treatment of parkinson's disease

Question 1

Cardinal features of Parkinson’s

Answer 1

Tremors
Rigidity
Akinesia/Bradykinesia

Question 2

Idiopathic PD initial presentations

Answer 2

Asymmetric
Positive response to levodopa or apomorphine
Postural instability and falls not present
Less rapid progression
Autonomic dysfunction not present

Question 3

Morbidity in PD

Answer 3

Unable to perform basic ADLs
Dysphagia
Falls due to postural imbalance

Question 4

Pathology

Answer 4

Significant loss of dopaminergic neurons in the substantia niagra 
Age-related
Environmental toxins 
Genetics 
- Predisposition to toxins/insults 
- Genetic abnormalities

Question 5

Non-movement symptoms

Answer 5

Cognitive impairment
Sleep disorders
Psychiatric disorders
Autonomic dysfunction

Question 6

Goal of treatment

Answer 6

Manage symptoms

Maintain function and autonomy

Question 7

Non-pharmacological treatment

Answer 7

PT
OT
Speech and swallowing
Surgery

Question 8

Levodopa

Answer 8

Most effective for bradykinesia and rigidity

Causes N/V, hypotension

Question 9

Levodopa PK

Answer 9

A: proximal part in small intestines
Increased F with benserazide/carbidopa
Decreased absorption with high fat/protein meals

Question 10

DOPA decarboxylase inhibitors

Answer 10

Do not cross BBB
75-100mg daily for saturation of dopa decarboxylase (1:1 action)
1:4 – Sinemet, Madopar
1:10 – Sinemet

Question 11

Levodopa AE

Answer 11

N/V
Orthostatic hypotension 
Drowsiness, sudden sleep onset
Hallucinations, psychosis
Dyskinesia within 3-5y

Question 12

Levodopa DI

Answer 12

Pyridoxine (Vit B6) - cofactor for dopa decarboxylase 
Iron 
Protein
Antidopaminergic drugs 
- Metoclopramide, prochlorperazine
- 1st gen antipsychotics 
- Risperidone

Question 13

Dopamine agonists MOA

Answer 13

Act on D2 receptors in the basal ganglia

Mimic action of dopamine

Question 14

Dopamine agonists PK

Answer 14

Longer half-life and duration of action than levodopa
Ropinirole metabolised in liver to inactive metabolites, DA in hepatic impairment
Pramipexole excreted largely unchanged in urine, DA in renal impairment

Question 15

Dopaminergic agonists AE

Answer 15

N/V
Orthostatic hypotension
Hallucinations 
Somnolence, daytime sleepiness
Compulsive behaviours
Fibrosis
Valvular heart disease
Leg edema

Question 16

MAO B Inhibitors

Answer 16

Selegiline and rasagiline both irreversible inhibitors
Effective as monotherapy
Selegiline metabolised to amphetamines

Question 17

MAO B inhibitors dosing

Answer 17

Selegiline 5mg OM to BD

Rasagiline 0.5-2mg OD

Question 18

MAO B inhibitors DI

Answer 18

SSRI, SNRI, TCA
Dopamine
Sympathomimetics
Another MAOi 
Penthidine, tramadol 
Linezolid
Dextromethorphan

Question 19

COMT inhibitors

Answer 19

Decreases “off” time, useful in wearing off phase

Not effective without concurrent levodopa

Question 20

Entacapone

Answer 20

Selective, reversible COMT inhibitor
Must be taken at the same time as levodopa 
DI: 
- Iron, calcium 
- Catecholamine drugs 
- Enhances warfarin 
Diarrhoea, urine discolouration
May cause dyskinesia upon initiation 
May potentiate other dopaminergic effects

Question 21

Anticholinergics

Answer 21

Primarily used to control tremor
Ipatropium
Hyoscine
Tolterodine

Question 22

Anticholinergics SE

Answer 22

Dry mouth
Sedation
Constipation
Urinary retention

Question 23

NMDA Antagonists

Answer 23

Amantadine
Glutamate activates NMDA receptor activity which activates processes that encourage cell death
Improvement in levodopa-induced dyskinesia – used for management

Question 24

NMDA Antagonist PK

Answer 24

Renally excreted
Can be stimulating
AE: N, light-headedness, insomnia, confusion, hallucinations, livedo reticularis

Question 25

Alternative medicines

Answer 25

``` Co-enzyme Q10 Creatinine Vit E Glutathione Riboflavin Lipoic acid Acetyl carnitine Curcumin ```

Question 26

Vascular Parkinsonism

Answer 26

Pathology due to vasculature in the brain Usually bilateral No resting tremor Stepwise in progression Vascular risk factors present Increasing age is risk factor Mostly not caused by infarct/lesions in basal ganglia

Question 27

Drug-induced parkinsonism

Answer 27

``` Improvement with drug withdrawal in 80% of patients in 8w No improvement with levodopa Occurs bilaterally Women at higher risk May unmask existing PD onset ~3m ```

Question 28

Drugs that may cause drug induced parkinsonism

Answer 28

1st gen antipsychotics Antiepileptics Metoclopramide

Question 29

Parkinsons Hyperpyrexia Syndrome

Answer 29

``` Caused by changes in dopaminergic treatment Provoked by trauma and infections Loss of consciousness Rhabdomyolysis Immobility Disseminated intravascular coagulation ```

Question 30

PHS management

Answer 30

Reinstate previous treatment and increase dose of levodopa gradually Rotigotine patch Dantrolene PO/IV Bromocriptine