Alzheimer's Disease

Question 1

hallmarks of AD pathology

Answer 1

amyloid plaques, neurofibrillary tangles, loss of cholinergic neurons

Question 2

genes involved in early onset AD

Answer 2

PSEN1, PSEN2, APP

Question 3

2 copies of _ gene makes it 8x more likely to get AD

Answer 3

APOE4

Question 4

Name acetylcholinesterase inhibitors for treating AD

Answer 4

donepezil, rivastigmine, galantamine

Question 5

NMDA receptor antagonist

Answer 5

Memantine (reduce excitotoxic damage)

Question 6

amyloid vaccine

Answer 6

Aducamumab

Question 7

first anti-cholinesterase, why no longer prescribed?

Answer 7

tacrine; nausea, liver damage

Question 8

which anti-cholinesterase is now available as a generic?

Answer 8

Donepezil

Question 9

half-life of donepezil

Answer 9

70hours

Question 10

side effects of donepezil

Answer 10

nausea, diarrhoea, vomiting, fatigue, muscle cramps, bradycardia

Question 11

which anticholinesterase has more affinity for brain cholinesterase than peripheral?

Answer 11

Rivastigmine

Question 12

what is the MOA of rivastigmine?

Answer 12

inhibits both acetylcholinesterase and butylcholinesterase

Question 13

plasma half-life of rivastigmine and admin

Answer 13

2 hours, transdermal patch

Question 14

MOA of galantamine?

Answer 14

(i) competitive and reversible inhibitor of AChE
(ii) positive allosteric modulator of pre and post synaptic nicotinic ACh receptors, increases ACh release and activity

Question 15

NMDA Receptor antagonism, why is this targeted?

Answer 15

NMDA is a glutamate receptor, in AD brain there is glutamergic overstimulation leading to excitotoxicity. blocking the receptor will reduce the glutamate neurotransmission and subsequently reduce excitotoxicity

Question 16

what drugs can memantine be used with?

Answer 16

anticholinesterase inhibitors

Question 17

memantine half life

Answer 17

60-80 hours

Question 18

what are side effects (mild to severe) of cholinergic drugs?

Answer 18

cardiac: bradycarida, dysrhythmias, hypotension
GI: increased output of gastric acid, nausea, vomiting, abdominal cramps, diarrhea
excessive salivation
bronchoconstriction