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Pharmacology > Alzheimers Dementia > Flashcards

Alzheimers Dementia Flashcards

1
Q

What are the diff severity of Alzheimer’s dementia?

A

Mild cognitive impairment
Mild Alzheimers
Moderate Alzheimers
Severe Alzheimers

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2
Q

Where do these types of alzheimers dementia spread to?

A

Mild cognitive imapriment: medial temporal lobe of the brain

Mild Alzheimer’s = L temporal and parietal lobes

Moderate Alzheimers = Frontal lobe

Severe Alzheimers = Occipital lobe

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3
Q

What are the symptoms of these types of Alzheimers dementia?

A

Mild cognitive impairment = short-term memory loss
Mild alzheimers = reading probs, poor object recognitiion, poor direction sense

Moderate alzheimers = poor judgement, impulsitivity, short attention span

Severe alzheimers = visual problems

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4
Q

What is the most common form of dementia?

A

Alzheimers dementia

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5
Q

What are other types of dementia?

A

Frontotemporal dementia
Dementia with Lewy bodies
Vascular dementia

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6
Q

What are 2 important proteins in ALzheimers?

A

Beta-Amyloid proteins
Tau proteins

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7
Q

What protein fragment has toxic effect on the neurons if clustered togther disrupting cell-to-cell communication?

A

Beta-amyloid proteins

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8
Q

What are clusters from larger deposits found in Beta amyloid proteins?

A

Amyloid plaques

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9
Q

What are proteins found in alzheimers dementia that play a part in internal suport to neurons & transport system?

A

Tau proteins

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10
Q

Tau proteins change shape and organize themselves into what?

A

Neurofibrillary tangles

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11
Q

What are lesions in ALzheimers dis?

A

Neuritic plaques
Neurofibrillary tangles

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12
Q

What are other mechanisms involved in Alzheimers dis?

A

Inflammatory processes
Dysfunction of neurovasculature
Mitochindtrial dysfunction
Oxidative stress

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13
Q

What is the most essential NT for processing of memory & learning found to be DEC in alzheimers?

A

Acetylcholine

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14
Q

What are extracellular lesions found in brain & cerebral vasculature?

A

Neuritic plaques/amyloid/senile plaques

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15
Q

What is the amyloid cascade hypothesis?

A

Altered apolipoprotein processing —> overproduction of BAP —> plaque formation —> INC neurodegeneration -> neuronal loss -> dementia

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16
Q

What is the glutamatergic hypothesis?

A

Overactivation of N-methyl-d-aspartate receptors by glutamate, sustained low-level activation of NMDA receptors?

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17
Q

What are the 10 warning signs of alzheimers?

A
  1. Memory loss that disrupts daily life
  2. Challenges in planning/solving problems
  3. Difficulty completing familiar tasks at home, work, or leisure
  4. Consution w/ time or place
  5. Trouble undestanding visual images/spatial relations
  6. New problems with words in speaking or writing
  7. Misplacing things and losign the ability to retrace steps
  8. Decreased or poor judgement
  9. Withdrawal from work or social activities
  10. Changes in mood & personality
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18
Q

What are the different symptoms of alzheimers?

A

Memory impairment
One or more of the ff cognitive disturbances:
- aphasia
- apraxia
- agnosia
- anosmia
- amnesia

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19
Q

What are the diff scoring in mini mental status exam?

A

25-30: Qnably significant
- clin signs of cog impairments are present, formal assesssment of cog may be valuable
- clin significant but mild eficit likely most demanding activigties of daily living

20-25: Mild
- formal assessment may be helpful to better determine patten & extent of deficits
- signifcant effect may require some supervision, suport, and assistance

10-20: Moderate
- formal assessment may be helpful if there aer other specific clin indications
- clear impariment
- may require 24H supervision

0-10: Severe
- Px not likely to be testable
- marked impairment
- likely to require 24H supervision & assistance

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20
Q

What are potentially safety issues of dementia?

A

Ambulation
Dizziness
Independence
Wandering behavior
Agitation
Manage finances
Driving
Level of superision

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21
Q

What are therapeutic objectives in txing dementia?

A

To delay the progession of the disease
To improve behavioral symptoms
To identify supportive measures applciable to the px

22
Q

What are non-pharmacological measures of dementia?

A

Px and caregiver support
Psychotherapy => behaioral, reality orientation, interpersonal
Alternative therapies => aromatherapy, art activities, gardening, dance/music, pets

23
Q

What are diff pharmacolgoical tx for dementia?

A

Cholinesterase inhibitors
- RIvastigmine oral or patch
- Donepezil oral
- Galantamine

NMDA receptor antagonist
- Memantine

24
Q

What are the diff management of non-cognitive symptoms of dementia?

A

Evalute for sleep disturbanec if present
Treat psychosis and agitation
Assess and tx depressio

25
Q

What is lola G’s tx?

A

Mild: AChEIs
Moderate: Combination of cholinesterase inhibitors (ChEIs) + Memantine
Severe: Memantine, add an approved ChEI as needed

26
Q

What hypothesis says that there is progressive loss of neurons resulting in marked DEC in choline acetyltransferase & other markers of cholinergic activity?

A

Cholinergic deficiency hypothesis

27
Q

What is the first-line agent for tx of mild-moderate Alzheimers dis?

A

Acetylcholinesterase Inhibitors

28
Q

What are significant AEs of Cholinesterase Inhibitors?

A

Common: Nausea, vomiting, diarrhea, anorexia

INC risk of falls & fracutres

29
Q

What is a long-acting CjEI and muscarinic modulator that is the 1st drug shown to have benefit in ALzheimers?

A

Tacrine

30
Q

Why is Tacrine no longer used and is now replaced by newer ChEIs?

A

Hepatic toxicity

31
Q

WHat are newer ChEIs?

A

Donepezil
Rivastigmine
Galantamine

32
Q

What are the diff AEs of newer ChEIs?

A

Nausea
Vomitng
Diarrhea
Weight loss
Loss of appetite
Muscle weakness

33
Q

What is the PD of Donepezil?

A

Selective reversible non-competitve inhibitor of AChE

34
Q

What is a significant AE of Donepezil?

A

Vivid dreams or nightmares

35
Q

What is the PD of RIvastigmine?

A

Pseudoirreversible inhibitor of AChE & BChE

36
Q

What is the meaning of pseudo-irreversible?

A

No covalent bond formed by mimics action of the other drugs

37
Q

WHat is the PD of Galantamine?

A

Reversible inhibitor of AChE
Presynaptic modulator of nicotinic AChE

38
Q

What is the diff betw R & irreversible inhibitors in terms of type of bonds with enzyme, removal, activitity restoration?

A

Irreversible inhibitors
- Type of bonds w/ E: inhibitors bind COVALENTLY with enzyme
- Removal: CANNOT BE REMOVED by dialysis or other way
- Activity of restoration: PERMANENTLY MODIFY active sitre residues -> enzymes becomes inactive

REversible Is
- Type of bonds w/ enzyme: inhibitors bind NONCOVALENTLY
- removal: removed by dialysis
- Activity restoration: removal of inhibitor RESTORES enzyme activity

39
Q

What are common drug interactions of diff drugs & its effects w/ DONEPEZIL?

A

Ketoconazole = inhibit metab of Donepezil
Risperidone = worsening of extrapyramidal symptoms
B blocker = protentiate bradycardia

40
Q

What are common drug interactions of diff drugs & its effects w/ Rivastigmine ?

A

Haloperidol = exacerbation of EPS
Tobacco = INC clearance of rivastigmine by 23%

41
Q

What are other precautions of cholinergic agents?

A
  • can reduce seizure threshold (those w/ hx)
  • msucle cramps & weakness
  • taking NSAIDs is no no
  • Asthma & COPD can be exacerbated
42
Q

What drugs are given for moderatre to severe cases?

A

NMDA antagonist

43
Q

What is the Glutamate hypothesis of cognitive deficiency

A

NMDA receptor is coincidence detector and allows inflow of ions

44
Q

What are NMDA receptor antagonists?

A

Memantine - main
Ketamine
AMantadine

45
Q

What are soluble forms of Abeta & Tau working idnependtly & accumulate into plaques & tangles?

A

NMDA rceptors

46
Q

WHat are factors that afffect NMDA receptor signalling?

A

Glutamate availability
Modulaltion of channel

47
Q

What are important AEs of NMDA receptor antagonist?

A

Dizziness
Headache

48
Q

What NMDA antagonist reduces abnormal activation of glutamate neurotransmission?

A

Memantine

49
Q

What is the PD of Memantine?

A

Inhibits prolonged influx of Ca ions

50
Q

What re comon side effects of ChEIs?

A

Nausea
Vomiting
Diarrhea
Weight loss
Loss of appetite
Muscle weakness
Vivid dreams/nightmares

51
Q

What are common symptoms of NMDA receptor antagonist/Memantine?

A

Dizziness
HEadaches
Cosntipation
COnfusion

52
Q

What are other issues of treatment?

A

Vitamin E = harmful in higher doses
NSAIDs
Statins & insulin sensitizers
Lecithin or Acetyl L-carnitine

Pharmacology (19 decks)

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