A Longitudinal Study of Predictors of Constipation Severity in Oncology Outpatients With Unrelieved Pain

ContextAlthough constipation is a common symptom in oncology patients, it often goes unrecognized and untreated. In addition, little is known about characteristics associated with interindividual differences in constipation severity.ObjectivesTo describe prevalence, characteristics, and management of constipation; evaluate interindividual differences in constipation severity over 10 weeks; and identify demographic, clinical, and symptom characteristics associated with higher constipation severity scores.MethodsIn this prospective, longitudinal study, 175 oncology patients with unrelieved pain were recruited from eight outpatient cancer settings in the U.S. Patients completed demographic and symptom questionnaires at enrollment. Constipation severity was evaluated over 10 weeks using the Constipation Assessment Scale (CAS). Hierarchical linear modeling was used to identify characteristics associated with higher CAS scores.ResultsAt enrollment, 70.1% of the patients reported constipation [i.e., CAS score of >2; mean CAS score: 3.72 (±3.11)]. While over the first week of the study patients used one to two constipation treatments per day, a large amount of interindividual variability was found in CAS scores. Higher percentage of days with no bowel movement, higher number of constipation treatments, higher state anxiety scores, and higher analgesic side effects scores were associated with higher CAS scores at enrollment. Higher percentage of days with no bowel movement was associated with interindividual differences in the trajectories of constipation.ConclusionOur findings underscore the high prevalence of and large amount of interindividual variability in constipation severity. The characteristics associated with worse CAS scores can assist clinicians to identify high-risk patients and initiate prompt interventions.     

Effect of sedative-hypnotics,anesthetics and analgesics on sleep architecture in obstructive sleep apnea

The perioperative care of obstructive sleep apnea (OSA) patients is currently receiving much attention due to an increased risk for complications. It is established that postoperative changes in sleep architecture occur and this may have pathophysiological implications for OSA patients. Upper airway muscle activity decreases during rapid eye movement sleep (REMS). Severe OSA patients exhibit exaggerated chemoreceptor-driven ventilation during non-rapid eye movement sleep (NREMS), which leads to central and obstructive apnea. This article critically reviewed the literature relevant to preoperative screening for OSA, prevalence of OSA in surgical populations and changes in postoperative sleep architecture relevant to OSA patients. In particular, we addressed three questions in regard to the effects of sedative-hypnotics, anesthetics and analgesics on sleep architecture, the underlying mechanisms and the relevance to OSA. Indeed, these classes of drugs alter sleep architecture, which likely significantly contributes to abnormal postoperative sleep architecture, exacerbation of OSA and postoperative complications.     

Buprenorphine and buprenorphine/naloxone soluble-film for treatment of opioid dependence

Introduction: Opioid dependence is a chronic relapsing disorder that shows excess mortality and comorbidity with somatic and psychiatric disorders. Methadone and buprenorphine/naloxone are widely accepted and are used as first-line maintenance treatments for opioid dependence. Fatal intoxications with these agents, risk of diversion, and accidental intoxications, especially in children, are apparent risks and are of increasing public concern. Buprenorphine/naloxone sublingual tablet is an established treatment for opioid dependence. A novel buprenorphine/naloxone film has been developed with improved pharmacokinetics and a hopefully lower risk of diversion and accidental intoxications.

Areas covered: This review evaluates the available preclinical and clinical data on the novel buprenorphine/naloxone film for the treatment of opioid dependence. Literature was identified though a comprehensive PubMed search and data sources included official FDA information.

Expert opinion: This is an interesting new formulation of a well-established medication in opioid dependence. However, few data have been published on its safety and efficacy. In an experimental study, the new formulation suppressed symptoms of opioid withdrawal as expected. Results of an unpublished study made public by the FDA suggest a spectrum of adverse events similar to that of the conventional sublingual tablet. Some data show patients may prefer the novel film over the sublingual tablet. The estimated lower risk for diversion and especially for accidental poisoning in children cannot be assessed in clinical studies but requires data from emergency room visits.     

Pharmacokinetics and safety of fentanyl sublingual spray and fentanyl citrate intravenous: a single ascending dose study in opioid-naïve healthy volunteers

Objective: Fentanyl sublingual spray offers rapid pain relief in opioid-tolerant cancer patients, and may be useful in acute or post-operative pain. Both opioid-naïve and non-tolerant patients are likely to receive opioids in these settings. Understanding the relationship between systemic exposure of fentanyl sublingual spray and effects on respiratory function in opioid-naïve or non-tolerant populations is important to ensure patient safety. This study evaluated single-dose fentanyl sublingual spray in opioid-naïve participants.

Research design: Participants were randomized to receive single-dose fentanyl sublingual spray (100, 200, 400, 600, 800?mcg) or fentanyl citrate IV in one of five cohorts. Dosing occurred following a 10-h fast, with fasting continuing for 4?h post-dose. Dose proportionality was assessed using analysis of variance and linear regression techniques. PK assessments and safety monitoring were performed through 24?h post-dose. Safety assessments, including adverse event (AE) monitoring, occurred from dosing through Day 7.

Results: Fifty participants (19?53 years) received fentanyl sublingual spray or fentanyl citrate IV. Mean maximum plasma concentrations were reached between 0.27–0.60?h post-dose for fentanyl sublingual spray. Peak (C_max) and total (AUC_0–t, AUC_0–∞) fentanyl exposures increased in a linear, but more than dose-proportional manner, with higher doses. The most common AEs were somnolence, nausea, and vomiting. All AEs were mild or moderate in severity. Doses at 400, 600, and 800?mcg were associated with nausea and vomiting, requiring pharmacologic intervention. Hypoxia episodes requiring nasal cannula oxygenation were observed with 600mcg and 800mcg doses.

Conclusions: Overall, single-dose fentanyl sublingual spray (100–800?mcg) was generally well tolerated, with greater incidences of AEs (e.g. nausea, vomiting, hypoxia) at higher doses. Doses up to 200?mcg may be safely administered to healthy opioid-naïve individuals with routine monitoring; doses between 400–800?mcg may be administered in settings with nasal cannula oxygenation.     

Aspects of pharmacokinetics and pharmacodynamics of sufentanil in pediatric practice

Sufentanil is a potent synthetic opioid. Like other opioids, sufentanil creates a stable hemodynamic environment in cardiovascularly compromised pediatric patients. Clearance, expressed as per kilogram, is increased in children compared to adults. The P450 CYP3A4 enzyme is responsible for the major metabolic N‐dealkylation pathway. Enzyme activity is reduced in neonates but the maturation of sufentanil clearance is not described. The free active fraction is affected by age because of the reduced α₁‐acid glycoprotein plasma concentrations in neonates. Intranasal administration of sufentanil is a possible option for premedication, procedural sedation and analgesia in children, as this option has been found to be safe and effective. Studies concerning the pharmacokinetics and dynamics of sufentanil administered as a bolus or continuous infusion in children are few.     

Naltrexone in the treatment of opioid‐dependent pregnant women: the case for a considered and measured approach to research

The present paper considers naltrexone to treat opioid dependence during pregnancy. The public health problem of opioid dependence and its treatment during pregnancy is reviewed first. Next, the naltrexone and opioid dependence treatment literature is summarized, with overviews of the pre‐clinical and clinical research on prenatal naltrexone exposure. Finally, considerations and recommendations for future medication research for the treatment of opioid dependence in pregnant women are provided. The efficacy of long‐acting injectable naltrexone relative to placebo, its blockade of opioid agonist euphoric effects, its lack of abuse and tolerance development and its modest adverse effect profile make it a potential medication for opioid‐dependent pregnant women. However, it is not without seriously concerning potential drawbacks, including the difficulty surrounding medication induction that may lead to vulnerability with regard to relapse, physical dependence re‐establishment, increased risk behaviors, treatment dropout and resulting opioid overdose. Before embarking on future research with this medication, the benefits and risks for the mother–embryo/fetus/child dyad should be weighed carefully. Should future research be conducted, a multi‐level commitment to proactive ethical research is needed to reach the ultimate goal of improving the lives of women and children affected by opioid dependence.     

The Medical Consumption of Opioids in Colombia, 1997–2007

ABSTRACT

The World Health Organization classifies opioid analgesics as essential medicines in the treatment of severe pain and recommends their increased availability. The combination of availability, training of professionals, and a legal framework granting access to these medicines has led to a sharp increase in the consumption of morphine and other opioids in developed countries. However, in Colombia, consumption of opioid analgesics appears to fail to meet patient needs. To analyze the current trends in medical consumption of opioids in Colombia, the numbers of defined daily doses of opioid analgesics for total inhabitants and the population that died of cancer between 1997 and 2007 were calculated and compared. The import of raw materials and medicines varied greatly every year. However, from 2003, a trend toward the increased consumption of morphine, hydromorphone, and methadone was observed. Availability was inconsistent and opioid consumption showed an increase when calculated for total inhabitants and for cancer deaths. The unreliable availability of opioid analgesics may be responsible for their limited consumption. Chronic underuse and a trend toward increased consumption have been confirmed. Monitoring of consumption to promote rational use is recommended.