Nifedipine

Chemical Name 1,4-dihydro-2,6-dimethyl-4-(2 -nitrophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester 

2-Nitrobenzaldehyde Acetoacetic acid methyl ester Ammonia 

45 grams 2-nitrobenzaldehyde, 80 cc acetoacetic acid methyl ester, 75 cc methanol and 32 cc ammonia are heated under reflux for several hours, filtered off, cooled and, after 

Trade Name Manufacturer Country Year Introduced 

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Another important reaction of diketene derivatives is the Hant2sch pyridine synthesis (101). This synthesis is the preparation of 1,4-dihydropyridines (14) starting either from two acetoacetic esters, which react with an aldehyde and ammonia or a primary amine or from 3-aminocrotonates and 2-alkyhdene acetoacetic esters, both diketene derivatives. Several such dihydropyridines such as nifedipine [21829-25-4] (102), nimodipine [66085-59-4] and nicardipine [55985-32-5] exhibit interesting pharmaceutical activity as vasodilators (blood vessel dilation) and antihypertensives (see Cardiovascularagents). 

Na+ K+ Ga + TTX, DDT, veratridine, scorpion toxins, procaine, Hdocaine quinidine, tolbutamide, diazoxide, glyburide, minoxidil nifedipine, diltiazem, verapamil, moUusc and spider toxins ... 

The side effects of diltia2em therapy are less than those of verapamil or nifedipine therapy. Side effects occur in about 4% of the patients (1,98,99). 

Po adrninistered nifedipine is almost completely absorbed. The onset of action is 20 min and peak effects occur at 1—2 h. The principal route of elimination is through hepatic metaboHsm by oxidation to hydroxycarboxyHc acid and the corresponding lactone. These metaboHtes are pharmacologically inactive. Almost 70—80% of dmg is eliminated in the urine during the first 24 h. About 15% is excreted in the feces. The elimination half-life of nifedipine is about 1—2.5 h (1,98,99). Frequency of occurrence of side effects in patients is about 17% with about 5% requiring discontinuation of therapy (1,98,99). 

Calcium Channel Blockers. Because accumulation of calcium is one of the facets of the mote involved process leading to atherosclerosis, it would foUow that the antihypertensive calcium channel blockers might be effective in preventing atheroma. Both verapamil (Table 1) and nifedipine (Table 3) have been shown to stimulate the low density Upoprotein (LDL) receptor (159). This specific receptor-mediated pathway could theoretically improve Upid metaboUsm in the arterial wall, and thereby prove antiatherogenic. These effects have been proven in animals. 

In addition to the vascular effects, calcium channel blockers (Table 6) such as isradipine, nifedipine (Table 3), and nitrendipine, produce natriuretic... 

Nifedipine, verapamil, and diltiazem are all efficacious in the treatment of mild and moderate hypertension, but nifedipine is more efficacious than diltiazem and verapamil in the control of severe hypertension. Nifedipine does not cause significant reflex tachycardia or orthostatic hypotension. Nifedipine benefits the older and black patients and patients with low PRA. 

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. 

Diltiazem inhibits calcium influx via voltage-operated channels and therefore decreases intracellular calcium ion. This decreases smooth muscle tone. Diltiazem dilates both large and small arteries and also inhibits a-adrenoceptor activated calcium influx. It differs from verapamil and nifedipine by its use dependence. In order for the blockade to occur, the channels must be in the activated state. Diltiazem has no significant affinity for calmodulin. The side effects are headache, edema, 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). 

FIGURE 17.25 The structures of nifedipine and ryanodine. Nifedipine binds with high affinity to the Ca" -release channels of t-tubules. Ryanodine binds with high affinity to the Ca" channels of SR terminal cisternae. 

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-... 

Nicarpi dine 2 150 Nicergoline 2, 478 Niclosamide , 94 Nicotinic acid 1, 253 Nicordanil 3, lT8 Nicotinyl aTcohol 253 Nidroxyzone 1, 228 Nifedipine 283 Nifenazone 1, 234 Nifluminic acid 1, 256 Nifuratrone 2, 2T8 Nifurdazil 2, 239 Nifurmide 239... 

Acetoacetic acid methyl ester Nifedipine Acetoacetic ester Dipyridamole Acetoin... 

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