Angiotensin II receptor antagonists

Angiotensin II receptor antagonists (ARBs), also known as angiotensin receptor blockers, sartans, or AT1-receptor antagonists, are a group of pharmaceuticals that modulate the renin-angiotensin-aldosterone system (RAAS). Their primary use is in the management of hypertension (high blood pressure), but they are also used in treating heart failure, chronic kidney diseases, and diabetic nephropathy.

Mechanism of Action

Angiotensin II receptor antagonists work by blocking the action of angiotensin II, a potent vasoconstrictor, by selectively antagonizing the angiotensin II receptor type 1 (AT1) on blood vessels and other tissues. This blockade prevents angiotensin II from exerting its effects, leading to vasodilation, reduced secretion of vasopressin, and decreased production and secretion of aldosterone. As a result, ARBs lower blood pressure, reduce salt and water retention, and decrease workload on the heart.

Indications

ARBs are primarily indicated for the treatment of primary hypertension. They are also beneficial in patients with heart failure, particularly in those who are intolerant to ACE inhibitors due to cough or angioedema. Other indications include chronic kidney disease and diabetic nephropathy, where they help to slow the progression of kidney damage.

Adverse Effects

While generally well-tolerated, ARBs can cause some side effects such as dizziness, headaches, and drowsiness. Rarely, they may lead to angioedema (swelling similar to hives but under the skin) and kidney impairment. They are contraindicated in pregnancy due to the risk of birth defects.

Examples

Commonly prescribed angiotensin II receptor antagonists include:

• Losartan
• Valsartan
• Irbesartan
• Candesartan
• Telmisartan
• Olmesartan

Comparison with ACE Inhibitors

ARBs and ACE inhibitors both act on the renin-angiotensin system but at different points. ACE inhibitors block the conversion of angiotensin I to angiotensin II, thereby reducing the production of angiotensin II. ARBs, on the other hand, block the action of angiotensin II after it is formed. Both classes of drugs are effective for the same indications, but ARBs may be preferred in patients who experience cough or angioedema with ACE inhibitors.

Pharmacokinetics

The pharmacokinetics of ARBs vary among different agents. Most have good oral bioavailability and are metabolized in the liver. They are excreted primarily by the bile and feces, with minimal renal excretion, making them safer in patients with renal impairment compared to ACE inhibitors.

Future Directions

Research continues into the development of new ARBs with additional beneficial properties, such as antioxidant effects or novel mechanisms of action. Studies are also exploring the potential benefits of ARBs in treating conditions beyond their current indications, such as migraine and Alzheimer's disease.