What is known and objective
Opioid use in the United States has reached unprecedented—some would even say crisis—levels. Although many individuals use opioid drugs as part of legitimate pain ...management plans, a significant number misuse prescription or illicit opioids. With regular opioid use, individuals develop tolerance and physical dependence; both are predictable, physiologic responses to repeated opioid exposure. However, a substantial number of individuals who misuse opioids will develop opioid use disorder (OUD), a complex, primary, chronic, neurobiological disease rooted in genetic, environmental and psychosocial factors. This article discusses OUD, opioid receptor physiology, and opioid withdrawal symptomatology and pathophysiology, as well as current treatment options available to reduce opioid withdrawal symptoms in individuals with physical dependence and/or OUD.
Methods
The research articles regarding OUD and its management have been reviewed thoroughly based on a PubMed literature search using keywords related to opioid dependence, its pathophysiology and current treatment strategies.
Results and discussion
Tolerance/physical dependence and the behavioural characteristics associated with OUD reflect complex neurobiologic adaptations in several major systems of the brain, including the locus ceruleus and mesolimbic systems. Physical dependence is responsible for the distressing withdrawal symptoms individuals experience upon abrupt cessation or rapid dose reduction of exogenous opioids. Opioid withdrawal symptoms are a key driver behind continued opioid use, and a barrier to opioid discontinuation. Several opioid‐based medications are available to treat patients with OUD; these treatments can diminish opioid withdrawal symptoms and cravings as well as block opioid effects in the event of relapse. Additionally, non‐opioid drugs may be used during acute detoxification to help alleviate opioid withdrawal symptoms.
What is new and conclusion
The opioid crisis has produced many challenges for physicians, one being the need to determine which patients would benefit most from maintenance therapy and which may be candidates for opioid discontinuation. In addition to summarizing current understanding of OUD, we provide a new algorithm for determining the need for continued opioid use as well as examples of situations where management of opioid withdrawal symptoms is indicated.
Opioid abuse has reached epidemic levels and includes many chronic pain patients. This review discusses opioid receptor physiology and opioid withdrawal symptomatology and pathophysiology, as well as current treatment options available to assist in the withdrawal process in individuals with physical dependence and/or opioid use disorder.
Epidemiological and basic science evidence suggest a possible shared pathophysiology between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). It has even been hypothesized that AD might ...be ‘type 3 diabetes’. The present review summarizes some of the evidence for the possible link, putative biochemical pathways and ongoing clinical trials of antidiabetic drugs in AD patients. The primary and review literature were searched for articles published in peer‐reviewed sources that were related to a putative connection between T2DM and AD. In addition, public sources of clinical trials were searched for the relevant information regarding the testing of antidiabetic drugs in AD patients. The evidence for a connection between T2DM and AD is based upon a variety of diverse studies, but definitive biochemical mechanisms remain unknown. Additional study is needed to prove the existence or the extent of a link between T2DM and AD, but sufficient evidence exists to warrant further study. Presently, AD patients might benefit from treatment with pharmacotherapy currently used to treat T2DM and clinical trials of such therapy are currently underway.
The Zika virus: Lurking behind the COVID‐19 pandemic? Pergolizzi, Joseph; LeQuang, Jo Ann; Umeda‐Raffa, Sumiyo ...
Journal of clinical pharmacy and therapeutics,
April 2021, Letnik:
46, Številka:
2
Journal Article
Recenzirano
Odprti dostop
What is known and objective
The sudden and extensive outbreak of coronavirus (SARS‐CoV‐2) has overshadowed another developing viral threat: the Zika flavivirus. Of particular concern is that pregnant ...women can pass Zika virus to the foetus, and there is a strong implication of an association between Zika virus infection and foetal microcephaly. Currently, there is no vaccine, and there is no cure.
Methods
Published literature and Internet sources were searched for information related to Zika virus, its transmission, its clinical presentation and sequalae, prevention and implications (practice and regulatory) for healthcare providers. The identified English sources were reviewed, assessed and synthesized. Emphasis was placed on providing an overview of the problem, and identification of unmet needs and future directions.
Results and discussion
Zika virus poses a major challenge for healthcare providers, particularly in areas unaccustomed to it, since it is transmitted to humans by the vector Aedes aegypti mosquito. The outbreak impacts every healthcare provider, because every provider is required to report cases of Zika infection to their state or local health agencies––whether the infection is confirmed or merely suspected. Since the virus has become a worldwide crisis, healthcare providers will need to work across national boundaries and medical disciplines in order to educate patients about Zika symptoms and the mosquito vector. Until further information is known, infected patients (male and female) are being advised to avoid conceiving a child.
What is new and Conclusion
Until a vaccine is developed or effective treatment for Zika virus is discovered, healthcare providers must be AVP (aware, vigilant and proactive) in order to lessen the spread and impact of the implicated devastating birth defects (microcephaly) and other neurological disorders (eg Guillain‐Barré Syndrome) of this infection. Unfortunately, many knowledge gaps exist. There is an urgent need for a reliable, inexpensive diagnostic test, an effective treatment and an approved and readily available vaccine.
Until a vaccine is developed or effective treatment for Zika virus is discovered, healthcare providers must be proactive to lessen its spread and impact of implicated birth defects (eg, microcephaly) and other neurological disorders (eg, Guillain‐Barré Syndrome). Unfortunately, knowledge gaps exist. There is urgent need for a reliable, inexpensive diagnostic test, effective treatment and readily available vaccine.
Bone fractures during the time of coronavirus Umeda‐Raffa, Sumiyo; Pergolizzi Jr, Joseph V.; Raffa, Robert B.
Journal of clinical pharmacy and therapeutics,
April 2021, 2021-Apr, 2021-04-00, 20210401, Letnik:
46, Številka:
2
Journal Article
Recenzirano
Odprti dostop
What is known and Objective
In response to rapid spread of coronavirus (SARS‐CoV‐2) and lack of vaccine or effective treatment for COVID‐19 disease, governments imposed measures that resulted in a ...shift from work and school to isolation at home. Studies from three countries (China, Belgium and the United States) report the consequences on traumatic bone fractures.
Comment
The coronavirus pandemic has resulted in a widespread change to a relative sedentary lifestyle and decreased exposure to light (vitamin D). A consequence of the stay‐at‐home policies is a negative change in bone‐health and environmental surroundings that has led to age‐related changes in the number of traumatic bone fractures.
What is new and conclusion
A consequence of stay‐at‐home policies has been a decline in bone fractures for young and middle‐aged adults; but an increase for the elderly. The trends are predicted to reverse, and present new problems, when isolation restrictions are removed.
Introduction
The distinct properties of the centrally-acting analgesic tapentadol derive from the combined contributions of an opioid component and a nonopioid component. However, the opioid ...component’s relative contribution to analgesic and adverse effects has not previously been elucidated. Tapentadol’s analgesic effect derives from the combined contribution of an opioid mechanism and a nonopioid mechanism, the extent of which can vary for different pains. Likewise, the interaction can vary for various adverse effects. Hence, the contribution of each mechanism to adverse effects can be different from the contribution to analgesia. We here estimate the percent contribution of each component of the mechanism of action to analgesia and to adverse effects.
Areas Covered
Several approaches to in vitro and in vivo data to estimate the contribution of tapentadol’s opioid component to analgesia and to the two important opioid adverse effects, respiratory depression and constipation. The results are then compared with clinical data.
Expert Opinion
Traditional opioids, such as morphine, oxycodone, and others, produce their analgesic effects primarily through a single mechanism—the activation of µ-opioid receptors (MOR). Therefore, the contribution of the opioid component to adverse effects is 100%. In contrast, the newer strong analgesic tapentadol produces its analgesic effect via two separate and complementary analgesic mechanisms, only one of which is µ-opioid. We applied standard drug–receptor theory and novel techniques to in vitro and in vivo data to estimate by several different ways the μ-load of tapentadol (the % contribution of the opioid component to the adverse effect magnitude relative to a pure/classical µ-opioid at equianalgesia) in respiratory depression and constipation, and we compared the results to clinical evidence. The estimate is remarkably consistent over the various approaches and indicates that the μ-load of tapentadol is ≤ 40% (relative to pure MOR agonists, which have, by definition, a µ-load of 100%).
Funding
Grünenthal GmbH.
Abstract
Objective
An expert panel convened to reach a consensus on common misconceptions surrounding buprenorphine, a Schedule III partial µ-opioid receptor agonist indicated for chronic pain. The ...panel also provided clinical recommendations on the appropriate use of buprenorphine and conversion strategies for switching to buprenorphine from a full µ-opioid receptor agonist for chronic pain management.
Methods
The consensus panel met on March 25, 2019, to discuss relevant literature and provide recommendations on interpreting buprenorphine as a partial µ-opioid receptor agonist, prescribing buprenorphine before some Schedule II, III, or IV options, perioperative/trauma management of patients taking buprenorphine, and converting patients from a full µ-opioid receptor agonist to buprenorphine.
Results
The panel recommended that buprenorphine’s classification as a partial µ-opioid receptor agonist not be clinically translated to mean partial analgesic efficacy. The panel also recommended that buprenorphine be considered before some Schedule II, III, or IV opioids in patients with a favorable risk/benefit profile on the basis of metabolic factors, abuse potential, and tolerability and that buprenorphine be continued during the perioperative/trauma period. In addition, switching patients from a full µ-opioid receptor agonist to buprenorphine should be considered with no weaning period at starting doses that are based on the previous opioid dose.
Conclusions
These recommendations provide a framework for clinicians to address most clinical scenarios regarding buprenorphine use. The overall consensus of the panel was that buprenorphine is a unique Schedule III opioid with favorable pharmacologic properties and a safety profile that may be desirable for chronic pain management.
Sunscreen bans: Coral reefs and skin cancer Raffa, Robert B.; Pergolizzi, Joseph V.; Taylor, Robert ...
Journal of clinical pharmacy and therapeutics,
February 2019, 2019-Feb, 2019-02-00, 20190201, Letnik:
44, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Summary
What is known and objective
Hawaii will ban two major ingredients of sunscreens. This article reviews the reasons and future directions. Hawaii recently enacted legislation that will ban the ...use of two major ingredients of the majority of commonly used sunscreens. The reason for the ban is the ingredients’ putative deleterious impact on marine ecosystems, particularly coral reefs. But sunscreens also save lives by decreasing the risk of UV‐induced skin cancers. We review both sides of the issue and potential implications for the healthcare system.
Comment
Coral reefs consist of organisms in delicate equilibria that are susceptible to small changes in their surroundings. Recent natural and man‐made disruptions, direct or indirect, such as changes in ocean temperature and chemistry, ingress of invasive species, pathogens, pollution and deleterious fishing practices, have been blamed for the poor health, or even the outright destruction, of some coral reefs. The most popular sunscreen products contain two ingredients—oxybenzone and octinoxate—that have also been implicated in coral toxicity and will be banned. This creates a healthcare dilemma: Will the protection of coral reefs result in an increase in human skin cancers?
What is new and conclusion
Concentration estimates and mechanism studies support an association—direct or indirect (via promotion of viral infection)—of sunscreens with bleaching of coral reefs. A ban on the two most common sunscreen ingredients goes into effect in Hawaii on January 1, 2021. Proponents suggest that this is a trend, just the first of many such bans worldwide; opponents warn of a dire increase in human skin cancers. As a result, alternative sunscreen compounds are being sought.
Hawaii will ban two major ingredients of sunscreens. This article reviews the reasons and future directions. Hawaii recently enacted legislation that will ban the two major ingredients of the majority of commonly used sunscreens in order to protect marine ecosystems, particularly coral reefs. But sunscreens also save lives by decreasing the risk of UV‐induced skin cancers. This article reviews the issues and potential implications for healthcare providers.
On subclasses of opioid analgesics Raffa, Robert B.
Current medical research and opinion,
12/2014, Letnik:
30, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Abstract
Background:
The history of discovery of analgesic drugs has followed a trajectory from original serendipitous discovery of plant-derived substances to laboratory creation of customized ...molecules that are intentionally designed to interact with specific receptors of neurotransmitters involved in either the transmission of the pain signal or the attenuation of such a signal. The drugs most recently developed have been designed to provide incremental greater separation between pain relief and adverse effects. The result has been drugs that have individualized pharmacodynamic and pharmacokinetic characteristics that represent specific advances in basic science and translate into unique clinical profiles. Several of the drugs include non-opioid components. They retain some of the features of opioids, but have distinct clinical characteristics that differentiate them from traditional opioids. Thus they defy simple classification as opioids.
Scope:
A summary is provided of the development of the modern view of multi-mechanistic pain and its treatment using analgesics that have multi-mechanisms of action (consisting of both opioid and non-opioid components). Descriptions of examples of such current analgesics and of those that have pharmacokinetic characteristics that result in atypical opioid clinical profiles are given.
Findings:
By serendipity or design, several current strong analgesics have opioid components of action, but have an additional non-opioid mechanism of action or some pharmacokinetic feature that gives them an atypical opioid clinical profile and renders them not easily classified as classical opioids.
Conclusion:
An appreciation that there are now opioid analgesics that differentiate from classical opioids in ways that defy their simplistic classification as opioids suggests that recognition of subclasses of opioid analgesics would be more accurate scientifically and would be more informative for healthcare providers and regulators. This would likely lead to positive outcomes for the clinical use and regulatory control of the current drugs, and provide direction/strategy for the discovery of new drugs.
Health care providers in the United States are facing challenges in selecting appropriate medication for patients with acute and chronic pain in the midst of the current opioid crisis and COVID-19 ...pandemic. When compared with conventional opioids, the partial micro-opioid receptor agonist buprenorphine has unique pharmacologic properties that may be more desirable for pain management. The formulations of buprenorphine approved by the US Food and Drug Administration for pain management include intravenous injection, transdermal patch, and buccal film. A comparison of efficacy and safety data from studies of buprenorphine and conventional opioids suggests that buprenorphine may be a better-tolerated treatment option for many patients that provides similar or superior analgesia. Our benefit-risk assessment in this narrative review suggests that health care providers should consider that buprenorphine may be an appropriate alternative for pain management over other opioids. Keywords: buprenorphine, buprenorphine buccal film, analgesia, pain, opioids
Despite the increasing clinical use of transdermal buprenorphine, questions have persisted about the possibility of a ceiling effect for analgesia, its combination with other μ‐opioid agonists, and ...the reversibility of side effects. In October 2008, a consensus group of experts met to review recent research into the pharmacology and clinical use of buprenorphine. The objective was to achieve consensus on the conclusions to be drawn from this work. It was agreed that buprenorphine clearly behaves as a full μ‐opioid agonist for analgesia in clinical practice, with no ceiling effect, but that there is a ceiling effect for respiratory depression, reducing the likelihood of this potentially fatal adverse event. This is entirely consistent with receptor theory. In addition, the effects of buprenorphine can be completely reversed by naloxone. No problems are encountered when switching to and from buprenorphine and other opioids, or in combining them. Buprenorphine exhibits a pronounced antihyperalgesic effect that might indicate potential advantages in the treatment of neuropathic pain. Other beneficial properties are the compound's favorable safety profile, particularly in elderly patients and those with renal impairment, and its lack of effect on sex hormones and the immune system. The expert group agreed that these properties, as well as proven efficacy in severe pain and favorable tolerability, mean that buprenorphine can be considered a safe and effective option for treating chronic cancer and noncancer pain.
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