Antiepileptics Flashcards
What are seizures/convulsions/fits?
A series of abnormal discharge in a group/groups of neurons in the brain
What is epilepsy?
A chronic disorder characterised by recurrent seizures
(a) Primary Epilepsy
(b) Secondary Epilepsy - infection, tumour, anoxia, drugs, injury etc.
What are the different types of seizures?
Generalised Seizures:
- Tonic and Clonic (Grand Mal)
- Absence (Petit Mal) - children
- Myoclonic
- Atonic
Partial Seizures:
- Simple partial seizures (consciousness not impaired, only motor movement)
- Complex partial seizures (impaired consciousness) - Associated with abnormal discharges in the Temporal Lobe (TL). AKA TL epilepsy, psychomotor seizures
- Partial seizures which become generalised
Status Epilepticus
What are the drugs used for Tonic and Clonic (Grand Mal) and Partial Seizures?
- Phenytoin
- Carbamezepine
- Phenobarbitone
- Valproate
What is the mechanism of action of Phenytoin and Carbamezepine?
- Increases brain GABA
- Decreases Membrane Excitability by altering Na+ and Ca2+ conductance during action potential
- Increase refractory period via K+ current (hyperpolarisation)
What is the mechanism of action of Phenobarbitone?
Binds to GABA receptor channel complex Potentiates the action of GABA Low doses (GABA dependent): Potentiates GABA action by increasing the frequency of GABA channel opening induced by GABA (similar to Benzodiazepines - antianxiolytic) High doses (GABA independent): Independent of GABA, prolongs channel opening --> Death
What is the mechanism of action of Valproate?
- Increases GABA by preventing its breakdown (inhibits GABA transaminase)
- Hyperpolarises membrane potential by increasing K Conductance
What are the routes of administration of Phenytoin?
Oral: Slow but complete, depends on the formulation, Tmax varies varies between from 2-12hrs
IM: Unpredictable
IV: Used in status epilepticus
What are the pharmacokinetics of Phenytoin?
Low plasma concentration:
1st order kinetics
High plasma concentration (above therapeutic levels):
0 order kinetic (toxic levels as liver enzymes are saturated)
Which of the antiepileptics are hepatic enzyme inducers?
Phenytoin
Carbamezapine
Phenobarbitone
Hence, half life shortens with repeated doses
What is the clinical application of antiepileptics being hepatic enzyme inducers?
*DDI
Increase dosage due to increase breakdown will cause hepatic enzymes to be induced to breakdown other drugs instead
Eg. Contraindication with paracetamol - Increase toxic metabolites of paracetamol
What are the pharmacokinetics of Valproate?
- DDI
1. Highly bound to plasma protein, displaces other anti-epileptics (increases their free concentration and hence effect)
2. Displaces diazepam from binding proteins (increases their free concentration and hence effect)
3. Hepatic Enzyme Inhibitor: Inhibits the metabolism of other anti-epileptics + diazepam
What are additional therapeutic uses of carbamezapine?
Trigeminal Neuralgia
Mood Disorders
What are the adverse effects of phenytoin?
Dose Dependent systemic effects: Decrease vitamin D Gum hypertrophy Neurological Sedation Low B12 folate Skin: Hirsutism Immunlogical Drug Fever Lymph Node
Overdose:
Convulsion
Cerebellar Ataxia
Hypersensitivity Idiosyncratic
Skin: rashes, lupus-like
Bone Marrow
Liver: Necrosis
Teratogenic
What are the adverse effects of Carbamezapine?
Dose Dependent: GI upset Dyplopia Nystamus Drowsiness Folate Vit D Deficiency Antidiuretic effect
Overdose:
Ataxia
Confusion
Behavioural Disturbances
Hypersensitivity: Bone marrow Rash SLE Stevens Johnsons Syndrome Lymphadenopathy Hepatitis
Teratogenic
