Pharmacology Anti-epileptic drugs Flashcards
What is seizure?
A paroxysmal event due to an abnormal, hypersynchronous discharge from a mass of CNS
neurons
Diverse manifestations ranging from convulsion (observable) to an experience (subjective)
Single seizure due to a correctable or avoidable circumstance (ie provoked) is not necessarily epilepsy
– Alcohol
– Hypoglycemia
– Pyrexia
– Sleep deprivation
**Classification of Recurrent seizures
– Lower Risk (30-50%)
– Single seizure
– Normal EEG
– Normal brain scan
**Recurrent seizures
– Higher Risk (80%)
- Previous (undiagnosed) seizures
– Epileptiform EEG
– Abnormal brain scan
Appropriate investigations for epilepsy and its purpose
- Blood tests (Liver function, blood
chemistry)
– EEG
– Brain Scan (CT/MRI)
Purpose: To determine risk of recurrent seizures
Pathophysiology of seizures
Neuronal depolarization (“firing”) depends on membrane potential
- A seizure occurs when there is excessive synchronous
depolarization, usually starting from defined regions (“foci”) and
spreading to other regions - Due to unbalanced excitatory and inhibitory receptor / ion channel
function which favour depolarization -> dysregulated discharge
Causes of epilepsy
Congenital or hereditary
- Brain injury, scarring or tumor
- Infections: meningitis or encephalitis
- Blood glucose alterations
- Metabolic disorders, eg., adrenal insufficiency leading to hyponatremia
Epilepsy classification
Generalized seizures
a) Tonic clonic (Grand mal)
b) Absence (Petit mal)
c) Myoclonic
d) Atonic
- Partial seizures
a) Simple (consciousness not impaired)
b) Complex (consciousness impaired)
- Status epilepticus
***Rationale for antiepileptics
Decrease membrane excitability by altering Na+ and Ca2+ conductance during action potentials.
Enhance effects of inhibitory GABA
neurotransmitters.
Note: not all compounds are effective
against all types of seizures
***1) Phenytoin blockade of
2) Phenytoin suitable for all types of seizures except _________.
1) Blockade of voltage-depedent Na+ channels.
2) except absence seizures.
***1) Valproate blockade of
2) also inhibits
3) suitable for all types of seizures, including
1) voltage-dependent Na+ and Ca2+
channels
2) GABA transaminase -> increased GABA
3) absence seizures
***1) Carbamazepine blockade of
2) Suitable for all types of seizures
1) voltage-depedent Na+ channels (like phenytoin).
2) except absence seizures
***Antiepileptics – Adverse Effects (General)
Dose Related Side Effects:
– drowsiness, confusion, nystagmus, ataxia, slurred speech, nausea, unusual behavior, mental changes, coma
Non-Dose Related:
– hirsutism, acne, gingival hyperplasia, folate
deficiency, osteomalacia, hypersensitivity reactions (including Stevens-Johnson syndrome)
Benzodiazepines: Mechanism of action
GABA—inhibitory transmitter in brain
regions: acts via GABAA receptors Cl- (chloride) channels
Potentiates influx of Cl- ions leading to hyperpolarization ->
neurons not firing
Enhance effects of inhibitory GABA neurotransmitters.
Drug Treatment of Epilepsy
Which antiepileptic drug should be chosen initially?
Antiepileptic drug treatment strategy should be individualised according to the seizure type, epilepsy syndrome, co-medication, comorbidity and the
individual’s lifestyle and preferences (and/or those of their family and/or carers as appropriate).
Patients should be commenced on monotherapy initially. Should the patient develop an adverse
reaction to the initial drug or if the initial monotherapy is unsuccessful, monotherapy using another drug should be tried.
All antiepileptic drugs licensed for monotherapy have similar efficacy in newly diagnosed epilepsy. For this reason, the medicine the prescribing physicians are most familiar with can be used.
Carbamazepine, phenytoin and sodium valproate can be
considered first line treatments for newly diagnosed partial and generalized tonic clonic seizures.
When are antiepileptic drug levels tested?
Antiepileptic drug levels may help clinical management under the following clinical indications:
(1) Assessment of compliance to drug treatment for patients with refractory epilepsy
(2) Assessment of symptoms due to possible antiepileptic drug toxicity
(3)Titration of phenytoin dose.
Routine checking of antiepileptic drug levels without a clear clinical indication is not required, and is not
cost effective.
