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 28%
  • Half-life 15 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

Pharm 101 700

Pharmacology 101

Top 200 drugs

MBBS (UWA) CCPU (RCE, Biliary, DVT, E-FAST, AAA) Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Editor-in-chief of the LITFL ECG Library. Twitter: @rob_buttner

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.