Anticonvulsants interaction with other drugs

Carbamazepine, phenytoin, pheno-barbital, and other anticonvulsants (except for gabapentin) induce hepatic enzymes responsible for drug biotransformation. Combinations between anticonvulsants or with other drugs may result in clinically important interactions (plasma level monitoring ). 

Acetaminophen can interact with other drugs, both in good and bad ways. For example, hospitals often combine acetaminophen with the narcotic pain reliever codeine (CoTylenol ) to treat more severe pain. Caffeine can increase the effectiveness of acetaminophen similarly to the way it does with aspirin. Brand names that use a combination of aspirin, caffeine, and acetaminophen include Excedrin and Vanquish . Combining these ingredients for their additive effects also reduces the dose needed for each one and thereby reduces the risk of side effects. However, there are a few drugs that should not be mixed with acetaminophen. These include anticonvulsants and alcohol, both of which increase the risk of liver damage. 

The manufacturers caution if enzyme-inducing anticonvulsants, particularly phenytoin, are used with modafiniL There is speculation, based on in vitro studies, about some possible interactions with other drugs, such as warfarin. Modafinil is an inducer of CYP3A4 and therefore may be expected to interact with substrates of this isoenzyme. 

St John s wort may help in mild/moderate depression, but advise caution preparations often have unclear doses and can interact with other drugs, e.g. oral contraceptives, anticoagulants, anticonvulsants. 

Pharmacokinetics. Carbamazepine is extensively metabolised one of the main products, an epoxide (a chemically reactive form), has anticonvulsant activity similar to that of the parent drug but may also cause some of its adverse effects. The t) of carbamazepine falls from 35 h to 20 h over the first few weeks of therapy due to induction of hepatic enzymes that metabolise it as well as other drugs, including corticosteroids (adrenal and contraceptive), theophylline and warfarin. Cimetidine and valproate inhibit its metabolism. There are complex interactions with other antiepilepsy drugs, which constitute a reason for monodrug therapy. 

Most interactions of trimethoprim and co-trimoxazole with other drugs are due to fohc acid antagonism. This may be more pronounced with co-trimoxazole than with either drug alone. Such interactions have previously been suspected with anticonvulsants, such as barbiturates, phe-nytoin, and primidone, which themselves produce folic acid deficiency and megaloblastic anemia (88). In order to circumvent the risk of folate deficiency, folic acid or folinic acid can be given. There is some concern that folate replacement may antagonize the desired antimicrobial effect, particularly in some protozoal parasites, but this concern has been debated (89). 

Less than 3% of a dose is excreted unchanged in the urine or through the feces. The elimination half-life from plasma is 10-15 h when valproic acid is used alone, but interaction with other anticonvulsant drugs can reduce the half-life to 4-10 h. It may be much longer in hepatic-impaired individuals, the elderly, and young children. 

Wilder BJ, Willmore LJ, Bruni J, Villarreal HJ. Valproic acid interaction with other anticonvulsant drugs. Neurology (1978) 28, 892-6. 

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],... 

As with any other medication prescribing there must be awareness of drug interactions, with important ones for methadone relating to antivirals, psychotropics, anticonvulsants and antibiotics. 

Buspirone has selective anxiolytic effects, and its pharmacologic characteristics are different from those of other drugs described in this chapter. Buspirone relieves anxiety without causing marked sedative, hypnotic, or euphoric effects. Unlike benzodiazepines, the drug has no anticonvulsant or muscle relaxant properties. Buspirone does not interact directly with GABAergic systems. It may exert its anxiolytic effects by acting as a partial agonist at brain 5-HTia receptors, but it also has affinity for brain dopamine D2 receptors. Buspirone-treated patients show no... 

The interactions of benzodiazepines with other nervous system depressants, especially alcohol and other GABA-ergic drugs, have been reviewed (152). Other drugs with nervous system depressant effects (opioids, anticonvulsants, general anesthetics) also can add to, and complicate, the depressant action of benzodiazepines. 

Levetiracetam. Levetiracetam is a new anticonvulsant agent that does not as yet present any drug interactions. Dizziness and somnolence occurred to a statistically significant extent (14.8% versus 8.4% of the placebo patients) (18). This side effect occurred more frequently with patients receiving levetiracetam in combination with other anticonvulsant agents. 

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