W20 Parkinson's and Dementia (AG) Flashcards
What is Parkinson’s disease?
- Parkinson’s disease (PD) is a chronic neurodegenerative disorder
- It is caused by the loss of dopamine-containing cells in the substantia nigra.
Risk Factors for Parkinsons’s disease? (5)
- Increasing age
- Male gender
- Head trauma
- Common genetic mutations (e.g. LRRK2, GBA, SNCA)
- Environmental toxin (e.g. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine [MPTP]) exposure
Symptoms – What are the Classical motor symptoms of idiopathic PD? (3)
other symptoms?
- Bradykinesia (slowness of movements, impared dexterity, delay in initiating movements, hypomimia-limits accurate expression of emotion)
- Parkinson’s tremor ( Involuntary tremor)
- Rigidity
Other symptoms:
Dystonia
Freezing
Postural instability
What are the Non-motor symptoms of PD?
- Constipation
- Sleep disorders (e.g. excessive daytime sleepiness, insomnia)
- Autonomic disturbances (e.g. urinary urgency, sweating, erectile dysfunction)
- Neuropsychiatric symptoms (e.g. anxiety, dementia, depression, hallucinations, delusions, mild memory and thinking difficulties)
- Speech and swallowing impairments (impaired swallowing, drooling, voice/speech disorder)
- Eye problem (e.g. excessive tearing)
- Pain (musculoskeletal pain)
- Fatigue
- Olfactory disturbance
Disease progression pattern- PD:
How many stages?
Stage 1: Mild symptoms that do not interfere with daily activities; for example, one sided tenors, posture, facial expressions
Stage 2: Symptoms worsen and daily tasks become more difficult and time-consuming. For example, tremors and rigidity affecting both sides of the body
Stage 3: Mid-stage of disease. Loss of balance and slowness of movement, resulting in increased falls. Still independent but simple activities such as dressing and eating may be difficult
Stage 4: Symptoms are severe and limiting. Movement may require a walker. Movement may require a walker. Patient needs help with daily activities and is unable to live alone
Stage 5: Stiffness in the legs may make it impossible to stand or walk. Patient requires a wheelchair or is bedridden. Around-the clock nursing needed. Patient may experience hallucinations and delusions. Important to manage both motor and non-motor symptoms.
Parkinson’s disease
Diagnosis:
- Prodromal phase lasting up to 20 years before diagnosis is emerging
- Differential diagnosis:
-Diseases that exhibit Parkinsonian symptoms but are not idiopathic PD include multiple system atrophy, progressive supranuclear
palsy, vascular PD and drug-induced Parkinsonism.
-Medications: older generation antipsychotics, antihistamines such as cinnarizine, methyldopa and antiemetics, such as metoclopramide — typically inhibit the actions of dopamine in the brain. - Diagnosis of PD is based on clinical presentation, as there is no reliable diagnostic test.
The need for multidisciplinary teams
(MDTs): PD
- GPs are not qualified to manage Parkinson’s meds= Consultant Neurologist
- Pharmacist- managemnt of motor and non-motor symptoms. Assess drug + food interactions
- PD Nurse specialist- clinical monitoring and medicines adjustment
- SALT- prevention exercises e.g. voice coaching
- Occ Physi- exercise, strengthening and stability
- Dieticians
Parkinson’s disease - Management
- Overall treatment is specific to the patient and the symptoms they experience.
- Symptoms can be variable from day to day or even hour to hour;
- Therefore, it is important that patients have a good understanding of their treatment, disease, coping mechanism, support system and regular reviews.
- Life expectancy can be normal.
- More advanced symptoms can lead to increased disability and poor health, which may make someone more vulnerable to complications (e.g. infection).
Pharmacological Management of Motor Symptoms: PD
3 drugs?
1.Administration of DA precursor (e.g. levodopa preparations such as co-careldopa);
2.Activation of DA receptors using DA agonists (e.g. ropinirole);
3.Enzyme inhibition to prevent the breakdown of DA (e.g.monoamine oxidase B inhibitors [MAO-B] and catechol-O-methyl transferase [COMT] inhibitors).
Parkinson’s disease - Levodopa Therapy
(DA precursors)
What is an example?
What is caused with long-term use?
Problems with missed dose?
- Levodopa + cabidopa or benserazide (dopa-decarboxylase inhibitors) (co-careldopa or co-beneldopa) to enable levodopa to cross the BBB and prevent break down of levodopa to DA in the gut (reducing side effects, such as N&V).
- Long-term use of levodopa can result in the patient experiencing dyskinesia and motor fluctuations (where the patient experiences ‘off-time’ periods, as the drug wears off and symptoms re-emerge). Also causes excessive daytime sleepiness.
- The short half-life and reducing duration of action make it important that patients get their medication on time every time.
- Late and missed doses contribute to risks of severe complications (e.g.** pneumonia and falls**)
Parkinson’s disease - DA agonists
- Preparations include M/R and I/R tablets (e.g. pramipexole and ropinirole), patches (rotigotine) and injections (apomorphine).
- There are two subclasses of DA agonists — ergoline and non-ergoline agonists — which both target DA D2-receptors.
1. Ergoline DA agonists, which include bromocriptine, pergolide, lisuride and cabergoline, are no longer routinely used in the treatment of PD because of adverse fibrotic^ reactions.
2. Non-ergoline DA agonists remain widely used and include ropinirole and pramipexole
^= thickening/scarring of tissue
Parkinson’s disease - DA agonists
What is the benefit of their use over levodopa?
When are Rotigotine or Apomorphine used?
Side effects?
▪ DA agonists may be less likely to cause dyskinesia and motor fluctuations than levodopa.
▪ Rotigotine is delivered transdermally via a patch, which can be particularly useful where patients have a high tablet burden or where patients have swallowing difficulties.
▪ Apomorphine is considered in advanced PD.
▪ Typical side effects include addictive gambling, hypersexuality, binge eating and obsessive shopping, somnolence, day-time sleepiness and hallucinations. Incidence increases with higher doses
Parkinson’s disease - DA agonists
Apomorphine S/C Injection:
Why is it given?
What to monitor?
Refractory motor fluctuations in Parkinson’s disease (‘off’ episodes) inadequately controlled by co-beneldopa or co-careldopa or other dopaminergics (for capable and motivated patients
Monitoring of patient parameters:
* Monitor hepatic, haemopoietic, renal, and cardiovascular function.
* With concomitant levodopa test initially and every 6 months for haemolytic anaemia and thrombocytopenia (development calls for specialist haematological care with dose reduction and possible discontinuation
Parkinson’s disease - COMTIs:
What is used and why?
- The inhibition of COMT prevents peripheral breakdown of levodopa, allowing more levodopa to reach the brain and prolonging the effect of levodopa dosing.
- As a result, concurrent levodopa doses need to be reviewed and possibly reduced by up to 30%.
- The COMT inhibitor entacapone is usually taken with each levodopa dose and is available alone or as a combination product with levodopa and carbidopa (which can be helpful in reducing tablet burden).
- An alternative is opicapone, which is taken just OD.
Parkinson’s disease – Adjuvant therapy e.g. Glutamate Antagonists
Example?
Why are they used?
▪ Glutamate antagonists, such as amantadine, are generally used to reduce dyskinesia caused by levodopa therapy.
▪ They can be used in all stages of PD, but are often prescribed when alternative strategies have not effectively managed motor complications.
dyskinesia= uncontrolled, involuntary movement
