CHOICE OF ANTIEPILEPTIC DRUG.ppt

1、CHOICE OF ANTIEPILEPTIC DRUG,Magnitude of the problem,Epilepsy affects: approximately 1 in 50 children and 1 in 100 adults.,PHARMACOTHERAPY OF EPILEPSY: The issues,Is treatment justified? When to start treatment? How to start drug treatment? Which AED? Which dosage? When should AED combinations be u

2、sed? Risks associated AED treatment? How long should treatment be continued?,PHARMACOTHERAPY OF EPILEPSY: The issues,Is treatment justified? When to start treatment? How to start drug treatment? Which AED? Which dosage? When should AED combinations be used? How long should treatment be continued?,18

3、40,1860,1880,1900,1920,1940,1960,1980,2000,0,5,10,15,20,Bromide,Phenobarbital,Phenytoin,Primidone,Ethosuximide,Sodium valproate,Benzodiazepines,Carbamazepine,Vigabatrin,Zonisamide,Lamotrigine,Felbamate,Gabapentin,Topiramate,Fosphenytoin,Oxcarbazepine,Tiagabine,Levetiracetam,More,Year,AEDs,Antiepilep

4、tic drug development,Major considerations in choosing an AED,Type of seizure Type of epileptic syndrome Adverse effect profile Age drug of choice Absence seizures: Valproate, Ethosuximide,Best first AED,Differentiation of partial Versus Generalised epilepsy is not always possible in infants Eg: Drav

5、ets syndrome ( severe myoclonic epilespy of chiildhood) usually presents with hemiconvulsion. Infantile spasm: Pattern can change from generalised to partial seizures,Best first AED,Efficacy: If the seizure can not be typed Valproate, lamotrigine or topiramate, Levitiracetum,Best first AED,Tolerabil

6、ity: Valproate Newer AEDs are costly compared older ones,Newer AEDS,What is real advantage of these newer drugs? Are they going to replace older drugs? Does high cost of these drugs justify its usefulness? What are the situations where we can use these drugs?,Newer drugs,No major differences in effi

7、cacy between drugs Major differences in side effects profiles Drug interaction potential also differs Drug choice should be tailored to the patient,EFFICAY OF NEWER AED AS MONOTHERAPY,RCT have shown no major difference in seizure control between: LTG vs CBZ* LTG better tolerated LTG vs DPH* LTG bett

8、er tolerated OXC vs CBZ* CBZ increased allergy OXC vs VPA* No difference OXC vs DPH* withdrawal more in DPH GBP vs CBZ* Withdrawal more in GBP GBP vs LTG TPM vs CBZ FLE, BECTS, LKS, BEOP, Angelmans syndrome Negative myoclonus Use AEDs with favourable pharmacokinetic interactions: e.g. valproate and

9、lamotrigine. (enabling lower doses of lamotrigine to be used); Avoid combinations with similar mechanisms of action and/or unhelpful phamacokinetic interactions: e.g. Carbamazepine and phenytoin Carbamazepine and Lamotrigine,If combination therapy fails!,Consider surgery! If this is not an option; G

10、o back to the combination that gave optimum, control,INFANTILE SPASMS,ACTH, Vigabatrin Zonisamide ( open label studies) Levitiracetum,PHARMACOTHERAPY OF EPILEPSY: The issues,Is treatment justified? When to start treatment? How to start drug treatment? Which AED? Risks associated AED treatment? Which

11、 dosage? When should AED combinations be used? How long should treatment be continued?,Getting the dosage right,As important as choosing the right drug! Some AEDs require slow titration e.g. CBZ, LTG, TPM and TGB Dosage should be tailored to meet individual needs Monitoring drug levels may help with

12、 dose tailoring,EPILEPSY - MANAGEMENTDRUG DOSE Preferably avoid in infants with Abnormal LFT, multiorgan failure, polytherapy or in those where exact aetiology is unclear,Tolerability in infants It is a high-affinity synaptic vesicle protein 2A (SV2A) ligand inhibitory activity at neuronal voltage-d

13、ependent sodium channels High responder rate ( 55% versus 16%) Excellent tolerability,Emerging new AEDS,Carisbamate. Adjunctive treatment for partial-onset seizures It inhibits voltage-gated sodium channels has a broad-spectrum of activity in a number of animal models of seizure and drug refractory

14、epilepsy Responder rate( 28% versus 6%) Mode of action: unknown Efficacy INH increases it. Anti HIV agents increases the level of Lamotrigine, Levitiracetum Oral Clobazam Oral Topiramate,NEWER DRUGS IN STATUS:I/V valproate,CSF penetration is similar to I/V diazepam Good alternative to phenytoin. Sei

15、zure control in 80% of patients More effective than Phenytoin (66% vs 42%) No significant side effect: No sedation, No hypotension.,NEWER DRUGS IN STATUS:I/V valproate,Dose: I/V bolus: adult dose: 15-30 mg/kg Children; 20-40 mg/kg At the rate of 50mg /mt Adverse effects: Hyperammonemic encephalopath

16、y Pancreatitis Thrombocytopenia Contraindication Children with acute liver failure Patients with inherited metabolic diseases,NEWER DRUGS IN STATUS:I/V Levetiracetum,Advantages: Rapid titration. No drug interaction Good safety profile Excellent choice in hepatic failure I/V dose; 1000 mg i/v Efficac

17、y: 100% efficacy in BZD resistant SE,NEWER DRUGS IN STATUS:Topiramate,Oral loading Topiramate: 10mg/kg followed by 5mg/kg/day,USE Partial, secondarily generalised, Absences, myoclonus LGS, ESES Alcohol withdrawal seizures Benign childhood partial epilepsies Intermittent therapy in catamenial epileps

18、y,CLOBAZAM,Side effects; Behavioral disturbances, irritability Sedation Tolerance,Topiramate,Broad spectrum: Partial, secondarily generalised Primary generalised LGS Childhood epilepsy syndromes Infantile spasms SMEI Atypical absence Reduced visual acuity, myopia, and increased intraocular pressure

19、Combination of topiramate with valproate can be hepatotoxic. Renal stones Hypohidrosis,Levitiracetum,Broad spectrum; Partial seizures, secondarily generalised Photosensitive epilepsy Idiopathic generalised epilepsy Absences Myoclonus-JME,Levitiracetum,Advantages: Highly effective Generally well tole

20、rated No significant drug interaction Main disadvantge: Mood ,Side effects; Ataxia, dizziness Mental slowing, Impaired concentration. Hypohidrosis-heat stroke Renal calculi Weight loss,Lamotrigine,Broad spectrum: Partial, generalised. LGS, Infantile spasm Advantage: Moderate effectiveness, well tole

21、rated. Main side effect: High instance of rash (appears within 4 weeks) Slow titration Extensive drug interactions,PHARMACOTHERAPY OF EPILEPSY: The issues,Is treatment justified? When to start treatment? How to start drug treatment? Which AED? Risks associated AED treatment? Which dosage? When shoul

22、d AED combinations be used? How long should treatment be continued?,# Factors to be considered: 1. Probability of relapse 2. Presence of adverse effect 3. Psychological attitude 4. Legal implications,DRUG TREATMENT -When to stop?,When to stop AED,Recurrence risk in all types of epilepsy after 2 year

23、s of seizure free period : 29% Most Recurrences occur in the first year If a patient is seizure free for more than 2 years after stopping treatment, subsequent recurrent risk is very low.,When to stop AED,RISK FACTORS FOR HIGH RECURRENCE : Patients with abnormal EEG Known structural lesion and /or neurol.deficit Occurrence of many seizures before control Long duration between therapy & seizure control More than one type of seizure Adult onset complex partial seizure The seizure type,When to stop AED,Early versus late withdrawal ( 2 yrs)Early discontinuation was associated with grea