In general, anticonvulsants are:
- Well absorbed orally
- Highly protein bound
- Hepatically metabolised by CYP450 enzymes, and induce their own metabolism (as well as that of other drugs)
- Renally eliminated
- Interact with each other
|Uses||GTCS, partial seizures, trigeminal neuralgia, ventricular arrhythmias||Partial seizures||Antiepileptic, trigeminal neuralgia||GTCS, partial seizures, myoclonic seizures, seizure prophylaxis|
|Presentation||Capsules, syrup, solution. IV formulation incompatible with dextrose.||Tablets, syrup, solution||Tablets, suppositories, syrup||Tablets, oral liquid, IV liquid|
|Route of Administration||PO, IV, IM||PO, IV||PO||PO, IV (over 15 minutes)|
|Dosing||15-20mg.kg-1 load, aiming plasma levels 10-20mcg.ml-1||300-1250mg BD||50-800mg BD||Typically 1g loading, then 500mg BD increasing up to 1.5g BD. Dose adjusted in renal impairment.|
|Mechanism of Action||Stabilises Na+ channels in their inactive state, inhibiting generation of further action potentials.||Stabilises Na+ channels in their inactive state and GABAergic inhibition||Stabilises Na+ channels in their inactive state and potentiates GABA||Unknown, but different to other antiepileptics and may be related to inhibition of N-type Ca2+ currents|
|Absorption||Slow PO absorption. PO bioavailability 90%||PO bioavailability 100%||95% PO bioavailability||Near 100% PO bioavailability|
|Distribution||Highly protein bound||Highly protein bound||Highly protein bound||Nil significant protein binding, VD ~0.5L.kg-1|
|Metabolism||Hepatic hydroxylation with highly individual variation in dosing. Obeys first-order kinetics in the therapeutic range, and zero-order kinetics just above the therapeutic range. Metabolised by CYP450. Induces warfarin, benzodiazepines, OCP metabolism. Inhibited by metronidazole, chloramphenicol, isoniazid. Genetic polymorphism results in reduced metabolism in 5-15% of patients.||Hepatic to inactive and active metabolites||Hepatic||Hepatic hydrolysis to inactive metabolites|
|Elimination||Renal elimination of inactive metabolites and active drug||Renal elimination of metabolites and active drug||Renal elimination||Renal of active drug (major route) and metabolite (minor route)|
|CVS||↓ BP, heart block, and asystole with rapid administration, antiarrythmic properties||Antiarrhythmic|
|CNS||↑ Seizure threshold, paraesthesia, ataxis, nystagmus, slurred speech, tremor, vertigo.||↑ Seizure threshold||↑ Seizure threshold||↑ Seizure threshold, anxiolytic. Minimal ↓ in seizure threshold on cessation.|
|Renal||Water retention from ADH-like effects||Rarely precipitates AKI|
|GIT||Hepatotoxicity (idiosyncratic). Nausea and vomiting.||Hepatotoxicity.|
|Haeme||Aplastic anaemia and other blood dyscrasias||Thrombocytopenia, leukopenia (requires regular testing)||Thrombocytopenia|
|Other||Requires monitoring due to narrow therapeutic window and significant pharmacokinetic variation.
May precipitate porphyria.
|Reduces efficacy of aminosteroids.
- Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
- Smith S, Scarth E, Sasada M. Drugs in Anaesthesia and Intensive Care. 4th Ed. Oxford University Press. 2011.
- CICM March/May 2010
- Petkov V. Essential Pharmacology For The ANZCA Primary Examination. Vesselin Petkov. 2012.
- Levetiracetam - Drug Information. FDA. 2009.