Epilepsy Flashcards
Phenytoin
Voltage-gated Na+ channel block.
Inhibits action potential propagation.
Induces CYP enzymes, increasing metabolism of other drugs such as carbamazepine, warfarin and OCs. Gradual effects include hyperplasia of gums and hirsutism. Can cause foetal malformations including cleft plate. A small increase in drug concentration can lead to a large increase in drug concentration. Narrow TI, large individual variation.
Tonic-clonic and partial seizures.
Carbamazepine
Voltage gated Na+ channel block.
CYP inducer, increases oestrogen metabolism (so use of a non-hormonal contraception advised), may cause neural defects in pregnancy.
Tonic-clonic and partial seizures.
Ethosuximide
T-type Ca++ channel block.
Decreases the firing rhythm of thalamic relay neutrons. Inhibits uncontrolled bursts of APs.
Works against absence seizures.
Phenobarbital
- non-selective CNS depressant used as an anticonvulsant in children
- positive allosteric modulator - enhances GABA transmission by increasing GABA pore opening duration
- inhibits glutamate transmission
- ADRs: dangerous in OD (resp depression), tolerance, dependence, drug-drug interactions, CYP inducer, decreases plasma concentration of steroids, OCs and warfarin. - Given IV for status epileptics.
- Broad spectrum AED.
Benzodiazepines
GABA receptor activation. Opens channel allowing Cl- into the cell - brings neuron further away from threshold. Problematic for chronic use due to dependency. Given IV for status epilepticus.
Broad spectrum AED.
Sodium Valproate
Also valproic acid and valproate. Has multiple mechanisms: t-type calcium channel blocker, inhibition of GABA transaminase, and Na+ channel blocker. Can cause hepatotoxicity and neural tube defects in pregnancy.
Broad spectrum AED.
Lamotrigine
Newer anti-epileptic. Dual MoA: blocks Na+ channels and inhibits glutamate release.
Broad spectrum AED.
What is epilepsy?
A chronic disorder of the brain resulting in tendency to have recurrent seizures. Disorder in the brain affects the function of cerebral cortex causing neurons to fire uncontrollably. As a result, the body receives mixed signals resulting in seizure.
What are the triggers of epilepsy?
- flashing lights
- flickering from TV/computer
- sudden loud noises or repetitive sounds
- alcohol consumption
- cigarette smoking
- stress
- headaches
- lack of sleep
What are the types of seizures?
Two main categories: partial or focal (remain conscious), and generalized (lose consciousness). In partial seizures only part of the brain is involved, whereas in generalized seizures the whole brain is affected.
What are the two main types of generalized seizures?
Tonic clonic - strong extensor muscle spasm followed by synchronous jerks.
Absence seizures - appearance of day dreaming or staring, most common in children 4-14 y.o.
What is the principle of drug therapy for epilepsy?
- Some forms of epilepsy may be worsened by certain drugs
- Particular types of epilepsy respond best to certain drugs
- Successful therapy depends on correct diagnosis
- Plasma level monitoring may be required
- Numerous drug interactions to be aware of
What is the main MoA for anti epileptics?
- act to stabilize the abnormally hyper-excitable epileptogenic focus of neurons and prevent the spread of the seizure
- many drugs have multiple actions and precise mechanisms are not understood
What are the differences between traditional and newer AEDs?
Traditional: vast clinical experience, incomplete efficacy, unfavourable kinetics, narrow TI, adverse CNS effects, and numerous drug interactions, enzyme inducers and inhibitors.
Newer: safer, more expensive, may help with partial seizures, less drug interactions.
What drug/s is used to treat absence seizures?
Ethosuximide
What drug/s is used to treat tonic clonic seizures?
Carbamazepine, phenytoin
What are the broad spectrum AEDs?
Valproic acid, lamotrigine, phenobarbital, BZDs
