Parkinsons Flashcards
Dopamine: inhib or excitatory
Parkinsons = too little or too much dopamine?
Inhibitory transmitter
Parkinsons = too little dopamine
Acetylcholine: inhib or excitatory ?
Parkinsons= too little or too much?
Acetylcholine (ACh)= Excitatory transmitter
Parkinsons = too much ACh
2 main categories of drugs to treat Parkinsons
- dopaminergic agents
2. Anticholinergic
5 types of dopaminergic agents
~Dopamine replacement: Promotes dopamine synthesis
(Levodopa )
~Dopamine agonists: Stimulate dopamine receptors directly
(pramipexole)
~COMT inhibitors: Enhance effects of levodopa by blocking its degradation
(entacapone)
~MAO-B inhibitors: Inhibit dopamine breakdown
(selegiline)
~Antiviral: Promotes dopamine release
(amantadine)
class promotes dopamine SYNTHESIS
~Dopamine replacement: Levodopa
class STIMULATES dopamine RECEPTORS directly
Dopamine agonists:(pramipexole)
class enhances effects of levodopa by BLOCKING its DEGRADATION
~COMT inhibitor: entacapone
Class INHIBITs dopamine BREAKDOWN
MAO-B inihibitor : selegiline
class promotes dopamine RELEASE
antiviral: amantadine
most effective drug for parkinsons disease
Levodopa/Carbidopa
How does Levodopa/Carbidopa fxn? What enzyme is at play here?
FXN:levodopa converts to dopamine in the brain (dopamine replacement)
- leovdopa crosses BBB to convert to dopamine
- Levodopa in peripheral circulation comes into contact with enzyme DDC
- Enzyme DDC breaks down levodopa so only small portion (2%) can cross BBB
- Add in CARBIDOPA to decrease the breakdown of levodopa in the periphery by DDC and increase the amount (10%) that crosses the BBB.
- carbidopa = no other effect
Benefits of having Levodopa with Carbidopa
- ->use less drug
- -> less side effect from levodopa
Levodopa/Carbidopa onset and duration
- Delayed full effect (months)
- Effect doesn’t last (<5 years)
- –>reserved, don’t use in younger patients
- –> no drug holiday anymore!
do we give young people Levodopa/Carbidopa
try not to
7 side effects of Levodopa/Carbidopa
- *Nausea/Vomiting: give with food initially. Avoid high-protein meals. start low dose and increase
- Dyskinesia: ie: dystonic movements
- Cardiovascular
- *Postural hypotension: increase salt and water to prevent
- Dysrhythmias - Psychosis
- No 1st generation antipsychotic meds w/ parkinsons b/c block dopamine receptors and make PD worse
- use 2nd generation antipsychotic - CNS Effects
- Anxiety, agitation, memory issues - Darkened sweat and urine
- Can activate malignant melanoma
2 aspects of “acute loss effect” of Levodopa/Carbidopa
“Wearing Off”
• sxs start returning at the end of the dosing interval
-Dosing must be on time
“On-Off” • Abrupt loss of effect -Can occur at anytime -Lasts from minutes to hours -Avoid high protein meals
minimize wearing off of levodopa/carbidopa by
- Shorten interval
- Give a drug to prolong half life
- Give direct acting dopamine agonist
prototype for dopamine agonist
pramipexole (Mirapex)
1st line therapy for mild to moderate sxs of parkinsons
pramipexole (Mirapex) (Dopamine AGONIST)
how does pramipexole (Mirapex) fxn?
Direct activation of dopamine receptors in striatum
indication for use of pramipexole (Mirapex)
- Used in younger patients who are more likely to handle side effects
- Also used in Restless legs syndrome
onset of pramipexole (Mirapex)
weeks (quicker than carvidopa/levodopa)
Adverse effect of pramipexole (Mirapex) as monotherpay vs combined with levodopa
-Monotherapy-
nausea, dizziness, *Sleep attack: daytime somnolence, insomnia, constipation, weakness, and *hallucinations
- Combined with levodopa–
- orthostatic hypotension & dyskinesia and double rate of hallucinations
really unique side effect of pathologic gambling and other compulsive self-rewarding behaviors
with which drug?
pramipexole (Mirapex) (Dopamine AGONIST)
prototype for COMT inhibitor?
entacapone (Comtan)
how does entacapone (Comtan) fxn?
- Increases the amount of levodopa that enters the brain
- ->Inhibit the breakdown of levodopa in the periphery
- When DDC is blocked by carbidopa body starts trying to break down levodopa w/ another enzyme COMT
- No direct therapeutic effects of their own –> prevents breakdown of levodopa/carbadopa
- ->Levodopa “Boosters”
adverse effects of entacapone (Comtan)
- Increased levodopa levels—dyskinesias; orthostatic hypotension, nausea, hallucinations, sleep disturbances, impulse control
- GI distress; yellow/orange discoloration of urine
prototype for MAO-B inhibitors
selegiline (Eldepryl)
how does selegiline (Eldepryl) fxn?
Can suppress destruction of dopamine derived from levodopa and prolong the effects of levodopa
- Combination with levodopa
- can reduce the wearing-off effect
duration of selegiline (Eldepryl)
1-2 weeks
adverse effects of selegiline (Eldepryl)
Insomnia (give in am)
Orthostatic hypotension
Dizziness
GI symptoms
prototype for antiviral parkinsons med?
amantadine
what does amantadine due to dopamine?
promotes dopamine release in brain
indication for using amantadine
used for dyskinesias caused by levodopa
onset/duration of amantadine
works w/in 2-3 days, lasts several months
adverse effects of amantadine
- CNS (anxiety)
- Anticholinergic
- Livedo reticularis (mottled discoloration of skin)
“a man has a tic on his dick”
anticholinergic prototype for parkinsons drugs?
benztropine (Cogentin)
how does benztropine (Cogentin)
fxn?
Block muscarinic receptors
-Centrally acting
indication for using benztropine?
Reduce tremors and rigidity
is benztropine a first or 2nd line therapy for parkinsons?
2nd
what patient population do we give benztropine to?
younger
adverse effects for benztropine?
anticholingeric
agitation/hallucination in elderly
how do we treat orthostatic hypotension with levodopa/carbidopa
give salt!
how do we prevent “acute loss effect” of Levodopa/Carbidopa?
avoid high protein meals, give meds on time
