An estimated one million people in the United States have been diagnosed with Parkinson’s Disease (PD) making it one of the most common neurological disorders in patients. This number is estimated to double in the next 30 years as PD is associated with increasing age. PD patients have a deficiency of dopamine in their brain and many of their medications are used to increase this neurotransmitter. They are frequently very sensitive to missing even one dose of their Parkinson medications and may exhibit increased rigidity, loss of balance, agitation, and confusion if their dosing schedule is delayed. Neuroleptic malignant syndrome or parkinsonism-hyperpyrexia syndrome can develop if their medications are held too long or as a result of serious infection.1 Many drugs used in the perioperative period, such as metoclopramide, butyrophenones (haloperidol, droperidol), and phenothiazines (promethazine, prochlorperazine) have anti-dopaminergic activity that can worsen the symptoms of PD. Show Depression is a common neuropsychiatric manifestation of PD and many of these patients will be taking serotonergic antidepressants that can interact with serotonergic medications administered in the perioperative period and cause the potentially fatal serotonin syndrome. The potent monamine oxidase inhibitor (MAOI) methylene blue is a frequent precipitator of serotonin toxicity in the hospital in patients who are taking other serotonergic medications. Methylene blue predominantly inhibits MAO-A which is responsible for deaminating serotonin. PD patients may be prescribed selective MAOI-B medications such as selegiline and rasagiline that inhibit metabolism of dopamine. Though caution is still advised, several studies have demonstrated that the risk of serotonin syndrome with these selective MAOI-B drugs is extremely low, even in combination with serotonergic antidepressants. Acetylcholinesterase inhibitors for PD dementia (rivastigmine, donepezil, and galantamine) are commonly prescribed, and these drugs have been associated with a prolonged effect of succinylcholine (up to 50 minutes) and increased resistance to non-depolarizing neuromuscular blocking drugs. Treatment for PD is polypharmacy with the potential for numerous adverse drug interactions with perioperative medications. Anesthesia professionals should be aware of the symptoms and signs of PD exacerbations, neuroleptic malignant syndrome (parkinsonism-hyperpyrexia syndrome), and serotonin toxicity2 and understand which commonly used anesthetic drugs possess anti-dopaminergic and serotonergic activity.3 In addition, PD patients have difficulty swallowing and are at increased risk for aspiration and falls. They have increased lengths of stay and increased complications with surgery.1 Because of these concerns, the Institute for Safe Medication Practices (ISMP) issued a recent medication
safety alert with recommendations on the medication management and perioperative care of PD patients (https://www.ismp.org/newsletters/acutecare The authors have no conflicts of interest to declare for this article. Dr. Lee is Co-Editor of the APSF Newsletter and Professor of Anesthesiology and Neurological Surgery at Vanderbilt University Medical Center in Nashville, TN. Dr. Meyer is Regional Director and Associate Professor of Anesthesiology at Baylor Scott & White Health, Texas A&M College of Medicine in Temple, TX. References
Problem: One-third of all patients with Parkinson’s disease visit an emergency department or hospital each year, making it a surprisingly common occurrence.1 The disease affects about 1 million people and is currently the fourteenth leading cause of death in the US. Hospitalization can be risky for patients with Parkinson’s disease when viewed from the perspective of pharmacological management. Patients with Parkinson’s disease require strict adherence to an individualized, timed medication regimen of antiparkinsonian agents. Dosing intervals are specific to each individual patient because of the complexity of the disease. It is not unusual for patients being treated with carbidopa/levodopa to require a dose every 1 to 2 hours. When medications are not administered on time, according to the patient’s unique schedule, patients may experience an immediate increase in symptoms.2,3 Delaying medications by more than 1 hour, for example, can cause patients with Parkinson’s disease to experience worsening tremors, increased rigidity, loss of balance, confusion, agitation, and difficulty communicating.2 Studies show that three out of four hospitalized patients with Parkinson’s disease do not receive their medications on time, or have had doses entirely omitted.4 According to the National Parkinson Foundation, 70% of neurologists report that their patients do not get the medications they need when hospitalized.2 Undergoing surgical procedures can be particularly risky for patients with Parkinson’s disease. Antiparkinsonian agents have been inappropriately withheld because patients were NPO for surgery, and surgical patients have been given a contraindicated anesthetic agent, or a centrally acting antidopaminergic drug such as haloperidol, metoclopramide, or prochlorperazine, postoperatively. One in three patients with Parkinson’s disease has been prescribed contraindicated drugs during hospitalization. Serious complications, mostly neuropsychiatric, have occurred in more than half of these patients.4,5 Two case examplesThe first case reported to ISMP involved a woman with Parkinson’s disease who was admitted to a hospital with a urinary tract infection. Upon admission, the patient’s medications were recorded during medication reconciliation. The patient told the nurse that she needed her medications right away. But she had been uncertain about the dose of a few medications, and it took several hours to collect further information about these doses. Once ordered, the medications were scheduled using the hospital’s standard administration times. However, for patients with Parkinson’s disease, it is safest to administer antiparkinsonian drugs according to the scheduled times the patient takes the medications at home. 2,4 In this case, the patient received all of her antiparkinsonian medications several hours late. While awaiting the medications, the patient found it hard to talk and communicate with hospital staff and her family. Her tremors intensified and she had difficulty maintaining her balance. She became so confused and agitated from not receiving her medications that her physician ordered haloperidol 5 mg intramuscularly. The physician was not aware that haloperidol can worsen the symptoms of Parkinson’s disease,6,7 and the pharmacist and nurse did not detect the prescribing error. The adverse symptoms worsened after receiving haloperidol, thus lengthening the patient’s hospitalization. Later, when this patient required hospitalization for an elective surgery, the family selected a facility associated with the patient’s neurologist. The family assumed the staff would be more knowledgeable about the disease, but they ran into similar problems. The patient did not receive her medications on time and experienced the same symptoms as during the previous hospital admission. Once again, this extended her hospital stay unnecessarily. In another case, reported to the National Parkinson Foundation, a hospitalized patient with Parkinson’s disease had surgery for a herniated disc.2 During the admission process, the patient’s wife alerted the staff about the need to administer her husband’s antiparkinsonian drugs exactly according to his schedule at home. She found staff were unaware of the need for timely drug administration and, thus, repeated the warning with each shift change. However, when the patient’s wife was not by her husband’s side, he did not get his medications on time. He was also prescribed and administered a contraindicated drug. The patient suffered significant hallucinations and was unable to communicate until his medications were readjusted to his schedule at home. Other medication safety concerns Even with correct medication administration timing based on the patient’s home schedule, dosing errors have been reported with carbidopa/levodopa. The drug is available in many different strengths and forms, from an orally disintegrating tablet to extended- and immediate-release formulations. Levodopa, which converts to dopamine in the brain, can cause episodes of acute psychosis and dyskinesia when given in large doses, which can unnecessarily extend hospitalization. Also, patients may take different strengths of carbidopa/levodopa each time throughout the day, increasing the risk for errors. Even if well understood, documenting a complex schedule may be difficult and even more challenging in some electronic health records. Dysphagia is another manifestation of Parkinson’s disease and can affect the patient’s ability to swallow medications. The symptoms include frequent coughing while drinking and taking medications and a gurgling voice.8 Safe Practice Recommendations: When hospitalized patients with Parkinson’s disease experience problems with incorrect timing of drug administration, or receive drugs that exacerbate disease symptoms, their stay may be prolonged. Also, the loss of disease control at the hands of those who should be experts undermines the patient’s faith in their healthcare team. Healthcare providers should consider the following recommendations to improve the medication management of hospitalized patients with Parkinson’s disease. Expedited reconciliation. Establish an expedited medication reconciliation process upon admission for all patients with Parkinson’s disease. Set the goal of obtaining an accurate list of medications within 2 hours of admission that includes the exact doses and timing of medications that the patient took as an outpatient, whenever possible. Consider an automatic pharmacy consultation when patients with Parkinson’s disease are admitted to assist with timely medication reconciliation. Some patients with Parkinson’s disease have memory impairment, so family members who have close contact with the patient may need to be contacted. This may also require calling the patient’s neurologist. Build a unique schedule. Establish a method and process to create and communicate the patient’s individualized medication schedule in order to control symptoms throughout the day. This requires clear communication between the patient care unit and the pharmacy so patient-specific schedules are not overridden with standard dosing schedules. Avoid nonformulary delays. To the extent possible, ensure that your formulary provides common Parkinson’s disease medications and doses so that drug administration is not delayed while the pharmacy obtains nonformulary medications. Know the symptoms. Upon admission, obtain information regarding the patient’s current symptoms, ability to carry out daily activities, and mental status as a baseline to observe for increasing symptoms potentially due to the effects of drug therapy. Avoid contraindicated drugs. Some medications alter the brain’s dopamine receptors causing symptoms, while others chemically interact with antiparkinsonian medications causing side effects. These contraindicated medications (e.g., dopamine blockers; older antipsychotics and antidepressants; certain antiemetics, pain medications, and anesthesia agents) should be avoided.9 If the patient is taking selegiline or rasagiline, other medications must also be avoided, for example, meperidine, traMADol, methadone, mirtazapine, St. John’s Wort, cyclobenzaprine, dextromethorphan, pseudoephedrine, phenylephrine, and ePHEDrine. There are alternative choices within these categories of medications that are safer to use for patients with Parkinson’s disease. Build alerts. Develop strategies to alert prescribers and pharmacists to drug-drug and drug-disease interactions. For example, develop a pop-up warning to alert prescribers and pharmacists when a contraindicated drug is ordered for a patient who is already receiving carbidopa/levodopa and/or selegiline or rasagiline. Neurology consultation. When patients with Parkinson’s disease are hospitalized, consider consulting the patient’s neurologist or other specialist to evaluate antiparkinsonian medications to ensure safety. At a minimum, let the patient’s neurologist know the patient has been hospitalized. (Only 25% of neurologists are confident they would be contacted if their patients were admitted to the hospital.2) If the neurologist is not consulted, require a clinical pharmacist or expert in Parkinson’s disease to review the patient’s medications on the first day of admission. If possible, generate a computer alert, triggered by the patient’s diagnosis or prescribed drugs, to let the knowledgeable clinician know that a patient has been admitted, thus enabling their involvement early in the course of the admission.4 Manage NPO status. If there is any plan to keep a patient with Parkinson’s disease NPO that would interfere with the patient’s unique schedule of medication administration, a neurologist or neurology team should oversee the medication regimen change to avoid complications. Do not abruptly discontinue medications. Never abruptly discontinue antiparkinsonian medications. Serious reactions such as neuroleptic malignant-like syndrome can occur when antiparkinsonian medications are discontinued or the dose of levodopa has been reduced abruptly.10 This can result in a high fever, sweating, unstable blood pressure, stupor, muscular rigidity, and autonomic dysfunctions, that can be life-threatening. Promote swallowing. When taking medications, patients should be asked to sit upright with their hips flexed at 90 degrees, and to remain sitting if possible for 45 minutes. They should also be encouraged to swallow twice after taking pills or drinking liquid.8 Do not crush or allow the patient to chew extended- or controlled-release medications (e.g., SINEMET CR). Optimal surgery time. When possible, schedule surgery as early in the day as possible (8 a.m. to 9 a.m. is optimal) for patients with Parkinson’s disease to promote best symptom management.11 Antiparkinsonian medications should be administered as close as possible to the patient’s medication schedule pre- and postoperatively, and restarted immediately after surgery. Focused education. Educate staff regarding the importance of timing with antiparkinsonian medications—that they must be on time, every time. Focusing education in particular areas such as the emergency department, orthopedic units, and key medical units, may be the most effective strategy given that many units will have a low census of patients with Parkinson’s disease.4 Identify when patient symptoms are not controlled/managed and consult the neurologist. Also remind staff to be alert to the risk of falls. Patient education. In preparation for Parkinson’s Awareness Month in April, obtain a free copy of an Aware in Care kit provided by the National Parkinson Foundation for patients and caregivers with an aim to ensure every patient with Parkinson’s disease receives the best care possible during hospitalization. The kit includes a plan for hospitalization; a medical identification bracelet; a Medical Alert Card that states, “I have Parkinson’s disease….I am not intoxicated,” along with space for listing current medications and emergency contacts; medication forms; disease fact sheets; and more. Teach patients how to obtain their own Aware in Care kit by calling 800-473-4636 or visiting: www.awareincare.org. Report adverse reactions. All adverse drug events or reactions that happen to patients with Parkinson’s disease should be reported to the primary neurologist who is taking care of this patient, because a dose adjustment, change to a different medication, or gradual discontinuation of a medication may be necessary.12 ISMP thanks Amy Fox, PharmD Candidate at Ohio Northern University, for providing the research and framework for this article. ISMP also thanks Mohammed Aseeri, BS, PharmD, BCPS, FISMP, from King Abdulaziz Medical City-Jeddah in Saudi Arabia for contributing content to this article. References
What medications interact with selegiline?Some products that may interact with selegiline include: antidepressants (including bupropion, maprotiline, mirtazapine), other MAO inhibitors (isocarboxazid, linezolid, metaxalone, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, tranylcypromine), appetite suppressants (such as ...
What medication is contraindicated in Parkinson's disease?These drugs include Prochlorperazine (Compazine), Promethazine (Phenergan), and Metoclopramide (Reglan). They should be avoided. Also, drugs that deplete dopamine such as reserpine and tetrabenazine may worsen Parkinson's disease and parkinsonism and should be avoided in most cases.
What should I avoid while using selegiline?What should I avoid while taking selegiline?. air dried meats, aged or fermented meats, sausage or salami (including cacciatore and mortadella), pickled herring;. any spoiled or improperly stored beef, poultry, fish, or liver;. beer from a tap, beer that has not been pasteurized;. What medication is contraindicated with levodopa?The use of levodopa is contraindicated with the concurrent use of monoamine oxidase inhibitors (MAOIs) because it can lead to a hypertensive crisis.
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