Tolerance to Long-term Maintenance Methadone Therapy

A study was conducted in patients receiving long-term methadone for opioid maintenance treatment.  It was aimed to study the development of opioid tolerance within these patients.  The study focused on the dose and duration of treatment along with the racemic drugs methadone and levomethadone.  All of the patients displayed DSM IV criteria to receive the treatment for opioid dependence.

The treatment used for a mean of 7.5 years was 370 patients using racemic methadone and 309 using levomethadone.  There was a significant correlation between dosage and duration of treatment.  Only those receiving the treatment for over a year were considered in this study.  The longer the duration of treatment, the larger the dose was.  This is interpreted as a development of tolerance.

Many patients within the study were long-term treatment patients with having up to 30 years of treatment.  There may have been a gradual loss of efficacy of the methadone which would require the increase of dose.  This correlation exists within levomethadone as well.

It was considered that within the past 30 years, the dosing therapy has been changed, and that patients who initially started on the methadone maintenance treatment had initially started with a large dose.  Also, it is taken into consideration that the study is based on self-reported, although anonymous, data which might limit the quality of results.

Overall, the study concluded that there is an increase in tolerance when utilizing long term methadone maintenance therapy in correlation with an increase in dose.  There wasn’t a significant difference between the development of tolerance in patients using methadone or levomethadone.

Although the study may be considered a bit bias, it makes practical sense that an increase in dose would be due to an increase in tolerance.  Is this therapy supposed to be long term?  Shouldn’t the patient be gradually taken off of the treatment?  What can a pharmacist do to intervene with this methadone maintenance treatment?

Gutwinski S, Schoofs N, Stuke H, et al. Opioid tolerance in methadone maintenance treatment: comparison of methadone and levomethadone in long-term treatment. Harm Reduction Journal. 2016;13(7). 

Antibiotic Resistance in Infants 2 months old

Researchers conducted a study about antibiotic resistance in infants under three months year old, specifically those experiencing uropathogens.  Within the study, previously healthy infants with urinary tract infections were observed.  Because there are limited data on antibiotic resistance of uropathogens in young infants, this study was of interest to the researchers.  The infants’ susceptibility to antibiotics was recorded, and this was conducted utilizing a urine sample or supra-pubic aspiration.

There has been a problem in which sepsis in neonates and UTIs in children are occurring due to antimicrobial resistance in Gram-negative bacteria (GNBs).  Many of the infants observed in this study who had UTIs were caused by GNBs that were resistant to several antibiotic classes.  The resistance rates observed were 73.7% to ampicillin, 22.1% cefazoline, 21.8% ampicillin/clavulanate, 7.8% cefuroxime, and 7% gentamicin.

The current standard treatment for infants with UTIs who are less than two months old is by IV.  It is an inpatient therapy, but there is evidence that there is equal efficacy in oral therapy.  Regardless of route of administration, gram-negative uropathogens express resistance even at two months of age.  This challenges the empirical therapy and compromises oral treatment options.  For this, antibiotic resistance and therapy choices should be monitored in infants to determine the correct antibiotic for them.

It was surprising to me how infants can experience antibiotic resistance prior to any exposure in the past.  Resistance is troublesome in any patient, but the idea of resistance in infants creates a different struggle.  What, as pharmacists can we do to assist in treating infants with antibiotic resistance?  When should the baby be screened for resistance?  Should it wait until the diagnosis and when the infant starts treatment?

Segal Z, Cohen MJ, Engelhard D, et al. Infants under two months of age with urinary tract infection are showing increasing resistance to empirical and oral antibiotics.  Acta Paediatricia. 2015:1-5.

The Effect of Atorvastatin on Physical Activity

There was a study conducted that observed different effects that can occur while taking a statin.  The muscle pains and weaknesses often associated with the use of a statin may limit physical activity.  This article highlights the study that examines the effect of atorvastatin on physical activity levels in healthy adults.  The participants of this study were new to statins and were exposed to either a atorvastatin or a placebo for 6 months.  Their physical activity was measured to determine if there was any decrease in frequency or intensity.

The participants were middle-aged Caucasian women and men.  They were overweight with an above optimal LDL with normal BP, HDL, total cholesterol and TG.  The male participants were borderline average for their fitness level, and the women were above average.  Both of the participant groups (placebo and atorvastatin) spent most of their days sedentary with time spent with light-intensity and moderate-intensity of physical activity.  There was not much time spent in high-intensity physical activity.  Overall, there was not a significant difference between the level of physical activity conducted by the placebo group or the atorvastatin group.

After 6 months of the medication and testing, there was a reduction in overall physical activity when the participants were taking both the atorvastatin and the placebo.  The purpose of the study was to determine if statins significantly decrease physical activity levels among health individuals.  The researchers conclude that the findings of their study reinforce the importance of maintaining a habit of physical activity while on a statin therapy.  This could prevent, treat and control dyslipidemia.

What can pharmacists counsel to patients who are just starting a statin therapy?  What is the significance of this study?

Panza GA, Taylor BA, Thompson PD, et al. The effect of atorvastatin on habitual physical activity among healthy adults.  Medicine & Science in Sports & Exercise. 2016;48(1):1-6

Possible Reversible Treatment in those with Obesity-related Type 2 Diabetes

This article highlighted a study which focused on the islet Beta-cell proinsulin synthesis in relation to progressive type 2 diabetes.  Many patients with type 2 diabetes need many therapies that are glucose-lowering due to the loss of beta-cell mass.  Impaired proinsulin production contributes to the beta-cell dysfunction.  This study has shown that islet beta-cell proinsulin synthesis is increased.  The study was conducted in two obese mice which serve as a model for type 2 diabetes.

There is accelerated, dysfunctional proinsulin processing which is causing the beta-cell failure.  It is found that a reduction in mature and the increase in immature insulin granules (in the islets) as well as the incorporation of L-leucine into proinsulin, indicates the failure of normal proinsulin processing.  Another process which has been evident to cause beta-cell failure is deficits in proinsulin synthesis.  The failure of the proinsulin synthesis was folds higher in mice which are obese than those which are not.  The beta-cells of obese mice attempt to compensate for the increased insulin need, but there is not enough capacity of the cells to sustain the normal maturation of insulin granules.  This results in continuous efforts of proinsulin processing.

Overall, this study concluded that it is the deficiencies in proinsulin processing and insulin granule formation may be more important in beta-cell failure in obesity-related type 2 diabetes than deficiencies in proinsulin synthesis.  Some islet beta-cells have inherent predisposition to respond to excess nutrients and stressors, which are at greatest risk for dysfunctional proinsulin processing.  This process is reversible if discovered early enough.  These types of interventions may include therapies that slow beta-cell metabolism, slow proinsulin synthesis, etc.  Because it is a reversible condition when caught early enough, prevention and treatment of this condition with appropriate therapies is key.

Type 2 diabetes is such a prevalent disease within our country.  Should screening for this proinsulin dysfunction occur earlier, such as when someone is obese without a diagnosis of type 2 or even prediabetes?  Are there any current drugs that act upon this pathway to slow the processing down?

Nolan CJ, Delghingaro-Augusto V. Reversibility of defects in proinsulin processing and islet beta-cell failure in obesity-related type 2 diabetes.  Diabetes. 2016;65(2):352-354.

Medical Marijuana as a Potential Treatment for GI Disorders

As it has been seen throughout these past few years, medical marijuana is becoming legalized in more and more states throughout this country.  Despite a majority of the public’s belief that it has medical benefits, it is still a schedule I drug.  This means that this drug has a high risk for abuse with no accepted medical use.  For this, the research to determine the potential clinical benefits is tightly regulated and restricted.  Much of the data that exists today on the benefit of medical marijuana are from observational studies.

This article highlights the potential benefit of marijuana for GI disorders.  Surveys taken by patients with medical marijuana prescriptions have reported that it certainly improves abdominal pain, nausea, and appetite.  There was a study which was conducted as a randomized controlled trial in which patients used marijuana to treat the symptoms of Crohn’s disease.  Patients claimed that there was a reduction in pain and appetite was regulated.  Other randomized controlled trials have indicated that cannabinoids are likely to be utilized in patients undergoing chemotherapy to reduce nausea and vomiting.

There is a perception that marijuana is safer than other available therapies.  Other GI medications have many adverse risks.  Marijuana has many risks as well, such as driving impairment, dependence, and other known risks.  The author highlights that the safety profile of marijuana compares favorably to other drugs including narcotics.  The overdose rate for those taking prescription narcotics is astronomically higher than the deaths caused by marijuana overdose, which is zero.

Isfort, Robert W., and Mark E. Gerich. “High Hope for Medical Marijuana in Digestive Disorders.” The American Journal of Gastroenterology (2016): n. pag. 2 Feb. 2016. Web. 14 Feb. 2016.

This article highlights a potential future of medicine.  It is non-conventional and controversial, but the potential medical benefit should be explored.  What are the potential risks for dispensing medical marijuana?  What do you think the risks of drug diversion would be?  As future pharmacists, what should our concern be involving the potential legalization of medical marijuana?

Are E-Cigarettes as Effective as we Thought for Smoking Cessation?

As people may have noticed, the prevalence of e-cigarettes has increased throughout the years.  They are advertised as an intervention to reduce cigarette smoking in the hopes of the cessation of cigarette use.  E-cigarettes are considered a safer alternative to standard cigarettes due to the lack of combustion and the toxic gases released from this reaction.  The use of e-cigarettes has gained popularity because it reduces the harm that normal cigarettes cause, but it does not replace the nicotine use.

A study conducted in France has focused on the potential recreational smoking habit that adolescents are doing in response to the prevalence and availability.  Researchers studied which adolescents utilize e-cigarettes as a smoking cessation tool.  They had studied the frequency of those who smoke e-cigarettes without ever smoking normal cigarettes.  They also studied whether the use of the e-cigarettes was the utilize it as a smoking cessation tool.  The researchers also conducted a second stage of analyses in which they assessed the sociodemographic variables and the use of e-cigarettes.

The researchers concluded that experimentation with e-cigarettes in adolescents is high (relatively the same as those who have tried standard cigarettes).  However, many of the adolescents who have tried e-cigarettes have not tried standard cigarettes.  The use of e-cigarettes, in this case, is not associated with smoking cessation.  Higher socioeconomic status and age positive predicted the use of e-cigarettes.

The researchers concluded this article indicating that there is a need of further investigation about the harmful effects that e-cigarettes have.  Many adolescents are experimenting with this, and it is a potential “gateway” to smoke standard cigarettes.  E-cigarettes are not being utilized as a smoking cessation tool in this case.

This study, although conducted in France, provides an interesting outlook on the use of e-cigarettes.  It seems as if it would be a useful smoking cessation tool for those who are trying to quit.  However, the accessibility allows younger adults to take it up as a habit.  What are ways to prevent adolescents from starting e-cigarettes?  What role, as pharmacists, do we have in this type of situation?  E-cigarettes are sometimes compared to the use of the patch for smoking cessation, so is this something that pharmacists should recommend for use?

Rennie, Laura J., Cecile Bazillier-Bruneau, and Jacques Rouesse. “Harm Reduction or Harm Introduction? Prevalence and Correlates of E-Cigarette Use Among French Adolescents.” Sciencedirect.com. Journal of Adolescent Health, 3 Feb. 2016. Web. 10 Feb. 2016. <http://www.jahonline.org/>.

Gene Identification associated with Epigenetics of Type 2 Diabetes

Type 2 Diabetes is the most prevalent type of diabetes accounting for 90% of all cases.  The disease is also a major risk factor for cardiovascular events.  In a recent study, researchers discovered an epigenetic mechanism that occurs when regulating blood sugar levels.  Epigenetic mechanisms such as DNA methylation has been associated with several processes such as aging or pathologies.  This study provides evidence that DNA methylation of the TXNIP gene is associated with type 2 diabetes.  As many people know, this disease has a genetic component as well as environmental factors.  Many of the environmental factors have been studied in the past, so researchers are beginning to focus on the epigenetics of diabetes.

This study’s aim was to associate type 2 diabetes with DNA methylation.  The setup of the experiment was a two cohort approach which included comparing non-diabetes patients with patients with diabetes, as well as two different groups of diabetics based on their control of blood glucose levels (well-controlled or poorly controlled).  As a result, a new methylation was associated with diabetes and A1C levels.

The study concluded that there is a binding correlation with glucose import and chaperone binding.  Methylation differences in where they bind may alter the regulation of genes which correlate with glucose exposure.  The expression of the TXNIP gene for glucose-responsiveness is elevated in the muscle of pre-diabetics and diabetic patients.  DNA methylation may be able to modulate the expression and work as a biomarker of altered glucose levels.

This article demonstrates the importance of genomics in disease.  Identifying possible genetic components invested in prominent diseases such as diabetes can be a step in the right direction for a cure.  How could pharmacists use these types of studies in their practice?  Pharmacogenomics is a hot topic these days, how could this study benefit diabetes drug development?

Carolina Soriano-Tárraga, Jordi Jiménez-Conde, Eva Giralt-Steinhauer, Marina Mola-Caminal, Rosa M. Vivanco-Hidalgo, Angel Ois, Ana Rodríguez-Campello, Elisa Cuadrado-Godia, Sergi Sayols-Baixeras, Roberto Elosua, Jaume Roquer. Epigenome-wide association study identifiesTXNIPgene associated with type 2 diabetes mellitus and sustained hyperglycemia. Human Molecular Genetics, 2016; 25 (3): 609 DOI: 10.1093/hmg/ddv493

Utilizing Brain Waves to Predict Dosing of Anesthesia

A conflicting issue today is that there is no direct way to measure the sedative effects of anesthesia administered by anesthesiologists other than the patient’s level of awareness.  Concentrations in the brain cannot be determined.  A study conducted by Chennu et al., utilized an EEG to experiment a better way to study dose administration of sedative-hypnotics.

It is difficult for scientists to quantitatively measure the consciousness of the brain.  When utilizing anesthetics, measuring level of sedation and the ability to track this parameter is difficult by the variability between individuals and their susceptibility to anesthetics.  Within this study conducted by Chennu et. al., the researchers utilize high-density electroencephalography in tandem with propofol  (a sedative-hypnotic), and the changes in the brain were measured.  An EEG can easily measure brain waves from the surface of the scalp, but it is not universally utilized.  This change could solve the need for reliable anesthesia monitoring during use of a sedative.  The researchers conducted assessments prior to, during and after the administration of the sedative.  The participant’s behavioral responsiveness and the drug concentrations in the blood were measured within these assessments.  All of these experiments were conducted on healthy volunteers.  When administering the propofol, key changes in the brain waves were observed.

The researchers highlight that the alpha waves are compromised during sedation.  There is a spectral connectivity when considering the alpha waves in sedated participants.  This is an indicator of susceptibility to propofol which varies between individuals.  The concentration of drug was measured at each level of sedation.  Correlations were also found between the alpha waves and behavioral impairment.  These results can assist in dosing the patient correctly instead of injecting medication until unconscious.

Chennu S, O’Connor S, Adapa R, Menon DK, Bekinschtein TA. Brain Connectivity Dissociates Responsiveness from Drug Exposure during Propofol-Induced Transitions of Consciousness. PLOS Computational Biology. 2016.

Given the advanced technology present in the medical world, I was surprised that EEGs are not universally utilized when sedating patients for surgery.  The variability between individual patients’ susceptibility to anesthetics such as propofol has been observed in the past.  This article highlights the need that individuals should be receiving different doses of this drug to sedate them accordingly.  This has me thinking of other procedures conducted within the hospital that potentially conducts dosing based on behavioral assessment.

What should pharmacists do if a drug is dosed based on bias or strictly behavioral results?  What is the responsibility of the pharmacist within this type of scenario?