Drugs for Alzheimers Disease

Affects hippocampus

1. memory

Early S+S of alzheimers:

1. speech, perception, reasoning and other higher functions

2. subsequent decline in cerebral volume Al

Later cerebral cortex symptoms of Alzheimers

1. levels of ACH are 90% below normal

2. critical to forming memories.

3. loss of cholinergic function

Alzheimer’s reduced cholinergic transmission: [3]

1. Advancing age

2. family hx

Alzheimers major/known risk factors [2]

1. female

2. head injury

3. low educational level

4. production of apolipoprotein e4

5. High levels of homocysteine

6. low levels of folic acid

7. estrogen/progestin therapy

8. nicotine in cigarette smoke

9. sedentary lifestyle

Possible risk factors for Alzheimers [9]

1. memory loss

2. confusion

3. feeling disoriented

4. impaired judgement

5. personality changes

6. difficulty with self-care

Symptoms of Alzheimers [6]

typically begin after 65 but may as early as 40

When do alzheimers symptoms start?

Could be 20 years or more, but is usually 4-8 years

Life expectancy from symptom onset

Improve symptoms and reverse cognitive decline Dr

Goal of alzheimers treatment

Because of the modest benefits. Can be clinically marginal.

Why is it not recommended that all patients receive alzheimers drugs>

Cholinesterase inhibitors

drugs that may delay or slow progression of disease but will not stop it

Drugs that block cholinergic receptors

1. first-gen antihistamines

2. tricyclic antidepressants

3. conventional antipsychoticsChol

What drugs can reduce individual’s response to cholinesterase inhibitors?

PRevents breakdown of ACH

Cholinesterase inhibitor MOA

1. cholinergic side effects

2. gastrointestinal effects

3. dizziness

4. headache

5. bronchoconstriction

Adverse effects of cholinesterase inhibitors [5]

Donepezil [Aricept, Aricept ODT]

Drug indicated for milk, moderate, or severe Alzheimers

Causes reversible inhibition of cholinesterase

Donepezil [Aricept, Aricept ODT] MOA

1. nausea and diarrhea

2. bradycarda

3. fainting

4. falls

5. fall related fracturesDr

Adverse effects of Donepezil [Aricept]

Galantamine [Razadyne, Reminyl]

Drug indicated for mild-moderate alzheimers. (not severe)

Reversible cholinesterase inhibition

Galantamine [Razadyne, Reminyl] MOA

1. Nausea, vomiting, diarrhea, weight lossm anorexia

2. Bradycardia, fainting, falls, fractures

3. more Fbronchoconstriction

Galantamine [Razadyne, Reminyl] adverse effects

Memantine [Namenda, Namenda XR]

First drug in new class, N-methyl-D-aspartate receptor antagonist

Moderate to severe AD. Better tolerated than cholnesterase inhibitors

Memantine [Namenda, Namenda XR] indicated for who?

1. Dizziness

2. Headache

3. Confusion

4. Constipation

Adverse effectsof Memantine [4]

1. Risperidone [Risperdal]

2. Olanzapine [Zyprexa]

Drugs for neuropsychiatric symptoms of AD [2]

Treats neuropsychiatric symptoms with modest benefitsm but can slightly increase mortality from CV events and infection

Risperidone [Risperdal] and Olanzapine [Zyprexa] have what benefits for AD