Slide 1Alzheimer's DiaseaseCholinesterase inhibitors for ADSeizuresDrug treatmentSlide 6DilantinSlide 8TegretolSlide 11DepakoteDepakoteEthosuximide (Zarontin)Phenobarbital (Luminal)Newer agentsStatus EpilepticusDepressionClassification of antidepressnats:Tricyclic antidepressantsSelective Serotonin Reuptake Inhibitors (SSRI’s)Serotonin/norepinephrine reuptake InhibitorsMonoamine Oxidase Inhibitors (MAOI’s)MAOI’sBupropion (Wellbutrin)Serotonin syndromeLiver FunctionBipolar DisorderLithiumLithiumPsychosisClassification of antipsychoticsConventional antipsychoticsDepot preparation of antipsychoticsAtypical antipsychoticsExample of atypical antipsychoticsAnxietyDrugs for sleepBenzodiazepinesBenzosBenzo-likeBarbituatesAntihistamines for insomniaTobaccoAlcoholADHDNSG 3259/16NeurologyPsychiatryWhat is it? Neuronal degeneration of hippocampus (involves memory) and cerebral cortex (speech, perception, reasoning, motor function…)◦Associated with low levels of acetylcholineSymptoms: progressive dementia, typically begins > 65 yearsCause: unknown Diagnosis: no specific testTreatment: cholinesterase inhibitors that work inBrain(To help with this, review parasympathetic, muscarinic,acetylcholine)Alzheimer's DiaseaseThe drugs:◦Donepezil (Aricept®)- reversibly inhibit cholinesterase◦Rivastigmine (Exelon®)-irreversibly inhibit cholinesteraseMechanism of action: prevent breakdown of acetylcholine by acetylcholinesterase in the brain  increases availability of acetylcholine. Reversible.◦Not a cure. May slow progression, not stop it.ADR’s:◦Cholinergic effects : nausea, vomiting, diarrhea, dizziness headache, bronchoconstrictionDrug interactions: anticholinergicsCholinesterase inhibitors for ADEpilepsy: a group of disorders characterized by excessive excitability of neurons in CNS.Causes: congenital defects in brain, hypoxia at birth, head trauma, brain tumors, hypoglycemiaClassification:◦Partial: Simple or complex◦Generalized:Tonic-clonic, absence; febrile, othersSeizuresTherapeutic goals:◦Reduce seizure frequency to an extent that enables patient to live as normal a life as possible◦Avoid side effects as much as possibleDrug selection:◦Most drugs work only for certain types of seizures◦Accurate diagnosis of seizure type essentialDrug levels are often obtained for antiepileptic drugs:◦Used as a guide to adjust dosage so that levels are within therapeutic range◦A way to monitor complianceDrug treatmentTraditional (Older) antiepileptics:◦Phenytoin (Dilantin®)/Fosphenytoin (Cerebrex)◦Carbamazepine (Tegretol®)◦Valproic acid (Depakene®, Depakote®)◦Ethosuximide (Zarontin®)◦Phenobarbital (Luminal®)◦OthersMechanism of action: suppresses activity of seizure-generating neurons by blocking Na channels of neuronsPharmacokinetic considerations:◦Absorption and metabolism vary widely among patientsDosages must be individualized◦Very narrow therapeutic range (10-20 )Appropriate drug levels difficult to achievePatients must adhere strictly to regimenDilantinMain uses:◦All major types of seizures except absence◦Drug of choice for tonic-clonic in adults and older children◦Cardiac dysrhythmiasADR’s at therapeutic doses:◦Gingival hyperplasia (20%)◦Skin rash (2-5%)◦IV injection-hypotension; arrhythmiasPregnancy: Category Dimportant ADR’s at toxic doses:◦Nystagmus- may also occur at therapeutic doses◦Sedation◦Ataxia◦Diplopia◦Cognitive impairmentImportant drug interactions:◦Decreases effectiveness of warfarin◦CNS depressants- increases sedationWithdrawal: Slowly. If rapid  status epilepticusPhenytoin:Dilute in saline. Infusion rate NMT 50 mg/min. Filter needleFosphenytoin more soluble; may use dextrose; give IV or IMMechanism of action: same as Dilantin®Therapeutic uses:◦Partial seizures- drug of first choice◦Tonic-clonic seizures◦Bipolar disorderADR’s:◦Many neurologic symptoms, but not associated with cognitive impairment (like Dilantin®)◦Bone marrow suppression (CBC’s should be monitored regularly)TegretolPregnancy: Category DImportant drug interactions:◦Decreases effectiveness of warfarinImportant food interaction:◦Grapefruit juice- increases toxicity of carbamazepineMechanisms of action: (3)◦Same as Tegretol® and Dilantin®◦Also suppresses calcium channels◦Also enhances GABATherapeutic uses:◦A first-line drug for all seizure types, including absence.◦Bipolar disorder◦Migraine headachesDepakoteMost common ADR:◦GI effectsMost serious ADR:◦Liver toxicity- rare, but can be fatalMore common at higher doses, children less than 2 on multidrug therapyPregnancy: Category DDepakoteMechanism of action: inhibits calcium currents in the thalamusTherapeutic use: ◦Drug of first choice for absence seizures◦Not effective for other seizure typesADR’s:◦Generally well-tolerated◦Rare, but serious reactions include lupus-like syndrome, aplastic anemia, and leukopenia Ethosuximide (Zarontin)Mechanism: enhances effects of GABA◦Member of barbiturate family◦One of oldest antiseizure drugsUses: ◦tonic-clonic and partial seizures, not absence seizures◦insomniaADR’s: lethargy most common. Physical dependence a risk. Also sedation, depressionToxicity: respiratory depression and death if overdoseWithdrawal: slowly to prevent SEPhenobarbital (Luminal)Gabapentin (Neurontin) ◦Analogue of GABA; enhances GABA release ◦Well tolerated; common side effects are somnolence◦Eliminated by the kidneysLevetiracetam (Keppra)◦approved for adjunctive therapy for partial seizures in adults◦common effects are drowsiness and asthenia Topiramate (Topamax) is approved as adjunct for partial seizures in adults; migraines, weight loss; may cause metabolic acidosis-monitor bicarbonateNewer agentsDefinition of generalized SE: continuous tonic-clonic seizures that last > 20-30min.◦Associated with increased HR, BP, temperature◦Hypoglycemia and acidosis can occur◦Permanent neurologic injury/death can occurInitial therapy to end seizures quickly:◦Benzodiazepines (IV)Lorazepam (Ativan®) or diazepam (Valium®)Follow-up therapy to suppress seizures:◦Phenytoin (Dilantin®)Status EpilepticusMost common psychiatric illness◦Underdiagnosed, undertreatedPrincipal symptoms: depressed mood, loss of pleasure or interest in usual