More HTN & HF Drugs

Question 1

Verapamil

Answer 1

Calcium Channel Blocker-Non-dihydropyridines
Indication – angina, hypertension
Mechanism – blocks Ca2+ channels in vascular smooth muscle, myocardium, and SA/AV nodes

Adverse effects –
peripheral edema, flushing secondary to vasodilation
AV block; caution in cardiac conduction disturbances or heart block

Interactions with digoxin, β-blockers (same effect)

Question 2

Hydralazine

Answer 2

Vasodilator
Indication: Hypertension, heart failure.
Mechanism: Stimulates release of NO from endothelium – acts on arterioles not veins

Adverse Effects: reflex tachycardia, headache, dizziness, fatigue (secondary to hypotension), systemic lupus erythematosus (SLE)

Question 3

Carvedilol

Answer 3

Indication: HF, hypertension
Mechanism: mixed ß1 and α1 blockade
ß1 block: Decreases HR, AV conduction, contractility – careful dosing needed to reduce excessive work of the heart but not reduce heart function too much
ß1 block: Decreases renin release (benefits of RAAS block)
α1 block: Vasodilation (α2 function preserved)

Beta blockers have been shown in trials to lengthen life in HR. Reducing work of heart allows “reset” of the compensation that has been feeding forward in the disease. However, if HF is severe or the disease has “gone too far” beta blockade may cause worsening HF and a beta agonist (or something that increases cAMP by another mechanism in cardiomyocyte) is necessary.

Question 4

Dopamine

Answer 4

Ionotrope

Indication: heart failure, hypoperfusion, acute renal failure (in-hospital IV administration)

Adverse effects: Tissue necrosis (because of excessive local vasoconstriction)

Drug interactions: MAOI and tricyclic antidepressants (because dopamine is inactivated by MAO), general anesthetics (sensitize myocardium to dopamine)

Question 5

Digoxin

Answer 5

Ionotrope

Indication: HF, atrial fibrillation
Mechanism: inhibits Na+K+ATPase pump
Increases myocardiocyte intracellular Ca2+ -> inotropic effect (contractility)
arterial pressure (because of CO) -> reflex sympathetic drive on heart and vessels -> HR, renin, preload
Direct inhibition of renin release (via Na+K+ATPase inhibition)

Inhibition of Na+K+ATPase in kidney reduces Na+ reabsoption which reduces renin release

Digoxin reduced symptoms but doesn’t prolong life.
Hyperkalemia – therapeutic effect of dig is reduced
Hypokalemia – digoxin effects are enhanced (toxicity)