Musculoskeletal pain is a challenging condition for both patients and physicians. Many adults have experienced one or more episodes of musculoskeletal pain at some time of their lives, regardless of ...age, gender, or economic status. It affects approximately 47% of the general population. Of those, about 39–45% have long-lasting problems that require medical consultation. Inadequately managed musculoskeletal pain can adversely affect quality of life and impose significant socioeconomic problems. This manuscript presents a comprehensive review of the management of chronic musculoskeletal pain. It briefly explores the background, classifications, patient assessments, and different tools for management according to the recently available evidence. Multimodal analgesia and multidisciplinary approaches are fundamental elements of effective management of musculoskeletal pain. Both pharmacological, non-pharmacological, as well as interventional pain therapy are important to enhance patient’s recovery, well-being, and improve quality of life. Accordingly, recent guidelines recommend the implementation of preventative strategies and physical tools first to minimize the use of medications. In patients who have had an inadequate response to pharmacotherapy, the proper use of interventional pain therapy and the other alternative techniques are vital for safe and effective management of chronic pain patients.
Physicians who prescribe opioid analgesics for patients with moderate to severe chronic pain face a balancing act in the wake of the current publicity regarding abuse (nonmedical use) of prescription ...pain killers. There is a spectrum of opioid abuse ranging from those who misuse the drug by not following doctor’s orders to those who take the drugs to achieve a high or divert the drugs to the street market for profit. Formulations of opioid analgesics designed to resist or deter abuse have been proposed, and are now either on the market or in the pipeline. These are innovative formulations that make the drug less convenient or less desirable to abusers. This article examines three such new products along with clinical studies that report on their safety and effectiveness. These drugs include extended-release morphine with sequestered naloxone (Embeda®), controlled-release oxycodone in a high-viscosity hard gelatin capsule (Remoxy®) and an immediate-release oxycodone tablet with subtherapeutic niacin as an aversive agent (Acurox® with niacin tablets).
Extended-release morphine with sequestered naltrexone offers a pharmacological barrier in that pellets of morphine surround an internal core of naltrexone (ratio 100: 4 of morphine: naltrexone), which is released if the tablet is compromised by chewing or crushing. The hard gelatin capsule of controlled-release oxycodone was designed to resist tampering and the drug cannot be extracted with a needle. The immediate-release oxycodone formulation with subtherapeutic niacin uses a gel-forming ingredient designed to inhibit inhalation and prevent extraction of the drug for injection. The subtherapeutic niacin is intended to induce flushing and other unpleasant effects if the drug is taken in an excessive quantity. While these drugs hold individual promise, it remains undetermined if they can truly prevent abuse. Drug-seeking individuals are extremely resourceful and show little loyalty to a particular drug when other drugs are available. It is possible that abuse-deterring formulations may divert such individuals to find other drugs that are easier to compromise. Nevertheless, these formulations are important innovations and warrant further study to assess their appropriate role as analgesics.
Introduction
There is a medical need for a safe, effective nonopioid postoperative analgesic for older subjects, including those with mild to moderate renal impairment.
Methods
Participants (≥ ...65 years) were stratified by no, mild, or moderate renal impairment defined as creatinine clearance 60–89 mL/min for mild and 30–59 mL/min for moderate. Subjects were randomized to receive a loading dose of 6.25 mg of ketorolac tromethamine drug candidate NTM-001 followed by a 1.75 mg/h continuous intravenous (IV) infusion over 24 h or an IV bolus injection of ketorolac tromethamine (KETO-BOLUS) of 15 mg every 6 h. There were four treatment periods of 24 h for each subject with a minimum 7-day washout between them. This was a crossover study so subjects served as their own controls. Blood drawn from the subjects was used to plot concentration–time profiles against target profiles. Adverse events were monitored.
Results
Thirty-nine subjects enrolled. Concentration–time profiles showed low intersubject variability. Model-predicted curves for those with renal impairment closely matched observed plasma concentrations. Continuous infusion maintained higher mean plasma concentrations than the bolus regimen. No serious or unexpected adverse events were observed. No deaths occurred.
Conclusions
NTM-001 was considered safe and well tolerated in this population of participants ≥ 65 years, including in those with mild or moderate renal impairment. There were fewer adverse events in the continuous infusion group. The predictable pharmacologic properties and blood concentration levels suggest that continuous IV infusion of ketorolac can be used as an effective postoperative pain reliever in older subjects.
Plain Language Summary
Controlling postoperative pain can lead to faster recovery. Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID), like ibuprofen and naproxen, that can be as effective as morphine without the same risks. In hospitals, ketorolac is usually administered intravenously (IV) either continuously or as a bolus injection. A bolus of ketorolac may result in adverse gastrointestinal side effects. In this study, a new formulation of ketorolac tromethamine, NTM-001, was administered IV as a continuous 24 h infusion compared to IV boluses of ketorolac tromethamine every 6 h in volunteers. Volunteers were older (≥ 65 years) and had no, mild, or moderate kidney dysfunction. One randomized group received a starting IV dose of 6.26 mg followed by a continuous IV infusion of 1.75 mg/h of over 24 h. The other group received single NTM-001 IV bolus injections of ketorolac tromethamine 15 mg every 6 h over 24 h (4 doses, 60 mg) over the 24 h. After completing the first study, subjects waited at least a week and then switched groups, giving the study a crossover design so it could be observed how each subject responded to both regimens. Blood drawn from the subjects was tested for standard pharmacokinetic (PK) parameters. The data show that blood concentrations of NTM-001 can be reliably predicted. Side effects were mild and the continuous infusion reduced side effects. No unexpected adverse events occurred. These data show that NTM-001 can be used safely in older individuals, including those with mild or moderate kidney impairment.
The 2016 CDC guidelines for opioid prescribing by primary care physicians have exposed some shortfalls in our thinking about opioid use and stranded many chronic pain patients with inadequate ...analgesia. Opioid prescribing rates started to decline in 2012, but still remain high. The response from providers to the 2016 guidelines have led to unintended consequences. Some of the CDC guidance seems arbitrary and not supported by evidence (the 90 MME per day cutoff). Patient and prescriber education, the role of buprenorphine (an atypical Schedule III opioid), and abuse-deterrent opioids are not mentioned at all but could play crucial roles in reducing abuse. Opioid use disorder (OUD) is not defined by the guidance which calls on primary care physicians to recognize and treat it. Opioid withdrawal syndrome is not mentioned and tapering plans, although advised, are not described in a practical way. While the morbidity and mortality associated with OUD are public health crises, so is untreated pain. Chronic pain patients deserve consideration, yet emerge as the silent epidemic within the opioid crisis. To be sure, there is much good in the CDC guidance or any guidelines that urge caution and care in opioid prescribing. Pain specialists must speak out to advocate for patients dealing with pain, to educate patients and prescribers about analgesic options, and to make sure that pain is adequately treated particularly in vulnerable populations.
Abuse-deterrent opioid formulations are receiving renewed interest in light of the increasing legitimate medical use of prescription opioids for the adequate treatment of pain. Unfortunately, there ...is an inevitable associated potential for misuse, diversion, and abuse. The challenges of deterrence are significant: opioid abusers are a heterogeneous population; studies on drug "liking" and opioid "attractiveness" are informative, but mainly rely on reports from users who are not reliable respondents; drug "liking" scores are useful, but it is unclear how much drug "liking" must be reduced in order to achieve an actual reduction in abuse levels; and the most popular drugs among opioid abusers appear to be those that meet a complex combination of both positive and negative criteria including things like availability, pricing, and how easily the drug's illicit use can be concealed. Several abuse-deterrent formulations have been introduced or are in development. Epidemiological studies will have to be conducted to evaluate their effectiveness. Although there are currently more questions than answers, such products are clearly of medical and societal importance.
Chronic postsurgical pain (CPSP) is a prevalent condition that can diminish health-related quality of life, cause functional deficits, and lead to patient distress. Rates of CPSP are higher for ...certain types of surgeries than others (thoracic, breast, or lower extremity amputations) but can occur after even uncomplicated minimally invasive procedures. CPSP has multiple mechanisms, but always starts as acute postsurgical pain, which involves inflammatory processes and may encompass direct or indirect neural injury. Risk factors for CPSP are largely known but many, such as female sex, younger age, or type of surgery, are not modifiable. The best strategy against CPSP is to quickly and effectively treat acute postoperative pain using a multimodal analgesic regimen that is safe, effective, and spares opioids.
This is a narrative review of the literature.
Every surgical patient is at some risk for CPSP. Control of acute postoperative pain appears to be the most effective approach, but principles of good opioid stewardship should apply. The role of regional anesthetics as analgesics is gaining interest and may be appropriate for certain patients. Finally, patients should be better informed about their relative risk for CPSP.
Abstract Objective Identify the risk factors for prescription opioid misuse among patients taking prescription opioids to deal with chronic pain. Methods We examined the literature for a variety of ...dynamic risk factors associated with opioid misuse among the chronic pain population in order to present a narrative review. Considered were: taking single or multiple opioids, pain intensity, mental health disorders, including a history of preadolescent sexual abuse, personal and familial history of substance abuse, a history of legal problems, being a crime victim, drug-seeking behaviors, drug craving, and age. Results A variety of risk factors have been studied in the literature. Risk factors in chronic opioid therapy patients are dynamic in that they can change with disease progression, tolerance, changes in pain quality, mental health, comorbidities, other drug therapies or drug interactions, and changes in the patient's lifestyle. Conclusion Opioid analgesic therapy must be tailored to carefully monitor all patients in order to minimize misuse and abuse, since the risk is constant and dynamic and therefore every patient is at some degree of risk for opioid misuse.
The pharmacological management of dental pain Pergolizzi, Joseph V; Magnusson, Peter; LeQuang, Jo Ann ...
Expert opinion on pharmacotherapy,
03/2020, Letnik:
21, Številka:
5
Journal Article
Recenzirano
: Dental pain is primarily treated by dentists and emergency medicine clinicians and may occur because of insult to the tooth or oral surgery. The dental impaction pain model (DIPM) has been widely ...used in clinical studies of analgesic agents and is generalizable to many other forms of pain.
: The authors discuss the DIPM, which has allowed for important head-to-head studies of analgesic agents, such as acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and combinations. Postsurgical dental pain follows a predictable trajectory over the course of one to 3 days. Dental pain may have odontic origin or may be referred pain from other areas of the body.
: Pain following oral surgery has sometimes been treated with longer-than-necessary courses of opioid therapy. Postsurgical dental pain may be moderate to severe but typically resolves in a day or two after the extraction. Opioid monotherapy, rarely used in dentistry but combination therapy (opioid plus acetaminophen or an NSAID), was sometimes used as well as nonopioid analgesic monotherapy. The dental impaction pain model has been valuable in the study of analgesics but does not address all painful conditions, for example, pain with a neuropathic component.
The most common type of idiopathic interstitial pneumonia is idiopathic pulmonary fibrosis (IPF), an irreversible, progressive disorder that has lately come into question for possible associations ...with COVID-19. With few geographical exceptions, IPF is a rare disease but its prevalence has been increasing markedly since before the pandemic. Environmental exposures are frequently implicated in IPF although genetic factors play a role as well. In IPF, healthy lung tissue is progressively replaced with an abnormal extracellular matrix that impedes normal alveolar function while, at the same time, natural repair mechanisms become dysregulated. While chronic viral infections are known risk factors for IPF, acute infections are not and the link to COVID-19 has not been established. Macrophagy may be a frontline defense against any number of inflammatory pulmonary diseases, and the inflammatory cascade that may occur in patients with COVID-19 may disrupt the activity of monocytes and macrophages in clearing up fibrosis and remodeling lung tissue. It is unclear if COVID-19 infection is a risk factor for IPF, but the two can occur in the same patient with complicating effects. In light of its increasing prevalence, further study of IPF and its diagnosis and treatment is warranted.
Opioid analgesia for acute painful conditions has come under increasing scrutiny with the public health crisis of opioid overdose, leading clinicians to seek nonopioid alternatives, such as ...nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (paracetamol).
This perspective evaluates recent clinical trials of nonopioids, opioids, and combination therapy for use in acute pain. Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) often provide adequate analgesia, although these agents are not without risks. Combination therapy using a small amount of opioid together with a nonopioid pain reliever has been shown effective and reduces opioid consumption.
The short-term use of opioids under close clinical supervision, such as in-hospital use of opioid analgesics for postoperative pain, may be appropriate, but even here, combination therapy or nonopioid therapy may be preferred. The use of opioids even for acute pain of short duration has been questioned. The ideal analgesic has yet to be developed, but effective pain control pharmacological regimens for acute pain are available.
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