Disease and treatment regime in Epilepsy
Drugs
The mechanism of epilepsy treatments tend to be drugs that increase inhibition in the brain. This can be through positive allosteric modulation, blocking of channels that carry APs, or as a substrate that acts like GABA etc.
Levetiracetam
This is often a first line antiepileptic, and has an unproven MOA, it may inhibit synaptic synaptic vesicle protein 2A which has important function in regulating number of vesicles ready to release NTs. Inhibition of SV2A acts to decrease release of NTs and acts to decrease signalling.
It has limited drug interactions
This is especially used for focal and GTC seizures. It may worsen myoclonic seizures.
Cautions
Use in caution in patients with mood disorders and kidney dysfunction.
Side effects
- Dizziness
- Headache
- Irritability
- Loss of strength and energy
- Mood and behaviour changes
- Sleepiness
Phenytoin
Phenytoin inhibits the coltage gated Na+ ion channels, leading to decreased depolarisation and inhibitory effects.
This is not a first line drug due to the many side effects and drug interactions
Side effects
- 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 CYP3A4. This means it increases production of CYP3A4 enzymes which means higher action of this enzyme. 40% of drugs are metabolised by CYP3A4 and so taking this drug will lead to increased plasma levels of many drugs.
Valproate
Valproate acts to inhibit GABA transaminase, therefore leading to increase synaptic concentrations of GABA. it is also used to treat mania, in bipolar disease.
It is used to treat focal, GTC, absence, and myoclonic seizures.
Side effects
- Feeling tires
- Dizziness
- Upset stomach
- Vomiting
- Tremor
- Hair loss
- Weight gain
- Changes in behavior
Interactions
Carbepenem antibiotics increase excretion of valproate, and will need to be accounted for as lower blood concentration of valproate can lead to increased risk of seizure.
Valproate inhibits the metabolism of lamotrigine (sometimes used as a antiepileptic). Therefore increasing effect of antiseizure medication, (and adverse effects) when prescribed together.
Gabapentin
Gabapentin inhibits voltage gated L-type calcium channals. This prevents calcium influx in neurons and therefore less presynaptic vesicle release. This will lead to inhibitory effects, due to lowered of glutamate concentration in the synaptic cleft.
This is a second line therapy and can also be used for neuropathic pain.