Lecture 5 & 6: Parkinsons Disease Pathophysiology, Pharmacology And Pharmaceutical Care Flashcards
1
Q
What is Parkinson’s disease?
A
- A lifelong, chronic & progressive neurodegenerative disorder that primarily affects movement and can involve non-motor symptoms (not movement related)
2
Q
At what age does Parkinson’s disease mainly affect individuals?
A
Over 65
3
Q
What happens to neurons in Parkinson’s disease?
A
- Nerve cells in the substantia nigra become damaged or die, leading to decreased dopamine production.
- This leads to the symptoms
4
Q
Who is responsible for diagnosing Parkinson’s disease?
A
A hospital clinician with expertise.
5
Q
What are the common symptom of Parkinson’s disease?
A
- Tremor
- Rigidity
- Bradykinesia
6
Q
What does rigidity in Parkinson’s disease refer to?
A
- Stiffness and resistance to limb movement caused by increased muscle tone.
- Excessive contraction of muscles and joint pain
7
Q
Define bradykinesia in the context of Parkinson’s disease.
A
- Slow movement, difficulty planning, initiating, and executing movement.
- Problems w/ fine motor movement (writing)
8
Q
Name some other symptoms associated with Parkinson’s disease.
A
- Depression
- REM sleep behavior disorder
- Gait instability (difficulty maintaining balance when walking. Stooped posture)
- Eye problems
- Fatigue
9
Q
What is postural hypotension?
A
A fall in blood pressure when rising.
10
Q
What are the affected dopamine pathways in Parkinson’s disease?
A
- Nigrostriatal
- Mesocortical
- Mesolimbic
- Tubero-infundibular
11
Q
What is the role of the nigrostriatal pathway?
A
- Transmits dopamine from the substantia nigra to the striatum, crucial for voluntary movements.
- Typical symptoms
12
Q
What symptoms are associated with the mesolimbic pathway dysfunction and what does it control?
A
- Depression, reduced motivation, and pleasure.
- Links the ventral tegmental area (VTA) to the Limbic system
- It regulates emotion, reward and motivation
13
Q
What happens to the tuberoinfundibular pathway when dopamine levels are reduced?
A
- This pathway connects dopamine neurons to the arcuate nucleus of the hypothalamus to the pituitary gland
- Prolactin secretion increases, leading to hyperprolactinemia and galactorrhea (milk production not associated with/ breastfeeding)
14
Q
What is the consequence of dopamine depletion in Parkinson’s patients?
A
- Normal: Substantia Niagra has dopanergic neurons and signal travels to basal ganglia and striatum in which dopamine binds to D1 and D2 receptors
- In the striatum dopamine controls/ regulates GABAergic activity (inhibitory). This system/ neurotransmitter is inhibited therefore glutamergic system (motor cortex and frontal lobe) is activated. This promotes excitatory and causes movement
- In Parkinsons Patient: Dopamine depletion reduces activation of receptors; Inhibitory mechanism is overactive (more GABA) – difficulty moving
15
Q
What are the different strategies to be used in treatment:
A
- Promote more dopamine to be made
- Activate receptors with agonist (not dopamine)
- Reduce breakdown of dopamine (MAO)
16
Q
How is dopamine synthesised?
A
- Tyrosine (amino acid) -> L-DOPA (produced by enzyme Tyrosine Hydroxylase) -> dopamine (produced by DOPA decarboxylase)
17
Q
What are common long-term side effects of L-DOPA therapy?
A
- Dyskinesia (uncontrollable/ eratic movement)
- End of dose deterioration (effect of first dose will wear off before next dose)
- Freezing (Walk then just stop)
- Dopamine dysregulation (amount of dopamine is dysregulated in the brain)
18
Q
What is the role of monoamine oxidase in the context of Parkinson’s disease?
A
- It metabolizes dopamine in the CNS, particularly MAO-B.
- Therefore need something to inhibit this so dopamine remains (Selegiline/rasagiline)
19
Q
What does COMT do in relation to dopamine?
A
- Breaks down catecholamines like L-DOPA and dopamine in peripheral & CNS
- therefore inhibitors increase dopamine (Tolcapone).
- Given in conjunction w/ L-DOPA
20
Q
Fill in the blank: The pathway that connects dopaminergic neurons in the arcuate nucleus of the hypothalamus to the pituitary gland is called the _______.
A
Tubero-infundibular
21
Q
What is the function of carbidopa when combined with L-DOPA?
A
Inhibits the enzyme (DOPA decarboxylase) that converts L-DOPA to dopamine in the periphery.
22
Q
What is the function of the mesocortical dopamine pathway?
A
- Connects the VTA to the prefrontal cortex, regulating cognition, attention, and executive function.
- Difficulty with planning and decision-making.
23
Q
What is first line, second line and third line symptomatic treatments of early Parkinsons Disease?
A
- Levodopa + decarboxylase inhibitor (can use domperidone alongside to reduce N&V)
- Oral/transdermal dopamine agonists: Bind w/ receptor + combined with levodopa. Mimics effect. Dont offer ergot derived for first line
- Monoamine oxidase B inhibitors (Rasagiline) used alongside levodopa to reduce end of dose deterioation
24
Q
What are some complications of Parkinsons Disease?
A
- Communication
- Family/carers
- Non-motor symptoms - distracted/ diminished attention
25
What is the difference between early and late Parkinsons Disease?
* Early Disease: Functional disability and require symptomatic therapy
* Late Disease: People on levodopa who have developed motor complications
26
What are some issues with ergot derived dopamine agonists?
* Cabergoline - long half life
* Associated w/ cardiac valvulopathy & pleural fibrosis
* Monitoring needed: renal function tests. (usage has declined)
27
What are some side effects of ergot and non-ergot derived agonists?
* Impulse control disorders
* Daytime drowsiness
* Peripheral oedema
* Nausea & dizziness & constipation
28
Why are Anticholinergic and beta blockers not used in early Parkinsons Disease?
* Anticholinergic: Less dopamine seceretion promotes activity of cholinergic in brain (dementia) & cause sedation/ glaucoma & constipation
* Beta Blockers: Risk of falls and changes to BP
29
What are symptoms of later Parkinsons Disease?
* Physical symptoms no longer controlled by meds
* Medication side effects (problematic)
* End of dose deterioration and akinesia (loss of movement)
* Dyskinesia
* Freezing
* Levodopa tolerance
30
How do you treat long term treatment side effects w/ Levodopa?
* Dopamine agonist can be used to reduce motor fluctuations
* Use non-ergot. If ergot given monitoring required
31
What are treatment strategies for later Parkinsons Disease?
* Levodopa + dopa decarboxylase inhibitor
* Oral/ transdermal dopamine agonists
* Monoamine oxidase B inhibitors
* COMT inhibitors
* Amantadine
* Apomorphine
* Intestinal gels & produodopa (new subcutaneous
32
What is apomorphine?
* Non-ergot dopamine agonist
* Delivered injections/ continuous infusion (avoids first pass metabolism)
* Those who have severe off periods that arent responsive to changes in oral meds
* Risk of confusion and hallucinations
33
What is amantadine?
* Weak dopamine agonist with modest effects
* Increase dopamine release
* Weak antagonist of the NMDA type glutamate receptor
* Less effective than levodopa
* Can be used alongside levodopa to improve muscle control & reduce stiffness
34
What should be done/given when patient is drooling, N&V and constipation?
* Drooling: SALT review/ botulinum toxin A injected into salivary gland (specialist)
* N&V: Low dose domperidone
* Constipation: Lifestyle/ fibre/ laxatives
35
What should be done/given when patient is Pain, sleep disorder & depression?
* Pain: simple analgesia/ exercise
* Sleep disorder: sleep hygiene
* Depression: SSRI (watch for worsening restless legs), TCA (cognitive impairment and falls risk)
36
What are some prescribing points of Parkinsons Disease meds?
* Shouldnt be withdrawn suddenly or allowed to fail due to poor absorption (to avoid potential akinesia - loss of voluntary movement or neuroleptic malignant syndrome - rare but life threatening w/ fever/ muscular rigidity
* Dose timing is critical - missed/late should be avoided
* Doses should be given as close to usual times
* Avoid drugs that act as dopamine antagonists: metoclopramise, haloperidol
37
Patient arm shakes approx 1 hour before dose and gets painful cramps at night. What alterations should be given to minimise effects?
* Reduce amount given in each dose
* Increase administration to last longer
* More prolonged release
* Management of pain
* Administer MAO-B inhibitors
