SV_Antiseizure Drugs.pptx

Antiepileptic Drugs , Antiseizure Drugs, Anticonvulsants Dr. Abel Used to treat epilepsy – A disorder characterized by excessive excitability of neurons in the CNS causing seizures (convulsions, unconsciousness etc) and problems with learning, memory, and mood. Seizure Types Seizure - Initiation and...

Antiepileptic Drugs , Antiseizure Drugs, Anticonvulsants Dr. Abel Used to treat epilepsy – A disorder characterized by excessive excitability of neurons in the CNS causing seizures (convulsions, unconsciousness etc) and problems with learning, memory, and mood. Seizure Types Seizure - Initiation and Spread Seizures are initiated by synchronous, highfrequency discharge from a group of hyperexcitable neurons called a focus. Seizures are abnormal electrical activity in the brain Sodium Channels Outside Inside ↑ neuronal firing ↓ neuronal firing Other: Calcium Channels Other: Glutamate Receptors – Allow influx of Na+, K+, Ca++ GABA Receptor-Chloride Channel Outside Inside ↓ neuronal firing GABA is the primary inhibitory neurotransmitter in the brain. Therapeutic Considerations Eliminate or reduce seizures Match seizure type with drug Evaluate drug effectiveness Measure plasma drug levels Withdraw drug Increased risk of suicidality in the young Drug groups – Traditional vs. Newer Phenytoin – (Dilantin®) 1. Mechanism - reduces neuronal excitability, inhibits sodium channels in hyperactive nerves. 2. Uses – partial, generalized and tonic-clonic seizures, worsens absence seizures. 3. Pharmacokinetics - variable absorption and metabolism, metabolism depends on drug dose, narrow therapeutic range 4. Adverse effects CNS: sedation, ataxia, nystagmus, diplopia. Decreased vitamin D and bone mineral density; gingival hyperplasia. Rare: agranulocytosis, anemia, liver failure Can be teratogenic. 5. Drug interactions can increase metabolism of other drugs – oral contraceptives Phenytoin – (Dilantin®) Traditional Drug 1-2 Valproic Acid – (Depakene ®) Traditional Drug Uses: Partial seizures Generalized seizures Tonic-clonic seizures Absence seizures Bipolar disorder Migraine headache Valproic acid (Depakene®) 1. Mechanism – inhibits sodium channels, increases GABA, blocks Ca ++ channels, inhibits seizure development. 2. Uses – All seizure types, bipolar disorder (mood stabilizer), migraine prevention. 3. Pharmacokinetics - taken orally, effectively absorbed, metabolized in the liver 4. Adverse effects GI: nausea, vomiting Rare: serious liver or pancreas toxicity Potential fetal abnormalities high Rash, weight gain, tremor 5. Drug interactions- can increase plasma levels of phenytoin Oxcarbazepine (Trileptal ®) Newer Drug 1. Mechanism – blocks sodium channels, inhibits seizure spread. 2. Uses – partial seizures. Generally fewer adverse effects than traditional drugs. 3. Pharmacokinetics - absorbed orally, metabolized in the liver to an active metabolite 4. Adverse effects CNS: dizziness, sedation, diplopia, ataxia Low plasma sodium Skin reactions, Stevens Johnson Syndrome Multiorgan hypersensitivity reactions Can be teratogenic 5. Drug interactions - decreased plasma levels of oral contraceptives Stevens Johnson Syndrome Other Anticonvulsant Drugs 1. Carbamazepine (Tegretol) Traditional – used for generalized tonic-clonic seizures, partial seizures, bipolar disorder, trigeminal neuralgia. Avoid grapefruit juice. 2. Ethosuximide (Zarontin) Traditional – used for absence seizures only, not useful for other seizures, fewer adverse effects. 3. Gabapentin (Neurontin) Newer – used with other drugs for seizures, treats neuropathic pain, migraine, fibromyalgia. Other Anticonvulsant Drugs 4. Topiramate (Topamax) Newer – used for partial and generalized seizures, migraine headache, weight loss, neuropathic pain, binge-eating. 5. Pregabalin (Lyrica) Newer – used for seizures, fibromyalgia and neuropathic pain. 6. Diazepam (Valium) and lorazepam (Ativan) - benzodiazepines used i.v. for status epilepticus – generalized tonic-clonic seizures continuing for at least 20 min. More Other Anticonvulsant Drugs Newer = lacosamide (Vimpat) levetiracetam, (Keppra), lamotrigine (Lamictal), rufinamide (Banzel), tiagabine (Gabitril), vigabatrin (Sabril), felbamate (Felbatol), zonisamide (Zonegran). Traditional = primidone (Mysoline), phenobarbital (Luminal). Traditional vs. Newer Anticonvulsants 1. Effectiveness - Generally, equally effective to reduce seizures. 2. Clinical history - More clinical experience with traditional vs. newer agents. 3. Therapeutic uses - Traditional established and narrower uses vs. newer less established and broader uses. 4. Pharmacokinetics and metabolism - Traditional complex vs newer less complex. 5. Adverse effects - Traditional more vs. newer less. 6. Pregnancy - Traditional generally more dangerous vs. newer generally safer. 7. Traditional generally cheaper and newer more costly. Comparison of Anticonvulsant Drugs Pregnancy Categories