Hypotension losartan

ANGIOTENSIN II RECEPTOR ANTAGONISTS IMATINIB t plasma concentrations of losartan, irbesartan and valsartan Imatinib is a potent inhibitor of CYP2C9 isoenzymes, which metabolize these angiotensin II receptor blockers Monitor for toxic effects of losartan, e.g. hypotension, hyperkalaemia, diarrhoea, cough, vertigo and liver toxicity... 

The safety profile of angiotensin II receptor antagonists is so far remarkably good. Except for hypotension, virtually no dose-related adverse effects have been reported. Headache, dizziness, weakness, and fatigue are the most common adverse effects. There have been reports of raised liver enzymes (9), cholestatic hepatitis (10), and pancreatitis (11) with losartan. Several cases of angio-edema have been reported but no other obvious hypersensitivity reactions. 

Losartan was evaluated in 406 patients with end-stage renal insufficiency undergoing hemodialysis (24). Only 15 patients discontinued losartan because of adverse effects. In seven the adverse reaction was hypotension. Two patients reported a possible anaphylactoid reaction on treatment with AN69 dialysis membranes. However, nine patients with a history of previous anaphylactoid reactions on treatment with AN69 have not shown this complication with losartan and AN69. 

ACE inhibitors prevent the conversion of angiotensin I to angiotensin II and lower blood pressure by decreasing both the formation of aldosterone formation and the vasoconstrictive action of AH at AT-1 receptors. ACEIs also inhibit the metabolism of bradykinin, and this leads to additional hypotensive effects, because bradykinin is an endogenous vasodilator. Unfortunately, increases in bradykinin are associated with side effects, including cough and angioedema. Losartan, which blocks AT-1 receptors, does not increase bradykinin levels. 

Losartan is mechanistically the most specific interrupter of the renin-angiotensin reaction sequence presently in use. Its clinical advantage resides in its once-a-day dosing (improved patient compliance) and its very gradual onset of action. The latter almost eliminates the hypotensive overshoot which is a common side effect during early treatment with most other agents. 

In 11 healthy subjects the pharmacokinetics and hypotensive effects of a single 50-mg dose of losartan and its active metabolite, E-3174, were not significantly affected by itraconazole 200 mg daily for 4 days. Inhibition of the cytochrome P450 isoenzyme CYP3A4 alone (caused by itraconazole) does not appear to prevent the conversion of losartan to E-3174. No special precautions would appear to be needed if these drugs are used con-eurrently. 

Symptomatic hypotension may occur when an angiotensin II receptor antagonist is started in patients taking high-dose diuretics. Potassium levels may be either increased, decreased or not affected. No clinically relevant pharmacokinetic interactions appear to occur between candesartan, eprosartan, irbesartan, losartan, telmisartan or valsartan and hydrochlorothiazide, although the bioavailability of hydrochlorothiazide may be modestly reduced. Similarly, there is no clinically significant pharmacokinetic interaction between valsartan and furosemide. 

Comparative studies In a double-blind comparison of losartan 50 and 150 mg/day in patients with heart failure, high-dose losartan had a beneficial effect on mortality and hospital admissions with heart failure [52 ]. However, hyperkalemia, hypotension, renal impairment, and angioedema were more common in the high-dose group. 

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