Nifedipine, calcium channel blocking

Despite the growth in interest in calcium blockers, there are comparatively few calcium channel blocking agents currently in clinical use. These drugs are characterised by the fact that they belong to classes of compounds which are chemically unrelated like Diltiazem , Nifedipine , Verapamil , Fluspirilene and some others (Scheme 1). 

This section deals with the application of molecular orbital (MO) calculations in structure-activity relationship (SAR) analyses. Calcium channel-blocking 1,4-dihydropyridine (DHP) derivatives such as nifedipine (Fig. 9.10) are widely used in the therapy of cardiovascular disorders. 

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. 

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. 

Kumar PP, Stotz SC, Paramashivappa R et al. (2002) Synthesis an evaluation of a new class of nifedipine analogs with T-type calcium channel blocking activity. Mol Pharmacol 61(3) 649-658... 

Calcium channel blocking agents, such as verapamil and nifedipine are also satisfactory antihypertensive agents. These drugs reduce the influx of calcium ions into vascular muscle cells following excitation and so cause vasodilation. They act mainly on arterial vessels in the circulation. 

Some quantum mechanical parameters were also foimd to be useful in accounting for the variance in calcium channel blocking activity of nifedipine analogues. For the same set of compounds as treated by Coburn et al. (Table 3), Gaudio et al. [16] had correlated the contractile response inhibition data as... 

A calcium-channel blocking drug, e.g. nifedipine or diltiazem, is an alternative to a p-adrenoceptor blocker use especially if coronary spasm is suspected or if the patient has myocardial insufficiency or any bronchospastic disease. It can also be used with a p-blocker, or... 

HaU-Craggs M, Light PD, Peters RW. Development of immune complex nephritis during treatment with the calcium channel-blocking agent nifedipine. Hum Pathol 1984 15(7) 691. ... 

In order to determine if ( )-ka n had calcium channel blocking properties, experiments using nifedipine were performed (Table 6.1). Nifedipine inhibited contractions evoked by BAY K 8644 and by substance P. Even at high concentrations (1 XM), nifedipine failed to completely block contractions evolsd by carbachol (10 XM). After pre-incubation with 1 XM nifedipine, carbachol (lOjlM) evoked 18.2+4.3% contraction of pre-incubation control value. The remaining response was completely abolished by high concentrations of ( )-kavain (400 lM). 

Double-blind placebo-controlled trials have shown that both nifedipine and diltiazem are effective in controlling the symptoms of Raynaud s phenomenon [213-215]. Nifedipine increases fingertip blood flow by decreasing fingertip vascular resistance [216]. At present, the sole calcium channel blocking drug to have been licensed in the U.K. for the treatment of Raynaud s phenomenon is nifedipine. Since all calcium channel blockers produce vasodilation, they may all eventually prove to be effective in counteracting vasoconstriction in patients with Raynaud s phenomenon, but this has yet to be established. 

In patients with pulmonary hypertension, calcium channel blocking drugs have been found to produce pulmonary artery dilation and therefore improvement in cardiac output and relief of hypoxia [233, 234]. Most of the studies have used short-term administration to carefully selected patients. Thus, the beneficial effects need to be confirmed in longer studies using more patients with advanced pulmonary hypertension. Detrimental deterioration in right ventricular performance has been found in some patients with severe right ventricular dysfunction following the administration of verapamil or nifedipine [233]. 

Nifedipine is a calcium-channel-blocking agent that inhibits movement of calcium ions across cell membrane in systemic and coronary vascular smooth muscle and myocardium. It decreases peripheral vascular resistance reduces myocardial oxygen demand and relaxes and prevents coronary artery spasm. It is indicated in chronic stable angina (except Adalat CC, Afeditab CR, Nifediac CC) vasospastic angina (except Adalat CC, Afeditab CR, Nifediac CC) hypertension (except Procardia) (see also the description of Nicardipine). 

B. Calcium Channel-Blocking Agents Calcium channel blockers (eg, nifedipine, verapamil,... 

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