Dementia: Pharmacological Treatment of Alzheimer's Disease Flashcards
What two categories of agents are used to treat Alzheimer’s disease?
-
Agents to treat cognitive issues
- Cholinesterase inhibitors
- NMDA noncompetitive antagonist
-
Agents to treat behavioral symptoms
- Atypical antipsychotics
- Mood stabilizers
- Antidepressants
Delirium is produced by _________ medications.
Anti-cholinergic
- Deficiency in cholinergic transmission
- Plasma concentrations of these meds are directly related to increased delirium risk
- ACh helps but is used in other parts of the body
- SLUD
- Salivation
- Lacrimation
- Urination
- Defecation
What is the 1st line therapy to treat cognitive impairments in mild to moderate dementia?
- Reversible, centrally acting cholinesterase inhibitors
- AD, dementia w/ Lewy bodies, vascular dementia
Cholinesterase inhibitors
- Examples
- Side effects
- Contraindications
- Donepezil, Rivastigmine, Galantamine
- Modest improvement
- Many side effects
- GI problems
- Muscle cramping
- Abnormal dreams
- Caution in patients w/ bradycardia or syncope (vagotonic properties)
AD, like all neurodegenerative disorders, includes _______, _______ and _______.
excitotoxicity
oxidative stress
neuroinflammation
NMDA channel blocker
- Example
- Effectiveness
- Side effects
- Memantine
- Non-competitive antagonist
- Blocks flux of Ca2+ through channel
- Glutamate receptor
- Significantly reduces the rate of clinical deterioration in patients w/ moderate-severe AD
- Can be used together w/ anticholinergics (different mechanisms of action)
- Side effects: headache & dizziness
What are the behavioral & psychiatric symptoms in dementia? (BPSD)
Common, middle stage of disease
- Irritability & agitation
- Paranoia & delusional thinking
- Wandering
- Anxiety
- Depression
- Caregiver distress & nursing home placement
What anti-psychotics are used to treat AD?
What symptoms do they treat?
What is the dosing?
What are the side effects?
- Atypicals: Risperidone, Olanzapine, Quetiapine
- Treat agitation & psychosis
- Low doses, short intervals
- Limited by adverse effects:
- Parkinsonism
- Sedation & falls
- NO ANTIPSYCHOTIC DRUG IS APPROVED FOR DEMENTIA-RELATED PSYCHOSIS
What is the Black Box Warning of atypical antipsychotics?
- The use of atypical antipsychotics in elderly patients w/ dementia-related psychosis is associated w/ a higher risk for stroke & overall mortality
- 1.6-1.7 FOLD INCREASE IN MORTALITY COMPARED TO PLACEBO
- Mortality is due to HF, sudden death or pneumonia
- Equivalent risk for typical & atypical suggests that it’s reduced D2 receptor signaling
What are the Mood Stabilizers used to treat AD?
What are their benefits & risks?
- Carbamazepine: some benefits, but numerous risks in elderly
- Lithium: some benefit, but narrow therapeutic window in elderly patients
- Benzodiazepines: occasional control of acute agitation; not good for long-term treatment b/c of adverse effects on cognition
- Haloperidol: useful for acute aggression; sedation & EPS limit long-term use
What are the anti-depressants used to treat AD?
- Tricyclics have anticholinergic effects, so should be avoided
- SSRIs are favored & generally well-tolerated if needed
Summary: Treatment of AD
Upon presentation, _________ treatment is intiated.
As disease progresses, __________ can be added.
Mild behavioral problems should be treated with ___.
Severe behavioral symptoms should be treated with ________.
Cholinesterase inhibitor
Memantine
SSRI
Atypical antipsychotics
It is important to eliminate or avoid drugs that can aggravate cognitive impairments. What are some examples?
- Anticholinergics
- Benzodiazepines
- Sedative/hypnotics
What effect do NSAIDs have on AD?
- Observational studies: NSAIDs, especially ibuprofen, are associated w/ a lower risk of AD
- However, prospective studies, randomized clinical trials did NOT find significant reduction in AD w/ NSAIDs
What effect does estrogen have on AD?
- Retrospective studies: estrogens are beneficial for cognition & delayed onset of AD
- Estrogen-progestin therapy INCREASES number of women diagnosed w/ dementia
