Wednesday, 6 March 2019

Epilepsy treatment | Epilepsy medication | Overview

• Epilepsy overview
• Epilepsy types
• Classification of drugs
• Epilepsy treatment
• Epilepsy medication
• Top 10 antiepileptic drug

EPILEPSY OVERVIEW 

Epilepsy is a Greek word that means convulsions.
Epilepsy is a disorder of brain function characterized by paroxymal cerebral dysrhythmia, manifesting as brief episodes ( seizures) of loss or without characteristic body movements (convulsions), sensory or psychiatric phenomena.



EPILEPSY TYPES

GENERALIZED SEIZURES 

1. Generalized tonic-clonic seizures (GTCS, grand mal epilepsy) : It is characterised by the following sequence of symptoms: Aura-epileptic cry-loss of consciousness-fall to the ground-tonic phase-clonic phase-period of relaxation-post-epileptic automatism with confusional states.

2. Absence seizures  (petit mal epilepsy) : It is characterised by sudden onset of starting, unresponsiveness with momentary loss of consciousness.

3. Myoclonic seizures : It consist of single or multiple sudden, brief, shock-like contractions.

PARTIAL SEIZURES

1. Simple partial seizures (SPS) : The manifestations depend on the region of the cortex involved. There may be convulsions or light flashes without loss of consciousness.

2. Complex partial seizures  (CPS) : It is characterised by aura-amnesia-abnirmal behaviour and automatism.

CLASSIFICATION

1. Barbiturate : Phenobarbitone 
2. Deoxybarbiturate : Primidone
3. Hydantoin : Phenytoin
4. Iminostilbene : Carbamazepine 
5. Succinimide : Ethosuximide
6. Aliphatic Carboxylic acid : Valproic acid
7. Benzodiazepines : Clonazepam, Diazepam
8. Phenyltriazine : Lamotrigine
9. Cyclic GABA analogue : Gabapentin
10. Newer drugs : Vigabatrin, Topiramate, Levetiracetam

EPILEPSY TREATMENT 

Antiepileptic drugs suppress seizures but do not cure the disorder; the disease may fadeout though after years of successful control.

The cause of epilepsy should be searched in the patient; if found and treatable, an attempt to remove it should be made.

General principles of symptomatic treatment with antiepileptic drugs are here :

Choice of drug and dose is according to the seizure type and need of the individual patient.

Initiate treatment early, because each seizure episode increases the propensity to further attacks.

Start with a single drug, preferably at low dose---gradually increase dose till full control of seizure or side effects appear.

If full control is not obtained at maximum tolerated dose of one drug, substitute another drug. 

Use combinations when all reasonable monotherapy fails.

Therapy should be as simple as possible. A seizure diary should be maintained.

All drug withdrawals should be gradual (except in case of toxocity), abrupt stoppage of therapy without introducing another effective drug can precipitate status epilepticus.

Prolonged therapy is needed - may be life long or at least 3 years after the last seizure.

When women on antiepileptic therapy conceive, antiepileptic drugs should not be stopped. Though most antiseizure drugs have been shown to increase the incidence of birth defects, discontinuation of therapy carries a high risk of status epilepticus.

Fits occuring during pregnancy themselves increase birth defects and may cause mental retardation in the offspring.


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EPILEPSY MEDICATION 

Top 10 antiepileptic drugs used are :
1. Phenobarbitone 
2. Primidone
3. Phenytoin
4. Carbamazepine
5. Valproic acid
6. Gabapentin
7. Topiramate
8. Clonazepam
9. Clobazam
10. Ethosuximide

Phenytoin 

Mechanism of action 
Phenytoin acts by stabilizing the neuronal membrane and prevents the spread of seizure discharges.

The sodium channels exist in three forms: resting, activated and inactivated states.

Phenytoin delays the recovery of Na+ channels from inactivated state, thereby reduces the neuronal excitability.

At high concentrations, phenytoin inhibits Ca2+ influx into the neuron, reduces glutamate levels and increases responses to GABA.

Pharmacokinetics 
Absorbed slowly through GIT,
Widely distributed and highly bound to plasma protiens,
Metabolized in liver.

Adverse effect 

Hypertrophy and Hyperplasia.
Hypersensitivity reactions.
Hirsutism.
Hyperglycaemia.
Megaloblastic anaemia.
Osteomalacia.
Hypocalacaemia.
Foetal Hydantoin syndrome.

Carbamazepine

Mechanism of action 
Like phenytoin, Carbamazepine slows the rate of recovery of Na+ channels from inactivation, thereby reduces the neuronal excitability.

Pharmacokinetics 
Absorbed slowly from GIT,
Binds to plasma protiens,
Well distributed in the body including the CSF and metabolized in the liver.


Repeated use of drug causes enzyme induction and reduces the effectiveness of drug itself.

Adverse effect 

Sedation, drowsiness, ataxia, vertigo, blurred vision, nausea, vomiting, mental confusion.
Rashes
Eosinophilia
Lymphadenopathy
Hepatitis
Bone marrow depression 
Aplastic anaemia 
Agranulocytosis

Valproic acid 

Mechanism of action 
Valproate delays the recovery of Na+ channels from inactivation.
It blocks T-type Ca2+ current in thalamic neurons.
Increases the activity of GABA in brain by...

By increasing synthesis of GABA by stimulating GAD (glutamic acid decarboxylase).
By decreasing degradation of GABA by inhibiting GABA-T (GABA transaminase) enzyme.

Pharmacokinetics

Rapidly and completely absorbed from GIT.
Highly bound to plasma protiens.
Metabolized in liver.
Excreted in urine.

Adverse effect 
Common - Nausea, vomiting, anorexia, abdominal discomfort.
CNS - Sedation, ataxia, tremor.
Rashes, alopecia, curling of hair.
Rare but serious complication is fulminant hepatitis.
Teratogenicity




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