Alzheimer's pharm 1/22

Question 1

alzheimer’s path

Answer 1

from plaques containing beta-amyloid,tangles containing phosphorylated tau,cortical hippocampal atrophy

these can lead to destruction of cholinergic neurons in basal nucleus of meynert in basal forebrain which provides cholinergic innervation to cerebral cortex.See short-term memory in early stages

Question 2

causes of alzheimer’s

Answer 2

not clear.oxidative stress,inflammation or failure to clear A-beta-amyloid

chronic NSAIDs can reduce risk

Question 3

diagnostic tests

Answer 3

Pittsburgh imaging compound B (PIB) is a radioactive tracer which binds amyloid in brain and can be imaged using PET–>PIB-PET:aggregation process starts before symptoms

Question 4

tau proteins

Answer 4

normally provide structural supports to neurons

in alzheimer’s,they become detached and clump in tangles

Question 5

other diagnostic tests using tau proteins

Answer 5

measure tau proteins in CSF.Also look for decreasing level of beta amyloid which occurs as peptide removed from fluid to deposit in brain

increased tau and decreased beta-amyloid–>advanced disease

Question 6

diagnostic and monitoring imaging

Answer 6

volumetric MRI=measures shrinkage of brain as neurons expire

fluorodeoxyglucose-PET(FDG-PET)=gauges metabolic status of neurons

Question 7

mutations in amyloid precursor proteins (APP)

Answer 7

leads to formation of either A-beta amyloid in general or a particular type of A-beta that is highly prone to forming deposits

Question 8

pts with down’s

Answer 8

higher incidence of Alzheimer’s at a younger age

3 copies of chromosome 21 instead of two.this chromosome contains APP

Question 9

mutations in presenilin1 and 2

Answer 9

essential for the functioning of gamma-secretase

Question 10

variant of apolipoprotein called E4

Answer 10

pts with this variant involved in lipid metabolism–>higher risk for atheresclerosis and alzheimer’s

Question 11

other risk factors

Answer 11

obesity in mid-life,HTN,HC

Question 12

potential Tx options

Answer 12

1) inhibitors of enzyme producing beta-amyloid:block action of gamma secretase resulting in reduced APP–>amyloid peptides
2) vaccines or Ab that clear beta-amyloid:severe side effects in human.Bapineuzimab currently investigated
3) beta-amyloid aggregation blockers
4) Anti-tau compounds:
5) Neuroprotective agents:Nerve Growth Factor (NGF)

Question 13

current Tx against Alzheimer’s

Answer 13

modest effect

AChEI used to treat mild-moderate

NMDA antagonist for moderate-severe

Question 14

tacrine

Answer 14

first centrally acting CEI

generally not used due to severe hepatotoxicity

Question 15

donepezil

Answer 15

reversible CEI in CNS and periphery

long 1/2 life,dosed once daily

side effects:n/d,headache,insomnia,anorexia,pain,urinary incontinence

contra:arrhythmias,seizures,asthma,COPD

may accentuate effect of succs,CYP450

Question 16

galantamine

Answer 16

may be for alzheimer’s with cerebrovascular component

CEI and positive allosteric modulator of nicotinic receptors

two actions work together to enhance activation of nicotinic receptors

same side effects as donepezil

Question 17

rivastigmine

Answer 17

CEI and butyrylCEI in glia

when cortical neurons die,gliosis occur–>butyrylCEI is important

GI side effects more severe than others. Could reduce with a skin patch

Question 18

memantine

Answer 18

NMDA receptor antagonist

amyloid plaques cause small continuous release of glutamate that is excitotoxic

drug only blocks open NMDA channels with low to moderate affinity.also fast on and off time.Not powerful to block all NMDA transmission

also used for huntington,AID dementia and vascular dementia

Question 19

side effects of memantine

Answer 19

dizziness,confusion,headache,HTN,

raising urine pH will reduce elimination

don’t combine with other NMDA blockers like ketamine,amantadine,dextromethorphan

Also vit.E as antioxidant

Question 20

Non-pharm approaches

Answer 20

exercise and CV health (metformin)

support caregiver

behavioral approaches like distraction or close-ended questions

environmental modification

developing and maintaining routines

sensory intervention:music,pet therapy

Question 21

other behavioral changes of dementia

Answer 21

psychotic:hallucinations,delusions,delusional misidentification

non-psychotic:agitation,wandering,aggression

Question 22

atypical antipsychotics

Answer 22

first line of therapy

once daily at night for sedation

Quetiapine is lease likely to increase symptoms in Parkinson’s

Question 23

typical antipsychotics

Answer 23

haloperidol at low doses to manage acute agitation and delirium

Question 24

anticonvulsants

Answer 24

when psychosis leads to aggressive behavior as second-line

valproic acid or carbamazepine

Question 25

anti-depressants

Answer 25

SSRI for depressions

avoid TCA

Question 26

Benzos

Answer 26

first line for anxiety

may worsen behavior due to amnesia and disinhibition

should be used to only manage acute symptoms

use ones with short 1/2 lives and no active metabolites