Parkinson's Disease Flashcards
Pathophysiology of Parkinson’s?
degeneration & loss of dopaminergic neurons with Lewy body inclusions in substantial nigra
Does dopamine and levodopa pass thru BBB?
Dopamine: no
Levodopa: yes
Lifecycle of dopamine?
L-tyrosine -> levodopa by tyrosine hydroxylate -> dopamine by DOPA decarboxylase -> breakdown to HVA by COMT & MAO-B or recycled
Symptoms of Parkinson’s?
Motor: TRAP:
Tremors
Rigidity
Akinesia / bradykinesia
Postural instability & gait
Non-Motor:
- cognitive impairment (dementia, confusion)
- psychiatric sx (depression, psychosis)
- sleep disorders
- autonomic dysfunction (constipation, OH)
- others (fatigue, choking etc)
Non Pharm of Parkinson’s?
- physiotherapy
- occupational therapy
- speech & swallowing
- surgery
1st line treatment for Parkinson’s? Other treatment options?
1st line: levodopa-DCI (carbidopa, benserazide)
Other options: dopamine agonists, MAO-B inhibitors, COMT inhibitors
Examples of dopamine agonists used for Parkinson’s?
Ropinirole, pramiprexole
Examples of MAO-B inhibitors used for Parkinson’s?
Selegiline, rasagiline
Examples of COMT inhibitors used for Parkinson’s?
Entacopone
MOA of:
- levodopa-DCI
- dopamine agonists
- MAO-B inhibitor
- COMT inhibitor
- levodopa-DCI: covered to dopamine, DCI prevents peripheral conversion of levodopa to dopamine by DOPA decarboxylase/MAO/COMT
- dopamine agonists: mimic dopamine (act on D2 receptors)
- MAO-B inhibitor: irreversibly inhibits MAO-B -> inhibit breakdown of dopamine
- COMT inhibitor: selectively & reversibly inhibit COMT conversion -> inhibit breakdown of dopamine
Special adm instructions for levodopa-DCI?
- Space apart from heavy meals (less absorption with high fat / protein meals)
- space apart from iron
Dose adjustment when switching b/w immediate & controlled release forms of levodopa-DCI?
- IR to CR: increase dose
- CR to IR: decrease dose
Ratio of levodopa:DCI for Madopar?
4:1
What dose of DCI is required to prevent conversion of levodopa into dopamine outside the brain?
75-100mg/day
SE of levodopa-DCI?
- N/V
- OH
- drowsy
- hallucinations
- dyskinesias (reduce with amantadine or CR)
What antiemetic is preferred for pts with Parkinson’s? Why not the others?
Domperidone
(metoclopramide and prochlorperazine cross BBB)
When is dopamine agonists indicated?
- monotherapy in young-onset PD
- adjunct to levodopa in moderate/severe PD
- management of motor complications caused by levodopa
SE of dopamine agonists?
- N/V
- OH
- drowsy
- hallucinations
- leg edema
- compulsive behaviours (e.g. gambling, shopping, eating etc)
If selegiline is taken BD, when should the second dose be taken and why?
2nd dose in the afternoon; hepatically metabolised to amphetamines (stimulant), cause insomnia
SE of MAO-B inhibitors?
- heartburn, loss of appetite
- anxiety, palpitation
- insomnia, nightmares, visual hallucination
If switching from MAO inhibitors to SSRIs, SNRIs and TCAs, what should be done?
washout period of 14D
Major interaction of MAO-B inhibitors with what food item?
Tyramine (e.g. aged cheese) -> HTN crisis
When are COMT inhibitors indicated?
Adjunct to levodopa (must be used together with levodopa)
SE of COMT inhibitors?
- diarrhoea
- urine discolouration (orange)
- visual hallucinations
- drowsy
What are anticholinergics used for in Parkinson’s? Examples?
- symptomatic tx for tremors & stiffness (not bradykinesia)
- benztropine, trihexyphenidyl (benzhexol)
What is amantadine used for in Parkinson’s?
Adjunct to manage levodopa-induced dyskinesias
What drugs can cause Parkinsonism?
- antipsychotics
- ASM
- metoclopramide, prochlorperazine
- non-DHP CCB
