Alzheimer's disease treatment

Question 1

what are the 2 pharmacotherapeutic approaches of AD and why

Answer 1

1. Acetylcholinesterase inhibitors AchEI

> Cholinergic basal forebrain neurons are among the first to die in AD, resulting in decreased levels of Ach in the brain
so AchEI increases levels of Ach by inhibiting the enzyme that breaks it down

2. Glutamate NMDA receptor antagonist
   > excitotoxicity (overactivity of glutamatergic synapses) is proposded to be part of AD pathology

Question 2

Give the 4 examples of AchNase inhibit we need to know

Answer 2

Tacrine, Donepezil, Rivastigimine, Galantamine

Question 3

Give the example of Gultamate NMDA receptor inhibitor we need to know

Answer 3

Memantine

Question 4

list the benefits of Acetylcholinesterase inhibitors

Answer 4

it is symptomatic, does not change the pathology of disease, but rather improves symptoms and delay progression:

1. delays progression to the severe stage by 6 - 12 m onths (30 - 60%) of patients)
2. patients experience improvements in :
   > cognitive function (Ach increase)
   > behavioural symptoms (Ach increase)
   > daily activities (Ach increase)

Question 5

which type of drug between Acetylcholinesterase inhibitors and Gultamate NMDA receptor inhibitor is the main approved drug and which stages of AD is it recommended for

Answer 5

Acetylcholinesterase inhibitors
mild to moderate (stage 1 - 2) because theres no point in severe as most of these neurons will have died anyway

Question 6

what is the negatives of Acetylcholinesterase inhibitors

Answer 6

significant side effects due to peripheral actions of drugs

peripheral: affecting, or being part of the peripheral nervous system

Question 7

is tacrine is used clinically

Answer 7

NO

Question 8

what is tacrine and what is its MOA

Answer 8

One of the first An Acetylcholinesterase inhibitor that had therapeutic effect on AD

the MOAs:

> Long acting AchEI
Blocks M1, M2 and nicotinic receptors
increases the release of Ach from nerve ending
inhibits MAO (Monoamine oxidase)
increase release of NA, 5HT, and DA from nerve ending : we dont want this due it it’s significant side effects

Question 9

what are the significant side effects of tacrine

Answer 9

> Nausea and vomiting which is due to increased peripheral Ach levels
Hepatic toxicity (life threatening)

Question 10

what is Donepezil , which stage is it indicated for, and what is its MOA

Answer 10

An Acetylcholinesterase inhibitor indicated for mild to moderate AD, but can be used for moderate to severe

MOA:

> Reversible centrally active AchEI

Question 11

what is the effects of donepezil in patients

Answer 11

Modest improvements in cognitive and behavioural scores in AD patients

Question 12

what are the side effects of donepezil

Answer 12

Nausea and vomiting
Hallucinations, Aggression, Agitation
Urinary incontinence
Gastric and duodenal ulcers

Question 13

what is rivastigmine, which stage is it indicated for and what is it MOA

Answer 13

An Acetylcholinesterase inhibitor indicated for mild to moderate AD

MOA:
> reversible AchEI

Question 14

what are the side effects of Rivastigimine

Answer 14

Nausea and vomiting
Hallucinations, Aggression, Agitation, Confusion, Insomnia
Extrapyramidal S/Es (worsening of PD)

Question 15

which disease is rivastigmine also indicated for

Answer 15

Dementia in parkinson’s disease

Question 16

what is Galantamine, which stage is it indicated for and what is it MOA

Answer 16

An Acetylcholinesterase inhibitor indicated for mild to moderate AD

MOA:
> Reversible AchEI
> An allosteric modulator / agonist at nicotinic Ach receptor -> stimulates further Ach release

Question 17

what are the side effects of Galantamine

Answer 17

Nausea and vomiting
Hallucinations, Aggression, Agitation, Confusion, Insomnia
Muscle spasms
Bradycardia and syncope

Question 18

what is Memantine , which stage is it indicated for and what is it MOA

Answer 18

A Glutamate NMDA Receptor Antagonists . indicated for moderate to sever AD

Question 19

what are the positive effects of memantine

Answer 19

improving cognitive, functional, behavioural and daily activity scores

Better tolerated than AchEIs

Question 20

when is memantine used

Answer 20

it is added to the AchEI regimen during the progression (decline) of the disease

Question 21

what is the MOA of memantine

Answer 21

it is a non competitive NMDA receptor antagonist

Question 22

what are the side effects of memantine

Answer 22

Constipation
Drowsiness, dizziness, headache, fatigue and hypertension

Question 23

what is used to treat the depression and anxiety symptoms of AD

Answer 23

SSRIs (Citalopram; Sertraline)
AEDs (Carbamazepine; Oxcarbazepine)

Question 24

what is used to treat the aggression and agitation symptoms of AD

Answer 24

AEDs (Sodium Valproate)
Antipsychotics (risperidone; quetiapine)

Question 25

What is the NICE dementia intervention step 2 - 4

Answer 25

step 2: interventions for cognitive symptoms and

Question 26

which cholinergic pathway is relevant to AD

Answer 26

Nucleus of meynert, located in the base of the brain. These cholinergic neurons project the cortex and release Ach and Ach is important for learning and memory

Question 27

describe the cholinergic pathway for AD AchEI

Answer 27

the drug is chemical inhibitor that blocks the functioning of achetylcholinesterase.

it doesn’t just work in the brain but systematically throughout the body&raquo_space;> high number of side effects