Antiepileptics Flashcards
What is epilepsy?
A chronic disorder characterized by recurrent seizures (abnormal discharges of neurons in the brain)
Primary epilepsy
Secondary epilepsy: febrile seizures in young children with high fevers and infection, anoxia and after alcohol withdrawal
What are complex partial seizures?
Consciousness is not lost but impaired, associated with temporal lobe
What is status epilepticus?
Epilepsy which cannot be stopped, medical emergency where you have to administer IV benzodiazepines
What are the actions of antiepileptics?
Decreases membrane excitability to cause neurons to fire less frequently
Enhance effects of GABA inhibitory neurotransmitter effects on ligand gated chloride channels
What drugs are used for tonic clonic (grand mal) and partial seizures?
Phenobarbitone
Phenytoin
Carbamazepin
Valproate
How does phenytoin work?
Increases CNS GABA
Decreases membrane excitability by inhibiting sodium and calcium channels activation to stop action potential generation, reducing speed and effectiveness of sodium channels, stopping the neuron from sending repeated messages
Also increases refractory period via K+ current
How does carbamazepine work?
Increases CNS GABA
Decreases membrane excitability by inhibiting sodium and calcium channels activation to stop action potential generation, reducing speed and effectiveness of sodium channels, stopping the neuron from sending repeated messages
Also increases refractory period via K+ current
How does phenobarbitone work?
Binds to GABA receptor channel complex, potentiating GABA effects
At low doses, potentiates GABA by increasing frequency of channel opening induced by GABA
At high doses, independent of GABA and causes prolonged channel opening and death
How does valproate work?
Increases GABA by preventing its breakdown, inhibiting GABA-transaminase
Hyperpolarizes membrane potential by increasing K+ influx, thus reducing excitability of neurons
Absorption of phenytoin?
Oral: slow but complete
IM: unpredictable
IV: used in status epilepticus, immediate
Metabolism of phenytoin?
Hydroxylation and conjugation in the liver
Elimination of phenytoin?
First order in normal therapeutic range
When above therapeutic range, becomes zero order kinetics where elimination rate plateaus, can result in accumulation and toxicity
Therefore doesn’t go into steady state concentration
PK of phenobarbitone and carbamazepine?
Hepatic enzyme inducers, increasing metabolism of drugs and may result in other drug concentrations dropping below MEC
T1/2 shortens with repeated doses
PK of valproate?
Highly bound to plasma protein to displace other anti-epileptics like diazepam
Inhibits other anti-epileptic drug metabolism
What is carbamazepine used for?
Trigeminal neuralgia
Seizures
Mood disorders
Adverse effects of phenytoin?
Dose dependent systemic effects, may cause gum hypertrophy, hirsutism, with overdose can cause convulsions, cerebellar lesion (diplopia, cant walk properly), vestibular lesion (loss of balance) and folate Vit D deficiency
Can result in idiosyncratic hypersensitivity, lupus-like skin, bone marrow issues and liver necrosis
Can be teratogenic in pregnant patients, esp 1st trimester, can cause deformities in fetus
Adverse effects of phenobarbitone?
Sedation
Drowsiness
Ataxia
Diplopia
Behavioral disturbances like hyperactivity
Loss of concentration
Depression
Adverse effects of carbamazepine?
Dose dependent GI upset, diplopia, nystagmus, drowsiness, folate Vit D def, antidiuresis
Overdose can cause ataxia, confusion, behavioural disturbances
Hypersensitivity causing bone marrow issues, rashes, SLE, stevens johnson, lymphadenopathy, hepatitis
Teratogenic in animals
