Parkinson Drugs Flashcards
What are the signs of Parkisons Dz?
Bradykinesia; muscular rigidity; tremors; gait abnormalties; postural instability
What neurotransmitter pathway is affected in PD?
Dopaminergic pathway (inhibitory neurons) in the substantial nigra and corpus striatum (neurotransmitter ratio shifts toward the decreased DA and increased Ach)
What does increased levels of DA in the tuberoinfundibular tract lead to?
Decreased prolactin levels
What does increased levels of DA in the CTZ lead to?
increased emesis
What does increased levels of DA in the mesolimbic-mesocortical tracts lead to?
increased psychomotor activity; psychosis; schizophrenia; increased reinforcement
Which DA receptor subtype is implicated in PD?
D2 receptor subtype (inhibitory receptor subtype that decreases cyclic adenosine monophosphate [cAMP] levels in corpus striatum
Given the abnormal DA/ACh shift in the striatum, give two pharmacologic strategies in the treatment of PD?
- Medicaitons that will increase DA levels
2. Medications that will increase Ach
Do anti-parkinson meds effect pathology, symptoms or both?
symptoms
Name 2 antimuscarinic medications that are used in the treatment of PD:
- Benztropine
2. Trihexyphenidyl
Is benzodiazepine more or less lipid soluble than atropine?
More lipid soluble (therefore greater CNS penetration)
Which characteristic of PD is not affected by anticholinergics?
Bradykinesia
Is benzotropine useful in the treatment of tar dive dyskinesia?
No, it may actually exacerbate tar dive dyskinesia
What are the adverse effects of benzotropine & tihexyphenidyl?
Xerostomia; blurred vision; constipaiton;urinary retention; sedation; mydriasis
How does amantadine work in the treatment of PD?
May inhibit reuptake of DA into presynaptic neurons; may increase DArelease from presynaptic fibers
Amantadine is used to treat what condition other than PD?
Influenza A
What is the name of the dermatologic adverse effect caused by Amantadine?
Livedo reticularis
What is lived reticularis?
A network pattern discoloration of the skin cause dby dilation of capillaries and venules
Which characteristic is not affected by amantadine?
Tremors
Which selective MAO-B inhibitor is commonly used as first line treatment of PD?
Selegiline
What is the MOA of Selegiline?
Inhibition of DA metabolism in presynaptic neurons located in the CNS via inhibition of MAO-B
What are the two active metabolites of Selegiline?
- Amphetamine
2. Methamphetamine
What are the main adverse effects of Selegiline?
Cardiovascular stimulation (hypertension, palpitations; arrhythmias; angina)
Name two ergot derivatives that acts DA agonists in the nigrostriatal system:
- Bromocriptine
2. Pergolide*?
Bromocriptine is used to treat what conditions other than PD?
Prolactin secreting microadenomas; NMS; acromegaly; postpartum lactation
What are the adverse effects of bromocriptine?
Headache; dizziness; nausea; orthostatic hypotension; dyskinesia; hallucinations; confusion; psychosis
Name two non-ergot DA agonists:
- Pramipexole
2. Ropinirole
What are the adverse effects of non ergot DA agonists?
Sedation; syncope; nausea; vomiting; hallucinations; dyskinesia
What is the mechanism of action of Tolcapone and entacopone?
Inhibition of peripheral catechol-O-methyltransferase (COMT), thereby increasing CNS uptake of L-dopa
What reaction does COMT catalyze?
Conversion of L-dopa to 3-O-methyldopa (partial DA agonist) in peripheral tissues
What are the adverse effects of COMT inhibitors
Orthostatic hypotension; headache; fatigue; nausea; diarrhea; anorexia; dskinesia; muscle cramps; brown-orange urine; discoloration; hallucinations; diaphoresis
Which of the COMT inhibitors is hepatotoxic?
Tolcapone
Are COMT inhibitors used as first line therapy, adjunctive therapy, or both in the treatment of Parkinsons?
Adjunctive therapy in combo with carbidopa/levodopa
Are the non ergot DA agonist used as first-line therapy, adjunctive therapy, or both in the treatment of PD?
Both
What is the precursor of DA?
Levodopa (L-dopa)
What enzyme converts L-dopa to DA?
Dopa decarboxylase DDA
Does DA cross the BBB
NO
Does Levodopa cross the BBB
yes, it does and is subsequently converted to DA by dopaminergic neurons in the substance nigra
Is levodopa effective in treating PD when all the dopaminergic neurons in the substantial nigra have been destroyed?
No, since dopinergic neurons in the substaia nigra are required to convert levodopa to DA
What is the MOA of carbidopa
Inhibition of peripheral DDC, thereby increasing the amount of levodopa that is available to cross the BBB. this allows for lower doses of levodopa needed, thereby decreased levodopa adverse effects
Does carbidopa cross BBB
no, so only inhibits peripheral DDC
How does levodopa work in the treatment of PD
Decreases symptoms of PD such as rigidity bradykinesia and tremors
What is the “on off phenomenon” of parkinsons
Levodopa has such a short half life (1-2 hours) that plasma concentrations may decline rapidly causing patient to experience sudden rigidity, bradykinesia, and tremors
Which amino acids compete with levodopa for GI absorption
Isoleucine; leucine
What are the adverse effects of levodopa
Anorexia; nausea; vomiting; tachycarida; hypotension; discoloration of saliva and urine; mydriasis; hallucinations; dyskinesia; incrased intraocular pressure; cardiac arrhythmias
Why should vitamin B6 (pyridoxine) not be used in combo with levodopa?
pyridoxine enhance metabolism of levodopa.
