Term
| pharmacotherapy options for PD |
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Definition
increase dopamine synthesis (brain)
stimulation of dopamine release from presynaptic sites
direct stimulation of dopamine receptors
decreasing uptake of dopamine at presynaptic sites
decreasing dopamine catabolism |
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Term
| final steps in dopamine biosynthesis |
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Definition
[image]
TH = tyrosine hydroxylase
AADC = amino acid decarbosylase |
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Term
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Definition
[image]
2 main enzymes involved in the metabolism of dopamine: catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO)
COMT will only add the methyl group to the OH in the meta position
MAO oxidizes the carbon NEXT TO the amine group. amine group is eliminated and during the oxidation |
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Term
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Definition
inhibits the formation of dopamine from levodopa in the periphery to decrease ADRs and increase amount of levodopa that can enter the CNS
[image] |
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Term
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Definition
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Term
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Definition
[image]
COMT, AADC
NOT MAO!!! |
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Term
| dopamine agonists: ergot alkaloids |
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Definition
pergolide
bromocriptine
cabergoline |
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Term
| dopamine agonists: non-ergot alkaloids |
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Definition
apomorphine
ropinirole
pramipexole
rotigotine |
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Term
receptor affinity of pergolide
[image] |
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Definition
D2 receptor affinity
induces valvular heart disease; withdrawn in 2008 |
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Term
receptor affinity of cabergoline
[image] |
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Definition
D2 receptor affinity
used in the treatment of hyperprolactinemia |
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Term
receptor affinity of bromocriptine
[image] |
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Definition
D2 receptor agonist; D1 receptor antagonist/partial agonist
rapidly absorbed (oral administration)
low systemic bioavailability
the metabolites are excreted primarily in the bile and feces |
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Term
metabolism of bromocriptine
[image] |
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Definition
3 main metabolic reactions of bromomcriptine:
[image] |
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Term
| drug interactions with bromocriptine |
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Definition
dopamine antagonists: aggravate Parkinson's symptoms
highly plasma protein bound
substrate and weak inhibitor of CYP3A4 |
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Term
properties of apomorphine
[image] |
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Definition
aporphine alkaloid of the benzoquinoline class
highly lipophilic
poorly absorbed (oral)
completely absorbed (parenteral)
CSF
short plasma half life
significant degree of interpatient variability
does not have any opioid actiivty
structure is similar to DA |
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Term
apomorphine metabolism
[image] |
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Definition
[image]
sulfation
N-demethylation
glucuronidation
oxidation |
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Term
properties of pramipexole
[image] |
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Definition
rapid and good oral absorption
pharmacokinetic properties differ between men and women: AUC greater in women
minimal hepatic biotransformation
excreted unchanged in the urine (renal tubular secretion)
drug interactions: drugs excreted by renal tubular secretion
also used to treat restless leg syndrome |
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Term
receptor affinity of ropinirole
[image] |
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Definition
D2 agonist
rapidly absorbed after oral administration
rapidly and extensively distributed
low plasma protein binding
also used to treat restless leg syndrome |
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Term
metabolism of ropinirole
[image] |
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Definition
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Term
properties of rotigotine
[image] |
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Definition
silicone-based, self-adhesive matrix, transdermal system
90% bound to plasma proteins
low bioavailability by the oral route
excreted in the urine and feces
somnolence is a common adverse reaction |
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Term
metabolism of rotigotine
[image] |
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Definition
[image]
extensive metabolism |
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Term
properties of tolcapone
[image] |
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Definition
COMT inhibitor
rapidly absorbed after oral administration
highly bound to plasma albumin
low first pass metabolism
completely metabolized in the liver
acts in the brain and periphery
hepatotoxic |
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Term
properties of entacapone
[image] |
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Definition
COMT inhibitor
rapidly absorbed after oral administration
high plasma protein binding
acts mostly in periphery |
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Term
properties of selegiline
[image] |
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Definition
MAO-B inhibitor
readily absorbed from GI
well distributed and it penetrates the CNS
high apparent volume of distribution
extensive metabolism
transdermal delivery
drug interactions:
with fluoxetine may produce a "serotonin" syndrome
with meperidine could result in agitation, seizures, diaphoresis, and fever, which may progress to coma, apnea, and death
drug reactions may occur several weeks following withdrawal (takes a while for the enzyme to be reproduced) |
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Term
metabolism of selegiline
[image] |
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Definition
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Term
properties of rasagiline
[image] |
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Definition
MAO-B inhibitor
rapidly absorbed
plasma protein binding
inhibitors of the CYP1A2 may increase plasma concentrations of rasagiline up to 2 fold |
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Term
rasagiline metabolism
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Definition
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Term
| pharmacotherapy options for alzheimer's disease |
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Definition
acetylcholinesterase inhibitors
NMDA antagonists
secretase inhibitors
antioxidants
anti-inflammatory drugs
chelating agents |
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Term
| acetylcholinesterase inhibitors |
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Definition
rivastigmine
glantamine
donepezile
tacrine |
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Term
| mechanism for acetylcholinesterase hydrolysis |
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Definition
[image]
in the AChE active site the 3 main amino acids are serine, histadine, and glutamate
glutamate anchors the ACh (puts the molecule in the correct position)
the OH of serine attacks the carboxylic acid of ACh
the histadine serves as a base
the choline portion of ACh is eliminated and the enzyme becomes acetylated
water attacks the acetylated enzyme and the enzyme is regenerated as a free serine and an acetic acid |
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Term
properties of rivastigmine
[image] |
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Definition
centrally selective arylcarbamate
pseudo-irreversible: releases from the enzyme very slowly
forms a stable acetylated enzyme so the reaction does not continue further and the enzyme is no longer active
butyrylcholinesterase inhibitor as well as cholinesterase inhibitor
low hepatotoxicity |
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Term
properties of donepezil
[image] |
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Definition
centrally acting
selective for AChE
non-competitive
low hepatotoxicity
CYP2D6 and CYP3A4 |
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Term
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Definition
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Term
properties of tacrine
[image] |
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Definition
AChE
first one used for AD
non-selective
hepatotoxic |
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Term
properties of galantamine
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Definition
natural product
reversible and competitive
some activity on butyrylcholinesterase as well as AChE
CYP 2D6 and CYP3A4
reversible:
galantamine will leave the enzyme and the enzyme is free to start again
competitive:
galantamine will win with a higher dose
not competing for the same active site
galantamine acts at an allosteric site (not at the active site).
once it binds to the allosteric site, the conformation of the enzyme will change and become inactive |
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Term
metabolism of galantamine
[image] |
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Definition
[image]
O-demethylation
N-oxidation
glucuronidation
oxidation
N-demethylation |
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Term
properties of memantine
[image] |
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Definition
glutamate receptor antagonist
low affinity voltage-dependent non-competitive antagonist
binds with higher affinity than Mg
inhibit the prolong influx of Ca |
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