Parkinson's Flashcards
What are the approaches to treating Parkinson’s
- Increase endogenous dopamine
- Decrease cholinergic activity
- Activate dopamine receptors with synthetic dopamine agonists
- Block adenosine A2A receptor activity
How do you increase endogenous dopamine?
- Use of L-dopa
- Inhibit metabolism of dopa decarboxylase
- Inhibit metabolism by COMT
- Inhibit central/peripheral metabolism by MAO-B
- Increase dopamine release and inhibits reuptake
Drugs that inhbit COMT
- Entacapone
- Tolcapone
- Opicapone
Drugs that inhbit MAOB
- Rasagiline
- Selegiline
- Safinamide
What PK drugs that induce endogenous dopamine can also be used as monotherapy?
MAOB inhibitors
Which PK drug can produce methamphetamines if a toxicology report is done?
Selegiline
What PK drug increases dopamine release and inhibits it reuptake?
Amantadine
Dosing for Rasagiline as adjunctive and as monotherapy
Adjunctive: 0.5 mg
Monotherapy: 1 mg
What should you be cautious with in Safanimide therapy?
Hepatic impairment (Child Pugh Class C)
Abrupt discontinuation - withdrawal emergent NMS-like syndrome
What is the effect of Amantadine?
It reduces rigidity, tremor, bradykinesia and L-Dopa induced dyskinesia
What should you monitor with Amantadine dosing?
Renal elimination; adjust dose with renal impairment
What’s a transient adverse effect of Amantadine
Livedo reticularis; mottling of the skin
What is a side effect of selegiline?
It can cause insomnia and jitteriness
What PK drug is potentially disease modifying?
Rasagiline
What is the PKPD and dosing strategy surrounding Opicapone?
With a mod fat/calorie meal, its Cmax, AUC and Tmax decrease
It is also to be dosed at bedtime at least 1 hour before and 1 hour after eating
What PK drug is available in combo with Carbidopa/Levodopa?
Entacapone (200 mg)
STALEVO
True or False. Carbidopa can be used a monotherapy to help treat Parkinson’s
False. Never you give it alone
True or False. COMT inhibitors can be used as monotherapy to help treat Parkinson”s
False. No effect in absence of L-Dopa
True or false. MAOB inhibitors can be used as monotherapy to help treat Parkinson’s.
True
How can you activate dopamine receptors?
With the use of synthetic dopamine agonists
True or False. Dopamine agonists can be used a monotherapy to help treat Parkinson’s
True. Only in young healthy patients
What are your synthetic dopamine agonsits?
- Pramipexole
- Ropinirole
- Rotigotine
- Apomorphine
What is the benefit of using a synthetic dopamine agonist over L-Dopa
It has a reduced risk of developing motor complications when used as monotherapy
What are the side effects of dopamine agonists?
Impulsive behaviors, psychosis
n/v, vivid dreams, daytime sedation, orthostatic hypotension
What formulation is Rotigotine and what is a side effect?
Patch
Application site reaction
When is Apomorphine used?
In advanced Parkinson’s as needed for “off” episodes
How should you initiate Apormorphine therapy?
A test dose of 2mg SC done under medical supervision
Be sure to pre-treat with an antiemetic that is is not a 5HT3 antagonist or an antidopamingeric
What is the PK profile of Apormorphine?
It has a short half life of 40 mins that is why it is used for refractory, acute off episodes.
What is a serious DDI with Apomorphine pre-treatment?
It is contraindicated with 5HT3 antagonits and antidopaminergics due to hypotensive effects
Why might we need to block adenosine A2A receptor activity?
Its appears as so that inhibition of motor function occurs when there is overactivation of adenosine A2A receptor pathway
What drug can you use to block adenosine A2A receptor activity?
Istradefylline (A2A receptor antagonist)
How is Istradefylline used?
It’s used in combo with levodopa/carbidopa in patients experiencing off episodes
When might you need to dose adjust Istradefylline?
In concomitant tobacco smoking by increasing the dose
What are your non-pharm options for treatment of Parkinson’s
- Surgery: Deep Brain Stimulation
- Physical therapy/Exercise
- Nutrition (Fluids, Fiber, Omega 3)
- Occupational Therapy
What are L-Dopa related long term complications?
There are fluctuations in motor performance with wearing off and response deterioration as well as peak effect dyskinesia phenomenon
There is also dyskinesias/abnormal involuntary movement
What should you do if there is a wearing off or an “on-off” response?
Increase the frequency or switch to Sinemet CR or use an adjunctive dopa agonist/COMTi/MAOBi
*The med isn’t working long enough
What should you do if there is an “off, no on” response?
Increase the dose, the frequency or drink more water with med OR use an ODT. If it’s advanced Parkinson’s use Apomorphine.
*The med isn’t working well enough
What should you do if there is a delayed onset of the medication?
Take on an empty stomach, drink a lot of water and avoid protein. You can also switch to Sinemet CR or add IR to CR
*The med isn’t working fast enough
What should you do if you have peak-effect dyskinesia?
Decrease the dose, increase the frequency, add amantadine, use Sinemet CR, dopa agonist
What should you do if you experience dystonia?
Take in early morning, take Sinemet CR at bedtime, a dopa agonist, baclofen or botox
What should you do if you experience freezing?
Increase dose, dopa agonist, gait modification, physical therapy***
What can you give a Parkisnson’s patient with depression?
Pramipexole or Venlafaxine
How can you manage dementia and cognitive impairment in Parkinson’s patients?
Anticholinesterase inhibitors
How should you deal with Psychosis in Parkinson’s
- Evaluate hypoxia, infection or Elyte imbalance
- Simply regime; d/c anticholi’s, taper, selegiline
- Consider atypicals like quietapine and clozapine (and nuplazid)
What new drug is indicated for hallucinations and delusions in Parkinson’s?
Nuplazid
How does Nuplazid work?
inverse agonist at the 5HT2A/2C receptor
