NAPLEX 2026 - Parkinson Disease

What is Parkinson disease (PD) and when does it occur?

Degenerative neurological disorder

Occurs when neurons die in the basal ganglia, which inckudes the substantia nigra, striatum, and thalamus

- these cells produce dopamine, which enables smooth, coordinated muscle function and movement

What are the symptoms of PD?

Pathophysiology: less DA - less instructions to the brain - movement problems referred to as "TRAP"

TRAP major symptoms:

- Tremor: when resting

- Rigidity: in legs, arms, trunk, and face

- Akinesia/bradykinesia: lack of/slow start in movement

- Postural instability: imbalance, falls

Additional symptoms:

- small, cramped handwriting

- shuffling walk, stopped posture

- muffled speech, drooling, dysphagia

- depression, anxiety (psychosis in advanced disease)

- constipation, incontinence

What drugs can worsen PD?

Dopamine blocking drugs

- phenothiazines (prochlorperazine)

- butyrophenones (haloperidol)

- FGAs and SGAs (lowest risk with quetiapine)

- metoclopramide

What psychiatric conditions are related to PD?

Depression:

- SSRIs or SNRIs commonly used for treatment

- Alternative: TCAs (preferably secondary amines)

Psychosis (with advanced disease) or due to side effects of treatment:

- quetiapine preferred for treatment due to low risk of movement disorders (can cause metabolic complications)

- clozapine also has a low risk of movement disorders but has a high risk of seizures and agranulocytosis

Abrupt withdrawal of levodopa or dopamine agonists can lead to a condition similar to NMS

- slowly taper when discontinued

What are the treatment principles for PD?

Primary treatment: replace dopamine

- give a drug that mimics DA (DA agonist)

- give a drug that increases DA (levodopa)

- give other drugs for specific symptoms

What's the most effective drug for PD?

Levodopa (prodrug of dopamine)

- carbidopa given with levodopa to prevent its breakdown outside of the CNS

May be better tolerated than DA agonists for initial treatment in older adults

When are dopamine agonists used? COMT inhibitors? MOA-B inhibitors?

Eventually used in most patients

As disease progresses, treatment goals include reducing "off" periods and limiting diskinesias

- this requires multiple drug classes such as COMT (-)s and MOA-B (-)s

When are centrally-acting anticholinergics used for PD?

Used for tremor-predominant disease in younger patients

Carbidopa/Levodopa (Sinemet): MOA and dosing

Levodopa is a precursor of dopamine

Carbidopa inhibits the dopa decarboxylase enzyme, preventing peripheral metabolism of levodopa

Dosing:

- titrate cautiously

- IR starting dose: 25/100 mg PO TID

- ER tablet can be cut in half

Sinemet: contraindications

Non-selective MAO inhibitors within 14 days

Narrow angle glaucoma

Sinemet: side effects

Nausea, dizziness, orthostasis, dyskinesias, hallucinations, psychosis

Can cause brown, black, or dark discoloring of bodily fluids

Positive Coombs test: discontinue drug (hemolysis risk)

Usual sexual urges, priapism

How many mg per day of carbidopa are required to inhibit dopa carboxylase?

70-100 mg/day

What is important to know about long term use of Sinemet?

Fluctuations in response and dyskinesias

Do not discontinue abruptly, must be tapered

COMT inhibitors: MOA, drugs, and dosing

Increase the duration of action of levodopa

- inhibit the enzyme catechol-O-methyltransferase to prevent peripheral conversion of levodopa

- should only be used with levodopa (decrease in levodopa dose of 10-30% usually necessary)

Entacopone

- 200 mg PO with each dose of Sinemet

Opicapone

Tolcapone

Dopamine agonists: MOA and drugs

Act similar to dopamine at the dopamine receptor

Pramipexole (Mirapex)

Ropinirole

Rotigotine

Dopamine agonists: warnings

Somnolence (including sudden daytime sleep attacks)

Orthostasis

Hallucinations

Dyskinesias

Rotigotine patch: application site reactions

Do not discontinue abruptly

Rotigotine patch counseling points

Apply once daily at the same time each day to the stomach, thigh, side of body, shoulder, or upper arm

Do not use the same site for at least 14 days

Remove patch before an MRI

Avoid if sensitivity/allergy to sulfites

Apomorphine: MOA and use

Dopamine agonist

Used as a "rescue" movement drug for "off" periods

Apomorphine: contraindications

Do not use with 5-HT3 antagonists (Zofran) due to severe hypotension and loss of consciousness

Apomorphine: side effects

Severe nausea/vomiting

- for emesis prevention: trimethobenzamide

Hypotension

- must be started with a test dose in a medical office

Amantadine: MOA and use

Blocks dopamine reuptake into presynaptic neurons and increases dopamine release from presynaptic fibers

Primary used to treat dyskinesias associated with peak-dose of Sinemet

Amantadine: warnings

Somnolence

Compulsive behaviors

Psychosis

Amantadine: side effects

Dizziness

Orthostasis hypotension

Cutaneous reaction called livedo reticularis

Selective MAO-B inhibitors: MOA, use, and drugs

Block the breakdown of dopamine, which increase dopaminergic activity

Primarily used as adjunctive treatment to Sinemet

Drugs:

- selegiline

- rasagiline (indication for monotherapy)

- safinamide

MAO-B inhibitors: contraindications

Use in combination with other MAO inhibitors (including linezolid), opioids, and SNRIs

Xadago: severe hepatic impairment

MAO-B inhibitors: warnings

Serotonin syndrome

Hypertension

MAO-B inhibitors: drug interactions

Do not eat foods high in tyramine

- aged or matured cheese

- air-dried or cured meats

- sauerkraut

Centrally-acting anticholinergics: MOA, use, and drugs

Have anticholinergic and antihistamine effects

Primarily used for tremor

Drugs:

- benztropine

- trihexyphenidyl

Centrally-acting anticholinergics: side effects

Dry mouth

Constipation

Urinary retention

Blurred vision

Myadriasis

Somnolence

Confusion