ANTICONVULSANTS PHENYTOIN - rEMERGs

More documents

Recommendations

Info

Other ‣ ‣ ‣ ‣ ‣ ‣ ‣ ‣ ‣ ‣ Phenytoin > 60 umol/L: nystagmus Phenytoin > 120: ataxia Phenytoin > 200: lethargy, slurred speech, movement disorders Can be toxic at lower levels with low albumin (more free drug) Seizures can occur but are VERY rare Choreas and opisthotonic movements more common in children and elderly No cardiotoxicity reported from oral doses IV doses has caused hypotension (propylene glycol), negative inotropy, decreases SVR all leading to hypotension Extravasation can cause tissue necrosis Increased toxicity in low albumin, neonates, elderly, as well as certain coingestants (salicylates, vlaproate, sulfonamides) Diagnostic Testing ‣ Total phenytoin level measures bound and unbound drug: conversion factor for albumin level required ‣ Conversion Phenytoin = measured/(0.25 X measured) + 0.1 MANAGEMENT Supportive care is the mainstay Activated charcoal (caution in seizure d/o patients as may ppt seizure) MDAC if levels increasing or persistently elevated Serial examinations for resolution of ataxias NO routine cardiac monitoring required Follow serial levels as absorption unpredictable and may be delayed Dyskinesis during therapeutic administration usually self limited and resolve after few hours Hemodialysis of little benefit b/c highly protein bound No specific antidotal therapy CARBEMAZEPINE INTRODUCTION Tegretol Structurally similar to TCAs (think of TCA of anticonvulsants!!) Only available for oral use Considered best anticonvulsant by many PHARMACOLOGY MOA: Na channel block Lipophilic, slow absorption Levels may not peak for 24hrs after acute ingestion Some anticholinergic properties; delays ingestion even further There is not a simple relationship between dose and levels Metabolized by P450 system
First order kinetics and doses often have to be increased Elimination T ½ is 10-20 hours Therapeutic level = 17 - 51 umol/L Adverse effects of Therapeutic dosing ‣ Irritability, impaired cognition/memory ‣ Rashes, Steven’s-Johnson ‣ Hepatitis ‣ Drug induced SLE ‣ Leukopenia, aplastic anemia ‣ Anticonvulsant hypersensitivity syndrome CLINICAL MANIFESTATIONS Neurologic ‣ Nystagmus, ataxia, dysarthria ‣ Lethargy, coma with large ingestions ‣ Seizures more common than dilantin od: increased seizure frequency may be only presenting feature of carbamezepine chronic toxicity ‣ Can have status epilepticus ‣ Peds: dystonic reactions, choreoathetosis, seizures Cardiovascular ‣ Tachycardia: anticholinergic effect ‣ Hypotension: myocardial inhibition ‣ Wide QRS and prolonged QT 15% of acute ingestions have QRS > 100 msec 50% of acute ingestions have QT > 420 msec Can also occur with chronic ingestions May present delayed (absorption can be delayed) Terminal 40 msec right axis not documented in literature Chronic Overdoses ‣ Seizures, headaches, ataxia, diplopia, SIADH Diagnostic Testing ‣ Measure carbemazepine levels ‣ Levels need to be repeated as absorption is highly variable and may be delayed ‣ Therapeutic levels 17-51 umol/L ‣ Levels > 120: coma, seizures, resp depression, cardiotoxicity ‣ Can be toxic with levels in therapeutic range as there are ACTIVE METABOLITES (especially if combination therapy with valproate, etc) MANAGEMENT Activated charcoal MDAC is indicated and helpful as there is prominent enterohepatic circulation Delayed rise in levels can reflect concretions Hemodialysis ineffective Cardiac Toxicity ‣ Cardiac monitoring required ‣ Sodium Bicarb for QRS > 100 msec (not studied): as per TCAs
Page 1: ANTICONVULSANTS GENERAL Relatively
Page 5 and 6: Diagnostic Testing ‣ Valproic aci

ANTICONVULSANTS PHENYTOIN - rEMERGs

Create successful ePaper yourself

Delete template?

Save as template?