Parkinson's (2Q) Flashcards
Parkinsonism: Essentials of Diagnosis
Any combination of tremor, rigidity, bradykinesia, and progressive postural instability. May include cognitive impairment.
Parkinsonism: Epidemiology
Equally affects all ethnicities and has equal sex distribution.
Parkinson’s: Pathophysiology
dopamine depletion due to degeneration of dopaminergic nigrostriatal system leads to an imbalance of dopamine (not enough) and Ach (too much) @ the striatum.
In general, how do pharmacologic approaches to Parkinsonism work?
Symptomatic only (not disease altering). Rebalance the dopaminergic and cholinergic stimulation of the striatum by either increasing dopamine or blocking cholinergic stimulation.
Parkinsonism: clinical presentation
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.
Parkinsonism DDx: old age
mild hypokinesia and slight tremor in isolation are common in old age.
Parkinsonism DDx: depression
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.
Parkinsonism DDx: Wilson disease
Wilson will have earlier age of onset, will have other abnormal movements, Kayser-Fleischer rings, and chronic hepatitis (inc. copper in tissues).
Parkinsonism DDx: Huntington’s disease
Huntington’s may present with rigidity and bradykinesia but should also have family Hx and dementia.
Parkinsonism DDx: multisystem atrophy
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.
Parkinsonism DDx: progressive supranuclear palsy
Bradykinesia and rigidity are accompanied by supranuclear disorder of eye movements, pseudobulbar palsy (difficulty controlling facial expressions), emotional lability, and axial dystonia.
Parkinsonism DDx: Jakob-Creutzfeldt disease
parkinsonism+dementia, myoclonic jerking, ataxia, and pyramidal signs (spasticity, hyperactive reflexes, a loss of the ability to perform fine movements, and Babinski sign)
Parkinsonism DDx: corticobasal degeneration
asymmetric parkinsonism accompanied by conspicuous signs of cortical dysfunction (apraxia-disorder of motor planning, sensory inattention, dementia, aphasia)
When should medical treatment be considered for Parkinson’s?
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.
Amantadine
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.
Levodopa- mechanism
Converted to dopamine (most peripheral) and improves all major symptoms, including bradykinesia.
L-dopa side effects
nausea, vomiting, HTN, arrhythmias.
Later in course of use: dyskinesias, restlessness, confusion , behavioral changes. “on-off” phenomenon.
What is the “on-off” phenomenon?
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.
Carbidopa
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).
carbidopa-levodopa (Sinemet)
combination of L-dopa and carbidopa, in fixed formulation.
Diet changes for Parkinson’s treatment
Limit protein intake to recommended minium, and try to take it with the last meal of the day.
L-Dopa: CI
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.
Pramipexole and ropinirole
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.
Dopamine agonist side effects
fatigue, somnolence, nausea, peripheral edema, dyskinesias, confusion, postural hypotension, desire to sleep at hazardous times.
