Antiepileptics interactions

NERVOUS SYSTEM DRUGS ANTIEPILEPTICS Interactions between antiepileptics... 

The a28 subunit 1 and 2 bind gabapentin with high affinity. This interaction may be causally related to its antiepileptic and neuropathic pain alleviating property. 

Analyze potential drug interactions with antiepileptic drugs. 

TABLE 27-4. Common Drug Interactions with Antiepileptic Drug36-38... 

Drug Interactions Carbamazepine induces the hepatic metabolism of many drugs, including other antiepileptic drugs, antipsychotics, some antidepressants, oral contraceptives, and... 

TABLE 52-5 1 Interactions between Antiepileptic Drugs (Continued) 1 ... 

From the examination of structure-activity relationships, it has been concluded that a phenyl moiety at C-6 as well as a 4-hydroxypiperidine side-chain attached to C-3 of the pyridazine system is essential for anticonvulsant activity in this class of compounds [184], Compounds (54) and (55) have been found to have similar anticonvulsant profiles in animals (mice, rats and baboons) [165, and literature cited therein] and to represent potent broad-spectrum antiepileptic drugs. Their potency with regard to antagonizing seizures (induced by electro-shock or various chemicals) has been compared with standard anticonvulsants like carbamazepine and phenobarbitone [185, 186], A quantitative electroencephalographic analysis of (55) has been published [187]. From in vitro studies it has been concluded that the anticonvulsant activities of these compounds are not mediated by an enhancement of GABAergic transmission or by an interaction with benzodiazepine receptor sites [ 165,186,187], On the other hand, in vivo experiments showed that (54), at anticonvulsant doses, increases the affinity of flunitrazepam for its central receptor site [ 186], Investigations of (54) and (55) in a behavioural test predictive of antianxiety activity revealed a marked difference in the pharmacological profiles of these structurally closely related compounds the dichloro compound SR 41378 (55) has also been found to possess anxiolytic (anticonflict) properties [165],... 

In switching drugs, the half-life of elimination that is being stopped should be considered if drug interactions are to be avoided. The time taken for the withdrawal of a drug depends on the duration of treatment sedatives, antiepileptics and anxiolytics may take several weeks to withdraw. 

Drug/Lab test interactions Because false-positive readings were reported with the Ames N-Muitistix SG dipstick test for urinary protein when gabapentin was added to other antiepileptic drugs, the more specific sulfosalicylic acid precipitation procedure is recommended to determine the presence of urine protein. 

There are some clinically important pharmacodynamic drug-drug interactions to be mentioned. Antipsychotics will potentiate the central depressant effects of sedatives and of alcohol. They will also increase the risk of respiratory-depressant effects of opiates. Inducers of drug metabolic enzymes like for example rifampicin and several antiepileptics, may increase the elimination rate of antipsychotic agents and thus decrease their efficacy. 

Methylphenidate is an inhibitor of drug metabolizing enzymes of the cytochrome P450 family and several interactions with drugs like some antiepileptics, antidepressants and oral anticoagulants, have been described. 

As it inhibits microsomal cytochrome P450 cimetidine has a high potential for drug interactions not shared by the other H2 receptor antagonists. The oxidative metabolism of agents such as anticoagulants, most antiepileptics, some beta-blockers, warfarin, theophylline and many hypnotics, neuroleptics and antidepressants may be reduced, leading to increased effects. 

Isoniazid inhibits cytochrome P450 enzyme function and thus can interact with drugs that are subject to cytochrome P450 mediated metabolism like warfarin and the antiepileptic agents phenytoin and car-bamazepine. 

Recent drug development studies have centered on the capacity of known antiepileptic drugs (AEDs) to interact with ion channels, and it is now established that several agents appear to be exerting their effects primarily by inhibiting ion channels. Modulation of neuronal sodium channels decreases cellular excitability and the propagation of nerve impulses. Inhibition of sodium channels appears to be a major component of the mechanism of action of several anticonvulsant drugs. 

Hachad, H., Ragueneau-Majlessi, I., and Levy, R.H. (2002) New antiepileptic drugs review on drug interactions. Drug Monit 24 91-103. 

Ram beck, B., Specht, U., and Wolf, P. (1996) Pharmacokinetic interactions of the new antiepileptic drugs. Clin Pharmacokinet 31 309-324. 

Two patients stabilized on a phenytoin regimen suffered a loss of seizure control after taking shankhapushpi, an Ayurvedic antiepileptic medicine, three times a day. There was also a significant decrease in serum phenytoin concentration from 9.6 to 5.1mg/L. To investigate the possible mechanisms, multiple doses of shankhapushpi were administered to rats and resulted in decreased plasma phenytoin concentrations, whereas single-dose administration was reported to interfere with the antiplatelet effect of phenytoin, thereby implying both a pharmacokinetic and pharmacodynamic basis for the interaction (73). 

---