Neurology - Drugs used in PD and other movement disorders

Question 1

What are the 4 types of dopaminergic drugs used in PD?

Answer 1

1) Dopamine receptor agonists
2) Levodopa
3) Monoamine oxidase -B (MAO-B) inhibitors
4) Catechol-O-methyltransferase (COMT) inhibitors

Question 2

Mechanism of action of dopamine receptor agonists - when can they be used in PD?

Answer 2

Direct effect on striatal dopamine receptors

Do not depend on functional capacity of nigrostriatal neurones (unlike Levodopa) so may be more effective in late PD

Question 3

Examples of dopamine receptor agonists

Answer 3

Bromocriptine (ergot derivatives)
Cabergoline (ergot derivatives)
Lisuride
Pergolide
Ropinirole

Question 4

Absolute contraindications to dopamine receptor agonists

Answer 4

Hx of fibrotic disease
Cardiac valve disease

Echo, creatinine and chest x ray should be done prior to starting

Question 5

Name some relative contraindications for dopamine receptor agonists

Answer 5

Arrhythmias
Pregnancy and breast feeding
Confusion and hallucinations

Question 6

What are the common side effects of dopamine receptor agonists?

Answer 6

• Confusion, hallucinations, diplopia, neuroleptic malignant syndrome
• Hypotension, syncope, tachicardia
• Pleural effusion
• Rash, fever, Raynauds
• Fibrotic reactions (uncommon) - pulmonary, cardiac valvular, pericardial, retroperitoneal

Warn patients that they cause impulsivity

Question 7

What is Levodopa?

Answer 7

Metabolic precursor of dopamine
Decarboxylated in pre-synaptic terminals of dopaminergic neurones in the striatum
Dopamine is either transported back into dopaminergic terminals or metabolised by the action of MAO or COMT enzymes

Question 8

What should be co-administered with Levodopa?

Answer 8

Peripherally acting decarboxylase inhibitor - e.g. carbidopa (i.e. co-careldopa) or benserazide (i.e. co-beneldopa)
Reduces peripheral conversion of levodopa to dopamine
- Limits side effects of nausea, vomiting and cardiovascular effects
- Allows effective concentrations to be achieved in the brain

Question 9

Examples of Levodopa therapies

Answer 9

Sinemet ( = carbidopa + levodopa)

Madopar (= benserazide + levodopa)

Question 10

What are “late” side effects?

Answer 10

Side affects appearing 2-5 years (on average) after starting L-DOPA therapy

• Motor fluctuations - e.g. “wearing off” = response to a given dose is shorter lived than previous ones; “on-off phenomena” = patient may switch from being well controlled (“on”) to an akinetic rigid state (“off”) but without any obvious relationship to the timing of drug doses
• Dyskinesias - related to high dopamine levels (“peak dose dyskinesia”) or painful dystonia as dopamine levels weak off (“wearing off dystonia”)

Question 11

What are the absolute contraindications to L-DOPA use?

Answer 11

Pregnancy and breast feeding

Glaucoma

Question 12

Significant interactions of L-DOPA

Answer 12

1) HyPERtensive crisis with MAOI antidepressants
2) Enhanced hypotensive effect of all antihypertensives
3) Effects of L-DOPA are antagonised by antipsychotics

Question 13

What is selegiline and when can it be used in PD?

Answer 13

Selegiline = MAO-B inhibitor
Normally used early in PD delaying the need for L-DOPA
Can be used late in PD when the side effects of L-DOPA become more problematic

Question 14

Are patients taking selegiline at risk of the “cheese reaction”?

Answer 14

Cheese reaction = hypertensive crisis when tyramine rich foods are eaten
Selegiline is a specific MAO-B inhibitor which is not responsible for noradrenaline breakdown
Non specific MAOIs need care to avoid the cheese reaction

Question 15

What are the absolute contraindications for taking MAO-B inhibitors (e.g. selegiline and rasagiline)?

Answer 15

Pregnancy, breast feeding

Gluacoma

Question 16

Side effects of MAO-B inhibitors

Answer 16

• Nausea
• Confusion, hallucinations, agitation
• Postural hypotension
• Headache

Question 17

Significant interactions of MAO-B inhibitors

Answer 17

CNS toxicity and fever with opiates
CNS system excitation with antidepressants
Enhances effects and toxicity of other dopaminergics

Question 18

What are COMT inhibitors?

Answer 18

Block the catabolism of L-DOPA and dopamine
This increases plasma half life and the amount of each administered dose that reaches the CNS
E.g. entecapone, tolcapone

Question 19

Absolute contraindications for COMT inhibitors

Answer 19

Liver disease (can cause life threatening hepatotoxicity)
Dyskinesia

Question 20

When are anti-muscarinic drugs used in movement disorders?

Answer 20

Used to block cholinergic excess in extra-pyramidal diseases caused by dopamine deficiency
NOT normally used in PD because dopaminergic drugs are more effective - used in other forms of Parkinsonism

Question 21

Examples of anti-muscarinic drugs used in Parkinsonism

Answer 21

Benzatropine
Orphenadrine
Procyclidine

Question 22

Absolute contraindication for anti-muscarinics

Answer 22

GIT obstruction

Question 23

Riluzole

Answer 23

Drug used in ALS (MND) - modest effect in delaying disability

Question 24

Name the drug used in Huntington’s disease

Answer 24

Tetrabenazine

Depletes nerve endings of dopamine