Anti epileptic drugs

2.Carbemazepine (tegretol), oxcarbazepine (TRICYCLIC GROUP): It is structurally related to anti-depressants (Imipramine). Mechanism of action: blocking Na channels. Kinetics: • It is absorbed slowly • It cross BBB rapidly (high lipid solubility) • It acts as enzymes inducer • Its metabolism in liver is inhibited by cimetidine and valproate

Uses 1. all partial seizures (the drug of 1st choice) 2.tonic clonic seizure. 3.It mostly used in trigeminal neuralgia. 4.manic depressive patients Side effects: 1.CNS:Drowsiness, vertigo, ataxia and blurred vision also may produce stupor, coma and respiratory depression with chronic administration. 2.GIT:Irritation of stomach and may cause nausea and vomiting. (anemia ) aplastic with 3.granulocytosis and thrombocytopenia. 4.it may cause liver toxicity

Uses: 3. Barbiturates group: A. Phenobarbital: long acting barbiturates act by enhancing the activity of GABA. Uses: 1- simple partial seizure 2- febrile convulsions in children (1st choice ). B. Primidone • It metabolized in the body to phenobarbitone and phenyl ethyl malonamide. • Much of its anti-convulsive activity is related to phenobarbitone

Uses 1.Tonic clonic 2. partial simple epilepsy 3.Phenyl ethyl malonamide is effective in partial complex seizure • Primidone can be used with carbemazepine and phenytoin allowing smaller doses of these drugs to be used ..It has high plasma protein binding • It is well absorbed orally Side effects similar to that of phenobarbitone.

4- Sodium valproate and valproic acid(carboxylic group) : This drug acts by: 1.inhibiting the enzyme responsible for break down of GABA ( GABA transaminase ) leading to increase GABA. 2.increasing the activity of GAD (glutamic acid decarboxylase) which increases GABA synthesis. Uses It is effective against myoclonic seizure It is effective in absence attack It is effective in tonic clonic seizure But what limits its use is its hepatic toxicity.

Kinetics: • It is bound to plasma ptn . It is effective orally and absorbed rapidly • It is bound to plasma ptn • It is metabolized by the liver. • Produces enzyme inhibition so it inhibits its own metabolism and that of other drugs as phenobarbitone, phenytoin and carbemezepine. • It displaces phenytoin from its plasma ptn binding

Side effects: • Produces some GIT symptoms like nausea and vomiting. But the main side effect is hepatic toxicity or liver failure which occurs after maximally 2-12 weeks, there will be transient increase in liver enzyme. • It might produce coagulation disorders due to inhibition of platelets aggregation. • In contrast to other anti-epileptic drugs it produce increase in awareness and increase in appetite weight increase which might be unwanted effect. • Also a special effect is that it causes fall of hair followed by growing of new hair which is curved and has different color

Side effects 5. Ethosuxamide(succinimide group): It is the drug of choice in the treatment of absence seizures. - It acts by blocking Ca+2 currents in thalamic neurons. -Absorbed orally not bound to plasma ptn. -25% excreted unchanged, 75% metabolized in the liver. Side effects - Irritating to the stomach causes nausea, vomiting, in addition to drowsiness, lethargy, sedation, anxiety, agitation and inability to concentrate. - it produce idiosynacrytic skin allergic reaction- called (Steven Johnson Syndrome) which is characterized by complete denudation of skin and mucous membrane Also may cause some blood problems like leucopenia, aplastic anemia and thrombocytopenia

6. Benzodiazepines: These drugs enhance the action of GABA they are among the safest and the most well tolerated drugs in the treatment of epilepsy. • Diazepam: it is the drug of first choice in status epilepticus. • Clonazepam: is effective in absence seizure • Clorazepate • Lonazepam ………….

7. Others 1.Vigabatrin: it is structurally related to GABA, acts by irreversibly inhibiting GABA transaminase enz. Similar to Na­ valproate. • Used in treatment of generalized and partial seizures when other drugs are inadequate. • It is not metabolized nor induce hepatic enzyme (doesn't affect the liver metabolism. • Its side effects similar to other drugs as confusion, psychosis and also may cause weight gain (may be considered as side effect).

2.Lamotrigine: either used as monotherapy or combined with other drugs Stabilizes neuronal membrane by -blockage of Na­ channels, -also it may lead secondarily to decrease release of excitatory a.a as glutamate and aspartate. It has similar efficacy as other drugs with less frequent CNS side effect It might cause maculopapular rash.

3-Gabapentin: it is an analogue to GABA but doesn't appear to work through GABA pathway but it may interfer with metabolism or reuptake of GABA, it has no effect on the liver (doesn't interfere with it) It is excreted unchanged.

4-Topiramate: It is one of the sugars (sulphamate substituted Monosaccharide) • It acts by: 1. blockage of voltagE sensitive Na+ channels, 2. Increase GABA activity and. 3.Blocks some glutamate receptors

5- Tigabine: block GABA uptake into pre synaptic neuron. 6- Acetazoleamide: • It is an old drug used as diuretic. • It is carbonic anhydrase enz. inhibitor. • This enz. which is present in (kidneys and brain) and causes acidosis which might affect seizure

7-Felbamate: receptor NMDA blocker via glycine binding site. 8-Zonisamide: act by blocking of Na and Ca channel, effective in infantile spasm. 9-Levetiracetam: unknown Mechanism.

Pregabalin binds to the alpha-10 subunit of voltage-gated calcium channels in the CNS, inhibiting excitatory neurotransmitter release. 11- Divalproex sodium valproate is a combination of sodium valproate and, valproic acid and GIT it reduced to valproate when it reach .

Divalproex and barbiturates should be avoided in pregnancy

Notes: Drugs of 1st choice: • Absence seizure: clonazepam, ethosuxamide and Na­valproate • Myoclonic seizure: Valproate. • Tonic-clonic: nearly all • Partial seizure: nearly all with exception that ethosuxamide work only in absence seizure.

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