Frieda Wiley, PharmD

Frieda Wiley, PharmD, BCGP, is a writer and pharmacist. 

The term vasculitis refers to a rare and complex family of diseases that can cause inflammation of the aorta and other arteries, veins, and blood vessels. Vasculitis manifests in many forms, involving different parts of the body and presenting with a diverse range of severity and duration.

Kawasaki disease (KD),a form of vasculitis that is exclusive to children,is known to inflame blood vessels throughout the body, especially those feeding the heart. Currently, the CDC is investigating reports of multisystem inflammatory syndrome associated with coronavirus disease 2019 (COVID-19) in children, which may present with KD-like features.

Recent studies suggest that, although rare, KD may be triggered by underlying infections such as COVID-19 or flu.

 KD produces clinical signs such as prolonged fever; swollen lymph nodes; bloodshot eyes sans drainage; rash; red, cracked lips and tongue; swollen lymph nodes on 1 side of the neck; and a fever of 100.4 °F or more that persists for 5 days or longer. KD typically occurs in children under 5 years of age but can also affect older children.

The coronavirus family has been suspected of playing a role in the onset of KD for the past 2 decades. In a 2005 study, a group of researchers in Connecticut, identified a novel strain of the disease, human coronavirus New Haven, in the respiratory secretions of 8 of 11 children who had KD versus 1 out of 22 controls.

COVID-19 was initially pegged as a disease that primarily affects the respiratory system. However, that changed with news of potential cutaneous involvement in certain populations in Italy in spring 2020, following reports of strange lesions on children’s skin. The results were published in The Lancet in May 2020. The Italian province of Bergamo, which had the highest number of COVID-19 infections and deaths in the Mediterranean country, experienced a 30-fold increase in incidence compared with the monthly incidences recorded during the previous 5 years.

During the month of April, investigators observed an increased incidence of what they referred to as “Kawasaki-like disease.” Between February 18 and April 20, 2020, 10 children (aged 7.5 years [SD, 3.5]) received diagnoses of KD. Children were admitted to the hospital and, on average, presented with fever on day 6 (range, 4 to 8). Half the patients presented with typical manifestations of KD, including cutaneous involvement such as polymorphic rash; hand and feet anomalies such as firm induration, erythema, or both; and nonexudative conjunctivitis. Investigators observed altered appearance of the lips and/or oral cavities of 80% of patients. The remaining 5 patients presented with incomplete forms of KD.

However, truly discerning the connection between COVID-19 or other members of the coronavirus family requires additional study.

KD manifestations often resolve on their own, and many children recover fully. However, children who fail to receive appropriate medical evaluation and treatment face heart damage and other complications. Because no specific test can diagnose KD, a fever lasting for more than 5 days is often used as an indicator of potential disease. To help determine whether a patient has KD, a physician might run blood and urine tests, an electrocardiogram, and an echocardiogram.

KD has 2 primary treatments: prolonged aspirin therapy, initiated every 6 hours and then decreased to once-daily dosing, and intravenous immunoglobulin to curtail swelling in blood vessels.

Vasculitis. American College of Rheumatology. Updated March 

https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Vasculitis

Kawasaki disease (KD). American College of Rheumatology. March 2019. Accessed May 28, 2020. 

https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Kawasaki-Disease-KD

Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicenter of the SARS-CoV-2 epidemic: an observational cohort study. 

 2020;395(10239):1771-1778. doi:10.1016/S0140-6736(20)31103-X

Articles

A Kawasaki-like inflammatory disease has affected children who have coronavirus disease 2019.

Investigators Find COVID-19 Connection in Vasculitis

An estimated 32 million individuals 12 years and older used psychedelic medicine in the United States in 2010, according to a US population survey. As the opioid epidemic has eclipsed concerns about illegal drugs in recent years, the medical community and the federal government alike have begun reexamining certain illicit drugs as potential alternatives to opiates in pain management.

Perhaps no other "illicit" substance has played a greater role in turning the tides recently than medical cannabis. Its slow but steady serial legalization and decriminalization at the state levels to treat a variety of complaints, including pain, have helped bring cannabis, cannabis products, and other stigmatized  drugs to the forefront.

"It is most surprising that even though cannabis has been used for a number of ailments for thousands of years—even dating back to the 28th century BC—it is now being recognized as a valid treatment option," said Swathi Varanasi, PharmD, an integrative health pharmacist and medical cannabis consultant in Los Angeles, California. "However, because of the way cannabis has been criminalized, it hasn't been integrated into standard treatment algorithms.'

Regulatory measures aside, pharmacists and other members of the medical profession often wrestle with safety when assisting patients who use cannabis for medicinal purposes. Cannabis has been studied extensively for numerous uses, including its potential benefits in neuropathic pain, chronic pain, and inflammation. A 2014 study found that most patients cited relief from chronic pain as the most common reason for their medicinal use of cannabis. Yet the plant's psychoactive properties continue to draw concerns regarding abuse potential, owing to the effects of 1 phytochemical, Delta-9-tetrahydrocannabinol, known for its psychoactive properties.

However, these are not the only challenges pharmacists face when it comes to assisting patients. "The biggest pitfall in advising patients on cannabis is that dosing is so difficult to standardize," Victoria Starr, RPh, a cannabis pharmacist at SageLife, LLC, in Portland, Oregon, told 

Cannabis for medicinal purposes is highly complex, largely because of its high number of phytochemicals, called constituents. To date, the plant has been found to contain more than 560 constituents. When individuals consume these as the whole plant, the chemicals ofery synergistic and therapeutic benefits while mitigating potential toxicities, what's known as the entourage effect. Synthetic cannabis typically contains only 1 active ingredient and lacks additional chemicals that can help regulate undesirable effects. However, customizing cannabis dosing to even the individual patient is no small feat.

"Besides attaching medical benefits to each of these components, the combination of synergistic benefits needs to be determined, along with the proper ratio and dose," Starr explained. "So unlike Western medicine, in cannabis, there exists a multitude of different medications—with a wide range of potencies, targeting a vast array of medical conditions—made up of varied combinations of cannabinoids, terpenes, and flavonoids.

Psilocybin, the primary ingredient found in mushrooms that produce psychoactive effects, in enjoying an increased share of popularity and renewed exploratory use.

It’s exciting that patients are starting to ask their pharmacist about psilocybin,” said Emily Kulpa, PharmD, an integrative health pharmacist and psychedelic medicine consultant based in Milwaukee, Wisconsin.

Although psychedelic mushrooms have been used for millennia, they gained popularity in the United States for recreational use during the 1960s and had spawned some academic interests as well. From 1960 to 1962, psilocybin, along with psychedelic relatives lysergic acid diethylamide (LSD) and mescaline, became the focus of a series of trials known as the Harvard Psilocybin Project. At the time, these drugs were legal. Criminalization of these drugs would later erupt in the following decade as safety concerns grew.

Fast-forward to the new millennium. Psilocybin sparked some interest in its potential analgesic effects in cluster headaches and migraines. Psilocybin agonizes the 5-hydroxytryptamine receptor and may interact with nociceptive and antinociceptive processing. The results from one 2016 retrospective study Googling the keywords “cluster headache discussion forums” and “migraine discussion forums” found that patients who self-treated themselves with psychedelic tryptamines such as psilocybin and LSD reportedly experienced a reduction in cluster frequency and severity.

Although these claims may warrant clinical study in pain management, research has focused on the role of psilocybin in mood disorders. Kulpa credits events in popular culturwith helping bring psilocybin into the mainstream. In the fall of 2019, Johns Hopkins announced the opening of the Center for Psychedelic & Consciousness Research, the first institution in the United States devoted exclusively to psychedelic research.

Indigenous to Thailand, Malaysia, Myanmar, and other regions of Southeast Asia, kratom (Mitragyna speciosa) belongs to the coffee family and also exhibits dose-dependent sedative and stimulatory effects. The plant is typically consumed in pill, capsular, or extract form, although some individuals brew dried or powdered leaves as a tea. Others may chew, smoke, or consume the leaves in food. However, because of kratom’s harmful adverse effects and abuse potential, the FDA warns individuals against using the substance.

Kratom contains mitragynine, an alkaloid bearing a tryptaminelike structure that exhibits µ- and ∂-opioid receptor agonist activity that results in dose-dependent stimulatory and analgesic effects. In lower doses, mitragynine produces stimulatory effects, whereas higher doses result in opioid-like activity. However, its metabolite, 7-α-hydroxymitragynine, exhibits significantly stronger µ-opioid receptor agonist behavior.

Although kratom is not an opioid, the CDC found an association between kratom use and overdose deaths, also involving opioid and nonopioid use, in the State Unintentional Drug Overdose Reporting System. Moreover, based on toxicology results, medical examiners or coroners determined kratom as the culprit in deaths in 11 states from July 2016 to June 2017 and 27 states during the last 6 months of 2017.

“There is no legitimate medical use for kratom in the [United States],” the Drug Enforcement Administration (DEA) wrote in a report on its website.8 On August 16, 2016, the DEA announced its intent to classify kratom as a Schedule I controlled substance, noting that the plant had been “abused for its ability to produce opioidlike effects” and “was often marketed as a legal alternative to controlled substances.”

Pharmacists should be aware of the substance so they can educate patients about the potential harms.

Varanasi believes the importance of cannabis in pain management will only continue to grow. “Preliminary evidence demonstrates cannabis’ ability to provide significant pain relief as well as [to help individuals] taper off opioids [particularly in the setting of addiction],” she said. “Though the research is inconclusive, patient anecdotes support the continued use of cannabis in pain management.”

In Oregon, the Oregon Psilocybin Program Initiative will appear on ballots in November 2020. “If passed, it would [be] the first state-sanctioned program for the administration of psilocybin services between a certified practitioner and a patient,” Varanasi said. “This would not only set the standard for other states but also support published studies reporting that a strong patient-practitioner relationship improves overall health outcomes.”

In the meantime, patients and practitioners alike will have wait to see how these and other psychedelics will alter integrative medicine and the world of health care.

. Over 30 million psychedelic users in the United States. F1000RED. Preprint posted online March 28, 2013. doi:10.12688/F1000research.2-98.v1

Light MK, Orens A, Lewandowski B, Pickton T. Market size and demand for marijuana in Colorado. The Marijuana Policy Group. 2014 [November 17, 2016]

ElSohly MA, Radwan MM, Gul W, Chandra S, Galal A. Phytochemistry of cannabis sativa L. 

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Doyle J. Legend of a mind: Timothy Leary & LSD. November 26, 2014. Updated March 20, 2020. Accessed June 1, 2020. 

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Whelan A, Johnson MI. Lysergic acid diethylamide and psilocybin for the management of patients with persistent pain: a potential role? 

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Andersson M, Persson M, Kjellgren A. psychoactive substances as a last resort—a qualitative study of self-treatment of migraine and cluster headaches. 

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About. Johns Hopkins Center for Psychedelic & Consciousness Research. Accessed June 1, 2020. 

). Drug Enforcement Administration. November 2019. 

https://www.deadiversion.usdoj.gov/drug_chem_info/kratom.pdf. 

What is kratom? National Institute on Drug Abuse. April 2019. 

https://www.drugabuse.gov/publications/drugfacts/kratom

FDA and Kratom. FDA. Updated September 11, 2019. Accessed June 4, 2020. 

https://www.fda.gov/news-events/public-health-focus/fda-and-kratom

Olsen EO, O’Donnell J, Mattson CL, Schier JG, Wilson N. Notes from the field: unintentional drug overdose deaths with kratom detected — 27 states, July 2016–December 2017. 

Kruegel AC, Uprety R, Grinnell SG, et al. 7-Hydroxymitragynine is an active metabolite of mitragynine and a key mediator of its analgesic effects. 

DEA announces intent to schedule kratom. News release. Drug Enforcement Administration. August 30, 2016. https://www.dea.gov/press-releases/2016/08/30/dea-announces-intent-schedule-kratom

Once largely stigmatized, illicit substances are breaking into the field of pain management. 

Psychedelic Medicines for Pain Go Mainstream

In the wake of the novel coronavirus 2019 (COVID-19) pandemic, pharmacists face an ongoing challenge with helping patients optimally manage chronic conditions.

In HIV care, for example, pharmacists play a key role in monitoring treatments, counseling patients, and assisting with adherence challenges, all of which current social distancing measures can make more difficult. Furthermore, the potential effects of the COVID-19 virus on patients with HIV remain uncertain, even as reports indicate that other chronic conditions such as diabetes and hypertension may put affected individuals at higher risk.

“So far, there is no major report to suggest that HIV patients are more or less susceptible to COVID-19 than individuals who do not have HIV or are otherwise healthy,” Rodney Ho, PhD, professor of pharmaceutics at the University of Washington School of Pharmacy in Seattle, told 

According to a statement on Aidsinfo, a US Department of Health & Human Services website, the “limited data currently available do not indicate that the disease course of COVID-19 in persons with HIV differs from that of persons without HIV.” However, the website subsequently states that the use of effective antiretroviral therapy (ART) in the HIV population might be responsible for the current trend. Before the introduction of ART, a CD4 cell count below 200/mm3 was considered a risk factor for complications resulting from other respiratory infections. At press time, the website stated that whether HIV increases COVID-19 risk is still unknown. Until experts know for sure, the scientific consensus is that proactive measures to limit risk and exposure to COVID-19 should bear little difference to the measures taken by individuals who are generally healthy.

Health care systems have taken precautions to mitigate exposure and risk for patients with HIV. Perhaps the most significant change involves encouraging patients to stay home unless clinicians feel an office visit is medically necessary.

Clinicians are also taking proactive measures to prevent drug shortages and limit onsite visits. As a result, mail order use has surged. “We reach out to patients via phone around 5 to 10 days ahead of their next refill, so we can mail out their prescriptions to enhance adherence,” said a Houston, Texas–area HIV pharmacist who practices at an outpatient pharmacy located in a health center and wants to remain anonymous. “Sometimes we match the date with the patient’s next clinic visit and have their medications ready, making it easier for them to have access during the pandemic.”

In addition to enacting medication synchronization, the pharmacist’s organization now issues emergency fills and early refills to reduce or eliminate multiple trips to the pharmacy. Patients who pick up their prescriptions must maintain a 6-foot distance from other patients. The clinic also requires these patients to fill out a COVID-19 screening form that helps pharmacists determine who needs additional assistance or medical attention.

Physical distandistancing in the HIV community has driven a massive uptick in telemedicine services. Many patient interactions, such as follow-up visits and education, now occur remotely. Although the industry trend indicates that most services for this patient population have gone remote, exceptions may apply with at-risk populations.

For example, providers at ChristianaCare’s William J. Holloway, MD, Community Program in Wilmington, Delaware, might require a site visit for patients who are older than 60 years or have certain disease states, such as lung disease and hypertension. “We are using virtual and telephonic visits, as well as preset algorithms for COVID,” said Kelly Cantwell-McNelis, PharmD, AAHIVP, a clinical pharmacy specialist with the community program.

In the outpatient pharmacy based in Houston, Texas, pharmacists make adherence calls to patients to monitor refills while screening them for signs and symptoms of the virus. “Since HIV patients are immunocompromised, we ask them if they are experiencing dry cough, fever, or chills currently, and document them in our pharmacy software,” the HIV pharmacist at the clinic said.

Phone calls and tracking prove critical because the clinic has a high number of patients with CD4 counts falling below 200 mm3, a sign of full-blown AIDS. These patients receive regular phone calls to monitor and address adherence, as well as to screen patients for opportunistic infections. Because of the pandemic, patients are now given the COVID-19 screening questionnaire over the phone.

Although telemedicine interventions have made operations more efficient, there have been hurdles. For instance, helping patients understand why they should call the pharmacy before making a trip has become a teaching opportunity that requires vigilance. “It took us a couple of weeks to get patients to understand that they should call us first and let us triage their symptoms,”said Cantwell-McNelis.

On the virtual front, Dan Scales, PharmD, AAHIVP, director of collaborative care pharmacy at Vivient Health and owner and founder of Scales Pharmacy in Denver, Colorado, and his colleagues have worked diligently to get up to speed on a new technological platform. He said that he thinks the process has gone generally well but recognizes that success also depends on the patient’s resources. Scales noted major obstacles with a patient living in a rural area. “We have to use video relay because the patient’s internet connection is not stable enough to hold a conversation in real time,” Scales said. Because the patient is deaf, interaction also requires a sign language interpreter.

Historically, the health care industry has wrestled with telemedicine navigating the nebulous web of integration and reimbursement. If there is any benefit from the pandemic, it is the swift action to establish and bill for telemedicine services, according to Cantwell-McNelis. She cited a recent 

 article highlighting the near-overnight transition. “The speed of the transition has been dizzying. Changes that would typically encompass months of planning, pilot testing, and education have been compressed into days,” the authors wrote.

With no viable cure or treatment for COVID-19 yet, investigators are exploring the potential benefit of antiviral protease inhibitors (PIs) routinely used in HIV medicine. The findings’ effects on the HIV population continue to unfold with emerging data and research.

At press time, 15 studies exploring the effects of PIs on COVID-19 were found on ClinicalTrials.gov. Results from a randomized, controlled, open-label clinical trial on lopinavir-ritonavir (Kaletra) following 199 patients in China showed that the drug did not speed recovery or reduce the viral load in patients with COVID-19.

“Until we know more about how PIs affect COVID-19, people with HIV should not switch their HIV medicine in attempt to prevent or treat COVID- 19,” Scales warned.

Sources predict lasting changes in the post-COVID era of pharmacy. Scales and Cantwell-McNelis foresee telemedicine becoming a mainstay of treatment. Ho believes that the dynamics of the virus will further elevate the demand and profile of pharmacists’ contributions to the health care system by serving as a resource to the physician.

“Many physicians are emergency room doctors or heart specialists who are not trained in infectious diseases or to think about DDIs [drug-drug interactions] and how to monitor for heart conditions,” Ho said. “The pharmacist’s role is to serve as an expert when the physicians are caring for patients by looking for data to provide the best evidence available and being able to develop appropriate time-sensitive information.”

Virtual care takes center stage amid the pandemic.

Pharmacists Fight HIV

The uptick in dietary supplement use and integrative health and medicine practices in the United States creates both opportunities and concerns for pharmacists and health providers, who need to stay well informed to help patients avoid harmful effects. Some patients may seek vitamin or herbal supplements for health and wellness, often believing that these are safer than conventional OTC and prescription pharmaceutical products. However, so-called natural remedies come with their own set of health risks.

“Dietary supplements are very helpful and really needed when they are chosen correctly and properly,” said Farzana Kennedy, RPh, FACA, owner and president of Dalitso, an integrative pharmacy in Alexandria, Virginia. “Often, they can be harmful if not properly monitored or checked for interactions or contraindications in a patient who has preexisting conditions.”

Dietary supplement use has reached an all-time high, with 77% of Americans reportedly using these products, according to a 2019 survey conducted by the Council for Responsible Nutrition. The increased patient demand for non-pharmacologic health options has created unprecedented opportunities for pharmacists to expand their interactions with patients.

Many patients consider community pharmacies the ideal place to purchase vitamins and other dietary health supplements. Pharmacists can positively affect the patient experience by:

Providing supplement education Making supplement recommendations

Assessing for interactions, contraindications, and toxicities Collecting a patient’s complete medication history, including supplements

Assessing for drug-drug, drug- micronutrient, and drug- supplement interactions

Helping patients evaluate natural products for quality-related issues

Pharmacists can also educate patients about the potential effects of taking dietary supplements on laboratory test validity and results.

“In general, validating and interpreting laboratory test results can be key tools in helping health care professionals optimize clinical decisions related to their patients’ health,” said Cathy Rosenbaum, PharmD, RPh, MBA, CHC, CDP, a holistic clinical pharmacist and founder and CEO of Rx Integrative Solutions in Blue Ash, Ohio. “Pharmacists are uniquely poised to prospectively educate the public on any laboratory test interferences with medications, supplements, or micronutrients to minimize safety risks.”

Biotin: A Lesson in Disclosing Supplement Use

Through their frequent interaction, patients and pharmacists often build a strong rapport and a trusting relationship in which patients feel comfortable discussing supplements. Pharmacists should advise their patients to also report all dietary supplement and natural product use to physicians prior to any blood testing, Rosenbaum said.

A laboratory-testing interaction involving biotin illustrates several important ways pharmacists can help keep patients safe through counseling. Many patients who pick up a bottle of biotin, a water-soluble B vitamin, view it as a harmless supplement to enhance physical appearance (eg, skin, hair, nails). Rosenbaum warns that this assumption can be problematic because of the lack of clinical research with standardized biotin dosing to support these claims. The scientific community has long known that biotin functions in the body as a cofactor for enzymes involved in carboxylation reactions, and it plays a role in fatty acid and carbohydrate oxidation. Daily amounts of biotin needed for general health is defined in different ways because there is no standardized recommended dietary allowance or nutrient intake for this nutrient. A generally suggested intake for adults is between 30 mcg and 100 mcg a day.

OTC biotin products come in many doses that are significantly higher than the amount provided in adequate nutrition, some as much as 10,000 mcg per dose for therapeutic indications.

Several reports link high-dose biotin supplementation to falsely elevated levels of the thyroid hormones triiodothyronine and levorotatory thyroxine and falsely low thyroid-stimulating hormone levels, all used to diagnose and monitor thyroid disease. Taking supplemental biotin at 20 mg or more on a daily basis may interfere with thyroid bioassays that use streptavidin–or avidin–biotin systems.

Excessive biotin intake can lead to misdiagnosis, inappropriate treatment, or even death. For example, biotin supplementation can produce altered levels of troponin, one of the biomarkers elevated during acute myocardial infarctions. According to a November 28, 2017, FDA statement on biotin concerns, a patient who took high doses of biotin died because of complications related to falsely low troponin levels found in a test that relied on biotin technology. Because patients may be unaware of biotin interference, they may not report taking biotin supplements, and may even be unaware they are taking the supplement at all, according to the FDA.

CBD and Medical Cannabis: Countering Ads that Overpromise

The challenges of providing patient guidance in integrative medicine are not exclusive to biotin. The recent explosion of cannabis and cannabidiol (CBD) products presents more issues because these products are routinely promoted as completely safe, with no risks. Buying into this hype could have deleterious consequences for patients.

“Pharmacists providing direct patient care by providing medical cannabis or hemp-based CBD products must know and understand patient diagnoses, treatment plans, and how to monitor patients for interactions,” Kennedy told Drug Topics®.

“One big problem is that cannabis dosing is not standardized, and therefore, pharmacists should educate themselves to help patients receive optimal care regarding the product and dose that will sit well with them without [adverse] effects or other undesired feelings.”

Kennedy also stated that the ubiquitous deluge of CBD products from companies draws increasing concern about quality. She urges pharmacists to practice due diligence, vetting ingredients and confirming that there has been third-party testing for impurities, heavy metals, and other substances.

CBD products are often erroneously advertised as devoid of drug interactions. Evidence shows that CBD is well tolerated sans psychotic effects, provided doses do not exceed 600 mg. However, CBD potently inhibits CYP3A4 and CYP2D6 enzymes, which could cause higher-than-normal increases in serum concentrations of calcium channel blockers, benzodiazepines, antihistamines, antiretrovirals, statins, cyclosporine, and other drugs cleared through these enzymes.

For more information and to stay up-to-date on issues in dietary supplements and integrative health, visit 

Patients seeking vitamin or herbal supplements for health and wellness often believe that these are safer than conventional OTC and prescription pharmaceutical products; however, so-called natural remedies come with their own set of health risks.

Author | Frieda Wiley, PharmD

Articles

Investigators Find COVID-19 Connection in Vasculitis

Psychedelic Medicines for Pain Go Mainstream

Pharmacists Fight HIV

Integrative Medicine Presents Opportunities, Poses Challenges