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Chapter 41

Chapter 41. Medications for Dementia. Drug Overview. Cognitive Function Cholinesterase inhibitors donepezil (Aricept) rivastigmine (Excelon) galantamine (Razadyne) NMDA receptor antagonist memantine hydrochloride (Namenda). Drug Overview. Cholinesterase Inhibitors

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Chapter 41

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  1. Chapter 41 Medications for Dementia

  2. Drug Overview • Cognitive Function • Cholinesterase inhibitors • donepezil (Aricept) • rivastigmine (Excelon) • galantamine (Razadyne) • NMDA receptor antagonist • memantine hydrochloride (Namenda)

  3. Drug Overview • Cholinesterase Inhibitors • Management of mild to moderate Alzheimer’s-type dementia • Often initiated by PCPs or after consultation • NMDA Receptor Antagonists • Moderate to severe dementia of Alzheimer’s type • May be given in addition to cholinesterase inhibitors • May be initiated by PCP or after consultation

  4. Mechanism of Action • Cholinesterase Inhibitors • Block enzyme that degrades acetylcholine in the brain resulting in more acetylcholine at the synaptic cleft and enhances cholinergic transmission • Diminishes signs and symptoms of dementia and improves function and slows progression

  5. Mechanism of Action • NMDA Receptor Antagonist • NMDA receptor is linked to learning and memory • Stimulated by glutamic acid • Excessive stimulation leads to excitotoxicity • Blockade of this receptor blocks excitotoxic effects associated with abnormal transmission of glutamate

  6. Treatment Principles • Standardized Guidelines • Screening for dementia: Recommendation and rationale • Practice Parameter • Diagnosis of dementia (an evidence-based review): Report on the Quality Standards Subcommittee of the American Academy of Neurology

  7. Treatment Principles • Cardinal Points of Treatment • Evidence suggests that cholinesterase inhibitors stabilize cognitive and functional ability for approximately 1 year • Tacrine is not widely prescribed because of the need for frequent liver monitoring and qid dosing • Consider donepezil as first line • Potential drug interactions • All metabolized through the CYP 450 enzyme system

  8. Treatment Principles • Cardinal Points of Treatment • Patients with moderate to severe dementia may be started on memantine, which may be given concurrently with donepezil • Identify and treat presence of depression and/or delirium • Avoid medications with sedating or anticholinergic effects • Treat any metabolic disorders, infections, and comorbid illnesses

  9. How to Monitor • Monitoring of Functional Ability and Staging • Folstein Mini-Mental State Exam (MMSE) • Global Deterioration Scale (GDS) • Katz Assessment of ADLs and IADLs • Clinical Evaluation and Family Observation • Laboratory Tests • Liver function tests • CBC • Routine serum chemistry

  10. How to Monitor • Assessment • HR, BP • Signs and symptoms of toxicity

  11. Patient Variables • Geriatrics • Age does not influence metabolism or clearance of cholinesterase inhibitors • Use galantamine with caution in patients with severe renal impairment • Reduce dose of memantine and use with caution in patients with severe renal impairment (CrCl, 5 to 29 ml/min)

  12. Patient Variables • Pediatrics • Efficacy not established • Pregnancy and Lactation • Category C: donepezil • Category B: rivastigmine, galantamine, memantine • No controlled studies in pregnancy • Unknown secretion of drugs into breast milk

  13. Patient Variables • Race and Gender • Plasma concentrations are up to 50% higher in women

  14. Patient Education • Do Not Change Dose Without Consulting Provider • Advise of Initial and Long-term/Delayed Side Effects • Advise of Purpose, Expectations from Treatment, and Time Frame to Note Improvement, Not Cure • Counsel Regarding Behavioral and Environmental Management of Disease

  15. Patient Education • Advise Patient Regarding Long-Term Care, Including In-Home Services, Adult Day Care, Assisted Living Facilities, and Nursing Homes

  16. donepezil (Aricept) • Precautions • May exaggerate succinylcholine-type muscle relaxation in anesthesia • Vagotonic effects on HR may be provoked; use with caution in patients with conduction abnormalities • May increase gastric acid secretion • May cause bladder outflow obstruction • Use with caution in patients with asthma

  17. donepezil (Aricept) • Pharmacokinetics • Absorption: 100% • Peak level: 3 to 4 hours • Half-life: 70 hours • Steady state: 15 days • Metabolization: P450 2D6 and 3A4 • Excretion: Urine (17%)

  18. donepezil (Aricept) • Adverse Effects • Nausea (5% to 19%) • Diarrhea (8% to 15%) • Insomnia (5% to 14%) • Vomiting, fatigue, muscle cramping, anorexia (3% to 8%) • Drug Interactions • CYP 3A4 and 2D6 substrates • No effect on pharmacokinetics of theophylline, cimetidine, warfarin, and digoxin

  19. memantine (Namenda) • Precautions • Seizures, severe renal impairment, genitourinary conditions, concomitant use of other NMDA antagonists • Adverse Effects (8%) • Hypertension, tachycardia, dizziness, headache, back pain, gait abnormalities, arthralgia, confusion, somnolence, hallucinations, others

  20. memantine (Namenda) • Drug Interactions • acetazolamide • cimetidine • dichlorphenamide • hydrochlorothiazide • methazolamide • nicotine • ranitidine • sodium bicarbonate

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