Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The calcium antagonists are a heterogeneous class of drugs which block the inward movement of calcium into cells through 'slow channels' from extracellular sites. By inhibiting phase 0 depolarisation in cardiac pacemaker cells and phase 2 plateau in myocardium, and by depressing calcium ion flux in smooth muscle cells of blood vessels, these agents may exert profound effects on the cardiovascular system, particularly in susceptible individuals or in overdose. Sinus node depression, impaired atrioventricular (AV) conduction, depressed myocardial contractility, and peripheral vasodilatation may result. Pharmacokinetic features of calcium antagonists include rapid and complete absorption from the gastrointestinal tract, with extensive first-pass hepatic metabolism yielding generally low bioavailability. The volume of distribution is generally large and protein binding is high. Elimination is almost entirely by the liver. Impaired renal function does not affect pharmacokinetics. Verapamil is the most potent inhibitor of cardiac conduction and contractility, with diltiazem also showing such effects. Nifedipine is the most potent vasodilator, but only occasionally impairs the sinus node or AV conduction. Significant pharmacodynamic effects are common during combination therapy with calcium antagonists, especially verapamil and beta-blockers. Verapamil may significantly elevate serum digoxin concentrations and may exert additive negative effects on chronotropism and dromotropism when this combination is used. Overdoses of calcium entry blockers are becoming more frequent and reflect an extension of the known pharmacodynamic profile of these agents. Typical features include confusion or lethargy, hypotension, sinus node depression and cardiac conduction defects. Onset of symptoms may be delayed if a sustained release preparation is ingested. Management of calcium antagonist overdose includes gut decontamination with lavage and activated charcoal. All symptomatic patients and patients with a history of ingesting a sustained release preparation should be admitted for ECG monitoring. If bradycardia and/or conduction defects contribute to hypotension, atropine or isoprenaline (isoproterenol) may accelerate the ventricular rate. Transvenous pacing may be required. Depressed myocardial contractility usually responds well to calcium chloride or calcium gluconate administration, but further inotropic support may be required. Peripheral vasodilation should be managed with intravenous fluids and a pressor agent such as dopamine or norepinephrine (noradrenaline).
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PMID:Poisoning due to calcium antagonists. Experience with verapamil, diltiazem and nifedipine. 179 22

Topiramate (TPM), a new generation antiepileptic drug was investigated for its anticonvulsant effects in various models of genetically determined and chemically induced epilepsy in rodents. In addition, based on recent electrophysiological data suggesting that TPM may interact with L-type Ca(2+) channels, we evaluated the effects of a concomitant administration of L-type Ca(2+) channel modulators on TPM's antiepileptic properties. TPM, dose-dependently, protected against audiogenic seizures in DBA/2 mice. Concomitant treatment with TPM and a low dose of L-type Ca(2+) channel antagonists nifedipine or verapamil or with the L-type Ca(2+) channel agonist, S(-)-1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-3-pyridinecarboxylic acid methyl ester (Bay k 8644) was able to increase the ED(50) for this drug. TPM also protected against seizures induced by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), 4-aminopyridine (4-AP) and pentylenetetrazole (PTZ), but this activity was not significantly modified by nifedipine. TPM, dose-dependently, reduced the number and duration of epileptic spike-wave discharges (SWDs) both in WAG/Rij rats and lethargic (lh/lh) mice, two genetic models of absence epilepsy. Nifedipine decreased TPM's activity in WAG/Rij rats but paradoxically enhanced it in lh/lh mice, whereas Bay k 8644 displayed opposite effects in both absence models. These results confirm TPM's broad spectrum of anticonvulsant activity and support the proposal that a modulation of neuronal L-type Ca(2+) channel activity plays an important role in its antiepileptic activity.
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PMID:Nifedipine affects the anticonvulsant activity of topiramate in various animal models of epilepsy. 1503 46