Nifedipine, hypertension, angina

Stason WT3, Schmid CH, Niedzwiecki D, et al. Safety of nifedipine in angina pectoris a meta-analysis. Hypertension. 1999 3 3 (1) 24—31. 

Several reports have linked renal dysfunction with nifedipine. In a study of hypertensive diabetics with renal insufficiency, nifedipine increased proteinuria and worsened renal function (SEDA-16, 196). Others have reported mild reversible renal impairment in patients with chronic renal insufficiency taking nifedipine for angina or hypertension a biopsy in one of the patients, who had heavy proteinuria, showed focal and segmental glomerulosclerosis (30). Immune-complex nephritis was reported in a patient taking nifedipine, but the proteinuria persisted (and indeed worsened) on changing to verapamil (31). 

Nifedipine (Table 3) is a potent vasodilator that selectively dilates resistance vessels and has fewer effects on venous vessels. It does not cause reflex tachycardia during chronic therapy. Nifedipine is one of the first-line choices for black or elderly patients and patients having concomitant angina pectoris, diabetes, or peripheral vascular diseases. Nifedipine, sublingually, is also suitable for the treatment of hypertensive emergencies. Nifedipine does not impair sexual function or worsen blood Hpid profile. The side effects are flushing, headache, and dizziness. 

Procardia XL. Procardia XL extended-release capsules, marketed by Pfizer Labs Division of Pfizer, Inc., contain nifedipine [21829-25-4] a calcium channel blocker of mol wt 346.3. The extended release tablet is formulated as a once-a-day controlled release capsule for oral adrninistration dehvering either 30, 60, or 90 mg nifedipine. Procardia XL is indicated for use in the management of vasospastic angina, chronic stable angina, and hypertension (see Cardiovascularagents). 

The so-called calcium channel blockers constitute a class of cardiovascular agents that have gained prominence in the past few years. These drugs, which obtund contraction of arterial vessels by preventing the movement of calcium ions needed for those contractions, have proved especially useful in the treatment of angina and hypertension. Dihydropyridines such as nifedipine (30) are par-... 

Amlodipine and nifedipine are dihydropyridine calcium-channel blockers. Amlodipine differs from nifedipine in that it has a longer duration of action and can therefore be given once daily, unlike nifedipine. Both are indicated in hypertension and angina and tend to cause ankle oedema that does not respond to diuretic therapy. Neither amlodipine nor nifedipine are available as spray formulations. 

Nifedipine is used for preventing and relieving angina pectoris attacks, for hypertension, and as an ingredient in combination therapy for chronic cardiac insufficiency. Synonyms of this drug are adalat, corinfar, procardia, and nifecor. 

As mentioned before, nifedipine was the first marketed dihydropyridine CCB. Initially, the drug indication was exclusively for angina, but the more recently developed extended release (ER) formulations are used off-label primarily for hypertension (Bayer, 2004). The extended-release tablets use a cellulose coat that extends their release time. The half-life of the ER formulation is reported as 7 h, whereas the immediate-release formulation has a half-life of 2 h (Bayer). 

Step, aldol condensation to form the benzylidene derivative (12-3). Conjugate addition of a second mole of acetoacetate would then afford the 1,5-diketone (12-4). Reaction of the carbonyl groups with ammonia will lead to the formation of the dihydropyridine ring. Alternatively, acetoacetate may go on to form the imine (12-5) reaction of this with the aldol product (13-3) will give the same dihydropyridine. The product, nifedipine (12-6) [13], has been used extensively for the treatment of angina and hypertension. 

Nifedipine is a dihydropyridine calcium channel modulator, often used in the treatment of hypertension and angina. CYP3A4, with a minor contribution from CYP3A5, is the principal enzyme involved in the metabolism of nifedipine (81). Smith et al. examined the effect of St. John s wort (900mg/day... 

Nifedipine 45-70 4 Angina, hypertension, Raynaud s phenomenon 3-10 mcg/kg IV 20-40 mg orally every 8 hours... 

In addition to angina, calcium channel blockers have well-documented efficacy in hypertension (see Chapter 11) and supraventricular tachyarrhythmias (see Chapter 14). They also show moderate efficacy in a variety of other conditions, including hypertrophic cardiomyopathy, migraine, and Raynaud s phenomenon. Nifedipine has some efficacy in preterm labor but is more toxic and not as effective as atosiban, an investigational oxytocin antagonist (see Chapter 17). 

Nifedipine (a dihydropyridine) Block of vascular L-type calcium channels > cardiac channels Like verapamil and diltiazem less cardiac effect Prophylaxis of angina, hypertension Oral, duration 4-6 h Toxicity Excessive hypotension Interactions Additive with other vasodilators... 

The calcium ion antagonists nifedipine 21829-25A] (62), verapamil [52-55-9] (63), and flunarizine [52468-60-7] (64) exhibit antitussive effects in a dose-dependent manner in guinea pigs (91). Pretreatment with a subthreshold dose of nifedipine also markedly increased the antitussive effects of morphine, dihydrocodeine, and dextromethorphan. However, none of the calcium ion antagonists are used clinically as antitussive agents. They are used in the treatment of angina and hypertension (see Cardiovascularagents). 

There has been some concern about the safety of the calcium channel blockers. In particular, reports indicated that certain calcium channel blockers, such as the short-acting form of nifedipine, may be associated with an increased risk of myocardial infarction in certain patients (older patients with hypertension, patients with unstable angina).21,29... 

Nitrendipine 14.4 Investigational for angina, hypertension 20 mg orally once or twice daily Probably similar to nifedipine... 

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). 

Nifedipine (Fig. 7.1) is the lead compound which was first introduced for the treatment of coronary angina. However, its use in the treatment of hypertension was blunted by a short plasma half-life (in the range of 1.5-2 h) this led to the need for multiple daily administration, and consequently blood pressure control and patient compliance were not fully achieved. However, slow-release formulations - for example, the once-daily Nifedipine Oros - made possible the wide use of nifedipine in cardiovascular therapy. 

In conclusion, all dihydropyridines show a potent calcium channel antagonist activity, which is in turn translated into direct arteriolar spasmolytic effect that results in a beneficial vasodilatory activity. This is useful in some cardiovascular diseases, such as hypertension and angina, in which the peripheral resistances are raised due to increased calcium entry into the cells. Many analogues of nifedipine have been synthesized and introduced into the market, and each of these presents some common features and some peculiar differences. In particular ... 

In the past, the difficulties presented in the administration of drugs in the treatment of hypertensive emergencies were largely overcome with the use of nifedipine administered sublingually. The onset of action was rapid, and the drug was also used sublingually for the treatment of acute attacks of angina pectoris. Presently, two types of formulation of nifedipine are available, both intended primarily for peroral administration. The sustained-release formulation is... 

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