Pharmacology: Mechanism of Action: Amlodipine is a calcium entry blocker of the dihydropyridine class and produces marked vasodilation in peripheral and coronary vascular beds with minimal effect on the sinoatrial and atrioventricular nodes or on cardiac contractility. Amlodipine has a sustained but gradual onset of action and has substantial antihypertensive and antianginal efficacy, when administered as a once-daily regimen. It is well tolerated in patients with essential hypertension or angina pectoris and some of the undesirable effects of postural hypotension, sinus node suppression, impaired atrioventricular conduction and cardiac function do not appear to occur, while reflex tachycardia occurs only infrequently. It offers an effective alternative to other antihypertensive and antianginal agents with certain pharmacokinetic, pharmacodynamic and tolerability properties that should be advantageous in many patients with cardiovascular disease.
Pharmacodynamics: Amlodipine inhibits the slow channel influx of calcium into cardiac vascular tissue producing peripheral and coronary vasodilation. In patients with mild to moderate essential hypertension, amlodipine has a sustained and gradual onset of action. Medium term once-daily dosage of 2.5-10 mg produces 10-18% reduction in systolic and diastolic blood pressure, increase renal blood flow, glomerular filtration rate and reduces renovascular resistance. Plasma renin activity, aldosterone and catecholamine levels are not significantly affected. Urine volume and urinary sodium excretion are unchanged suggesting that amlodipine has no long-term effect on sodium homeostasis.
Amlodipine has no significant cardiodepressant activity and it markedly reduces peripheral vascular resistance and therefore afterload, increases myocardial oxygen supply, reduces demand and improves exercise capacity in patients with symptomatic myocardial ischaemia. It also has cardioprotective effect.
Pharmacokinetics: After oral administration, amlodipine is slowly and almost completely absorbed. Peak plasma concentrations are attained within 6-12 hrs. It has a relatively high oral availability of 60-65% which is not influenced by food. Amlodipine appears to have a linear pharmacokinetic profile. Steady-state plasma concentrations are achieved after 7 once-daily oral doses. It has a large volume of distribution of 21 L/kg and is >95% bound to plasma proteins. It is extensively and slowly metabolized by the liver. None of the metabolites have pharmacological activity.
Amlodipine has a relatively long elimination t½ of 35-50 hrs permitting once daily administration. Ten percent of the dose is excreted unchanged, 60% is recovered in urine and 20-25% in the feces.
In patients with hepatic cirrhosis and in the elderly, amlodipine elimination is significantly reduced and dosage adjustment should be made accordingly. The pharmacokinetic profile is not altered with renal impairment.
Treatment of hypertension and prophylaxis of angina pectoris.
Amlodipine should be initiated at a dosage of 5 mg once daily orally and increased to 10 mg once daily if the desired therapeutic response has not been achieved after 2 weeks.
Therapeutic Efficacy: In patients with chronic stable angina, it improves both subjective and objective symptoms. It also improves subjective symptoms in vasospastic angina.
Amlodipine in oral regimens of 2.5, 5 and 10 mg once daily significantly reduces supine and standing systolic and diastolic blood pressure in a dose-dependent manner in patients with essential hypertension. Amlodipine 5-10 mg once daily also significantly reduces mean ambulatory blood pressure throughout a 24-hr dose interval in hypertensive patients. These antihypertensive effect are achieved without reflex tachycardia or postural hypotension.
Children: Not recommended.
Elderly: It would be clinically prudent to initiate treatment with the lowest recommended dosage and titrate upwards to achieve the desired response.
Use in Hepatic Cirrhosis: Use with caution.
Use in Renal Impairment: Normal dosage.
Known hypersensitivity to dihydropyridines.
Use in pregnancy & lactation: Amlodac should not be administered during pregnancy or lactation or to women of childbearing potential unless effective contraception is used.
Amlodipine is generally well tolerated. The main side effects, edema and flushing, occur as a result of vasodilation but are usually mild or moderate in severity. Other adverse effects reported occasionally include muscle cramps, frequency of micturition/nocturia, coughing, impotence, asthma, epistaxis, nervousness and conjunctivitis.
No effect in digoxin's pharmacokinetics. Cimetidine does not alter the kinetic profile of amlodipine and no interaction occurs between amlodipine and nitroglycerin.
Store at temperatures not exceeding 30°C. Protect from light and moisture.
C08CA01 - amlodipine ; Belongs to the class of dihydropyridine derivative selective calcium-channel blockers with mainly vascular effects. Used in the treatment of cardiovascular diseases.
FC tab 5 mg x 100's. 10 mg x 100's.