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Flashcards in Anti-Parkinsons Deck (15):
1

Classes of antiparkinsonian agents

-Dopamine precursor
-Dopamine agonists
-Monoamine Oxidase Inhibitor
-COMT inhibitor
-Cholinergic antagonist
-Antiviral

2

Dopamine precursor

L-DOPA/
carbidopa

3

L-DOPA/carbidopa MOA, uses, admin

-MOA: precursor to dopamine
if there is a severe loss of dopaminergic neurons, there will not be enough left to convert DOPA to dopamine
-ADMIN: dopamine does not cross the BBB but L-DOPA does (has both a positive and negative charge)
-only 1% of oral dose gets into brain b/c DOPA decarboxylase is found throughout body → so give L-DOPA with a peripheral DOPA decarboxylase inhibitor (carbidopa)
- L-DOPA rapidly absorbed from intestine; rate is influenced by gastric emptying rate, local pH, food
-drug holidays of 3-21 days may be used to manage some neurological and behavioral AE
-longest half life
-USE: first line drug for Parkinson’s
-most effective at diminishing bradykinesia

4

L-DOPA/carbidopa AE

-signs of improvement once therapy is begun may take several weeks
-first symptoms to improve are mood and vigor, then sense of well-being, then improvement in bradykinesia, akinesia, and then tremor
-tolerable doses diminish with time; efficacy diminishes with time
-all patients will develop side effects
Short-term effects:
-Anorexia, nausea, vomiting (↓ w/ Carbidopa, food, or divided doses. tolerance develops (chemoreceptor trigged zone in the medulla)
-Orthostatic hypotension (centrally mediated, ↓ w/ Carbidopa, tolerance develops)
Tachycardia (due DOPA → norepinephrine)
-advantages generally outweigh disadvantages
Long-term effects requiring alteration in dose:
-Dyskinesias (80% of pts get): facial grimacing, restless feet. may be fleeting or severely debilitating → w/ large doses → choreiform movements (involuntary jerks). titrate dose to prevent dyskinesia but provide relief. NO tolerance develops → previously well tolerated doses can begin inducing dyskinesias. Carbidopa may ↑dyskinesias
-Psychiatric, behavioral: nightmares, anxiety
- when ↑dose: paranoia, hallucinations, mania (overstimulation of dopamine receptors)
- aphrodisiac effect → improve mood
Response fluctuations (wearing-off, on/off phenomena)
- between dyskinesia and bradykinesia
- manage w/ dopamine agonists, alteration of diet, slow-release L-DOPA
-Drug interactions: pyridoxine (B6) is a cofactor for DOPA decarboxylase; but this vitamin should not have an effect in the presence of a peripheral DOPA decarboxylase inhibitor
-Do not administer with MAO A inhibitors → hypertensive crisis
-do not use in psychotic patients or patients with history of melanoma, and use extra care with patients who have open angle glaucoma, cardiac disease, peptic ulcer disease, or non-specific MAO inhibitors

5

Dopamine antagonists

Bromocriptine
Pramipexole, Ropinirole

6

Bromocriptine

-Class :Bromocriptine
-MOA: directly activates dopamine receptors at D2, D3
-Pharm/Admin: an ergot alkaloid
-admin orally, excreted in the bile and feces
-USE:-first line drug for Parkinson’s
-patients that are unresponsive to controlled release DOPA or used as a first line drug because there may be less dyskinesias
-may be used in combo with L DOPA
-at low doses also used to treat hyperprolactinemia
-restless leg
-AE: less chance of response fluctuations and dyskinesia
-hypotension, cardiac arrhythmias
-painful swollen feet, digital vasospasm, stroke or MI
-anorexia, nausea, vomiting (all reduced when taken with food)
-dyskinesia but less than L DOPA (related to the half life)
-hallucinations, mental confusion
-fibrosis of body organ membrane lining

7

Pramipexole, Ropinirole

-Class :Bromocriptine
-MOA: directly activates dopamine receptors
-Pramipexole D3>D2, Ropinirole D2, D3
-USE: first line Parkinson’s (same as above)
-restless leg
-AE: more likely to cause sudden sleep episodes
-CV side effects are reduced but hypotension is more common
-they also cause dyskinesia and hallucinations

8

Monoamine Oxidase Inhibitor

Selegine

9

Selegine

-Class: Monoamine Oxidase Inhibitor
-MOA: inhibits MAO B activation at low concentrations → retards the breakdown of dopamine and prolongs the effect of DOPA
-USE: Parkinson’s
-Depression
-used as an adjunctive therapy; may allow a DOPA dose reduction
-AE: since it’s a specific MAO B inhibitor, it can be used with L-DOPA
-may reduce mild on-off phenomena and wearing off phenomena
-in some patients enhances the AE of L-DOPA
-contraindicated in patients taking tricyclic antidepressants and serotonin uptake blockers and a meperidine

10

COMT inhibitor

Tolcapone, Entacapone

11

Tolcapone, Entacapone

-Class: COMT inhibitor
-MOA: Inhibits methylation of dopamine → they stabilize DOPA and make it more available to the brain
-USE: Parkinson’s → they increase the duration of the effect of each DOPA dose without increasing the peak level of DOPA
-may be useful in “wearing off” phenomenon
-AE: they are never used alone
-may have to reduce DOPA levels to minimize dyskinesias and other dopamine related side effects
-tolcapone requires frequent blood tests to monitor liver function (it causes liver toxicity so it isn’t used as much any more.

12

Cholinergic antagonist

Benztropine

13

Benztropine

-Class: Cholinergic antagonist
-MOA: Blockade of muscarinic receptors on interneuron in the caudate
-USE: Parkinson’s → improves rigidity/tremor and only has a minor effect on bradykinesia
-AE: CNS (drowsiness, restlessness, hallucination, dyskinesias)
-AE may be additive with other drugs that have anti-muscarinic properties
-avoid use in prostatic hypertrophy, obstructive GI disease and glaucoma

14

Antiviral

Amantidine

15

Amantidine

-Class: antiviral
-MOA: Stimulate dopamine release blockade of NMDA receptors
-it’s an antiviral drug that causes dopamine release in the striatum and may also block muscarinic and/or glutamate receptors
-USE: Parkinson’s → used in initial treatment or late treatment to control L-DOPA induced dyskinesias (benefit may be transient)
-Influenza A
-AE: CNS (restlessness, agitation, hallucination)
-livedo reticularis (peripheral vascular condition – reddish blue skin)
-peripheral edema
-avoid use in patients prone to seizure and who have CHF