Calcium channel antagonist cardiovascular effects

Romero M, Sanchez I, Pujol MD. New advances in the field of calcium channel antagonists cardiovascular effects and structure-activity relationships. Curr Med Chem Cardiovasc Hematol Avents. 2003 1 113-141. 

Acute intoxication with amphetamine is associated with tremor, confusion, irritability, hallucinations and paranoid behaviour, hypertension, sweating and occasionally cardiac arrhythmias convulsions and death may occur. The cardiovascular effects of the stimulants may be treated by beta-blockers, or by the combined alpha- and beta-blocker labetalol calcium channel antagonists such as nifedipine may correct the arrhythmias, while intravenous diazepam is of value in attenuating seizures. 

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 ... 

Calcium channel antagonists relax smooth muscle by inhibiting calcium entry and, therefore, have similar functional effects and therapeutic applications to the ATP-gated potassium channel agonists just discussed. Calcium channel antagonists have been widely used therapeutically to treat cardiovascular disorders and were available prior to the discovery of compounds such as cromakalim. 

Although there is no evidence that the neuronal degeneration of AzD results, as in cardiovascular ischaemia, from the excitotoxicity of increased intracellular Ca +, some calcium channel blockers have been tried in AzD. They have had little effect but surprisingly a pyrrolidone derivative nefiracetam, which opens L-type voltage-sensitive calcium channels (VSCCs) reduces both scopolamine- and )S-amyloid-induced impairments of learning and memory in rats (Yamada et al. 1999). This effect can be overcome by VSCC antagonists, but nefiracetam has not been tried in humans. 

Many different drug classes have shown to cause hypotension and orthostatic reactions and drugs for cardiovascular conditions, psychoactive medicines and polypharmacy, can all have this side effect (Box 5.15). Among the most frequently used drugs in the elderly are diuretics, ACE-inhibitors, angiotensin II antagonists, calcium channel blockers and antidepressants. 

Calcium antagonists can cause serious toxicity or death with relatively small overdoses. These channel blockers depress sinus node automaticity and slow AV node conduction (see Chapter 12). They also reduce cardiac output and blood pressure. Serious hypotension is mainly seen with nifedipine and related dihydropyridines, but in severe overdose all of the listed cardiovascular effects can occur with any of the calcium channel blockers. 

This pharmacological class is one of the most complex since its members act on a variety of newly discovered calcium channels within the central nervous system with either synaptic or somatic localization and numerous functions. Little is known about the impact of calcium antagonists on chemical neurotransmission, neuronal functions and intracellular calcium homeostasis, particularly in neurones and glial cells. This wide area of research and the action of these drugs on cerebral vascularization have been the subject of a number of recent reviews [95, 128-130]. For dihydropyridines, it is also important to note the peripheral (cardiovascular) effects which in turn affect the central nervous system. 

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