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