ANTICONVULSANTS PHENYTOIN - rEMERGs

More documents

Recommendations

Info

VALPROIC ACID INTRODUCTION Valproate, Epival, Depakene, Depacon,Depakote Di-n-propylacetic acid Uses: seizures, bipolar, migraines SR preparations are very common Common presentation of mild symptoms, discharged after few hours, delayed absorption and later crashes with decreased LOC 6-12hrs later due to delayed absorption (consider WBI) PHARMACOLOGY MOA: GABAergic effect (decreases degredation of GABA), some Na+ channel effects Therapuetic levels = 347 - 833 umol/L Complex metabolism in liver Valproic acid metabolism is dependant on carnitine as a cofactor (see 41-2 in goldfranks) ‣ Complicated interaction with carnitine ‣ Valproate DECREASES carnitine stores through various mechanisms ‣ Carnitine depletion or deficiency decreases metabolism of valproic acid ‣ Carnitine depletion has other metabolic effects: impaired transport of fatty acids, inhibition of ketoacid oxidation, and inhibition of the urea cycle resulting in an increased ammonia ‣ Valproate therapeutic or overdose setting DECREASED CARNITINE INCREASED AMMONIA Adverse effects of Therapeutic dosing ‣ Elevated liver enzymes ‣ Toxic hepatitis --------> can be fatal ‣ Reye’s syndrome ‣ Hyperammonia ‣ Carnitine deficiency CLINICAL MANIFESTATIONS Most are benign Hallmarks = COMA and RESPIRATORY DEPRESSION Neurologic ‣ Decreased LOC ‣ Ataxia, nystagmus, dyarthria do NOT occur Other ‣ Increased Ammonia: 40% of those on chronic therapy, may occur after acute ingestion also, levels > 60 umol/L ‣ Decreased Carnitine ‣ Metabolic acidosis: secondary to lactate, can be severe, poor prognostic sign ‣ Leukopenia, anemia, thrombocytopenia ‣ Renal failure ‣ Hepatotoxicity
Diagnostic Testing ‣ Valproic acid levels ‣ Repeat 2-3 hours and monitor closely ‣ Carnitine and ammonia levels MANAGEMENT Supportive is mainstay Activated charcoal MDAC for large ingestions and rising levels Whole bowel irrigation for SR preps Dialysis may have a role Narcan ‣ Case reports of increased LOC with narcan ‣ Other reports show no effect ‣ Not dangerous but unlikely to make much difference ‣ ? mechanism related to GABA Carnitine ‣ Role not well defined ‣ No controlled studies ‣ Pediatric neurology society recommends that all children on valproic acid should have prophylactic carnitine supplementation ‣ Others recommend carnitine supplementation only for those children who have acutely ingested > 400 mg/kg ‣ Unclear if carnitine will DECREASE HEPATOTOXICITY incidence ‣ Generally, carnitine prophylaxsis is indicated for < 2yo, malnurished, other anticonvulsants, ketogenic diets ‣ Role in acute ingestion undefined ‣ Carnitine = 100mg/kg/d divided into 3 doses orally Dialysis ‣ Rapid clinical deterioration ‣ Hepatic failure ‣ Rising levels despite MDAC or WBI ‣ Serum levels > 1000 mg/L (? SI units) OTHER <strong>ANTICONVULSANTS</strong> GABAPENTIN Sedation, ataxia, slurred speech No major toxicities or deaths reported Supportive care Activated charcoal No dialysis No specific antidote
Page 1 and 2: ANTICONVULSANTS GENERAL Relatively
Page 3: First order kinetics and doses ofte

ANTICONVULSANTS PHENYTOIN - rEMERGs

Create successful ePaper yourself

Delete template?

Save as template?