Movement Disorder Drugs Flashcards
What two enzymes prevent dopamine distribution to the brain?
- COMT - degrades to inactive product
2. DOPA decarboxylase - dopamine product (dopaminergic side effects in periphery)
Why do you give carbidopa with levodopa?
1) Peripheral inhibitor of DOPA decarboxylase - reduces peripheral side effects
2) Increases oral bioavailability (more is able to reach the CNS)
Why give levodopa instead of dopamine?
LDOPA can cross BBB
Function of PD drugs
1) Increase dopaminergic function
2) Inhibit cholinergic function
How does inhibiting cholinergic function help movement disorders?
Addresses the dopamine/acetylcholine imbalance in the indirect pathway
Two types of ways PD drugs can lose efficacy
1) Wearing off
2) On-Off Effect
Wearing off
Mobility declines after a few hours of each dose
On-Off Effect
Appears later than wearing off, not correllated with drug regimen
What are adverse effects of levodopa
1) Prone to motor fluctations
2) N/V
3) Postural hypertension (B receptor)
4) Arrythmias (B receptor)
5) dyskinesias with chronic use
6) GI issues
When do you give dopamine agonists?
1) Monotherapy early in disease
2) Adjunct later in disease to smooth out fluctuations and reduce levodopa dose
Pramipexole
- selective D2 receptor agonist
- similar adverse effects as LDOPA (daytime sleepiness)
- excreted unchanged by kidney
Ropinirole
- metabolized in liver (CYP1A2)
- risk of interaction with caffeine and warfarin
When do you give apomorphine
- rescue drug
- limited to termination period when no other drugs work
- relative non-selective agonist against DA receptors
Apomorphine side effects
SEVERE nausea, CV (angina, syncope, orthostatic HTN), CNS (confusion, somnolence, hallucinations)
MAO-B Inhibitors
Irreversible inhibitors -> must synthesize more to overcome
Use of MAO-B
1) monotherapy early in disease
2) adjunts to reduce fluctuations and reduce LDOPA dosage
MAO-B Inhibitors
1) Selegiline
2) Rasagiline
MAO-B Inhibitors Adverse Effects
Serotonin syndrome (with SSRIs or meperidine) at high doses
Selegiline metabolites?
- amphetamine and methamphetamine metabolites (insomnia and confusion)
- hypertensive crisis with dietary tyramine interaction
Rasagiline
1) more selective for MAO-B receptors
2) effective monotherapy
3) no amphetamine metabolites
Amantadine
antiviral (anticholinergic)
Uses of amantadine
Monotherapy for PD (rel benign) for mild symptoms
What drugs induce parkinsonianism?
1) Antipsychotic treatments block D2 receptors
2) Poisoning by MPTP
How do you administer apomorphine
Subcut
