Ayesha M. Khan, PharmD, BCPS, is a clinical assistant professor of pharmacy practice at Chicago State University College of Pharmacy (CSU-COP) and maintains a practice site at Rush University Medical Center. She received her Doctor of Pharmacy from Midwestern University Chicago College of Pharmacy in 2012 and then completed a PGY-1 Pharmacy Practice Residency at The University of Toledo Medical Center in Toledo, Ohio.

Ayesha Khan, PharmD, BCPS

About 7000 cases of toxicities associated with synthetic cannabinoids (ie synthetic marijuana, K2, or Spice) are reported annually to US poison control centers, and that reportedly accounted for two-thirds of overall substance abuse between 2005 and 2011.

Synthetic cannabinoids were first introduced in the United States in 2008 but have been used in Europe since 2004. They are classified as a Class I controlled substance by the Drug Enforcement Administration.  

Natural marijuana consists of an active ingredient known as delta-9- tetrahydrocannabinol (THC), which is one of the most psychoactive cannabinoid, whereas synthetic cannabinoids are analogs of natural marijuana that are chemically synthesized.  These synthetic compounds have similar symptoms to intoxication compared with natural marijuana, and these symptoms can be life-threatening. It is also known that there are many changes made to these analogs by the companies in order to avoid quality control.  

Synthetic cannabinoids have a higher potential to cause serious neuropsychiatric toxicity than marijuana. They are analogs of cannabis that are added to other herbals or hallucinogenic plants and act as full or partial agonists of the cannabinoid receptor CB1. Their drug effects are directly proportional to the amount being used. Compared with THC molecules found in marijuana, synthetic products are a 2 to 800 times more potent agonist of the CB1 receptor. It is evident that the products added to these analogs contribute to their increased toxicity. Symptoms can include ataxia, sedation, slurred speech, tachycardia, and vomiting. Severe toxicities were associated with delirium, dystonia, hallucinations, life-threatening bleeding, psychosis, and seizures.

There have been 155 cases of synthetic cannabinoids toxicities reported in Illinois since March 7 2018, including 4 deaths caused by severe bleeding, according to the Illinois Department of Public Health.

 It was found that synthetic cannabinoids used in Illinois and other regions of the United States recently were contaminated with a long-acting vitamin K antagonist called brodifacoum, which is commonly used in rat poison. It is also known as “superwarfarin," which refers to compounds that are used with cannabis analogs to enhance their effects. Some of the “superwarfarins,” such as bromadiolone, coumafuryl, and difenacoum, are known to be 100 times more potent than warfarin, with half-lives extending to weeks and months. Thus, it is important to screen for this compound in patients who present with bleeding after the use of synthetic cannabinoid. Lab values, such as an increased prothrombin time, international normalized ratio (INR), and activated partial thromboplastin time in patients using synthetic cannabinoids are helping in guiding this diagnosis. 

 provides treatment recommendations based on the INR and presence of bleeding, and table 2 outlines titration recommendations for vitamin K after treatment initiation. Based on patient presentation, supportive management, such as airway support or intravenous (IV) fluids, may also be needed.

Table 1.  Treatment Recommendation Based on INR and Presence of Bleeding

Severe or life-threatening bleeding with any elevated INR

10 mg IV vitamin K in 50ml IV fluid over 30 minutes

*Once the treatment has been initiated, monitor INR daily while inpatient. Dose is to be titrated to achieve a goal INR of <2.5.

Table 2.  Titration of Vitamin K After Treatment Initiation

INR Between Normal and < 2.5 for 48 hours

If otherwise clinically stable, discharge patient with outpatient follow-up instructions.

Consider decreasing the vitamin K dose and discharge patient with outpatient follow-up instructions.

Patients presenting with bleeding from synthetic marijuana use usually require substantial amounts of vitamin K for a prolonged period, because of longer half-lives of the marijuana components. To ensure optimal treatment and patient outcomes, have all the vitamin K supply available for outpatient therapy before the patient is discharged. Additionally, initial follow up intervals of 2 to 3 days is required after discharge and then every 1 to 2 weeks. When decreasing the vitamin K dose, the INR should be checked within 2 to 3 days of the dose reduction.

With the evolving make-up of synthetic cannabinoids, it is important for health care providers to routinely re-assess these recommendations. The CDC and local poison control centers offer useful guidance for best practices. 

This article was reviewed by Ayesha M. Khan, PharmD, BCPS.

Articles

The CDC and local poison control centers offer useful guidance for best practices.

How to Address Bleeding Reversal in Synthetic Cannabinoid Users

infection (CDI) is still considered the most common healthcare associated infection in the United States. CDI differs from most other infections as it usually occurs after treatment with antimicrobial therapy.

Some of the most commonly associated agents that CDI is associated with include clindamycin, ampicillin, cephalosporins, and fluoroquinolones. It is estimated that CDI costs the United States healthcare system $5 billion every year, and that the incidence for CDI has increased over the past 2 decades.

The Infectious Diseases Society of America (IDSA) in conjunction with the Society for Healthcare Epidemiology of America (SHEA) play a significant role in reducing the burden of 

 with their publication of clinical practice guidelines. Recently, the IDSA and SHEA have made an update to the previously published practice guidelines for CDI in 2010.  While many of the recommendations remain the same, there are a few key changes that the update has addressed:

Inclusion of specific pediatric guidelines

Discussion on laboratory guided diagnosis in adults

Discussion on fecal transplantation utilization

One of the first aspects that the update addresses is CDI in the pediatric population. The updated guidelines reflect the inclusion of diagnosis, surveillance, and treatment for the pediatric population, which the 2010 guidelines failed to address.

In addition the added guidelines regarding children, the update has clarified its recommendations for diagnosis of the disease. 

 is traditionally diagnosed by a variety of methods which include the past medical history of the patient, symptoms (such as the number of unformed stools in a 24 hour period), and laboratory test results. However, the previous guidelines were unclear due to the types of tests available for 

diagnosis. The updated guidelines attempt to clarify the previously unclear recommendations for laboratory testing in 

 patients. Before the emergence of testing methods like the Nucleic Acid Amplification Test (NAAT or molecular testing), institutions utilized Enzyme Immunoassay (EIA or toxin testing) to detect the presence of the organism in a particular sample. However, NAAT has increasingly become the benchmark method for laboratory testing of

The updated guidelines provide a much clearer algorithm for laboratory testing. The initial step of this algorithm is centered upon each institution’s practice.  To clarify, if the institution uses only specimens from patients who are not taking laxatives and have at least 3 or more unformed stools in a 24 hour period, then using the NAAT alone is satisfactory.  In addition, institutions may recommend using a stool toxin test in a multistep algorithm to satisfy the recommendation.  On the other side of the algorithm, the recommendation is an initial testing for 

 with glutamate dehydrogenase (GDH), which is then followed by a toxin test. If the immunoassay comes back negative, then the algorithm recommends follow-up with the NAAT. These recommendations are a slight departure from the current preoccupation of NAAT as a standalone method of testing.

One of the most striking changes that can be observed in the updated guidelines is the fact that metronidazole is no longer recommended as a first line treatment, which was previously recommended in the 2010 guidelines. Since then, metronidazole has been widely adopted in clinical practice as an indispensable tool in the fight against the disease. Rather, the new guidelines recommend vancomycin and fidaxomicin as first line treatments for 

. Two important caveats must be added; first, despite the seeming demotion of metronidazole from its original place in therapy, metronidazole can still be considered as first line treatment in situations where accessibility to vancomycin and fidaxomicin is limited. Of importance, metronidazole can be considered so long as the disease classification is mild-to-moderate and not severe. This appears to be a very reasonable concession, considering the fact that metronidazole is considerably cheaper than both vancomycin and fidaxomicin. The second noteworthy caveat involves the consideration of fidaxomicin as a first-line agent, as this drug was only approved by the FDA in 2011 (one year after the publication of the previously published 2010 guidelines).

Another considerable treatment change includes the recommendation on Fecal Microbiota Transplantation (FMT) therapy. This technique, otherwise known as the stool transplant, has now been recommended for the treatment of multiple recurrences of the disease. Previously, FMT was not recommended as an alternative therapy, but the panel has no taken into consideration the superior efficacy of this technique over the conventional antibiotic therapy for multiple recurrences of 

In recent years, probiotic use has become more and more prevalent. While probiotics such as 

 have been associated with some reduction in 

 recurrence, significant results demonstrating efficacy in controlled clinical trials have yet to be seen. Thus, standard utilization of probiotics in the setting of 

One challenge clinicians may face is the need to initiate antibiotic therapy soon after completion of 

 treatment. In an effort to avoid the recurrence of 

, use of prophylaxis vancomycin 125mg daily or fidaxomicin 200mg daily may be considered. Alternatively, treatment duration may be extended beyond 10-14 days. Further investigation of specific dosing and patient factors to guide prophylaxis dosing and patient selection criteria have yet to be seen in prospective, randomized trials. However, initial studies can provide clinicians with some guidance.

Overall, these updates to the clinical practice guidelines for 

 infection in adults and children have clarified many aspects of the previous 2010 guidelines.  With these changes, it is the responsibility of healthcare professionals, including pharmacists, to ensure that these updates are taken into consideration when treating patients with 

Roecker A, Bates B, Martin S. Gastrointestinal Infections and Enterotoxigenic Poisonings. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds.

Pharmacotherapy: A Pathophysiologic Approach, 10e 

The IDSA and SHEA have made a recent update to the previously published practice guidelines for CDI. While many of the recommendations remain the same, there are a few key changes that the update has addressed.

Practice Pearls from the 2018 Clostridium Difficile Treatment Guidelines

Prescribed medications are a primary cause of hyperkalemia in 35-75% of hospitalized patients.

High-risk patients are those with underlying renal impairment, hypoaldosteronism, and taking combination of drugs that can increase potassium level. Several classes of medications can induce hyperkalemia by different mechanisms.

Recognition and close monitoring of those medications is necessary to reduce morbidity and mortality related to hyperkalemia.

Drug-induced hyperkalemia may range from asymptomatic to life threatening.

Symptoms are mainly related to cardiac and muscular functions. The most serious manifestations include muscle weakness or paralysis, respiratory failure, cardiac conduction abnormalities, and cardiac arrhythmias.

There are 3 major mechanisms of drug-induced hyperkalemia:

Drug classes that are known to cause hyperkalemia are listed below (table 1).

Table 1. Drugs known to cause hyperkalemia and their mechanism of action

				Intravenous cationic amino acids (lysine, arginine)

Drug-induced hyperkalemia can be prevented by slow dose titration and close monitoring of serum potassium within the first week of therapy and after each dose adjustment. NSAIDs, especially chronic use, should be avoided in the elderly, dehydrated patients, patients with renal insufficiency, and those taking other drugs known to increase potassium. Alternative therapies with non-NSAID analgesics or topical agents should be recommended.

Management of acute hyperkalemia should be guided by the serum potassium level and severity of symptoms.

													Increases renal excretion of potassium

													Removes potassium from the gut in exchange of sodium

This article was primarily authored by Halina Mydra, PharmD Candidate at Chicago State University College of Pharmacy and reviewed by Ayesha Khan, PharmD, BCPS. 

Treatment Options for the Management of Acute Hyperkalemia

Medical missions provide unique learning and professional development opportunities for pharmacy students. Several pharmacy programs offer opportunities to participate in medical missions during APPE’s or as an extracurricular activity. During medical missions, pharmacy students work in interdisciplinary teams to deliver medical and pharmacy services to indigent communities across the globe. This allows students to be more culturally competent, build upon their clinical skills, develop better communication skills, and have increased empathy toward patients. It also gives students a chance to step out of traditional pharmacy roles and further contribute to patient care.

Listed below are some services pharmacy students may participate in during a medical mission:

Medication counseling is one of the key services provided by pharmacy. This is a great way for students to apply their knowledge from the didactic portion of their curriculum and apply it to direct patient care. This can be a challenge due to language or cultural barriers; however medical interpreters are typically available if needed. Having this direct patient interaction affords students the opportunity to become comfortable interacting and connecting with patients.

Students may be expected to provide this service alongside medication counseling. Health and wellness education is highly individualized depending upon each patient and their medical history, which challenges students to adapt to different situations. Disease-state management, disease prevention, diet, and exercise are some of the common subjects covered with patients.

Pharmacy students who are bilingual can participate in this service, especially when there is a shortage of interpreters. It also opens up more opportunities for interdisciplinary team work. For example, a pharmacy student who is fluent in the local language can be paired with medical student who is not to work-up a patient and develop a care plan. This cultivates a great learning environment and exposes pharmacy students to unique disease states.

Triage is a process used to document pertinent patient information prior to being seen by providers. It requires succinctly summarizing the information gathered and creating a prioritized problem list. It is a perfect place for pharmacy students to practice their patient interview skills. Pharmacy students are familiar with follow-up questions to ask patients regarding their complaints. They understand the importance of collecting information on past medical history, social history, past surgeries, medications, and allergies to direct patients to the correct medical service needed.

Overall, participating in medical missions is a rich and rewarding experience for pharmacy students. These unique opportunities allow students to provide valuable healthcare services to underserved populations and in doing so also enrich their own learning and self-development as a pharmacist. Pharmacy students interested in participating in a medical mission or international learning experience should contact their college’s experiential learning department (APPE/IPPE director). Additionally, students can seek opportunities through the organizations listed below:

This article was primarily authored by Ana Nevarez, PharmD Candidate 2017 and reviewed by Ayesha Khan, PharmD, BCPS. 

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