General

Action at focus to reduce discharge reduction of propagation from focus Prolong inactivation state of Na channels Reduce Ca channel entry gate open but inactivated

Specic Drugs act at >1 site Inhibition of reuptake and receptor antagonism Drugs act in the periphery as well as in the brain Therapeutic effects in brain and side effects in periph Neuronal selectivity

Reduce ow through T-type Ca Reducing Pacemaker current underlying peaks in Absence seizures Increase Cl- ch opening through GABAa-BZD receptor complex

Selectivity
CNS Selectivity

Enhance GABAa mediated inhibition

Inhibition of GABA-Transaminase Inhibition of GABA uptake

Drugs

Reduce glutamate-NMDA mediated excitation

Reduction in release of glutamate Na and Ca channels

2nd most common neurological disorder after stroke 0.5-1 % of population Seizure: Sudden abnormal discharge of impulses from a group of neurons Symptoms determined by site (focus) and spread (localised/generalised) of discharge as well as amplitude No LOC Some LOC Discharge from focus with rapid spread to other brain areas 3 Hz discharge between thalamus and cortex Absence (Petite mal) Brief, sudden LOC and return Generalized Widespread polyphasic Repetitive contractions and relaxations Unconsciousness Brief, jerking movements Repeated seizures No recovery of consciousness Potentially life threatening Carbamezepine MOA Increase clearance of self and other drugs Phenobarbitone Carbamazepine Phenytoin Valproate Induction of hepatic microsomal enzymes Vigabatrin Use Inhibition of GABA-T enhancing brain GABA Add on therapy for refractory partial seizures Monotherapy? Sedation Occular Mental Minimal drug interaactions Na ch Decrease Glutamate release Add on therapy for refractory partial seizures Monotherapy Sedation Occular GIT Rash Minimal drug interactions Valproate Use Status epilepticus Myoclonus Tonic/Clonic Grand Mal Phenytoin S/E Classical anticonvulsants MOA Use Simple Seizures Complex Seizures Classication Phenobarbitone

MOA

Enhances GABAa Decreases glutamate release

Epilepsy
S/E

Highly sedative Behavioral changes Enzyme inducer No longer front line General T/C > Partial Enzyme inducer Prolongs inactivation state of Na channels reducing likelihood of repetitive discharge gen T/C, partial (status epilepticus) Occular, ataxia (sedation) Gingival hyperplasia Hirsuitism Dysmorphogenic (cleft palate) Lower doses, normal 1st order kinetics (constant fraction cleared/unit time Pharmacokinetics higher doses eliminate saturation mechanisms; constant amount cleared/unit time Small increase in dose gives large increase in conventration giving toxicity Na channels Partial-complex gen T/C Mod stabiliser Occular ataxia GIT Aplastic anaemia Agranulocytosis Enzyme inducer Na ch CA Enhance GABA gen T/C Absence Myoclonus Mood stabiliser GIT Tremor Hepatotoxicity Enzyme inhibitor Dysmorphogenic - Spina bida T-type Ca channel (NOT L-type Ca ch blockers MOA Ethosuxamide Use s/E MOA BZD Use Absence seizures GIT Enhance GABAa Diazepam (status epilepticus) Clonazepam (Absence, Myoclonus) Sedation Tolerance

Use

AntiConvulsants

MOA

Use

Decreases clearance of phenytoin phenobarbitol, and others giving toxicity

Drug interactions
Inhibition of hepatic microsomal enzymes S/E interactions with other Drugs

S/E

enzyme inhibitors such as cimetidine decrease clearance of phenytoin to give toxicity

Newer Agents
MOA

MOA

Lamotrigine

Use

S/E

S/E

S/E