Seizures caused toxicity

The major dose-limiting toxicides of didanosine include peripheral neuropathy and pancreatitis. The neuropathy is typically symmetrical distal sensory neuropathy, which is reversible, and typically causes paresthesias, numbness and pain in lower extremities. Didanosine also causes retinal changes and optic neuritis. Other adverse effects include diarrhea, skin rash, headache, insomnia, seizures, hepatic toxicity, elevated hepatic transaminases and asymptomatic hyperuricemia. 

Early signs of tricyclic antidepressant toxicity are due to anticholinergic effects and include tachycardia, mydriasis, dry mouth, low-grade fever, diminished bowel sounds, CNS excitation, and delirium. More serious toxicity is manifested by coma, respiratory depression, seizures, and cardiovascular toxicity including conduction disturbances, hypotension, ventricular arrhythmias, and asystole. Seizures cause hyperthermia, rhabdomyolysis, and metabolic acidosis. Clinical deterioration can be rapid and catastrophic in patients with tricyclic antidepressant overdose. Death most often occurs due to dysrhythmia and circulatory collapse. The typical therapeutic dose of a tricyclic antidepressant is 2-4 mg kg day Doses of 15-20 mg kg are potentially lethal. Therapeutic drug levels for most tricyclic antidepressants range from 100 to... 

Anti-infective drugs Ciprofloxacin can greatly increase the risk of seizure induction in patients taking anticonvulsants. Erythromycin produces a rapid 100-200% rise in carbamazepine levels. There is a possibility of reduced plasma levels of the protease inhibitors indinavir and saquinavir with carbamazepine. Isoniazid increases carbamazepine serum levels, and leads to the possible emergence of toxicity (disorientation and aggression). Mefloquine may antagonize the anticonvulsant effect of carbamazepine. Ritonavir, a protease inhibitor, may cause toxicity by raising carbamazepine plasma levels. 

The incidence of phenytoin toxicity may be increased in the eideriy, or in those patients with hepatic or renal impairment, because of alterations in its pharmacokinetics. Plasma level determinations may be indicated in these cases. Although a role for P-glycoprotein transporter alleles in the development of phenytoin toxicity remains controversial, phenytoin is a robust substrate for the non-ABC efflux transporter RLIP76. Because RLIP76 has been found to be overexpressed in excised human epileptic foci, its action may account for treatment failures conversely, inhibition of transport may cause toxicity (34). There is a 2 to 3% increase in the risk of fetal epilepsy syndrome if the mother is taking phenytoin. Phenytoin is contraindicated in cardiac patients with bradyarrhythmias. Induction of CYP2C19 by ginkgo biloba may increase phenytoin clearance and precipitate serious seizures (35). 

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