Movement disorders pharm Flashcards
dopamine agonists (DA)
bromocriptine pramipexole ropinirole rotigotine apomorphine
monoamine oxidase inhibitors
rasagiline
selegiline
COMT inhibitors
entacapone
tolcapone
antimuscarinic agents
benztropine biperiden orphenadrine procyclidine trihexyphenidyl
levodopa MOA
agonist at D2R
levodopa PK
take 30-60min before meals
only 1-3% reaches brain
combo w/carbidopa reduces peripheral meta of levodopa
levodopa GI
w/o 80% experience anorexia, nausea, and vomiting
levodopa CV
postural hypotension
tachycardia, ventricular extrasystoles, rarely afib
d/t increased peripheral catecholamines
HTN can occur w/large doses
levodopa behavioral
depression anxiety agitation insomnia somnolence confusion delusions hallucinations nightmares euphoria more common w/combo
levodopa dyskinesia
80% of pt taking drug >10yrs
wearing off phenomenon
each dose of L-dopa effective for 1-2hrs with rapid return of rigidity and akinesia
on-off phenomenon
marked akinesia alternating with improved movement with no coordination to timing of drugs
DDIs levodopa
Pyridoxine- increases extracerebral metabolism may prevent therapeutic effect unless peripheral decarboxylase inhibitor
MAOIs-HTN, do not give if taking MAOIs or w/in 2 wks of discontinuation
DA MOA
act directly on postsynaptic DRs
do not require enzymatic conversion
no potentially toxic metabolites
do not compete w/another substance for transport across BBB
uses of DAs
certain pts respond better to certain drugs
1st line therapy for parkinsons
use is associated w/less fluctuations and dyskinesias then L-dopa
generally those who do not respond to L-dopa do not respond to DAs
can be added to L-dopa
bromocriptine
ergot alkaloid derivative
D2 agonists
extensive first pass
can also be used for endocrine disorders
pramipexole
D3Rs
renal insufficiency- must be dose adjusted
RLS
ropinirole
D2Rs
RLS
rotigotine
DA
may have serious site application rxns
DA GI
anorexia, nausea, vomiting (should be taken w/meals)
DA CV
postural hypotension ergot derivatives (bromocriptine)- painless digital vasospasm
DA dyskinesias
dose dependent
DA mental disturbances
confusion, hallucinations, delusions
disorders of impulse control
DA misc ADRs
HA, nasal congestion
increased arousal
pulmonary infiltrates, pleural and retroperitoneal fibrosis
pramipexole and ropinirole can cause pts to fall asleep at inappropriate times
DA CIs
history of psychotic illness, recent MI, active peptic ulcer disease ergot derivatives (bromocriptine)- should be avoided in peripheral vascular disease
MAO types
monoamine oxidase A- metabolizes NE, serotonin, and dopamine
monoamine oxidase B- metabolizes dopamine selectively
selegiline MOA
selective inhibitor of MAO B decreasing dopamine breakdown
selegiline uses
adjuct for declining effectiveness of L-dopa
should be taken and breakfast and lunch to prevent insomnia
rasagiline MOA
irreversible inhibitor MAO-B
more potent then selegiline
rasagiline uses
neuro-protective and early parkinsons
MAOI DDIs
non-selective MAOIs should not be combined w/L-dopa b/c can cause HTN crisis cannot be combined w/: -meperdine -tramadol -methasone -propoxyphene -cyclobenzaprine -st. johns wort -dextropmethorphan -OTC cold preps
COMT inhibitors
inhibitions of dopa decarboxylase is associated w/compensatory activation of other pathways of L-dopa metabolism, especially COMT which increases 3-O-methyldopa which competes w/L-dopa to cross BBB
COMT inhibitors MOA
prolong action of L-dopa by diminishing peripheral metabolism
uses of COMT inhibitors
pts who have developed response fluctuations
tolcapone- central and peripheral effects
entacpone- peripheral only
COMT inhibitors ADRs
related to increased L-dopa diarrhea abdominal pain orthostatic hypotension sleep disturbances orange urine tolcapone- rare acute hepatic failure
apomorphine MOA
potent non-ergot dopamine agonists
post synaptic D2R in caudate and putamen
uses of apomorphine
temporary relief (rescue) of off perioids
ADRs of apomorphine
nausea at drug initiation
can preTx with trimethobenxamide
dyskinesias, drowsiness, sweating, hypotension, injection site bruising
amantadine MOA
antiviral
unclear, but may potentiate dopamangeric fnx
uses of amantadine
less efficasious then L-dopa
benefits short lived (wks)
may favorably impact bradykinesia, rigidity, tremor
may help reduce iatrogenic dyskinesias in advanced disease
amantadine ADRs
restlessness, depression, irritability, insomnia, agitation, excitement, hallucinations, and confusion, as well as HA, heart failure, postural hypotension, urinary retention, and GI disturbances
may cause livedo reticularis
amantadine CIs
Hx of seizures or heart failure
antimuscarinic MOA
centrally actin, mAChR antagonists
antimuscarinic use
may improve tremor and rigidity of parkinsonism, but little effect on bradykinesia
antimuscarinic ADRs
common peripheral antimuscarinic effects:
sedation, mental confusion, constipation, urinary retention, blurred vision
parkinson’s disease
dopaminergic therapy early stage
avoid Tx until disability
start w/one of these: rasafiline, amantadine, and antimuscarinic
w/progression switch to DA +/- carbidopa-levodopa
end-stage ass COMT inhibitor
tremor
beta blockers antiepileptic drug primidone (small dose) topiramate alprazolam botulinum toxin A
Huntingtons Tx
reserpine and tetrabenzine to deplete dopamine stores
block DRs: olanzapine, pehnothiazine, butyrophenones,
can also use: GABA, glutamic acid decarboxylase, and choline acetyltransferase
Tics
ANTIPSYCHOTICS
alpha adrengerics
botulinum toxins
RLS
DAs levodopa diazepam clonazepam opitates
wilsons disease
penicillamine
potassium disulfide
penicillamine MOA
chelating agent
penicillamine ADRs
nausea, vomiting, neprhotic syndrome, myastehnia, optic neuropathy, blood disorders
potassium disulfide
reduces intestinal absorption of Cu
