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 brains 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 SEIZURESGeneralized seizures Partial seizuresBegin in one area of the brain & Begin in a specific area of therapidly spread throughout both brain & often indicate a localizedhemispheres of the brain brain lesion such as birth injury, trauma, stroke or tumor
PARTIAL SEIZURES GENERALIZED SEIZURES - Tonic-clonic / major motor seizure (common) • Tonic – involves contraction of skeletal- Simple partial seizures muscles (consciousness is not • Clonic – rapid rhythmic & symmetric jerking movements of the body affected) - Absence seizure (abrupt alterations in - Complex partial consciousness, lasts few seconds; etc seizures (level of blank, staring expression consciousness is with/without blinks of the eyelids) decreased) - Myoclonic type ( contraction of a muscle or group of muscles) - Akinetic type (absence of movement ) - Mixed seizures
CAUSES OF SEIZURES CHILDREN MIDDLE YEARS ELDERLY• Birth traumas • Head injuries • Brain tumors• Infections • Infections • Strokes• Congenital • Alcohol abnormalities stimulant drugs• High fevers • Medication side effects
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