Anti-PD and Movement Disorders

Question 1

Carbidopa/levodopa General Principles

Answer 1

L-dopa is readily absorbed from GI Tract, Crosses the BBB, is decarboxylated to form DA, Carbidopa prevents peripheral decarboxylation, Secreted in urine

Question 2

Purpose of Carbidopa

Answer 2

Without Carbidopa most of L-dopa converted in periphery to NE and adrenaline

Question 3

Advantages of L-dopa/Carbidopa

Answer 3

Increases life span, Bradykinesia, rigidity and tremor respond immediately, Flat affect and shuffling gait - less responsive

Question 4

Side Effects of L-dopa/Carbidopa

Answer 4

Beta Adrenergic Effects (tachycardia, cardiac arrhythmias, hypertension), Orthostatic Hypotension, GI effects, and Tolerance

Question 5

L-dopa and Vitamin B6

Answer 5

Vit B6 Is a Cofactor for Decarboxylation of L-Dopa–>

Vit B6 Enhances Conversion of L-Dopa to DA in Periphery–> less drug to cross BBB

Question 6

Major SEs of L-dopa/Carbidopa

Answer 6

“Wearing-off” or “on-off” effects due to receptor supersensitivity, “Peak dose” side effects (grimacing and dyskinesia), Behavioral side effects (psychosis, confusion, hallucinations), and Dementia

Question 7

Direct Dopamine Agonists (ergot derivatives)

Answer 7

Bromocriptine and Pergolide

Question 8

Direct Dopamine Agonists (non-ergot derivatives)

Answer 8

Pramipexole and Ropinirole and Apomorphine (preferred over ergot derivatives)

Question 9

Bromocriptine

Answer 9

D2 receptor agonist and D1 receptor antagonist, adjunctive therapy with L-DOPA because it only works in patients responsive to L-DOPA
Negative side effect: Orthostatic hypotension and cardiac arrhythmias (don’t see this with the non-ergot derivatives)

Question 10

Pergolide

Answer 10

Withdrawn from market due to heart valve regurgitation

Question 11

Pramipexole

Answer 11

D2 receptor agonist. Most effective in early mono-therapy, but also used in adjunctive therapy: its reduces L-DOPA “on-off” effects by ~25%

Question 12

Ropinirole

Answer 12

D2 receptor agonist. Most effective in early mono-therapy with good GI absorption (~to Pramipexole), but also used in adjunctive therapy.

Question 13

Selegiline (drug type and MOA)

Answer 13

MAO-B inhibitor - prevents catabolism of DA and enhances DA in brain

Question 14

Selegiline (clinical use)

Answer 14

Early mono-therapy or in combination with L-DOPA, Improves cognitive functions associated with PD (early stages), Adjunctive therapy when L-DOPA effects start to decline

Question 15

Selegiline (drug contraindications)

Answer 15

• Tricyclic anti-depressants and SSRIs due to risk of serotonin syndrome (hyperthermia, confusion, myoclonus, CV collapse, flushing, diarrhea, and seizures)
• MAO-A inhibitors due to risk of hypertensive emergency

Question 16

COMT inhibitors

Answer 16

Tolcapone and Entacapone

Question 17

COMT inhibitors primary use

Answer 17

Primary use in patients whose have received prolonged L-DOPA/Carbidopa treatment for 5-7 years + motor side effects induced by L-DOPA, Effective in patients that develop “freezing”, Primary use to ameliorate peak dose dyskinesia

Question 18

Tolcapone

Answer 18

inhibits CNS and peripheral COMT

Question 19

Entacapone

Answer 19

inhibits peripheral COMT only

Question 20

COMT inhibitors benefits

Answer 20

Reduce L-DOPA-induced motor side effects, Attenuates the “wearing-off” time, Reduce the clearance of L-DOPA by enhancing its bioavailability, and Enable lowering the dose of L-DOPA by 25-30% (Tolcapone)

Question 21

Amantadine General info

Answer 21

anti-viral agent (against influenza A and rubella) to treat PD bradykinesia and ridigity

• May increase dopamine release or block re-uptake
• Anticholinergic action: muscarinic receptor antagonist
• NMDA receptor antagonist

Question 22

Amantadine Benefits

Answer 22

Relatively effective to attenuate dyskinesia and motor fluctuations (esp. bradykinesia); specifically used in those with early-onset PD (young population)

Question 23

Amantadine Short-fall

Answer 23

Not effective to attenuate PD tremor; Toxicity= ataxia

Question 24

What drugs are contraindicated in females who are pregnant or breast-feeding?

Answer 24

Direct acting agents: Bromocriptine, Pramipexole, and Ropinerole
Amantidine (anti-viral)

Question 25

What drugs might give you depression, anxiety, and hallucinations?

Answer 25

Direct acting agents: Bromocriptine and Pramipexole & Ropinirole (mostly hallucinations)

Question 26

What do we use to treat Tourette’s Syndrome?

Answer 26

Neuroleptics–> Haloperidol
Alpha-2 agonists: Clonidine (pt must have normal BP)
SSRIs: fluoxetine

Question 27

What do we use to treat ALS?

Answer 27

Baclofen (GABA agonist)

Riluzole (reduces glutamate release)

Question 28

What do we use to treat Benign Essential Tremor?

Answer 28

Primidone (anti-convulsant); abuse potential

Question 29

What drug is contraindicated for Tourette’s Syndrome?

Answer 29

Stimulant medications, e.g. methylphenidate (Ritalin)

Question 30

How do we treat dystonias?

Answer 30

Botulinum toxin (botox)