Drugs for Seizures Flashcards
Which types of seizures are indicated for use of drugs that inhibit Na+ channels?
Generalized tonic-clonic & Focal seizures (simple & complex)
Most Na+ channel blockers make which kind of seizures worse?
Absence seizures
What are the indications for using Ca 2+ ion channel blockers?
Simple absence seizures
Which type of seizure will worsen w/ use of Ca 2+ channel blockers?
Tonic-clonic seizures
What is a SE of drugs that enhance inhibition produced by GABA?
Sedation
What is seen w/ tolerance to pts on benzodiazepines?
Tolerance to anti-seizure effect w/ LT use
Which drug is the exception for benzodiazepine tolerance?
Clonazepam
What is Clonazepam used for?
Myoclonic, absence & atonic seizures
Bipolar affective disorder
What is the DOC for terminating status epilepticus?
Lorazepam
What are the 1st line drugs for generalized-onset Tonic-clonic seizures?
- Valproic acid
- Lamotrigine
- Topiramate
What are the alternative or adjuncts to generalized-onset tonic-clonic seizures?
- Zonisamide
- Phenytoin
What are the 1st line drugs for Focal seizures?
- Lamotrigine
- Carbamazepine
- Oxcarbazepine
- Phenytoin
- Levetiracetam
What are the alternatives or adjunts to Focal seizures?
- Zonisamide
- Valproic acid
- Tiagabine
- Gabapentin
- Lacosamide
What are the 1st line drugs for Typical absence seizures?
- Valproic acid
- Ethosuximide
What are the alternatives or adjuncts to Typical absence seizures?
- Lamotrigine
- Clonazepam
What are the 1st line drugs for Atypical absence, Myoclonic or Atonic seizures?
- Valproic acid
- Lamotrigine
- Topiramate
What are the alternatives or adjuncts to Atypical absence, Myoclonic or Atonic seizures?
- Clonazepam
- Felbamate
Which drugs are effective in all types of seizures?
Valproate & Lamotrigine
(not 1st line drug for every seizure)
What is a benefit of using Valproate as tx for generalized tonic-clonic seizures?
Little clouding of consciousness
What are the SE of Valproate?
- G.I. (frequent, and troubling)**
- Hepatic damage (monitor liver enzymes when starting the drug)
- Teratogenic – doubles the probability of spina bifida
What can Valproate also be used for?
Migraines & bipolar affective disorder
What can reduce the epigastric distress caused by Valproate?
Depakote formulation (a mixture of Na-valproate + valproic acid)
Who is Valproate hepatotoxicity worse in?
Children
What FDA category does Valproate fall under?
Pregnancy category D
What is Lamotrigine effective against?
Broad spectrum of seizures
What is the MOA of Lamtotrigine?
Na+ channel blocker
(other actions)
What is the disadvantage of using Lamotrigine
Plateau conc has to be approached slowly. If dose is too high or conc are raised too quickly, the probability of allergic phenomena is increased
What should you warn pt who are using Lamotrigine about?
Rash→ impending Steven-Johnson synd
What are the SE of Lamotrigine?
- Sedation
- Insomnia
- Vivid dreams & nightmares
Who is more effected by Lamotrigine SE?
Women
What are the indications of Topiramate?
Tonic-clonic, absence, myoclonic & atonic seizures
Prophylaxis of migraines & tx of obesity
What are the SE of topiramate?
Related to CNS sedation & appetite reduction
Low rate when used alone
What are the GI SE of Carbamazepine & Oxcarbazepine?
N/V/D, constipation, & anorexia
What are the skin SE of Carbamazepine & Oxcarbazepine?
Rashes, erythema – b/c of the blood dyscrasias issue with carbamazepine, the occurrence of a rash is usually a reason to stop this drug
What are the CNS SE of Carbamazepine & Oxcarbazepine?
Toxicity leads to double vision (diplopia), dizziness, drowsiness, or confusion, ataxia in high doses
What does Carbamazepine (Tegretol) cause?
Blood formation issues–allergic rxn produces BM depression. Also causes hyponatremia & makes absence seizures worse
What are the indications for Phenytoin?
All types of epilepsy except absence
now 2nd line drug
What is a CI of Phenytoin use?
Pregnancy
What are the unusal pharmokinetics of Phenytoin?
- 1st-order elimination in the low to mid-therapeutic range
- Zero-order elimination at high therapeutic range and above
What is the oral absorption of Phenytoin like?
Slow & incomplete
How is Phenytoin transported in the body?
70-90% bound
Salicylicates & thyroxine will displace from albumin
Where is Phenytoin metabolized?
Liver
susceptible to drug interactions (warfarin & disulfiram)
What is the MOA of Phenytoin (Dilantin)?
Na+ channel antagonist
What happens in Phenytoin toxicity?
- Cerebellar & vestibular systems (diplopia)—look drunk
- Gingival hyperplasia (20% of pts on chronic med)
- Hypertrichosis, hirsutism
- Osteomalacia
- Hypersensitivity, hyperexcitability in children
- Teratogen: Cardiac damage, cleft palate
Why is Levetiracetam not a 1st line drug?
It is not as effective for focal seizures when used alone & has a lot of SE
What is the primary drug for typical absence seizures?
Ethosuximide
What are the SE of Ethosuximide?
- GI: pain, N/V.Tolerance dev
- CNS sedative SE Tolerance dev
- Blood dyscrasias (some have been fatal). Monitor blood.
- Behavioral changes (increased aggressiveness; restlessness; anxiety)
What is the MOA of Ethosuximide (Zarontin)?
Inhibits T-type Ca current in thalamic neurons
What is Ethosuximide (Zarontin) used for?
Absence seizures (petit mal)
What can Ethosuximide (Zarontin) worsen?
Generalized tonic-clonic
no effect on seizure spread
What is Lorazepam used for?
DOC for Status Epilepticus
What is the MOA of Lorazepam?
Benzodiazepine – enhances neurotransmission at GABA-A synapses
Why is Diazepam no longer the DOC for status epilepticus?
Highly lipid soluble, enters the brain extremely rapidly & redistributes to tissues in the periphery extremely rapidly
Why is Lorazepam a better choice than diazepam?
More water soluble→ slower onset of action, but a much slower offset of action
What are the SE of Benzodiazepines when given IV to tx status epilepticus?
Cardiovascular & respiratory depression
Usually requires very rapid administration
What are the SE of chronic oral benzodiazepine use?
Sedation & ataxia
(some tolerance)
What are the behavior disturbances assoc w/ Benzodiazepine use?
Disinhibition of behvaior
What is Levetiracetam (Keppra) used for?
Variety of types of seizures
Pediatric & refractory seizures
Can Levetiracetam (Keppra) be used as monotherapy?
Yes but more adverse SE
What is Zonisamide (Zonegran) used for?
Adjuctive therapy for refractory partial seizures
What is the MOA of Vigabatrin (Sabril)?
Irreversible inhibitor of GABA-transaminase
What is Vigabatrin (Sabril) used for?
Adjunctive or 2nd-line therapy of partial seizures, West’s Syndrome.
Why must a drug never be stopped abruptly?
Danger of seizure increased
Replace drug gradually
When are combinations of anti-seizure drugs appropriate?
- Not controlled w/ single drug
- 2 or more seizure types present
- Potentiate seizure control while reducing adverse effects by permitting lower doses
What is West’s syndrome?
Infantile spasms
What is used for tx of West’s syndrome?
- Corticosteroids (corticotropin, prednisone, dexamethasone)
- Benzodiazepines (clonazepam)
- Vigabatrin (Sabril)
What is the cause of Status Epilepticus?
- MC d/t cessation of anti-convulsant medication
- In infants, likely due to high fever
What is the initial tx of Status Epilepticus?
IV Lorazepam
What is the continuing tx of Status Epilepticus?
IV fosphenytoin (minimum 15 minute onset, so must start with a benzodiazepine)
What tx should be used if pt is unreponsive to Fosphenytoin?
- IV phenobarbital
- Midazolam
- Diazepam
What tx is used in Absence status epilepticus?
IV valproate
Why is alcohol use CI in epilepsy?
Lowers seizure thresholds
What does binge drinking trigger?
Microseizures
(makers further seizures more likely)
What does cessation of drinking cause?
Inc risk of seizure d/t up regulation of glutamate & down regulation of GABA
