Anticonvulsants

Used in treatment of epileptic seizures. Epilepsy is a condition in which intermittent abnormal high-frequency firing of localized group of cerebral neurons results in seizures. The discharge may remain localised or may spread to other regions of the brain. The goal of an anticonvulsant is suppress the rapid and excessive firing of neurons that start a seizure

What is a seizure an abnormal, synchronized electrical depolarization of neurons in the central nervous system. Name five major causes of seizures 1. Idiopathic, CNS infection, fever, metabolic defects, cerebral trauma. List of different types of seizures Partial (simple/complex), generalized (tonic-clonic, wide spread, polyphasic, repetitive contraction/relaxation, unconsciousness), status epiepticus, absence (3HZ discharge, brief sudden loss of consciousness), febrile (seizure triggered by a rise in body temp), myoclonic (brief jerking movements, occurs at any age). Partial seizures- abnormal discharges occur from a focal area within brain. Simple partial seizure involves a neurological symptom that can be sensory (gustatory/olfactory hallucination), motor or psychomotor. Consciousness always retained. A complex partial seizure is when discharge spreads and causes unconsciousness and postictal (post seizure) confusion. Most complex partial seizures originate in the TEMPORAL LOBE. Generalized tonic clonic seizures involve entire cerebral cortex. Tonic loss of bowel, bladder control, consciousness. Rigidity occurs. Clonic Jerking movement of entire body A partial seizure can progress into grand mal seizure and is known as partial seizure with secondary generalization. Status epilepticus seizure without regaining of inhibitory mechanisms. Continuous seizures not separated by periods of regained consciousness. This is a medical emergency.

Drug
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Mechanism of Action and Use

Prolong inactivation state of Na+ channels. Reduce Ca2+ channel entry Enhance GABAA mediated inhibition. Reduce glutamate-NMDA mediated excitation. -

Side Effects
Highly sedative Behavioural changes Inhibition of hepatic microsomal enzymes to give toxicity.

Phenobarbitone

Uses - Generalized Tonic-Clonic > Partial - Induction of hepatic microsomal enzymes

Phenytoin
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Prolongs inactivation state of Na+ channels, reducing likelihood of repetitive discharge. Low doses1st order kinetics [constant fraction cleared per unit/time] Higher doses elimination mechanisms saturated 0 order kenetics followed. Constant amount cleared per unit/time. Meaning small increase in dose gives large increase in concentration, hence toxicity. Enzyme inhibitors such as cimetidine decrease clearance of phenytoin to give toxicity.

Ocular Ataxia Sedation Gingival hyperplasia Hirsuitism dysmorphogeniccleft palate

Uses - Generalized Tonic Clonic - Partial - Induction of hepatic microsomal enzymes

Carbamazepine

Uses - Partial Complex and Generalized Tonic-Clonic - Mood stabilizer - Induction of hepatic microsomal enzymes (increases clearance of itself)

Prolong inactivation state of Na+ channels

Occular Ataxia GIT problems Aplastic anaemia Agranulocytosis Enzyme inducer

Valproate

Prolong inactivation state of Na+ channels Reduce Ca2+ channel entry Enhance GABAA mediated inhibition.

Uses - Generalized Tonic Clonic, absence, myoclonus - Mood stabilizer - Reduce T-type Ca channel entry.
2+

Ethosuximide

Uses - Gneralized Absence seizures (petit mal)

Enhances GABAA mediated inhibition

GIT problems Tremor Hepatotoxicity Inhibition of hepatic microsomal enzymes (decrease clearance of phenytoin) Dysmorphogenic spina-bifida GIT problems such as:dyspepsia vomiting nausea cramps constipation diarrhea Sedation Tolerance

Benzodiazepines Uses
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1. Diazepam Generealized Status epiepticus seizures 2. Clonazepam Generalized absence and myoclonus seizures

NEW AGENTS Gabapentin

Its therapeutic action on neuropathic pain is thought to involve voltage-gated N-type calcium ion channels. Binds to the 2-1 subunit of the voltagedependent calcium channel in the CNS. Sedation Ataxia Minimal drug interactions

Uses Add-on therapy for refractory partial seizures Monotherapy?

Lamotrigine

Decreases glutamate mediated excitation Prolong inactivation state of Na+ channels

Sedation Ocuclar GIT problems Rash Minimal drug interactions