Antihypertensive Drugs: Types, Mechanism of Action & Side Effects

Antihypertensive drugs are used to lower high blood pressure (hypertension) and stop problems including stroke, heart attack, kidney damage, and heart failure from happening. These medications function by changing how the heart, blood vessels, kidneys, and nervous system control blood pressure.

Types of Antihypertensive Drugs

1. Diuretics: help the kidneys get rid of extra water and salt.
2. ACE inhibitors, like enalapril, stop the body from making angiotensin II, a substance that makes blood arteries smaller.
3. Angiotensin II Receptor Blockers (ARBs), like losartan, stop angiotensin II from attaching to its receptor.
4. Calcium Channel Blockers (e.g., amlodipine) – Relax blood vessels by reducing calcium entry into muscle cells.
5. Beta-Blockers (e.g., atenolol) – Reduce heart rate and the force of contraction.
6. Alpha-Blockers (e.g., prazosin) – Relax certain muscles and help small blood vessels remain open.
7. Centrally Acting Agents (e.g., methyldopa) – Act on the brain to lower blood pressure.
8. Vasodilators (e.g., hydralazine) – Directly relax the muscles in blood vessel walls.

Managing high blood pressure is all about knowing how each drug class works and what to watch out for. Here’s a quick, conversational rundown of the major antihypertensive classes, their mechanisms, and to remember.

 

ACE Inhibitors 

 

Figure: Renin-Angiotensin-Aldosterone System (RAAS) showing how ACE inhibitors (ACEi) and ARBs interrupt Angiotensin II formation or action.

• Common drugs: Lisinopril, enalapril, captopril, ramipril.
• Mechanism: Block angiotensin-converting enzyme (ACE), so Angiotensin I can’t become Angiotensin II. This blunts the RAAS cascade (↓ aldosterone). The result is vasodilation (↓ afterload) and reduced blood volume (↓ preload).
• side effects: Great for HTN, heart failure, and protecting kidneys in diabetes. Watch for a dry cough (↑ bradykinin), hyperkalemia (↓ aldosterone), and angioedema (rare). Avoid in pregnancy and bilateral renal artery stenosis.

Visual aid suggestion: A simple RAAS pathway diagram (like above) really helps see where ACE inhibitors act.

ARBs (Angiotensin II Receptor Blockers) 

• Common drugs: Losartan, valsartan, candesartan, irbesartan, etc.
• Mechanism: Block the Angiotensin II Type 1 (AT1) receptor on blood vessels and adrenal glands. This prevents Angiotensin II from causing vasoconstriction or aldosterone release. The effect is very similar to ACEi (↓ afterload and volume).
• side effects: Useful if a patient develops an ACEi cough (ARBs don’t raise bradykinin). They still can cause hyperkalemia and hypotension, and impair renal function in renal artery stenosis. Like ACEi, ARBs are contraindicated in pregnancy. They generally lack the cough/angioedema side effects of ACEi.

 

Calcium Channel Blockers 

• Classes & drugs:
  • Dihydropyridines (DHP): Amlodipine, nifedipine, nicardipine – these mainly dilate arterioles.
  • Non-DHP: Verapamil and diltiazem – these affect the heart (↓ heart rate and contractility) as well as vessels.
• Mechanism: All block L-type voltage-gated Ca²⁺ channels. By reducing calcium entry into smooth muscle cells, DHPs cause arterial dilation (↓ peripheral resistance) while NDHPs slow AV/SA node conduction and reduce cardiac contractility.
• side effects: DHPs (amlodipine) often cause ankle edema, headache, and reflex tachycardia. NDHPs (verapamil, diltiazem) can cause bradycardia, AV block, and constipation (especially verapamil). Avoid NDHPs in heart failure with reduced EF because of their negative inotropic effect. CCBs are great for isolated systolic HTN and Prinzmetal’s angina (DHP) or rate control in atrial fibrillation (NDHP).

 

Beta-Blockers 

• Common drugs: Cardioselective β₁ blockers like metoprolol, atenolol; nonselective β₁/β₂ blockers like propranolol; plus mixed α/β blockers like labetalol and carvedilol.
• Mechanism: Block β-adrenergic receptors (β₁ in the heart and β₂ in lungs/vessels). This blunts the effects of adrenaline (epinephrine/norepinephrine). The heart slows down (↓ heart rate and contractility) and renin release from the kidney drops, lowering blood pressure.
• side effects: First-line for post-MI, angina, heart failure, and certain arrhythmias. They cause bradycardia and hypotension; nonselective ones can trigger bronchospasm (so use β₁-selective in asthmatics) and cold extremities. All can mask hypoglycemia symptoms. Don’t stop abruptly (risk rebound tachycardia/HTN). Beware fatigue and sexual dysfunction as side effects.

 

Diuretics (especially Thiazides) Antihypertensive Drugs

• Common drugs: Hydrochlorothiazide, chlorthalidone, indapamide. (also loops like furosemide, K-sparing like spironolactone in broader regimens).
• Mechanism: Thiazides inhibit the Na⁺/Cl⁻ cotransporter in the distal convoluted tubule.. This causes modest salt and water excretion. Acutely they drop blood volume (↓ cardiac output), and chronically they lower peripheral vascular resistance.
• side effects: Great first-line agents for uncomplicated HTN. They deplete K⁺ (risk arrhythmias), and can raise blood sugar and lipids. Classically cause hypercalcemia (helpful in preventing kidney stones/bone loss) but also hyperuricemia (gout). They can also cause erectile dysfunction. If higher diuresis is needed (edema, heart failure), loops (e.g. furosemide) are used. Potassium-sparing diuretics (spironolactone, amiloride) can be added to counteract K⁺ loss.

 

Alpha-Blockers Antihypertensive Drugs

• Common drugs: Prazosin, terazosin, doxazosin (selective α₁ blockers); nonselective agents like phenoxybenzamine (irreversible) and phentolamine (reversible) are used mostly for pheochromocytoma or cocaine toxicity. Tamsulosin/alfuzosin are α₁A-selective (for BPH).
• Mechanism: Block α₁-adrenergic receptors on vascular smooth muscle. This relaxes both arterioles and veins, reducing peripheral resistance and venous return.
• side effects: Useful for HTN in patients with BPH (or PTSD nightmares – prazosin). The big kicker is orthostatic hypotension, especially with the first dose (“first-dose syncope”), plus reflex tachycardia. Also causes nasal congestion, dizziness, and headache. Start low and titrate slowly.

 

Centrally Acting Agents Antihypertensive Drugs

• Common drugs: Clonidine, guanfacine (α₂ agonists), and methyldopa.
• Mechanism: Stimulate α₂ receptors in the brainstem, which turns down sympathetic outflow. (Methyldopa is a prodrug that’s converted to an α₂ agonist in the CNS.) The result is lower heart rate and vasodilation.
• side effects: Can be very effective for resistant HTN. However, they often make patients sedated, dizzy, and dry-mouthed. Clonidine patches require caution (abrupt stop → dangerous rebound HTN). Methyldopa is special: it’s safe in pregnancy but can cause liver toxicity and Coombs-positive hemolytic anemia.

Direct Vasodilators Antihypertensive Drugs

• Common drugs: Hydralazine and Minoxidil. (Nitroprusside is also a direct dilator used in emergencies, but outside this scope.)
• Mechanism: These drugs directly relax arteriolar smooth muscle. Hydralazine’s exact action is unclear, but it appears to inhibit intracellular Ca²⁺ release in smooth muscle. Minoxidil opens ATP-sensitive K⁺ channels, causing hyperpolarization and relaxation. Neither drug acts on veins (so mostly lowers afterload).
• side effects: They are potent vasodilators, so the body fights back with reflex tachycardia and salt retention. Always pair with a β-blocker (to blunt tachycardia) and a diuretic (to prevent edema). Hydralazine can cause a lupus-like syndrome (anti-histone Abs) and headaches. Minoxidil famously causes hypertrichosis (used as a hair-growth agent!) and can lead to pericardial effusion; it must be monitored carefully. Hydralazine is used IV in eclampsia and oral in resistant HTN; minoxidil is reserved for truly refractory cases.

 

Class	Examples	Mechanism (MOA)	Side Effects
ACE Inhibitors	Lisinopril, enalapril, etc.	Block ACE → ↓ Ang II and ↑ bradykinin	↓Afterload/preload; cough (bradykinin), ↑K⁺, angioedema. Renal-protective. Avoid in pregnancy.
ARBs	Losartan, valsartan, etc.	Block Ang II AT₁ receptors	Similar to ACEi without cough. ↑K⁺, hypotension, renal impairment.
Calcium Channel Bkrs	Amlodipine (DHP); Verapamil (non-DHP)	Block L-type Ca²⁺ channels	DHP→arteriolar dilation (edema, reflex tachy). Non-DHP→↓HR/contractility (bradycardia, heart block).
β-Blockers	Metoprolol (β₁); Propranolol (β₁+β₂)	Block β receptors (↓ HR, ↓contractility)	↓ cardiac output; use in angina/MI/HF. Side: bradycardia, asthma risk (β₂ block), mask hypoglycemia.
Thiazide Diuretics	HCTZ, chlorthalidone	Inhibit Na⁺-Cl⁻ cotransporter in DCT.	↓Volume & PVR. ↑ Ca²⁺ retention. Side: hypokalemia, hyperglycemia, hyperlipidemia, ↑uric acid..
Alpha-Blockers	Prazosin, terazosin, etc.	Block α₁ receptors on vessels	Vasodilation; use in HTN/BPH. Side: orthostatic hypotension (1st dose), reflex tachycardia.
Centrals (α₂)	Clonidine, methyldopa	α₂-agonism in brain ↓ SNS outflow	↓HR/BP; sedating. Rebound HTN if stopped. Methyldopa: safe in pregnancy but causes anemia/liver issues.
Direct Vasodilators	Hydralazine, minoxidil	Direct arteriolar relax (↑NO or K⁺ channel open)	↓Afterload. Reflex tachycardia/fluid retention. Hydralazine: lupus-like syndrome. Minoxidil: hypertrichosis, pericardial effusion.