Parkinson's disease Flashcards
What is PD?
A chronic, progressive neurodegenerative condition resulting from a loss of dopamine-containing cells of the substantial niagra.
What age group has highest PD incidence?
Incidence increases with age- highest in over 80s
What is the presentation triad seen in PD?
- Bradykinesia- slowness of movement
- Muscle rigidity
- Tremor
These 3 symptoms are known as parkinsonisms- they can be PD but can also be present in drug use, brain damage e.g. stroke
What are the non-motor PD symptoms?
Depression, anxiety
fatigue
cognitive impairement
sleep disturbance
constipation
hyposmia- dencreased sense of smell
excessive sweating
bladder problems
pain
hypotension
excess saliva or drooling
Which dopamine pathway is responsible for the motor symptoms?
Nigrostriatal
Which dopamine pathway is responsible for the behavioural symptoms?
mesolimbic and mesocorticol
Which dopamine pathway is responsible for the endocrine symptoms?
tuberohypophyseal
What are the motor symptoms of PD?
- Bradykinesia- slowness of voluntary movements.
Can include mask-like lack of facial expressions
Hypophonia- soft or monotone voice
Micrographia- small handwriting
difficulty in fine motor actions e.g. doing buttons
shuffling gait- smaller steps - Rigidity- increased muscle tension
mostly affects flexor muscles of trunk and limbs
stooping posture
increased falls, decreased balance
muscle pain - Tremor
not in all patients
presents at rest
1 or both hands
‘pill-rolling’- moving fingers in a circular motion
NOTE- lots of meds can cause a tremor so review to see if these can be adjusted e.g.
Anti-psychotics e.g. haloperidol
Beta-agonists e.g. salbutamol, salmeterol
Anti-emetics e.g. metoclopramide, prochlorperazine
What are the causes of PD?
Often unknown
- can be inherited genetics e.g. 𝛼-synuclein point ,station, PARKIN gene mutation, Lewy body formation
- main is increasing age
- environmental - prescription drugs e.g. APs, anti-emetics or recreational drugs.
- Physical e.g. cerebral ischaemia, viral encephalitis, brainstem injury, dementia pugilistic
What is encephalitis lethargy?
A viral illness that had an epidemic in the 1920s- gradually patients seized up and had drowsiness and rigidity- eventually became permanent
- levodopa provides short time relief
How is PD diagnosed?
- Often patient presents in primary care with gradual symptoms
- Refer to a specialist
- there is no conclusive diagnostic test- instead it is based on symptoms, medical history and neurological ecm
- MRIs may be used for differential diagnoses
- DATSCAN- measures density of nigrostriatal dopamine transporter sites (loss of dopaminergic neurones) - but even an abnormal DATSCAN cam exlusively confirm pd diagnosis
- improvements with PD meds confirm a diagnosis
What is the recommended first line treatment for motor symptoms?
Levodopa
What are the treatment guideline for motor symptoms?
1st line:
- Offer Levodopa in early PF where motor symptoms affect pt quality of life
- Consider dopamine agonists, levodopa, MAO-B inhibitors for early PD whose motor symptoms do not affect QOL.
Adjuvant therapies:
ensure 1st line is optimised
When: dyskinesias or motor fluctuations develop inc wear off episodes of meds, offer:
Choice of dopamine agonists, monoamine oxidase B inhibitors to COMT inhibitors as an adjuvant to levodopa
- if dyskinesia not adequately controlled, consider amantadine
What are acute side effects of levodopa?
Nausea
anorexia
hypotension
anxiety, depression, insomnia, nightmares, hallucinations
- on off phenomenon- increase in symptoms as dose wears off and may cause freezing
How is levodopa always given?
As a combination product with carbidopa and benserazide
As these decrease the peripheral metabolism of levodopa and decrease peripheral side effects- they do not cross the BBB
Carbidopa + levodopa = co-careldopa e.g. Sinemet
Benserazide + levodopa = co-beneldopa e.g. Madopar
What are examples of COMT inhibitors?
Entacaponr
Tolcapone- rarely used due to risk of liver toxicity
What are Stanek, Stavelo and Sastravi?
A co-careldopa + entacapone formulation
- these potentiate the effects of levodopa
- Helps counteract the fluctuations in plasma conc of levodopa
- entacapone isn’t useful alone
What are the side effects of entacapone?
Colours urine bright red/orange- need to counsel patient
Diarrhoea
May worsen Levodopa side effects e.g. nausea, psychological effects, dyskinesia
How is levodopa administered?
- in divided daily doses to reduce peaks and troughs- max of 800mg per day
- Often as a MR prep before bed
Should you take levodopa with food?
Proteins inhibit the absorption- so wait 30-60 mins after medication before eating
What is important when prescribing/dispensing levodopa?
it is brand specific
Can you take iron supplements with levodopa?
Yes but you must wait 2 hours before taking any supplements- chelates can form in GIT and affect absorption
What are examples of ergot and non-ergot derived dopamine agonists? What are the differenced between them?
Ergot-derived
e.g. Lisuride, Pergolide, Brompocriptine, cabergoline
- These are limited by side effects e.g. N+V, Fibrotic reactions of lungs and heart valves
- Are only used if non-ergot derived have inadequate responses.
Non-ergot derived:
e.g. ropinorole, rotigotine, pramiprexole
- are better tolerated
- can cause ha;;inclinations and compulsive behaviours
Ergot derivatives, older dopamine agonists, interact not only with dopamine D1 and D2 receptors but many other neurotransmitter receptors such as serotonin and adrenergic receptors. Newer dopamine agonists, which are non-ergot agents, have a high affinity to dopamine D2 and D3 receptors
What patch is often used in patients with PD who can’t take oral meds adequately?
Rotigotine transdermal patch
What can disorders can dopamine agonists cause?
Impulse control disorders
e.g. Gambling, hypersexuality, binge eating, obessive shopping
onset can be 4-5 years after starting treatments
- more common in younger age groups, males, history of smoking or alcohol abuse.
if occurs:
- gradually decrease dose of dopamine agonists and monitor whether ICD improves
- offer specialist CBT to target ICD
What are examples of MAOB inhibitors?
Selegeline
Rasagiline
How come some conditions where MAO inhibitors are used, the patients are told to avoid aged foods?
Because the MAO inhibitors used in PD, are MAO-B specific and these inhibitors don’t interact with tyramine found in aged foods e.g. cheese, wine, dried meats.
However, in other conditions MAO-A inhibitors can be used which do have these recommendations as MAO enzyme breaks down excess tyramine in the body, If levels of tyramine increases it can cause highly raised blood pressure.
What are possible side effects of MAO-B inhibitors?
nausea
postural hypotension
dyskinesia
confucion- esp in elderly
When is amantadine used in PD?
Is only used as an add-on as shows mils benefit to symptoms of treating dyskinesia in Parkinson’s patients receiving levodopa
What are the side effects of Amantadine?
Psychological e.g. hallucinations, delusions, paranoia, sleep disturbances
GI- N+V, anorexia, weight loss, dry mouth
hypotension
palpitations
If the effectiveness of Amnatadine starts to decrease, what may increase it again?
Slowly withdrawing the drug and then re-introducing it may prolong its effectiveness.
Why is consistent dosing of levodopa important?
Missing or delaying a dose can cause:
- Acute dyskinesia- inability to initiate movement
- unable to communicate
- lose ability to swallow- increased risk of aspiration
- increased risk of falls and fractures
- Risk of neuroleptic-like malignant syndrome- this is very rare but dangerous:
Symptoms: fever, rigidity, altered consciousness, leukocytosis, increased creatine kinase
This is caused by a sudden and marked decrease in dopamine activity wither from withdrawal of dopaminergic gents or blocking of dopamine receptors.
This is more common in more severe PD symptoms or patients on high doses of Levodopa
What is a rare but serious complication of missing doses of Parkinsons medications?
Risk of neuroleptic-like malignant syndrome- this is very rare but dangerous:
Symptoms: fever, rigidity, altered consciousness, leukocytosis, increased creatine kinase
This is caused by a sudden and marked decrease in dopamine activity wither from withdrawal of dopaminergic gents or blocking of dopamine receptors.
This is more common in more severe PD symptoms or patients on high doses of Levodopa
How do you treat depression in PD (treatment of non-motor symptoms)?
1st line: SSRIs
How do you treat dementia in PD (treatment of non-motor symptoms)?
Consider Rivastigmine (unlicensed) or off-label use of donepezil or galantamine
How do you treat hallucinations/confusion in PD (treatment of non-motor symptoms)?
1st line: Quetiapine
2nd line: Clozapine- needs specialist monitoring
Can you give anti-psychotics to patients with PD?
Avoid Ads where possible as they can cause EPSEs which worsen the condition
How do you treat constipation in PD (treatment of non-motor symptoms)?
Stimulant laxative PRN e.g. bisacodyl or Senna
AND softener laxative on repeat e.g. lactulose
How do you treat postural hypotension in PD (treatment of non-motor symptoms)?
Midodrine- 1st line
or Fludrocortisone- has cardiac risks so mididrine is first line
How do you treat salivation/drooling in PD (treatment of non-motor symptoms)?
Glycopyrronium
or can use anti-cholinergics e.g. hyoscine- but use in caution
or if severe, refer for Botulinum Toxin A
How do you treat bladder dysfunction in PD (treatment of non-motor symptoms)?
anti-muscarinics e.g. Oxybutynin
How do you treat sexual dysfunction in PD (treatment of non-motor symptoms)?
PDE5 inhibitors e.g. Sildenafil
What anti-emetics should never be used in PD?
Metoclopramide
Prochlorperazine
What anti-emetics are recommended for use in patients with PD?
1st line: Domperidone
- Consider use of cyclising or ondansetron
- Also can give dose with a low protein snack e.g. cracker or biscuit if patient feeling sick
How can you manage pain in patients with PD?
Follow the WHO ladder
- Consider the SEs of analgesias e.g. cognitive effects, need for GI protection, fracture risk
- physiotherapy
What drugs can be used for sedation and day time sleepiness in PD?
- Persistent day time sleepiness- Modafinil (requires specialist use)
- caution with sedatives as they can cause cognitive side effects and falls
How can you prevent pressure sores in PD patients?
- barrier creams
- Change position every 2 hours
- pressure relieving mattresses and cushions
