Describe ACE inhibitors and angiotensin receptor blockers with their uses and adverse effects.

Renin–angiotensin–aldosterone System

Reduced renal perfusion, low sodium or sympathetic (beta1) stimulation → renin released from juxtaglomerular cells → Renin converts angiotensinogen → angiotensin I → angiotensin converting enzyme (ACE), chiefly in the lung, converts it to angiotensin II → Angiotensin II → vasoconstriction (AT1), aldosterone release, thirst, ADH release, sympathetic facilitation, and cardiac and vascular remodelling → ACE also degrades bradykinin — which is why inhibiting it raises bradykinin and causes cough and angio-oedema

ACE Inhibitors and Arbs Compared

Uses

• Hypertension — particularly in the young, in diabetics and in chronic kidney disease
• Cardiac failure — improve symptoms and survival, and limit ventricular remodelling
• After myocardial infarction, especially with left ventricular dysfunction
• Diabetic nephropathy and proteinuric renal disease — they dilate the efferent arteriole, lowering intraglomerular pressure and reducing proteinuria; this is renoprotection beyond the fall in blood pressure
• Scleroderma renal crisis — captopril is specifically effective

Adverse Effects and Cautions

• Dry cough — the commonest reason for stopping an ACE inhibitor
• Hyperkalaemia — aldosterone falls; dangerous with potassium-sparing diuretics, potassium supplements, NSAIDs or renal impairment
• First-dose hypotension, particularly in volume-depleted patients on diuretics; the first dose is small and given at bedtime
• Renal impairment — a small rise in creatinine is expected and acceptable; a large rise suggests bilateral renal artery stenosis, in which these drugs precipitate acute renal failure by removing the efferent constriction that maintains filtration
• Teratogenicity — renal dysgenesis, oligohydramnios, skull hypoplasia and fetal death; absolutely contraindicated in pregnancy
• Angio-oedema — may involve the tongue and larynx; the drug must never be given again, and the whole class avoided

Applied Aspects

• Check creatinine and potassium before starting and 1 to 2 weeks after, and after every dose increase
• A rise in creatinine of up to about 30% is acceptable and reflects the intended haemodynamic effect; a greater rise requires investigation, not automatic withdrawal
• Withhold during acute illness with dehydration — diarrhoea, vomiting or sepsis — since the combination with an NSAID and a diuretic (the "triple whammy") is a well-recognised cause of acute kidney injury
• Ask every woman of childbearing age about pregnancy and counsel on contraception before prescribing
• Switch to an ARB for cough, not to a different ACE inhibitor — the cough is a class effect
• Do not combine an ACE inhibitor with an ARB; trials showed more hyperkalaemia, hypotension and renal impairment with no additional benefit