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Antiepileptics

QuestionAnswer
What is a partial seizure? Seizure that involves a small, localized part of the brain?
What is a simple-partial seizure? Seizure that is confined to twitching of a limb or unusual tastes/sensations. No loss of consciousness.
What is a complex-partial seizure? Often has loss of consciousness, mental distortions, and motor dysfunction.
What is a general seizure? Seizure that involves the entire brain
What is a tonic-clonic seizure? Loss of consciousness followed by alternating muscle relaxation and rhythmic tightening.
Why is a myoclonic seizure? Abrupt jerking of limbs or brief muscle spasms, usually no loss of consciousness
What is an absence seizure? Brief loss of consciousness, no other major disturbances
What is absence seizure often mistaken as? Daydreaming in children
What is a febrille seizure? Caused by sudden elevation of body temperature in children
What is a status epilepticus? Recurrent seizures between which the patient doesn't fully recover or prolonged seizures (i.e. 30 minutes)
Is status epilepticus life threatening? Yes because it can last a long time. (i.e. 30 min)
What seizure is called "seizure beget seizures"? Status epilepticus
How long does febrille seizure last? Seconds to minutes
Why is an antiepileptic meidcation used for a febrille seizure? Prevent further attacks during illness or to stop complex febrille seizures that last more than 10 minutes or continue to reoccur within 24 hours
Do febrille seizures cause epilepsy later in life? No
What are some warning associated with antiepileptics? Sudden stoppage of AED's can precipitate life-threatening status epilepticus. Increased risk of suicidal thoughts/behaviors
In general, what can most antiepileptic drugs be divided into? Decrease sodium influx in neuronal cells or increase GABA activity in brain
Why role does sodium influx play in epilepsy? Sodium influx is needed to initiate an action potential. Too much can cause neuronal hyperactivity and seizures.
What is the implication of decreasing sodium influx in neuronal cells? Less likely for neuron to send an AP
What role does GABA play in the brain? GABA - inhibitory neurotransmitter and can dampen excess activity in the brain
What are some antiepileptics that fall under decreasing sodium influx in neuronal cells? Phenytoin, carbamazepine
What are some antiepileptics that fall under increasing GABA activity in the brain? Phenobarbital, primidone, valproic acid, benzodiazepines
What are some antiepileptics that fall under other? Ethosuximide, gabapentin
What kind of seizures do phenytoin treat? Simple-partial, complex-partial, tonic-clonic, status epilepticus
What kind of seizures does carbamazepine treat? Simple-partial, complex-partial, tonic-clonic
What kind of seizures do valproic acid treat? Myoclonic, absence, status epilepticus?
What kind of seizures does clonazepam treat? Myoclonic, absence
What kind of seizures does diazepam and lorazepam treat? Febrille and status epilepticus
What kind of seizures does phenobarbital treat? Status epilepticus
What is the preferred drug for simple-partial? Phenytoin and carbamazepine
What is the preferred drug for complex seizures? Phenytoin and carbamazepine
What is the preferred drug for tonic-clonic? Phenytoin and carbamazepine
What is the preferred drug for myoclonic? Calproic acid and clonazepam
what is the preferred drug for absence? Ethosuximide
What is the preferred drug for febrille seizures? Diazepam.lorazepam
What is the preferred drug for status epilepticus? Phenytoin, diazepam/lorazepam
What is the therapeutic mechanism of phenytoin? Decrease influx of Na ions across neuronal membranes therefore stabilizes them to depolarization
What are the therapeutic uses of phenytoin? Common used - partial seizures, tonic-clonic, status epilepticus. Prevention and treatment of seizures during or following neurosurgery
What seizure does phenytoin not commonly prescribed? Absence
Phenytoin is no longer considered appropriate for what diseases? Digoxin toxicity, toxin-induced seizures, alcohol withdrawal symptoms
How is phenytoin metabolized? Metabolized in liver, excreted in kidneys
What is the relationship between liver enzymes and phenytoin plasma levels? Become saturated at high range phenytoin plasma levels. Once saturation occurs, even a small increase in dose can increase half life.
What is the implication of the increase in half-life past saturation? Push phenytoin levels into toxic range
What is the relationship between folate absorption and phenutoin? Phenytoin inhibits folate absorption and folate activity (by inhibiting enzyme that breaks down folate polyglutamates)
What is the implication of inhibition of folate by phenytoin? Megaloblastic anemia - red blood cells that are larger than normal. Usually from deficiency of folic acid of B12
What are some CNS adverse effects of phenytoin? Nystagmus, ataxia, slurred speech, decreased coordination, mental confusion, dizziness, insomnia, headaches
What are some GI adverse effects of phenytoin? Nausea/vomiting, constipation
What are some CV adverse effects (IV administration)? Hypotension or arrhythmia with rapid infusion. Depress spontaneous ventricular depolarization
Because of its adverse CV effects, what is phenytoin contraindicated in? Bradycardia or heart block
What teratogenic effects in the offspring of mothers treated with phenytoin occur? Cleft lip/palate, congenital heart disease, slowed growth and mental deficiency
Why would a pregnant woman be treated with anti-epileptics? Frequency of seizures during pregnancy can increase which can lead to anoxic episodes and yield even higher incidence of congenital birth defects.
What are some hematopoietic adverse effects of phenytoin? Megaloblastic anemia, fatal complication via reduced blood cells, lymphadenopathy (benign lymph node hyperplasia and lymphoma)
What are some liver adverse effects of phenytoin? Hepatotoxicity - can be fatal
What are some other adverse effects of phenytoin? Inhibition of insulin release - hyperglycemia and glycosuria. Gingival hyperplasia - regresses upon discontinuation of drug.
What are some dermatological conditions that can occur with phenytoin? Mild-measles like. Severe - includes TEN and SJS.
What should you do if a rash develops with an antiepileptic? Discontinue. If mild, may resume but CI if rash comes back again.
What is TEN? Toxic epidermal necrolysis. Extensive epidermal loss resembling severe scalding and is potentially life-threatening. Usually drug induced.
What is SJS? Steven Johnson Syndrom. Serious systemic allergic reaction with a characteristic rash. Complications include nephritis, hepatitis, GI bleed, pneumonia, and more.
What are the most common causes of death in TEN? Septicemia and multi-system organ failure.
Why would septicemia happen with TEN? Epithelial loss results in vulnerability to bacterial and fungal infections.
What is DRESS? Drug Reaction Eosinophilia and Systemic Symptoms. Can involve multiple organs and be fatal.
What drugs decrease phenytoin metabolism? Cimetidine, diazepam, estrogens, phenothiazines
Why would a decrease in phenytoin metabolism be a problem? It can lead to toxic levels.
What drug increase phenytoin metabolism? Carbamazepine
Why would an increase in phenytoin metabolism be a problem? Be ineffective
What drugs does phenytoin increase the metabolism of? Other antiepileptics, anticoagulants, oral contraceptives
What is the take home message for phenytoin drug interactions? Whenever combining phenytoin with any other drug, always check for liver metabolism interactions and adjust doses accordingly.
What is the therapeutic mechanism behind carbamazepine? Block sodium channels in brain
What are the therapeutic uses of carbamazepine? Partial seizures, tonic-clonic, and trigeminal neuralgia.
What part of the body would experience pain in trigeminal neuralgia? Trigeminal nerve so front of face
Why does carbamazepine work for trigeminal neuralgia? Blocks NA channels and prevents depolarization for AP (block signals)
Do you think it would be good to use as a general analgesic? No, specific to trigeminal nerve and can be toxic (advil and others work better)
How is carbamazepine metabolized? Metabolized in liver, excreted in kidney. Induces own liver metabolism but auto-induction stops after 3-5 weeks of treatment.
What does the doctor have to do since autoinduction stops after 3-5 weeks of treatment with carbamazepine? Monitor blood levels to find proper dose
What are the usual categories for adverse effects of antiepileptics? CNS, GI, CV, hematopoietic, teratogenic, hepatotoxicity
What are the CNS adverse effects of carbamazepine? Nystagmus, ataxia, slurred speech, decreased coordination, mental confusion, dizziness, insomnia, headaches
What are the GI adverse effects of carbamazepine? Nausea/vomiting, constipation
What are the CV adverse effects of carbamazepine? CHF, edema
What are the hematopoietic effects of carbamazepine? Megaloblastic anemia, Blood cell deficiencies (agranulocytosis and aplastic anemia)
What is agranulocytosis? Low concentration of active WBC
What is aplastic anemia? Low concentration of RBS and other blood cells
What is megaloblastic anemia? Red blood cells that are larger than normal
What are the dermatological effects of carbamazepine? TEN, SJS
What drugs inhibit carbamazepine metabolism? Cimetidine, diltiazem, erythromycin
What drugs increase carbamazepine metabolism? Phenytoin
What drugs does carbamazepine induce metabolism for Anticoagulants, imipramine, haloperidol, oral contraceptives, and other antiepileptics
What is the therapeutic mechanism behind phenobarbital? Potentiation of inhibitory GABA effects
Why is phenobarbital no longer the drug of choice for chronic use? Dependence/withdrawal symptoms, potential for fatal overdose
What is phenobarbital classically used as? Anxiolytic or hypnotic
What is the first line treatment for neonates? Phenobarbital
What is the therapeutic use for phenobarbital? Seizures unresponsive to other treatments, including status epilepticus
What impairment of which B-vitamin absorption may cause megaloblastic anemia? B12 and folate
Is the skin rash in phenobarbital the same as phenytoin and carbamazepine? No, not as serious
What is the relationship between tolerance and dependence for phenobarbital? It (tolerance and dependence) can develop with prolonged use of higher doses
What are the CNS effects of phenobarbital Sedation, ataxia, confusion, insomnia, dizziness. Acute overdose: slurred speech, nystagmus.
What are the GI effects of phenobarbital? Nausea/vomiting, constipation
What are the CV effects of phenobarbital? Bradycardia, hypotension
What drugs are the metabolism induced from phenobarbital? Anticoagulant, antihistamines, oral contraceptives
What is the relationship between CNS depressants and phenobarbital? Additive CNS depressant effect
What is the therapeutic mechanism behind primidone? GABA agonist activity. Metabolites are also active in treating seizures.
What are the metabolites of primidone? Phenobarbital and phenyethylmalonamide
What are the therapeutic uses of primidone? Partial seizures and tonic-clonic
What are the CNS effects of primidone? Ataxia, vertigo, nystagmus, drowsiness
What are the GI effects of primidone? Nausea, vomiting
What are the hematologic effects of primidone? Agranulocytosis, megaloblastic anemia
What are the therapeutic mechanisms behind valproic acid? Increases in brain GABA concentrations
What are the therapeutic uses for valproic acid? Partial and general seizures
What is the drug of choice for myoclonic seizures? Valproic acid
What is the effects of the liver from valproic acid? Liver toxicity elevated with this drug. Death from liver failure has been reported.
What are the hematological effects of valproic acid? Megaloblastic anemia
What are other effects of valproic acid? Pancreatitis (can be life threatening). Valproic-induced hyperammonemic encephalopathy
Because of the hyperammonemic encephalopathy, what is it CI in? Patients with urea cycle disorders
What is the urea cycle used for? To get rid of ammonia. If already having problems with getting ammonia out then problematic effect is going to amplify.
What are some CNS effects of valproic acid? Sedation, tremor, dizziness, ataxia, nystagmus
What are some GI effects of valproic acid? Nausea and vomiting
What are some hematological effects of valproic acid? Thrombocytopenia, megaloblastic anemia
What drug is converted to valproic acid in the GI? Divalproex
What is divalproex used for? Manic episodes in bipolar disorders, prophylaxis of migraines
What drugs increase valproate metabolism? Phenytoin, carbamazepine, phenobarbital (primidone)
What drugs are the metabolism inhibited by balproate? Phenobarbital, ethosuximide
What is the take home message for valproic acid? When combining antiepileptics, be prepared to monitor drug levels and adjust doses.
Is it true that drug monotherapy for epilepsy is usually preferred to drug combos? Yes
What is the therapeutic mechanism for benzodiazepines? Potentiating GABA effects
What is considered the sagest drug for epilepsy? Benzodiazepines
What is benzodiazepine usually classified as? Anxiolytics/hypnotics
What are some adverse effects for benzodiazepines, outside of the usual anti-epileptic ones? Abnormal thinking, behavioral changes, tolerance, dependence, withdrawal effects.
What specific agents are used for myoclonic and absence seizures, under benzodiazepines? Clonazepam
What specific agents are used fro status epilepticus and febrille seizures, under benzodiazpines? Diazepam and lorazepam
How often can you give benzodiazepines for febrille seizures? With each attach to reduce frequency of further attacks during an illness
What is the method of administration for febrille seizures for benzodiazepines? Rectally to get effect 10 minutes after attack
What is the implication of the rectal administration of diazepam for febrille seizures? Good for complex febrille seizures that last up to 15 or re-occur multiple times in 24 hours.
What is the therapeutic mechanism for ethosuximide? Depresses motor cortex, elevates seizures threshold. Possibly due to block of specific calcium channels
What is the therapeutic use for ethosuximide? Absence
What is the first line for absence seizures? Ethosuximide
Besides absence seizures, are there any indications for ethosuximide? No
What are the CNS effects of Ethosuximide? Drowsiness, dizziness, ataxia, headache
What are the GI effects of Ethosuximide Nausea and vomiting
What are the hematopoietic effects of ethosuximide? Leukopenia, agranulocytosis, aplastic anemia
What is the hematopoietic warning of ethosuximide? Blood dyscrasias
What are some other warnings for ethosuximide? KD and LV damage. Systemic lupus erythematosus, fatal blood dyscrasias, serious dermatological conditions
What is blood dyscrasias? Blood diseases in which components of blood are abnormal or present in abnormal quantities: leukemia, hemophilia
What drug is used as an adjunct therapy in treatment of partial seizures? Gabapentin
Does gabapentin have significant drug interactions with other drugs? No
What is the implication of gabapentin not having a significant drug interaction with other drugs? Added when patient is refractory to monotherapy
What is the therapeutic mechanism behind ggabapentin? Related to GABA. Structural analogue of GABA but have little activity at GABA receptors. May activate GABA receptor subtypes that lead to reduced NT release (excitatory)
What are some other therapeutic uses for gabapentin? Analgesic for herpes zoster nerve damage - shingles, postherpetic neuralgia
Why are the adverse effects of gabapentin hard to isolate? Because it is given as adjunct therapy
What are some adverse effects of gabapentin? CNS effects - fatigue, ataxia, dizziness. GI complaints - nausea.
Created by: nnguyen44
 

 



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