Neuro: Parkinson's Disease

Question 1

what non-drug treatments are avaialable for PD patients?

Answer 1

physiotherapy for balance/motor probs, speech and language therapy if the pt develops communication, swallowing or salive problems, occupational therapy for daily activities.

Question 2

whats the 1st line options for PD patients whose motor symptoms affect their QoL?

Answer 2

levodopa with carbidopa or benserazide

Question 3

what are the 1st line options for patients whose motor symptoms do not affect their quality of life?

Answer 3

levodopa
non-ergot derived dopamine agonists (pramipexole, ropinirole or rotigotine)
monoamine oxidase B inhibitors (rasagiline, selegiline)

Question 4

what adverse reactions from antiparkinsonian drugs should you inform patient/carer about?

Answer 4

psychosis
excessive sleepiness
sudden onset of sleep
impluse control disorder with all dopaminergic therapy

Question 5

what class of PD drug can cause sudden onset of sleep?

Answer 5

dopamine receptor agonists

Question 6

why musn’t PD drug concentrations fall suddenly? - give 2 reasons why they might fall suddenly

Answer 6

to avoid potential for akinesia or neuroleptic malignant syndrome
due to poor absorption (constipation) or abrupt withdrawal

Question 7

name 4 impulse control disorders

Answer 7

compulsive gambling, hypersexuality, binge eating, excessive shopping

Question 8

breifly summarise the pathology behind PD

Answer 8

decreased dopamine due to loss of dopaminergic neurons in substantia nigra - presence of lewy bodies which contain alpha synuclein

Question 9

why can’t dopamine be administered so why is levodopa given?

Answer 9

because dopamine does not pass BBB so would be metabolised in the gut so give LDOPA (the intermediate)

Question 10

what’s the rate limiting step in the conversation of tyrosine to dopamine?

Answer 10

tyrosine hydorxylase - so means we can’t convert tyrosine to dopa even if we supplement with excessive amount of dopa

Question 11

what converts l-dopa to dopamine?
what happens to dopamine if this conversion happens in the gut?
why is l-dopa never given on its own?
what is is given with?

Answer 11

• amino acid decarboxylase
• if this happens in the gut DA will be broken down by MAO and COMT
• because no DA would reach the brain if this occured
• given with a peripherally acting dopa decarboxylase inhibitor which blocks AADC in periphery allowing more l-dopa to cross the brain to be converted intp DA

Question 12

name 2 peripheral dopa decarboxylasei nhibitors

Answer 12

carbidopa
benserazide

Question 13

what class of drugs are impulse disorders associated with?
when are they used?

Answer 13

• dopamine D2 receptor agonists
• used alone in early (mild) disease to try and delay SE of L-dopa, or add on therapy with L-dopa to help balance SE

Question 14

what’s secondary parkinsonism?
what type of drugs may be given to help?
is this the first port of call?

Answer 14

PD symptoms due to a cause other than idopathic PD - usually caused by drugs
- dopaminergic drugs can be given (levodopa, ropinerole, pramipexol)
- 1st line of action is to discontinue offending drug

Question 15

what are the 2 types of D2 receptor agonists?
what’s the difference in their action?
what ones aren’t used often due to cardiac problems?
give examples

Answer 15

• ergot (cabergoline) and non-ergot (ropinerole, pramipexol)
• ergot are older and are more selective towards D1 and D2 wherear non-ergot are newer and have more selectivity to D2 and D3
• ergot ones have cardaic problems

Question 16

what does COMT stand for?
give an example
what effect to COMT inhibitors have on the action of levodopa?

Answer 16

catechol methyl transferase
entacapone (formulated as stalevo)
increases duration of action of levodopa as help more get to brain

Question 17

what therapy should be added if patients develop dyskineisa/motor fluctuations despite optimal levodopa therapy?

Answer 17

non-ergot receptor agonist, monoamine oxidase B inhibitor, or COMT inhibitor

Question 18

when could you consider an ergot dopamine agonist?
what drug should be considered if dyskinesia is not managed by modifying existing therapy?

Answer 18

• only to be added to levodopa if symptoms are not adequtely controlled with anon-ergot dopamine agonist
  amantadine hydrochloride

Question 19

give 2 examples of monoamine oxidase B inhibitors
why aren’t drugs that inhibit MAOA used?
what interaction must you counsel patients on?

Answer 19

• rasagiline and selegiline
• becuase MAOB predominate in CNS and MAOA inhibitors would have more side effects
• interactio with dextramethorphan (antitussive) = increased hypertensive effect, risk of psychotic episode

Question 20

what drug should be considered to help daytime sleepiness once reversible pharmacological and physical causes have been excluded?

Answer 20

modafinil

Question 21

what is nocturnal akinesia?
what are the 1st and 2nd line treatment options?

Answer 21

• loss of ability to move muscles voluntarily at night
• levodopa or oral dopamine receptor agonists as first line
• rotigotine second line

Question 22

what class of drug is rotigotine?

Answer 22

non-ergot receptor agonists

Question 23

what are the pharmacological options to manage postural hypotension in PD once drug treatment has been reviewed?

Answer 23

1st line = midodrine hydrochloride
2nd = fludrocortisone (unlicensed)

Question 24

how do you manage the psychotic symptoms of PD such as hallucinations/delusions?
what’s the 1st line?
is this a licensed use?

Answer 24

• don’t need to treat if hallucinations well tolerated
• otherwise, review dosage of PD drugs that may have triggered hallucinations
• quetiapine (unlicensed) can be considered
• if not effective then clozapine

Question 25

what antipsychotics medicine can worsen PD motor features?

Answer 25

phenothiazines (chlorpromazine, prochlorperazine, levomepromazine)
butyrophenones (haliperidol, benperidol)

Question 26

when should drug treatment for drooling saliva be considered and what are the options?

Answer 26

• when non-drug treatments such as SALT is not available/effective
• 1st line = glycopyronium (unlicensed)
• botulinium toxin type A is second line

Question 27

what class of drug should be offered to patients with mild-moderate PD dementia and what should be considered if this is contraindicated/not tolerated?

Answer 27

acetylcholinesterase inhibitor - donepizil, rivastigmine, galantamine
offer memantine if not tolerated

Question 28

what are the 3 options for advanced PD?

Answer 28

1. apomorphine as intermittend injection or continuous infusion
2. levodopa-carbidopa intestinal gel (given via portable pump directly into duedenum or upper jejunum)
3. deep brain stimulation

Question 29

what antiemetic can be used to control N&V with apomorphine?
what is the associated risk?
what measures are put in place to reduce this risk?
what antiemetics must be avoided?

Answer 29

1. domperidone
2. arrhythmia due to QT prolongation
3. MHRA recommend assessment of cardiac risk factors and ECG monitoirng to ensure benefits outwiegh risks
4. metoclopramide (DA agonist) and cyclizine

Question 30

what supplement can reduce levodopa absorption?

Answer 30

iron - must leave gap
protein affects absoprtion at BBB