Management of seizures

MANAGEMENT OF SEIZURES

DR.PRAVEEN NAGULA

1.APPROACH TO A CASE OF A SEIZURE 2.ANTIEPILEPTIC DRUG CLASSIFICATION 3.MECHANISM OF ACTION AT RECEPTORS 4.DRUGS IN EACH SEIZURE DISORDER 5.INDIVIDUAL DRUG DESCRIPTION 6.STATUS EPILEPTICUS 7.SPECIFIC SCENARIOS 8.CONCLUSION

Approach to a case of seizure

SEIZURE DISORDER

GENERALISED

PRIMARY GENERALISED SEIZURES

CONVULSIVETONIC CLONIC

SEIZURES

TONICCLONIC

NONCONVULSIVEMYOCLONICATONIC

AUTOMATISM

SECONDARY GENERALISED SEIZURES

FOCALSIMPLE FOCAL SEIZUR

ES

COMPLEX

FOCAL SEIZUR

ES

FOCAL TO

GENERALISED SEIZUR

ES

Investigations 1.EEG 2.CT scan 3.MRI 4.ROUTINE INVESTIGATIONS- serum

electrolytes,blood glucose levels,ABG. 5.LUMBAR PUCTURE

FOUR PARTS 1.Use of anti epileptic drugs 2.Surgical excision of epileptic foci 3.Removal of causative and precipitating factors 4.Regulation of physical and mental activity

Course of a case of EPILEPSYPRINICIPLES

60- 70% are treated by complete medications.20-25% attacks are reduced in severityStart with one drug..

Increase the dose to maximum level

Shift to other drug in case of no response Adequate trial of each drug to be givenIncrease the dose of the substituting drug while decreasing the weaning drug

TRADITIONAL AEDs 1.BROMIDES 2.PHENOBARBITAL 3.PHENYTOIN 4.CARBAMAZEPINE 5.BENZODIAZEPINES 6.ETHOSUXIMIDE 7.PRIMIDONE 8.VALPROIC ACID

NEWER ANTIEPILEPTICs 1.OXCARBAZEPINE 2.PREGABALIN 3.GABAPENTIN 4.TOPIRAMATE 5.LAMOTIRIGINE 6.LEVETIRACETAM 7.TIAGABINE 8.FELBAMATE 9.ZONISAMIDE 10.FOSPHENYTOIN

EXCITATORY GLUTAMATERGIC SYNAPSE

PHENYTOINCARBAMAZEPINE

LAMOTRIGINE

ETHOSUXIMIDELAMOTRIGINEGABAPENTINPREGABALIN

RETIGABINE

LEVETIRACETAM

LACOSAMIDE

PHENOBARBITALTOPIRAMATELAMOTRIGINE

FELBAMATE

GLUTAMATE

INHIBITORY GABA ergic SYNAPSE

GAT -1 TIAGABINE

GABA-TVIGABATRIN

GABA A BENZODIAZEPINES

Choice of AEDs by type of adult seizure disorder

SEIZURE TYPE INITIAL CHOICE SECOND LINE

1.TONIC CLONIC Carbamazepine,valproate,phenytoin

Lamotrigineoxcarbazapine

2.MYOCLONIC valproate Topiramate,Levetiracetam,zonisamide

3.FOCAL Carbamazepine,phenytoin

ValproateLamotrigineOxcarbazepinelevetiracetam

4.ABSENCE valproate Ethosuximide,lamotrigine

5.UNCLASSIFIABLE valproate lamotrigine

COMBINATION of AEDs for REFRACTORY seizuresCOMBINATION INDICATION

VALPROATE and LAMOTRIGINE or LEVETIRACETAM

Focal or generalized seizures

VALPROATEand ETHOSUXIMIDE Generalised absence

CARBAMAZEPINE and VALPROATE

Complex partial seizures

LEVETIRACETAM,LAMOTRIGINE or TIAGABINE

Partial seizures

TOPIRAMATE and LAMOTRIGINE or LEVETIRACETAM

Numerous types

PHENYTOIN Oldest non sedative antiseizure drug More soluble parenteral drug is fosphenytoin M.O.A- blocks sustained high frequency repetitive firing

of action potentials –Na channels – at therapuetic concentrations Inhibits release of serotonin,NEPromotes uptake of dopamine Inhibits MAO activityStabilization of membraneReduces calcium permeability

Accumulates in liver,brain,muslce fat. Elimination is dose dependent. T1/2 -24 hours When oral therapy is started -300mg/day regardless of

the body weight.Increased the dose by 25-30 mg in adults

Drug interactions – sulfonamides displace phenytoin High affinity for Thyroid binding globulin Conc. is with use of phenobarbitone,carbamazepine concentration of phenytoin –isoniazid Toxicity – nystagmus,diplopia,ataxia,sedation Gingival hyperplasia,hirusitism Coarsening of facial features Mild peripheral neuropathy Osteomalcaia Causal relation to hodgkin’ s lymphoma agranulocytosis

PHENYTOIN METABOLISM

CARBAMAZEPINE Closely related to IMIPRAMINE M.O.A –similar to phenytoin – blocks Na channels Potentiates post synaptic action of GABA Inhibits uptake ,release of NE Uses – focal seizures,GTCS,trigeminal neuralgia,BPD Not sedative INDUCES MICROSOMAL enzymes Valproic acid its levels, Phenytoin ,phenobarbitone – levels Only oral form. 15-25mg/kg/d – children 1gm/day -adults

CARBAMAZEPINE metabolism

Phenobarbital Oldest of the available antiseizure drugs –sedative DOC in seizures of infants M.O.A –exact is unknown

Enhancement of inhibitory processes,dimintion of excitatory transmission

Na channel blocking at high doses GABAa receptor action

May worsen absence ,atonic ,infantile spasms In febrile seizures <15ug/ml -ineffective

VIGABATRIN Irreversible inhibitor of GABA T

(degrades GABA) Increases GABA at synaptic sites Inhibits GABA transporter FOCAL seizures,WEST syndrome T1/2 -6-8 hrs 500mg bid 2-3 g/day Toxicity -drowsiness,dizziness,weight gain

Lamotrigine Similar to phenytoin in action Absence attacks in children –voltage gated Ca

channels Add on treatment Linear kinetics T1/2 -24 hrs

Felbamate M.O.A –not known Third line drug because of aplastic anemia,hepatitis NMDA receptor blockade via glycine binding site Increases phenytoin levels,valproate Decreases carbamazepine Lennox gestaut syndrome

Gabapentin,Pregabalin GABAPENTIN –analog of GABA Spasmolytic,antiseizure drug Does not act on GABA receptors Adjunctive drugs Not metabolised Not bound to plasma proteins Excreted via renal

Topiramate Substituted monosaccharide M.O.A –phenytoin Potentiates GABA action 200- 600 mg/ da TIAGABINE –inhibitor of GABA uptake LEVETIRACETAM – analog of piracetam ,M.O.A

unknown,not metabolised by cytochrome P450 Linear kinetcis

Ethosuximide Pure petit mal drug Reduces T TYPE CALCIUM CURRENTS in thalamus Inhibits na k ATPase Depresses cerebral metabolic rate Inhibits GABAaminotransferase Not protein bound Decrease the dose with valproic acid

Valproic acid Sodium salt,or free acid Fatty carboxylic acid Branching,unsaturation – increases lipophilicty Effective agianst absence seizures Effective in myoclonic seizures Hepatotoxicity 90% bound to plasmaproteins Sedation with phenobarbital use Bipolar disorders,migraine prophylaxis

Benzodiazepines 6 Lorazepam –long acting than dioazepam Diazpeam –short acitng,GTCS,respiratory depression Clobazam – 1.,5 benzodiazepine Nitrazepam Clobazate Acetazomaide –mild acidosis in brain,rapid

tolernace

Drug interactions

Teratogenic effects Valproic acid

Surgical treatment

STATUS EPILEPTICUS

Classification of STATUS EPILEPTICUS

AEDs In Pregnancy

Doses

NEWER drugs in pipeline

answers

REFERENCES 1.KATZUNG’S 11 th Ed PHARMACOLOGY 2.LIPPINCOTT ‘S PHARMACOLOGY 3.MEDICINE UPDATE 2009 4.HARRISON’S PRINCIPLES OF INTERNAL MEDICINE

17 th Ed 5.ADAM and VICTOR’S NEUROLOGY,9 th Ed 6.www.medscape.com 7.www.ilae.org 8.www.netterimages.com

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