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ACE inhibitors


  • ACE is an enzyme that converts:
    • inactive angiotensin I → vasoconstrictor peptide angiotensin II;
    • vasodilator peptide bradykinin → inactive fragments;
  • ACE is found in endothelial cells lining all blood vessels as well as in the lung, brain, kidney, adrenals, GIT, & reproductive system;
  • ACE inhibition thus:
    • interrupts renin-angiotensin-aldosterone cascade →
      • decr. circulating angiotensin II → vasodilatation & decr. symp.N.S.;
        • decr. aldosterone secretion → short-term natriuresis & decr. K losses;
        • ⇒ incr. renin levels;
      • decr. local tissue angiotensin II
        • → decr. GFR esp. if GFR dependent on AG-II maintaing efferent tone:
        • eg. low RBF such as renal artery stenosis esp.bilat.;
    • inhibition of bradykinin breakdown → incr. PG production → vasodil.;
    • THUS → vasodilatation → decr. TPR → hypotension;
    • HT:
      • C.O., LVEDF, HR unchanged;
      • HR not changed as decr. resetting baro. & incr. vagal
    • NB. in CCF:
      • HR unchanged but decr. LVEDF → incr. C.O.
    • BUT:
      • peripheral blood flow, esp. cerebral is maintained;
      • normal haemodynamic response to exercise/stress/GA maintained;
      • postural effects are minimal unless hypovolaemia is present;

clinical uses:

essential hypertension:

  • ACE inhib. are effective, well tolerated in most types & grades of severity of hypertension & in mild-severe essential HT are as potent & effective single agent Rx as beta-blockers or diuretics;
  • Their efficacy can be improved by combination with a low Na diet, or a K-losing diuretic or Ca antagonist.
  • They are ideal in the elderly except care if renal impairment or extensive vascular disease;

accelerated/malignant hypertension:

  • ACE inhib. lower BP smoothly & rapidly within 20min (captopril) & 1hr (enalapril) whilst maintaining cerebral & renal blood flow but care with dosage as the hypovolaemia potentiates hypotensive effect of ACE inhib.

renovascular hypertension:

  • As HT in this case is Renin-AG dependent, ACE inhib. are very effective & the Rx of choice for unilat.renal A stenosis whilst awaiting Sx but may precipitate ARF if bilat. stenoses or stenosis to sole kidney as there will not be any compensatory incr. GFR in good kidney to maintain renal function!!

hypertension assoc. with renal disease & ESRF:

  • ACE inhib. effective as also maintains RBF & control BP without significant hypovolaemia & may slow the decline in renal function in diabetic nephropathy.
  • Not for pregnancy as teratogenic!

heart failure:

  • ACE inhib. are the single most important advance in Rx CCF since diuretics.
  • They improve cardiovasc. haemodynamics (as above) resulting in:
    • improved symptoms;
    • incr. exercise tolerance;
    • improved heart size;
    • incr. LV ejection fraction;
    • improves cardiac remodelling after AMI;
    • decr. ventricular ectopic beats & arrhythmias:
      • ? via incr. K status;
      • ? via decr. symp. N.S. activity;
    • prolongs life reducing overall mortality in severe CCF by 27%;
  • ACE inhib. is usually combined with K-losing diuretics ± digoxin;

combinational therapy:

  • with diuretics:
    • NEVER with K-sparing diuretics!!!!
    • K-losing diuretics good in CCF or essential HT;
    • good in HT with IHD or if severe/resistant HT;
    • not particularly effective;
    • potent combination (eg. prazosin);
    • but rarely necessary as high risk of hypotension;


  • History of HS reaction to ACE inhib.
  • History of angioneurotic oedema assoc. with ACE inhib.;
  • Pregnancy (category D) / lactation

special precautions:

  • Impaired renal function:
    • bilat. renal A stenosis or stenosis lone kidney → reversible ARF;
    • most ACE inhib. are renally excreted;
    • occasional incr. urea/CRN assoc. with ACE inhib. may indicate decr. dose needed;
  • Hyperkalaemia:
    • avoid using K-sparing diuretics as well;
    • esp. if: renal insuff.; D.M.; K supplements;
  • Impaired liver function:
    • Reversible abn. LFT's have occurred during Rx with ACE inhib.
    • Use with care if impaired liver function;
  • General Anaesthesia:
    • Agents that produce hypotension which is normally compensated by renin release may produce uncompensated hypotension if ACE inhib.
  • Persistent cough esp. females & on lying down may need decr. dose or cessation;
  • Safety not established in children;
  • Best to withdraw drugs that raise plasma renin levels before commencing ACE inhibitors, for example: diuretics, potent vasodilators;

drug interactions:

adverse reactions:

  • 3-10% dizziness; headache; hypotension; N/V/D; cough; rash; angina;
  • others less common incl. rarely angioneurotic oedema;


  • 1898, renin is discovered and appeared to increase blood pressure
  • 1939, renin was found not to cause the rise in blood pressure, but was an enzyme which catalyzed the formation of the substances that were responsible, namely, angiotensin I (Ang I) and Ang II
  • 1976, the 1st ACEI was captopril was synthesized
    • developed following research into the hypotensive effects of the Brazilian Pit Viper snake venom
  • enalapril, patented in 1978 and approved for medical use in 1984
  • lisinopril, patented in 1978 and approved for medical use in the United States in 1987
  • 1979, saralasin synthesized as an analogue of angiotensin II but with competitive angiotensin II receptor antagonist activity
  • perindopril (Coversyl), patented in 1980 and approved for medical use in 1988
  • quinapril, patented in 1980 and came into medical use in 1989
  • ramipril, patented in 1981 and approved for medical use in 1989
  • benazepril, patented in 1981 and came into medical use in 1990
  • cilazapril, patented in 1982 and approved for medical use in 1990
  • fosinopril introduced into US in 1991 and is the 1st phosphonate ACEI (and currently the only one of this type)
  • trandolapril, patented in 1981, and approved for medical use in 1993
  • imidapril, patented in 1982 and approved for medical use in 1993
  • 1995, 1st angiotensin II receptor blockers (ARBs) approved for medical use - losartan
aceis.txt · Last modified: 2023/07/30 08:26 by gary1

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