Nifedipine pharmacology

Thomason JM, ElUs JS, Kelly PJ, Se3nnour Nifedipine pharmacological variables as risk factors for gingival overgro in organ-transplant patients. Clin OralInvestig( 991) 1,35-9. 

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). 

The effects of the prototypical calcium channel blockers are seen most prominently in the cardiovascular system (Table 19.1), although calcium channels are widely distributed among excitable cells. The following calcium channel-blocking drugs are clinically the most widely used compounds in this very extensive class of pharmacological agents amlodipine, diltiazem, isradipine, nifedipine, nicardipine, nimodipine, and verapamil. 

SOOl 2 Molina Cuevas, V., M.L. Arruzazabala, D. Carbajal Quintana, R. Mas Ferreiro, and S. Valdes Garcia. Effect of policosanol on arterial blood pressure in rats. Study of the pharmacological interaction with nifedipine and propranolol. Arch Med Res 1998 29(1) 21-24. 

If a patient s blood pressure is greatly increased, pharmacological treatment should be instituted. Treatments for MAOI-induced hypertension include administration of the calcium channel blocker nifedipine and use of drugs with a-adrenergic-blocking properties, such as phentolamine (5 mg intravenous). Because treatment with phentolamine may be associated with cardiac arrhythmias or severe hypotension, this approach should be carried out only in an emergency department setting. 

Application of part of the classical Hantzsch pyridine synthesis leads to nifedipine (87) (81 AG(E)762, 68SAP6801482), a calcium antagonist useful in the treatment of angina. The pharmacology of a chemically related drug, nisoldipine (88), has recently been studied (80AF2144). Both compounds inhibit the transmembrane movement of calcium into activated smooth and cardiac muscle. Nisoldipine, however, is characterized by a high potency and uniqueness of action and may well prove to be of considerable therapeutic value. 

Coadministration of nifedipine with grapefruit juice is to be avoided (see Clinical Pharmacology and Precautions )... 

The pharmacokinetic properties of these drugs are set forth in Table 12-5. The choice of a particular calcium channel-blocking agent should be made with knowledge of its specific potential adverse effects as well as its pharmacologic properties. Nifedipine does not decrease atrioventricular conduction and therefore can be used more safely than verapamil or diltiazem in the presence of atrioventricular conduction abnormalities. A combination of verapamil or diltiazem with 3 blockers may produce atrioventricular block and depression of ventricular function. In the presence of overt heart failure, all calcium channel blockers can cause further worsening of heart failure as a result of their negative inotropic effect. Amlodipine, however, does not increase the mortality of patients with heart failure due to nonischemic left ventricular systolic dysfunction and can be used safely in these patients. 

The classical Hantzsch reaction, the formation of dihydropyridines from an aldehyde, a 5-keto ester and an amine, was first described in 18826. In the 1940s, the interest for this substance class increased due to its pharmacological activity, for example, 4-aryl-1,4-dihydropyrdines form an important class of calcium channel antagonists such as Nifedipin. 

Nearly a century later with the recognition that DHPMs possessed similar pharmacological profiles to the Nifedipine class [9a] of DHP calcium channel modulators 2 (formed via the Hantzsch condensation 1882, Scheme 11.2 [9b]), the Biginelli reaction witnessed a dramatic upsurge in popularity [10],... 

J. S. Grundy and R. T. Foster. The nifedipine gastrointestinal therapeutic system (GITS). Evaluation of pharmaceutical, pharmacokinetic and pharmacological properties. Clin. Pharm. 30 28-51, 1996. 

The reaction of ethyl acetoacetate, benzaldehyde, and urea leads to ethyl 1,2,3,4-tetrahydro-6-methyl-2-oxo-4-phenyl-5-pyrimidinecarboxylate. This reaction (the so called Biginelli reaction) was discovered over 100 years ago [93T6937], Interest in these dihydropyrimidines has increased rapidly mainly due to their close structural relationship to the pharmacologically important dihydropyridine calcium channel blockers of the nifedipine-type [93T6937], The dibromo (51) and monobromo derivatives (55) of the most simple Biginelli compounds mentioned above are readily obtained by bromination [93T6937], and the reactions of these derivatives with sodium azide have been studied recently [90LA505] [91 JCS(P1)1342],... 

Schug BS, Brendel E, Chantraine E et al. (2002) The effect of food on the pharmacokinetics of nifedipine in two slow release formulations pronounced lag-time after a high fat breakfast. Br J Clin Pharmacol 53 582-588 Stoepel K, Heise A, Kazda S (1981) Pharmacological studies of the antihypertensive effect of nitrendipine. Arzneimit-tel Forsch 31 2056-2061... 

Owing to their large caliber, the proximal coronary segments do not normally contribute significantly to flow resistance. However, in coronary sclerosis or spasm, pathological obstruction of flow occurs here. Whereas the more common coronary sclerosis cannot be overcome pharmacologically, the less common coronary spasm can be relieved by appropriate vasodilators (nitrates, nifedipine). 

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