Pharm 101: Captopril

Class

ACE-inhibitor

Pharmacodynamics

• ACE-I inhibit the Renin-Angiotensin-Aldosterone (RAA) system, and stimulate the Kallikrein-Kininogen (KK) system, by inhibiting peptidyl dipeptidase (angiotensin converting enzyme), an enzyme that:
  • Hydrolyses angiotensin I to angiotensin II
  • Inactivates bradykinin, a potent vasodilator
• Angiotensin II is a potent vasoconstrictor and also leads to aldosterone secretion that causes Na and water retention

Pharmacokinetics

• Bioavailability 65%
• Half-life 2 hours
• Renal excretion

Clinical uses

• Hypertension
• Chronic renal failure:
  • Diminish proteinuria and stabilise renal function (even in absence of lowering BP_
  • Recommended in diabetes even in absence of hypertension
• CCF
• Reduced mortality post-MI

Adverse effects

• Marked first-dose hypotension, particularly in dehydrated patients
• Acute kidney injury, especially with bilateral renal artery stenosis or solitary kidney
• Hyperkalaemia, especially with K sparing diuretics, diabetes or CRF
• Dry cough and angioedema (due to bradykinin and substance P)
• Neutropenia or proteinuria if given in high doses to CRF patients
• Minor toxic effects in 10% of patients:
  • Altered sense of taste
  • Allergic skin rash
  • Drug fever

Precautions/contraindications

• Pregnancy:
  • First trimester: teratogenic
  • Second/third trimester: fetal hypotension, anuria and renal failure
• Dose should be reduced in renal failure
• Drug interactions:
  • Potassium supplements or potassium sparing diuretics, which can result in hyperkalaemia
  • NSAIDs can impair the hypotensive effects of ACE-I by blocking bradykinin-mediated vasodilation, which is at least partially prostaglandin mediated
  • Lithium –> lithium toxicity
  • General anaesthetics –> hypotension
  • Other diuretics/anti-hypertensives –> hypotension

Further Reading

• Nickson C. Severe Heart Failure Management