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Current Opinion in Anaesthesiology Aug 2020The present review aims to address the feasibility of opioid free anesthesia (OFA). The use of opioids to provide adequate perioperative pain management has been a... (Review)
Review
PURPOSE OF REVIEW
The present review aims to address the feasibility of opioid free anesthesia (OFA). The use of opioids to provide adequate perioperative pain management has been a central practice of anesthesia, and only recently has been challenged. Understanding the goals and challenges of OFA is essential as the approach to intraoperative analgesia and postsurgical management of pain has shifted in response to the opioid epidemic in the United States.
RECENT FINDINGS
OFA is an opioid sparing technique, which focuses on multimodal or balanced analgesia, relying on nonopioid adjuncts and regional anesthesia. Enhanced recovery after surgery protocols, often under the auspices of a perioperative pain service, can help guide and promote opioid reduced and OFA, without negatively impacting perioperative pain management or recovery.
SUMMARY
The feasibility of OFA is evident. However, there are limitations of this approach that warrant discussion including the potential for adverse drug interactions with multimodal analgesics, the need for providers trained in regional anesthesia, and the management of pain expectations. Additionally, minimizing opioid use perioperatively also requires a change in current prescribing practices. Monitors that can reliably quantify nociception would be helpful in the titration of these analgesics and enable anesthesiologists to achieve the goal in providing personalized perioperative medicine.
Topics: Analgesia; Analgesics, Non-Narcotic; Analgesics, Opioid; Humans; Pain Management; Pain, Postoperative; United States
PubMed: 32530891
DOI: 10.1097/ACO.0000000000000878 -
Minerva Anestesiologica Dec 2019Intranasal dexmedetomidine, although still off-label, recently boasted an increasing consensus for different uses, namely, in diagnostic non-painful procedures, in... (Review)
Review
Intranasal dexmedetomidine, although still off-label, recently boasted an increasing consensus for different uses, namely, in diagnostic non-painful procedures, in painful procedures and in surgical premedication. However, at present, there is no consensus regarding indications, dosage and timing for administration. This article aims to provide a comprehensive literature analysis and summarize the more recent evidence of research on pediatric intranasal dexmedetomidine, in the effort to better delineate usefulness and limits for each specific indication. In summary, available pediatric evidence confirms efficacy and safety of dexmedetomidine for intranasal administration. Pharmacological profile for the various pediatric ages and procedures still needs quality studies and pharmacokinetic in-depth analysis.
Topics: Administration, Intranasal; Analgesics, Non-Narcotic; Child; Dexmedetomidine; Humans; Treatment Outcome
PubMed: 31630510
DOI: 10.23736/S0375-9393.19.13820-5 -
CNS Drug Reviews 2006Paracetamol (acetaminophen) is one of the most popular and widely used drugs for the treatment of pain and fever. It occupies a unique position among analgesic drugs.... (Review)
Review
Paracetamol (acetaminophen) is one of the most popular and widely used drugs for the treatment of pain and fever. It occupies a unique position among analgesic drugs. Unlike NSAIDs it is almost unanimously considered to have no antiinflammatory activity and does not produce gastrointestinal damage or untoward cardiorenal effects. Unlike opiates it is almost ineffective in intense pain and has no depressant effect on respiration. Although paracetamol has been used clinically for more than a century, its mode of action has been a mystery until about one year ago, when two independent groups (Zygmunt and colleagues and Bertolini and colleagues) produced experimental data unequivocally demonstrating that the analgesic effect of paracetamol is due to the indirect activation of cannabinoid CB(1) receptors. In brain and spinal cord, paracetamol, following deacetylation to its primary amine (p-aminophenol), is conjugated with arachidonic acid to form N-arachidonoylphenolamine, a compound already known (AM404) as an endogenous cannabinoid. The involved enzyme is fatty acid amide hydrolase. N-arachidonoylphenolamine is an agonist at TRPV1 receptors and an inhibitor of cellular anandamide uptake, which leads to increased levels of endogenous cannabinoids; moreover, it inhibits cyclooxygenases in the brain, albeit at concentrations that are probably not attainable with analgesic doses of paracetamol. CB(1) receptor antagonist, at a dose level that completely prevents the analgesic activity of a selective CB(1) receptor agonist, completely prevents the analgesic activity of paracetamol. Thus, paracetamol acts as a pro-drug, the active one being a cannabinoid. These findings finally explain the mechanism of action of paracetamol and the peculiarity of its effects, including the behavioral ones. Curiously, just when the first CB(1) agonists are being introduced for pain treatment, it comes out that an indirect cannabino-mimetic had been extensively used (and sometimes overused) for more than a century.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Pain
PubMed: 17227290
DOI: 10.1111/j.1527-3458.2006.00250.x -
Science (New York, N.Y.) Sep 2022Because nonopioid analgesics are much sought after, we computationally docked more than 301 million virtual molecules against a validated pain target, the α-adrenergic...
Because nonopioid analgesics are much sought after, we computationally docked more than 301 million virtual molecules against a validated pain target, the α-adrenergic receptor (αAR), seeking new αAR agonists chemotypes that lack the sedation conferred by known αAR drugs, such as dexmedetomidine. We identified 17 ligands with potencies as low as 12 nanomolar, many with partial agonism and preferential G and G signaling. Experimental structures of αAR complexed with two of these agonists confirmed the docking predictions and templated further optimization. Several compounds, including the initial docking hit '9087 [mean effective concentration (EC) of 52 nanomolar] and two analogs, '7075 and PS75 (EC 4.1 and 4.8 nanomolar), exerted on-target analgesic activity in multiple in vivo pain models without sedation. These newly discovered agonists are interesting as therapeutic leads that lack the liabilities of opioids and the sedation of dexmedetomidine.
Topics: Adrenergic alpha-2 Receptor Agonists; Analgesics, Non-Narcotic; Animals; Dexmedetomidine; Drug Design; Drug Discovery; Humans; Ligands; Mice; Molecular Docking Simulation; Pain; Pain Management; Structure-Activity Relationship
PubMed: 36173843
DOI: 10.1126/science.abn7065 -
Ibuprofen in the treatment of children's inflammatory pain: a clinical and pharmacological overview.Minerva Pediatrica Feb 2019Unlike fever, which is often over-treated especially in children, pain is underestimated and under-treated in pediatric age. The pharmacological agents approved for... (Review)
Review
Unlike fever, which is often over-treated especially in children, pain is underestimated and under-treated in pediatric age. The pharmacological agents approved for treating pain in these patients are few, also considering the recent limitation for codeine in children younger than 12 years. Paracetamol and the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen are the most used at this purpose. The aim of this overview was to analyze the therapeutic appropriateness of ibuprofen in children based on its pharmacological properties. This work is a critical review of the pediatric literature over the last 20 years on efficacy and adverse events associated with the use of ibuprofen as analgesic in the pediatric population. Ibuprofen resulted effective in several pain conditions in children such as musculoskeletal pain, ear pain and acute otitis media, toothache and the inflammatory disease of the oral cavity and pharynx. The drug is a reasonable and efficacious alternative in postoperative pain, including tonsillectomy and adenoidectomy. It remains the treatment of choice for pain in chronic inflammatory diseases such as arthritis. Side effects and adverse events associated with ibuprofen are mild. It has the lowest gastrointestinal (GI) toxicity among NSAIDs, although some cases of GI toxicity may occur. Its renal effects are minimal, but dehydration plays an important role in triggering renal damage, so ibuprofen should not be given to patients with vomiting and diarrhea. Ibuprofen showed a good safety profile and provided evidence of effectiveness for mild-moderate pain of different origin in children. In case of fever or pain, the choice about the drug to be used should fall on ibuprofen in a clinical context where there is an inflammatory pathogenesis.
Topics: Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Child; Humans; Ibuprofen; Inflammation; Pain; Pain, Postoperative; Treatment Outcome
PubMed: 30574736
DOI: 10.23736/S0026-4946.18.05453-1 -
Journal of Pain and Symptom Management Nov 2013Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is...
Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is available on www.palliativedrugs.com. Country-specific books (Hospice and Palliative Care Formulary USA, and Palliative Care Formulary, British and Canadian editions) are also available and can be ordered from www.palliativedrugs.com. The series editors welcome feedback on the articles ([email protected]).
Topics: Acetaminophen; Analgesics, Non-Narcotic; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Humans; Pain; Treatment Outcome
PubMed: 24128822
DOI: 10.1016/j.jpainsymman.2013.08.001 -
Lakartidningen Jan 2018
Topics: Acetaminophen; Analgesics, Non-Narcotic; Delayed-Action Preparations; Humans; Legislation, Drug
PubMed: 29360129
DOI: No ID Found -
American Family Physician Jul 2016
Review
Topics: Analgesics, Non-Narcotic; Carbamazepine; Electrocoagulation; Humans; Microvascular Decompression Surgery; Radiosurgery; Trigeminal Neuralgia
PubMed: 27419329
DOI: No ID Found -
British Journal of Hospital Medicine... Sep 2022Intentional and accidental drug overdose, recreational drug use and exposure to toxic substances are common reasons for people presenting to emergency departments.... (Review)
Review
Intentional and accidental drug overdose, recreational drug use and exposure to toxic substances are common reasons for people presenting to emergency departments. Although the mortality rate associated with these presentations is low in the UK, they can lead to significant morbidity and prolonged hospital admissions. This review discusses new developments in the management of paracetamol overdose. Several new protocols for the infusion of acetylcysteine, the antidote for paracetamol overdose, have been proposed in the past decade and evaluated in clinical studies. The 12-hour Scottish and Newcastle Acetylcysteine Protocol regimen and 20-hour Australian two-infusion bag protocol have been widely adopted into clinical practice and endorsed in national guidelines because of their shorter duration, reduction in adverse effects and efficacy in treating overdose. This article includes a care pathway that can facilitate the implementation of the Scottish and Newcastle Acetylcysteine Protocol. This article also discusses the emergency management of ingested button batteries, describes the emerging threat of novel psychoactive substances, and provides an update on new UK antidote guidelines. Further up-to-date guidance on management of clinical toxicology is available to healthcare professionals on the internet database TOXBASE.
Topics: Acetaminophen; Acetylcysteine; Analgesics, Non-Narcotic; Antidotes; Australia; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Emergency Service, Hospital; Humans
PubMed: 36193928
DOI: 10.12968/hmed.2022.0313 -
Trends in Pharmacological Sciences Nov 2020Chronic pain is a life-altering condition affecting millions of people. Current treatments are inadequate and prolonged therapies come with severe side effects,... (Review)
Review
Chronic pain is a life-altering condition affecting millions of people. Current treatments are inadequate and prolonged therapies come with severe side effects, especially dependence and addiction to opiates. Identification of non-narcotic analgesics is of paramount importance. Preclinical and clinical studies suggest that sphingolipid metabolism alterations contribute to neuropathic pain development. Functional sphingosine-1-phosphate (S1P) receptor 1 (S1PR1) antagonists, such as FTY720/fingolimod, used clinically for non-pain conditions, are emerging as non-narcotic analgesics, supporting the repurposing of fingolimod for chronic pain treatment and energizing drug discovery focused on S1P signaling. Here, we summarize the role of S1P in pain to highlight the potential of targeting the S1P axis towards development of non-narcotic therapeutics, which, in turn, will hopefully help lessen misuse of opioid pain medications and address the ongoing opioid epidemic.
Topics: Analgesics, Non-Narcotic; Animals; Chronic Pain; Humans; Lysophospholipids; Molecular Targeted Therapy; Pain Management; Signal Transduction; Sphingosine; Sphingosine-1-Phosphate Receptors
PubMed: 33010954
DOI: 10.1016/j.tips.2020.09.006