MANAGEMENT OF SEIZURES DR.PRAVEEN NAGULA
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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