Nifedipine cardiovascular effects

Alternate treatments. Mood-stabilization and control of manic or hy-pomanic episodes in some subtypes of bipolar illness may also be achieved with the anticonvulsants valproate and carbamazepine, as well as with calcium channel blockers (e.g., verapamil, nifedipine, nimodipine). Effects are delayed and apparently unrelated to the mechanisms responsible for anticonvulsant and cardiovascular actions, respectively. 

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. 

Lusardi P, Piazza E, Fogari R. Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine a 24-hour study. Br J Clin Pharmacol 2000 49(5) 423-7. 

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. 

Data on the effect of calcium antagonists on cardiovascular disease risks in patients with hypertension are available from one moderate-to-large scale randomized, placebo-controlled trial. In the Systolic Hypertension in Europe (Syst-Eur) trial, nitrendipine-based therapy produced an approximate 10/5 mmHg reduction in SBP-DBP in patients with systolic hypertension and a 42% reduction in the risk of stroke. Similar results were observed in two large, nonrandomized, placebo-controlled trials (with alternate treatment assignment), i.e. the Shanghai Trial of Nifedipine in the Elderly and the Systolic Hypertension in China (Syst-China) trial. 

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. 

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 ... 

It has been suggested that calcium channel blockers can be used to treat cocaine dependence, and some studies have shown reductions in cocaine-induced subjective and cardiovascular responses with nifedipine and diltiazem. The cardiovascular and subjective responses to cocaine have been evaluated in a double-blind, placebo-controlled, crossover study in five subjects pretreated with two dosage of nimodipine (393). Nimodipine 60 mg attenuated the rise in systolic, but not diastolic, blood pressure after cocaine. In three subjects nimodipine 90 mg produced greater attenuation than 60 mg. The subjective effects of cocaine were not altered by either dose of nimodipine. 

The possibility that calcium channel blockers can cause cardiovascular adverse effects in pregnancy has been widely debated (SED-14, 598) (SEDA-20, 185) (SEDA-21, 208) (SEDA-22, 214). An uncomplicated non-Q wave myocardial infarction has been reported during nifedipine therapy for preterm labor (43). 

Verapamil, nifedipine, and diltiazem lower blood pressure with an efficacy comparable to that achieved by other commonly used agents. Their specific effects on the cardiovascular system are as follows ... 

During activation of postganglionic sympathetic nerves there is an exocytotlc release of norepinephrine which is dependent upon the movement of calcium across the neural cell membrane. The effects of CEB on stimulus-secretion coupling in S3nnpathetlc nerves has been studied in several different preparations. Verapamil does not affect the neural release of norepinephrine in either Isolated cat heart or in the pithed rat. In the latter model nifedipine blunted increases in blood pressure due to activation of sympathetic nerves but did not affect cardiovascular responses to exogenous norepinephrine suggesting a prejunctional site of inhibition. 

Howie MB, Mortimer W, Candler EM, McSweeney TD, Frolicher DA. Does nifedipine enhance the cardiovascular depressive effects of bupivacaine (1989) 14,19-25. 

There is evidence that most NSAIDs can increase blood pressure in patients treated with antihypertensives, although some studies have not found the increase to be clinically relevant. In various small studies, indometacin appeared not to reduce the hypotensive effects of amlodipine, felodipine, nicardipine, nimodipine or verapamil, but it did in one of two studies with nifedipine, and one study with nitrendipine. Similarly, ibuprofen caused a small reduction in the antihypertensive effects of amlodipine. Diclofenac and sulindac appear not to interact with nifedipine, nor ibuprofen, naproxen, piroxicam or sulindac with verapamil, nor naproxen with nicardipine. Low-dose aspirin did not alter the antihypertensive effect of felodipine or nifedipine in one study, and long-term aspirin did not alter the cardiovascular benefits of nitrendipine in another. Diclofenac reduces verapamil serum levels and raises those of isradipine, but these changes are probably unimportant. 

An isolated report describes acute hyperkalaemia and cardiovascular collapse when dantrolene was given to a patient taking verapamil, but not when he was subsequently given nifedipine. Animal studies have found similar effects with the combination of dantrolene and verapamil or diltiazem, but not with nifedipine or amlodipine. 

Dihydropyridine (DHP) drugs such as nifedipine, nicardipine, amlodipine, and others are effective cardiovascular agents for the treatment of hypertension [63], DHPs have been explored for their calcium charmel activity and are foimd as a constituent in a variety of bioactive compounds which show many biological activities such as vasodilator, bronchodilator, antiatherosclerotic, antitumor, antidiabetic, geroprotec-tive, heptaprotective [64], etc. 

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