IC14 Pharmacology III Parkinson's & Alzheimer's disease Flashcards
What is Parkinson’s disease?
It is a neurodegenerative disease that causes extrapyramidal motor symptoms due to striatal dopaminergic deficiency.
Examples of EPS are:
- Tremors
- Rigidity
- Bradykinesia
What are the 4 motor symptoms of Parkinson’s Disease?
- Tremor at rest
- Bradykinesia - slowness of movement
- Rigidity
- Gait disturbance and postural instability
What is the theorized pathophysiology of Parkinson’s disease?
- Failure to clear toxic proteins(a-synuclein)
- Resulting in accumulation of Lewy bodies
- Apoptosis of brain neuronal cells
What are possible treatments for Parkinson’s Disease?
- Levodopa
- COMT inhibitors (entacapone OR tolcapone)
- MAO-B inhibitors (selegiline OR rasagiline)
- Dopamine agonist (pramipexole)
- Amantadine
- Anticholinergics (trihexyphenidyl)
What is the pathway of dopamine synthesis?
L-tyrosine → Levodopa → Dopamine
Comparing levodopa and dopamine, which of the 2 can pass through the blood brain barrier?
Levodopa can pass through the blood brain barrier.
Dopamine is not able to pass through the blood brain barrier.
How do we treat Parkinson’s disease?
We give patients Levodopa.
Levodopa is often given together with carbidopa or benserazide.
Carbidopa and benserazide helps to block the dopamine enzymes, allowing more levodopa to reach the brain.
What are the side effects of levodopa?
The side effects of levodopa are:
1. Dyskinesia
2. N&V
3. Postural hypotension
Dyskinesia - involuntary, erratic, writhing movements of the face, arms, legs or trunk.
If a patient were to develop dyskinesia after using levodopa, it is permanent and does not go away once it develops.
Hence, while levodopa is highly effective, we would like to try other alternatives before starting patients on levodopa.
What is the MOA of COMT inhibitors?
COMT inhibitors help to block COMT from converting dopamine/levodopa to an inactive form.
Examples of COMT inhibitors:
- Entacapone
- Tolcapone
How are COMT inhibitors used?
They are often used as adjunct to levodopa.
They help to increase more available levodopa that enters the brain.
What are the side effects of COMT inhibitors?
- Dyskinesia - ↑ abnormal movements
- Liver dysfunction - associated w Tolcapone
- Nausea, diarrhoea
- Daytime sleepiness, sleep disturbances
What is the MOA of MAO-B inhibitors?
MAO-B inhibitors help to inhibit monoamine oxidase B, preventing the breakdown of dopamine.
Examples of MAO-B inhibitors:
- Selegiline
- Rasagiline
Selegiline can be used as 1st line monotherapy for early stages of Parkinson’s disease symptoms.
What are the SEs of MAO-B inhibitors?
- GI: Heartburn, loss of appetite
- Anxiety, palpitation, insomnia
- Nightmares, visual hallucinations
Hallucinations can be caused by too much dopamine. MAO-B inhibitors can lead to too much dopamine and this can trigger visual hallucinations.
What is an example of dopamine agonist & what is its MOA?
An example of a dopamine agonist:
- Pramipexole
MOA of dopamine agonists:
- Act directly on dopamine receptors in the brain to reduce symptoms of PD
Effects of dopamine agonists are still not superior to levodopa. Levodopa is still the GOLD standard.
Why do we use dopamine agonists instead of starting levodopa in younger pt w PD?
Despite levodopa being more efficacious, we are afraid of the development of dyskinesia.
Once dyskinesia develops, it is permanent. Hence, we use dopamine agonist in younger PD pt to reduce the risk of developing dyskinesia.
What are the SEs of dopamine agonists?
- N&V
- Postural hypotension
- Headache
- Dizziness
- Cardiac arrhythmia
- Sedation
- Somnolence
- Daytime sleepiness
What is amantadine?
Amantadine is an antiviral drug that has mild antiparkinsonian effect (dyskinesia, tremor, etc.)
How is amantadine given to a patient?
It is often given as monotherapy or adjunct to levodopa.
What is the MOA of amantadine?
- It helps to enhance the release of stored dopamine.
- It functions as a dopamine agonist
- It is an anti-glutamate agent
What is the special property of amantadine?
It is able to help reduce dyskinesia in pt w PD.
However, it does not completely eliminate dyskinesia.
What are the side effects of amantadine?
- Difficulty concentrating
- Hallucination
- Insomnia
- Nightmares
- Livedo reticularis*
Livedo reticularis - venule swelling due to thromboses. It causes discolouration of limbs, while being able to see veins on the surface of the skin.
What is an example of anticholinergics & how is it used?
Example of anticholinergic:
- Trihexyphenidyl - brand name: Benzhexol
Anticholinergic agents may be used as monotherapy or adjunct therapy to levodopa.
What are anticholinergic agents used for?
It can be used to treat tremors, stiffness and sialorrhoea.
Sialorrhoea - a debilitating symptom which occurs when there is excess saliva in the mouth beyond the lip margin.
What are the side effects of anticholinergics?
- Dry mouth
- Sedation
- Constipation
- Hallucination
- Delirium
- Confusion
- Urinary retention
