Alzheimer's disease treatment Flashcards
what are the 2 pharmacotherapeutic approaches of AD and why
- 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
- Glutamate NMDA receptor antagonist
> excitotoxicity (overactivity of glutamatergic synapses) is proposded to be part of AD pathology
Give the 4 examples of AchNase inhibit we need to know
Tacrine, Donepezil, Rivastigimine, Galantamine
Give the example of Gultamate NMDA receptor inhibitor we need to know
Memantine
list the benefits of Acetylcholinesterase inhibitors
it is symptomatic, does not change the pathology of disease, but rather improves symptoms and delay progression:
- delays progression to the severe stage by 6 - 12 m onths (30 - 60%) of patients)
- patients experience improvements in :
> cognitive function (Ach increase)
> behavioural symptoms (Ach increase)
> daily activities (Ach increase)
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
Acetylcholinesterase inhibitors
mild to moderate (stage 1 - 2) because theres no point in severe as most of these neurons will have died anyway
what is the negatives of Acetylcholinesterase inhibitors
significant side effects due to peripheral actions of drugs
peripheral: affecting, or being part of the peripheral nervous system
is tacrine is used clinically
NO
what is tacrine and what is its MOA
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
what are the significant side effects of tacrine
> Nausea and vomiting which is due to increased peripheral Ach levels
Hepatic toxicity (life threatening)
what is Donepezil , which stage is it indicated for, and what is its MOA
An Acetylcholinesterase inhibitor indicated for mild to moderate AD, but can be used for moderate to severe
MOA:
> Reversible centrally active AchEI
what is the effects of donepezil in patients
Modest improvements in cognitive and behavioural scores in AD patients
what are the side effects of donepezil
Nausea and vomiting
Hallucinations, Aggression, Agitation
Urinary incontinence
Gastric and duodenal ulcers
what is rivastigmine, which stage is it indicated for and what is it MOA
An Acetylcholinesterase inhibitor indicated for mild to moderate AD
MOA:
> reversible AchEI
what are the side effects of Rivastigimine
Nausea and vomiting
Hallucinations, Aggression, Agitation, Confusion, Insomnia
Extrapyramidal S/Es (worsening of PD)
which disease is rivastigmine also indicated for
Dementia in parkinson’s disease
what is Galantamine, which stage is it indicated for and what is it MOA
An Acetylcholinesterase inhibitor indicated for mild to moderate AD
MOA:
> Reversible AchEI
> An allosteric modulator / agonist at nicotinic Ach receptor -> stimulates further Ach release
what are the side effects of Galantamine
Nausea and vomiting
Hallucinations, Aggression, Agitation, Confusion, Insomnia
Muscle spasms
Bradycardia and syncope
what is Memantine , which stage is it indicated for and what is it MOA
A Glutamate NMDA Receptor Antagonists . indicated for moderate to sever AD
what are the positive effects of memantine
improving cognitive, functional, behavioural and daily activity scores
Better tolerated than AchEIs
when is memantine used
it is added to the AchEI regimen during the progression (decline) of the disease
what is the MOA of memantine
it is a non competitive NMDA receptor antagonist
what are the side effects of memantine
Constipation
Drowsiness, dizziness, headache, fatigue and hypertension
what is used to treat the depression and anxiety symptoms of AD
SSRIs (Citalopram; Sertraline)
AEDs (Carbamazepine; Oxcarbazepine)
what is used to treat the aggression and agitation symptoms of AD
AEDs (Sodium Valproate)
Antipsychotics (risperidone; quetiapine)
What is the NICE dementia intervention step 2 - 4
step 2: interventions for cognitive symptoms and
which cholinergic pathway is relevant to AD
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
describe the cholinergic pathway for AD AchEI
the drug is chemical inhibitor that blocks the functioning of achetylcholinesterase.
it doesn’t just work in the brain but systematically throughout the body»_space;> high number of side effects
