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Antiepileptics
| Question | Answer |
|---|---|
| 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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