Gianpietro Zampogna

Peripherally acting μ-opioid receptor antagonists as treatment options for constipation in noncancer pain patients on chronic opioid therapy

Opioid-induced constipation (OIC), a prevalent and distressing side effect of opioid therapy, does not reliably respond to treatment with conventional laxatives. OIC can be a treatment-limiting adverse event. Recent advances in medications with peripherally acting μ-opioid receptor antagonists, such as methylnaltrexone, naloxegol, and alvimopan, hold promise for treating OIC and thus extending the benefits of opioid analgesia to more chronic pain patients. Peripherally acting μ-opioid receptor antagonists have been clinically tested to improve bowel symptoms without compromise to pain relief, although there are associated side effects, including abdominal pain. Other treatment options include fixed-dose combination products of oxycodone analgesic together with naloxone.

Perspectives on Intravenous Oxycodone for Control of Postoperative Pain.

Intravenous (IV) analgesia has particular advantages in the immediate postoperative period. For example, IV administration results in a faster onset of pain relief and results in more predictable pharmacokinetics than does administration by other routes. It also allows for convenient dosing before or during surgery, permitting the initiation of effective analgesia in the early phase of the postoperative period. In addition, when patients are able to tolerate oral intake, they can be switched from IV to oral dosing based on maintaining the predictable analgesia established by the IV route. IV morphine is widely used for the control of postoperative pain, but there is a trend toward the use of oxycodone. Oxycodone (which may be mediated partly through kappa‐ as well as mu‐opioid receptors) offers several potential advantages. Published studies comparing IV oxycodone to other IV opioids for postsurgical pain report that oxycodone is a safe and effective analgesic. Some studies show that IV oxycodone may be associated with greater pain control, fewer or less severe adverse events, and faster onset of action, although the results are not consistent across all studies. Oxycodone has been reported to be safe in the geriatric and other special populations when adequate clinical adjustments are made. Thus, the clinical reports and oxycodones pharmacologic profile make intravenous oxycodone a potentially important “new” old drug for postoperative pain control.

A Guide for Pain Management in Low and Middle Income Communities. Managing the Risk of Opioid Abuse in Patients with Cancer Pain.

Most patients who present with cancer have advanced disease and often suffer moderate to severe pain. Opioid therapy can be safe and effective for use in cancer patients with pain, but there are rightful concerns about inappropriate opioid use even in the cancer population. Since cancer patients live longer than ever before in history (and survivors may have long exposure times to opioid therapy), opioid misuse among cancer patients is an important topic worthy of deeper investigation. Cancer patients with pain must be evaluated for risk factors for potential opioid misuse and aberrant drug-taking behaviors assessed. A variety of validated screening tools should be used. Of particular importance is the fact that pain in cancer patients changes frequently, whether it is related to their underlying disease (progression or remission), pain related to treatment (such as painful chemotherapy-induced peripheral neuropathy), and concomitant pain unrelated to cancer (such as osteoarthritis, headache, or back pain). Fortunately, clinicians can use universal precautions to help reduce the risk of opioid misuse while still assuring that cancer patients get the pain therapy they need. Another important new “tool” in this regard is the emergence of abuse-deterrent opioid formulations.

Concise review of the management of iatrogenic emesis using cannabinoids: emphasis on nabilone for chemotherapy-induced nausea and vomiting

Chemotherapy-induced nausea and vomiting (CINV) is a prevalent, distressing, and burdensome side effect of cancer chemotherapy. It is estimated to affect the majority of patients receiving certain anti-cancer drug regimens and can be treatment-limiting, even for life-saving medications. Despite seemingly numerous options, such as antimuscarinic anticholinergics, antihistamines, 5-HT3 receptor antagonists, dopamine receptor antagonists, and neurokinin-1 receptor antagonists, preventative therapies are often inadequately effective, particularly for “delayed CINV”—leaving an important unmet clinical need. Cannabinoid receptor agonists, by virtue of their unique mechanism of action and efficacy and safety data reported in clinical trials, appear to offer a useful additional option. The mechanistic value of cannabinoids has been well known for many years, but these agents may have been underutilized in the past because of the notoriety and legal status of marijuana. While botanical marijuana contains nearly 500 components, including the psychoactive tetrahydrocannabinol (THC), nabilone is an established, single-entity synthetic cannabinoid receptor agonist that has become the focus of renewed interest. We review the basic pharmacology and clinical trial data of nabilone for use in prophylaxis and treatment of CINV.

Management of moderate to severe chronic low back pain with buprenorphine buccal film using novel bioerodible mucoadhesive technology.

With a global prevalence of ~9%–12%, low back pain (LBP) is a serious public health issue, associated with high costs for treatment and lost productivity. Chronic LBP (cLBP) involves central sensitization, a neuropathic pain component, and may induce maladaptive coping strategies and depression. Treating cLBP is challenging, and current treatment options are not fully satisfactory. A new BioErodible MucoAdhesive (BEMA®) delivery system for buprenorphine has been developed to treat cLBP. The buccal buprenorphine (BBUP) film developed for this product (Belbuca™) allows for rapid delivery and titration over a greater range of doses than was previously available with transdermal buprenorphine systems. In clinical studies, BBUP was shown to effectively reduce pain associated with cLBP at 12 weeks with good tolerability. The most frequently reported side effects with the use of BBUP were nausea, constipation, and vomiting. There was no significant effect on the QT interval vs placebo. Chronic pain patients using other opioids can be successfully rotated to BBUP without risk of withdrawal symptoms or inadequate analgesia. The role of BBUP in managing cLBP remains to be determined, but it appears to be a promising new product in the analgesic arsenal in general.

Long-term efficacy, safety and tolerability of Remoxy for the management of chronic pain.

Historically, chronic pain generally went under-treated for a variety of objective and subjective reasons, including difficulty to objectively diagnose and manage over a long period of time, potential serious adverse effects of commonly available medications, and patient, healthcare and societal concerns over opioid medications. More recently, in an effort to redress the under-treatment of pain, the number of prescriptions of opioid analgesics has risen dramatically. However, paralleling the increased legitimate use has been a concomitant increase in opioid abuse, misuse and diversion. Pharmaceutical companies have responded by developing a variety of opioid formulations designed to deter abuse by making the products more difficult to tamper with. One such product is Remoxy®, an extended-release formulation of the strong opioid oxycodone. We review the efficacy, safety and tolerability of this formulation based on the available published literature.

Analgesia for Moderate Chronic Non-Cancer Pain : Low Dose Transdermal Buprenorphine A Novel Option in Mexico

Chronic non-cancer pain is prevalent in Mexico and its pharmacologic treatment requires clinicians to balance the risks and beneits of various analgesic agents. NSAIDs and paracetamol (acetaminophen) can be efective for mild to moderate pain, but safety considerations place limitations on their use. Opioids are safe and efective, but have opioid-associated side efects plus the potential for abuse. Against this background, it is important to appraise other options with regard to favorable eicacy and safety – such aslow-dose transdermal buprenorphine. Buprenorphine, both in transdermal and oral formulations, has been available in Mexico for a number of years yet just recently a Low-Dose Transdermal Patch formulation has been available for the management chronic non-cancer pain of moderate intensity in adults. Buprenorphine is an opioid agent with a unique pharmacological proile, such that it has a ceiling efect for respiratory depression, but no ceiling efect for analgesia. It can be used without dose adjustment in the elderly and in patients with impaired kidney function (unique among opioids). Its small lipophilic molecule makes it well suited to transdermal formulations, which ofer steadystate round-the-clock analgesia after three days with clinical convenience and easier patient compliance. Buprenorphine is an efective analgesic in chronic non-cancer pain patients, and its good tolerability and lower abuse potential may make lowdose transdermal buprenorphine appropriate for a broad range of patients. Corresponding author: Joseph V. Pergolizzi, MD, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, E-mail:drpergo@gmail.com

Pain Specialists Awareness of Topical Analgesics and Their Use in Pain Control: Survey Results

Background: Over-the-counter (OTC) topical analgesics are an important part of the armamentarium for pain management, but it was not clear if and to what extent prescribers discussed the option of topical analgesics with their patients. Objective: The objective was to assess the extent to which pain specialists were aware of topical analgesics and how often and under what circumstances they recommended topical pain relievers to their patients to help control painful symptoms. Methods: The authors conducted a convenience-sample survey at the PAINWeek® meeting in Las Vegas in September 2014. The survey was distributed during the conference and there were 81 respondents (healthcare providers). Results: Eight-ive percent of all respondents (100% of pain physicians) indicated that they recommended OTC topical analgesics to patients and 81.5% said they had no concerns about the safety and tolerability of such products. When asked if topical analgesics could be a good irst step in relieving muscle and joint pain, 98.8% of all respondents and 100% of pain specialist physicians expressed agreement. Conclusion: OTC topical analgesics represent an important option for treating muscle and joint pain. They may ofer speciic advantages over other pain relievers in that they do not require high serum concentrations of the active agent and therefore may be associated with fewer side efects. OTC topical analgesic products can be easily obtained, self-administered, and allow for improved accessibility. Healthcare professionals specializing in pain are aware of topical analgesics and consider them safe, efective, and a good irst-step product in for treating musculoskeletal pain. Clinically tested OTC topical analgesics can be used with conidence as a irst-line treatment for acute musculoskeletal pain. Corresponding author: Joseph V. Pergolizzi, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA, Tel: 239.597.3662/239.908.4442, Fax: 239.908.4432; E-mail: jpjmd@msn.com

Revisiting transdermal scopolamine for postoperative nausea and vomiting

Postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting (PDNV) in ambulatory patients remain serious problems that affect a substantial subset of surgical patients. Guidelines recommend that patients be stratified for risk, and patients at moderate-to-high risk be administered prophylactic PONV/PDNV therapy. Risk stratification on the four-point Apfel scale assigns one point for each of the following: female sex, nonsmoking status, history of PONV or motion sickness, and the use of postoperative opioids. Patients who score 2 or higher are considered to be at moderate-to-high risk. Other risk factors have been evaluated and discussed in the literature, such as type and duration of surgery. Surprisingly, although PONV/PDNV is more common in the first 24 hours after anesthesia, it may occur for days following surgery, and so, continuous treatment is advantageous. Transdermal scopolamine is a well-established agent with a history of safety and efficacy for PONV/PDNV prevention. Scopolamine is an anticholinergic agent that is generally well tolerated; side effects tend to be mild to moderate. The most frequently reported side effects with transdermal scopolamine are visual disturbances and dry mouth. Once adhered to the skin, the patch administers an initial dose and then a continuous dose of medication over 72 hours. Transdermal scopolamine is easy to administer, safe, effective, and relatively cost-effective, and it should be considered as an important tool to help prevent PONV/PDNV, whether administered as monotherapy or in combination with other agent(s).

The Role of Opioids in Chronic Non-Cancer Pain Management.

Chronic pain is prevalent in Asia as well as worldwide, and physicians must carefully consider which pharmacologic or non-pharmacologic analgesic strategy is appropriate based on its availability, adverse effects, abuse liability, potential drug-drug interactions, onset of action, tolerability, cost, and—above all—effectiveness. NSAIDs increase the pain threshold by inhibiting cyclooxygenase (COX) and are the first step of the World Health Organization “pain ladder,” but they have been associated with gastrointestinal complications, possible renal failure, and hypertension. Acetaminophen (paracetamol) is an effective pain reliever for mild to moderate pain, but is associated with liver toxicity at high doses. Opioids are effective pharmacologic treatment and standard therapy for moderate to severe cancer pain, but their long-term use for non-cancer pain is controversial. Opioid-associated side effects may be transient, treatable, or treatment limiting. Not all chronic non-cancer pain patients are candidates for opioid therapy, particularly if there are risk factors for misuse or abuse. Combining an opioid and a nonopioid (such as acetaminophen or NSAID) in combination therapy can create synergistic analgesic effect and reduce the patient’s total opioid consumption while still achieving good analgesic results. Adjuvant agents such as anticonvulsants or tricyclic antidepressants can be useful to deal with multimechanistic pain, including pain with a neuropathic component, frequently observed in chronic non-cancer pain patients.