ACE inhibitors

ACE inhibitors

Angiotensin-converting enzyme (ACE) inhibitors are now the established first-line treatment in younger patients with hypertension and are also extensively used to treat heart failure. They are known to be less effective in treating hypertensive Afro-Caribbean patients. ACE inhibitors are also used to treat diabetic nephropathy and have a role in the secondary prevention of ischaemic heart disease.

Mechanism of action:

• inhibits the conversion angiotensin I to angiotensin II
  • → decrease in angiotensin II levels → to vasodilation and reduced blood pressure
  • → decrease in angiotensin II levels → reduced stimulation for aldosterone release → decrease in sodium and water retention by the kidneys
• renoprotective mechanism
  • angiotensin II constricts the efferent glomerular arterioles
  • ACE inhibitors therefore lead to dilation of the efferent arterioles
    The renoprotective effects of ACE inhibitors are mediated through dilation of the glomerular efferent arteriole
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    Importance: 70
    → reduced glomerular capillary pressure → decreased mechanical stress on the delicate filtration barriers of the glomeruli
  • this is particularly important in diabetic nephropathy
• ACE inhibitors are activated by phase 1 metabolism in the liver
  ACE inhibitors are activated by phase 1 metabolism in the liver
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Side-effects:

• cough
  • occurs in around 15% of patients and may occur up to a year after starting treatment
  • thought to be due to increased bradykinin levels
    ACE inhibitors prevent the breakdown of inflammatory peptides such as bradykinin and cough is a frequent side effect.
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    Importance: 41
• angioedema
  Drug-induced angioedema without urticaria is most frequently associated with angiotensin converting enzyme inhibitors or, less frequently, angiotensin II receptor blockers
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  Importance: 69
  : may occur up to a year after starting treatment
• hyperkalaemia
  hyperkalaemia
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• first-dose hypotension: more common in patients taking diuretics

Cautions and contraindications

• pregnancy
  pregnancy
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  and breastfeeding - avoid
• renovascular disease
  renovascular disease
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  - may result in renal impairment
• aortic stenosis
  aortic stenosis
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  - may result in hypotension
• hereditary of idiopathic angioedema
• specialist advice should be sought before starting ACE inhibitors in patients with a potassium >= 5.0 mmol/L
  specialist advice should be sought before starting ACE inhibitors in patients with a potassium >= 5.0 mmol/L
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Interactions

• patients receiving high-dose diuretic therapy (more than 80 mg of furosemide a day)
  • significantly increases the risk of hypotension

Monitoring

• urea and electrolytes should be checked before treatment is initiated and after increasing the dose
  urea and electrolytes should be checked before treatment is initiated and after increasing the dose
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  • a rise in the creatinine and potassium may be expected after starting ACE inhibitors
  • acceptable changes are an increase in serum creatinine, up to 30% from baseline
    acceptable changes are an increase in serum creatinine, up to 30% from baseline
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    and an increase in potassium up to 5.5 mmol/l.
  • significant renal impairment may occur in patients who have undiagnosed bilateral renal artery stenosis
    bilateral renal artery stenosis
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Examples of common ACE inhibitors

• ramipril
• enalapril
• lisinopril

+PassMedicine Notes

Angiotensin-converting enzyme (ACE) inhibitors are now the established first-line treatment in younger patients with hypertension and are also extensively used to treat heart failure. They are known to be less effective in treating hypertensive Afro-Caribbean patients. ACE inhibitors are also used to treat diabetic nephropathy and have a role in the secondary prevention of ischaemic heart disease.

Mechanism of action:

• inhibits the conversion angiotensin I to angiotensin II
• --> decrease in angiotensin II levels --> to vasodilation and reduced blood pressure
• --> decrease in angiotensin II levels --> reduced stimulation for aldosterone release --> decrease in sodium and water retention by the kidneys
• renoprotective mechanism
• angiotensin II constricts the efferent glomerular arterioles
• ACE inhibitors therefore lead to dilation of the efferent arterioles --> reduced glomerular capillary pressure --> decreased mechanical stress on the delicate filtration barriers of the glomeruli
• this is particularly important in diabetic nephropathy
• ACE inhibitors are activated by phase 1 metabolism in the liver

Side-effects:

• cough
• occurs in around 15% of patients and may occur up to a year after starting treatment
• thought to be due to increased bradykinin levels
• angioedema: may occur up to a year after starting treatment
• hyperkalaemia
• first-dose hypotension: more common in patients taking diuretics

Cautions and contraindications

• pregnancy and breastfeeding - avoid
• renovascular disease - may result in renal impairment
• aortic stenosis - may result in hypotension
• hereditary of idiopathic angioedema
• specialist advice should be sought before starting ACE inhibitors in patients with a potassium >= 5.0 mmol/L

Interactions

• patients receiving high-dose diuretic therapy (more than 80 mg of furosemide a day)
• significantly increases the risk of hypotension

Monitoring

• urea and electrolytes should be checked before treatment is initiated and after increasing the dose
• a rise in the creatinine and potassium may be expected after starting ACE inhibitors
• acceptable changes are an increase in serum creatinine, up to 30% from baseline and an increase in potassium up to 5.5 mmol/l.
• significant renal impairment may occur in patients who have undiagnosed bilateral renal artery stenosis

Examples of common ACE inhibitors

• ramipril
• enalapril
• lisinopril

pdd566.png Flow chart showing the management of hypertension as per current NICE guideliness