Pharmacology of epilepsy Flashcards
Define epilepsy?
enduring predisposition to generate (recurrent unprovoked) epileptic seizures and the associated cognitive, psychological and social consequences
Give examples of causes of provoked seizures?
- drugs
- head trauma
To be diagnosed with epilepsy what must you have?
1) 2 unprovoked seizures (more than 24 hours apart)
2) 1 unprovoked seizure and more than 60% risk of further seizures
3) epilepsy syndrome (symptoms of epilepsy
Are most people seizure free after taking anti-epileptics?
yes only 36% are considered parmacoresistant
Are most people seizure free after taking anti-epileptics?
yes only 36% are considered pharmacoresistant
What factors should be considered when choosing an AED?
- Type of seizures
- efficacy
- co-morbidities
- tolerability
- pharmacokinetics
What are the three seizure types?
Focal onset
Generalised onset
Unknown onset
What is focal onset seizure?
- starts in one area of brain at one point in time
How will seizures in frontal lobe present?
- speech disturbance
- motor problems if in motor cortex
How will seizures in parietal lobe present?
- sensory disturbance if in somatosensory cortex
What are the different targets of the AED’s?
- GABA receptors, open channels resulting in inhibitory response of GABA, inactivating the neurone
- Glutamate receptors (AMPA & NMDA), block transmission reducing excitation
What are the main anti-epileptic drugs?
Carbamazepine Phenytoin Sodium valproate lamotrigine Levetiracetam Topiramate
What drugs should be given to those with absence and myoclonic seizures?
Lamotrigine or levetiracetam
- as these work for the seizure type and have least co-morbidities
When is sodium valproate used?
- very efficacious
- but lots of side effects
- so used in drug resistant patients
What are the problems associated with Carbamazepine?
Hepatic inducer of CYP3A4 so interacts with lots of other drugs
can also cause disturbance of liver function
What are the side effects of Carbamazepine?
- Dose dependent: Diplopia, ataxia, sedation and fatigue
- fatigue, nausea, rash and GI disturbances (get with all AED’s)
- Bone marrow suppression, hypersensitivity, hepatic derangement and rash
What is the MOA of carbamazepine?
Sodium channel blocker
What is the MOA of phenytoin?
Sodium channel blocker
What are the side effects of Phenytoin?
acute - ataxia, diplopia, nystagmus, rash, sedation at high levels
chronic - gym hyperplasia, coarse face, hirsutism, osteopenia, low folate and peripheral neuropathy
Exclusive to phenytoin - fever, rash, lymphadenopathy and teratogenic
What are the problems with phenytoin?
- hepatic enzyme inducer so interacts widely with other drugs
- any enzyme inhibiting or inducing drugs will change levels of phenytoin
What is the major issue with sodium valproate?
teratogenic - can’t give to pregnant women or those trying to get pregnant
What is the MOA of sodium valproate?
sodium channel blocker, GABA and glutamate receptor actions
What are the side effects of sodium valproate?
generally well tolerated most important is teratogenic VALPROATE Appetite inc + weight gain Liver failure Pancreatitis Reversible hair loss Oedema Ataxia Teratogenicity, tremor and thrombocytopenia Encephalopathy
What are the advantages of levetiracetam?
- few side effects
- no sig interactions
- almost no teratogenic properties
What are the disadvantages of levetiracetam?
- side effects of irritability and behavioural changes make patients ‘not themselves’
What are the side effects of levetiracetam?
- irritability
- anxiety
- fatigue
- dizziness
- behavioural changes
- bone marrow
- (rare) psychosis
What is the MOA of lamotrigine?
sodium channel blocker
What are the side effects of lamotrigine?
- Stevens-Johnson rash (important as can be fatal)
- insomnia
- less cognitive effects
- stabilises mood so good for patients with depression
What are the interactions of lamotrigine?
- combined pill
- valproate
What is the MOA of topiramate?
- sodium/calcium channel blocker
- GABA and Glutamate effects
What are the side effects of topiramate?
- sedation
- anorexia
- weight loss
- psychiatric
- word finding difficulties
- Possibly teratogenic and rare kidney stones and glaucoma
What anti-epileptic drugs are associated with weight gain?
- Valproate
- Topiramate
What should be prescribed along with carbamazepine to maintain bone health?
Vitamin D
What AEDs are most associated with mental health problems?
- Levetiracetam
- must discuss suicide risk
- some AEDs can interact with anti-depressants (most don’t)
What other conditions can carbamazepine be used to treat?
Neuropathic pain (pain caused by damage to somatosensory system)
What AEDs are used to treat bipolar disorder?
- carbamazepine
- lamotrigine
- valproic acid
What AEDs are used to treat migraine?
Topiramate
What AEDs are used to treat Trigeminal neuralgia?
Carbamazepine
What AEDs are used to treat obesity?
topiramate
What AEDs are used to treat anxiety?
clobazam
pregabalin
