Introduction
Angiotensin II Receptor Blockers (ARBs) are a major class of antihypertensive drugs. They selectively block the angiotensin II type 1 (AT1) receptor, reducing blood pressure and protecting organs from damage caused by chronic hypertension.
Commonly used ARBs include:
- Losartan
- Valsartan
- Telmisartan
- Olmesartan
- Irbesartan
ARBs are widely prescribed for managing:
- Hypertension
- Heart failure
- Diabetic nephropathy
- Post-myocardial infarction
- Chronic kidney disease
Because of their safety profile and efficacy, they are commonly tested in exams such as USMLE, NCLEX, NAPLEX, GPAT, and NEET-PG.
Stepwise Mechanism of Action of ARBs
- Blockade of AT1 Receptors
ARBs selectively block angiotensin II type 1 (AT1) receptors, preventing angiotensin II from binding to its main target on vascular smooth muscle and the adrenal cortex. - Reduced Vasoconstriction
Angiotensin II is a potent vasoconstrictor. By blocking AT1 receptors, ARBs promote vasodilation and reduce systemic vascular resistance. - Decreased Aldosterone Secretion
Angiotensin II stimulates aldosterone release from the adrenal cortex. ARBs inhibit this effect, leading to decreased sodium and water reabsorption, and lower blood volume. - No Effect on Bradykinin Breakdown
Unlike ACE inhibitors, ARBs do not affect bradykinin metabolism, resulting in fewer side effects such as dry cough or angioedema. - Organ Protection
ARBs provide renal and cardiovascular protection, especially in patients with diabetes and chronic kidney disease.
Pharmacokinetic Parameters of ARBs
| Parameter | General Values (Varies by Drug) |
|---|---|
| Bioavailability | 25–60% (oral) |
| Onset of Action | 1–2 hours |
| Half-life | 6–24 hours (drug-dependent) |
| Protein Binding | >90% |
| Metabolism | Hepatic (CYP2C9 for losartan) |
| Excretion | Renal and biliary |
Clinical Uses of ARBs
- Essential hypertension
- Heart failure with reduced ejection fraction (HFrEF)
- Diabetic nephropathy
- Chronic kidney disease (CKD)
- Post-myocardial infarction
- Stroke prevention (in combination with thiazide)
Adverse Effects of ARBs
- Hyperkalemia
- Hypotension, especially after first dose
- Dizziness, fatigue
- Headache
- Angioedema (rare, lower incidence than ACE inhibitors)
- Fetal toxicity – contraindicated in pregnancy
- Renal function decline in bilateral renal artery stenosis
Comparative Analysis: ARBs vs ACE Inhibitors
| Feature | ARBs | ACE Inhibitors |
|---|---|---|
| Target | AT1 receptor | ACE enzyme |
| Bradykinin effect | None | Increases bradykinin |
| Dry cough risk | Low | High |
| Angioedema risk | Low | Higher |
| Use in ACEI-intolerant | Yes | No |
Practice MCQs
Q1. What is the main site of action of ARBs?
a. ACE enzyme
b. Renin
c. AT1 receptor ✅
d. Beta-1 receptor
Q2. Which of the following effects is blocked by ARBs?
a. Bradykinin breakdown
b. Angiotensin II receptor activation ✅
c. Sodium excretion
d. Renin secretion
Q3. Why do ARBs cause less cough than ACE inhibitors?
a. They inhibit renin directly
b. They do not affect bradykinin metabolism ✅
c. They increase dopamine release
d. They are administered intravenously
Q4. ARBs are contraindicated in which condition?
a. Asthma
b. Pregnancy ✅
c. Anemia
d. Hyperlipidemia
Q5. Which ARB undergoes significant first-pass hepatic metabolism?
a. Valsartan
b. Telmisartan
c. Losartan ✅
d. Irbesartan
Q6. A common electrolyte disturbance with ARBs is:
a. Hypocalcemia
b. Hyperkalemia ✅
c. Hypernatremia
d. Hypokalemia
Q7. In a patient who developed cough with an ACE inhibitor, the next best alternative is:
a. Calcium channel blocker
b. ARB ✅
c. Diuretic
d. Beta-blocker
Q8. ARBs are considered renoprotective in:
a. Acute kidney injury
b. Diabetic nephropathy ✅
c. UTI
d. Glomerulonephritis
Q9. ARBs are typically combined with which drug for enhanced blood pressure control?
a. Statin
b. Beta-blocker
c. Thiazide diuretic ✅
d. Nitrate
Q10. Which of the following is NOT an expected effect of ARBs?
a. Vasodilation
b. Decreased aldosterone
c. Cough ✅
d. Lower blood pressure
FAQs
Q1: Are ARBs safe in pregnancy?
No, they are contraindicated due to their teratogenic effects, especially in the second and third trimesters.
Q2: Can ARBs be combined with ACE inhibitors?
Generally not recommended, due to increased risk of hyperkalemia and renal dysfunction.
Q3: Do ARBs affect bradykinin levels?
No, which is why dry cough and angioedema are much less common compared to ACE inhibitors.
Q4: Are ARBs nephroprotective?
Yes, they slow the progression of diabetic nephropathy and CKD by reducing glomerular hypertension.
References
- KD Tripathi – Essentials of Medical Pharmacology
- Goodman & Gilman – The Pharmacological Basis of Therapeutics
- Review of Pharmacology – Sparsh Gupta
- American College of Cardiology Guidelines
- NCBI: https://www.ncbi.nlm.nih.gov/books/NBK470410/