5.3 Anticonvulsants Flashcards
What is the definition of a seizure?
Seizures are the clinical manifestation of epilepsy – these can be manifestations of sensory, motor or autonomic phenomena, memory disturbances and emotion changes
What is the definition of epilepsy?
Epilepsy is a condition defined as a tendency to recurrent, unprovoked seizures.
what is the epileptogenic zone in focal epilepsy?
defined localized cortical region, capable of triggering an epileptic seizure
What is required for the diagnosis of epileps?
The diagnosis of epilepsy requires an evaluation of seizure type (semiology), underlying predispositions, medical and family history and the electroencephalogram and brain imaging findings.
How are seizures classified under the ILAE guidelines
Seizures, the clinical manifestations, are classified into focal, generalized or unknown onset.
Which drugs enhance GABA mediated inhibition?
Benzodiazepines and phenobarbitone
Which drugs inhibits fast excitatory neurotransmission, principally that mediated by the excitatory neurotransmitter glutamate
Gabapentin and topiramate
Which drug inhibits neuronal action potentials by blocking voltage-gated sodium channels?
Phenytoin, carbamazepine, lamotrigine
Which drugs are neuronal calcium channels?
ethosuximide
Which drug has more than one mechanism of action?
topiramate
Which drugs are usually used as first line agents for focal epilepsy?
carbamazepine (CBZ), lamotrigine (LTG) or levetiracetam (LEV)
Which drugs are usually used for generalized epilepsies?
valproic acid (VPA), lamotrigine (LTG), levetiracetam (LEV)
which drugs worsen seizures in generalized epilepsies?
Carbamazepine (CBZ), vigabatrin (VGB) and gabapentin (GPT)
What drugs to use when in doubt what type of epilepsy?
Valproic acid (VPA), topiramate (TPM), lamotrigine (LTG) or levetiracetam (LEV).
Where is therapeutic drug monitoring mainly useful in?
- Phenytoin (but 1/3 still controlled on “sub-therapeutic” levels)
- Polytherapy (complex drug interactions)
- Assessing of compliance
- Suspected toxicity
- Intensive care setting
Phenytoin is a commonly used anti-epileptic drug. It undergoes hepatic metabolism and displays saturable kinetics. It is highly protein bound, hence free levels of phenytoin need to be monitored or calculated in low albumin states.
- Hepatic metabolism: oxidation (______________), followed by hydroxylation then conjugation and renal excretion of non-active metabolites
- Large inter-individual variation in metabolism
- ___________ kinetics, that is concentration dependent. ie., non-linear kinetics (rising quickly after point of enzyme saturation)
- Dosage: Start low (In UK, usual adult dose is 100-200mg daily, with increments of 50mg every 2/52 to 300mg daily, then 25mg increment. In Singapore usually started at _____________mg once daily, to about ______________ maintenance dose)
- If urgent, can load IV (20mg/kg at a rate of less than 50mg/min). Requires cardiac monitoring
- Highly (70-90%) protein bound so free PHT levels helpful in some circumstances (displacement by some drugs, low albumin states)
- P450 enzyme inducer - hence large number of important D/Is
- Phenytoin is a p450 enzyme inducer (CYP2C9 and CYP2C19) and hence may lower drug levels of other drugs such as oral contraceptive pills.
CYP2C9 >2C19;
Saturable;
230 – 400;
5mg/kg/day ;
Indication for PHT?
Partial epilepsy and status epilepticus
