parkinson's Flashcards
l-DOPA (Larodopa; Sinemet)
l-DOPA plus Carbidopa (Sinemet), Parcopa
l-DOPA plus Carbidopa plus Entacapone (Stalevo)
Dopaminergic Agents
precursor, converted to dopamine in dopamine neurons in CNS
(dopamine itself does not cross BBB + has CV effects)
Bromocriptine (Parlodel)
Dopaminergic Agent
ergo derivative, act as non-sp DA rec agonists
less effective than l-DOPA but can be used when not tolerated, dec. “on-off” phenomenon, can be used in combo with l-DOPA
SEs: N/V, post hypotns, mental disturbs, endocrine disturbs: inhib prolactin secretion
*used to be used to tx ammenorrhea and galactorrhea assoc. with hyperprolactinemia, caused psych rxns and seizures
use Carbergoline instead
Pramipexole (Mirapex)
Dopaminergic Agent
stimulates post-synaptic dopamine receptors
Non ergot
antioxidant and neuroprotecitive effects, may slow disease progression
“restless leg syndrome”
Ropinirole (Requip)
Dopaminergic Agent
not effective at symptom control as L-Dopa
FLD and add-ons
similar to Dopa
stimulates post-synaptic dopamine receptors (D2, D3)
Amantadine (Symmetrel)
Dopaminergic Agent
causes release of DA
anti-influenza(viral)
stim. rel of DA from nerve endings
L-D>aman>antichol.
SEs: mental disturbs, hyperexcita., ataxia, confusion, convulsions, choreiform movements
excr. in kidney, adjust for pts with imp. renal function
Selegiline/Deprenyl (Eldepryl, Zelapar)
MAO-B Inhibitor
inhib. L-dopa brkdwn
used in later stages of park.
dec. “on-off”
SE: like l-DOPA, less sev.: choreiform movements, tremor, dyskinesias, hallucinations, agitation, behavior changes, nausea, wl, “cheese toxicity” at high doses
Rasagiline (Azilect)
MAO-B Inhibitor
inhibit L-dopa breakdown
used in early and late stages
SE: like l-DOPA, less sev.:
choreiform movements, tremor, dyskinesias, hallucinations, agitation, behavior changes, nausea, wl, “cheese toxicity” at high doses
Entacapone (Comtan)
COMT Inhibitor
inhibits dopamine metabolism
Stalevo: combo product: l-DOPA + carbidopa + entacapone
Benztropine (Cogentin)
Antimuscarinic Agent (centrally acting)
("remove weight from ACh side, enhancing DA side")Trihexyphenidyl (Artane)
Antimuscarinic Agent (centrally acting)
Diphenhydramine (Benadryl)
Antihistamine (centrally acting)
(blocks muscarinic as well, enhances DA)
used in ER
disturbances in Parkinsons
Autonomic Disturbances (sweating, difficulty in swallowing, drooling, etc…)
Apathy, Social Withdrawal, Cognitive Impairment, Dementia
classification of parkinsonism
primary/Idiopathic: death of dopaminergic neurons in the nigrostriatial dopamine pathway
Iatrogenic (anti emetics, antipsychotics-block DOPA rec in striatum)
secondary: post traumatic, post encephalitic, or atherosclerotic
damage striatal pathway
pathway
substantia nigra–>dopamine containing neurons–>striatum
dopamine: inhibitory
ACh: excitatory
balance
between dopamine and acetlycholine
too little DA, parkinsonism
-blockade of DA receptors or degeneration of striatal pathway?
too little ACh, GABA: choreiform moevents
drug-induced parkinsonism: resolve?
tx??
yes, some may take a day
tx to alleviate pt w. benadryl: antihistamine, blocks muscarinic rec.
parkinsons drug SEs
choreiform type movements (tilted see-saw other way)
drugs to not cure disease, tx symptoms
MPTP oxidized to ??? in parkinson’s via ??
to what effect??
MPP+ via MAO-B
MPP+ is (toxic) destroys nigrostriatal dopamine neurons
Parkinson’s: genetic?
weak genetic, mostly aging and environmental
GABA antagonists not used for Parkonsinism
cause seizures
Huntington’s chorea
aut. dom, mid 30s, motor
DA-antagonist
Cholinesterase inhibitors
benzodiazepines (enhance GABA)
L-dopa used in combo with…
Carbidopa:
inhib. L-dopa conversion in periphery, does not enter CNS
L-dopa(via DOPA decarboxylase)–>Dopamine (some may happen in periphery even tho we want in CNS)
L-dopa SEs: GI
N/V, triggers CRTZ, tolerance may develop
CRTZ is outside BBB, administering with carbidopa helps
L-dopa tx as disease progresses
less pronounced effect
does not halt progression
L-dopa SE: CV
hypotensn
tachy
arrythmias
*carbidopa helps dec. freq/sev, but still use caution in pts with existing CV disease
L-dopa SE: CNS
depression, psychotic reactions, hallucinations, exacerbation of psychoses, nightmares, euphoria, mood and personality changes
increased libido, release of inhibitions, compulsive behavior
more common w. combo prep
take “drug holidays” or lower dose
use ?? for managing L-dopa psych SEs
atypical antipsychotic clozapine (Clozaril)
*only one that doesn’t cause extrapyrimadal motor problems
Clozapine (Clozaril) is associated with…
agranulocytosis -monitor!
end of dose phenomenon
decline in blood levels of l-DOPA near the end of the dosage interval
show sudden parkinsonism after good period
on-off phenomenon
can occur at any time in the dosage interval and appears to be related to the progression of the disease
v. worrisome
* use sustained release prep or add DA agonist +/- COMT inhibitor to regimen*
L-Dopa SE: endocrine
dec. prolactin secretion
used to be used for women who choose not to breast feed
L-Dopa contraindications
cardiac arrhythmias psychosis melanoma glaucoma active peptic ulcer disease
L-dopa drug interaction
pyridoxine:enhancement of extracerebral metabolism decreases therapeutic effects
antipsychotics (DA antagonists)
MAO inhibitors: HTN crisis (not when MAO-B inhibs used @ approp. dose)
tricyclic antideps. : HTN crisis
mild-mod parkinsons tx
L-Dopa most effective
amantadine, dopamine agonist, MAO-B inhibitors or anticholinergics,
pramipexole and ropinirole (becoming pop. FLDs)
mod-sev parkinsons tx
L-Dopa and carbidopa +/- entacapone
non-responsive pts tx
add a dopamine agonist, seligiline, amantadine or anticholinergics
L-dopa and carbidopa tx: early in course?
recommended by some, others recommend DA agonist (pramipexole)
Huntington’s tx
decreasing dopaminergic activity
(antipsychotics) or enhancing the effects of GABA (benzodiazepines) or acetylcholine (physostigmine, rivastigmine) (BOARDS stuff)
seligeline for early use?
not approved, use rasaligine
L-dopa misc. effects
glaucoma gout hot flashes taste/smell disturbs elev. of liver enzymes \+ Coomb's test blood dyscrasias exacerbation of malignant melanoma
Ropinirole and Pramipexole SEs
choreiform, dyskinetic movements
nausea
dizzness, confusion, sedation, behav. changes, hallucinations
iatrogenic park. tx
stop/dec. drug, add anticholinergic for rapid reversal
