Dementia Drugs

Question 1

Which class of drugs should be used for EARLY STAGE Alzheimer’s disease? What is the goal of starting this class of drugs?

Answer 1

CHOLINESTERASE INHIBITORS (GALANTAMINE + RIVOSTIGMINE + DONEPEZIL) - Goal is to induce temporary reprieve from progression OR reduce decline rate

Question 2

Which class or classes of drugs is (are) used once Alzheimer’s has started progressing? MODERATE-SEVERE AD

Answer 2

CHOLINESTERASE INHIBITOR (GRD) + NMDA ANTAGONIST (MEMANTINE)

Question 3

Which agents should be AVOIDED when treating pts with dementia?

Answer 3

Drugs that AGGRAVATE cognitive impairment:

1) ANTICHOLINERGICS
2) BENZODIAZEPINES + Sedatives/Hypnotics
3) SECONDARY ANTI-CHOLINERGICS - DIPHENHYDRAMINE (benadryl anti-histamine) + TCAs [e.g. IMIPRAMINE]

Question 4

Pathogenesis of Alzheimer’s: Which 2 neurons are degenerated with progression of Alzheimer’s?

Answer 4

LOSS of hippocampal and cortical neurons -> Memory and cognitive impairment in Alzheimer’s

Question 7

CLASS 1 CHOLINESTERASE INHIBITORS: What are the 2 rationales/hypotheses for using CHOLINESTERASE inhibitors for Alzheimer’s?

Answer 7

Hypothesis 1) Ach deficiency = Cognitive Loss in Alzheimer’s

Hypothesis 2) Central cholinergic antagonists (ATROPINE) = Induces confusional state resembling dementia

Question 8

CLASS 1 CHOLINESTERASE INHIBITORS: Name the 3 common cholinesterase inhibitors for cognitive decline.

Answer 8

“GRD”
GALANTAMINE - competitive inhibitor
RIVASTIGMINE - non-competitive inhibitor
DONEPEZIL - non-competitive inhibitor

Question 9

CLASS 2 NMDA ANTAGONIST: Name the 1 NMDA antagonist used for Alzheimer’s Disease.

Answer 9

MEMANTINE

Question 10

BPSD: What are the behavioral and psychiatric symptoms of dementia?

Answer 10

Depression/Anxiety
Irritability/agitation
Paranoia/ delusional thinking
Wandering

Question 11

BPSD: Which drugs are useful for treating the ANXIETY and DEPRESSION symptoms of BPSD (behavioral and psychiatric symptoms of dementia)?

Answer 11

SSRIs: FLUOXETINE, FLUVOXAMINE, PAROXETINE, SERTRALINE, CITALOPRAM, ESCITALOPRAM

Question 12

BPSD: Which drugs are useful for treating the irritability, agitation, and psychosis of BPSD?

Answer 12

ATYPICAL ANTIPSYCHOTICS - 
OLANZAPINE 
RISPERIDONE
ARIPIPRAZOLE
QUETIAPINE
* Olanzapine and risperidone - limited due to Parkinsonism, sedation, and falls*

Question 13

BPSD: Which drug is useful to treat BPSD, ONLY if aggression is presented for ACUTE ALZHEIMER’S? What are side effects of this drug that limit its usage?

Answer 13

TYPICAL ANTI-PSYCHOTIC (HALOPERIDOL) - Sedation and EPS limit its usage

Question 14

CLASS 2 NMDA ANTAGONIST: What is the mechanism of action of MEMANTINE?

Answer 14

Non-competitive NMDA-Glu receptor antagonist -> Reduces Glu activity without impairing its function

Question 15

CLASS 2 NMDA ANTAGONIST: What stage of Alzheimer’s does MEMANTINE treat?

Answer 15

Moderate-Severe AD

Decreases AD deterioration rate