Flashcards in PHARM: Movement Disorders Deck (65):
What are the 4 main clinical symptoms of Parkinson's Disease?
-Postural instability/impaired gait
What is the pathological hallmark of Parkinson's Disease?
selective loss of 70-80% of the pigemented neurons in the substantia nigra pars compacta
What effect does the direct pathway have on the thalamus?
increase thalamic output
What effect does the indirect pathway have on the thalamus?
decrease thalamic output
What part of the basal ganglia is responsible for the tonic inhibition of the thalamus?
What initiates the direct pathway?
SN pars compacta stimulates striatum D1 receptors
What is the result of stimulating D1 receptors in the striatum?
GABAergic/SP neurons from striatum are sent out to inhibit GPi
What stimulates the indirect pathway?
cortex stiulates the striatum
What occurs when the cortex stimulates the striatum?
sends out GABA/ENK neurons to inhibit GPe
What does GPe do naturally?
inhibits the subthalamic nucleus (STN)
What does the STN do when not inhibited by GPe?
sends out glutamergic neurons to stimulate GPi (for increased tonic inhibition)
How are D2 receptors involved in the indirect pathway?
the SNpc can stimulate them to inhibit the inhibitory pathway (via blockage of the cholinergic interneurons that also stimulate GABA/ENK neurons)
What are the 5 strategies to treat PD?
-Stimulate D2 receptors
-Enhance DA release
-Inhibit DA metabolism
-Alter DA/Ach balance
What drugs are employed in the "replace DA" strategy to treat PD?
L-Dopa + Carbidopa
What drugs are employed in the "stimulate D2 receptors" strategy to treat PD?
What drug is employed in the "enhance DA release" strategy to treat PD?
What drugs are employed in the "inhibit DA metabolism" strategy to treat PD?
What drugs are employed in the "alter DA/Ach balance" strategy to treat PD?
What are some issues with the fact that L-Dopa is an oral drug?
-Competes with L-amino acids in food in the GI tract (so you need to NOT take it with food)
What problem does L-Dopa have with B6?
Need to give with a decarboxylase inhibitor because B6 breaks it down
Why does L-Dopa have to be given in such large oral doses when given alone?
99% is converted in the periphery to DA by ALAD
How long is L-Dopa effective, and what consequence does this have on prescribing it?
Only good for 3-5 years, so save it for later stages
Which drug has the following contraindications?
What is carbidopa?
ALAD (aromatic L-amino acid dicarboxylase) inhibitor that prevents the peripheral metabolism of L-Dopa to DA
What drug needs to be given with L-Dopa + carbidopa?
antipsychotics (because carbidopa has behavioral side effects)
What are the major side effects of L-Dopa + carbidopa?
Behavioral changes and dyskinesias (reduces dosage of L-Dopa needed by 75%, so those side effects are not problematic)
What are the major side effects of L-Dopa?
GI (anorexia or N/V)
Cardiac (orthostatic hypotension, Tachycardia, Arrhythmias)
True or false: L-Dopa may exascerbate PD progression.
What drug is a D2 and partial D1 agonist?
What drug is a D2 selective agonist and free radical scavenger?
What drug is a D2 selective agonist?
What drug is a D1 and D2 agonist?
What is the major advantage of using dopamine agonists to treat parkinson's disease?
more selective so less adverse effects
What drug is an antiviral agent that may enhance release and synthesis of DA and inhibit DA uptake?
What drugs are selective MAO-B inhibitors?
What is MAO-B?
MOA-B is the enzyme that pre-synaptically metabolizes dopamine to DOPAC so that it is not packaged into vesicles for release
What drugs are selective inhibitors of COMT?
What is the role of COMT?
-metabolizes DA in the synaptic terminal to HVA
-increases production of 3OMD which competes with L-Dopa for transport across the GI an BBB
What drugs block cholinergic activation in the striatum to decrease GABAergic output to the GPe (to inhibit the indirect pathway)?
What drugs CANNOT be taken with meperidine, TCAs or SSRIs?
What drug causes restlessness, depression, irritability, confusion, and psychosis with overdose?
What drugs are contraindicated in prostatic hyperplasia, OBD, glaucoma, and in people taking antimuscarinics?
What drug is contraindicated with a history of seizures or heart failure?
Which of the COMT inhibitors has central and peripheral effects?
What COMT inhibitor requires signed patient consent? Why?
Tolcapone leads to elevated liver enzymes and hepatic failure
What drugs lead to dry mouth, constipation, N/V, drowsiness, mental slowness, and inattenation?
What drugs are given as early treatment for PD?
What drug can be used in early PD alone but has modest and short-lived effects?
What dopamine agonist is metabolized by CYP1A2?
What drug is used in patients who are losing responsiveness to L-Dopa and is NEVER used alone?
Which is more potent, selegiline or rasagiline?
Rasagiline (can be used alone in early PD)
Which drugs are used to increase the bioavailability of L-dopa and decrease "off time"?
What is a potential new target for the treatment of PD?
L-type Ca2+ channels (if you block these with isradipine, it will convert them to a more juvenile state that may prevent disease progression)
What converts tyrosine to DOPA?
What converts DOPA to DA?
What packages DOPA into vesicles in the pre-synaptic membrane?
In what gene does the trinucleotide expansion for HD occur?
IT15 (causes huntingtin to become a transcriptional regulator--gain of function)
What neurons are lost in HD?
cholinergic neurons in striatum
GABAergic neurons projecting to the GPe
(which typically stimulate the indirect pathway)
What are the major clinical symptoms of HD?
-Slowing of mental processing (ex. planning)
-Reducitons in memory (how to process/acquire new information)
What classes of drugs are used to treat HD related depression?
What other classes of drugs are used to treat HD?
-VMAT inhibitors (deplete central DA)
-D2 receptor antagonists (inhibit inhibition of indirect pathway)
What VMAT inhibitors are used in HD?
What D2 receptor antagonists (drugs that lead to parkinsonism) are used in HD?
What calss of drugs are used in early HD to prevent chorea?