Anti epileptic drugs.

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Presentation transcript:

Anti epileptic drugs

Anti epileptic drugs Seizure: is a transient alteration in behavior due to a disordered rhythmic depolarization of a population of brain neurons. Epilepsy: a disorder of brain function that is characterized by periodic and unpredictable occurrence of seizure

Normally when we move any muscle of our body there are signals arising from the brain resulting from firing (depolarization) of certain neurons, while in epilepsy there is uncontrollable spontaneous firing of some neurons in the brain. Classification of epileptic seizures: 1-partial seizure the loss of consciousness may occur after the occurrence of the seizure. 2-generalized seizures. there is loss of consciousness from the beginning

1. Generalized seizure: a- Absence seizure: occur in young children characterized by brief loss (30 second) of consciousness. By other words (abrupt onset of impaired consciousness associated with stunning and cessation of ongoing activity). b. Myclonic seizure: brief shock-like contraction of muscle.

C. Tonic clonic seizure: generalized seizure characterized by tonic followed by clonic contraction. d- Febrile seizure: attack associated with fever in children. e- Status epilepticus: a process in which the seizures tend to occur one after the other. 2. Partial seizure: A. Simple partial: it is associated with preservation of consciousness. B. Complex partial: it is associated with loss of consciousness (impaired), associated with movement.

partial secondarily generalization is other type which means that it begins as partial and then go to tonic - clonic seizure. The antiepileptic drugs can act by 3 approaches: 1.Block Na + or K+ or Ca++ channels 2.Increase the activity of inhibitory neurotransmitter (GABA). 3.Decrease the activity of excitatory neurotransmitter like glycine and glutamate. Groups of antiepileptic drugs: One of the most important groups of drugs 1.Hydantoins: The most important drug of this group is Phenytoin ,fosphenytoin,Mephenytoin, Ethotoin and phenacemide

Mechanism of action: Therapeutic uses: Phenytoin suppresses the repetitive firing of neurons by 1-decreasing the movement of Na and K in neurons in the resting and during depolarization stage. Also may decrease Ca++ influx during depolarization. 2-At high conc. It may enhance the activity of GABA But it produces some degree of drowsiness and lethargy without progression to hypnosis (bs phenytoin is not generalized CNS depressant). Therapeutic uses: 1. all partial seizures (simple or complex) 2. tonic-clonic seizures. 3.Status epilepticus (by I.V.) .

Pharmacokinetics: 1-Pharmaceutical form (the company may contain some additives) will greatly affect the bioavailability of phenytoin, so if we change the company change the bioavailability. 2.It has a plasma protein binding activity, so anything interferes with its binding may increase its activity. 3.Phenytoin is subjected to zero order kinetics and at therapuetic level it transfers to 1st order kinetics. 4.It is hepatic enzyme inducer. it induces insignificantly its own metabolism but the metabolism of other drugs Significantly induced including other antiepileptic drugs.

5. Affected by liver enzymes inhibitors e. g 5.Affected by liver enzymes inhibitors e.g. Sodium valproate cimetidine, and erythromycin. Note: The only 3 drugs subjected to zero order kinetics are phenytoin, alcohol, and aspirin. Side effects: 1. Decrease the ability to learn. Also impairment of cognitive function 2. CNS side effects including: sedation up to delirium .It might produce acute cerebellar disorder, ataxia, loss of balance and even convulsions. 3. peripheral neuropathy. 4.Skin rashes , this is dose related. 5.Inhibition of collagenase enz. This leads to inhibition of collagen catabolism which causes gum hypertrophy (hyperplasia) and coarsening of facial features.

6.It may cause duputriens contracture 7.Megaloblastic anemia ( decrease folic acid). 8.Osteomalacia ( decrease metabolism of Vit D). 9. Hirsutism, Hyperglycemia or glucosuria and Abnormal ADH release. Note: phenytoin uses as 1-anti-arrhythmic in cardiac arrhythmia (stabilizing effect to the tissues ). 2- trigeminal neuralgia.

2.Carbemazepine (tegretol), oxcarbazepine (TRICYCLIC GROUP): It is structurally related to anti-depressants (Imipramine). Mechanism of action: blocking Na channels so it stabilize membrane to depolarization. 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 and blocking of Na channel. 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.

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