Objectives:
- Describe the major types of epilepsy and their drug treatment
- Explain other uses of anti-epileptic drugs
- Review the possible mechanisms of action of anti-epileptic drugs
- Describe some of their adverse side effects
- Remember core drug list anti-epileptics: levetiracetam, phenytoin, valproate, gabapentin
What is epilepsy
This lecture defines epilepsy as an imbalance between inhibition and excitation. Too much excitatory brain activity will lead to an epileptic seizure. 1/3rd of people will not respond to medication and have uncontrolled seizures.
Epilepsy is diagnoses as at least 2 unprovoked seizures occurring more then 24 hours apart or 1 unprovokes seizure and the probability of further unprovoked seizures that is wimilar to the recurrence risk of 2 unprovoked seizures.
or a diagnosis of an epilepsy syndrome
Main types of Seizures
The main classes of seizures are focal, generalised or unknown.
focal seizures are ictal (seizure related) activity coming from a distinct brain region. can include loss of conciousness and progress to generalised seizure
generalised seizures are ictal activity in both hemispheres. Can include muscle jerking, or reduced muscle tone.
main types of seizures include
- tonic clonic
- clonic
- myoclonic
- atonic
- and absence
Epilepsy prognosis recurrent serizures in 28%-40% of patients recurrent seizures are associated with a 1.6 to 9 fold increase in mortality following first 2 yrs of diagnosis 64%-82% of generalised seizure patients become seizure free 25-75% of patients with focal seizures become seizure free
new drugs dont change incidence of seizure free periods but the side effects are more tolerable.
there is poor adherence in 30-40% of patients
treatment of epilepsy
start with antiepileptic at low dose and uptitrate every seizure until no more seizures. if max dose reached and seizures still are occuring then add another.
Causes of neuronal hyperactivity (not in lecture slides)
Anti epileptic drugs & Mechanisms of Action & Adverse Side Effects
Levetiracetam
- for focal and GTC seizures (generalised tonic-clonic seizures)
- may worsen myoclonic seizures Unproven MOA Hypothesis is it inhibits synaptic vesicle protein 2a SV2A regualtes readily releaseable pool size (numebr of viscles) inhibition of this reduces number of vesicles ready to go and therfore less release of glutamate
use in caution with patients with mood disorders and kidney dysfunctin
adverse effects
- Dizziness
- headache
- irritability
- loss of stregth and energy
- mood and behaviour changes
- sleepiness
limited drug interactions - (so lower compared to others?)
Phenytoin
- for focal and GTC seizures (generalised tonic-clonic seizures)
- may worsen myoclonic seizures
MOA: in
Valproate
- Focal, GTC seizures, absence, and myoclonic seizures
MOA: inhibitor of GABA transaminase, an enzyme which breaks down gaba in the axon terminal
also used to treat mania in bipolar
Adverse side effects
- feeling tired
- dizziness
- upset stomach
- vomiting
- tremor
- hairloss
- weight gain
- changes in behaviour
drug interactions: Carbepenem antibiotics
- Increase in valproate excretion
- this leads to increased seizure risk from lack of drug valproate inhibits metabolism of lamotrigine
Gabapentin
- for focal and GTC seizures (generalised tonic-clonic seizures)
- may worsen myoclonic seizures
- lower efficacy than others MOA: this inhibits voltage fated L-type Ca2+ ion channels. prevents calcium influx which Prevents depolarisation and release of neurotransmitters recheck
Phenytoin
This blocks voltage-gated Na+ ion channels. preventing depolarisation and no release of neurotransmitters. (no signalling at all actually).
This is not a first like drug due to side effects and drug interactions
Side effects being:
- jerking movements of the eyes
- decreased coordination
- shaking of the hands
- slowed thinking and movement
- memory problems
- slurred speech
- poor concentration
drug interactions: phenytoin is an inducer of CYP3A
Acute seizures
Benzodiazepines can be used for acute seizures, it is a GABAa pam