Calcium channel-blocking drugs effects

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. 

Tab. 3.15 The effects of calcium channel-blocking drugs on the main phase transition ofdimyristoylphosphatidylcholine (DMPC) adapted from ref. 155.

This last section presents recent experiments involving effects of calcium channel blocking drugs in whole animals. It is suggested that the following results reflect modification of brain neurotransmitter secretion by blockade of calcium channels. 

Relationship between membrane binding sites for calcium channel blocking drugs and effects on calcium channels in intact cells 275... 

The structural features leading to optimal activity of the 1,4-dihydropyridines have been studied in detail. This group comprises the largest number of calcium channel blocking drugs and the individual compounds vary both in potency and selectivity. 1,4-Dihydropyridine compounds have been developed which show agonist effects at the calcium channel. 

Figure 7.2. Some intracellular processes that may be affected by calcium channel blocking drugs. Calcium channel blocking drugs inhibit calmodulin-dependent sarcolemmal Ca2 -A TPase (7), myosin light-chain kinase (MLCK) (2) and phosphodiesterase (PDE) (7). Passive Na -Ca2 exchange (4) may also be inhibited, whilst (Na +K )-ATPase (J) is stimulated. Ca2 release from mitochondria (MIT) in exchange for Na ( ) may be inhibited, but the effect of calcium channel blocking drugs on Ca2 uptake into sarcoplasmic reticulum (SR) via Ca2 -ATPase (7) is variable.

Thus, the individual pharmacological effects exerted by each calcium channel blocker may depend upon the extent to which the drug affects other intracellular systems as well as its potency at the calcium channel. Many of the effects described here would tend to increase the vasodilator action of the drugs, such as inhibition of calmodulin-dependent enzymes. However, these other effects are subsidiary to blockade of the calcium channel, as they occur mainly at concentrations higher than those required to block the channels therefore, at low concentrations the actions of the calcium channel blocking drugs are relatively specific. 

As a result of their ability to relax smooth muscle, calcium channel blocking drugs have numerous therapeutic applications, mainly in the treatment of cardiovascular disorders but possibly also in therapy for bronchial asthma, gastrointestinal muscle spasms and uterine disorders. The in vivo effects of the... 

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]. 

Fukusaki M, Tomiyasu S, Tsujita T, Ogata K, Goto Y. Interaction of cardiovascular effect of calcium channel blocking drugs and those of inhalation anesthetics in humans. Masui (1993) 42, 848-55. 

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