Angiotensin Converting Enzyme Inhibitors

Commonly Lisinopril/Ramipril

Mechanism of Action

• Inhibit the conversion of angiotensin I to angiotensin II
  • Angiotensin II is a potent vasoconstrictor, promotes aldosterone release (which further increases blood pressure via increased sodium/water reabsorption) and facilitates sympathetic activity
• NB ACEIs act synergistically with diuretics (which partly activate the RAAS)

Indications

• Heart failure (usually in combination with a beta-blocker, usually bisoprolol)
  • Usually start low(ish) dose
• Hypertension in younger people (except Afro-Caribbean patients)
• Diabetic nephropathy
• Post MI (secondary prophylaxis)
• Post stroke/TIA (usually perindopril)

Cautions

• Check renal function and FBC prior to initiation/increasing dose (risk of hyperkalaemia; agranulocytosis in collagen vascular disease)
• Potassium supplements/Potassium sparing diuretics should be stopped (or decreased dose) prior to initiation of ACEIs (risk of hyperkalaemia)
• Profound first dose hypotension may occur in patients already taking diuretics (particularly high dosages- use with caution)
• Use with caution in patients with
  • Hypovolaemia; hyponatraemia; hypotension; unstable heart failure; receiving high dose vasodilator treatment; known renovascular disease (unilateral) OR other peripheral vascular disease (increased risk of renovascular disease)
• In general, DO NOT co-prescribe NSAIDs (risk of renal injury)
• In severe liver dysfunction, there is a small risk of hepatic necrosis so should be avoided or closely monitored (likewise, if liver function deteriorates in otherwise healthy individuals, discontinue)
• In renal dysfunction, monitor closely for any deterioration or hyperkalaemia

Contraindications

• Bilateral renal artery stenosis (reduce GFR and can precipitate renal failure)
• Severe/symptomatic aortic stenosis (decreased BP could decrease cardiac output and precipitate heart failure)
• Hypersensitivity

Side effects (NB Most are well-tolerated)

• Profound hypotension- Particularly on first doses (if this is the case, reduce dose and increase as required later)
• Renal Impairment
• Dry cough
• Hypersensitivity- angioedema (more common than most drugs; onset may be delayed; more common in Afro-Caribbeans); rash
• Pancreatitis
• URTIs e.g. sinusitis; rhinitis; sore throat
• GI- nausea, vomiting; dyspepsia; diarrhoea; constipation; abdominal pain; deranged LFTs; jaundice; hepatitis; fulminant hepatic necrosis; hepatic failure
• Hyperkalaemia; hypoglycaemia
• Thrombocytopenia; leucopenia; neutropenia; haemolytic anaemia
• Taste disturbance and skin rashes