Parkinson's disease Flashcards
what is PD?
A progressive neurodegenerative condition
resulting from the death of the dopamine-containing cells of the substantia nigra
what is the most common type of PD?
Idiopathic PD (85%)
what are the two main types of idiopathic PD?
PIGD – Postural instability gait disorder
– Tremor dominant PD
what genes can be linked with PD?
Parkin gene, DJ-1
what can cause secondary parkinsonism?
- Drugs – Induce Parkinsonian syndrome
- Toxins - MPTP
what can cause vascular parkinsonism?
restrictive blood supply to the brain eg stroke
cerebral infarction
what causes parkinson’s plus syndrome?
- Multiple system atrophy
- Progressive supra-nuclear palsy
- Lewy Body Dementia
how do drugs cause parkinsonian syndrome?
Any drug that blocks the action of dopamine- Stop drug
give examples of drugs that causes parkinsonian syndrome?
– Neuroleptics
– Anti-psychotics (e.g. haloperidol, chlorpromazine )
– Anti-depressants
– Anti-emetics: (e.g. metoclopramide, prochlorperazine)
– Others: (e.g. cinnarizine, CCB, lithium, donepezil
what are the signs/ symptoms of PD?
- Tremor (most common PC)
– Rest
– ‘pill – rolling’
– 7/10 patients only - Rigidity
– Increased tone – stooping posture
– ‘cog wheeling’ - Hypokinesia (akinesia, bradykinesia)
– Slowness of movement
what autonomic dynsunctions may a person with PD have?
– Constipation
– Excess sweating
– Saliva pooling and drool
– Dysphagia
– Weight loss
– Urinary dysfunction
– Aphasia and speech/volume changes
– Postural instability/Postural hypotension
– Sleeping issues
what other symptom may a person with PD have?
– Mask like face
– Shuffling gait
– Flexed postures of neck, trunk, limbs
– Cognitive decline
– Dementia (8/10)
– Anxiety (4/10)
– Pain/dystonia
– Restless Leg Syndrome
– Depression
– REM sleep disorder ( common- but not all patients)
how do you diagnose PD?
- Diagnosis is made predominantly on clinical
presentation - Review diagnosis on a 6 – 12 monthly basis in
case of an inaccurate diagnosis
what is the aim of treatment?
improve symptom control, medication does
not alter the progression of the disease
what are the agents available to treat?
- Levodopa
- Dopamine Agonists
- MAO-B Inhibitors (Monoamine oxidase B)
- Amantadine
- COMT Inhibitors (catechol-O-methyl
transferase) - Anticholinergics (rarely used
when is levodopa used?
used in all stages of PD
what and why is levodopa given with?
- Given with a dopa-decarboxylase inhibitor
(benserazide or carbidopa)
– To reduce the peripheral conversion of levodopa to dopamine
– Limits side-effects experienced by the patient
how should you dose levodopa?
- Start with a low dose and increase gradually
- Keep dose as low as possible to maintain good function in order to reduce the development of motor complications
- Usually commenced BD or TDS
- Increased as per clinician preference
when should you be cautious with levodopa?
– Severe pulmonary and cardiovascular disease
– Psychiatric illness
– Dyskinesia
what are the side effects of levodopa?
- Impulse Control
Disorder - Nausea and vomiting
- Taste disturbances
- Dry mouth
- Postural hypotension
- Drowsiness
- Fatigue
- Confusion
- Psychosis
- Dystonia
- Dyskinesia
what dose should you avoid with levodopa?
Try and keep to 800mgs or less where possible
but less than 2g daily
what are the different preparations of levodopa?
- Madopar (Co-beneldopa)
- Capsules (62.5mg, 125mg, 250mg)
- Dispersible tablets (62.5mg, 125mg)
- MR capsules (125mg)
- Sinemet (Co-careldopa)
- Tablets (62.5mg, 110mg, 125mg, 275mg)
- MR Tablets
– Half Sinemet CR 125mg
– Sinemet CR 250m
what are the counselling points surrounding levodopa?
- May discolour the urine
- Take with or just after food or a meal
- Driving: care as can cause sudden onset of sleep and
hypotensive reactions - Explain differences in name
- MR: swallow whole; don’t take indigestion remedies
2 hours before or after - Dispersible: can be dispersed in water or orange
squash or swallowed whole - Will always leave a little white residue
what should you do when switching from MR levodopa to dispersible co-beneldopa?
reduce by aprox 30%
how do dopamine agonists work?
- Direct action on the dopamine receptors
- Can be used alone in early stages of PD and in
combination with levodopa in advanced PD - Low doses and titrat
what are the two different types of dopamine agonists? give examples
- Ergot derived: bromocriptine, pergolide,
cabergoline – Not first line
– Rarely used - Non-ergot derived: apomorphine,
pramipexole, ropinorole, rotigotine
what are the side effects of ergot derived dopamine agonists?
– Fibrotic reactions
– Exclude cardiac valvuopathy
what are the side effects of dopamine agonists?
– Psychiatric
– Impulse control disorders
– Sudden onset of sleep
– Hypotensive reactions
– Nausea and vomiting
– Constipation
– Dyspepsia
– Hallucinations/delusions/confusion
– Most common in younger men, particularly those
on levodopa
what cautions are there with non-ergot dertived dopamine agonists?
psychiatric disorders, regular eye
tests, cardiovascular disease
what is the counselling surrounding dopamine agonists?
– Impulse control disorders
– Driving
– Take with or just after food or a meal
– Cabergoline: dispense in original container
– Patch: apply to dry, non-irritated skin on torso, thigh,
or upper arm, removing after 24 hours
– Put replacement patch on a different area
– Do not cut
how should you initiate a rotigotine patch?
- Monotherapy: 2mg/24 hour patch
- Adjunct: 4mg/24 hour patch
if you are switching from levodopa /dopamine agonist to a rotigotine patch what conversion needs to be made?
– Find differences in practice
– Consider – side-effects especially hallucinations
and ensuring PD symptoms are adequately
controlled eg
– Madopar 62.5mg BD = 2mg/24 hours
– Madopar 62.5mg TDS = 4mg/24 hours
– For every 100mg levodopa mr = 2mg/24hours
how do MAO-B inhibitors work? give example
- Prevent the breakdown of dopamine
- Can use alone or in combination with other
agents
Rasagiline (tablets)
– Selegiline
what cautions are there with MAO-B inhibitors?
- Selegiline: gastric and duodenal ulcers,
uncontrolled hypertension, side-effects of
levodopa can be increased
what are the side effects of MAO-B inhibitors?
– Nausea
– Constipation
– Dry mouth
– Selegiline: mouth ulcers, hypertension, bradycardia,
psychosis, impaired balance, sedation
– Rasagiline- headache, dizziness ( in practice reports)
what counselling should you give with MAO-B inhibitors?
- Avoid food with too much tyramine as can
raise BP
– Aged cheese, sour cream, yoghurt, dry meats - Selegiline disp: place on the tongue and allow
to dissolve. Do not drink, rinse mouth out for
5 minutes after taking
how do COMT inhibitors work? give examples
- Prevent the peripheral breakdown of levodopa by inhibiting catechol-O-methyltransferse
- Adjunct agents to co-beneldopa and co-careldopa for patients with end dose deterioration
– Entacapone
– Tolcapone
– Opicapone
what cautions are there with COMT inhibitors?
IHD, levodopa dose may need to be
reduced (10-30%)
* Avoid in hepatic impairment
what side effects do COMT inhibitors have?
– Nausea and vomiting
– Abdominal pain
– Constipation
– Urine – reddish/brown
where can COMT inhibitors be found?
in a product containing
levodopa, Stalevo:
– Carbidopa
– Levodopa
– Entacapone
what counselling should be given with COMT inhibitors?
– Alter colour of urine
– Driving
– Avoid iron containing products at the same time of day
– Diarrhoea when starting, and a few months later
who can tolcapone be started by? why?
tolcapone- Only started by a specialist
* Caution: hepatotoxicity
* Side-effects:
– Constipation
– Dyspepsia
– Nausea and vomiting
how should you counsel someone on tolcapone?
How to recognise signs of liver disorders
and seek medical attention if they develop anorexia, nausea, vomiting, fatigue, abdominal pain, dark urine or pruritus
* Reinforce need to attend regular blood monitoring
what cautions/ side effects are there with opicapone?
- Caution: hepatic impairment, concurrent
levodopa dose, elderly over 85 years - Side-effects: constipation, dizziness,
drowsiness, dry mouth, hypotension,
movement disorders - Counselling:
– Take at bedtime, at least ONE hour before or after levodopa combinations
what is amantadine? when is it used?
Glutamate antagonist
* Used infrequently, usually for dyskinesia in
long term patients
* Use in combination with other agents
* Stimulatory effect: useful for tiredness
* Tolerance can occur
what cautions, c/i and side effects are there with amantadine?
- Cautions: CHF
- Contra-indicated: Epilepsy, Gastric ulceration
- Side-effects
– GI disturbances
– Anorexia
– Dry mouth
– Confusion
– Hallucinations
why are anticholinergics not first line?
- Not first choice due to limited efficacy and
propensity to cause neuropsychiatric side-effects
– Procyclidine
– Orphenadrine Hydrochloride
– Trihexyphenidyl Hydrochloride
when are anticholinergics useful?
- Useful in reducing symptoms caused by
antipsychotic drugs
what cautions, side effects and counselling is there for anticholinergic drugs?
Cautions: cardiovascular disease, hypertension
and psychiatric disorders
* Side-effects
– Confusion
– Dry mouth
– Constipation
– Blurred vision
* Counselling
– Driving
what counselling points should be given generally about PD meds?
- Take medication on time
– At home, in hospital - Avoid abrupt withdrawal
– Life-threatening
– Risk of neuroleptic malignant syndrome
(NMS) - Altered consciousness, fever, autonomic instability,
raised CK level - Should have CK level taken if abrupt withdrawal
how can food affect PD meds?
- Take medication on time
– At home, in hospital - Avoid abrupt withdrawal
– Life-threatening– Risk of neuroleptic malignant syndrome (NMS) - Altered consciousness, fever, autonomic instability, raised CK level
- Should have CK level taken if abrupt withdrawal
- If this occurs
– Levodopa 30 minutes before meals, ideally with a carbohydrate food like a cracker or biscuit
what should be told about impulse control disorder?
– Occurs with all dopaminergic therapy
– Can occur at any stage of the disease
– Must record this has been discussed with the
patient
– Provided with a contact in case this happens
– Patient can conceal the behaviour
– Different types: gambling, hypersexuality, binge
eating and obsessive shopping
what should be told about excessive sleepiness and sudden onset of sleep?
–– Inform patients not to drive if they suffer from
this/operate heavy machinery
– Inform DVLA of symptoms
what should be given in early PD?
– Early stage of PD where motor symptoms impact QOL:
* Levodopa
– If motor symptoms do not impact QOL:
* Levodopa
* Dopamine agonists
* MAO-B inhibitors
what adjuvant therapy can be given for motor symptoms?
- Adjuvant therapy for motor symptoms
–Dopamine agonists
– COMT inhibitors
– MAO-B inhibitors
what adjuvant therapy can be given with carbidopa/levodopa to aid off periods?
– Safinamide (Xadago; 2017)
– Levodopa inhalation powder (Inbrija; 2018)
– Istradefylline (Nourianz; 2019)
– Sublingual apomorphine (Kynmobi; 2020)
– Opicapone
how should you manage postural hypotension?
Review existing medication
– Consider midodrine
– Consider fludrocortisone if midodrine not
tolerated or contra-indicated
how should you initiate, monitor and what side effects does midorine have?
– Initiate at 2.5mg TDS and titrate to usual
maintenance of 10mg TDS
– Monitor
* Renal and hepatic function before and during treatment
– Side-effects
* Supine hypertension
* Administer last daily dose at least 4 hours before bedtime
how should you initiate. monitor and what side effects does fludrocortisone have ?
– Use lowest effective dose, usually between 100 – 400
micrograms daily
– Monitor
* Hepatic function
– Side-effects
* Weight gain, oedema, headache
how do you manage hallucinations/ dellusions?
– Review potential cause
* Treat underlying cause
* Review PD medication
– Reduce doses
– Consider quetiapine if there is no cognitive
impairment
– Clozapine if standard treatment fails
Do not treat if well tolerated by the
patient/family/carers
how should you manage constipation?
– Increase dietary fibre and fluid intake as well as exercise levels
– Consider laxatives
how should you manage nausea and vomiting?
– Mild: often related to levodopa or dopamine
agonist therapy
– Severe/persistent: low dose domperidone for
shortest time possible
* N.B. cardiovascular risks associated with domperidone
– Review P.D medication
how should you manage daytime sleepiness?
– Can consider modafinil
what are the alt formulations if dysphagia is present?
– Madopar capsules can be switch to dispersible
tablets- only where swallowing issues
– Switch Sinemet to Madopar dispersible where
swallowing issues
– Madopar MR capsules can be switched to
dispersible tablets
– Pramipexole – disperse in water (MR switch to IR
tablets and give a TDS regimen
– Rotigotine Patch- may be best option for long
term
what lifestyle advice should be given to someone with PD?
- Exercise
– Helps maintain your ability, strengthen muscles
and increase mobility in your joints
– Research: protects the dopamine producing nerve
cells that are lost in PD - Diet
– Take extra time when eating and drinking
– Balanced diet
