PD- Kline

What are the symptoms of Parkinson’s? Which are hallmarks?

Hallmark:

• bradykinesia

• tremor at rest

• rigidity

• postural instability

others:

• micrographia

• mental status change

• sleep disturbances

The incidence rate of PD is dependent on what?

• which gender more likely?

• what age is the usual diagnosis?

• incidence rate is age and sex dependent

• men > women

• usual diagnosis 55-65 yrs old

Nonpharm for PD?

• exercise

• physiotherapy

• yoga

• tai chi

• dance

What 2 surgeries/procedures can be used in parkinson’s?

• DBS surgery

• focused ultrasound

List the anticholinergics used in PD tx?

• benztropine (cogentin)

• trihexyphenidyl

Amantadine (Symmetrel) is most often used as what?

adjunct for L-dopa dyskinesia in pts. experiencing off episodes

What is the most effective medication for symptomatic tx of PD?

carbidopa/levodopa

What is the minimum amount of carbidopa required a day to inhibit the conversion of L-dopa into dopamine in the peripheries?

75mg

If you take carbidopa/levodopa with a COMT inhibitor, what does that do to the half-life of carbidopa/levodopa?

extends by 2-2.5 hours

Why does Carbidopa/Levodopa have variable peak plasma concentrations?

Due to differences in gastric emptying and absorption in the proximal duodenum via a saturable large neutral amino acid (LNAA) transporter.

Because L-dopa is absorbed in the intestines and can compete with large amino acids for absorption, what must be considered when taking the medication?

• consistent dosing with regards to meals is important

• can even consider low protein diets (in advanced disease to help responsiveness)

ADRs of carbidopa/levodopa?

• impulse control disorders

• drowsiness

• n

• dyskinesias/motor symptoms

What are the brand names of the IR/ER formulations of carbidopa/levodopa?

rytary, crexont

What is the brand name of the suspension formulation of carbidopa/levodopa?

What is a complication of this formulation?

duopa- may cause serious GI complications

What is the brand name of the inhaler formulation of carbidopa/levodopa?

inbrija

What are the 2 most common motor complications of L-dopa?

1. end of dose “wearing off” (symptoms return before next dose).

2. peak dose dyskinesias (involuntary movements at peak drug levels).

Possible tx’s for end of dose “wearing off” with L-dopa?

• increase dosing frequency

• add another drug (COMT, MAO-B, istradefylline, amantadine, dop agonist)

Possible tx’s for peak-dose dyskinesias with L-dopa?

• smaller doses at same or increased frequency

• reduce dose of dopamine agonist

• add amantadine

What is the name of the adenosine A2AR antagonist used in PD?

Istradefylline

Indication for Istradefylline?

adjunctive tx to L-dopa for pts. with “off” episodes

MOA of Istradefylline? What movement pathway is affected?

xanthine derivative that antagonizes adenosine A2AR in indirect movement pathway

Istradefylline is metabolized by CYP____ and CYP____.

CYP1A1 and CYP3A4

What class of drugs used for PD has a potential for serotonin syndrome?

MAO-B inhibitors

MAO-B inhibitors should be avoided/ used in caution with what other drugs?

• meperidine

• opioids

• SSRIs

What are the names of the MAO-B inhibitors? Are they irreversible or reversible?

• Rasagiline (Azilect)—> irreversible

• Selegiline (L-deprenyl)—> irreversible

• Safinamide —> reversible

An adverse effect of Rasagiline is ___________.

nausea

What MAO-B inhibitor can worsen preexisting dyskinesias or psychiatric symptoms?

Selegiline

COMTs do what to L-dopa?

reduce the peripheral conversion (allows enhancement of central L-dopa)

List the COMT inhibitors:

• Entacapone (Comtan)

• Opicapone

• Tolcapone

When are dopamine agonists useful as monotherapy? They can also be used for what?

monotherapy for mild/moderate PD, adjunct with carb/levo to reduce “off” time

Dopamine agonists should be avoided in what pt. population?

• in pts. with cognitive problems or dementia

• in pts. with history of impulsive/compulsive behaviors, delusions/psychosis, and sleep attacks

There are 2 categories of dopamine agonists, ergot-derived and non-ergot derived.

Which has a better safety profile?

non-ergot derived dopamine agonists

List the dopamine agonists. Which one is ergot-derived?

• Apomorphine

• Bromocriptine (Parlodel)- only ergot-derived agonist

• Pramipexole (Mirapex)

• Ropinirole (Requip)

To minimize adverse effects of dopamine agonists what can be done?

slow dose titration

PRACTICE:

Which PD medication should be avoided in pts. in psychosis?

A) Carbidopa/levodopa

B) Pramipexole

C) Benztropine

D) Safinamide

B

PRACTICE:

Why should selegiline be avoided with meperidine?

A) Risk of hypertensive crisis

B) Serotonin syndrome

C) Respiratory depression

D) QT prolongation

B

What is the name of the scale most commonly used to evaluate patient’s symptoms and disease progression in PD?

Unified Parkinson’s Disease Rating Scale (UPDRS)