Parkinson’s Flashcards
Parkinson’s disease is a progressive neurodegenerative condition resulting from the death of ______________ of the ___________ in the brain.
dopaminergic cells
substantia nigra
Parkinson’s disease is a _________ _____________ condition resulting from the death of dopaminergic cells of the substantia nigra in the brain.
Progressive
Neurodegenerative
Do patients with Parkinson’s disease typically have resting tremor or intention tremor?
Resting tremor
Patients with Parkinson’s disease classically present with motor-symptoms including ___________, __________, __________, _________, and _____________.
hypokinesia
bradykinesia
rigidity
rest tremor
postural instability
What are the typical non-motor symptoms of Parkinson’s disease? (7)
- Dementia
- Depression
- Sleep disturbances
- Bladder and bowel dysfunction
- Speech and language changes
- Swallowing problems
- Weight loss
When Parkinson’s disease diagnosis is confirmed, patients should be advised to inform the ________ and their ________.
DVLA
car insurer
What is the non-pharmacological management of Parkinson’s? (4)
- PT if balance or motor function problems are present
- SLT if patients develop communication, swallowing, or saliva problems
- OT if they experience difficulties with ADLs
- Dietitian referral should also be considered
What is the first-line treatment of Parkinson’s in patients whose motor symptoms DECREASE their quality of life?
Levodopa + Carbidopa (co-careldopa)
Or
Levodopa + Benserazide (co-beneldopa)
What is the first-line treatment of Parkinson’s in patients whose motor symptoms DO NOT decrease their quality of life?
Choice of:
- levodopa
- non-ergot-derived dopamine receptor agonists (pramipexole, ropinerole, rotigotine)
- MAO-B inhibitors (rasagiline, selegiline)
Which drugs are in the class of non-ergot-derived dopamine receptor agonists (3) and what are they used for?
First line treatment in patients with PD that does NOT significantly effect QoL
- Pramipexole
- Ropinirole
- Rotigotine
What are the two MAO-B inhibitors that are used in the treatment of Parkinson’s?
- Rasagiline
2. Selegiline
Patients and their carers should be informed about the risk of adverse reactions from antiparkinsonian drugs, including ____________ symptoms, excessive ____________ and sudden onset of _____________ with dopamine-receptor agonists, and ______________ disorders with all dopaminergic therapy (especially dopamine-receptor agonists)
psychotic
sleepiness
sleep
impulse control
Levodopa treatment is associated with motor complications, including _____________ and ____________.
response fluctuations
dyskinesias
Response fluctuations in patients taking levodopa are characterised by ______________, with ____________ during the ‘on’ period, and ____________ during the ‘off’ period.
large variations in motor performance
normal function
weakness and restricted mobility
‘End-of-dose’ deterioration with _________________ can also occur in patients taking Levodopa
progressively shorter duration of benefit
____________ preparations of levodopa may help with ‘end-of-dose’ deterioration or nocturnal immobility.
Modified-release
Modified-release preparations of levodopa may help with ______________ or ______________.
‘end-of-dose’ deterioration
nocturnal immobility
The overall improvement in motor performance is more noticeable with ______________ (levodopa/dopamine-receptor agonists) than with _______________ (levodopa/dopamine-receptor agonists), and motor complications are less likely to occur with ______________ (levodopa/dopamine-receptor agonists) when used alone long-term.
Levodopa
Dopamine-receptor agonists
Dopamine-receptor agonists
Excessive sleepiness, hallucinations, and impulse control disorders are more likely to occur with ______________ (levodopa/dopamine-receptor agonists) than with ______________ (levodopa/dopamine-receptor agonists).
Dopamine-receptor agonists
Levodopa
__________________ side effects are more likely to occur with levodopa, while _______________ side effects are more likely to occur with dopamine-receptor agonists
Motor
Neuropsychiatric (eg sleepiness, hallucinations, and impulse control disorders)
To avoid the potential for ____________ or _______________, antiparkinsonian drug concentrations should not be allowed to fall suddenly due to poor absorption or abrupt withdrawal
acute akinesia
neuroleptic malignant syndrome
To avoid the potential for acute akinesia or neuroleptic malignant syndrome, antiparkinsonian drug concentrations should not be allowed to ____________
fall suddenly (due to poor absorption or abrupt withdrawal)
If a patient with Parkinson’s disease develops ___________ or ____________, specialist advice should be sought before modifying antiparkinsonian drug therapy
dyskinesia
motor fluctuations
Patients who develop dyskinesia or motor fluctuations despite optimal levodopa therapy should be offered a choice of _____________, ____________, or ______________ as an adjunct to levodopa.
non-ergotic dopamine-receptor agonists (pramipexole, ropinirole, rotigotine)
monoamine oxidase B inhibitors (rasagiline or selegiline hydrochloride)
COMT inhibitors (entacapone or tolcapone)
COMT inhibitors include… (2)
Entacapone
Tolcapone
What is the mechanism of action of COMT inhibitors?
Inhibition of COMT leads to halt of peripheral degradation of levodopa, allowing a higher concentration to cross the BBB
What is the mechanism of action of MAO-B inhibitors?
Inhibits breakdown of dopamine in the CNS (vs COMT which inhibits breakdown peripherally)
MAO-B inhibitors include rasagiline and selegiline
What are the ergot-derived dopamine receptor agonists? (3)
Bromocriptine
Cabergoline
Pergolide
An ergot-derived dopamine-receptor agonist (bromocriptine, cabergoline or pergolide) should only be considered as an adjunct to levodopa if _______________
symptoms are not adequately controlled with a non-ergot-derived dopamine-receptor agonist
If dyskinesia in patients with PD is not adequately managed by modifying existing therapy, _____________ should be considered.
amantadine hydrochloride
If reversible pharmacological and physical causes of daytime sleepiness or sudden onset of sleep have been excluded in patients with PD, _______________ should be considered
modafinil; treatment should be reviewed at least every 12 months
What advice should be given to patients with Parkinson’s who have daytime sleepiness or sudden onset of sleep?
Should be advised not to drive, to inform the DVLA of their symptoms, and to consider any occupational hazards
What are first-line options for treating nocturnal akinesia in patients with PD? (2)
First line:
- Levodopa
- Oral dopamine-receptor agonists (pramipexole, ropinerole)
Second line:
- rotigotine (dopamine-receptor agonist, NOT oral)
What is the management of patients with PD who develop postural hypotension? (3)
- Review of drug treatment
- If drug therapy is required, midodrine should be considered first-line
- Fludrocortisone (unlicensed) may be used if midodrine is ineffective
Patients with Parkinson’s disease who develop postural hypotension should have their drug treatment reviewed to address any pharmacological cause. If drug therapy is required, _____________ should be considered as the first option and ____________ [unlicensed indication] as an alternative
midodrine hydrochloride
fludrocortisone
How are hallucinations and delusions in patients with PD managed?
No need to treat if they are well-tolerated
Otherwise, the dosage of antiparkinsonism drugs should be reduced, taking into account the severity of symptoms and possible withdrawal effects
In Parkinson’s disease patients with no cognitive impairment, ______________ [unlicensed indication] can be considered to treat hallucinations and delusions.
quetiapine
If standard treatment is not effective, ____________ should be offered to treat hallucinations and delusions in patients with Parkinson’s disease
clozapine
It is important to acknowledge that antipsychotic medicines such as ____________ and ___________ can worsen the motor features of Parkinson’s disease.
phenothiazines (eg chlorpromazine, prochlorperazine, etc)
butyrophenones (eg haloperidol)
What is REM sleep behavior disorder?
Sleep disorder in which patients physically act out vivid, often unpleasant dreams with vocal sounds and sudden, often violent arm and leg movements during REM sleep
How is REM sleep behavior disorder related to Parkinson’s disease?
Often a prodromal marker of PD
___________ [unlicensed indication] or ____________ [unlicensed indication] should be considered to treat rapid eye movement sleep behaviour disorder in Parkinson’s patients once possible pharmacological causes have been addressed
Clonazepam
melatonin
Drug treatment for drooling of saliva in patients with Parkinson’s disease should only be considered if ____________ is not available or is ineffective.
non-drug treatment such as speech and language therapy
What are the first and second-line pharmacological options for treatment of excessive drooling in patients with PD?
First line: glycopyrronium bromide (unlicensed)
Second line: botulinum toxin type A
*Other antimuscarinic drugs, should only be considered if the risk of cognitive adverse effects is thought to be minimal; TOPICAL preparations, such as atropine [unlicensed indication], should be used if possible to reduce the risk of adverse event
A(n) __________________ should be offered to patients with mild-to-moderate Parkinson’s disease dementia and considered for patients with severe Parkinson’s disease dementia
acetylcholinesterase inhibitor
If acetylcholinesterase inhibitors are not tolerated or contra-indicated, ______________ [unlicensed indication] should be considered
memantine hydrochloride
Patients with advanced Parkinson’s disease can be offered ________________ as intermittent injections or continuous subcutaneous infusions
apomorphine hydrochloride (dopamine agonist)
To control nausea and vomiting associated with apomorphine, the manufacturers recommend that administration of ____________ [unlicensed in those weighing less than 35 kg] will usually need to be started two days before apomorphine therapy, and then discontinued as soon as possible
domperidone
What are the risks associated with concomitant administration of domperidone and apomorphine?
Serious arrhythmias due to QT prolongation
*to minimize risk, assessment of cardiac risk factors and ECG monitoring should be undertaken to ensure that the benefits outweigh the risks when initiating treatment
The MHRA/CHM have released important safety information and restrictions regarding the use of domperidone for nausea and vomiting in those weighing less than ___ kg
35
Levodopa-carbidopa ___________ is used for the treatment of advanced levodopa-responsive Parkinson’s disease with severe motor fluctuations and hyperkinesia or dyskinesia.
intestinal gel
The gel is administered with a portable pump directly into the duodenum or upper jejunum.
______________ should only be considered for patients with advanced Parkinson’s disease whose symptoms are not adequately controlled by best drug therapy.
Deep brain stimulation
What are some of the impulse control disorders that may develop in patients with Parkinson’s disease who are on dopaminergic therapy at any stage of disease? (4)
- Compulsive gambling
- Hypersexuality
- Bing eating
- Obsessive shopping
Risk factors for impulse control disorders in patients being treated for PD with dopamine agonists include…? (3)
- Previous impulsive behaviors
- Alcohol consumption
- Smoking
Patients should be informed about the different types of impulse control disorders and that ________________ therapy may be reduced or stopped if problematic impulse control disorders develop
dopamine-receptor agonist
When managing impulse control disorders, dopamine-receptor agonist doses should be reduced gradually and patients should be monitored for symptoms of _______________
dopamine agonist withdrawal
Carbidopa-levodopa should be prescribed with caution in which patients? (13)
- Cushing’s syndrome
- DM
- Other endocrine disorders
- History of convulsions
- History of MI with residual arrhythmia
- History of peptic ulcer
- Hyperthyroidism
- Osteomalacia
- Pheochromocytoma
- Psychiatric illness (avoid if severe and discontinue if deterioration)
- Severe CVD
- Severe pulmonary disease
- Susceptibility to angle-closure glaucoma
Is Carbidopa-levodopa safe to use in pregnancy and breastfeeding?
Use with caution in pregnancy (toxicity in animal studies)
May suppress lactation; present in breast milk — avoid
Is Carbidopa-levodopa safe to use in hepatic and/or renal impairment?
Use with caution in both
Why should abrupt withdrawal of Carbidopa-levodopa be avoided?
Risk of NMS and rhabdomyolysis
When transferring patients from one levodopa/dopa-decarboxylase inhibitor preparation to another of a different strength, the previous preparation should be discontinued at least _____________ before.
12 hours
What is dopamine dysregulation syndrome? (DDS)
A complication of dopaminergic treatment in PD that may be very disabling due to the negative impact that compulsive medication use may have on patients’ social, psychological, and physical functioning
Symptoms include hypomania, euphoria, omnipotence, grandiosity when medication effects are maximum AND dysphoria (sadness, psychomotor slowing, fatigue, or apathy) when dopamine effects are withdrawn
What are the symptoms of dopamine dysregulation syndrome? (DDS)
When medication effects are maximum:
- hypomania
- euphoria
- omnipotence
- grandiosity
When dopamine effects are withdrawn:
- dysphoria
- sadness
- psychomotor slowing
- fatigue
- apathy
What additional information should be given to patients and carers regarding treatment with Carbidopa-levodopa? (2)
Should be informed about the risk of:
- developing dopamine dysregulation syndrome
- sudden onset of sleep (esp when driving or operating machinery)
Management of excessive daytime sleepiness in patients with PS should focus on the identification of an underlying cause, such as ____________ or ____________. Patients should be counselled on improving sleep behaviour.
depression
concomitant medication
While side effects dopamine agonists (antiparkinsonian drugs) include ____________, side effects of dopamine antagonists (antipsychotic drugs) include ____________
Psychoses and psychiatric disturbances (hallucinations, delusions, psychosis, dopamine dysregulation syndrome, anxiety, depression, sleep disorders, aggression, compulsions)
Parkinsonism and movement disorders (acute dystonia, akathisia, tardive dyskinesia, NMS)
Do ergot- and non-ergot-derived dopamine-receptor agonists differ in their propensity to cause impulse control disorders?
No, so switching between dopamine-receptor agonists will not control these side-effect
What monitoring is required for patients taking non-ergot derived dopamine receptor agonists?
Monitor BP due to the risk of postural hypotension (especially on initiation)
Can non-ergot-derived dopamine agonists be used in hepatic and/or renal impairment?
Avoid/adjust dose if Cr clearance is less than 30 mL/min
_______________ can occur in some patients taking dopamine-receptor agonists; these can be particularly problematic during the first few days of treatment and care should be exercised when driving or operating machinery
Hypotensive reactions
Can ropinerole be prescribed in patients with hepatic and/or renal impairment?
Avoid in hepatic impairment
Avoid in renal impairment if Cr clearance is less than 30 mL/min
What is the recommended managment if treatment with ropinerole is interrupted for one day or more re-initiation by dose titration should be considered—consult product literature.
re-initiation by dose titration should be considered
Cabergoline and bromocriptine have been associated with __________, ______________, and _____________ __________ reactions
pulmonary
retroperitoneal
pericardial
FIBROTIC
- Manufacturer advises exclude cardiac valvulopathy with echocardiography before starting treatment with these ergot derivatives for Parkinson’s disease or chronic endocrine disorders (excludes suppression of lactation); it may also be appropriate to measure the erythrocyte sedimentation rate and serum creatinine and to obtain a chest X-ray.
For patients taking cabergoline or bromocriptine, what investigation should be carried out before initiating treatment and monthly?
In addition to monitoring for fibrotic disease, pregnancy testing should be carried out…
Exclude pregnancy before starting and perform monthly pregnancy tests during the amenorrhoeic period.
Advise non-hormonal contraception if pregnancy is NOT desired; discontinue 1 month before intended conception
Can cabergoline be used during pregnancy and breastfeeding?
Discontinue if pregnancy occurs during treatment
Suppresses lactation; avoid breast-feeding if lactation prevention fails
Monitor __________ for a few days after starting treatment with cabergoline or bromocriptine and following dosage increase
blood pressure
What are the monitoring requirements of apomorphine?
Monitor hepatic, hemopoietic, and CV 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)
What is the mechanism of action of amantadine?
Weak dopamine agonist with modest antiparkinsonian effects
What are the contraindications of amantadine? (2)
- Epilepsy
2. History of gastric ulceration
Is amantadine safe to use in pregnancy and/or breastfeeding?
No, avoid due to reported toxicity in animal studies and in infants (present in breast milk)
Is amantadine safe to prescribe in patients with hepatic ad/or renal impairment?
Caution in liver disorders
Avoid/adjust dose if renal impairment
In addition to monitoring for fibrotic disease and blood pressure (initial days of treatment), what else should be monitored in patients being treated with bromocriptine?
Monitor for pituitary enlargement, particularly during pregnancy; monitor visual fields to detect secondary field loss in macro-prolactinoma
What are the contraindications to prescribing MAO-B inhibitors? (3)
- Active duodenal ulcer
- Active gastric ulcer
- Postural hypotension (when used in combination with levodopa)
In patients being treated with MAO-B inhibitors and levodopa, side-effects of levodopa may be increased—concurrent levodopa dosage can be reduced by _________% in steps of 10% every 3–4 days.
10–30%
Are MAO-B inhibitors safe to use in pregnancy and breastfeeding?
Avoid
Are MAO-B inhibitors safe to use in hepatic and/or renal impairment?
Caution in severe renal or hepatic impairment
