Epilepsy Flashcards
Most AEDs are metabolised hepatically in the liver and excreted in the urine. What are the four notable exceptions?
Gabapentin Vigabtrin Levetiracetam Pregabalin All excreted unchanged in urine.
What are the four main targets in the brain for AEDs?
Sodium ion channels
Caclium ion channels
The GABA system and receptor agonists
Glutamate receptor antagonists
Phenytoin, lamotrigine and carbamazepine work how?
Affecting the sodium channels of neurones impacting the propagation of action potentials.
Lamotrigrine also works at some calcium channels.
How does Topiramate work?
Blocks calcium channels and via glutamate receptors.
How does ethosuximide work?
It works specifically on reducing absence seizures by targeting and blocking the T-type calcium channel with is involved in the specific brain acitvity that hapens in absence seizures.
How does Gabapentin work in epilepsy?
Increases GABA, the main inhibitory neurotransmitter in the brain.
How does sodium valproate work in epilepsy?
Decreases the breakdown of GABA
How does vigabatrin work?
Decreases the breakdown of GABA
How do benzodiazepines such as clonazepam and clobazam work to treat epilepsy?
Increase how often GABA receptors open, as do the barbiturates (phenobarbitone)
How does perampanel work?
Via glutamate receptors as does topirmate (also via calcium)
How do beta-lactams lower the seizure threshold?
Beta-lactams, like penicillins, cephalosporins and carbapenems, interact with the GABAa receptor to interfere with the inhibitory effects of GABA in a concentration dependent manner.
Why is the seizure lowering ability of most beta-lactams not often clinically relevant?
What is the exception?
The CNS penetration of penicillins and cephalosporins is low, carbapenems however more readily penetrate the CNS and their use is associated with an increased risk of seizure.
Carbapenems also reduce valproate serum concentrations.
How does isoniazid lower the seizure threshold?
Isoniazid inhibits pyridoxine phosphokinase, the enzyme which converts pyridoxine to its active form, pyridoxal-5-phosphate which is an essential cofactor in the synthesis of GABA from glutamate. The resulting fall in inhibitory activity leads to a dose-dependent reduction in the seizure threshold.
Which antimalarials lower the seizure threshold?
Mefloquine and chloroquine.
Doxycycline and atovaquone/proguanil (Malarone) are safe options for malaria prophylaxis in people with epilepsy.
How do fluoroquinolones lower the seizure threshold?
They have comparatively high CNS penetration and they may inhibit the GABAa receptor.
Which opioids are capable of lowering the seizure threshold under certain conditions?
All of them.
How do NSAIDs reduce the seizure threshold?
NSAIDs inhibit cyclo-oxygenase enzymes, reducing the synthesis of prostaglandins from arachidonic acid. The effects of individual prostaglandins vary, but in general, they increase the seizure threshold, and NSAIDs accordingly have the potential to lower the seizure threshold.
What bronchodilators can lower the seizure threshold?
The bronchodilator theophylline and its soluble derivative aminophylline cause a significant reduction in the seizure threshold in animal models and in electroconvulsive therapy.
Thought to be due to adenosine A1-receptor antagonism.
What antipsychotics can lower the seizure threshold?
Clozapine and, to a lesser extent, other antipsychotics such as risperidone, olanzapine, lower the seizure threshold.
Which antipsychotic does not lower the seizure threshold?
Aripiprazole does not lower the seizure threshold during use, may have anticonvulsant properties. However, a rebound pro-convulsant effect may occur on withdrawal.
Which antidepressants can lower the seizure threshold?
Bupropion, other antidepressants, particularly TCA, in overdose.
Bupropion is an atypical antidepressant which inhibits reuptake or noradrenaline and dopamine.
When may anaesthetics lower the seziure threshold?
Sevoflurane.
Volatile and intravenous anaesthetics invariably suppress seizures at therapeutic doses, but may transiently lower the seizure threshold at subtherapeutic doses.
What are the most common type of seizure?
Tonic clonic seizures (previously known as grand mal seizures) are the most common type of seizure and affect the entire brain.
What is the first-line treatment for newly diagnosed tonic-clonic seizures? what is the exception to this rule?
Sodium valproate is the first-line treatment, except in premenopausal females where lamotrigine is the alternative choice.
