Parkinsons Flashcards
Levodopa
L-DOPA + carbidopa (Sinemet)
MOA:
L-dopa is transported across blood-brain barrier (same transporter in GI tract) and then into remaining SN DA-secreting neurons and converted to DA by aromatic amino acid decarboxylase (AADC)
Carbidopa blocks peripheral AADC
* always combined with L-DOPA
* prevents peripheral conversion to DA
* allows more L-DOPA to reach remaining DA neurons in
SN, but also other regions which can cause AEs
* reduces peripheral AEs mediated by DA
AEs:
Nausea/vomiting
Sleepiness/drowsiness (somnolence)
Headache
Dizziness
Orthostatic hypotension
Cardiac arrhythmias
Behavioral/psychiatric changes
hallucinations, agitation, confusion, psychosis
Dyskinesia (e.g. chorea)
Motor fluctuations
- “on/off” phenomenon
- “wearing off” phenomenon
Discoloration of urine, saliva, and sweat
Important Considerations:
- If patient doesn’t respond, probably not PD
- Drug of choice, especially in older patients (e.g., > 65 years old) or patients with more severe symptoms
- When starting, patients should take with food or snack to minimize N/V
- With more advanced disease and/or motor fluctuations, more effective if take on empty stomach and avoid high protein foods (amino acids compete with L-DOPA for transport
Entacapone
Tolcapone
COMT inhibitors
MOA: both inhibit peripheral COMT, preventing
metabolism of L-dopa to inactive metabolite 3-O- methyl dopa; significance of inhibition of central COMT
by tolcapone not clear
* allows more L-DOPA to reach remaining DA neurons in
SN, but also other regions which can cause AEs
* Combined with L-DOPA/carbidopa
AEs:
Increases L-DOPA AEs
Hepatotoxicity (tolcapone only)
- “l” for liver toxicity
Important Considerations:
- Ineffective when given alone but are useful L-DOPA
“extenders” in patients with motor fluctuations
Pramipexole
Ropinirole
Dopamine Agonists
MOA: stimulate DA receptors
- in the striatum, this bypasses the DA input
from the remaining SN neurons
AEs:
Similar to L-DOPA/carbidopa
- some less frequent than L-DOPA/carbidopa:
N/V, orthostatic hypotension, motor fluctuations and
dyskinesias
- some more frequent than L-DOPA/carbidopa:
adverse behavioral effects, somnolence
Disorders of impulse control
- compulsive gambling, shopping, eating, sexual behavior
Important Considerations:
- Used as monotherapy in younger patients (e.g., < 65
years old) or as an adjunct to L-DOPA/carbidopa
Trihexyphenidyl
Benztropine
Muscarinic Antagonists
MOA: block muscarinic receptors in the striatum
AEs:
“antimuscarinic”
xerostomia, blurry vision, constipation, urinary retention, impaired sweating, tachycardia
*Caution with BPH and narrow angle glaucoma
CNS
confusion, impairment of recent memory, hallucinations,
delusions
*Caution with older patients or patients with cognitive impairment
Important Considerations:
- Most useful for younger PD patients who have
resting tremor as predominant finding and preserved
cognitive function
Selegiline
Rasagiline
MAO-B Inhibitors
MOA: irreversible selective inhibition of MAO-B, which
decreases the oxidative metabolism of DA
Neuroprotective effects unclear
*Activation of selective DA neurotoxin MPTP to MPP+ requires MAO-B
*MAO-B inhibitors protect SN damage in animal models using MPTP
AEs:
Nausea
Orthostatic hypotension
Headache
Confusion
Hallucinations
Insomnia
Important Considerations:
- Have mild symptomatic benefit
- Often used in combination with L-DOPA/carbidopa and/or DA receptor agonists
Amantadine
NMDA Receptor Antagonist
MOA: Uncertain?
Blocking NMDA receptors may glutaminergic
transmission in BG (may help reduce L-DOPA
dyskinesias)
May DA release, block DAT, or stimulate DA
receptors
AEs:
Orthostatic hypotension
Dizziness
Confusion
Hallucinations
Insomnia
Nausea/vomiting
Livedo reticularis (rose-colored mottling of the skin)
- may be associated with peripheral edema
Important Considerations:
- Relatively weak PD drug with low toxicity that is most
useful for short-term use in early mild PD or later to
help with dyskinesias from L-DOPA/carbidopa therapy
