antiepileptics

Question 1

definition of epilepsy

Answer 1

a chronic disorder characterized by recurrent seizures

seizures: abnormal discharge in a group(s) of neurons in the brain

• pri epi (no known cause)
• sec epi (caused by drugs, tumour, anoxia - complete loss of o2 supply, infection, injury etc.)

Question 2

when faced w someone having seizure:

Answer 2

• note how long it lasts
• prevent injury (esp head) by moving nearby objects out of the way
• don’t restrict the person’s movement
• don’t put anything in the person’s mouth – accidentally swallow
• put person in recovery position so tongue doesn’t block airway

Question 3

types of seizures

Answer 3

generalized seizures
- tonic-clonic
- absence
- myoclonic
- atonic

partial seizures
- simple partial seizure (consciousness not impaired)
- complex partial seizure (consciousness impaired, temporal lobe affected)
- partial seizures that become generalized

status epilepticus
- more than 5min/more than 1 seizure in 5 min
medical emergency

Question 4

first-line tx of status epilepticus

Answer 4

IV benzodiazepine (lorazepam, diazepam)

Question 5

PD of antiepileptics

Answer 5

decrease membrane excitability

enhance effect of GABA (inhibitory neurotransmitter)

Question 6

drugs for tonic-clonic, partial seizures

Answer 6

PP C V

phenobarbitone (a barbiturate)
phenytoin
carbamazepine
valproate

Question 7

PD of phenytoin/carbamazepine

Answer 7

increase brain GABA

decrease membrane excitability by altering Na+, Ca2+ conductance during AP (stop the channels from being activated)

increase refractory period via K+ current

Question 8

PD of phenobarbitone

Answer 8

low dose: acts like BZ, potentiates GABA actions by increasing freq of Cl- channel opening induced by GABA (however, also increases duration of opening unlike BZ)

high dose: prolonged channel opening independent of GABA –> death

Question 9

PD of valproate

Answer 9

inhibits GABA transaminase (increase GABA)

hyperpolarises membrane potential by K+ conductance

Question 10

PK of phenytoin

Answer 10

oral: slow but complete (Tm 2-12h)
IV: immediate, used in status epilepticus

IM: unpredictable

metabolised by hyroxylation and conjugation in the liver

elimination: first-order kinetics in therapeutic range, zero-order kinetics when above therapeutic range

Question 11

PK of phenobarbitone/carbamazepine

Answer 11

hepatic enzyme inducer
- may decrease the bioavailability of other drugs which are metabolised by those enzymes, and may increase the bioavailability of drugs which require metabolism for their activation.

t1/2 shorten w repeated doses

Question 12

PK of valproate

Answer 12

highly bound to plasma proteins, displaces and inhibits the metab of other anti-epileptics

displaces diazepam from binding proteins (inhibits metab)

Question 13

therapeutic uses of carbamazepine

Answer 13

trigeminal neuralgia
seizures
mood disorders

Question 14

which anti-epileptic is contraindicated in pregnant pt?

Answer 14

phenytoin, carbamazepine, VALPROATE:
teratogenic – cause deformities

phenobarbitone can be given but there are safer options

Question 15

effect of anti-epileptics on other drugs

Answer 15

phenobarbitone, carbamazepine, phenytoin: CYP450 inducer
valproate: inhibits metab of other anti-epileptics and diazepam

• ask pt if they are on valproate before prescribing BZ: overdose effect