Anti-Epileptic Drugs Flashcards
What is the definition of epilepsy?
Episodic discharge of abnormal high frequency electrical activity in brain leading to seizure
Diagnosis requires evidence of recurrent seizures unprovoked by other identifiable causes
What causes epilepsy?
Increased excitatory activity
Decreased inhibitory activity
Loss of homeostatic control
Spread of neuronal hyperactivity
What are the two major categories of seizures?
Partial
General
Describe what is meant by a partial seizure.
Partial (or focal) seizures
Simple (conscious)
Complex partial seizures (impaired consciousness)
Secondary generalised seizures
Loss of LOCAL excitatory/inhibitory homeostasis
Increased discharges in focal cortical area
Symptoms reflect are affected:
- Involuntary motor disturbances
- Behavioural change
- Impending focal spread accompanied by ‘Aura’
- May become secondarily generalised
Describe what is meant by generalised seizures.
Generated centrally, spread through both hemispheres with loss of consciousness
Tonic-clonic seizures
Absence seizures
Many other types/sub-types recognised
What is status epilepticus?
Most seizures are short lived (up to 5 mins)
Some seizures prolonged beyond this or experienced as a series of seizures without a recovery interval
These are known as Status Epilepticus
Treated as a Medical Emergency
Untreated Status Epilepticus can lead to brain damage or death (SUDEP)
What are the dangers of epilepsy?
Uncontrolled epilepsy is not a benign condition
Physical injury relating to fall/crash
Hypoxia
SUDEP - sudden death in epilepsy
Varying degrees of brain dysfunction/damage
Cognitive impairment
Serious psychiatric disease
Significant adverse reactions to medication
Stigma/Loss of livelihood
How is epilepsy caused?
Primary
No identifiable cause - idiopathic
Secondary
Medical conditions affecting brain
Vascular disease
Tumours
What are some precipitants of epilepsy?
Sensory stimuli - Flashing lights, strobes Brain Disease/Trauma - Brain injury, stroke, drugs/alcohol, lesion Metabolic disturbances - Hypo - glycaemia/calcaemia/natraemia Infections - Febrile convulsions in infants Therapeutics - Some drugs can lower fit threshold
What are the therapeutic targets for AEDs?
Voltage Gated Sodium Channel Blockers
Enhancing GABA Mediated Inhibition
What is the mechanism of action of VGSC Blockers?
It only gets access to binding site during depolarisation
This prolongs the inactivation state and when there is abnormal firing it blocks those channels and prevents them from over firing
Then the VGSC blocker detaches from the binding site once the membrane potential is back to normal
Tell me about carbamazepine.
VGSC blocker
\well absorbed, 75% protein bound
Initial t1/2 = 30 hrs BUT strong inducer of CYP450
Affects it’s own phase I metabolism
Repeated use t1/2 = 15 hrs
Treats:
- Generalised Tonic-Clonic
- Partial - All
- NOT absence seizures
Drug monitoring
- Dosing to effect and adjust dosing as t1/2 decreases
- Check BNF with any other drugs given
What are the ADRs and DDIs of carbamazepine?
ADRs
CNS - dizziness drowsy ataxia motor disturbances numbness tingling
GI - upset vomiting
CV - can cause variation in BP
Contraindicated with AV conduction problems
Others: Rashes Hyponatraemia
DDIs Due to the CYP450 inducing Phenytoin (AED) \/ Warfarin \/ Systemic corticosteroids \/ Oral contraceptives \/ Antidepressants - SSRIs, MAOIs, TCAs interfere with action of carbamazepine
Tell me about phenytoin.
VGSC blocker
Well absorbed BUT 90% bound in plasma
Also CYP450 inducer
Very variable t1/2 = 6-24hrs
Treats:
Generalised Tonic-Clonic
Partial - All
NOT absence seizures
Drug monitoring
Close monitoring of free conc. plasma
What are the ADRs and DDIs of phenytoin?
ADRs CNS - dizziness ataxia headache nystagmus nervousness Gingival hyperplasia (20%) Rashes - hypersensitivity \+ Stevens Johnson (2-5%)
DDIs Competitive binding with: - Valproate (AED) - NSAIDS - Salicylate Increases plasma levels Exacerbates Non-Linear PKs Very wide range of interactions Oral contraceptives \/ Cimetidine - phenytoin /\
