Mohammad Waleed, PharmD Candidate

Health Care Professionals Should Be Aware of Classes of Medications and Conditions That May Affect Blood Glucose Levels.

Nearly half of American adults have diabetes or prediabetes, and every 21 seconds, another individual is given a diagnosis of diabetes,

 leading to almost 1.5 million diagnoses every year.

More than half of Americans take prescription medications regularly for a variety of conditions, 4 on average, according to 

 Rising prescription drug use means that patients on insulin are increasingly at risk for drug—drug interactions.

Insulin, a hormone produced in pancreatic β cells, regulates blood sugar. With sufficient insulin in the body, blood sugar does not spike. After a meal or a snack, the pancreas secretes insulin and signals the body to absorb glucose. In individuals with type 1 diabetes, insulin production is impaired. In those with type 2 diabetes, fat, liver, and muscle cells do not respond properly to insulin. This is known as insulin resistance.

Because the body produces insulin regularly, drug interactions with insulin differ from other drug—drug interactions. Practitioners should be aware of classes of medications and conditions that may affect blood glucose levels. By predicting the effect that a medication will have on patients’ blood glucose levels, prescribers can tailor insulin therapy appropriately.

An individual’s glycated hemoglobin (A1C) level reflects average glycemia over about 3 months and has strong predictive value for diabetes complications. A reasonable A1C goal for many nonpregnant adults is 7% or lower.

 That said, some providers suggest more stringent A1C goals, such as <6.5% for certain patients in the absence of significant hypoglycemia or other adverse effects. Less stringent A1C goals (eg, <8%) may be appropriate for patients who have a history of or are at risk for severe hypoglycemia.

Basal insulin is initiated in patients usually with metformin with or without another noninsulin agent.

 The American Diabetes Association recommends pharmacologic approaches to glycemic treatment in its 

Standards of Medical Care in Diabetes—2018

 describes the basic steps that clinicians need to follow to initiate and tailor treatment.

Glucocorticoids, or steroids, are the most frequently prescribed class of anti-inflammatory drugs for chronic inflammatory diseases. In addition to acting on glucocorticoid receptors, glucocorticoids cause varying degrees of β-cell dysfunction, including the reduction of insulin sensitivity.

 Glucocorticoids activate various genes involved in hepatic carbohydrate metabolism, causing hyperglycemia and increasing endogenous glucose production. Their ability to induce hyperglycemia depends on several factors, such as dose and duration of use.

Steroids’ effects are usually dose dependent, reversible, and transient. As steroid doses are reduced, their effect on endocrine metabolism returns to baseline and drug-induced hyperglycemia resolves.

Practitioners should increase normal insulin by 10% to 20% if a patient is known to have diabetes and is hyperglycemic and on steroid therapy.

Additionally, clinicians should adjust insulin doses based on changes in steroid doses to prevent hyperglycemia and/or hypoglycemia. They should adjust insulin to half the percentage in steroid change. For example, if a patient’s steroid dose is reduced by 50%, the insulin dose should be reduced by 25%.

 So, in a patient on 25 units of basal insulin daily and 20 mg of prednisone, reduction of the steroid dose to 10 mg of prednisone daily, a 50% reduction, should be accompanied by a basal insulin reduction of 25%. The patient will be on 19 units of basal insulin daily. 

Acute illness or injury may result in glucose intolerance, hyperglycemia, and insulin resistance. Results from numerous studies show a strong association between stress hyperglycemia and poor clinical outcomes, including infections, increased duration of hospitalization, morbidity, mortality, and overall complications.

Patients who are acutely ill and hospitalized may have an increased stress response mediated by the hypothalamic-pituitary-adrenal (HPA) axis. In certain cases, this response can lead to chronic hyperglycemia, which contributes to microvascular complications (eg, diabetic nephropathy, neuropathy, and retinopathy).

 Catecholamine, cortisol, and epinephrine all increase and result in multiple effects aimed at restoring homeostasis during stress. The HPA axis and proinflammatory cytokines act synergistically to induce stress hyperglycemia.

 Chronic hyperglycemia needs to be managed by a primary care provider in an ambulatory care setting.

For patients with stress hyperglycemia, results from randomized controlled studies do not support intensive insulin therapy. In fact, mild to moderate stress hyperglycemia is protective during critical illness and times of stress.

Clinicians should increase insulin cautiously in patients who are acutely ill and monitor blood glucose periodically. Treating the illness will lower blood glucose levels to baseline, but patients who have severe stress hyperglycemia (blood glucose exceeding 220 mg/dL) may benefit from insulin adjustment.

Common medications used in patients with diabetes may require insulin adjustments (

Patients with diabetes often take antipsychotics, β-blockers, corticosteroids, and thiazide diuretics. Clinicians must weigh the pros and cons of these medications in patients with diabetes. They are not contraindicated, but clinicians should adjust insulin in the context of these medications. Being aware of medications and conditions that may cause hyperglycemia or hypoglycemia helps ensure patient safety and provides better health outcomes.

Mohammed Waleed is a 2019 PharmD candidate at the University of Connecticut School of Pharmacy in Storrs.

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Articles

Patients Are Increasingly at Risk for Insulin-Drug Interactions

One of the most common diseases in the developed world is asthma. According to the CDC, 1 in 13 people have asthma. Yet, adherence to inhaled preventive asthma medication is suboptimal in more than 50% of people. More than 300 million people have asthma, and that number is expected to grow rapidly by an additional 100 million by 2025. As the most accessible healthcare professional, pharmacists have a duty to help people administer their preventer inhaler regularly, as prescribed.

Pharmacist-led interventions can increase medication adherence, and reduce its economic burden on healthcare. In a systematic review and meta-analysis recently published in the 

, researchers show how effective pharmacist-led interventions are in medication adherence.

Researchers looked at 20 studies that met their inclusion criteria, including looking at only participants with asthma and no other respiratory conditions. Researchers measured adherence by focusing on:

Electronic adherence monitoring devices (Doser, Smartinhaler)

Pharmacy based data (prescription refill rates)

Reports from healthcare professionals or caregivers.

Interestingly, researchers categorized the interventions based on pharmacist involvement. This categorization differentiates between telling patients that they should use their inhaler daily, and specifically targeting patients’ concerns with their inhalers.

Interventions were further categorized as non-PAPA (targeting only perceptions or practicalities), partial PAPA (targeting perceptions and practicalities), or full PAPA (tailored approach targeting perceptions and practicalities).

Of the 20 studies, 6 found a significant intervention effect on medication adherence. It’s important to note that the interventions included in this review were from all over the world, which may affect their findings. The findings from this review are in line with recent reviews targeting adherence to inhaled corticosteroids.

Pharmacists can fill the general practitioner gap, serving as medication experts by informing patients about the importance of sticking to their asthma medications, and addressing their concerns.

Mohammad Waleed, is a 2019 PharmD Candidate at the University of Connecticut.

Mes MA, Katzer CB, Chan AHY, et al. Pharmacists and medication adherence in asthma: a systematic review and meta-analysis. 

; in press (https://doi.org/10.1183/13993003.00485-2018).

Pharmacist-led interventions can increase medication adherence, and reduce its economic burden on healthcare.

Role of Pharmacists in Asthma Adherence

Benzalkonium chloride (BAK) is a preservative that has been used in ophthalmology since the 1940s, and is found in up to 70% of eye drops. BAK, a quaternary ammonium compound, acts as a detergent, lysing cell membranes, and killing microorganisms. This makes it very effective as a preservative.

Preservatives are used in ophthalmic medications because they are cost effective. A large bottle of eye drops can last an entire month when a preservative is added compared with preservative free (PF) counterparts.

. The supporting science is based on laboratory and animal studies demonstrating its toxicity. In one study, BAK stimulated an apoptotic response to corneal cells. At a molecular level, dose-dependent DNA damage has been associated with BAK.

The researchers searched for studies comparing preservative and PF drops. One variable researchers examined was ocular surface disease (OSD) which they define as “an umbrella term that includes dry eye, lid disease, conjunctivitis, and keratitis.” Many studies use different subjective measures when evaluating the severity of OSD.

A survey found that those on PF drops had roughly half the signs and symptoms of OSD compared to those on preserved drops. However, this should be taken with a grain of salt because several other clinical studies found little to no corneal toxicity from various concentrations of BAK.

One study limitation was the lack of masked randomized controlled trials (RCTs) that compare PF drops directly with the same drop containing preservative. That said, some studies have compared non-BAK preserved and BAK preserved eye drops. In these comparisons, BAK was no more toxic than other preservatives.

Pharmacists and other healthcare providers should recommend PF drops in patients with established OSD. In these patients, switching to PF medications has been shown to improve symptoms, signs and tolerability. Patients on multiple medications (3 or more) may also benefit from a PF preparation. Other factors to consider when selecting the right eye drop are cost, patient preference, tolerability, frequency, and duration of use.

Mohammad Waleed is a 2019 PharmD Candidate at the University of Connecticut.

Study suggests benzalkonium chloride, a preservative that has been used in ophthalmology since the 1940s, may be toxic to ocular structures.