UWORLD Chapter 68: Parkinson’s Disease

What is parkinson's disease? What is thought its pathophysiology?

a degenerative neurological disorder. Occurs when neurons die in the basal ganglia, which includes substantia nigra, striatum, and thalamus. These cells produce the neurotransmitter dopamine, which enables smooth, coordinated muscle function and movement.

What are major symptoms of parkinson's disease?

- Tremor when resting

- Rigidity in legs, arms, trunk and face

- Akinesia/bradykinesia (lack of/slow start in movement)

- Postural instability (imbalance, falls)

What are additional minor symptoms that can occur with parkinson's?

small, cramped handwriting (micrographia), Shuffling walk, stooped posture, muffled speech, drooling, dysphagia, depression, anxiety (psychosis in advanced disease), constipation, incontinence

What is used to determine severity of drug caused movements?

Abnormal Involuntary Movement Scale (AIMS)

What are drugs that can worsen parkinson's disease?

phenothiazines (prochlorperazine),

butyrophenones (haloperidol, droperidol),

FGAs and SGAs,

metoclopramide

What antipsychotic is preferred in parkinson's disease due to low risk of movement disorders?

quetiapine and clozapine

What can abrupt withdrawal of levodopa/dopamine agonists lead to?

a condition similar to NMS, so slow tapering should be done when discontinuing

What is levodopa?

prodrug of dopamine

What is carbidopa?

given with levodopa to prevent breakdown of levodopa outside of the CNS (peripheral metabolism) by inhibiting the dopamine decarboxylase enzyme

What do dopamine agonists do?

reduces off periods and limiting dyskinesias in parkinson's disease

What drugs are dopamine agonists?

COMT-Inhibitors and MAO-B inhibitors

When can centrally acting anticholinergics (benztropine) be used in parkinson's disease?

tremor predominant disease in younger patients

What is the brand name for carbidopa/levodopa tablets?

Sinemet

What dose is Sinemet started at?

25/100 mg TID

What is a counseling point for ER tablets of carbidopa/levodopa?

can be cut in half

What is an administration for Rytary?

can take whole or sprinkle

What are contraindications to carbidopa/levodopa use?

Nonselective MAO inhibitors within 14 days.

What are side effects for carbidopa/levodopa?

nausea, dizziness, orthostasis, dyskinesia, hallucinations, psychosis

Can cause brown, black, or dark colored urine; positive Coombs test; discontinue drug if occurs due to hemolysis risk, unusual sexual urges, priapism

How much mg/day are required of carbidopa to inhibit dopamine decarboxylase?

70-100 mg/day

What are side effects with long term use of carbidopa/levodopa?

fluctuations in response and dyskinesias

What is the mechanism of COMT inhibitors?

increase the duration of action of levodopa; inhibit the enzyme catechol-O-methyltransferase to prevent peripheral conversion of levodopa. Can only be used with levodopa.

How is entacapone dosed with carbidopa/levodopa?

200 mg PO with each dose of carbidopa/levodopa

What are the names of the COMT inhibitors?

Entacapone

Tolcapone

Opicapone

What is the brand name of pramipexole?

Mirapex ER

What are warnings with dopamine agonists?

somnolence (including sudden daytime sleep attacks),

orthostasis,

hallucinations,

dyskinesias (rotigotine has application (skin) reactions)

What are the administration instructions for the rotigotine patch?

Apply once daily, don't use the same site for at least 14 days. Remove the patch before an MRI. Avoid if have a sensitivity to sulfites

What dosage form is apomorphine?

SC injection

What are contraindications of apomorphine use?

Don't use with 5-HT3 antagonists due to severe hypotension and loss of consciousness

What are side effects of apomorphine?

severe nausea/vomiting, hypotension

What do you use to prevent emesis in apomorphine use?

trimethobenzamide

What must be done with the first dose of apomorphine?

test dose in a medical office

What is the mechanism of amantadine?

blocks dopamine reuptake into presynaptic neurons and increases dopamine release from presynaptic fibers.

What is amantadine primarily used to treat for parkinson's?

dyskinesia associated with peak dose of carbidopa/levodopa

What are warnings and side effects of amantadine?

somnolence, psychosis, dizziness, orthostatic hypotension, livedo reticularis (reddish skin mottling)

What are contraindications with MAO-B inhibitor use?

combination with other MAO inhibitors (including linezolid), opioids, SNRIs, etc.

Safinamide (Xadago): severe hepatic impairment

What are safety warnings for MAO-B inhibitors?

serotonin syndrome and hypertension

What is a counseling point for selegiline?

activating, don't take dose at bedtime

What are side effects of Benztropine?

Anticholinergic side effects, which include dry mouth, blurred vision, constipation, mydriasis, somnolence, confusion, urinary retention, and memory impairment.

What is istradefylline used for?

In combo with carbidopa/levodopa to reduce "off" episodes

What are side effects with droxidopa?

syncope, falls, headache

What are foods to be avoided with MAO-B inhibitors?

foods high in tyramine (aged or matured cheese, air dried or cured meats, sauerkraut, draft beer