Oral and Inhaled Corticosteroid Use and the Risk of Recurrent Pulmonary Embolism

The use of oral and inhaled corticosteroids is associated with a variety of adverse effects.  However, they are an accepted necessity in in the treatment of COPD, and provide necessary expansion of airways to help patients struggling to breath.  Many COPD patients suffer pulmonary embolism, and a significant proportion of these patients experience recurrent pulmonary embolism.  There is serious concern that the use of inhaled or oral corticosteroids may increase the lifetime risk of recurrent pulmonary embolism, and raise treatment related morbidity and mortality.  A recent study published in Thrombosis Research attempted to investigate a potential link between current or past use of corticosteroids and the incidence of recurrent pulmonary embolism among patients.

The researchers conducted a nested case-control study that looked at adult patients with a previous PE treated with Vitamin K antagonists.  The study analyzed 1414 PE patients, of which 384 were also later diagnosed with recurrent PE.  The study found that inhaled corticosteroid use only slightly associated with increased risk of recurrent PE, however oral medications did show increased odds of the disease.  In particular, current users of oral formulations were at increased risk (3.74 O.R., 95% CI 2.04-6.87), while past users were actually at a reduced risk (0.46 95% CI 0.28-0.74) compared to patients who never received corticosteroid therapy.  The researchers did admit the study design did not all them to discern whether the risk could be attributed solely on the medications or the underlying inflammatory disease as well.  However, they site evidence that corticosteroid medications show increased blood coagulation factors in healthy volunteers.

Inhaled and oral corticosteroids continue to be a mainstay of treatment for patients with chronic inflammatory diseases like COPD.  However, these disease states put the patients at increased risk for PE, and it would appear that the medications increase the risk of recurrent PE in the same patients.  Given the substantial risk of PE morbidity and mortality, these findings could have severe clinical impact for medication therapy of COPD and other inflammatory diseases of the pulmonary system.  As pharmacists, this association could have a large impact on the therapy management in future patients.  What steps should be taken to refine counseling points on corticosteroids, particularly in oral formulations?  Should the risk be assessed and accepted or denied on a patient-by-patient basis, or is there a better solution to the issue?

Article Link

Sneeboer, Marlous. Hutten, Barbara. Majoor, Christof. Bel, Elizabeth.  Oral and Inhaled Corticosteroid Use and the Risk of Pulmonary Embolism.  Thromres (2016); 140: 46-50.

The Burden of Opioid-Induced Constipation: Discordance Between Patient and Health Care Provider Reports

Opioid medications are the most commonly prescribed medications for the treatment of chronic non-cancer pain.  However, the side effects and risks of addiction often prevent problems with patients with long term use of opioids.  In particular, opioid-induced constipation (OIC) is one of the most common side effects that impact patient quality of life, with patient surveys suggesting that as many as 17-67% of opioid patients experiencing GI immobility while on the medication.  Although this is a commonly recognized issue related to opioid therapy, there appears to be a lack of communication between patients and physicians about treatment and the role it plays in patient quality of life.

A recent study published on behalf of AstraZeneca Pharmaceuticals attempted to look at the prevalence of OIC, and the differences in patient and provider perception of the issue.  The researchers performed a perspective, longitudinal cohort study on 489 patients being treated with opioids for chronic pain in the U.S, Canada, U.K., and Germany.  Patients were selected based on chronic pain conditions that would be treated for >6 months, diagnosed with OIC based on patient reported symptoms.  Both patients and health care providers were asked to complete online surveys to assess their experience with OIC, quality of life, treatment options, concerns, and patient-provider interaction.

The results of the study showed that most providers reported discussing the potential for OIC and its impact on the patients medication experience.  However, just over half of patients reported disclosing instances of OIC with their doctor.  Most patients took OTC laxatives to cope with the OIC, and many reported lower quality of life.  Some patients reported lowering their opioid dose to alleviate OIC symptoms, but reported a corresponding increase in their level of chronic pain.  There was a reported lack of communication between patients and providers about the problem, with both sides reporting confusion over who was the anticipated initiator of the conversation.  There was also a lack of understanding from patients in available options for OIC treatment, as well as provider reported differences in priority of OIC between patients and their physicians.  The study concluded that there is a noticeable rift between patients and their providers over the perceived impact that OIC has on pain management.  They believe that an increase in communication related to opioid side effects, and resolution discussions will help lower patient anxiety over symptoms and increase quality of life without sacrificing pain management.

This problem clearly highlights some of the issues that still plague the pain management care field.  Clearly there is a communication issue between patients and their doctors that needs to be resolved in order to reduce OIC incidence and impact on pain therapy.  As pharmacists, we have an opportunity to address concerns with OIC, offer medication treatment options, and open dialogue between the patients and their primary care physicians.  Is this an area that pharmacists should prioritize in patient care? If so what options are there for getting more involved in opioid therapy and the risk of OIC?

Article Link

Locasale, Robert. Datto, Catherine. Wilson, Hilary. Yeomans, Karen. Coyne, Karin. The Burden of Opioid-Induced Constipation: Discordance Between Patient and Health Care Provider Reports. J Manag Care Spec Pharm. 2016; 22 (3): 236-245.

Adverse Effects Associated With Proton Pump Inhibitors

Proton pump inhibitors (PPIs), such as omeprazole and pantoprazole, are commonly prescribed medications used to treat indigestion and prevent gastrointestinal bleeding in patients undergoing antiplatelet therapy. PPIs act by blocking gastric proton pumps, a necessary stage in the secretion of gastric acid. There is a widely held belief that PPIs have a very few amount of adverse effects and so result in them being overprescribed by physicians.

This journal article shows several adverse effects as a result of proton pump inhibitor use. These observed adverse effects include increased risk of kidney disease, hypomagnesemia, infections, cardiovascular events, and fractures. Researchers found that the risk of developing chronic kidney disease was 50% greater and the risk of acquiring acute kidney injury was three times greater in those who use PPIs compared to those who do not. Hypomagnesemia, or abnormally low levels of magnesium in the blood, had a 40% greater risk in PPI users and can lead to other illness such as muscle weakness, convulsions, and hypotension. Bacteria may colonize much easier in the gastrointestinal tract when PPIs reduce gastric acidity. Due to this, Clostridium difficile infections showed a 74% increase and pneumonia showed a 34% higher risk of developing in patients taking PPIs. As far as adverse cardiovascular events, those on PPIs and antiplatelet drug clopidogrel have a 30% increased risk in reduction of platelet inhibition due to both drugs competitively becoming metabolized by the same liver enzymes. PPI use can also decrease bone density by reducing intestinal calcium absorption. PPIs were associated with a 26% higher risk of hip fracture, a 58% higher risk of spine fracture, and a 33% higher risk for fracture at any site.

I feel as though greater caution is required when physicians decide to prescribe PPIs. Just because they were once thought to be seemingly harmless medications does not mean that new evidence demonstrating a connection to adverse effects should not be taken seriously. Special precautions should probably be taken in consideration for those patients who are at higher risk for any of the conditions indicated in this article. Also, histamine H2 receptor antagonists should perhaps be looked at as an alternative to PPI therapy if they do not show similar adverse effects.

Schoenfeld, Adam Jacob, and Deborah Grady. “Adverse Effects Associated With Proton Pump Inhibitors.” JAMA Intern Med. 176.2 (2016): 172. Web. 15 Mar. 2016.

http://resolver.ebscohost.com.pitt.idm.oclc.org/openurl?sid=google&auinit=AJ&aulast=Schoenfeld&atitle=Adverse+Effects+Associated+With+Proton+Pump+Inhibitors&id=doi%3a10.1001%2fjamainternmed.2015.7927&site=ftf-live

Metformin Treatment of Antipsychotic-Induced Dyslipidemia: An Analysis of Two Randomized, Placebo-Controlled Trials

Schizophrenic patients on antipsychotic medications tend to experience the adverse effect of dyslipidemia. At this time, no effective treatments have been established to treat this adverse effect. As a result, data was pooled from two randomized, placebo-controlled trials.  201 schizophrenic patients that experience antipsychotic-induced dyslipidemia were either given 1000 mg of metformin to take each day for 24 weeks, or a placebo.

After the 24 week period, the mean difference in the LDL values between individuals receiving metformin and those receiving the placebo treatment decreased by 1.02 mmol/L. Only 25.3% of patient in the metformin group had LDL levels greater than or equal to 3.37 mmol/L, while 64.8% of those in the placebo group had LDL levels greater than or equal to that. It is evident that metformin is effective in reversing antipsychotic-induced dyslipidemia. This study also showed that metformin helped people on antipsychotics lose weight, lowered their total cholesterol and triglyceride levels, and increased their HDL levels. Additionally, insulin resistance can be induced by antipsychotics, and metformin would help with this as well.

After reading about this study, I am wondering whether automatically putting schizophrenic patients on metformin as well as antipsychotics should become the normal protocol. Should this happen, or should we as pharmacists monitor their cholesterol and insulin levels while they are on antipsychotics and only suggest they begin metformin if they exhibit any of the aforementioned adverse effects? If we do put these patients on metformin,  how should we counsel and monitor them?

Mol. Psychiatry. 2016 Jan 26;doi:10.1038/mp.2015.221.

http://www.nature.com/mp/journal/vaop/ncurrent/pdf/mp2015221a.pdf