Drugs for Parkinson's and Movement Disorders Flashcards
What drug is a dopamine precursor, given orally, and absorbed in the small intestine?
Levodopa
Levodopa is used in combination with what other drug as a first-line treatment for Parkinson’s?
Carbidopa
When would you NOT want to use levodopa as a first line treatment for Parkinson’s?
When the patient is young
What enzyme and reaction does carbidopa affect, and where does it act?
AAD (aromatic amino acid decarboxylase) inhibitor, which prevents conversion of L-dopa to dopamine; acts in the periphery (does not cross BBB)
What class of drugs are contraindicated in a Parkinson’s patient who is taking levodopa and carbidopa?
MAO-A inhibitors are contraindicated
What Parkinson’s treatment is associated with on-off phenomenon, NMS (neuroleptic malignant syndrome), and possibly accelerating PD progression?
Levodopa+carbidopa
Which 2 Parkinson’s drugs are ergot derivatives? Which one is no longer used and why?
Bromocriptine and pergolide; pergolide is no longer used because it can cause cardiac valve regurgitation
What are 3 therapeutic uses for bromocriptine, what receptor does it affect to do its job, and is it an agonist or antagonist?
Treat mild Parkinson’s, NMS, and hyperprolactinemia; D2 receptor agonist
In what organ does bromocriptine (and pergolide) cause the most side effects? Give some specific examples
In the lung; ex. pulmonary effusions, cough, shortness of breath, and pulmonary fibrosis
What effects does the Parkinson’s drug bromocriptine have on dopamine receptors?
D2 receptor agonist and D1 receptor antagonist
What receptor is targeted by the Parkinson’s drugs pramipexol, ropinerole, and rotigotine? Which one is given using a transdermal patch?
D2 receptor (agonists); rotigotine
Of the 3 D2-selective non-ergot agonists, which ones are used together as first-line therapy for mild Parkinson’s? Which ones can also be used to treat restless leg syndrome?
Pramipexole and ropinerole are used together; Ropinerole and rotigotine are used for restless legs syndrome
Which non-ergot DA agonist can cause compulsive behavior as a side effect? What receptor in which area of the brain mediates this effect?
Pramipexol; D3 receptors in the nucleus accumbens
How effective are the non-ergots compared to the ergot derivative bromocriptine in treating Parkinson’s? How do their side effects compare?
Non-ergots are less effective at treating PD motor symptoms; they also have more acute side effects (psychosis, nausea/GI problems, edema) but less long-term side effects
Which non-ergot DA agonist can cause daytime sleep attacks as a side effect?
Ropinerole
What is apomorphine used for, and how is it administered?
Rescue from Parkinson’s “off” periods; given by injection only
What kind of drugs are contraindicated for a patient on apomorphine? Why?
Serotonin receptor antagonists, because they will cause hypotension
What two classes of drugs inhibit DA breakdown? Give the 2 drugs from each of these classes.
COMT inhibitors: entacapone and tolcapone
MAO-B inhibitors: selegiline and rasagiline
Do entacapone and tolcapone mostly act centrally or peripherally, and what Parkinson’s drug do they augment? Is their half-life long or short?
Peripherally (tolcapone has some central effects) to extend the half-life of levodopa; short (2 hours)
Why is tolcapone only to be used if entacapone fails?
Tolcapone can cause fatal hepatotoxicity
What receptors are targeted by benztropine, procyclidine, and ethopropazine? Are they agonists or antagonists?
Muscarinic cholinergic antagonists
What receptors are targeted by biperiden and trihexyphenidyl? Are they agonists or antagonists?
Muscarinic cholinergic antagonists
What is the primary theraputic use for anticholinergic drugs in Parkinson’s patients? What kind of patients should not be given these drugs?
To treat excessive drooling; contraindicated in demented Parkinson’s patients because the anticholinergics can cause mental problems like confusion, impaired memory and hallucinations
What kind of drug is amantidine? What 3 receptors does it affect and how?
Anti-viral (and anti-Parkinson’s); dopamine receptor agonist, ACh receptor antagonist, NMDA receptor antagonist
Name the only adjunct to levodopa+carbidopa that reduces dyskinesias in Parkinson’s. For what other disease is this adjunct used?
Amantidine; also used for Huntington’s
What part of the brain is targeted by deep brain stimulation, and what 3 therapeutic effects can this produce?
The subthalamic nucleus; treats dyskinesia refractory to other medications, reduces ‘off’ time, and may reduce levodopa dosage
What are 2 potential side effects of deep brain stimulation?
Intracerebral hemorrhage and cognitive impairment
What two drugs are used to treat spasticity in ALS?
Baclofen and tizanidine
What receptors are targeted by baclofen and tizanidine, and are they agonists or antagonists?
Baclofen: GABA-B agonist
Tizanidine: alpha2 agonist
What is the only drug used to treat ALS progression? What receptors does it affect and how?
Riluzole; kainate and NMDA (both glutamate receptors) antagonist
What is the most important possible side effect of riluzole? What drug can be used to reverse some of riluzole’s clinical actions?
Can cause hepatotoxicity; pertussis toxin
What drug is used to treat tardive dyskinesia in Huntington’s? How does it work?
Tetrabenazine; inhibits VMAT2 which decreases dopamine in the brain
What kind of drug is dantrolene, and what condition is it used to treat?
Muscle relaxant; treats malignant hyperthermia (associated with NMS)
Levodopa/carbidopa, amantadine, and tetrabenazine are all associated with what side effect, also seen with anti-psychotic drugs?
NMS
Which Parkinson’s drug is associated with side effects of psychosis, drowsiness, hypersexuality (increase in erections), and emesis? Pre-administration of trimethobenzamide or domiperidone can help alleviate these symptoms.
Apomorphine
Which 2 Parkinson’s drugs are associated with the side effect of urine discoloration, as well as the usual GI and DA overload problems?
Tolcapone and entacapone (the COMT inhibitors)
