1. Medications for Dementia
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 NMDA Receptor Antagonists
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 Practice Parameter
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 Pregnancy and Lactation
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 Drug Interactions
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 Adverse Effects (8%)
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