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Transcript
Losartar
Losartar
Systematic (IUPAC) name
(2-butyl-4-chloro-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazol-5-yl)methanol
Chemical data
Formula
Mol. mass
C22H23ClN6O
422.91
Pharmacokinetic data
Bioavailability
Metabolism
Half-life
Excretion
25–35%
Hepatic (CYP2C9, CYP3A4)
1.5–2 hours
Renal 13–25%, biliary 50–60%
Therapeutic considerations
Pregnancy cat.
Legal status
Routes
D(AU) D(US)
℞ Prescription only
Oral
Losartar is an angiotensin II receptor antagonist drug used mainly to treat high blood
pressure (hypertension). Losartar was the first angiotensin II receptor antagonist to be
marketed.

Clinical use
As with all angiotensin II type 1 receptor (AT1) antagonists, Losartar is indicated for the
treatment of hypertension. Losartar 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).
Although angiotensin II receptor antagonists are not usually considered first-line,
because of the proven efficacy and lower costs of thiazide diuretics and beta blockers,
Losartar may be used first-line in patients with increased cardiovascular risk. The LIFE
study demonstrated that Losartar 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 mortality for a comparable
reduction in blood pressure
Dosage Range
Combination with diuretic
Losartar is available in a combination formulation with a low dose thiazide diuretic to
achieve an additive antihypertensive effect.
Pharmacokinetics
Losartar is well absorbed following oral administration and undergoes significant firstpass metabolism to produce 5-carboxylic acid metabolite, designated as EXP3174. This
metabolite is a long-acting (6 to 8 hr), noncompetitive antagonist at the AT1 receptor
and contributes to the pharmacological effects of Losartar. This metabolite is 10-40
times more potent in blocking AT1 receptors than the original Losartar. Its bioavailability
is about 32%.
Research
Losartar 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.[4] Effects on TGF-β expression may also
account for its potential efficacy in Marfan syndrome and Duchenne muscular dystrophy
(DMD) – Losartar has been shown to prevent aortic aneurysm and certain pulmonary
complications in a mouse model of the disease
Losartar is being studied for use in the treatment of the 20% of breast cancer tumors
positive for AGTR1. The University of Michigan Comprehensive Cancer Center has
announced the result of an animal study which found Losartar to "block" - reverse
neoplastic changes - caused by this gene.
Mechanism of action & pharmacological actions
Losartar is a selective, competitive Angiotensin II receptor type 1 (AT1) receptor
antagonist, reducing the end organ responses to angiotensin II. Losartar 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 Losartar. Reduction in blood
pressure occurs independently of the status of the renin-angiotensin system. As a result
of Losartar dosing, plasma renin activity increases due to removal of the angiotensin II
feedback.
Other uses
Losartar is an uricosuric. Because Losartar can cause hyperkalemia, potassium
supplements or salt substitutes containing potassium should not be used without
consulting the prescribing physician.
Losartar is being researched as a possible drug for marked slowing of aortic
enlargement in Marfan and related syndromes.