Parkinson's Disease Flashcards
True or False - Parkinsons Disease is curable.
False - it is not.
What is the neurotransmitter that causes of PD?
Deficiency in dopamine in brain stem (substantia nigra)
Motor symptoms of PD
“TRAP”
T- tremors (at rest)
R - rigidity (stiff legs, ams, trunk joints)
A - akinesia (slow movement/lost dexterity)
P - postural instability (gait, cant walk, falls)
Non-Motor symptoms of PD
Constipation
incontinence
insomnia
depression/anxiety
drooling
sialorrhea
masked face
muffled speech
bent over body
Who are the members of a multidisciplinary health care team to treat someone with PD?
SLP
Occupational therapist
Physiotherapist
Dietitian
Treatment for MILD PD?
Irreversible MAO-b inhibitors
RASAGILINE
SELIGILINE
treatment for Moderate-Severe PD
1st line: levodopa
OR
Dopamine agonists: bromocriptine, pramipexole, ropinirole, rotigotine patch)
In which patients are dopamine agonists considered 1st line?
If patients are < 60 years old, and they accept the AE of dopamine agonists. If ineffective or intolerant, then switch to Levodopa.
DDIs with MAOB-i?
Drugs that can cause serotonin syndrome: triptans, SSRIs
What is the Wear off phase of Levodopa? (end dose)
a predictable decline in the effectiveness of Levodopa at the end of the dosing interval, occurs after 3-5 years after taking Levodopa.
What is dyskinesia?
abnormal and involuntary movement usually in the legs; can occur at the beginning or end of levodopa response cycle
How to manage dyskinesia due to levodopa or a dopamine agonist?
think of dyskinesia as overdose/toxicity of levodopa.
1. decrease dose of levodopa or dopamine agonist
or
2. switch to a different dopamine agonist
3. discontinue any anticholinergics, MAOi, or entacapone if worsening symptoms
how to manage the waring off effect or the on-off fluctuation effect from levodopa?
- increase frequency of levodopa
- change to CR (extends from 60 min to 90 min)
- Add Entacapone with Sinemet CR for further extension (~1 hr)
- Add on a dopamine agonist (bromo) or add rasagiline, amantadine for dyskinesia control.
- adjust diet - reduce protein intake, mix levodopa in water for a quick rescue
“Wear-Off” (End-Dose Effect) and “On-Off” Fluctuations
Sudden freezing episodes or loss of motor control due to fluctuations in drug efficacy.
Which types of food interferes with levodopa absorption?
protein competes with levodopa absorption
Should levodopa be taken with or without food?
with food
Patient X comes to the pharmacy asking for which medication to take for her nausea/vomiting. Her medical history includes Parkinson’s Disease. What is the drug of choice?
Domperidone - preferred because it does not cross the blood brain barrier, avoiding EPS symptoms
Dose considerations of domperidone to treat nausea or vomiting caused by levodopa or dopamine agonists?
adjust dose in cases of QT prolongation to minimize risk of arrhythmias.
max dose = 30 mg/day
Which drugs should be avoided in patients with PD?
AVOID:
-metoclopramide (crosses BBB = EPS symptoms)
-1st and 2nd gen antipsychotics - worsens parkinsons symptoms bc it blocks dopamine Rs (but Quetiapine or Clozapine are ok)
-Valproic acid, Lithium - worsens tremors/motor symptoms. (phenytoin is OK)
orthostatic hypotension related to PD?
caused by anti-PD meds, other meds, or PD itself
-get a lying and standing BP at each dr visit
How to manage orthostatic hypotension?
- Reduce dose of levodopa or dopamine agonist
- Add salt to diet
- Add domperidone or fludrocortisone
When should domperidone be taken?
30 minutes prior to each dose (of anti-PD drugs) - max dose of 30 mg/day*******
side effects of domperidone ?
increased ventricular arrhythmias, sudden cardiac death.
USE THIS FOR SHORT DURATION!
How to manage psychosis, confusion, agitation, hallucinations, delusions?
- reduce dose of levodopa or dopamine agonist
- discontinue anticholinergic drugs, amantadine, selegiline
What drugs can be used to treat psychosis in PD?
quetiapine or clozapine
Non-selective dopamine (D1 & D2) agonists
bromocriptine
Selective D2 agonists
pramipexole 0.5-1 mg TID
ropinirole 3-6 mg TID
rotigotine transdermal patches
Side effects of dopamina agonists
GI: N/V, constipation
Ortho hypotxn
Hallucinations, Psychosis
Erythromelalgia (burning pain, warmth, redness of extremities)
Sudden Sleep attacks
Compulsive behaviors like GAMBLING, HYPERSEXUALITY
Pleural fibrosis
Why must doctors do a base line chest X ray?
risk of pleural fibrosis if patient is prescribed dopamine agonists
Drug interactions with pramipexole ?
erythromycin (increases bioavailability by 200%)
what patient population should not take D2 agonists?
patients > 70 years old
What are the benefits of adding dopamine agonists to levodopa?
Can be used to extend the duration of exogenous levodopa dose (reduces wearing off effects), but will not delay motor complications like dyskinesia from levo.
Which class of drugs can cause sudden sleep attacks while driving?
Dopamine agonists
Why are non-ergot dopamine agonists more preferrable than ergot-derived dopamine agonists?
Non-ergots (prami, ropinirole) = better safety profile (but can still cause sleep attacks), but the ergots (bromocriptine) have the additional risk of fibrosis (scarring of tissues)
What is the benefit of switching Sinemet (levo/carb) –> Sinemet CR?
Dosing interval with CR is increased by 30-50% (i.e., from Q4hrs to Q6hrs), longer duration of the formulation
-CR provides steadier dopamine levels = helps reduce motor fluctuations (wearing-off effect)
-CR has a slower onset so may require a higher dose increased by 10-30%
dopamine precursors
levodopa/carbidopa
dosing of domperidone
10 MG with every dose of sinemet. avoid > 30 mg in patients with QT prolongation
drug interactions with levodopa
-anti-hypertensives
-phenytoin
-metoclopramide (eps)
-vitamin b6 (increased N/V)
side effects of levodopa
mnemonic: LEVODOPA
Lethargy
Euphoria
Vomiting
Orthostatic hypo
Delirium/delusion
On-off effect
Priapism
Athetosis (dyskinesia)
true or false- levodopa is preferable to take on an empty stomach 1hr before or after meals?
true.
but if n/v, can take with food to minimize
What is the role of amantadine?
drug of choice in drug-induced PD, to decrease dyskinesia caused by levodopa in later stages of disease
MoA amantadine
NMDA antagonist,
may increase dopamine release and inhibit dopamine reuptake
Side effects of amantadine
hallucinations
ankle or feet edema
livedo reticularis (rose-colored mottling of skin in lower legs/feet, swelling)
Drug interactions with amantadine
-memantine (do not combine!!!)
-possible toxicity due to drugs that impair renal function (ex. diuretics)
MAO-b selective inhibitors
selegiline
rasegiline
side effects of MAO-b inhibitors
insomnia
confusion
hallucinations
anorexia
diarrhea
increased dyskinesia
DDIs with MAOb inhibitors
drugs that can cause serotonin syndrome: SSRIs, TCas, MAOi, triptans, linzeolid, dextromethorphan
COCs: reduce dose of selegiline
Cipro or other 1A2 inhibitors (fluvoxamine)
Liver disease and MAOb inhibitors
-reduce dose if mild
-if severe, don’t use drug
True or false? Adding selegiline to levodopa increases mortality
TRUE
When is benztropine (an anticholinergic agent) indicated?
Drug-induced PD i.e., by antipsychotics.
effective for tremors, but not rigidity or bradykinesia
-use as monotherapy, or adjunct to dopamine drugs
Benztropine counselling points?
AEs: anticholinergic (constipation, blurred vision, dry mouth, urine retention)
-with food, or milk to reduce GI effects
In what patient populations should benztropine be avoided?
patients > 70 y/o
COMT Inhibitors
Entacapone 200 mg (max upto 8 times per day)
Role of entacopone
given with levodopa, helps extend the duration of levo’s effects by 1 hour (for wearing off effect)
helps decrease dyskinesia
requires special access program
Side effects of entacapone?
-dyskinesia
diarrhea (weeks-to months of initiation)
-nausea
-hallucination
-urine discoloration (Brown-orange color)
-dopamine activity in the brain = dyskinesia, confusion, hallucination
what is dyskinesia?
involuntary movement = jerking, twisting
Wearing-off effect
also known as “end of dose” effect from long-term use of LEVODOPA.
-Predictable, occurs at the later part of dosing interval.
-effects of the dose diminish before next dose is due, so patients have a gradual return of PD symptoms
-common in early stages of motor fluctuations
Management of wearing-off effect
1) Increase dosing frequency of levodopa.
2)Add adjunctive therapies like:
COMT inhibitors (e.g., entacapone): Extend levodopa’s half-life.
MAO-B inhibitors (e.g., rasagiline, selegiline): Reduce dopamine breakdown.
Dopamine agonists (e.g., pramipexole, ropinirole): Provide more continuous stimulation.
3)Use controlled-release levodopa to smooth out fluctuations.
Key diff between on-off effect and wearing off effect
O/F = unpredictable, unrelated to levo
W/O = predictable, related to levo dosing time
On-Off effect
unpredictable, sudden fluctuation between period of mobility (ON period) and immobility/worsening of symptoms (OFF period), UNRELATED to timing of levodopa dose, so it can happen even during a dose’s peak effectiveness.
how to manage on-off effect?
similar to wearing-off effect:
1. increase freq of levo
2. add DA, MAOi, or COMTi
