Mechanism of Action of Enalapril

Mechanism of Action of Enalapril

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Introduction

Enalapril is an angiotensin-converting enzyme (ACE) inhibitor widely used in the management of hypertension, heart failure, and diabetic nephropathy. It is a prodrug that is converted in the body to its active metabolite, enalaprilat. Enalapril is a high-yield drug in pharmacology, cardiology, and internal medicine examinations because it targets the renin–angiotensin–aldosterone system (RAAS), a central regulator of blood pressure and fluid balance.

MOA of enalapril
Mechanism of action of enalapril
Mechanism of action of enalapril
Enalapril Mechanism of Action Flowchart

Mechanism of Action (Step-wise)

Enalapril lowers blood pressure and reduces cardiac workload by inhibiting angiotensin II formation and aldosterone secretion.

  1. Activation of the Renin–Angiotensin System
    Reduced renal perfusion stimulates renin release, leading to formation of angiotensin I.
  2. Role of Angiotensin-Converting Enzyme (ACE)
    ACE converts angiotensin I into angiotensin II, a potent vasoconstrictor.
  3. Prodrug Conversion
    Enalapril is hydrolyzed in the liver to its active form, enalaprilat.
  4. ACE Inhibition
    Enalaprilat competitively inhibits angiotensin-converting enzyme.
  5. Reduced Angiotensin II Formation
    Decreased angiotensin II leads to:
    • Reduced vasoconstriction
    • Reduced sympathetic activity
  6. Decreased Aldosterone Secretion
    Lower angiotensin II reduces aldosterone release from the adrenal cortex.
  7. Reduced Sodium and Water Retention
    Decreased aldosterone causes natriuresis and diuresis.
  8. Increased Bradykinin Levels
    ACE inhibition prevents breakdown of bradykinin, causing additional vasodilation.
  9. Overall Hemodynamic Effects
    • Decreased peripheral vascular resistance
    • Reduced preload and afterload
    • Lower blood pressure and cardiac workload

Pharmacokinetics

  • Administration: Oral
  • Absorption: Moderate
  • Prodrug: Yes (converted to enalaprilat)
  • Distribution: Widely distributed
  • Metabolism: Hepatic conversion to enalaprilat
  • Elimination: Primarily renal
  • Half-life: Enalaprilat ~11 hours
  • Dose adjustment: Required in renal impairment

Clinical Uses

Enalapril is used in several cardiovascular and renal conditions:

  • Hypertension
  • Chronic heart failure
  • Asymptomatic left ventricular dysfunction
  • Diabetic nephropathy
  • Proteinuric chronic kidney disease
  • Post–myocardial infarction (to prevent remodeling)

Adverse Effects

Adverse effects are related to RAAS inhibition and bradykinin accumulation:

  • Common:
    • Dry cough
    • Hypotension (first dose)
    • Dizziness
  • Metabolic:
    • Hyperkalemia
  • Renal:
    • Acute renal failure (especially in bilateral renal artery stenosis)
  • Serious:
    • Angioedema (rare but life-threatening)

Contraindications:

  • Pregnancy
  • Bilateral renal artery stenosis

Comparative Analysis (must include a table + explanation)

Comparison of RAAS Inhibitors

FeatureEnalaprilLosartanAliskiren
Drug classACE inhibitorARBDirect renin inhibitor
Effect on bradykininIncreasesNo effectNo effect
Cough riskCommonRareRare
HyperkalemiaYesYesYes
Use in heart failureYesYesLimited

Explanation:
Enalapril reduces angiotensin II formation and increases bradykinin, providing potent vasodilation but causing cough and angioedema. ARBs such as losartan avoid bradykinin-related adverse effects but act downstream.

MCQs (10–15)

  1. Enalapril belongs to which drug class?
    a) Beta blocker
    b) Calcium channel blocker
    c) ACE inhibitor
    d) Diuretic

Answer: c) ACE inhibitor

  1. Enalapril is converted into its active form:
    a) In the kidney
    b) In the liver
    c) In plasma
    d) In the lungs

Answer: b) In the liver

  1. Enalapril reduces blood pressure mainly by decreasing:
    a) Heart rate
    b) Cardiac output
    c) Peripheral vascular resistance
    d) Blood volume directly

Answer: c) Peripheral vascular resistance

  1. ACE inhibition leads to accumulation of:
    a) Angiotensin II
    b) Aldosterone
    c) Bradykinin
    d) Renin

Answer: c) Bradykinin

  1. A common adverse effect of enalapril is:
    a) Bradycardia
    b) Dry cough
    c) Hypoglycemia
    d) Constipation

Answer: b) Dry cough

  1. Enalapril decreases aldosterone secretion, leading to:
    a) Hypokalemia
    b) Hyperkalemia
    c) Hyponatremia
    d) Hypernatremia

Answer: b) Hyperkalemia

  1. Enalapril is contraindicated in:
    a) Hypertension
    b) Heart failure
    c) Pregnancy
    d) Diabetes mellitus

Answer: c) Pregnancy

  1. Enalapril improves heart failure by reducing:
    a) Heart rate only
    b) Afterload and preload
    c) Contractility
    d) Blood viscosity

Answer: b) Afterload and preload

  1. Enalapril causes acute renal failure especially in patients with:
    a) Diabetes
    b) Liver disease
    c) Bilateral renal artery stenosis
    d) Asthma

Answer: c) Bilateral renal artery stenosis

  1. Enalapril increases sodium excretion by reducing:
    a) Renin
    b) Angiotensin I
    c) Aldosterone
    d) Bradykinin

Answer: c) Aldosterone

FAQs (minimum 5)

  1. What is the primary mechanism of enalapril?
    Inhibition of angiotensin-converting enzyme, reducing angiotensin II and aldosterone.
  2. Why does enalapril cause cough?
    Due to accumulation of bradykinin in the respiratory tract.
  3. Is enalapril a prodrug?
    Yes, it is converted to enalaprilat in the liver.
  4. Can enalapril be used in diabetic patients?
    Yes, it is beneficial in diabetic nephropathy.
  5. Why is enalapril contraindicated in pregnancy?
    Because it can cause fetal renal damage and death.
  6. Does enalapril reduce cardiac remodeling?
    Yes, by decreasing angiotensin II–mediated myocardial remodeling.

References

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