Parkinson's Disease Pharmacotherapy Flashcards
T/F: Treatments for Parkinson’s only manange the disease but do not delay or stop the disease
True
What are the six types of medications used to treat Parkinson’s Disease
1) Levodopa
2) Dopamine agonists
3) Monoamine oxidase (MAO) B inhibitors
4) Catechol-O-Methyl-Transferase (COMT) inhibitors
5) Amantadine
6) Anticholinergic agents
T/F: In Parkinson’s the Substantia Nigra is being destroyed leading to less Dopamine release causing the symptoms of the disease
True
How is Dopamine created and released at Nigrostriatal neurons
1) Tyrosine is converted to L-DOPA by tyrosine hydroxylase
2) L-DOPA is converted to dopamine by DOPA Decarboxylase (DDC)
3) Dopamine is stored in vesicles ready for release due to an action potential
4) Dopamine that is left over is brought back into the cell by the dopamine transporters
What is the enzyme that converts L-DOPA into an inert compound, converts Dopamine into an inert compound
COMT converts L-DOPA in 3-OMD, MAO-B and COMT convert dopamine into an inert compound
What drug is used to increase dopamine levels by being converted to dopamine
Levodopa
What are the dopamine agonists
Ropinirole, pramipexole, rotigotine, apomorphine
What are the MAO-B inhibitors
Selegiline, Rasagiline, Safinamide
What are the COMT inhibitors
Entacapone and Tolcapone
What drug has an unknown MOA but is theorized to cause exocytosis, agonist of dopamine and inhibit dopamine uptake
Amantadine
What is the benefit of using anticholinergics
Reduce how bad tremors are
Why cant just dopamine be given
It does cross the BBB
What is the biggest side effect of levodopa, why
Causes nausea and vomitting, when L-Dopa is converted to Dopamine in the periphery it binds to the chemoreceptor trigger zone (CTZ) outside the BBB thus causing nausea
T/F: Levodopa is given by itself so some patients can handle the nausea while others cannot
False: Carbidopa is given with Levodopa to cause less side effects
How does carbidopa aid in the efficacy of Levodopa
Carbidopa competitively inhibits Dopa Decarboxylase from converting Levodopa in the periphery allowing for less side effects and more Levodopa to enter the brain
What should be counseled about Carbi/Levo when given with food
Do not eat with a high protein meal because the bioavailability is reduced
What are the two most notable side effects of Carbi/Levo, others
Nausea and orthostatic hypotension/ confusion, delusions, agitation, psychosis, motor fluctuations, parkinsonism hyperpyrexia syndrome
What is a tip to not have nausea with Carbi/Levo
Slower transiotion with food, supplemental doses of carbidopa 30 minutes before, ondansetrons, certain anticholinergics
What should NOT be given with Carbi/Levo
Dopamine antagonist (Metoclopramide, Prochlorperazine, Promethazine)
What happens with longer Carbi/Levo use with regards to motor fluctuations
In the beginning the drug works quickly, however with disease progression and tolerance the drug wears off quicker and it takes higher concentrations to achieve an effect, there is also dyskinesia due to the drug as the disease progress ALL DUE TO INCREASED DEPENDENCE
T/F: Due to the wearing off effect of Carbi/Levo there is clenching of feet upon waking in the morning but this can be mittigated through wooden shoes and long acting Carbi/Levo
True
How is the off period managed
Take Carbi/Levo more frequently OR adding COMT inhibitors OR MAO-B inhibitor OR Dopamine Agonist
What are ways to manage dyskinesia due to Carbi/Levo use
Use lowest effective dose, addition of amantadine, change to or add MAO-B inhibitor, addition of COMT inhibitor, change to or add Dopamine agonist
What is Parkinsonism Hyperpyrexia Syndrome, symptoms
Patients are on Carbi/Levo for long periods of time and it is suddenly stopped/ mental status changes, rigidity, fever (possibly fatal)
T/F: Dopamine agonist work as adjuncts or monotherapy but are generally less effective
True
What are side effects of Dopamine agonists that occur more often than Carbi/Levo, what is the one benefit
Somnolence, constipation, dizziness, hallucinations, nausea, freezing of gait
What benefit does dopamine agonists have, what is the caveat
Less incidence of dyskinesia BUT the incidence of dyskenesia and Carbi/Levo converge over time
What are UNIQUE side effects of dopamine agonists
Peripheral edema, drowsiness and narcholepsy, Impulse control dissorders (gambling, sex, winning), Dopaminergic Dysregulation syndrome (addiction), Dopamine agonist withdrawl syndrome (night sweats, anxiety, depression, sweating, drug craving)
What are benefits of using MAO-B inhibitors with Carbi/Levo, problem
Improve off symptoms, provide extra hour of duration to Carbi/Levo (incosistent), worsens dyskinesia with Carbi/Levo
Which MAO-B inhibitors has multiple dosage forms
Selegiline
What are side effects of MAO-B inhibitors
Nausea/vomitting, headaches, confusion in ederly and hallucinations
What is something to be cautious about when it comes to selegiline more than rasagiline, how can this be avoided
Selegiline has two metabolites, L-amphetamine and L-methamphetamine, that cause insomnia/ should be taken twice a day with breakfast and lunch
What are the drugs that Contraindicated with MAO-B inhbitors,
Tramadol, St. John’s Wort, MAO inhibitors, Dextromethorphan, Methadone
Serotonin Syndrome
T/F: High blood pressure is associated with eating MAO-B inhibitors when eaten with protein
False: Foods that have tyramine, cheese wines cured meats and chocolates, cause the release of norepinephrine from vesicles of neurons increasing BP
T/F: COMT inhibitors are only used as adjuncts on Carbi/Levo while also increasing the half life
True
Which COMT inhbitor is no longer used
Tolacapone
What are the odd side effects of COMT inhibitors
Delyaed onset diarrhea and dark colored urine
When is amantadine usually used
Weakly effective but generally very well tolerated
What are the two anticholinergics, what are they used for
Benztropine and Trihexyphenidyl, first line for Parkinson’s tremor
What are the drug choices for dealing with mild tremor
Anticholinergic, Beta blocker, MAO-B inhibitor, Carbi/LEvo, Dopamine agonist
What is a drug added for severe tremor resistant to other therapies
Clozapine
What drugs are used for moderate postural instability and Gait Difficulty (PGID), severe
MAO-B inhibitor, Carbi/Levo, Dopamine agonist/ Carbi/Levo
What is used to treat Depression in Parkinson’s, Dementia
TCAs (exacerbating dementia and narrow angle glaucoma), Nortriptyline or Desipramine/ Reduce anticholinergics
What is used to treat Psychosis/Hallucinations in Parkinson’s, what must be monitored
Clozapine, WBC and ANC due to risk of agranulocytosis
What are way to improve orthostatic hypotension due to drugs or Parkinson’s
Increase salt and fluid consumption, elevate head of bed, Midodrine, fludrocortisone
