Amlodipine dosing

STE ACS class lla recommendation and NSTE ACS class I recommendation for patients with ongoing ischemia who are already taking adequate doses of nitrates and P-blockers or in patients with contraindications to or intolerance to P-blockers (diltiazem or verapamil for STE ACS and diltiazem, verapamil, or amlodipine for NSTE ACS). 

As described in the previous section, calcium channel blockers should not be administered to most patients with ACS. Their role is a second-line treatment for patients with certain contraindications to P-blockers and those with continued ischemia despite P-blocker and nitrate therapy. Administration of either amlodipine, diltiazem, or verapamil is preferred.2 Agent selection is based on heart rate and left ventricular dysfunction (diltiazem and verapamil are contraindicated in patients with bradycardia, heart block, or systolic heart failure). Dosing and contraindications are described in Table 5-2. 

Q69 At therapeutic doses the occurrence of o negative inotropic effect v/ith omlodipine is rarely seen. Amlodipine has greater selectivity for vascular smooth muscle than for myocardium. 

Amlodipine is a calcium-channel blocker that blocks the intracellular movement of calcium ions and hence slows the contractility of the myocardium and relaxes the vascular smooth muscle. The negative inotropic effects are rarely seen at therapeutic doses since amlodipine has a greater selectivity for vascular smooth muscle than for the myocardium. 

Hypertension - Usual dose is 5 mg once daily. Maximum dose is 10 mg once daily. Small, fragile, or elderly patients or patients with hepatic insufficiency may be started on 2.5 mg once daily this dose may also be used when adding amlodipine to other antihypertensive therapy. In general, titrate over 7 to 14 days proceed more rapidly if clinically warranted with frequent assessment of the patient. 

Dihydropyridine-CA have been developed with a certain degree of vascular selectivity, which implies that at therapeutic doses such compounds would have less negative influence on cardiac contractile force or none at all. Indeed, a few of such compounds are devoid of cardiodepressant (negative inotropic) activity. Examples of such compounds are amlodipine, felodipine, isradip-ine, lacidipine, lercanidipine and manidipine. 

Dosage Dose should be individualized by titration 180 mg/d with upward titrations if adequate response is not obtained Dose should be individualized 5 mg/d with a maximum dose of 10 mg/d Dose should be individualized by titration 2.5 mg to 5 mg amlodipine and 10 mg to 20 mg of benazepril once daily... 

Mibefradil is a tetralol derivative developed as a unique CCB. Its efficacy as an antihypertensive was demonstrated in phase III trials, where doses of 50 to 100 mg were compared to other CCBs (nifedipine SR, diltiazem CD, nifedipine GITS, amlodipine). Mibefradil was shown to be equally effective as or more effective than nifedipine SR, diltiazem CD, nifedipine GITS, or amlodipine in reducing blood pressure in mild to moderate hypertension. Average reductions of diastolic blood pressure of as much as 15 mmHg were seen with the 100-mg dose. It was also found to be effective in the treatment of chronic stable angina. Thus, it was indicated for use in hypertension and stable angina at doses of 50 or 100 mg once daily (15). 

CALCIUM CHANNEL BLOCKERS CICLOSPORIN 1. Plasma concentrations of ciclosporin are t when co-administered with diltiazem, nicardipine, verapamil and possibly amlodipine and nisoldipine. However, calcium channel blockers seem to protect renal function 2. Ciclosporin t nifedipine levels 1. Uncertain presumed to be due to impaired hepatic metabolism. Also, diltiazem and verapamil inhibit intestinal P-gp, which may t the bioavailability of ciclosporin. Uncertain mechanism of renal protection 2. Uncertain effect of ciclosporin on nifedipine 1. Monitor ciclosporin levels and i dose accordingly (possibly by up to 25-50% with nicardipine) 2. Monitor BP closely and warn patients to watch for signs of nifedipine toxicity... 

Amlodipine has a t) (40 h) sufficient to permit the same benefits as the longest-acting formulations of rtifedipine without requiring a special formulation. Its slow association with L-channels and long duration of action render it unsuitable for emergency reduction of blood pressure where frequent dose adjustment is needed. On the other hand an occasional missed dose is of little consequence. Amlodipine differs from all other dihydropyridines listed in this chapter in being safe to use in patients with cardiac failure (the PRAISE Study). 

Hypertensive patients taking amlodipine, in contrast to glyceryl trinitrate, had only a minor supplementary fall in blood pressure when challenged with a single dose of sildenafil, and a few had a mild to moderate headache (46). 

Of the CCBs, the nondihydropyradines (verapamil and dilti-azem) are the most effective because they lower heart rate in addition to lowering blood pressure. Nifedipine, because of its strong vasodilator properties, tends to cause hypotension and reflex tachycardia. In addition, nifedipine causes peripheral edema. These characteristics make it less useful in DHR Amlodipine is also effective because it reduces blood pressure. Initial doses are verapamil 120 to 240 mg/day, diltiazem 90 to 120 mg/day, and amlodipine 2.5 mg/day. 

The half-life of nifedipine is 2 to 5 hours, making repeated dosing necessary. The duration of amlodipine is much longer (T /2 = 35 hours), and is administered once daily. 

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