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| {{drugbox |
| | #REDIRECT [[Losartan#Pharmacology]] |
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| |image=Losartan_structure.png
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| |IUPAC_name = (1-((2'-(2''H''-tetrazol-5-yl)biphenyl-4-yl)methyl)-<br />2-butyl-4-chloro-1''H''-imidazol-5-yl)methanol
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| |CAS_number = 114798-26-4
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| | ATC_prefix = C09
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| | ATC_suffix = CA01
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| | PubChem = 3961
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| | DrugBank = APRD00052
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| | C=22 | H=23 | Cl=1 | N=6 | O=1
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| |molecular_weight = 422.91
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| |bioavailability = 25–35%
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| |metabolism = [[Hepatic]] ([[CYP2C9]], [[CYP3A4]])
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| |elimination_half-life = 1.5–2 hours
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| |excretion = [[Renal]] 13–25%, [[biliary]] 50–60%
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| |pregnancy_category = D (USA, Australia)
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| |legal_status = Rx-only
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| |routes_of_administration = Oral
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| }}
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| __NOTOC__
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| {{CMG}}
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| ==[[Losartan (patient information)|For patient information, click here]]==
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| ==Overview==
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| '''Losartan''' ([[International Nonproprietary Name|rINN]]) ({{pronEng|loʊˈsɑrtən}}) is an [[angiotensin II receptor antagonist]] drug used mainly to treat high blood pressure ([[hypertension]]). Losartan was the first angiotensin II receptor antagonist to be marketed. It is currently marketed by [[Merck & Co.]] under the trade name '''Cozaar'''.
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| ==Clinical use==
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| {{dablink|Main article: [[Angiotensin II receptor antagonist]]}}
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| As with all angiotensin II receptor antagonists, losartan is indicated for the treatment of hypertension. Losartan may also delay progression of [[diabetic nephropathy]] and is also indicated 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).<ref name="AMH2006">Rossi S, editor. [[Australian Medicines Handbook]] 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3</ref>
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| Although angiotensin II receptor antagonists are not usually considered first-line, because of the proven effectivity and lower costs of [[thiazide diuretic]]s and [[beta blockers]], losartan may be used first-line in patients with increased [[cardiovascular]] risk. The LIFE study demonstrated that losartan was significantly superior to [[atenolol]] in the primary prevention of adverse cardiovascular events ([[myocardial infarction]] or [[stroke]]), with a significant reduction in cardiovascular [[morbidity]] and [[death|mortality]] for a comparable reduction in blood pressure.<ref name="Dahlof2002">Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002;359(9311):995-1003. PMID 11937178</ref>
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| ===Combination with diuretic===
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| Losartan is available in a combination formulation with a low dose [[thiazide diuretic]], invariably [[hydrochlorothiazide]], to counteract the increase in [[renin]] and to achieve an additive antihypertensive effect. The losartan/hydrochlorothiazide combination preparation is marketed by Merck under the trade name '''Hyzaar'''.
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| ==Pharmacokinetics==
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| ===Absorption===
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| Losartan is well absorbed following oral administration.
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| ===Metabolism===
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| Losartan undergoes significant first-pass metabolism to produce 5-carboxylic acid metabolite, designated as EXP3174. This metabolite is long-acting (6 to 8 hr), noncompetitive antagonist at the AT1 receptor and contribute to the pharmacological effects of Losartan. It is 10-40 times more potent in blocking AT1 receptors than Losartan.
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| ===Bioavailability===
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| Losartan's [[bioavailability]] is about 32%.
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| ===Half life===
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| Losartan's half life is very short: i.e only 2 hrs.
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| ===Excretion===
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| Following oral administration, 6 % of Losartan is excreted unchanged in the urine.
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| ===Doses===
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| *Initial dose; 50mg/day
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| *Usual dose: 25-100 mg/day
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| ==Research==
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| Losartan has been found to downregulate the expression of [[transforming growth factor beta]] (TGF-β) types I and II receptors in the kidney of diabetic rats, which may partially account for its nephroprotective effects.<ref>Guo ZX, Qiu MC. [Losartan downregulates the expression of transforming growth factor beta type I and type II receptors in kidney of diabetic rat] Zhonghua Nei Ke Za Zhi 2003;42(6):403-8. PMID 12895325</ref> Effects on TGF-β expression may also account for its potential efficacy in [[Marfan syndrome]] and [[Duchenne muscular dystrophy]] (DMD) – losartan has been shown to prevent [[aortic aneurysm]] and certain pulmonary complications in a mouse model of the disease.<ref>Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome, and preserves muscle tissue architecture in DMD mouse models. Science 2006;312(5770):117-21. PMID 16601194</ref>
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| ==Mechanism of action & pharmacological actions==
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| Losartan is a selective, competitive [[Angiotensin II receptor type 1]] (AT<sub>1</sub>) receptor 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 stimulation of 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.
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| ==References==
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| [[Image:Cozaar.gif|thumb|Cozaar logo]]
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| {{Reflist}}
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| ==See also==
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| *[[Angiotensin II receptor antagonist]]
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| {{Angiotensin II receptor antagonists}}
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| [[Category:Angiotensin II receptor antagonists]]
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| [[Category:Drugs]]
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| [[de:Losartan]]
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| [[es:Losartan]]
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| [[hu:Lozartan]]
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| [[nl:Losartan]]
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| [[pl:Losartan]]
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| [[pt:Losartan]]
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