Anti-epileptics Flashcards
What are some types of epilepsy?
- Generalised seizures
- tonic & clonic (grand mal): whole body convulsions
- absence (petit mal): unconscious for that moment - Partial seizures
- simple partial seizures (consciousness not impaired, but blur n confused) - Status epilepticus
A seizure that lasts longer than 5 minutes, or having more than 1 seizure within a 5 minutes period, without returning to a normal level of consciousness between episodes is called status epilepticus.
Name the 4 types of anti-epileptic drugs.
- Phenobarbitone
- Phenytoin
- Carbamezapine
- Valproate
Phenytoin and Carbamazepine have the same ___________? How do they work?
Same Pharmacodynamics! (What the drug does to the body)
Phenytoin & Carbamazepine:
- increases brain GABA
- decreases membrane excitability: alter Na+ & Ca2+ conductance during action potential
- hyperpolarises membrane potential: increases refractory period via increases K+ conductance
Generally, what is the pharmacodynamics of anti-epileptic drugs?
Aka, how do anti-epileptic drugs work?
-
Decreases membrane excitability
Or - Enhance effect of inhibitory neurotransmitters, esp GABA
How does Phenobarbitone work? (PD)
Enhances effect of inhibitory neurotransmitters.
- binds to GABA-receptor channel complex => potentiates GABA actions
Low dose: increases frequency of GABA-gated Cl- channel opening
- potentiates GABA actions (not independent of GABA)
- action is like that of benzodiazepine here
High dose: increases duration of GABA-gated Cl- channel opening
- independent of GABA
- prolonged channel opening => death
Pharmacodynamics of Valproate?
- increase GABA: inhibits GABA-transaminase => inhibit GABA breakdown
- hyperpolarise membrane potential: increases refractory period via K+ conductance
Name the anti-epileptic that is an enzyme inhibitor.
Valproate.
- inhibits the metabolism of other anti-epileptics => AEs stay in body for longer at higher levels
- (under PK of valproate)
Name the anti-epileptics that are enzyme inducers.
Phenobarbitone & Carbamazepine (& phenytoin too?)
- hepatic enzyme inducers
- increases liver metabolism of drugs
- aka reduces half life, half life shortens w repeated doses
Pharmacokinetics of phenytoin?
Phenytoin is a trouble maker.
- half life/absorption time very unpredictable => time to reach max: Tm=2-12hrs
Elimination rate: changes based on conc.
At normal therapeutic range/doses: follows 1st order
At above therapeutic range/doses: follows zero order elimination
=> liver enzyme saturated, constant amt of drug elimination, independent of drug conc.
PK of valproate:
- highly bound to plasma protein, displaces other anti-epileptics
- displaces diazepam from binding proteins
- inhibits the metabolism of other anti-epileptics (enzyme inhibitor, decreases metabolism)
Name some adverse effects of phenytoin.
Dose-dependent effects
1. Gum hypertrophy
2. Skin hirstutism (hairy growth on skin)
Overdose
3. Convulsion
4. Cerebellar ataxia
Idiosyncratic Hypersensitivity
5. Skin: rashes, lupus-like
6. Liver necrosis => jaundice, cannot digest fat properly, oil in faeces
Teratogenic
7. Fetal abnomalities (phenytoin cannot be prescribed in pregnancies!!)
Name some adverse effects of phenobarbitone.
- Sedation
- Drowsiness
- Ataxia (difficult walking, poor muscle control)
- Diplopia (double vision)
- Behavioural disturbance including hyperactivity
- Loss of concentration
- Depression
Adverse effects of Carbamazepine.
Dose-dependent
1. Nystagmus (uncontrolled eye movements)
2. Diplopia
3. Drowsiness
Overdose
4. Ataxia
5. Confusion
Hypersensitivity
6. SLE
7. Stevens Johnson syndrome (rare, serious disorder of the skin and mucous membranes)
Teratogenic
Adverse effects of Valproate.
Dose dependent
1. Upset GI
2. Sedation
3. Weight gain
Hypersensitivity
4. Hepatotoxicity
5. Thrombocytopenia
Teratogenic
6. spina bifida (exposed spinal cord)
7. CVS
Drug interactions of Valproate.
Increases other Anti-epileptic levels
- enzyme inhibitor of other anti-epileptics
