Table of Contents
Introduction
ACE inhibitors (Angiotensin-Converting Enzyme Inhibitors) are a foundational class of antihypertensive drugs. They are used to treat hypertension, heart failure, and various forms of renal and cardiovascular disease.
Common examples include:
- Enalapril
- Lisinopril
- Ramipril
- Captopril
These drugs are frequently tested in both clinical exams and licensure tests due to their dual impact on the cardiovascular and renal systems.
Stepwise Mechanism of Action of ACE Inhibitors
- Inhibition of Angiotensin-Converting Enzyme (ACE):
ACE inhibitors block the conversion of angiotensin I to angiotensin II by inhibiting the ACE enzyme, which is primarily located in the pulmonary endothelium. - Reduced Angiotensin II Levels:
Angiotensin II is a potent vasoconstrictor and stimulates aldosterone secretion. Its reduction leads to:- Vasodilation
- Decreased sodium and water retention
- Reduced blood pressure
- Decreased Aldosterone Secretion:
With lower aldosterone, there is reduced sodium and water reabsorption in the distal nephron, promoting natriuresis and diuresis. - Increased Bradykinin Levels:
ACE also degrades bradykinin, a vasodilator. ACE inhibition increases bradykinin, further contributing to vasodilation but also increasing the risk of dry cough and angioedema. - Overall Effects:
- Decreased preload and afterload
- Reduced systemic vascular resistance
- Improved cardiac output in heart failure
- Renoprotective in diabetic nephropathy
Pharmacokinetic Parameters of ACE Inhibitors
| Parameter | General Range |
|---|---|
| Bioavailability | 25–75% (varies with each drug) |
| Onset of Action | 1–2 hours (oral); peak in 4–6 hours |
| Half-life | 2–40 hours depending on the drug |
| Protein Binding | 90% for most ACEIs |
| Metabolism | Hepatic (most are prodrugs except lisinopril) |
| Excretion | Renal (dose adjustment needed in CKD) |
Clinical Uses of ACE Inhibitors
- Hypertension (first-line in patients with diabetes, CKD)
- Congestive heart failure
- Post-myocardial infarction
- Diabetic nephropathy
- Proteinuria with chronic kidney disease
- Left ventricular dysfunction
Adverse Effects of ACE Inhibitors
- Dry cough (due to bradykinin accumulation)
- Hyperkalemia
- Hypotension, especially after first dose
- Angioedema (life-threatening in rare cases)
- Taste disturbances (metallic taste)
- Teratogenic – contraindicated in pregnancy
- Renal function deterioration in bilateral renal artery stenosis
Comparative Analysis: ACE Inhibitors vs ARBs
| Feature | ACE Inhibitors | ARBs (Angiotensin II Receptor Blockers) |
|---|---|---|
| Main Target | Inhibits ACE enzyme | Blocks angiotensin II receptor (AT1) |
| Bradykinin effect | Increases → cough, angioedema | No effect → fewer side effects |
| Use in dry cough | Avoid | Preferred |
| Potassium level | May cause hyperkalemia | May cause hyperkalemia |
| Fetal risk | Teratogenic | Teratogenic |
Practice MCQs
Q1. What is the primary enzyme inhibited by ACE inhibitors?
a. Renin
b. Angiotensinogenase
c. Angiotensin-converting enzyme ✅
d. Aldosterone synthase
Q2. Which substance increases as a result of ACE inhibition?
a. Aldosterone
b. Bradykinin ✅
c. Angiotensin II
d. Dopamine
Q3. Which of the following is a known side effect of ACE inhibitors?
a. Hypokalemia
b. Hypercalcemia
c. Dry cough ✅
d. Arrhythmia
Q4. ACE inhibitors are contraindicated in which of the following conditions?
a. Diabetes mellitus
b. Pregnancy ✅
c. Hypertension
d. Heart failure
Q5. Which of the following ACE inhibitors is not a prodrug?
a. Enalapril
b. Ramipril
c. Lisinopril ✅
d. Perindopril
Q6. The fall in blood pressure with ACE inhibitors is primarily due to:
a. Beta-blockade
b. Vasodilation via angiotensin II suppression ✅
c. Increased heart rate
d. Decreased blood volume only
Q7. Bradykinin accumulation leads to which adverse effect?
a. Rash
b. Hyperglycemia
c. Dry cough ✅
d. Hypokalemia
Q8. ACE inhibitors have renoprotective effects in:
a. Acute kidney injury
b. Nephrolithiasis
c. Diabetic nephropathy ✅
d. Glomerulonephritis
Q9. ACE inhibitors are especially useful in:
a. Asthma
b. Hyperthyroidism
c. Heart failure with reduced ejection fraction ✅
d. Acute MI with bradycardia
Q10. Which electrolyte abnormality is expected with ACE inhibitor use?
a. Hyperkalemia ✅
b. Hypokalemia
c. Hyponatremia
d. Hypermagnesemia
FAQs
Q1: Can ACE inhibitors be used in pregnancy?
No, they are contraindicated due to teratogenic effects, especially in the second and third trimesters.
Q2: Why do ACE inhibitors cause a dry cough?
Due to bradykinin accumulation in the lungs, which irritates airway receptors.
Q3: Can ACE inhibitors be combined with ARBs?
Generally avoided due to increased risk of hyperkalemia and renal dysfunction.
Q4: Are ACE inhibitors safe in chronic kidney disease?
Yes, but they should be used cautiously, with monitoring of serum creatinine and potassium.
References
- KD Tripathi – Essentials of Medical Pharmacology
- Goodman & Gilman – The Pharmacological Basis of Therapeutics
- Review of Pharmacology – Sparsh Gupta
- American Heart Association Guidelines
- NCBI: https://www.ncbi.nlm.nih.gov/books/NBK538507/