Parkinson's (2Q)

Question 1

Parkinsonism: Essentials of Diagnosis

Answer 1

Any combination of tremor, rigidity, bradykinesia, and progressive postural instability. May include cognitive impairment.

Question 2

Parkinsonism: Epidemiology

Answer 2

Equally affects all ethnicities and has equal sex distribution.

Question 3

Parkinson’s: Pathophysiology

Answer 3

dopamine depletion due to degeneration of dopaminergic nigrostriatal system leads to an imbalance of dopamine (not enough) and Ach (too much) @ the striatum.

Question 4

In general, how do pharmacologic approaches to Parkinsonism work?

Answer 4

Symptomatic only (not disease altering). Rebalance the dopaminergic and cholinergic stimulation of the striatum by either increasing dopamine or blocking cholinergic stimulation.

Question 5

Parkinsonism: clinical presentation

Answer 5

Tremor (pill rolling) relieved by purposeful movement, rigidity (increased resistance to passive ROM), bradykinesia, postural instability. Shuffling gait, leaning forward, turn en bloc, reduced arm swing.
Immobile facial expressions, widened palpebral fissures, infrequent blinking.

Myerson sign- repeated tapping on bridge of nose induces sustained blinking response.

NO muscle weakness (provided sufficient time to generate movement), NO change in DTRs, NO abnormal plantar reflex.

Question 6

Parkinsonism DDx: old age

Answer 6

mild hypokinesia and slight tremor in isolation are common in old age.

Question 7

Parkinsonism DDx: depression

Answer 7

expressionless face, poorly modulated voice, reduction in vocal activity are features of depression, which may or may not coexist. Sometimes a trial of antidepressant therapy is necessary.

Question 8

Parkinsonism DDx: Wilson disease

Answer 8

Wilson will have earlier age of onset, will have other abnormal movements, Kayser-Fleischer rings, and chronic hepatitis (inc. copper in tissues).

Question 9

Parkinsonism DDx: Huntington’s disease

Answer 9

Huntington’s may present with rigidity and bradykinesia but should also have family Hx and dementia.

Question 10

Parkinsonism DDx: multisystem atrophy

Answer 10

autonomic insufficiency (leading to postural hypotension, anhidrosis, disturbances of sphincter control, erectile dysfunction) may be accompanied by parkinsonism, pyramidal defects, and lower motor neuron signs or cerebellar dysfunction.

Question 11

Parkinsonism DDx: progressive supranuclear palsy

Answer 11

Bradykinesia and rigidity are accompanied by supranuclear disorder of eye movements, pseudobulbar palsy (difficulty controlling facial expressions), emotional lability, and axial dystonia.

Question 12

Parkinsonism DDx: Jakob-Creutzfeldt disease

Answer 12

parkinsonism+dementia, myoclonic jerking, ataxia, and pyramidal signs (spasticity, hyperactive reflexes, a loss of the ability to perform fine movements, and Babinski sign)

Question 13

Parkinsonism DDx: corticobasal degeneration

Answer 13

asymmetric parkinsonism accompanied by conspicuous signs of cortical dysfunction (apraxia-disorder of motor planning, sensory inattention, dementia, aphasia)

Question 14

When should medical treatment be considered for Parkinson’s?

Answer 14

It is not required in the early course of the disease. It is up to the patient, as long as they understand the clinical course of their disease and how the treatments work.

Question 15

Amantadine

Answer 15

This drug works by enhancing dopamine release from the remaining terminals and inhibiting its reuptake.
Good for patients with MILD symptoms and no disability. Ameliorates dyskinesia associated with L-dopa.

Side effects: restlessness, confusion, depression, skin rashes- rare at usual dose.

Question 16

Levodopa- mechanism

Answer 16

Converted to dopamine (most peripheral) and improves all major symptoms, including bradykinesia.

Question 17

L-dopa side effects

Answer 17

nausea, vomiting, HTN, arrhythmias.

Later in course of use: dyskinesias, restlessness, confusion , behavioral changes. “on-off” phenomenon.

Question 18

What is the “on-off” phenomenon?

Answer 18

abrupt but transient fluctuations in the severity of parkinsonism occur unpredictably but frequently during the day. “off” period is one of marked bradykinesia (falling levels of L-dopa). “on” period is of marked dyskinesia, with increased mobility.

Common in treatment of Parkinson’s with L-dopa.

Question 19

Carbidopa

Answer 19

inhibits breakdown of levodopa (by L-AAD) to dopamine, but does not cross BBB. Increases dopamine in CNS, but not PNS.

Reduces short-term side effects of L-dopa and reduces effective dose. Does NOT prevent later side effects (dyskinesias, on-off phenomenon).

Question 20

carbidopa-levodopa (Sinemet)

Answer 20

combination of L-dopa and carbidopa, in fixed formulation.

Question 21

Diet changes for Parkinson’s treatment

Answer 21

Limit protein intake to recommended minium, and try to take it with the last meal of the day.

Question 22

L-Dopa: CI

Answer 22

Psychotic illness, narrow-angle glaucoma, Pts taking MAO-A inhibitors (or within 2 weeks of withdrawal). Use with care in malignant melanoma, active peptic ulcer.

Question 23

Pramipexole and ropinirole

Answer 23

Dopamine R agonists. Lower incidence of response fluctuations and dyskinesias vs L-dopa.

Used to be reserved for patients who could no longer tolerate L-dopa, but now given before introducing L-dopa, or with Sinemet (levodopa+carbidopa). Give fixed dose of sinemet, titrate up dose of dopamine agonist.

Question 24

Dopamine agonist side effects

Answer 24

fatigue, somnolence, nausea, peripheral edema, dyskinesias, confusion, postural hypotension, desire to sleep at hazardous times.

Question 25

Selegiline

Answer 25

Selective MAO-B inhibitor reduces breakdown of dopamine in CNS (MAO-B is mainly in striatum). Improve fluctuations or declining response to levodopa.

Avoid tyrosine-rich foods due to possibility of hypertensive “cheese” effect (no evidence though).

Start early, may alter disease course (FDA says nope).

Question 26

Tolcapone and entacapone

Answer 26

COMT inhibitors- reduce metabolism of L-dopa to INACTIVE metabolite (3-O-dopa), this leaves more available for conversion to dopamine and more sustained plasma levels.

Indicated in patients as adjunct to carbidopa/levodopa with response fluctuations or otherwise inadequate response (dose-reduce sinemet)
**Will not delay eventual development of dyskinesias

Question 27

Who shouldn’t get tolcapone?

Answer 27

Patients with liver disease due to risk of fulminant liver failure. They can get entacapone though.

Question 28

Stalevo

Answer 28

combination of levodopa with carbidopa AND entacapone. Best for patients already stabilized on equivalent dose of carbidopa/levodopa + enttacapone.

It is cheaper than buying component meds separately and requires fewer pills.

Question 29

Anticholinergics

Answer 29

Better for alleviating tremor and rigidity than bradykinesia. Start with small dose and titrate up.
Side-effects limit routine use of these drugs (dry mouth, nausea, constipation, palpitations, arrhythmia, urinary retention, confusion, agitation)
CI: Narrow-angle glaucoma (inc. intraocular pressure), prostatic hyperplasia, obstructive GI disease. Also, avoid when predisposition to delerium exists.

Question 30

Olanzapine, quetiapine, risperidone. Most effective is clozapine.

Answer 30

Atypical antipsychotics. Confusion and psychoitc symptoms may occur as a side effect of dopaminergic therapy or as part of illness. These often respond to atypical antipsychotics

Get CBCs weekly with clozapine due to rare bone marrow suppression.

Question 31

Non-medical therapies for Parkinson’s

Answer 31

Physical therapy or speech therapy may help patients, as can aids to ADLs (bed rails, bannisters, large-handled cuttlery)

Question 32

Rivastigmine

Answer 32

Cholinesterase inhibitor, may help cognitive impairment and psychiatric sx of Parkinson’s.

Question 33

Surgical treatment for Parkinson’s

Answer 33

Thalamotomy or pallidotomy may help pts who are unresponsive to medical tratment or cannot tolerate antiparkinson agents (eg diffuse vascular disease, cognitive decline). Ablation should be limited to one side. This is rarely done and has largely been displaced by brain stimulation.

Question 34

Brain stimulation

Answer 34

Another treatment for refractory Parkinson’s. High frequency stimulation of subthalamic nuclei or globus pallidus internus. Benefits all major features of disease.

Reserved for patients without cognitive impairmen tor psychiatric disorder who have a good response to levodopa but in whome dyskinesias or response fluctuations are problematic.

Takes 3-6 months of tx to achieve optimal results. Side effects: depression, apathy, impulsivity, executive dysfunction, decreased verbal fluency.

Question 35

Gene therapy in Parkinson’s

Answer 35

Injections of adeno-associated viruses encoding various genes have been tried in stage I and II trials.

Question 36

bromocriptine

Answer 36

D2 receptor agonist used to treat Parkinson