EXAM #3: ANTIPARKINSON'S DRUGS Flashcards
What is the aggregate found in PD?
Intracytoplasmic aggregates of alpha-synuclein
When does PD typically onset?
50’s and 60’s
What is PD characterized by from a pathologic standpoint?
Progressive loss of dopaminergic neurons in the basal ganglia
What are the cardinal symptoms of PD?
1) Bradykinesia
2) Muscular rigidity
3) Resting tremor
4) Postural instability
Specifically what dopaminergic neurons are lost in PD?
Dopaminergic neurons in the SN that project into the Striatum
What is the definition of the Striatum i.e. what are the parts of the Basal Ganglia that compose the Striatum?
Putamen
Caudate Nucleus
Describe the pathophysiology of PD.
- Alpha-synuclein accumulates into Lewy Bodies
- Lewy body formation generates free radicals
What is the specific part of the Basal Ganglia that is degenerative in PD?
Substantia Nigra Pars Compacta
What is the outcome of SN pars compacta degeneration in PD?
- OVERACTIVITY of the indirect pathway leading to:
1) Inhibition of the VA/L thalamus
2) Reduced excitatory input to the cortex
3) Diminished execution of movement
What is the role of ACh in PD?
- Imbalance of DA and ACh in PD
- Thus, there is too much ACh in PD
What is the most common drug used to treat PD?
L-DOPA
Why is L-DOPA given instead of DA?
DA cannot cross the BBB
What enzyme converts L-DOPA into DA?
Dopa carboxylase
What symptoms does L-DOPA specifically improve in PD?
Bradykinesia
Rigidity
What drug is L-DOPA typically co-administered with?
Carbidopa
What is the MOA of Carbidopa?
Carbidopa is an inhibitor of Dopa Decarboxylase in the periphery
What is the effect of inhibiting Dopa Decarboxylase?
Inhibits the premature breakdown of L-DOPA in the periphery
What are the adverse effects associated with L-DOPA adminstration?
1) Dyskinesias
2) Response fluctuations
- Wearing off reactions
- On-off phenomenon
3) GI disturbance
4) Postural hypotenion/ tachycardia
5) Behavioral disturbances
What can be done to prevent the response fluctuations of L-DOPA?
Drug holidays i.e. periodic cessation
What is the drug interaction of L-DOPA with Pyridoxine?
This is Vitamin B6, a DOPA decarboxylase cofactor that enhances L-DOPA metabolism in the periphery
What is the drug interaction of L-DOPA with antipsychotics?
DA receptor blockade limits efficacy
What is the drug interaction of L-DOPA with MAO-inhibitors?
Hypertensive response (NE)
List the three DA receptor agonists.
Pramipexole
Ropinirole
Apomorphine
What is the clinical use of Apomorphine?
Given subcutaneously for rescue of L-DOPA induced dyskinesias
What is the MOA of the DA receptor agonists
D2 receptors agonsit
What are the two MAO-B inhibitors used to treat PD?
Rasagiline
Selegiline
What is the MOA of the MAO-B inhibitors?
Decreases breakdown of dopamine
What is the major behavioral issue seen with the administration of DA agonsits?
Impaired impulse control leading to:
- Compuslive gambling
- Shopping
- Betting
- Sex
What is the dose of MAO-B inhibitor that is needed to have a therapeutic effect in PD?
Low
What are the two drugs used as COMT inhibitors in the treatment of PD?
Entacapone
Tolcapone
What is the difference between Entacapone and Tolcapone?
Entacapone= peripheral COMT inhibitor ONLY
Tolcapone= central and peripheral COMT inhibition
What is the MOA of COMT inhibitors?
Block peripheral breakdown of L-DOPA–used as an adjunct
What is the MOA of Amantadine?
Increased DA release
What class of drug is Amantadine?
Anti-viral
What is the major adverse effect associated with Amantadine administration?
Livedo Reticularis
What are the anticholinergic agents used to treat PD?
Benztropine
Trihexyphenidyl
What is the MOA of Benztropine and Trihexyphenidyl?
Muscarinic antagonists
What is the general picture of muscarininc antagonist overdose?
“Dry-picture”
