Cardiovascular Pharmacology: ACE Inhibitors, ARBs, Beta-Blockers, Diuretics, and Vasodilators

Linsinopril Drug Class

Angiotensin Converting Enzyme (ACE) inhibitor

Linsinopril MOA

Angiotensin II inhibitor. Block the enzyme (ACE) that converts Ang I to Ang II in the lungs. Angiotensin Converting Enzyme (ACE) inhibitors also prevent degradation of bradykinin and other vasodilator peptides

Linsinopril Clinical Use

Heart failure, left ventricular dysfunction, prophylaxis of future cardiovascular events (e.g., MI, CAD, stroke) and nephropathy (+/- diabetes)

Linsinopril Side Effects

Hypotension, dry cough (common), angioedema (rare), hyperkalemia - avoid K+-sparing diuretics (monitor if combined), acute renal failure - particularly in patients with renal artery stenosis (renoprotective in patients without stenosis or hypovolemia); many drug-drug interactions

Losartan Drug Class

Angiotensin Receptor Blocker (ARB)

Losartan MOA

Angiotensin II inhibitor. Block the Ang II receptors (AT-1 receptors) in tissues. Angiotensin Receptor Blockers (ARBs), Contraindicated in pregnancy"

Losartan Clinical Use

Hypertension (first-line), diabetic nephropathy, HF, HF or left ventricular dysfunction after AMI, and prophylaxis of cardiovascular events

Losartan Side Effects

Similar to ACE with less dry cough and angioedema

Metroprolol Drug Class

Beta-1 selective beta-blocker

Metroprolol MOA

Competitive antagonist at beta-1 adrenergic receptors. Primary effects are in the heart; can also block renin release from the kidneys"

Metroprolol Clinical Use

Angina, arrhythmias, hypertension, heart failure, HF or reduced ejection fraction after AMI, and prophylaxis of cardiovascular events, migraine prevention

Metroprolol Side Effects

Potentiation/masking of hypoglycemia. Use caution with diabetes mellitus, dont combine with other negative inotropes (beta blockers, non-DHP CCBs)"

Carvedilol Drug Class

Non-selective (beta 1 & 2) beta-blocker with alpha-blocking activity

Carvedilol MOA

Competitive antagonist at beta-1, beta-2, and alpha-1 adrenergic receptors; also exhibits vasodilating activity unrelated to adrenergic receptor binding

Carvedilol Clinical Use

Angina, arrhythmias, hypertension, heart failure, HF or reduced ejection fraction after AMI, and prophylaxis of cardiovascular events

Carvedilol Side Effects

Bronchospasm, potentiation/masking of hypoglycemia, orthostatic hypotension (alpha-1 effect). Contraindicated in bronchospastic disease (asthma, COPD). Use caution in diabetes mellitus . Do not combine with other negative inotropes (beta-blockers, non-DHP CCBs)"

Prazosin Drug Class

Alpha-1 selective alpha-blocker

Prazosin MOA

Competitive antagonist at alpha-1 adrenergic receptors. Inhibits vasoconstriction; decreases peripheral vascular resistance; lowers blood pressure. Induces reflex tachycardia, but is less prevalent than with non-selective alpha blockers. Dilates internal sphincter of the bladder; relaxes prostate smooth muscle

Prazosin Clinical Use

Hypertension (not first-line), especially with concomitant benign prostatic hypertrophy

Prazosin Side Effects

orthostatic hypotension, syncope. Usually given at bedtime to minimize hypotensive effects; side effects are typically transient and subside with consistent dosing

C. Clonidine Drug Class

Centrally acting sympatholytic

C. Clonidine MOA

alpha-2 adrenergic receptor agonist; presynaptic receptors in the brainstem reduce norepinephrine release and decrease sympathetic outflow from the CNS to the periphery

C. ClonidineClinical Use

hypertension, opioid withdrawal, ADHD

C. ClonidineSide Effects

rebound tachycardia and hypertension upon withdrawal, safe during pregnancy but side effects make hydralazine preferred

Hydrochlorothiazide Drug Class

Thiazide diuretic (some related drugs are called "thiazide-like)

Hydrochlorothiazide MOA

block the Na+/Cl- co-transporter (NCC) in the distal convoluted tubule (DCT). Results in: ↑ luminal Na+ and Cl- in DCT, ↑ reabsorption of Ca2+ in DCT and proximal convoluted tubule, ↑ sodium and water diuresis

Hydrochlorothiazide Clinical Use

hypertension (first-line), mild heart failure, nephrolithiasis (calcium stones), nephrogenic diabetes insipidus

Hydrochlorothiazide Side Effects

hypokalemia, metabolic alkalosis

Furosemide Drug Class

Loop diuretic

Furosemide MOA

inhibit the luminal Na+/K+/2Cl- cotransporter (NKCC2) in the thick ascending limb of the loop of Henle. Results in: ↑ luminal Na+, K+, Cl-, ↓ back diffusion of K+ and positive potential, ↓ reabsorption of Ca2+ and Mg2+, ↑ diuresis, ion transport virtually nonexistent"

Furosemide Clinical Use

edema, heart failure, hypertension, acute renal failure

Furosemide Side Effects

hypokalemia with metabolic alkalosis (because the collecting duct secretes K+ & H+ to pull back Na+); ototoxicity—because there is an NKCC and physiologic Na/Cl/K transport in the inner ear; severe dehydration

Spironolactone Drug Class

Potassium-sparing diuretic

Spironolactone MOA

competitive antagonist of aldosterone receptors (ARs). ARs are also called mineralocorticoid receptors (MRs); these drugs are also called mineralocorticoid receptor antagonists. ARs are nuclear hormone receptors; act as transcription factors when activated. Normally, ARs upregulate Na+/K+ co-transporter that pulls Na+ out of the urine and back into the cells in exchange for excreting K+; spironolactone blocks this action. Also acts as competitive antagonist at androgen receptor (off-target effect)

Spironolactone Clinical Use

hyperaldosteronism, heart failure, hypertension, antiandrogenic uses in women (off-label) - hirsutism and acne vulgaris

Spironolactone Side Effects

hyperkalemia, metabolic acidosis

Hydralazine MOA

releases nitric oxide (NO) from endothelium, preferentially in arterioles > veins. NO leads to activation of the enzyme guanylyl cyclase, which increases cGMP leading to arteriolar smooth muscle relaxation

Hydralazine Clinical Use

First-line oral therapy for hypertension in pregnancy. Combination with nitrates is effective in patients with heart failure. Parenteral formulation useful in hypertensive emergencies

Hydralazine Side Effects

Can induce fluid and sodium retention. Headache, nausea, vomiting, anorexia, sweating, flushing, palpitations. Reflex tachycardia can provoke angina in patients with ischemic heart disease. Lupus-like syndrome (10% of long-term patients, reversible on drug withdrawl)"

Organic Nitrates (Nitroglycerin) Adverse Effects

Orthostatic hypotension, syncope, throbbing headache

Contraindication with concurrent use of phosphodiesterase-5 (PDE-5) inhibitors sildenafil, tadalafil, or vardenafil. Organic Nitrates (Nitroglycerin) MOA

"metabolized to NO, which activates guanylyl cyclase (like hydralazine)

Organic Nitrates (Nitroglycerin) Clinical Use

Used to treat hypertensive emergencies, heart failure, & angina

Organic Nitrates (Nitroglycerin) Pharmacodynamic Effects

Dilates both arterial and venous vessels—decreases TPR and venous return. Decreases both preload & afterload. Mainly relaxation of large veins ® ¯ venous return ® ¯ preload ® ¯ O2 demand (major effect), smaller ¯ in afterload