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Pharm III - Exam 2 > Alzheimer's > Flashcards

Alzheimer's Flashcards

1
Q

Environmental and other risk factors of Alzheimer’s

A
  • Age
  • Reduced brain size
  • Low education/occupation
  • Head injury
  • Down’s Syndrome
  • Depression
  • Herpes simplex
  • Vascular disease
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2
Q

What is the definitive marker to diagnose AD and when can it be diagnosed?

A

Only definitive marker - neurofibrillary tangles (found postmortem)

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3
Q

Meds a/w memory loss

A
  • Anticholinergics
  • Benzodiazepines (and other sedatives)
  • Opioids
  • Antipsychotics, anticonvulsants
  • NSAIDs
  • H2 blockers
  • Digoxin
  • Amiodarone
  • Steroids
  • Anti-HTNs
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4
Q

Stages of AD

A
  • Mild cognitive impairment
  • Mild AD (MMSE 26-18)
  • Moderate AD (MMSE 17-10)
  • Severe AD (MMSE 9-0)
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5
Q

What pharm therapy can prevent AD or stop accumulation of B-amyloid?

A

None

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6
Q

What do current pharm therapies aim to treat in AD?

A
  • Cholinergic system (cholinesterase inhibitors to stop breakdown of ACh, keep ACh in synapses)
  • Glutamatergic neurotransmission (NMDA antagonist)
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7
Q

What cholinesterase inhibitors are FDA approved for mild-mod AD?

A
  • Donepezil hydrochloride
  • Galantamine hydrobromide
  • Rivastigmine tartrate and transdermal
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8
Q

How does efficacy vary between the cholinesterase inhibitor agents?

A

All have similar efficacy

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9
Q

Describe the efficacy of cholinesterase inhibitors in the first 6 months and then after

A
  • First 6 months: 1-1.5 pt MMSE improvement, 2.8-4 pt ADAS-Cog improvement
  • After 6 months: declined efficacy but still better than not treating
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10
Q

How does the average AD patient not on meds decline on MMSE and AGAS-Cog?

A
  • 2-4 point decline on MMSE

- 7 point decline on AGAS-Cog

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11
Q

When is an AD therapy considered effective?

A

If decline is less than:

  • 2-4 points on MMSE
  • 7 points on AGAS-Cog
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12
Q

MOA of Donepezil

A

Reversible cholinesterase inhibitor

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13
Q

What is Donepezil specific for?

A
  • AChE but NOT butyrylcholinesterase

- Results in fewer peripheral adverse effects (NV, diarrhea)

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14
Q

Dosing of donepezil?

A
  • Take at lunch to lessen likelihood of nightmares and vivid dreams
  • NO adjustment required for hepatic/renal dysfunction
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15
Q

How long does donepezil stabilize AD?

A

6-12 months (followed by a gradual decline over a 5 year period)

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16
Q

How can Donepezil be given to pts with mod-severe AD?

A

High dose (after being on low-mid dosing for 3 months)

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17
Q

Drug interactions with Donepezil

A
  • Anticholinergics
  • NSAIDs (higher risk for GI bleeding)
  • Theoretical risk w/CYP2D6 or 3A4 inhibitors
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18
Q

ADRs of Donepezil

A
  • NV
  • HA
  • Diarrhea
  • Insomnia
  • Pain
  • Dizziness
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19
Q

MOA of Galantamine

A
  • Inhibits AChE

- Modulates nicotinic receptors (increased release and enhancement of cholinergic function)

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20
Q

Dosing and administration of Galantamine

A
  • Twice daily
  • IR, ER, and oral solution formulations available
  • Adjusted with hepatic/renal impairment
21
Q

How should dosing of Galantamine be adjusted in hepatic/renal impairment?

A

Do NOT exceed 16 mg/day in hepatic or renal (CrCl less than 70)

22
Q

When is Galantamine contraindicated?

A
  • CrCl less than 9

- Severe hepatic impairment

23
Q

ADRs of Galantamine

A
  • NV
  • Dizziness
  • Diarrhea
  • Abnormal dreams
  • HA
  • Depression
  • Insomnia
  • Wt loss
24
Q

MOA of Rivastigmine

A
  • Reversible cholinesterase inhibitor (but very slow dissociation from AChE)
  • Substantially inhibits butyrylcholinesterase
25
Q

Dosing and administration of Rivastigmine

A
  • Capsule, oral solution, transdermal patch available
  • Longer titration period may be needed to decrease GI symptoms
  • Take with food
  • NO adjustment w/renal or hepatic impairment
26
Q

ADRs of Rivastigmine

A
  • NV
  • Dizziness
  • Diarrhea
  • HA
  • Insomnia
  • Depression
  • Somnolence
27
Q

How should a CI be chosen to treat AD?

A
  • No randomized trials demonstrating one better than another

- Best outcomes from continuous, uninterrupted therapy

28
Q

What NMDA blockers are approved to treat AD?

A

Memantine

29
Q

MOA of Memantine

A
  • Specific, noncompetitive NMDA blocker w/moderate affinity (slows glutamatergic exitotoxic neurotoxicity)
  • Rapid association and dissociation w/the receptor
  • Does not interact w/other receptors, transporters, enzyme systems
30
Q

What is Memantine approved to treat?

A

Mod-severe AD

31
Q

PK of Memantine

A
  • 100% bioavailability
  • Rapidly crosses BBB
  • Renally excreted as the parent compound
32
Q

Dosing of Memantine

A
  • XR and oral solution formulations available

- Dose reduction if CrCl less than 30

33
Q

ADRs of Memantine

A
  • Dizziness
  • HA
  • Constipation
  • HTN
34
Q

What is the role of combo therapy in AD?

A
  • No trials have assessed dual CI use
  • Memantine and donepezil combo is not considered clinically significant, but can be tried in severe AD because minimal side effects
35
Q

MOA of Vitamin E in AD

A
  • Decrease in free oxygen radicals
  • May slow progression of existing AD
  • But needed in high doses and there is increased mortality a/w high doses
36
Q

Vitamin E’s role in AD treatment

A
  • NOT recommended

- Would need high doses, but high doses increases risk of mortality

37
Q

How could ASA be used to treat AD?

A
  • Vascular disease is a risk factor for AD
  • If pt can tolerate it, ASA could help attack vascular risk
  • Only 81 mg
38
Q

How could estrogen be used to treat AD?

A

We don’t recommend initiating it because of increased thromboembolic events

39
Q

How could NSAIDs be used to treat AD?

A

We don’t recommend initiating it (BESIDES ASA) because of CV risk

40
Q

How could lipid lowering agents be used to treat AD?

A

Can be used to potentially stabilize plaques, but we aren’t initiating high dose statins

41
Q

How could B vitamins be used to treat AD?

A

B6, B9, B12 can help - we can add it because there’s no big risk to taking it

42
Q

How could Ginkgo biloba be used to treat AD?

A

Can start a pt on it, but does have a bleeding risk

43
Q

What pharm therapies can be used to treat non-cognitive symptoms?

A
  • Antipsychotics (haloperidol, atypicals)
  • Antidepressants (SSRIs, SNRIs)
  • Anticonvulsants (carbamazepine, valproic acid)
  • Benzodiazepines
44
Q

What target symptoms do antipsychotics treat in AD?

A
  • Psychosis

- Disruptive behavior (agitation, aggression)

45
Q

What target symptoms do antidepressants treat in AD?

A

Depression

46
Q

What target symptoms do benzodiazepines treat in AD?

A
  • Anxiety
  • Restlessness
  • Insomnia
47
Q

What target symptoms do anticonvulsants treat in AD?

A

Agitation or aggression

48
Q

What are the only benzodiazepines used in older patients?

A
  • Lorazepam
  • Oxazepam
  • Temazepam
49
Q

What is Caprylidene?

A
  • Medical food that may help the brain of mild-mod AD patients
  • May increase TGs
  • Caution in pts at risk of ketoacidosis

Pharm III - Exam 2 (3 decks)

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