Kaplan Pharm Notes- Cardio

Drug Strategy
TPR
CO
body fluid volume
BP (homeostatic regulation): reflex tachy (attempt to undo lower BP, increases O2 demand
of heart), edema (RAS system in response to BP drop)
Autonomic Nervous System Drugs: lower BP through sympathetic autonomic nervous
system
o No reflex tachy due to increased symp activity so unlikely
o Orthostatic HTN no sympathetics to affect venoconstriction to encourage cardiac return
o Increased parasympathetic activity increased secretions, GI/GU problems (diarrhea,
incontinence)
Direct Acting Dilators: lower BP without sympathetic ANS
o Reflex tachy
o No orthostatic HTN
o No increased parasympathetic activity
Drugs Altering Sympathetic Activity
Alpha 2 agonists: clonidine & methyldopa
o Alpha 2 stimulation: sympathetic outflow ( alpha 1 & beta 1)& TPR (but also HR)
o Uses: mild to moderate HTN (both), opiate withdrawal (clonidine)
o HTN management in pregnancy (methyldopa) high plasma protein binding; can behave
as a hapten
o Side effects: positive coombs test (methyldopa- risk of hemolysis), CNS depression (both),
edema (both, renin/angiotensin/aldosterone)
o Drug interactions: tricyclic antidepressants antihypertensive effects of alpha 2 agonists
Drugs interfering with Storage Vesicles
o Reserpine: s CO & TPR (s NE in periphery)
s NE, dopamine & serotonin in CNS
Side effects: depression (often severe, suicide), edema (renin/angiotensin/aldosterone),
increased GI secretions (increased parasympathetic activity)
o Guanethidine: accumulated into nerve endings by reuptake; binds vesicles. Inhibits NE
release
Side effects: diarrhea, edema
Drug interactions: tricyclic antidepressants block reuptake & action of guanethidine
o Alpha 1 blockers: arteriolar & venous resistance
Reflex tachycardia only sympathetic altering drugs that cause this (still increase NE &
bind B1 receptors to cause tachy)
Drugs: prazosin, doxaxosin, terazosin
Uses: HTN, benign prostatic hypertrophy ( tone of urinary sphincters)
Side effects: first-dose syncope, orthostatic hypotension, urinary incontinence
Advantage: good effect on lipid profile
o Beta blockers: leave alpha 1 predominance; renin release
Side effects: cardiovascular depression, fatigue, sexual dysfunction, increase LDLS (
lipolysis dangerous in hyperlipidemia) & TGs
Caution in use: asthma, vasospastic disorders, diabetes (mask hypoglycemic events)
Direct-Acting Vasodilators
Drugs acting through Nitric Oxide
o Hydralazine: TPR via arteriolar dilation. Selective arterioloar dilator (only arterioles)
Use: moderate to severe hypertension
Side effects: SLE-like syndrome (high protein binding, can be used in pregnancy) & slow
acetylators, edema (use with diuretics), reflex tachycardia (use in conjunction with B1
blockers)

Nitroprusside: prodrug of nitric oxide; s TPR via dilation of arterioles & venules
Use: hypertensive emergencies DOC used IV
Side effect: cyanide toxicity (co-administered with nitrites & thiosulfate to toxicity)
Nitrites allow formation of Methemoglobin which allows cyanide to have more
binding sites so it cannot block complex 4 of ETC
Thiosulfate allows formation of thiocyanate for easier excretion
Drugs Acting to Open ATP Dependent Potassium Channels (arterioles & beta cells of
pancreas; result in hyperpolarization resulting in arteriolar dilation)
o Minoxidil & Diazoxide: open K+ channel, causing hyperpolarization of smooth muscle;
result in arteriolar vasodilation
o Uses: hypertensive emergences (diazoxide), severe hypertension (minoxidil), baldness
(topical minoxidil rogaine)
o Side effects: hypertrichosis (minoxidil), hyperglycemia ( insulin release, diazoxide treats
insulinomas), edema (renin-aldosterone-angiotensin effect, give diuretics), reflex tachy
Calcium-Channel Blockers
Block L-type Ca channels in heart & blood vessels; intracellular Ca, causes CO (verapamil
primarily to heart & diltiazem), TPR (all CCBs)
Drugs: verapamil, diltiazem, dihydropiridines (-dipines primarily blood vessel to vasodilate)
Diltiazem works on vasculature & heart
Uses: HTN, angina (vasospastic), antiarrhythmics (verapamil, diltiazem)
Side effects: reflex tachy (-dipines), gingival hyperplasia (-dipines), constipation (verapamil)
Diuretics: all urinary Na+
Thiazide & loop diuretics most commonly used
Osmotic Diuretics: Mannitol inhibits water reabsorption throughout tubule; increases urine
volume (primary site of action is proximal tubule)
o Uses: IOP in narrow angle glaucoma, intracerebral pressure, oliguric states (rhabdostatins)
o Side FX: acute hypovolemia
Carbonic Anhydrase Inhibitors: prevent Na reabsorption in proximal tubule; urinary K+,
urinary HCO3o Drugs: acetazolamide, dorzolamide
o Mechanism: H+ formation inside PCT cell, Na+/H+ antiport, Na & HCO3- in lumen,
diuresis
o Uses: glaucoma, acute mountain sickness, metabolic alkalosis
o Side FX: bicarbonaturia & acidosis, hypokalemia, hyperchloremia, paresthesias, renal
stones, sulfonamide HSR
Loop Diuretics: urinary Na+, urinary K+, Ca2+, Mg2+, Clo Drugs: ethacrynic acid & furosemide
o Mechanism: Na+/K+/2Cl- transporter inhibition resulting in intracellular K+ in TAL,
back diffusion of K+, positive potential, reabsorption of Ca2+ & Mg2+, diuresis
o Uses: acute pulmonary edema, acute renal failure, anion overdose, heart failure,
hypercalcemic states, HTN (vasodilate through prostaglandins), refractory edemas
o NSAIDS can cancel or diminish anti-hypertensive effect of loop diuretics
o Side FX: sulfonamide HSR (cross-allergencity w/ CA inhibitors, all loop diuretics except
ethacrynic, thiazides, sulfa antibiotics, celecoxib), hypokalemia & alkalosis, hypocalcemia,
hypomagnesemia, hyperuricemia, ototoxicity (etacrynic > furosemide)
o Drug interactions: aminoglycosides, lithium, digoxin
Thiazides: urinary Na+, K+, Cl-, Ca2+
o Drugs: hydrochlorothiazide, indapamide
o Mechanism: Na+/Cl- transporter inhibition, results in luminal Na & Cl in DCT & diuresis
o Uses: HTN, CHF, nephrolithiasis (calcium stones), nephrogenic diabetes insipidus
o Side FX: sulfa HSR, hypokalemia & alkalosis, hypercalcemia, hyperuricemia,
hyperglycemia, hyperlipidemia
o

Drug interxns & cautions: digoxin: toxicity due to electrolyte disturbances, avoid in pt
with DM (use ACEI, ARBs)
K+ Sparing Agents: urinary Na+, urinary K+
o Spironolactone
Uses: hyperaldosteronic state adjunct to K+ wasting diuretics, antiandrogenic uses,
CHF
Side FX: hyperkalemia & acidosis, antiandrogen
o Amiloride & Triamterene: Na+ channel blockers
Use: adjunct to K+ wasting diuretics, lithium induced nephrogenic DM
Side FX: hyperkalemia, acidosis
o Eplerenone is a selective aldosterone-receptor blocker devoid of antiandrogenic effect
o