Antiparkinsons

Question 1

What is parkinsons disease

Answer 1

A neurodegenerative disease, characterised by disorders of movement and gait.
Late stage involves cognitive impairment as well

Question 2

Pathophysiology of Parkinsons disease

Answer 2

Impaired clearing of abnormal/damaged intracellular proteins by ubiquitin-proteasomal system
Failure to clear toxic proteins → accumulation of aggresomes → apoptosis
Degeneration of dopaminergic neurons with Lewy body inclusions in substantia nigra, which has dopaminergic projections to basal ganglia, which facilitates motor movements initiated by motor cortex

Question 3

How is PD diagnosed?

Answer 3

Presence of clinical features, exclusion of alternative diagnoses

Question 4

What is Parkinsonism

Answer 4

Rest tremors, rigidity, bradykinesia

Question 5

When do non-motor manifestations of PD occur

Answer 5

Autonomic, neuropsychiatric, olfactory, sensory

Occurs during later stages of PD

Question 6

Do we need to treat all patients with PD?

Answer 6

Start low go slow. If coping well, may not even need oral medications.
More importantly, exercise regime, healthy and balanced diet, knowledge on disease, social support

Question 7

Oral medications available for PD

Answer 7

Levodopa
Anticholinergic agents
MAO-B/COM-T inhibitors
Dopamine agonists

Question 8

Levodopa preparations contain?

Answer 8

Levodopa with peripheral decarboxylase inhibitors to allow larger proportion of L-dopa to enter BBB
Allows for lower doses of levodopa to be administered to the patient

Question 9

Levodopa MOA

Answer 9

Precursor for dopamine

Question 10

SEs of levodopa

Answer 10

N/V, postural hypotension

Long term - motor fluctuations and dyskinesia

Question 11

Anticholinergic for PD

Answer 11

Trihexyphenidyl

Question 12

Advantages of trihexyphenidyl

Answer 12

Effective in controlling tremor

May be useful in controlling sialorrhea

Question 13

Side effects of trihexyphenidyl

Answer 13

Dry mouth, sedation, constipation, urinary retneion, delirium, confusion, hallucinations

Question 14

MAO-B inhibitors

Answer 14

Selegiline

May have disease modifying effects by reducing rate of death of dopaminergic neurons

Question 15

Which drugs can be combined with levodopa?

Answer 15

Trihexyphenidyl, entacapone, tolcapone, bromocriptine, pergolide, ropinirole, amantadine

Question 16

Selegiline can be used as monotherapy?

Answer 16

yes during early stages

Question 17

COMT inhibitors MOA

Answer 17

blocks enzyme that converts levodopa to inactive form

Question 18

COMT inhibitors

Can they be used as monotherapy?

Answer 18

entacapone, tolcapone

cannot be used as monotherapy, must combine with levodopa

Question 19

Dopamine agonists

Answer 19

Bromocriptine, pergolide, ropinirole

Question 20

Dopamine agonist MOA

Answer 20

act directly on dopamine receptors in the brain to reduce symptoms of PD

Question 21

side effects of dopamine agonists

Answer 21

similar to levodopa
fibrosis 
pedal edema
arrythmia
somnolence with ropinirole
restrictive valvular disease with pergolide

Question 22

What should younger patients use?

Answer 22

Dopamine agonists

Question 23

Amantadine MOA

Answer 23

Antiviral, works by enhancing release of stored dopamine, inhibit presynaptic uptake of catecholamine, dopamine receptor agonist, NMDA receptor antagonist

Question 24

Benefits of using amantadine with levodopa

Answer 24

It is a antidyskinetic

Question 25

Side effect of amantadine

Answer 25

Cognitive impairment, hallucination, insomnia, nightmares
Livedo reticularis
SJS
Suicidal ideation
Exacerbate seizures and psychiatric symptoms in schizophrenics