PHARM - Drugs for the Treatment of Neurodegenerative Disease - Week 8 Flashcards
(77 cards)
Define 6 characteristics of dementia.
Memory loss Loss of logical thinking and judgement Loss of speech and movements Personality changes Increased dependency for all needs Decreased mobility to being bedridden
What is the most common form of dementia?
Alzheimer’s disease
What are two hallmarks of Alzheimer’s disease?
Beta-amyloid plaques and neurofibrillary tangles
Describe beta-amyloid plaques and where they accumulate.
Dense deposits of protein and cellular material that accumulate outside and around the nerves.
Describe neurofibrillary tangles.
Twisted fibres that build up inside nerve cells.
What is the precursor to beta-amyloid protein?
Amyloid precursor protein
Describe briefly in three steps how beta-amyloid plaques form.
Amyloid precursor protein sticks through the neuron membrane
Enzymes cut it into fragments of protein which include beta-amyloid
Beta-amyloid fragments clump together and form plaques
What do beta-amyloid plaques interfere with?
The work of neurons
Name the protein which provides the structural integrity for nerves, what protein they are supported by, and what happens to them in Alzheimer’s disease.
Neurons have an internal support partly made up of microtubules.
A protein called tau helps stabilise them.
In Alzheimer’s disease, they change and clump together to form neurofibrillary tangles.
The microtubules collapse.
Describe the cholinergic hypothesis for Alzheimer’s disease and a possible treatment option based on it.
Loss of ACh in Alzheimer’s correlates with impairment of memory - cholinergic deficiency contributes to cognitive decline.
Enhancement of cholinergic function stabilise or improve cognitive function and mat affect behaviour and daily functioning.
Name 4 behavioural symptoms that cholinergic deficiency may contribute to in Alzheimer’s disease.
Psycosis-agitation
Apathy-indifference
Disinhibition
Aberrant motor behaviour
In what severity of Alzheimer’s do cholinesterase inhibitors have efficacy?
Mild/moderate
What class of drugs used to treat Alzheimer’s may be helpful for Lewy body disease?
Cholinesterase inhibitors
How do cholinesterase inhibitors work?
They decrease ACh breakdown
Name 16 adverse effects of cholinesterase inhibitors.
Nausea Vomiting Diarrhoea Anorexia Abdominal pain Headache Insomnia Vivid dreams Depression Fatigue Drowsiness Dizziness Urinary incontinence Increased sweating Tremor Muscle cramps
Does treatment of Alzheimer’s with cholinesterase inhibitors prevent cognitive decline?
Initially it may, however eventually cognitive decline will decline at the same rate as without treatment.
However, cognitive state with treatment will still be higher than if there was no treatment.
In other words, it transiently maintains cognitive abilities.
Describe the action of γ secretase.
Cleaves the amyloid precursor protein with its transmembrane segment
What is presenilin and what does it affect? What happens with a mutation to this protein?
It is a component of the γ secretase complex.
It affects APP processing.
If mutated, there is an increase in amyloid beta fragments.
Briefly describe the concept of anti-amyloid immunotherapy for Alzheimer’s treatment.
Subjects are immunised with beta amyloid and attenuates Alzheimer’s disease-like pathology
Do anti-amyloid drugs work?
Some studies suggest no.
What is the accumulation of beta amyloid linked to?
Degenerative changes in the brain.
Name three aims of Alzheimer’s disease therapy.
Improve cognitive function
Limit disease progression
Symptom control
Describe Parkinson’s disease.
A chronic, progressive neurodegenerative disease of muscle movement
Describe the pathology of Parkinson’s disease.
Degeneration of the dopaminergic neurons in the substantia nigra pars compacta
