Week 11 Flashcards
Benzodiazepines: MOA in Seizure Management
Bind to GABA-A receptors, enhancing the inhibitory effect of GABA by increasing chloride influx, leading to neuronal hyperpolarization and decreased excitability.
Benzodiazepines: Acute vs. Chronic Use
Used acutely for seizure emergencies like status epilepticus (e.g., diazepam, lorazepam). Chronic use is limited due to tolerance; clobazam and clonazepam may be used for specific seizure types.
Benzodiazepines: Routes of Administration
IV lorazepam preferred for status epilepticus. Diazepam is available in rectal and intranasal formulations for out-of-hospital use.
Benzodiazepines: Tolerance and Long-Term Use
Chronic use may lead to tolerance and decreased effectiveness. Typically reserved for short-term or adjunctive therapy.
Phenytoin: Mechanism of Action
Blocks voltage-gated sodium channels, stabilizing neuronal membranes and preventing repetitive firing.
Fosphenytoin vs. Phenytoin
Fosphenytoin is a water-soluble prodrug of phenytoin, safer for IV/IM use with fewer infusion-related complications.
Levetiracetam: MOA and Clinical Advantages
Binds to synaptic vesicle protein SV2A. Minimal drug interactions, renally excreted, fewer cognitive side effects. May cause mood changes.
Antiepileptic Drugs: Risks and Benefits
Selection based on seizure type, side effect profile, drug interactions, and patient-specific factors.
Phenytoin: Distribution
Highly protein-bound; nonlinear pharmacokinetics. Small dose changes can lead to large increases in serum levels.
Antiepileptics: Drug-Drug Interactions
Many anti-epileptic drugs induce or inhibit CYP enzymes. Phenytoin, carbamazepine, and phenobarbital are potent inducers.
AEDs and Contraceptives
Phenytoin, carbamazepine, topiramate, and clobazam can reduce effectiveness of hormonal contraceptives by increasing metabolism.
Acetylcholinesterase Inhibitors: Role in AD
Inhibit breakdown of acetylcholine, enhancing cholinergic transmission. Used for mild to moderate Alzheimer’s disease.
AChE Inhibitors: Common Agents
Donepezil (daily dosing), rivastigmine (oral and patch, used in PD-related dementia), galantamine (dual MOA).
AChE Inhibitors: Adverse Effects
GI effects (nausea, diarrhea), bradycardia, syncope, muscle cramps. Risk of falls due to vagotonic effects.
AChE Inhibitors: Interactions and Monitoring
Anticholinergics reduce efficacy; beta-blockers increase bradycardia risk. Monitor for GI effects and syncope.
NMDA Receptor Antagonist: Role in AD
Memantine blocks NMDA receptors to prevent excitotoxicity from excess calcium influx. Used in moderate to severe AD.
Memantine: Adverse Effects
Generally well tolerated. May cause agitation, confusion, dizziness, and headache, which may be difficult to differentiate from AD symptoms.
AEDs in Migraine Prevention
Topiramate and divalproex are effective options. Start low and titrate to avoid side effects.
Topiramate: Adverse Effects
Cognitive dysfunction, paresthesia, fatigue, weight loss, kidney stones, and glaucoma.
Valproate: Adverse Effects and Black Box Warnings
Hepatotoxicity, pancreatitis, teratogenicity (neural tube defects). Common side effects include nausea, tremor, weight gain.
Migraine AED Use in Reproductive-Age Patients
Avoid valproate due to teratogenic risk. Counsel on contraception and folic acid supplementation.
Topiramate and Divalproex: MOA in Migraine
Topiramate blocks sodium channels and enhances GABA. Divalproex increases GABA availability and suppresses neuronal firing.
Migraine Prevention: Efficacy and Onset
May reduce frequency and intensity of attacks by up to 50–70%. Benefits begin within weeks; maximum effect may take months.
Migraine Prevention: Adverse Effects
Includes weight changes, fatigue, cognitive changes, and teratogenicity. Monitor patients closely for tolerability.
