Mechanism of Action:
Angiotensin II subtype 1 (AT1) receptor antagonist (angiotensin II receptors are limited in adults). This class of drugs is often loosely described as ARBs (angiotensin receptor blockers). Indications are mostly the same as for ACE inhibitors (see Ramipril).
- Heart failure
- Prophylaxis after myocardial infarction
- Proteinuric renal disease, including diabetic nephropathy
- Microalbuminuria caused by diabetes
Angiotensin II, a potent vasoconstrictor, is part of the renin-angiotensin system, which controls blood pressure. Angiotensin III, a metabolite of Angiotensin II, stimulates aldosterone secretion from the adrenal cortex, which increases salt and water reabsorption from the kidney. This serves to increase extracellular fluid volume and so increase preload and cardiac output. (BP = CO x SVR) Therefore, angiotensin II directly and indirectly raises blood pressure and cardiac load. Losartan inhibits angiotensin II from binding to its receptor, thereby preventing it from exerting most of its effects.
Lecture and CAL materials:
- Lecture: Drugs used in the treatment of hypertension
- Angiotensin (edren textbook) has concise further info on renal effects
|Alternative drug name||not specified|
|Effects||Losartan blocks the effects of angiotensin II (vasoconstriction, aldosterone release). It is used to treat both hypertension and heart failure. Drugs in this class have been shown conclusively in randomized controlled trials in heart failure to improve outcome and reduce cardiovascular events. They are also of proven benefit in improving renal outcomes in proteinuric renal disease, including diabetic nephropathy.|
|Adverse actions||Normally mild side effects. Dizziness due to hypotension, especially in patients who have other risk factors (eg taking high-dose diuretics.) Occasionally, hyperkalaemia and angioedema. There is increased risk of AKI while taking these and similar drugs.|
|Dose||25-100 mg oral od.|
|Interactions||The most important interactions are with other drugs that tend to elevate potassium such as potassium sparing diuretics (eg spironolactone), ACE inhibitors (rarely used in combination), and potassium. There is a pharmacodynamic interaction with other drugs that lower blood pressure.|
Other Angiotensin II receptor antagonists include candesartan, irbesartan and valsartan. Angiotensin II receptor antagonists are similar in clinical effects to ACE inhibitors such as ramipril, which prevent the conversion of Angiotensin I to Angiotensin II. However, angiotensin II receptor antagonists have fewer side effects like dry cough because they do not inhibit the breakdown of bradykinin (inflammatory mediator) in the bronchial mucosa. This also means that they may be less effective vasodilators than ACE inhibitors.
They are commonly prescribed to patients who are unable to tolerate ACE inhibitors due to cough (10-20%). ARBs and ACE inhibitors should be avoided in patients with bilateral renal artery stenosis because they worsen renal function because of insufficient renal arterial pressure (heavily dependent on RAS activation) for glomerular filtration.
|Contributors||Updated by Neil Turner Nov 2016|