DISEASE
Parkinsonʼs patients have a diminished level of the naturally occurring neurotransmitter known as DOPAMINE. Estimates are that up to 70% of our nervous systems capacity for it is no longer available, when weʼre diagnosed. DOPAMINE is responsible for sending movement messages to all parts of our bodies. DOPAMINE is produced in a small part of the brain.
L–Dopa, also known as levodopa, is converted to DOPAMINE in the brain. The “gold standardˮ of drug therapy is known as Carbidopa/Levodopa.
A naturally occurring enzyme known as MAO–b breaks down DOPAMINE. MAO–b inhibitors slow this process.
A naturally occurring enzyme known as COMT breaks down levodopa. COMT inhibitors slow this process.
DOPAMINE agonist drugs “act likeˮ or mimic the action of DOPAMINE. They work throughout the nervous system in a similar manner to DOPAMINE.
The role of each class of Parkinsonʼs Drugs is to maintain a level of DOPAMINE activity that duplicates pre–Parkinson's amounts (normal production), thus relieving symptoms.
6 RX NOTES FOR PARKINSON’S DISEASE
A whimsical look at Dopamine's formation, utilization, and breakdown.ˮ
RX NOTES FOR PARKINSON’S DISEASE 7
DIAGRAM “
WHERE & HOW DRUGS WORK
(Originally written September 2020)
Letʼs look at our anatomy and physiology, so weʼll have a reference point for understanding where and how the different drug classes are working.
Transmission of neuronal messages occurs with the aid of neurotransmitters such as dopamine. This transmitter is the one mostly closely associated with PD. PD patients have decreased levels of dopamine at varying levels, and brain scans usually indicate a diminished substantia nigra.
To help us have a picture of neuronal transmission, try this simple exercise: fold your arms in toward your chest and make two fists, leave about two inches between fists. In this exercise the area from your elbows to your fists are nerve cells, and the gap in between is known as the synapse. The receiving end of the nerve cell is known as the dendrite, and the transmitting end is known as axiom. For a more detailed view of nerve cells visit this Khan Academy link:
https://www.khanacademy.org/science/biology/human-biology/neuron-nervous-system/v/neuronalsynapses-chemical
Absorption of drugs for the most part happens throughout the GI tract, but largely in the small intestine (approximately 22 ft. long)!
Elimination of a drug is handled mostly by the kidneys and liver. The liver is commonly known as the detox organ, and the kidneys clear via urination. Our lungs also play a role in maintaining our bodyʼs “homeostasisˮ (normal levels of acid/base known as pH and others).
The blood–brain barrier refers to the ability of a drug to pass from our blood into the brain and spinal column. Dopamine will not cross this barrier, but is carried to our brain by levodopa.
Half–life of a drug refers to a time frame in which the drugs elimination takes place. If a drug has a half–life of 6 hours, this means the initial dose has been diminished (cut in half) after 6 hours time. A drug half–life is important and influences dose timing and plasma concentration levels. Be sure to work with your neurologist on dosing drugs correctly.
TIDBITS
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Only cut a controlled release (CR) or sustained release (SR) drug in half on the recommendation of your physician. Never crush a CR or SR drug. The manufacturer has formulated this delivery system and it must remain intact.
Yogurt, applesauce, and smoothies may help you if swallowing has become an issue.
8 RX NOTES FOR PARKINSON’S DISEASE
REPLACING DOPAMINE (carbidopa/levodopa)
(Originally written October 2020)
Because dopamine given orally cannot cross the blood–brain barrier we use the precursor levodopa (L–dopa) to accomplish this. Levodopa is converted to dopamine in the brain and made available for the central nervous system. It is coupled with carbidopa to help this process and reduce nausea. The combination drug carbidopa/levodopa is available in many different forms, which can be found here:
https://www.parkinson.org/Understanding-Parkinsons/Treatment/Prescription-Medications
Because this list is extensive in dosage forms, duration of action, and method of delivery, your healthcare provider has many options from which to choose. This group of drugs does replace dopamine versus ones that either mimic, slow degradation, or work to give symptomatic relief. Should your healthcare provider place you on this combination, ask for the package insert at the pharmacy. A commonly used one is brand name Sinemet (carbidopa/levodopa) and the Sinemet FDA package insert may be found here: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/017555s069lbl.pdf
TIDBITS
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The dose should be taken at the prescribed time. A high protein meal will impede the uptake of levodopa. A high fat meal will slow the absorption of L–dopa. Pyridoxine (Vitamin B–6) may reduce the availability of L–dopa. Consider consulting a dietician for nutritional optimization.
The blood plasma half–life (the time required for half of the drug to be removed from the body) of Sinemet is 1.5 hours. This is a fairly short time, thus requiring frequent dosing. This is the advantage of extended release formulations.
At peak blood plasma levels, the drug has been known to cause dyskinesia (snake–like movements). Should you have an unwanted side effect, try to document the time in relation to your previous dose. This is beneficial for your physician to know.
Upon a recent review of Sinemet’s package insert we found that taking this medication with oral iron supplement (element Fe) lowered the absorption because the iron bound the medication in the GI tract. The OTC morning dose of multivitamin w/Fe was lowering one PD patients ability to convert levodopa into dopamine.
Administration of levodopa has been used by some clinicians as a diagnostic tool.
As with any drug, please be sure to read the patient information sheet that comes with your prescription and speak with your healthcare provider or pharmacist about any concerns.
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SLOWING DOPAMINE'S BREAKDOWN (MAO–B Inhibitors)
(Originally written February 2021)
We all have a naturally occurring enzyme in our bodies that breaks down dopamine along with other neurotransmitters. Itʼs commonly known as ‟MAO–Bˮ and affects dopamineʼs ability to transmit messages across the synapse (space between nerves; see Where & How Drugs Work), and throughout the central nervous system. The drug class known as MAO–B inhibitors slow the degradation of dopamine, thus improving symptoms related to PD. Generic names include selegiline (brand name Eldepryl), resagiline (brand name Azilect) and, more recently, safinamide.
Dosage forms, frequency of dosing, brand names, and side effect information may be found in the Medications guide available from The Parkinsonʼs Foundation.
Several drugs should be avoided by people taking MAO–B inhibitors, many of which are in the pain relief or muscle relaxer classes. Be sure to check with your healthcare provider or pharmacist to ensure safety. MAO–B drugs may be used as solo therapy or in conjunction with other PD medications.
TIDBITS
Keeping an individual drug profile with your prescription medications, over–the–counter medications, vitamin use and some commentary about your history can be beneficial information your individual practitioner to know.
Because many of us are taking some form of carbidopa/levodopa, please review with your healthcare provider whether your intervals between doses are okay. Side effects from plasma blood levels of dopamine being too high or too low may be problematic.
A medication therapy management review (MTM) can be done once a year by the pharmacist at the location where you get prescriptions. Most insurance companies will reimburse the pharmacist for doing this.
In the last two years a program to license individuals for ‟Board Certification in MTMˮ has become available. The Doctor of Pharmacy degree is awarded by an accredited School of Pharmacy and is known as the PharmD. To practice pharmacy in any state, the licensure exam known as the “State Boardˮ must be passed.
10 RX NOTES FOR PARKINSON’S DISEASE
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INHIBITING DOPAMINE BREAKDOWN (COMT Inhibitors)
The COMT inhibitors act to slow the breakdown of levodopa, a precursor of dopamine, thus prolonging dopamine’s effect. They are used to help with the “wearing offˮ effect of lower dopamine blood plasma levels.
There are 3 COMT inhibitors
1 2 3
Comtan (generic: entacapone); is NOT used without levodopa and is a single entity formulation. May change urine color to a harmless orange.
Ongentys (generic: opicapone); is NOT used without levodopa and is a single entity formulation.
Tasmar (generic: tolcapone); is NOT used without levodopa and is a single entity formulation. May change urine color to a harmless orange. This is the most potent of the 3 COMT inhibitors, however liver function must be monitored. Liver function tests should be done when beginning this drug and every 3–4 weeks up to six months, then every six months thereafter if therapy is continued.
Stalevo (combination of carbidopa, levodopa, and entacapone) is a combination drug manufactured in six different dosage forms.
All of these drugs enhance levodopa activity and may have side effects such as dyskinesia and confusion.
Side effects, generic names, dosage forms and dose frequency may be found in The Parkinson Foundations Medications guide.
TIDBITS
(Originally written July 2021) • •
Because keeping an effective blood plasma level of dopamine in PD patients is so important, you should consider journaling your drug doses and side effects: (i) for the week before seeing your physician or (ii) for the week after changing a medication. In both cases, it will help your healthcare provider optimize drug therapy.
Levodopa is a precursor of dopamine and the conversion to dopamine takes place in the brain.
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MIMIC DOPAMINE (Dopamine Agonists)
(Originally written November 2021)
The group of drugs that “act likeˮ dopamine are referred to as dopamine agonists (DA). They stimulate dopamine receptor sites so are also called “mimickersˮ of dopamine.
Examples are: 4
1 2 3
Requip, Requip XL (generic ropinirole)
Mirapex, Mirapex ER (generic pramipexole)
Neupro skin patch (generic rotigotine)
Apokyn subcutaneous injection (generic apomorphine)
These drugs improve motor symptoms of PD, and can be used as monotherapy early in PD or added to carbidopa/levodopa in later stage disease. In general, the group has longer half–lives than levodopa. The half–life of Mirapex is 8 hours in healthy adults, so the XL and ER versions in this class are sometimes given once daily. Your prescriber will determine the appropriate dose based on your therapeutic response.
TIDBITS
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The patient information sheet you receive at the pharmacy is usually a one or two–page summary while the manufacturers package insert (see Index) contains complete prescribing information. You may also ask your pharmacist for this document when picking up a prescription.
• • •
In patients with impaired kidney function the dose of Mirapex must be altered considerably. Youʼll gain insight into the many considerations the healthcare provider must make by reviewing this document.
Known side effects of dopamine agonists are: daytime sleepiness, visual hallucinations, confusion and swelling of the legs. A common major issue is worsening impulsive behaviors, and a condition known as punding (repeating purposeless activities). Your care partner’s role in relaying this information to your healthcare provider becomes important here because a dosage adjustment may be all that's necessary for proper outcomes.
Remaining active and personal contact is so important.
12 RX NOTES FOR PARKINSON’S DISEASE
OTHER DRUGS USED IN PD THERAPY
(Originally written December 2021)
The drug amantadine (brand name Symadine or Symmetrel) was developed in the 1960ʼs as an antiviral, but healthcare providersʼ noticed that it reduced tremors in PD patients. It can reduce levodopa induced dyskinesia. Amantadine is cleared by the kidneys so patients with impaired kidney function may require a lower dose. It can cause a rare side effect known as livedo reticularis (a purple discoloration of the skin).
Commercially available as:
1 2
Symmetrel, Symadine (generic: amantadine)
Gocovri, Osmolex ER (generic: extended–release amantadine)
Anti–cholinergic drugs were used early in PD therapy, but can cause confusion, dry mouth, blurry vision and urinary retention. Even OTC Benadryl can have a cognitive impact. When this class of drugs is used it generally is prescribed for younger patients.
Commonly used anti–cholinergics are:
1 2 3
Artane (generic: trihexyphenidyl)
Cogentin (generic: benztropine)
Parsitan (generic: ethopropazine)
TIDBITS
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Your healthcare provider may prescribe numerous drugs beyond the classes used for motor symptoms in PD. They will determine the most appropriate therapy for any issue you may have discussed with them.
You can access the drug companies full disclosure document, known as the “package insertˮ by plugging: “FDA—name of your drug”, into your search engine.
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PD PSYCHOSIS DRUGS
(Originally written April 2021)
PD patients may have seen recent drug advertising informing them about psychosis events such as hallucinations and delusions. Excessive or inadequate dopamine levels may contribute to these events.
Several of which are listed below:
Nuplazid
Approved by the FDA for use in PD psychosis in 2016.
Box warning in package insert; not for use in elderly with dementia.
Drugs that may alter EKG when used with Nuplazid: anti–arrhythmics, other antipsychotics, two antibiotics.
Drugs that may require a dose reduction of Nuplazid when used together: two antifungals, one antibiotic, one antiviral.
Drugs that may require a dose increase of NUPLAZID when used together: two antiepileptics, St. Johnʼs wort.
2 Clozaril
May cause a rare but serious side effect known as agranulocytosis (a reduction in white blood cells that interferes with the bodyʼs ability to fight infection).
Requires the patient to have a weekly blood test for the first six months, then every two weeks
Seroquel
Has fewer side effects, but there is limited evidence for its efficacy in people with PD.
TIDBITS
If you experience side effects that may be unknown, you may report them to the Food & Drug Administration at 800–FDA–1088
Keep the Poison Control Hotline posted on your refrigerator 800–222–1222
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MANAGING MEDICATIONS
(Originally written March 2021)
What we know
Dopamine replacement is vital to living well with PD. Should you have an aversion to taking pills, address this with your care provider or in your support group. Symptoms evolve throughout PD, so dosing and timing may require frequent adjustments.
Dosing frequency of drugs is determined by the half–life. An immediate release drug has a more frequent dosing schedule than a controlled release one (it’s because the manufacturer has developed this as a tool for the prescriber). We’re referring to the same drug in different formulas here.
Each one of the pills we consume is metabolized and eliminated at different rates.
An array of pill organizers is available for purchase, and a few companies will organize your meds into daily “pill packsˮ. You’ve seen them in weekly, daily, two or three day organizers; even broken down into dose/ day containers! It will all boil down to what you prefer, and what is best for you.
Dose timing in PD patients is absolutely critical for all of the Rx meds, but especially with carbidopa/ levodopa formulations. The levadopa component here helps maintain proper dopamine levels available to our nervous system.
If youʼre only taking two or three meds, you may well choose to not use pill organizers—itʼs always the patient’s and healthcare providersʼ choice.
Consider the following ideas on keeping meds organized:
Separate organizers… one for Rx meds and one for OTCʼs and supplements.
Letʼs go off the tracks for a bit and think about what we can do to maximize our drug therapy, keep our small mountain of prescriptions and supplements organized, and possibly live a better life while dealing with PD. The answer may be simple AND overlooked… it could just be the lowly pill box. • • • • •
Devise a plan for using the organizer in the best possible way (I use a lidded round pill box and put two days of meds in it, a total of seven pills per day). After I’ve taken three am pills, I lay the two noon pills on top of the container and so on. When outside of the home the small container easily fits in a front pocket.
Youʼll have to devise the best, least cumbersome method for you. The payoff may result in a more stress free and productive life.
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PHARMACY TIPS AND COMMENTS
(Originally written July 2020 – during Covid–19)
As our continued travel restrictions remain in place, maybe some tips on the pharmacy side could be beneficial to you and your caregivers.
Get to know the pharmacist in charge (corporate), or pharmacist owner (independent), and the lead pharmacy technician. These two individuals can prove invaluable for assistance with a number of issues.
Drug pricing. Contractual agreements between pharmacies and insurers obligate pharmacists to do certain things. Always ask what the “off insuranceˮ price would be—this is sometimes referred to as “the usual and customaryˮ price. You may be surprised to find on some occasions it is lower than your co–pay. Using this technique may keep you from entering the “donut holeˮ of your insurance later in the year too.
Ask if there a coupon program which would allow you to get a cheaper price (example: GoodRx. com). Same effect on “donut holeˮ. Should you have a generic drug with a seemingly high co–pay, ask the lead technician (that you now know) what tier this drug falls into. You may get this person to request a prior authorization, commonly known as a PA, from your insurer to move the drug to a different tier. This requires the healthcare provider to advocate for you, but the tech will handle this for you.
Most pharmacies can get reimbursed for a once–a–year MTM (medication therapy management) by your insurer. This is a comprehensive review of your meds, OTC usage, side effects, etc., done by your pharmacist (that you now know).
Ask for a “package insertˮ on your drug. This is the disclosure document by the manufacturer and is fairly technical reading, but youʼll learn something you may not know. I once took a med twice a day (8am & 8pm) because it was labeled this way. After reading the package insert, I learned it should be taken after breakfast and lunch and would be 3–4 times more bioavailable (useful) when taken with food. And Iʼm supposed to know better!
Keep your drug list up to date and available for your healthcare provider, hospital, pharmacist, or other healthcare providers. Try to keep your meds at one pharmacy if possible as their software program usually checks for drug interactions.
Get the Aware & Care kit from the Parkinsonʼs Foundation...itʼs free.
Learn to use your healthcare providersʼ online patient portal. Jot down your questions at home as you think of them, a couple weeks before your appointment. A few days before your appointment send the comprehensive list via e–portal to your healthcare provider, then hit “print screen.” You and your healthcare provider now have a copy of the list you wanted to discuss. A Journal sheet is available on the next page.
16 RX NOTES FOR PARKINSON’S DISEASE
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Parkinson’s Disease Fact Sheet for Nurses
Parkinson’s disease is a progressive, incurable neurological disorder associated with a loss of dopamine-generating cells in the brain that results in a complex array of symptoms. It is primarily associated with progressive loss of motor control, but there are many more non-motor symptoms. Parkinson’s impacts an estimated one million people in the United States.
Critical Clinical Care Considerations
• To avoid serious side effects, Parkinson’s patients need their medications on time, every time — do not skip or postpone doses.
• Do not substitute Parkinson’s medications or stop levodopa therapy abruptly. Doing so may cause a life-threatening condition called neuroleptic malignant syndrome (NMS).
• Write down the exact times of day medications are to be administered so that doses are given on the same schedule the patient follows at home.
• Resume medications immediately following procedures, unless vomiting or severely incapacitated.
• If an antipsychotic is necessary, use pimavanserin (Nuplazid), quetiapine (Seroquel) or clozapine (Clozaril). DO NOT use haloperidol (Haldol).
• Be alert for symptoms of dysphagia (trouble swallowing) and risk of pneumonia. Consult with SLP is recommended.
• Ambulate as soon as medically safe. Patients may require assistance. Consult with PT is recommended.
Medications That May Be Contraindicated in Parkinson’s Disease
Medical PurPose safe Medications Medications to avoid Antipsychotics pimavanserin (Nuplazid, FDA approved to treat Parkinson’s disease psychosis) quetiapine (Seroquel) clozapine (Clozaril)
Pain Medication most are safe to use, but narcotic medications may cause confusion/psychosis and constipation
Anesthesia request a consult with the anesthesiologist, surgeon and Parkinson’s doctor to determine best anesthesia given your Parkinson’s symptoms and medications
Nausea/GI Drugs domperidone (Motilium) trimethobenzamide (Tigan) ondansetron (Zofran) dolasetron (Anzemet) granisetron (Kytril)
Antidepressants fluoxetine (Prozac) sertraline (Zoloft) paroxetine (Paxil) citalopram (Celexa) escitalopram (Lexapro) venlafaxine (Effexor)
avoid all other typical and atypical antipsychotics
if patient is taking MAO-B inhibitor such as selegiline or rasagiline (Azilect), avoid: meperidine (Demerol)
if patient is taking MAO-B inhibitor such as selegiline or rasagiline (Azilect), avoid: meperidine (Demerol) tramadol (Rybix, Ryzolt, Ultram) droperidol (Inapsine) methadone (Dolophine, Methadose) propoxyphene (Darvon, PP-Cap) cyclobenzaprine (Amrix, Fexmid, Flexeril) halothane (Fluothane)
prochlormethazine (Compazine) metoclopramide (Reglan) promethazine (Phenergan) droperidol (Inapsine)
amoxapine (Asendin)
20 RX NOTES FOR PARKINSON’S DISEASE
downloaded from parkinson.org—resources for your patients fact sheet
The Parkinson’s Foundation Aware In Care campaign aims to help people with Parkinson’s get the best care possible during a hospital stay. For more information please visit Parkinson.org/AwareInCare or call 1-800-4PD-INFO (473-4636).
Common Symptoms of Parkinson’s Disease
Motor
• Bradykinesia (slowness of movement)
• Decreased ability to swallow (dysphagia) and drooling
• Freezing—being stuck in place when attempting to walk
• Lack of facial expression
• Low voice volume or muffled speech
• Stiffness/rigidity of the arms, legs or trunk
• Stooped posture
• Tremor or shaking at rest
• Trouble with balance and falls
Non-Motor
• Anxiety
• Cognitive decline and dementia
• Constipation
• Depression
• Hallucinations and psychosis
• Impulse control disorders
• Orthostatic hypotension
• Pain
• Sexual dysfunction
• Sleep disturbances
Typical Parkinson’s Medications
L-DOPA DOPAmine AgOnists
carbidopa/levodopa (Sinemet or Sinemet CR) carbidopa/levodopa oral disintegrating (Parcopa) carbidopa/levodopa/entacapone (Stalevo) carbidopa/levodopa extended-release capsules (Rytary) carbidopa/levodopa enteral solution (Duopa)
• Urinary dysfunction mAO-B inhiBitOrsAnti-ChOLinergiCsCOmt inhiBitOrsOther rasagiline (Azilect) selegiline (l-deprenyl, Eldepryl) selegiline HCL oral disintegrating (Zelapar)
ropinirole (Requip) pramipexole (Mirapex) rotigotine (Neupro) apomorphine (Apokyn)
trihexyphenidyl (formerly Artane) benztropine (Cogentin) ethopropazine (Parsitan)
entacapone (Comtan) tolcapone (Tasmar) carbidopa/levodopa/ entacapone (Stalevo) *has L-DOPA in formulation
amantadine (Symadine, Symmetrel) extended-release amantadine (Gocovri, Osmolex ER)
Special Alert: Drugs such as benzodiazepines, muscle relaxants, bladder control medications and other medications used for sleep and pain may lead to confusion, hallucinations and other symptoms.
Consequences of Untimely Medication Administration: As PD medications wear off motor symptoms return which can impact a patient’s ability to function. PD patients are at risk for:
• Falls — due to rigidity, postural instability, freezing and bradykinesia
• Aspiration pneumonia — due to dysphagia from impairment in the muscles needed for swallowing
• Incontinence — due to rigidity and bradykinesia which impairs the ability to get to the bathroom
• Skin breakdown — due to the inability to change position freely
• Emotional distress — due to feelings of helplessness, frustration, anxiety, fear, depression, embarrassment
If the patient has deep brain stimulation device (DBS) or uses Duopa Therapy consult the Deep Brain Stimulation (DBS) Precautions post card, Duopa Therapy Precautions post card, and the Special Considerations pages within the Hospital Action Plan.
downloaded from parkinson.org—resources for your patients fact sheet
RX NOTES FOR PARKINSON’S DISEASE 21
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