Parkinson's disease in practice

Question 1

what is PD?

Answer 1

•Chronic, progressive neurodegenerative
condition
•Loss of the dopamine-containing cells of the
substantia nigra
•Bradykinesia together with at least one of the
following: rigidity, tremor, and postural
instability
•Features usually present unilaterally initially,
but become bilateral as the disease
progresses

Question 2

who is PD most common in?

Answer 2

elderly- prevalence of 1-2% in people older than 65 years

Question 3

what are motor complications usually related to?

Answer 3

use of anti-parkinsonian medication

Question 4

what are some motor complications associated with PD?

Answer 4

• Deteriorating function
• Loss of drug effect
• Motor fluctuations
• Dyskinesia
• Freezing of gait
• Falls

Question 5

what are non-motor complications usually symptoms of?

Answer 5

symptoms of the disease or adverse effects of medication

Question 6

what are some antonomic dynsfunctions caused by the medication?

Answer 6

–Constipation
–Orthostatic hypotension
–Dysphagia and weight loss
–Excessive salivation and sweating
–Bladder and sexual problems

Question 7

what is neuroleptic malignant syndrome?

Answer 7

Rare, life-threatening idiosyncratic reaction
•May occur if dopaminergic drugs are stopped abruptly
•Symptoms include fever, altered mental state, muscle rigidity, raised CK, and autonomic
dysfunction

Question 8

how do you manage NMS?

Answer 8

–IV fluids
–Correct any metabolic abnormalities
–Cooling – blankets 
–IV dantrolene 
–Restart PD medications

Question 9

what is the function of levodopa?

Answer 9

•First line in NICE guidelines for people in early
stages of PD whose motor symptoms impact
of their QoL
•Improve motor symptoms and activities of
daily living, with few adverse effects

Question 10

what complications can levodopa cause?

Answer 10

can lead to more motor complications

Question 11

how should you initiate levodopa?

Answer 11

start at low dose and titrate up

Question 12

how does levodopa work?

Answer 12

it is converted (decarboxylated) to dopamine in the

brain

Question 13

what is levadopa coadministered with?

Answer 13

•Levodopa formulations also contain benserazide
(co-beneldopa) or carbidopa (co-careldopa)
–No therapeutic effect on their own
–Dopamine can’t cross blood brain barrier (BBB)

Question 14

how does the co-administration of levodopa work?

Answer 14

–Inhibit peripheral decarboxylation of levodopa before

it crosses the BBB

Question 15

what are the problems associated with levodopa?

Answer 15

•Becomes less effective over time
•Experience ‘wearing off’  
•Long term use can result in dyskinesia
•Impulsive and compulsive behaviours 
•Withdrawal symptoms 
•Common side-effects – N&V, hypotension, 
reduced appetite, hallucinations, sleep 
disturbances

Question 16

how should you take levodopa?

Answer 16

Absorption reduced when administered with
iron – separate
•Absorption reduced when administered with
protein – some patients take 30-60 minutes
before a meal

Question 17

what can happen if you take levodopa on an empty stomach?

Answer 17

–Can cause N&V on empty stomach – can advise to

take with a low protein snack e.g. crackers

Question 18

how can you improve n/v caused by levodopa?

Answer 18

Some patients take most of daily protein in

evening to improve daytime symptoms

Question 19

what are the forms of levodopa availible?

Answer 19

Co-beneldopa (Madopar®)- can come as dispersible tabs also

Co-careldopa (Sinemet®, Sinemet Plus®)- can come as gel also

Question 20

who are DA agonists a good choice of treatment for?

Answer 20

in the early stages of PD whose motor symptoms do not impact on their quality of life

Question 21

how do DA agonists work?

Answer 21

Act directly on dopamine receptors to mimic

effect of dopamine

Question 22

what are the two subclasses of DA agonists?

Answer 22

–Ergot derived e.g. cabergoline, bromocriptine,
pergolide
•No longer recommended due to risk of pulmonary,
retroperitoneal, and pericardial fibrotic reactions
–Non-ergot derived e.g. pramipexole, ropinirole,
rotigotine, apomorphine

Question 23

what are some problems with DA agonists?

Answer 23

•Fainting or dizziness
•Sudden onset of sleep
•Impulsive or compulsive behaviours
•Hallucinations or delusions
•Withdrawal 
•Other common side-effects: Nausea, 
constipation, hypotension, headaches, 
anxiety, depression, movement problems

Question 24

what caution should you be aware of with pramipexole?

Answer 24

Caution: BNF doses and strengths are stated in
terms of pramipexole (base) but some literature
refers to salt form

Question 25

what should you be cautious about when dispending ropinirole?

Answer 25

–Commonly LASA error – mixed up with risperidone –Dose adjustment might be necessary if smoking started or stopped during treatment –If dose missed for one day or more, re-initiation by dose titration should be considered

Question 26

how should you take rotigotine?

Answer 26

–24 hour patch –Contains aluminium – remove for MRI scan or cardioversion –Useful if swallowing difficulties –Can cause skin irritation – use different site each day

Question 27

how is apomorphine given?

Answer 27

–Subcutaneously via disposable pen, cartridge pen or infusion pump (using pre-filled syringe, ampoules or vials)

Question 28

how long does it take apomorphine to work?

Answer 28

Works within 5-10 minutes – injections used as | ‘rescue treatment’

Question 29

what are the s/e of apomorphine, what should be given before treatment starts?

Answer 29

–Causes nausea and sickness – domperidone given | 2 days before treatment starts

Question 30

who are MAO-b used in?

Answer 30

Potential choice for people in the early stages of PD whose motor symptoms do not impact on their quality of life

Question 31

how do MAO-b work?

Answer 31

Inhibit the breakdown of dopamine by MAO-B

Question 32

what are the problems associated with MAO-Bs?

Answer 32

* Interact dangerously with antidepressants * Worsen levodopa side-effects e.g. dyskinesia (may need to reduce dose of levodopa) * Impulsive and compulsive disorders * Withdrawal

Question 33

what other side effects are there with MAO-Bs?

Answer 33

Headaches, constipation, dry mouth, aching joints, indigestion, urinary urgency

Question 34

what caution should you be aware of with MAObs?

Answer 34

Risk of hypertension when high-dose selegiline is taken with tyramine-rich foods –Specific for MAO-B at low doses used for PD (5-10mg) so no dietary restrictions

Question 35

how should you take MAObs?

Answer 35

``` •Rasagiline –Once a day •Selegiline –Once a day –Selegiline oral lyophilisate if swallowing difficulties •tablet placed on tongue and disperses within 10 seconds –patient cannot drink, eat or rinse mouth out for 5 minutes after taking •1.25mg equivalent to 10mg tablet •Safinamide –Once a day ```

Question 36

who are COMT inhibitors good for?

Answer 36

Adjunct to levodopa for people who have developed dyskinesia or motor fluctuations despite optimal levodopa therapy •Improve motor symptoms and activities of daily living •Reduce ‘off’ periods •BUT more adverse effects

Question 37

how do COMT inhibitors work?

Answer 37

Inhibit peripheral methylation of levodopa to 3- O-methyldopa, allowing more levodopa to reach the brain

Question 38

what are the problems with COMT inhibitors?

Answer 38

•Colour urine bright red/orange •Diarrhoea •Risk of fatal liver damage with tolcapone •Worsen levodopa side-effects e.g. dyskinesia, N&V •Impulsive and compulsive behaviours •Common side-effects – confusion, dizziness, dry mouth, falls, hallucinations, sleep disorders, chest pain, fatigue

Question 39

how should you take entacapone?

Answer 39

``` –Take at same time as levodopa –Combination product: co-careldopa and entacapone (Stalevo®) –Avoid taking at same time as iron supplements – reduce absorption ```

Question 40

how should you take opicapone?

Answer 40

–Taken at bedtime, 1hour before or after levodopa

Question 41

when is amantadine used?

Answer 41

Consider as an adjunct if dyskinesia is not adequately managed by modifying existing therapy

Question 42

how does amantadine work?

Answer 42

Glutamate antagonist

Question 43

why is it so important to give PD medicine ontime?

Answer 43

If people with PD don’t get their medication at the right time it can seriously impact their health: –Reduced movement –Unable to get out of bed –Unable to swallow, walk or talk •Even a delay of 30minutes can be detrimental

Question 44

what if someone with PD is nil by mouth?

Answer 44

Avoid abrupt withdrawal – can be life-threatening •Need to convert critical oral medications to non-oral route: –Via NG tube e.g. dispersible co-beneldopa –Topical patch e.g. rotigotine patch

Question 45

when can you omit etacapone, seleginine, rasagiline and amantadine?

Answer 45

in acute situations

Question 46

how do you convert to rotigotine patches?

Answer 46

•If NG not suitable, convert levodopa dose to equivalent rotigotine patch (max. 16mg in total) •If patient is dopamine agonist naïve, caution and specialist review required asap as patients can be sensitive to effects –Risk of side-effects – vomiting, skin reactions, hypotension, hallucinations increased confusion –Usually start at lower dose (2-4mg) and increase gradually over a period of days

Question 47

what medications should you avoid in PD?

Answer 47

* Metoclopramide * Prochlorperazine (Stemetil®) * Haloperidol * Chlorpromazine * St John’s Wort * Decongestants e.g phenylephrine * Anticholinergics