Anti-PD and Movement Disorders Flashcards
Carbidopa/levodopa General Principles
L-dopa is readily absorbed from GI Tract, Crosses the BBB, is decarboxylated to form DA, Carbidopa prevents peripheral decarboxylation, Secreted in urine
Purpose of Carbidopa
Without Carbidopa most of L-dopa converted in periphery to NE and adrenaline
Advantages of L-dopa/Carbidopa
Increases life span, Bradykinesia, rigidity and tremor respond immediately, Flat affect and shuffling gait - less responsive
Side Effects of L-dopa/Carbidopa
Beta Adrenergic Effects (tachycardia, cardiac arrhythmias, hypertension), Orthostatic Hypotension, GI effects, and Tolerance
L-dopa and Vitamin B6
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
Major SEs of L-dopa/Carbidopa
“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
Direct Dopamine Agonists (ergot derivatives)
Bromocriptine and Pergolide
Direct Dopamine Agonists (non-ergot derivatives)
Pramipexole and Ropinirole and Apomorphine (preferred over ergot derivatives)
Bromocriptine
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)
Pergolide
Withdrawn from market due to heart valve regurgitation
Pramipexole
D2 receptor agonist. Most effective in early mono-therapy, but also used in adjunctive therapy: its reduces L-DOPA “on-off” effects by ~25%
Ropinirole
D2 receptor agonist. Most effective in early mono-therapy with good GI absorption (~to Pramipexole), but also used in adjunctive therapy.
Selegiline (drug type and MOA)
MAO-B inhibitor - prevents catabolism of DA and enhances DA in brain
Selegiline (clinical use)
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
Selegiline (drug contraindications)
- 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
COMT inhibitors
Tolcapone and Entacapone
COMT inhibitors primary use
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
Tolcapone
inhibits CNS and peripheral COMT
Entacapone
inhibits peripheral COMT only
COMT inhibitors benefits
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)
Amantadine General info
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
Amantadine Benefits
Relatively effective to attenuate dyskinesia and motor fluctuations (esp. bradykinesia); specifically used in those with early-onset PD (young population)
Amantadine Short-fall
Not effective to attenuate PD tremor; Toxicity= ataxia
What drugs are contraindicated in females who are pregnant or breast-feeding?
Direct acting agents: Bromocriptine, Pramipexole, and Ropinerole
Amantidine (anti-viral)
What drugs might give you depression, anxiety, and hallucinations?
Direct acting agents: Bromocriptine and Pramipexole & Ropinirole (mostly hallucinations)
What do we use to treat Tourette’s Syndrome?
Neuroleptics–> Haloperidol
Alpha-2 agonists: Clonidine (pt must have normal BP)
SSRIs: fluoxetine
What do we use to treat ALS?
Baclofen (GABA agonist)
Riluzole (reduces glutamate release)
What do we use to treat Benign Essential Tremor?
Primidone (anti-convulsant); abuse potential
What drug is contraindicated for Tourette’s Syndrome?
Stimulant medications, e.g. methylphenidate (Ritalin)
How do we treat dystonias?
Botulinum toxin (botox)