Behavior phenobarbital

The interaction of ketamine with each of the three anticonvulsant compounds was also tested. Ketamine, 15 mg/kg, a dose showing no anti-PTZ effect and causing no overt behavioral changes, potentiated the effect of phenobarbital (20 mg/kg) in delaying the clonic and tonic convulsive responses and lethality (figure 3). Ketamine also potentiated the ability of phenytoin (20 mg/kg) to delay... 

The results demonstrate anticonvulsant properties of PCP and ketamine in two quite different seizure models. On the one hand, ketamine was effective in antagonizing several components of PTZ activity. Others have previously reported anti-PTZ effects of ketamine. However, the present results demonstrate that the anticonvulsant effects of ketamine against PTZ seizures closely resembled the effects of phenobarbital in that both compounds delayed clonic convulsions and prevented tonic extension. Moreover, a low dose of ketamine, which alone showed no anticonvulsant effect or overt behavioral changes, potentiated the anti-PTZ effects of phenobarbita 1. These findings suggest that ketamine possesses selective anticonvulsant properties. The anticonvulsant mechanism of action for phenobarbital is not known. However, the similarities between ketamine and phenobarbital, and the interaction between the two compounds, suggest a common mechanism or site of acti on. 

Phenobarbital Ataxia Blood dyscrasias Behavior changes... 

Valproic acid causes hair loss in about 5% of patients, but this effect is reversible. Transient gastrointestinal effects are common, and some mild behavioral effects have been reported. Metabolic effects, including hyperglycemia, hyperglycinuria, and hyperammonemia, have been reported. An increase in body weight also has been noted. Valproic acid is not a CNS depressant, but its administration may lead to increased depression if it is used in combination with phenobarbital, primidone, benzodiazepines, or other CNS depressant agents. 

L.D. Middaugh, C.A. Santos III and J.V. Zemp, Effects of phenobarbital given to pregnant mice on behavior of mature offspring, Develop. Psychobiol., 8(4) (1975) 305-313. 

Behavioral and psychiatric disturbances are not uncommon (31). Although epilepsy is itself associated with an increased risk of such disturbances, drugs play an important role. Phenobarbital-induced behavioral disturbances, especially hyperkinesia, are especially common in children, with an incidence of 20-50% and need for drug withdrawal in 20-30% of cases, whereas it is unclear whether and to what extent adults are affected. 

Because it is cheap and of unquestioned efficacy, phenobarbital is stiU widely prescribed around the world, although in developed countries its use has fallen since the introduction of drugs that are better tolerated. Its most common adverse effects are sedation (to which partial tolerance develops), cognitive dysfunction, and in children hyperkinesia and other behavioral disturbances. 

In a 12-month trial in 109 epileptic children randomized to monotherapy with phenobarbital (maintenance dosage 3.0 mg/kg/day) or phenytoin (5.0 mg/kg/day) in rural India there were no significant differences in either efficacy or toxicity (3). In particular, behavioral adverse effects were not more common with phenobarbital. The findings suggest that phenobarbital is an acceptable first-line agent for childhood epilepsy in rural settings in developing countries. 

Since significant behavioral toxicity may be present despite the absence of overt signs of toxicity, the tendency to maintain patients, particularly children, on excessively high doses of phenobarbital should be resisted. The plasma phenobarbital concentration should be increased above 30-40 pg/mL only if the increment is adequately tolerated and only if it contributes significantly to seizure control. 

THERAPEUTIC USES Phenobarbital is an effective drug for generalized tonic-clonic and partial seizures. It is efficacious, inexpensive, and has low toxicity. However, its sedative effects and its tendency to disturb behavior in children have reduced its use. 

Chronic treatment with the enzyme inducer phenobarbital enhances the biliary excretion of drug molecules and their metabolites by increasing liver size, bile flow, and more efficient transport into the bile. This behavior is not shared by all inducers of the CYP450 monooxygenases. The route of administration also may influence excretion pathways. Direct administration into the portal circulation might be expected to result in more biliary excretion than could be expected via the systemic route. 

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