Drugs Acting on the Renin–Angiotensin–Aldosterone System (RAAS)

Flashcards about drugs and other factors that affect the Renin-Angiotensin-Aldosterone System (RAAS)

RAAS Overview

Regulates blood pressure, blood volume, and fluid and electrolyte balance.

RAAS Involvement

Hypertension, Heart Failure, and Myocardial Infarction

Renin Production

Juxtaglomerular cells of the kidney

Triggers for Renin Release

Hypotension, Decreased Renal Perfusion, Hyponatremia, and Beta-1 Stimulation

Renin Function

Converts angiotensinogen to angiotensin I (inactive).

ACE Location

Luminal surface of blood vessels (especially in lungs).

ACE Function

Converts Angiotensin I to Angiotensin II (active).

Angiotensin II Effects

Powerful vasoconstriction, promotes norepinephrine release, stimulates aldosterone and ADH release, causes cardiac hypertrophy and remodeling.

ACE Inhibitors Mechanism of Action

Inhibit conversion of Angiotensin I to II, resulting in vasodilation, decreased blood volume, and reduced cardiac remodeling.

Examples of ACE Inhibitors

Benazepril, Captopril, Enalapril, Lisinopril, Ramipril, Quinapril, Enalaprilat (IV)

ACE Inhibitors to Take Without Food

Captopril & Moexipril

Lisinopril Characteristic

Active as given (not a prodrug).

ACE Inhibitors Excretion

Excreted by kidneys (adjust dose in renal impairment).

Therapeutic Uses of ACE Inhibitors

HTN, HF, MI, Diabetic nephropathy, Diabetic retinopathy, prevention of MI/stroke/death in high CV risk.

Adverse Effects of ACE Inhibitors

First-dose hypotension, dry cough, hyperkalemia, angioedema, teratogenic effects.

Drug Interactions of ACE Inhibitors

Diuretics/antihypertensives, potassium supplements/sparing diuretics, lithium, NSAIDs.

ARBs Mechanism of Action

Block Angiotensin II receptors, leading to vasodilation, decreased aldosterone release, and decreased cardiac remodeling without affecting bradykinin.

Examples of ARBs

Losartan, Valsartan, Olmesartan, Irbesartan, Telmisartan

ARBs Uses

HTN, HF, Post-MI, Diabetic nephropathy & retinopathy, Stroke/MI prevention

ARBs Adverse Effects

Hypotension, renal failure, fetal harm, lower risk of cough and angioedema.

ARBs Contraindication

Renal artery stenosis.

Aliskiren Mechanism

Inhibits conversion of angiotensinogen to angiotensin I, decreasing plasma renin activity and stopping RAAS at the start.

Aliskiren Pharmacokinetics

Oral, poorly absorbed (decreased with high-fat meals), metabolized by CYP3A4, excreted partly unchanged in urine.

Aliskiren Uses

Hypertension

Aliskiren Adverse Effects

Diarrhea, fetal toxicity, lower risk of cough/angioedema/hyperkalemia.

Eplerenone (Inspra)

Selective aldosterone blocker used for HTN and HF; adverse effect is hyperkalemia; monitor liver & kidney function

Spironolactone (Aldactone)

Less selective aldosterone blocker used for HTN and HF; adverse effects include hyperkalemia, gynecomastia, menstrual irregularities, impotence, hirsutism, and deepened voice.

Calcium Channel Blockers (CCBs) Mechanism

Inhibit Ca²⁺ influx in vascular smooth muscle & cardiac tissue, leading to vasodilation and decreased cardiac contractility, HR, and conduction.

Nondihydropyridines

Verapamil, Diltiazem

Dihydropyridines

Nifedipine, Amlodipine

Nondihydropyridines Uses

HTN, Angina, Dysrhythmias

Nondihydropyridines Adverse Effects

Constipation, dizziness, flushing, HA, edema, gingival hyperplasia, bradycardia, AV block, HF.

Nondihydropyridines Contraindications

Certain arrhythmias, sick sinus syndrome, caution in HF, avoid grapefruit juice.

Nondihydropyridines Drug Interactions

Digoxin, Beta-blockers

Dihydropyridines Uses

HTN, Angina

Dihydropyridines Adverse Effects

Flushing, HA, dizziness, peripheral edema, reflex tachycardia, gingival hyperplasia; less likely: constipation, AV block, bradycardia.

Vessel Selectivity of Vasodilators

Arterioles: ↓ Afterload, Veins: ↓ Preload, Both: Combined effect

Uses of Vasodilators

HTN, Hypertensive crisis, HF

Adverse Effects of Vasodilators

Postural hypotension, reflex tachycardia, fluid retention.

Hydralazine (Apresoline)

Arteriole dilation leading to decreased peripheral resistance; adverse effects: lupus-like syndrome, reflex tachycardia, fluid retention.

Nitroprusside (Nitropress, Nipride)

Arterial and venous dilation, used IV in hypertensive crisis; rapid BP drop, fast offset; requires light protection & infusion pump.