Epilepsy Flashcards
What are the three main mechanisms of action for antiepileptic drugs?
- Blocking voltage-gated channels (Na+ or Ca2+).
- Enhancing inhibitory GABA-ergic impulses.
- Interfering with excitatory glutamate transmission.
Which voltage-gated channels do some antiepileptic drugs block?
Voltage-gated Na+ or Ca2+ channels.
How do some antiepileptic drugs affect GABA-ergic impulses?
They enhance inhibitory γ-aminobutyric acid (GABA)-ergic impulses.
How do some antiepileptic drugs interact with glutamate transmission?
By interfering with excitatory glutamate transmission.
What is the mechanism of action of benzodiazepines as antiepileptic drugs?
Benzodiazepines bind to GABA inhibitory receptors, reducing neuronal firing rate.
Which two benzodiazepines are used for treating epilepsy?
- Diazepam.
- Lorazepam.
What types of seizures do benzodiazepines treat?
- Myoclonic seizures.
- Partial seizures.
- Generalized tonic-clonic seizures.
How is diazepam is used for emergency seizure treatment?
Rectal administration to avoid prolonged generalized tonic-clonic seizures.
Which benzodiazepine is administered rectally in seizure emergencies for generalized tonic-clonic?
Diazepam.
What is the first-line treatment for status epilepticus (FDA guideline)?
Benzodiazepines.
What is the mechanism of action of carbamazepine?
Blocks sodium channels, inhibiting repetitive action potentials in epileptic focus and preventing their spread.
What types of seizures is carbamazepine effective for?
Partial seizures and secondarily generalized tonic-clonic seizures.
What non-epileptic conditions can carbamazepine treat?
Trigeminal neuralgia and bipolar disorder.
What is a key metabolic characteristic of carbamazepine?
It induces its own drug metabolism.
What is a dangerous side effect of the epoxide metabolite of carbamazepine?
Blood dyscrasias.
What enzyme families does carbamazepine induce?
CYP450s and UGT enzymes.
Why should carbamazepine not be prescribed for absence seizures?
It may cause an increase in seizures due to GABA receptor activation in the ventrobasal complex.
What are two ophthalmic side effects of carbamazepine?
Diplopia (double vision) and blurred vision.
What electrolyte imbalance can carbamazepine cause, and why?
Hyponatremia (due to ADH secretion).
What is the active form of oxcarbazepine?
Monohydroxy (MHD) metabolite.
How does oxcarbazepine exert its anticonvulsant effect?
Blocks sodium channels, preventing spread of abnormal discharge.
What type of seizures is oxcarbazepine used to treat?
Partial onset seizures.
How does oxcarbazepine compare to carbamazepine in enzyme induction?
Less potent inducer of CYP3A4 and UGT.
What is an advantage of oxcarbazepine’s lower enzyme induction?
Low drug-drug interactions.
List four common side effects of oxcarbazepine.
Nausea, vomiting, headache, and visual disturbances.
What is the primary mechanism of action of phenytoin and fosphenytoin?
Blocks voltage-gated sodium channels by selectively binding to the channel in the inactive state and slowing its rate of recovery.
What secondary effects does phenytoin have at very high concentrations?
a) Blocks voltage-dependent calcium channels.
b) Interferes with the release of monoaminergic neurotransmitters.
What types of seizures is phenytoin effective in treating?
- Partial seizures.
- Generalized tonic-clonic seizures.
- Status epilepticus.
Besides epilepsy, what other condition is phenytoin used to treat?
Trigeminal neuralgia.
Why should phenytoin not be used for absence seizures?
It has the potential to exacerbate absence epilepsy.
What enzyme system does phenytoin induce?
Drug-metabolized enzyme system.
How does phenytoin’s enzyme metabolism change at low serum concentrations?
It becomes saturable.
What can result from small increases in phenytoin’s daily dose?
Large increases in plasma concentration, potentially leading to drug-induced toxicity.
What CNS-related side effect can phenytoin cause?
Depression of the CNS, causing nystagmus (rapid involuntary eye movements) and ataxia.
What dental side effect is associated with phenytoin use?
Gingival hyperplasia.
What long-term neurological side effect may phenytoin cause?
Development of peripheral neuropathies.
What bone-related side effect is associated with long-term phenytoin use?
Osteoporosis.
What type of anemia is phenytoin associated with?
Risk of megaloblastic anemia.
What is fosphenytoin in relation to phenytoin?
Fosphenytoin is a prodrug that is rapidly converted to phenytoin in the blood.
Which antiepileptic drug is an analog of GABA?
Gabapentin.
What is the mechanism of action of gabapentin?
Unknown. It doesn’t bind to & activate GABA receptors.
What is the primary use of Gabapentin as an antiepileptic drug?
Adjunct therapy for partial seizures.
What is a non-epileptic use of Gabapentin?
Treatment of postherpetic neuralgia (nerve pain caused by varicella zoster virus).
What characteristic of Gabapentin’s pharmacokinetics is notable?
Nonlinear pharmacokinetics due to saturable transporter uptake in the gut.
Why is Gabapentin considered to have low drug-drug interaction potential?
It doesn’t bind to plasma proteins and is excreted unchanged through the kidneys.
Why is Gabapentin often preferred for older patients?
It is well tolerated due to its mild side effects.
What is the mechanism of action (MOA) of Tiagabine?
Blocks GABA uptake into presynaptic neurons.
How does Tiagabine’s MOA enhance inhibitory activity?
By permitting more GABA to be available for receptor binding.
For which type of epilepsy is Tiagabine effective?
Partial onset epilepsy.
Is Tiagabine approved for use in absence seizures?
No, it is not used for absence seizures.
What are the main mechanisms of action for lamotrigine?
Blocks sodium channels and high voltage-dependent calcium channels.
What types of seizures is lamotrigine used to treat?
- Partial seizures.
- Generalized seizures.
- Typical absence seizures.
Besides epilepsy, what other condition is lamotrigine used to treat?
Bipolar disorder.
How do enzyme-inducing drugs affect lamotrigine’s half-life?
They reduce it (e.g. carbamazepine).
How do enzyme-inhibitor drugs affect lamotrigine’s half-life?
They increase it (e.g. valproate).
What serious side effect can rapid titration of lamotrigine cause?
A rash, which may progress to a serious, life-threatening reaction in some patients.
Why is lamotrigine well-tolerated by the elderly population?
Due to minor side effects.
What is the proposed mechanism of action for levetiracetam?
Action is unknown, but most probably on synaptic vesicle protein SV2A.
What types of seizures is levetiracetam used to treat?
- Partial onset seizures.
- Myoclonic seizures.
- Primary generalized tonic-clonic seizures in adults and children.
How does levetiracetam interact with drug metabolism systems?
It does not interact with CYP or UGT metabolism systems, leading to low drug-drug interactions.
What is the primary mechanism of action for phenobarbital?
Enhancing the inhibitory effects of GABA-mediated neurons.
What is the main clinical use of phenobarbital in epilepsy treatment?
Used primarily in the treatment of status epilepticus.
Why is phenobarbital considered only for chronic therapy in refractory patients?
Because of its high side effects (sedation, enzyme induction, and osteoporosis).
What is the broad spectrum of action for felbamate?
Anticonvulsant action.
What are the proposed mechanisms of action for felbamate? (List 4)
1) Blocking voltage-dependent sodium channels.
2) Competing with the glycine binding site on NMDA glutamate receptor.
3) Blocking calcium channels.
4) Potentiating the action of GABA.
Why does felbamate have high drug-drug interactions?
It inhibits drugs metabolized by CYP2C19 and ß-oxidation, and induces drugs metabolized by CYP3A4.
Why is felbamate used only in refractory epilepsies?
Due to the risk of aplastic anemia and heart failure.
What side effect do carbamazepine and phenytoin share?
- Decrease bone proliferation.
- Decrease vitamin D.
What is divalproex sodium?
A combination of sodium valproate and valproic acid that converts to valproate in the gastrointestinal tract.
What is the purpose of using divalproex sodium instead of valproic acid alone?
To improve the gastrointestinal (GIT) tolerance of valproic acid.
What are the three main mechanisms of action for valproic acid and divalproex?
1) Sodium channel blockade.
2) Blockade of GABA transaminase.
3) Blockade action at t-type calcium channels.
What types of epilepsies are valproic acid and divalproex effective in treating?
Partial and primary generalized epilepsies.
Why does valproic acid have a high potential for drug-drug interactions?
It inhibits metabolism of CYP2C9, UGT, and epoxide hydrolase systems.
What is a rare but serious side effect of valproic acid?
Hepatic toxicity.
Why is valproic acid contraindicated in pregnancy?
It is teratogenic, causing neural tube defects in the fetus.
What are the five mechanisms of action for topiramate?
1) Blocks voltage-dependent sodium channels.
2) Increases chloride channel opening via GABA-A receptor.
3) Inhibits high-voltage calcium currents (L type), 4) Carbonic anhydrase inhibition, 5) May act at glutamate (NMDA) sites.
Besides epilepsy, what other condition is topiramate used to treat?
Migraine.
How does topiramate affect CYP2C19?
CYP2C19.
Which drugs induce topirmate?
It is sensitive of induction by phenytoin and carbamazepine.
How does topiramate affect oral contraceptives containing ethinyl estradiol?
It reduces ethinyl estradiol levels, potentially decreasing contraceptive efficacy.
What are five common adverse effects of topiramate?
1) Somnolence.
2) Weight loss.
3) Paresthesias.
4) Renal stones.
5) Glaucoma.
What is the mechanism behind topiramate-induced weight loss?
It causes anorexia.
What serious adverse effect can topiramate cause due to metabolic acidosis?
Renal stones.
What rare but potentially dangerous side effect can topiramate cause due to decreased sweating?
Hyperthermia (due to oligohidrosis).
What is the broad mechanism of action for Zonisamide?
Blockade of both voltage-gated sodium channels and t-type calcium currents.
What specific enzyme activity does Zonisamide affect?
Limited amount of carbonic anhydrase activity.
What type of epilepsy is Zonisamide used to treat?
Partial epilepsy.
What CNS-related side effect can Zonisamide cause?
CNS toxicity.
How does Zonisamide affect body temperature?
It can cause increased temperature.
What renal side effect is associated with Zonisamide?
Kidney stones (due to carbonic anhydrase inhibition leading to metabolic acidosis).
What fluid balance disorder can Zonisamide cause?
Oligohidrosis.
What is the primary mechanism of action for Ethosuximide?
Inhibits t-type calcium channels, reducing propagation of abnormal electrical activity in the brain
For which specific type of seizures is Ethosuximide primarily used?
Only primary generalized absence seizures (first line treatment).
Where are absence seizures triggered, and what causes them?
In the thalamus, when T-type calcium channels are activated, resulting in sustained-burst firing of neurons.
Why is the use of Ethosuximide limited?
Because of its very narrow spectrum of activity
What does vagal nerve stimulation for epilepsy require?
Surgical implant of a small pulse generator with a battery and a lead wire for stimulus.
How does electrical vagus stimulation affect seizure patients?
It prevents abnormal electrical activity.
When do patients activate the vagal nerve stimulator?
When they anticipate a seizure.
For which type of seizures is vagal nerve stimulation effective?
Partial onset seizures.
How does vagal nerve stimulation impact drug therapy for epilepsy?
It enables reduction of drug therapy.
What type of epilepsy patients is vagal nerve stimulation used for?
Refractory patients.
What should women with epilepsy take prior to conception?
High doses of folic acid.
Which antiepileptic drugs should be avoided during pregnancy?
Divalproex and barbiturates.
How should maintenance medication be adjusted when seizures are controlled during pregnancy?
Reduced to the lowest dose that provides control.
