Hot Topics

Question 1

Describe non-pharmacological management of alzeihmers

Answer 1

1) minimise anticholingeric drugs (REMEMEBER- in alzeihmers you have an acetylcholine deficiency ie reduced cholingeric effect, make sure not on oxybutynin)

2) correct sensory impairment (evidence that it helps for people AT RISK of dementia but lacking evidence for people who already have dementia)

3) cognitive stimulation therapy for mild-mod alzheimers disease (6 month delay in expected cognitive decline)

Question 2

What are some non-pharmacological treatment in alzeihmers that do not have a role?

Answer 2

acupuncture
ginseng, vitamin E
non-invasive brain stimulation
cognitive training (task-specific)
nutritional drinks

Question 3

What drugs can we use for alzeihmers?

Answer 3

1) acetylcholinesterase inhibition
2) NMDA receptor antagonism (meantime)
3) anti-amyloid therapies

Question 4

Describe when to use acetylcholinesterase inhibitors in alzeihmers dementia

Answer 4

Use in mild-mod dementia, MMSE score at least 10

options: donepezil, galantine, rivastigmine

if donepezil or galantine dont work, swap to rivastigmine as it doesnt only block acetylcholinesterase but also butyrylcholinesterase.

benefit in 40-70% of patients, improvement in cognitive and function

Question 5

Describe side effects, contraindications and precautions for acetylcholinesterase inhibition

Answer 5

Side Effects
- gastro: N/V, diarrhoea, anorexia, weight loss
- bradycardia, dizziness, syncope
- vivid dreams (mainly with donepezil)

Contraindications and precautions
- gastric ulcers (increase risk of bleeding)
- ureteric obstruction
- heart block or bradyarrhythmias

Question 6

Describe indications for NMDA receptor antagonism (memantine)

Answer 6

mod-severe AD
MMSE score 10-14
intolerant of or have a contraindication to AChEIs

NMDA respond to neurodegeneration driven by glutamate

Contraindications
- seizures

Question 7

Describe management of behaviour and psychological symptoms in alzeihmers disease

Answer 7

Depression- no clear evidence treatment
Agitation- SSRI
severe symptoms- antipsychotics (increased risk stroke, death), risperidone has the best evidence for psychosis

Question 8

Describe the anti-amyloid therapies and concerns with them

Answer 8

Lecanemab (every 2 weeks) and donanedab (every 4 weeks)

concerns: amyloid-rleated imaging abnormalities (ARIA)
- oedema (ARIA-E) or haemorrhage (ARIA-H)
- donanedab more likely to cause these

these side effects more likely to occur early on, drug cessation not usually required, just need to monitor.
headache, dizziness most common symptoms

need to have amyloid positivity to quality for this treatment via amyloid PET or CSF

Question 9

How do antibody drug conjugates work?

Answer 9

ADC bind to specific antigens on caner cells, then internalisation and drug release into the cancer cell.

Question 10

Describe S/E of trastuzumab deruxtican compared to trastuzumab emtansine

Answer 10

Trastuzumab deruxtican:
Common: nausea, hair loss, constipation, diarrhoea, LFT derangement

things that lead to discontinuation: pneumonitis, interstitial lung disease, pneumonia

Trastuxumab emtansine
common: thrombocytopenia , pneumonitis

Question 11

What is mirvatuximab soravtansine?

Answer 11

a folate receptor alpha
used in solid tumours such as ovarian cancer

Question 12

What is good about mirvatuximab soravtansine? and what is the main S/E

Answer 12

good: a lot less myelosuppression with mirvatuximab

main S/E: ocular toxicity