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4.15 Movement Disorders
By Dr. Winsauer
48
Pharmacology
Professional
04/15/2012

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Term
What are the known causes of parkinsonisms that are not age reated?
Definition
brain disease or injury (tumors, trauma, encephalitis), and exposure to environmental toxins such as carbon monoxide and manganese
Term
Describe the neurochemical imbalance of parkinson's disease.
Definition
imbalance between the inhibitory effects of DA and the opposing stimulatory effects of ACh in the extrapyramidal system adn basal ganglia
Term
What are the different drugs given to directly replace DA?
Definition
levodopa, carbidopa or benserazide, cabidopa/levodopa
Term
Why can't you give dopamine to treat parkinsons?
Definition
DA itself does not cross the blood-brain barrier so you give precursors to dopamine
Term
What is the oral bioavailability of levodopa?
Definition
can be given orally and crosses the BBB but 90% is destroyed in the gut
Term
What is another name for carbidopa?
Definition
benserazide
Term
What is the MOA of carbidopa?
Definition
inhibit DOPA decarbaxylase, the enzyme which converts levodopa to DA
Term
Why is it beneficial to give carbidopa/levodopa together?
Definition
a greater amout of DA leaves the gut and is thereofre available for transport to the brain
Term
What converts tyrosin to DOPA?
Definition
tyrosine hydroxylase
Term
What converts DOPA to dopamine?
Definition
aromatic amino acid decarboxylase
Term
What converts dopamine to norepinephrine?
Definition
dopamine beta hydroxylase
Term
What converts norepinephrine to epinephrine?
Definition
phenylethanolamine-N-methyltransferase
Term
What is the MOA of amantadine?
Definition
DA releaser
Term
When should amantadine be given?
Definition
early in disease course; not affective in advanced stages when stored pools of DA are low
Term
Name agonists at the postsynaptic DA receptor.
Definition
bromocriptine, pergolide, pramipexole, ropinirole
Term
Which DA receptor agonists are ergot derivatives?
Definition
bromocriptine and pergolide
Term
What's the difference between using DA direct replacement and agonists at post synaptic DA receptors?
Definition
DA agonists produce a greater incidence of psychiatric symptoms than L-DOPA
Term
What is the MOA of COMT inhibitors?
Definition
inhibit catechol-O-methyltransferase, an enzyme that is responsible for degrading dopamine
Term
Name some COMT inhibitors.
Definition
entacapone, tolcapone
Term
What is the MOA of selegiline?
Definition
MAO type B inhibitors
Term
What do you use after response to combination of carbidopa/levodopa begins to deteriorate?
Definition
selegiline
Term
What are the metabolites of selegiline?
Definition
amphetamine and methamphetamine
Term
Name some anticholinergics that can be used to treat parkinson's disease?
Definition
trihexlphenidyl and benztropine
Term
What is the MOA of trihexylphenidyl and when do you use it?
Definition
inhibits ACh activity in key excitatory pathways and can be used for treating early, mild parkinsonism or more often as an adjunct with dopaminergic drugs
Term
What is the MOA of benztropine?
Definition
centrally acting antimuscarinic
Term
What other drugs besides direct/indirect DA and anticholinergics can be used to treat parkinsons?
Definition
diphenhydramine, ethopropazine, procyclidine
Term
What is the MOA of diphenhydramine in treating parkinsons?
Definition
antihistamine that also seems to block reuptake of DA
Term
What is the MOA of ethopropazine?
Definition
phenothiazine with marked anticholinergic properties (very atypical of this class of drugs)
Term
How does procyclidine treat parkinsons?
Definition
atropine-like activity that is particularly useful for alleviating rigidity and excessive salivation
Term
What is the medical term for excessive salivation?
Definition
sialorrhea
Term
What are the most common side effects of drugs used to treat parkinsons?
Definition
nausea and vomiting
Term
What are the side effects of drugs used to treat parkinson's disease?
Definition
nausea and vomiting, anorexia, choreiform movements, ataxia, orthostatic hypotension, tachycardia, neuroleptic malignant syndrome
Term
In what situation would a patient taking medications for parkinson's disease get neuroleptic malignant syndrome?
Definition
if levodopa is withdrawn abruptly
Term
What are the problems associated with long-term treatment of Parkinsons disease?
Definition
dyskinesias, end-of-dose failure, on-off phenomenon, secondary levodopa failure
Term
What is secondary levdopa failure?
Definition
effective drops off after 2-5 years
Term
What are the two most noteworthy drug interactions with parkinsons treatmetn?
Definition
interaction with MAOI's and other drugs affect dopamine neurotransmission (this is a very dangerous interaction that can lead to acute hypertensive episode and a stroke); an indirect interaction that results from high levels of vitamin B6 which by itself increases gastrointestinal dopa decarboxylase activity
Term
Which neurons degenerate in ALS?
Definition
spinal, bulbar and cortical neurons
Term
Name the treatments used for ALS (aka antispasmodics).
Definition
riluzole, baclofen, tizanidine, muscarinic receptor antagonists
Term
What is the MOA of riluzole?
Definition
drug with both presynaptic and post synaptic effects. This drug inhibits glutamate relese, but it also blocks postsynaptic NMDA and kainate-type glutamate receptors and inhibits voltage-dependent sodium channels
Term
How effective is riluzole?
Definition
modest but genuine effects on the survival of patients with ALS (60 days)
Term
What are the side effects of riluzole?
Definition
generally well tolerated, although nausea and vomiting may occur
Term
What is the MOA of baclofen?
Definition
a GABA(B) agonist that is a useful treatment for the spasticity observed in ALS patients
Term
What is the MOA of tizanidine?
Definition
alpha type 2 receptor agonist; reduces muscle spaciticity and is assumed to act by increasing presynaptic inhibition of motor neurons
Term
What is tizanidine used to treat?
Definition
used most widely in the treatment of spasticity in multiple sclerosis or after stroke but it may also be effective in patients with ALS
Term
What limits the dose of tizanidine that can be used?
Definition
side effects like drowsiness, asthenia, and dizziness
Term
Name the muscarinic receptor antagonists used to treat ALS?
Definition
dicyclomine, flavoxate, oxybutynin, oxyphencyclimine, trihexylphenidyl
Term
Which muscarinic receptor antagonists are used for urological disorders?
Definition
flavoxate and oxybutynin
Term
What is the average age of onset of huntingtons?
Definition
35 to 45
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