Angiotensin-II Receptor Antagonist

The class of drugs called angiotensin receptor blockers (ARBs), as the class name suggests, are drugs that block the action of angiotensin. Specifically, ARBs prevent angiotensin II from binding to the angiotensin II receptor on blood vessels and other tissues. Angiotensin II is a very potent chemical that causes the muscles surrounding blood vessels to contract, thereby narrowing the blood vessels. Narrowing of blood vessels increases the pressure within the blood vessels and may lead to high blood pressure (hypertension). Reducing the binding and activity of angiotensin II leads to widening (dilation) of blood vessels and reduces blood pressure. ARBs are used alone or in combination with other drugs for controlling high blood pressure. They also are used for treating congestive heart failure, preventing diabetes or high blood pressure-related kidney failure, and reducing the risk of stroke in patients with hypertension and an enlarged heart. ARBs also may prevent the recurrence of atrial fibrillation. Since ARBs have effects that are similar to those of ACE inhibitors, they are often used when ACE inhibitors are not tolerated by patients because of side effects. ARBs are similar in action and side effects. They differ in how they are eliminated from the body and the extent to which they are distributed throughout the body. Some ARBs are converted to an active form in the body before they can exert their effects.Some ARBs are slightly better at reducing blood pressure than others; in some studies, irbesartan and candesartan were slightly more effective in reducing blood pressure than losartan.All ARBs usually are administered once daily for treatment of hypertension. Some patients may benefit from twice daily dosing of losartan if blood pressure is not controlled with once daily dosing. Common side effects include dizziness, headache, drowsiness, nausea, vomiting, diarrhea, cough, elevated potassium levels, low blood pressure, muscle or bone pain, and rash.ARBs cause cough less frequently than ACE inhibitors. Therefore, they are often substituted for ACE inhibitors when patients complain of cough with ACE inhibitors. Like other antihypertensives, ARBs are associated with sexual dysfunction.

CANDESARTAN:

Indications: hypertension; heart failure with impaired left ventricular systolic function in conjunction with an ACE inhibitor, or when ACE inhibitors are not tolerated.

Contraindications: Angiotensin-II receptor antagonists should be avoided in pregnancy.

Dose and Administration:

Hypertension, initially 8 mg (hepatic impairment 2 mg, renal impairment or intravascular volume depletion 4 mg) once daily, increased if necessary at intervals of 4 weeks to max. 32 mg once daily; usual maintenance dose 8 mg once daily

Heart failure, initially 4 mg once daily, increased at intervals of at least 2 weeks to ‘target’ dose of 32 mg once daily or to max. tolerated dose.

IRBESARTAN:

Indications: treatment of hypertension and treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (> 300 mg/day) in patients with type 2 diabetes and hypertension.

Contraindications: Angiotensin-II receptor antagonists should be avoided in pregnancy.

Dose and Administration:

Hypertension, initially 150 mg once daily, increased if necessary to 300 mg once daily (in haemodialysis or in elderly over 75 years, initial dose of 75 mg once daily may be used); child not recommended

Renal disease in hypertensive type 2 diabetes mellitus, initially 150 mg once daily, increased to 300 mg once daily if tolerated (in haemodialysis or in elderly over 75 years, consider initial dose of 75 mg once daily); child not recommended.

EPROSARTAN:

Indications: treatment of hypertension. It may be used alone or in combination with other anti hypertensives such as diuretics and calcium channel blockers.

Contraindications: Angiotensin-II receptor antagonists should be avoided in pregnancy.

Dose and Administration: 600 mg once daily (elderly over 75 years, mild to moderate hepatic impairment, renal impairment, initially 300 mg once daily); if necessary increased after 2–3 weeks to 800 mg once daily.

LOSARTAN:

Indications: hypertension (including reduction of stroke risk in hypertension with left ventricular hypertrophy); diabetic nephropathy in type 2 diabetes mellitus.

Contraindications: Angiotensin-II receptor antagonists should be avoided in pregnancy.

Dose and Administration: Usually 50 mg once daily (intravascular volume depletion, initially 25 mg once daily); if necessary increased after several weeks to 100 mg once daily; elderly over 75 years initially 25 mg daily. Pediatric Hypertensive Patients ≥ 6 years of age: The usual recommended starting dose is 0.7 mg/kg once daily (up to 50 mg total) administered as a tablet or a suspension Dosage should be adjusted according to blood pressure response. Doses above 1.4 mg/kg (or in excess of 100 mg) daily have not been studied in pediatric patients.

VALSARTAN:

Indications: hypertension; myocardial infarction with left ventricular failure or left ventricular systolic dysfunction.

Contraindications: Angiotensin-II receptor antagonists should be avoided in pregnancy.

Dose and Administration: Hypertension, usually 80 mg once daily (initially 40 mg once daily in intravascular volume depletion); if necessary increased at intervals of 4 weeks up to max. 320 mg daily; elderly over 75 years, initially 40 mg once daily. Myocardial infarction, initially 20 mg twice daily increased over several weeks to 160 mg twice daily if tolerated.

OLMESARTAN:

Indications: treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.

Contraindications: Angiotensin-II receptor antagonists should be avoided in pregnancy.

Dose and Administration: Dosage must be individualized. The usual recommended starting dose of Benicar is 20 mg once daily when used as monotherapy in patients who are not volume-contracted. For patients requiring further reduction in blood pressure after 2 weeks of therapy, the dose of Benicar may be increased to 40 mg.

TELMISARTAN:

Indications: treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.

Contraindications: Angiotensin-II receptor antagonists should be avoided in pregnancy.

Dose and Administration: Usually 40 mg once daily (but 20 mg may be sufficient), increased if necessary after at least 4 weeks, to max. 80 mg once daily.

Candesartan-Hydrochlorothiazide:

Indications: indicated for the treatment of hypertension. This fixed dose combination is not indicated for initial therapy.

Contraindications: Angiotensin-II receptor antagonists should be avoided in pregnancy and in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

Dose and Administration: The usual recommended starting dose of candesartan cilexetil is 16 mg once daily; Hydrochlorothiazide is effective in doses of 12.5mg once daily.

Irbesartan-Hydrochlorothiazide:

Indications: treatment of hypertension. may be used in patients whose blood pressure is not adequately controlled on monotherapy. also be used as initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals.

Contraindications: Angiotensin-II receptor antagonists should be avoided in pregnancy and in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

Dose and Administration: In patients not controlled on monotherapy with irbesartan the recommended doses, in order of increasing mean effect, are (irbesartan-hydrochlorothiazide) 150/12.5 mg, 300/12.5 mg, and 300/25 mg. The largest incremental effect will likely be in the transition from monotherapy to 150/12.5 mg

Eprosartan-Hydrochlorothiazide:

Indications: treatment of hypertension. It may be used alone or in combination with other anti hypertensives such as calcium channel blockers.

Contraindications: Angiotensin-II receptor antagonists should be avoided in pregnancy and in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

Dose and Administration: The usual recommended dose is 600 mg/12.5 mg once daily when used as combination therapy in patients who are not volume-depleted

Losartan-Hydrochlorothiazide:

Indications: treatment of hypertension. This fixed dose combination is not indicated for initial therapy of hypertension also indicated to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy.

Contraindications: Angiotensin-II receptor antagonists should be avoided in pregnancy and in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

Dose and Administration: A patient, whose blood pressure is not adequately controlled with losartan monotherapy, may be switched to losartan 50 mg/hydrochlorothiazide 12.5 mg once daily. If blood pressure remains uncontrolled after about 3 weeks of therapy, the dose may be increased to one tablet of losartan 100 mg/hydrochlorothiazide 25 mg once daily.

Valsartan-Hydrochlorothiazide:

Indications: indicated for the treatment of hypertension in patients whose blood pressure is not adequately controlled on monotherapy. It may be used as initial therapy in patients who are likely to need multiple drugs to achieve blood pressure goals.

Contraindications: Angiotensin-II receptor antagonists should be avoided in pregnancy and in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

Dose and Administration: Dose once daily. Maximum antihypertensive effects are attained within 2 to 4 weeks after a change in dose.

Olmesartan-Hydrochlorothiazide:

Indications: indicated for the treatment of hypertension. This fixed dose combination is not indicated for initial therapy.

Contraindications: Angiotensin-II receptor antagonists should be avoided in pregnancy and in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

Dose and Administration: Dosing should be individualized. Depending on the blood pressure response, the dose may be titrated at intervals of 2-4 weeks.

Telmisartan-Hydrochlorothiazide:

Indications: indicated for the treatment of hypertension. This fixed dose combination is not indicated for initial therapy.

Contraindications: Angiotensin-II receptor antagonists should be avoided in pregnancy and in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

Dose and Administration: A patient whose blood pressure is not adequately controlled with telmisartan monotherapy 80 mg may be switched to telmisartan 80 mg/hydrochlorothiazide 12.5 mg once daily.