- ochylomicorns in serum while fasting
Chylomicronemia syndrome Acute Pancreatitis, Lipemia Retinalis, Eruptive
Xanthomas, Heptamegaly (PATHOGNOMONIC)

Treatment approach:
o Cardiac Risk factors in pts w TG:
Hypertension, Smoking, HDL <40mg/dL (high/optimal >60mg/dl)
Fam hx of Premature Coronary Artery disease in 1st degree relative (male<55yrs/female
<65yrs)

Non-HDL cholesterol= LDL cholesterol + TG/5

This formula applies when TG <400mg/dl
Assume: Pt w TG>400 High Non-HDL- cholesterol levels

Goals for Hypertriglyceria w Cardiac disease: PPT!!!!

First line tx in TG <500mg/dl + >2 Cardiac Risk factors:

STATINS +Lifestyle changes
2nd line drugsStatins + Fabric Acid derivatives, Fish oils and/or Nicotinic acid
3rd line drug Statins + Fabric Acid derivatives, Fish oils and/or Nicotinic acid +
Ezetimibe
Nicotinic acid used especially when there are LOW LEVELS of HDL
Omega 3 Polyunsaturated FA (or fish oil) TG but little impact in plasma LDL or
HDL

First line tx in pt w Acute Chylomicranemia hospital Admission + supportive care (give

NOTHING by mouth and Hydrate w IV fluids)****
Diabetics Administer Insulin (Insulin will TG)
Non-diabetics Administer IV Glucose to prevent Hypoglycemia

First line tx in TG>500 mg/dL:

Fabric Acid derivatives, Fish oils and/or Nicotinic acid + Lifestyle changes
 Presentation include:
Chylomicoanemia w Abdominal Pain and/or Acute Pancreatitis (should be
admitted to the hospital) Give FLUIDS + HYDRATION (NOTHING BY MOUTH)
Diabetes (insulin treatment TG)- insulin should be given

In patients requiring combination therapy, long-term compliance may be improved in a subset of

patients by using a fixed-dose preparation:
o Lovastatin plus extended-release niacin (ADVICOR) or Sivastatin plus ezetimibe
(VYTORIN).

Metabolic Syndrome:
3 of the following:
o Central obestity (waist circumference >35 inch women; >40 inch males)
o TG >150 mg/dl
o HDL <50mg/dl in women; <40 mg/dl in male
o Fasting blood glucose >110mg/dl
o BP >130/85 mmHg
Pt have risk of morbitidy and mortality associated w CARDIOVASCULAR disease and DIABTES