ANTI-EPILEPTIC DRUG

EPILEPSY…????SEIZURE…????

SAWAN….???

FIT…???

Objectives

• To know types of drugs used in treating seizure/epilepsy

• To know the pharmacological actions of the drugs

• To know the effects of drugs on the specific functions of the system

Seizure

• 2nd neurologic disorder after stroke in US• brief episodes of brain dysfunction resulting from

abnormal electrical activity of cerebral neurons causing involuntary movement, sensations or thoughts

• Causes: diseases, infection, head injury, heredity etc• Epilepsy- chronic seizure (abnormal & excessive

electrical discharges of nerve cells)

Seizure

• A seizure occurs when the brain's nerve cells misfire and generate a sudden, uncontrolled surge of electrical activity in the brain

• During a seizure, each cell may fire as many as 500 times a second, much faster than the normal rate of about 80 times a second in the brain and spinal cord.

CLASSIFICATION OF SEIZURES

Generalized seizures Partial seizures

Begin in one area of the brain & rapidly spread throughout both hemispheres of the brain

Begin in a specific area of the brain & often indicate a localized brain lesion such as birth injury, trauma, stroke or tumor

PARTIAL SEIZURES

- Simple partial seizures (consciousness is not

affected)- Complex partial

seizures (level of consciousness is

decreased)

- Tonic-clonic / major motor seizure (common)

• Tonic – involves contraction of skeletal muscles

• Clonic – rapid rhythmic & symmetric jerking movements of the body

- Absence seizure (abrupt alterations in consciousness, lasts few seconds; etc

blank, staring expression with/without blinks of the eyelids)

- Myoclonic type ( contraction of a muscle or group of muscles)

- Akinetic type (absence of movement )- Mixed seizures

GENERALIZED SEIZURES

CAUSES OF SEIZURES

ELDERLYMIDDLE YEARSCHILDREN

• Birth traumas• Infections• Congenital

abnormalities• High fevers

• Head injuries• Infections• Alcohol

stimulant drugs• Medication side

effects

• Brain tumors• Strokes

Antiepileptic / Antiseizure Drugs

Tonic-clonic & partial seizures

Absence seizuresMyoclonic seizures Others

Carbamazepine (Tegrefol)Phenytoin (Dilantin)

Ethosuximide (Zarontin)

Valproic acid (Depakene)

Clonazepam (Klonopin)

Levetiracetam (Keppra)

Gabapentin (Neurontin)

Pharmacokinetic

• Slightly soluble; good absorption; 80-100% dose reaching circulation

• Not highly bound to protein plasma• Cleared by hepatic mechanism; active

metabolites cleared by liver• Medium-to long acting

Carbamazepine (Tegrefol)

• Strong inducing agent; therefore many drug interactions

• It is given orally• It is metabolized in the liver• Contraindicated in patients with previous bone

marrow depression

Phenytoin (Dilantin)

• Use for patients with tonic-clonic seizures and some partial seizures

• Acts to promote intracellular removal of sodium during the refractory period

• Antagonism (blocking) of Na+ channels to reduce excitability

• Antagonism of Ca++ channels• Adverse effects: CNS (ataxia, drowsiness) & GIT

(nausea, vomiting)

Ethosuximide (Zarontin)

• The main drug used to treat absence seizures, may be uses with other AEDs for treatment of mixed seizures

• Adverse effects: nausea and anorexia. (mental disturbances)

Clonazepam (Klonopin)

• Act by potentiating the actions of GABA causing neurotransmission inhibition (primarily in the CNS)

• Can be used to induce sleep (high dose), anticonvulsant therapy and reduction in muscle tone.

• Adverse effects: drowsiness, fatigue, dizziness, muscle hypotonia, co-ordination disturbances; also poor concentration, restlessness, confusion, amnesia

Valproic acid (Depakene)

• Thought to enhance the effects of GABA in the brain

• Used to treat manic reactions in bipolar disorder & to prevent migraine headaches

• Extensively metabolised in the liver• Rapidly transported across the blood brain

barrier• Adverse effects: Nausea, vomiting, anorexia,

abdominal pain, diarrhoea & weight gain

Gabapentin (Neurontin)

• Incompletely absorbed in the gut• Acts via:– Increased synthesis and release of GABA– Decrease degradation of GABA– Inhibition of Ca++ channels

• Adverse effects:– CNS effects (dizzy, drowsy, fatigue, headache, double visions)– Nausea and vomiting

• Contraindication: be careful with sudden withdrawal in the elderly due to kidney effects and alterations in acid-base balance.

Side Effects

• Antiepileptic drugs frequently produce CNS and gastrointestinal side effects

• Some antiepileptic drugs infrequently cause severe hematologic or hepatic toxicity

• Valproate and phenytoin cause birth defects