Parkinson's

Question 1

Understand the term ‘Parkinsonism’, what might cause it and the cardinal signs

Answer 1

Damage to basal ganglia –> main motor symptoms (tremor, bradykinesia, rigidity, postural instability)
Drug induced, toxicity, vascular, corticobasal degeneration

Question 2

Define Parkinson’s disease

Answer 2

A degenerative disorder of the CNS, death of dopamine generating cells in substantia nigra

Question 3

Describe the synthesis of dopamine

Answer 3

L-tyrosine –tyrosine hydroxylase-> L-dopa –DOPA carboxylase-> dopamine

Question 4

Understand the pathophysiology of Parkinson’s and how this influences the choice of pharmacological treatment

Answer 4

Basal Ganglia circuit:
Loss of dopaminergic neurones in substantial nigra –> less inhibition in neostriatum –> increased ACh production
Chain of abnormal signalling –> impaired mobility

Question 5

Describe the method of action and ADRs of Levodopa

Answer 5

MOA - absorbed by active transport, compete with amino acids, needs enzyme conversion (dopa decarboxylase inhibitor e.g. carbidopa)
ADRs - dyskinesia, on/off phenomena, psychosis, dry mouth, insomnia, involuntary movements
*DDIs - protein (food), vitamin B6, MAOIs, antipsychotics

Question 6

Describe the method of action and ADRs for dopamine agonists

Answer 6

E.g. bromocriptine (ergot derived), rotigotine (non-ergot)
MOA - agonist at dopamine receptors
ADRs - fibrosis, vasospasm, postural hypotension, drowsiness, neuropsych, impulse control disorders

Question 7

Describe the method of action and ADRs of MAO-B inhibitors

Answer 7

E.g. rasagiline, selegiline
MOA - prevent intraneuronal dopamine degradation
ADRs - GI upset, insomnia, postural hypotension
*used alone to delay L-dopa use or adjunct to L-dopa to decrease end of dose effects

Question 8

Describe the method of action and ADRs of COMT inhibitors

Answer 8

E.g. entacapone, tolcapone
MOA - decrease peripheral L-dopa breakdown
ADRs - reddish brown urine, dyskinesia, hepatotoxic
*no therapeutic effect alone, prolongs motor response to L-dopa

Question 9

Describe the method of action and ADRs of Amantidine

Answer 9

MOA - weak anticholinergic

ADRs - GI upset, sleep disturbance

Question 10

Describe the method of action and ADRs of anticholinergics

Answer 10

E.g. procyclidine, trihexyphenidydyl
ADRs - confusion, drowsiness, dry mouth, urinary retention
*only adjunct, treat tremor, no effect on bradykinesia