Antiepileptic Lecture 2 PDF

CENTRAL NERVOUS SYSTEM A group of chronic disorder characterized by recurrent unprovoked seizures. Seizure:is a transient alteration of behavior due to disordered synchronous and rhythmic firing of population of brain neurons Partial (focal) Generalized Abse...

CENTRAL NERVOUS SYSTEM A group of chronic disorder characterized by recurrent unprovoked seizures. Seizure:is a transient alteration of behavior due to disordered synchronous and rhythmic firing of population of brain neurons Partial (focal) Generalized Absence seizures Simple partial seizures Myoclonic seizures Tonic seizures Complex partial seizures Clonic seizures Partial seizures with Tonic clonic secondary generalization Atonic seizures 1. Evaluate type of epilepsy 2. Start with a single drug (dose adjusted to plasma concentration) if not available according to patient response and tolerance 3. Add another drug or substitute if single drug fails to treat epilepsy 4. Gradual drug withdrawal 5. Full drug therapy should continue for 2-3 years after the last fit then gradually withdrawn 6. Drug monitoring is important Choice of drug therapy  Status epilepticus:prolonged seizures(>20 min of any type Most common is life threatening generalized tonic clonic convulsion Drug of choice :diazepam I.V, clonazepam I.V Alternative: phenytoin I.V, general anesthesia  Classification of anti-epileptic Drugs block phenytoin, carbamazepine, oxcarbazepine, lamotrigine, and sodium channels topiramate Drugs potentiate valproic acid, benzodiazepines, GABA phenobarbitone, primidone topiramate. Drugs that block Ethosuximide, trimethadione Ca channels Drugs inhibit Felbamate glutamate activity Antiepileptic actions: Block Na+ channel leading to neuronal membrane stabilization. Effective against partial and grand mal seizures. Not effective against absence seizures. Antidysrhythmic actions: Phenytoin has membrane stabilizing action and act as class I B. It inhibits Na entery during phase 0 of the cardiac cycle.  Uses Treatment of generalized tonic-clonic seizures. Treatment of partial seizure, status epilepticus. Treatment of trigeminal neuralgia. Anti arrhythmic: In ventricular arrhythmias especially with partial heart block.  Adverse effects Confusion, nystagmus, ataxia and slurred speech. Gingival hyperplasia, coarsening of facial features & hirsutism (hydontoin facies → not preferred in female) Hypotension, bradycardia Nausea, vomiting, constipation, toxic hepatitis. teratogenic (cleft palat). Osteomalacia and megalobalstic anemia (due to disorder of metabolism). Hyperglycemia due to decrease of insulin secretion. lymphadenopathy ( misdiagnosed for lymphoma) and hypersensitivity. Contraindication Liver disease. During pregnancy. Hypersensitivity. Agranulocytosis  At therapeutic concentration, it blocks Na+ channels as Phenytoin. It acts presynpatically to decrease release excitatory neurotransmitter (anti-convulsant action). Recent evidence suggested that it potentiate post-synaptic action of GABA. Mood stabilizing and increase release of ADH.  Uses Generalized tonic-clonic seizures. Partial seizures with or without secondary generalization. Treatment of trigeminal neuralgia (drug of choice). Treatment of bipolar disorders (manic- depressive disease).  Adverse effects Drowsiness, dizziness, diplopia & cognitive impairment. Allergic reaction: fever, lymphadenopathy, rash, systemic lupus erythematosus, exofoliative dermatitis, blood dyscrasias e.g. aplastic anemia and agranulocytosis & jaundice (hepatic dysfunction). May exacerbate minor motor seizures. Water intoxication and hypernatremia.  Valproate BROAD SPECTRUM ANTIEPILEPTIC Dynamics: Blocks sodium channels. Increase GABA in brain At high doses it increase membrane potassium conductance. Block ca channels. Uses Treatment of absence seizures and myoclonic seizures. Used for the treatment of generalized tonic-clonic epilepsy and for partial seizures. Not used in status epilepticus. Treatment of bipolar disorder and migraine prophylaxis. Adverse effects Hallucination, ataxia, tremors, nystagmus, diplopia & sedation. GI disturbances Idiosyncratic pancreatitis, idiosyncratic hepatotoxicity. Teratogenic (neural tube defects). Alopecia (hair loss) and weight gain. Displace Phenytoin from plasma protein. ETHOSUXIMIDE (ZARONTIN) Dynamics: Block T type calcium channel of primary afferent neuron Uses: Treatment of absence seizures (drug of choice) Adverse effects Most common GIT adverse effects Drowsiness, headache, dizziness, euphoria. Gum hypertrophy, swelling of the tongue, leukopenia, agranulocytosis (uncommon). METHSUXIMIDE (COLONTIN) Uses: generalized absence (petit mal) seizures, generalized tonic-clonic or myoclonic seizures. Adverse effects: like ethosuximide.  PHENOBARBITONE Uses: 1- Generalized tonic-clonic seizures. 2- Partial seizures with or without secondary generalization.. PRIMIDONE (MYSOLINE) Structurally related to phenobarbitone. Well absorbed, partially metabolized to Phenobarbital and phenyl ethyl malonamide that responsible for its action. It used in tonic clonic and partial seizures Adverse effects: similar to Phenobarbital.  BENZODIAZEPINES Diazepam: drug of choice in status epilepticus. Clonazepam: BROAD SPECTRUM ANTI EPILEPTIC Used in status epilepticus 1 mg slow IV. Second choice in grand mal, petit mal, psychomotor epilepsy could be given orally New antiepileptic drugs LAMOTRIGINE TOPIRAMATE FELBAMATE VIGABATRIN GABAPENTIN TIAGABINE