L9- Parkinson's Disease Treatment (others) Flashcards
list the dopamine receptor agonists (indicate which type is used more and why)
Ergots: bromocriptine (D2 agonist)- not used b/c way more AEs
Nonergots: pramipexole, ropinirole, rotigotine (trans-dermal form)
what are the advantages of using dopamine agonists in comparison to levodopa
- it does not require conversion by active dopamine neurons, so the functional capacity Nigrastriatal pathway is not a factor — works better for advanced PD
- longer half-lives, dec dose frequency
______ is a dopamine agonist that can be given by TD administration
rotigotine- nonergot dopamine agonist, used once a day
name and describe the use of Nonergot Dopamine Agonists
Pramipexole, Ropinirole:
- increasing use as initial Tx (instead of levodopa adjunct)
- important in younger Pts as older Pts are more vulnerable to cognitive AEs
Dopamine Agonist AEs:
- (1) GI
- (2) CVS
1- anorexia, n/v, constipation, dyspepsia; bleeding from peptic ulceration
2- postural hypotension, cardiac arrhythmias, peripheral edema
Dopamine Agonist AEs: neurological
- dyskinesia: abnormal movements
- mental disturbances: confusion, hallucinations, delusions
- dopamine dysregulation syndrome = impaired impulse control
Dopamine Agonist AEs: miscellaneous by subtype
Ergots: HA, nasal congestion, inc arousal, pulmonary infiltrates, pleural / retroperitoneal fibrosis, erythromelalgia, painless digital vasospasm, cardiac valve fibrosis
Nonergots: uncontrollable somnolence (stop med if this occurs)
list the Dopamine agonist contraindications
- psychosis
- recent MI
- PVD
- PUD
Apomorphine:
- (1) MOA
- (2) explain how to avoid important AE
- (3) other AEs
1- dopamine receptor antagonist
2- pretreat with Trimethobenzamide (anti-emetic) to prevent vomiting
3- QT prolongation, dyskinesia, drowsiness, sweating, hypotension
______ are the inhibitors of dopamine metabolism
- MAOIs
- COMT inhibitors
list the useful MAOIs, explain MOA
**MOA: selective MAO-B inhibitors (MAO-B breakdown dopamine and tyramine) – [used as ADJUNCTs]
Selegiline: dec dopamine breakdown in brain –> enhances levodopa effects (allows for dec dose)
Rasagiline: enhances levodopa effect
what is the main difference between Selegiline and Rasagiline
Both are MAO-B inhibitors
- Selegiline –> metabolized to methamphetamine / amphetamine => insomnia, confusion in elderly
- Rasagiline –> not metabolized to amphetamines
list the COMT inhibitors and why which are chosen over the others
Tolcapone:
- preferred MOA b/c CNS and periphery
- not preferred b/c causes fulminating hepatic necrosis
- Entacapone:
- only periphery MOA
- *preferred b/c no AE
what are the main useful effects of COMT inhibitors
- dec levodopa metabolism
- dec plasma [3-O-methyldopa]
- inc uptake levodopa
- inc dopamine in the brain
(1) is the antiviral that has antiparkinsonian actions. (1) has a (2) MOA and is used specifically for (3) in PD.
1- amantidine
2- unclear MOA
3- levodopa-induced dyskinesias
what are the general effects of Amantidine in terms of PD
- high doses inc release and dec reuptake of dopamine
- upregulates D2 receptors
- NMDA antagonist
Amantidine:
- (1) common neuro AEs + (2) at high doses
- (3) common cardiac AE
- (4) less common AE that clears w/in a month of drug withdrawal
1- restlestness, agitation, confusion, hallucinations
2- acute toxic psychosis
3- peripheral edema (responds to diuretics), used with caution for patients with h/o HF, seizures
4- Livedo Reticularis: mottled reticulated vascular pattern that appears as a lace-like purplish discoloration of the skin
Amantidine:
- (1) common neuro AEs + (2) at high doses
- (3) common cardiac AE
- (4) less common AE that clears w/in a month of drug withdrawal
1- restlestness, agitation, confusion, hallucinations
2- acute toxic psychosis
3- peripheral edema (responds to diuretics), used with caution for patients with h/o HF, seizures
4- Livedo Reticularis: mottled reticulated vascular pattern that appears as a lace-like purplish discoloration of the skin
list the Antimuscarinics used to help treat PD + include MOA
(tertiary amines)
- benzotropine
- trihexylphenidyl
-inhibits excitatory cholinergic interneurons in Striatum
what are the effects of antimuscarinics in PD
- adjuvant therapy
- to improve tremor and rigidity
- little effect on bradykinesia
Antimuscarinic AEs (in PD)
mood changes, confusion, hallucinations
xerostomia, pupillary dilation
urinary retention
Antimuscarinic contraindication (in PD)
glaucoma
BPH
pyloric stenosis
