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Losartan, sold under the trade name Cozaar among others, is a medication mainly used to treat high blood pressure.
Common side effects include muscle cramps, stuffy nose, cough, and high blood potassium.
Losartan was approved for medical use in the United States in 1995.
1 Medical uses
2 Adverse effects
3 Mechanism of action
8 External links
As with all angiotensin II type 1 receptor (AT 1 ) antagonists, losartan is used to treat hypertension. It may also delay progression of diabetic nephropathy and is associated with a positive clinical outcome in that regard. It is a suitable pharmacological agent for the reduction of renal disease progression in patients with type 2 diabetes, hypertension, and microalbuminuria (>30 mg/24 hours) or proteinuria (>900 mg/24 hours).
Although evidence shows calcium channel blockers and thiazide-type diuretics are preferred first-line treatments for most people (due to both efficacy
In January 2014, the FDA issued a black box warning that losartan can cause fetal toxicity, and should be discontinued as soon as pregnancy is detected.
The most common side effects for losartan are upper respiratory infections or stuffy nose, dizziness, and back pain.
More serious side effects include low blood pressure and allergic reaction.
Losartan should not be taken by people who are diabetic and taking aliskiren.
Mechanism of action
Losartan is a selective, competitive angiotensin II receptor type 1 (AT 1 ) antagonist, reducing the end organ responses to angiotensin II. Losartan administration results in a decrease in total peripheral resistance (afterload) and cardiac venous return (preload). All of the physiological effects of angiotensin II, including release of aldosterone, are antagonized in the presence of losartan. Reduction in blood pressure occurs independently of the status of the renin–angiotensin system. As a result of losartan dosing, plasma renin activity increases due to removal of the angiotensin II feedback.
Losartan is a uricosuric. As a specific inhibitor of the urate transporter 1 ( SLC22A12, URAT1), losartan blocks the uptake of uric acid into cells, thus leaving more available in the bloodstream to be filtered and excreted by the kidneys.
Losartan is well absorbed following oral administration and undergoes significant first-pass metabolism to produce the 5- carboxylic acid metabolite, designated as EXP3174. About 14% of an oral dosage is converted to this metabolite, which is long-acting (6 to 8 hr) and a noncompetitive antagonist at the AT 1 receptor, contributing to the pharmacological effects of losartan. EXP3174 is 10-40 times more potent in blocking AT 1 receptors than losartan. In addition, the binding to the target enzyme is pH-sensitive, and the negatively-charged tetrazole ring, which is similar in size to the negative carboxylic acid derivative, may contribute to the activity of the drug.
Losartan’s bioavailability is about 32%.
Metabolism is primarily by cytochrome P450 isoenzymes CYP2C9 and CYP3A4. Peak plasma concentrations of losartan and EXP3174 occur about one hour and three to four hours, respectively, after an oral dose. Both losartan and EXP3174 are more than 98% bound to plasma proteins. Losartan is excreted in the urine, and in the feces via bile, as unchanged drug and metabolites. About 4% of an oral dose is excreted unchanged in urine, and about 6% is excreted in urine as the active metabolite. The terminal elimination half lives of losartan and EXP3174 are about 1.5 to 2.5 hours and 3 to 9 hours, respectively.
Losartan and other angiotensin-receptor antagonists exhibit fetal toxicity and should be avoided during pregnancy, particularly in the second and third trimesters.
Losartan is generally marketed as the (basic) potassium salt of the aromatized negatively charged tetrazole, called “losartan potassium.”
Discovery and development of angiotensin receptor blockers
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