Drugs for Parkinson's Disease

Question 1

Outline the clinical presentation of PD

Answer 1

Tremor = low frequency kill rolling rest tremor

Rigidity = lead pipe (resistance all the way through the movement), cog wheeling

Bradykinesia = exam with small repetitive motor movements

Postural instability = test with postural draw test, and gait (forward flex, shuffling gait)

Non motor = mood changes, pain, cognitive change, urinary symptoms, sleep disorder (don’t get REM sleep atonia), sweating

Question 2

What is the pathophysiology of PD?

Answer 2

Neurodegeneration

Lewy bodies

Loss of pigment

Reduced dopamine

1) loss of dopaminergic neurones in SN = reduced inhib in neostriatum 2) loss of inhib in neostriatum allows increased ACh 3) abnormal signalling = impaired mobility

Question 3

How is PD diagnosed?

Answer 3

Symptoms

Normal CT/MRI imaging structurally

Good response to trial of treatment

Question 4

What are the 5 Parkinson’s plus syndromes?

Answer 4

Multiple system atrophy (MSA)

Progressive supranuclear palsy (PSP)

Parkinsonism-dementia-amyotrophic lateral sclerosis complex

Corticobasal ganglionic degeneration (CBD)

Dementia with Lewy bodies (DLB)

Question 5

What are the clinical features of Parkinson’s plus syndromes

Answer 5

Early onset of dementia

Early onset of postural instability

Early onset of hallucinations or psychosis

Early autonomic symptoms: postural hypotension and urinary incontinence

Ocular signs

Question 6

What ADRs are associated with L-DOPA?

Answer 6

Dyskinesia = impaired vountary movements

Dystonia = painful contraction of muscles forming abnormal structure of a joint

Psychosis

Nausea/vomiting/hypotension

Question 7

What are the range of drug classes that treat PD?

Answer 7

L-DOPA

Dopamine receptor agonist

Monoamine oxidase B inhibitors

COMT inhibitors

Anticholinergics

Amantidine

Question 8

Discuss L-DOPA

Answer 8

Dopamine cant cross the BBB

L-DOPA = taken up by dopaminergic cells in SN = converted to dopamine

Give carbidopa = stops AADC (aromatic amino acid decarboxylase) from forming dopamine in the periphery = stops GI symptoms

Question 9

Discuss dopamine receptor agonists

Answer 9

Dopamine receptor agonist

ADRs = Nausea, postural hypotension, psychosis, confusion, sedation, impulse control disorders

Question 10

Discuss monoamine oxidase (MAO) B inhibitors

Answer 10

Stops the breakdown of dopamine in the peripheries = increased effectiveness of L-DOPA

Can be used alone

Question 11

Discuss COMT inhibitors

Answer 11

E.g. Entacapone

Increases the effectiveness of L-DOPA = prevents breakdown of Levodopa in the peripheries

Needs to be used with L-DOPA

Question 12

Discuss anticholinergics

Answer 12

Not widely used

Antagonistic effects to dopamine

Used in tremor predominant PD

ADRs = confusion, drowsiness, effects micturition

Question 13

Discuss amantidine

Answer 13

= enhanced dopamine release

Not used in PD anymore = little effect on tremor

Question 14

How can surgery treat PD?

Answer 14

Pt has to be dopamine responsive

DBS = target the subthalamic nucleus

Lesion = thalamus for tremor, globus pallidus interna for dyskinesias

Question 15

What is the pathophysiology of myathenia gravis?

Answer 15

Autoimmune disease, Ab to the ACh receptors

Fluctuating, fatiguable, weakness skeletal muscle

Question 16

How does myasthenia gravis present?

Answer 16

Extraocular muscles – commonest presentation

Bulbar involvement – dysphagia, dysphonia, dysarthria

Limb weakness – proximal symmetric

Respiratory muscle involvement

Question 17

What are the range of treatments for myasthenia gravis?

Answer 17

Acetylcholinesterase inhib = inhibits enzyme that mops up ACh = more present in synaptic cleft

Corticosteroids

Steroid sparing

IV immunoglobulin

Plasmapheresis