What is known and Objective
Food and Drug Administration (FDA) risk evaluation and mitigation strategies (REMs) encourage emergency responders, paramedics, law enforcement agents, and even laypeople ...to be trained in the administration of naloxone with the intent of rescuing individuals from a known or suspected opioid overdose.
Comment
Although naloxone is generally safe and effective at reversing respiratory depression caused by a conventional opioid such as morphine or heroin by competing with the opioid and displacing it from the μ‐opioid receptor, questions increasingly are arising as to whether naloxone can adequately reverse opioid overdoses that may involve the potent opioids fentanyl and its analogues (F/FAs). In other words, as more and more opioid overdoses involve F/FAs, can naloxone keep up?
What is new and Conclusion
As a competitive antagonist at μ‐opioid receptors, naloxone is often a life‐saving agent in cases of overdose caused by conventional opioids, but it may not be versatile or powerful enough to combat the rising tide of overdoses due to fentanyl and its illicit analogues, or in cases of overdose involving combinations of opioids and non‐opioids.
Despite the high prevalence of neck pain, few studies have addressed the pharmacological treatment of this condition.
We evaluated the effectiveness of tapentadol prolonged-release (PR) in patients ...with or without a neuropathic pain component, with a focus on functional movements, disability and Quality of Life (QoL).
Observational, retrospective study.
Ninety-four adult patients with severe neck pain not responsive to opioid step III treatment.
The primary endpoint was a ≥ 30% improvement of pain intensity at 4 weeks (W4). Several secondary outcomes were evaluated, including neck disability index (NDI), range of motion (ROM), and QoL.
Patients received tapentadol PR at the starting dose of 100 mg/day. Dose titration was allowed in 50 mg increments, up to 500 mg daily.
At W4, the primary endpoint of ≥30% improvement of pain was reported in 70% (n = 35; 95% confidence interval CI: 55-82%) of patients with a neuropathic pain component and in 69% (n = 20; 95% CI: 49-85%) of those without a neuropathic component. The percentage of patients reporting a neuropathic pain component significantly decreased from baseline (64.2%) to W4 (27.8%). NDI significantly improved in both groups at W12. ROM significantly improved in all three planes of motion (p < .01), with no difference between the two groups. Interference of pain with sleep and QoL also improved.
The reduction in pain provided by tapentadol is associated with functional recovery, which may in turn be linked to an improvement in QoL.
The opioid epidemic is associated with morbidity and mortality, and it has taken a vast toll on American society. While prescription opioid abuse is part of the opioid problem, it is by no means the ...entirety of it. Opioid abuse appears to have entered a technology-driven new world of clandestine labs all over the globe and many new synthetic analog, counterfeit, and adulterated drugs that arrive via the internet faster than the Drug Enforcement Administration (DEA) can catalog and outlaw them. To deal with opioid abuse, it must be recognized that it is more - far more - than a subset of chronic pain patients who become addicted. Indeed, to reduce the opioid epidemic to this population is to misunderstand it. The opioid epidemic involves illicit opioids, counterfeit opioids, new psychoactive substances, diverted opioids, and prescription opioids. The objective of this narrative review is to consider the roles of all substances that contribute to the opioid epidemic in America.
Statins and muscle pain Pergolizzi, Joseph V.; Coluzzi, Flaminia; Colucci, Robert D. ...
Expert review of clinical pharmacology,
03/2020, Letnik:
13, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Introduction: Statins remain among the most frequently prescribed drugs and constitute a cornerstone in the prevention of cardiovascular disease. However, muscle symptoms are often reported from ...patients on statins. Muscle symptoms are frequently reported as adverse events associated with statin therapy.
Areas covered: In the present narrative review, statin-associated muscle pain is discussed. It elucidates potential mechanisms and possible targets for management.
Expert opinion: In general, the evidence in support of muscle pain caused by statins is in some cases equivocal and not particularly strong. Reported symptoms are difficult to quantify. Rarely is it possible to establish a causal link between statins and muscle pain. In randomized controlled trials, statins are well tolerated, and muscle-pain related side-effects is similar to placebo. There are also nocebo effects of statins. Exchange of statin may be beneficial although all statins have been associated with muscle pain. In some patients reduction of dose is worth trying, especially in primary prevention Although the benefits of statins outweigh potential risks in the vast majority of cases, careful clinical judgment may be necessary in certain cases to manage potential side effects on an individual basis.
Objective: Abuse and misuse of prescription opioids is a significant public health concern. This review examines the strategies used to confer abuse-deterrent properties on opioid abuse-deterrent ...formulations (ADFs), the characteristics and supporting data for each of the available ADFs, and the role of opioid ADFs as part of a comprehensive opioid risk management plan.
Methods: A PubMed search was performed for articles published within the last 10 years using the search terms "abuse deterrent opioids". Articles were limited to clinical studies and reviews focusing on United States (US) Food and Drug Administration (FDA)-approved opioid ADFs in the US.
Results: There are currently nine extended-release and one immediate-release opioid pain medications with US FDA-approved ADF labelling. All use either physical and chemical barriers or agonist/antagonist combinations to deter manipulation and abuse. Evidence is mounting that introduction of opioid ADFs has been associated with decreased rates of abuse and diversion of opioids in the US.
Conclusions: Although not sufficient by themselves to prevent prescription opioid abuse and misuse, opioid ADFs are an important component of a healthcare provider's comprehensive opioid risk management plan (along with utilization of prescription drug monitoring programs, clinical assessment tools, urine tests, co-prescribing of naloxone to patients at risk of an overdose, access to non-pharmacological treatments and addiction/mental health resources, among others). Adoption of opioid ADFs should be considered as part of an overall public health opioid risk management plan involving all stakeholders to balance legitimate safe and effective use of opioids against misuse and abuse.
The use of anesthetics may result in depression of the hypoxic ventilatory response. Since there are no receptor-specific antagonists for most anesthetics, there is the need for agnostic respiratory ...stimulants that increase respiratory drive irrespective of its cause. The authors tested whether ENA-001, an agnostic respiratory stimulant that blocks carotid body BK-channels, could restore the hypoxic ventilatory response during propofol infusion. They hypothesize that ENA-001 is able to fully restore the hypoxic ventilatory response.
In this randomized, double-blind crossover trial, 14 male and female healthy volunteers were randomized to receive placebo and low- and high-dose ENA-001 on three separate occasions. On each occasion, isohypercapnic hypoxic ventilatory responses were measured during a fixed sequence of placebo, followed by low- and high-dose propofol infusion. The authors conducted a population pharmacokinetic/pharmacodynamic analysis that included oxygen and carbon dioxide kinetics.
Twelve subjects completed the three sessions; no serious adverse events occurred. The propofol concentrations were 0.6 and 2.0 µg/ml at low and high dose, respectively. The ENA-001 concentrations were 0.6 and 1.0 µg/ml at low and high dose, respectively. The propofol concentration that reduced the hypoxic ventilatory response by 50% was 1.47 ± 0.20 µg/ml. The steady state ENA-001 concentration to increase the depressed ventilatory response by 50% was 0.51 ± 0.04 µg/ml. A concentration of 1 µg/ml ENA-001 was required for full reversal of the propofol effect at the propofol concentration that reduced the hypoxic ventilatory response by 50%.
In this pilot study, the authors demonstrated that ENA-001 restored the hypoxic ventilatory response impaired by propofol. This finding is not only of clinical importance but also provides mechanistic insights into the peripheral stimulation of breathing with ENA-001 overcoming central depression by propofol.
Concern about coronavirus 2019 (COVID-19) morbidity and mortality has drawn attention to the potential role of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) ...because the SARS-CoV-2 uses the ACE2 receptor as its point of entry into the body. It is not clear if and to what degree the SARS-CoV-2 virus affects the renin-angoiotensin system. Early studies from China which speculated on the role of ACE inhibition and ARBs did not evaluate the drug regimens. A vast body of evidence supports the use of ACE inhibitors and ARBs in hypertensive patients and patients with heart failure, and very little evidence has been acquired about their role in COVID-19. There is good evidence in support of the use of ACE inhibitors and ARBs in indicated patients with hypertension and heart failure, and clinicians should be reticent about abruptly withdrawing these drugs based on a paucity of evidence.
The frequently prescribed drug class of statins have pleiotropic effects and have been implicated in neuropathic pain syndromes. This narrative review examines studies of statin-induced neuropathic ...pain which to date have been conducted only in animal models. However, the pathophysiology of diabetic neuropathy in humans may shed some light on the etiology of neuropathic pain. Statins have exhibited a paradoxical effect in that statins appear to reduce neuropathic pain in animals but have been associated with neuropathic pain in humans. While there are certain postulated mechanisms offering elucidation as to how statins might be associated with neuropathic pain, there is, as the American Heart Association stated, to date no definitive association between statins and neuropathic pain. Statins are important drugs that reduce cardiovascular risk factors and should be prescribed to appropriate patients with these risk factors but some of this population is also at elevated risk for neuropathic pain from other causes.
Cluster headache is a rare form of headache associated with sleep and even speculated to be a manifestation of a sleep disorder rather than a primary headache. Cluster headache exhibits both ...circadian and circannual rhythmicity. While attacks often occur during sleep, the implication that cluster headaches might be involved with rapid eye movement (REM) sleep phases has neither been fully established nor refuted. The regulatory mechanisms governing sleep including hypothalamic activity and the autonomic nervous system response may play a role. Hypothalamic activation has been observed in cluster headache patients during positron emission tomography testing, but only during attacks. While sleep apnea is associated with morning headaches in general, the link between sleep-disordered respiration and cluster headache remains elusive. Hypoarousal during sleep and periods of hypoxia are associated with cluster headache, the latter likely involving inflammatory processes rather than apnea. Further study is needed, as cluster headaches represent a serious primary cephalgia that is incompletely understood.
The numerous drugs in the NSAID class are often used to treat acute postoperative pain associated with oral surgery such as impacted third-molar extractions. These drugs are effective in this setting ...and dental pain studies often serve as models for acute pain relief and for registration of analgesics. With numerous cyclooxygenase (COX) inhibitors available as monotherapy, for use in combination with analgesic regimens, and in different doses and formulations, it was our aim to determine if there were clear-cut distinctions among these products and dosing regimens.
This is a literature review of recent randomized controlled clinical trials evaluating NSAIDs for use in postoperative pain management following oral surgery. Of particular interest were head-to-head studies, which might offer some insight into comparative effectiveness.
Postoperative oral surgery pain is largely managed in real-world clinical practice using NSAIDs, either alone or in combination, and there is good evidence supporting their use especially in multimodal therapy. Head-to-head and comparative studies do not show a clear-cut 'optimal NSAID' in this setting, although ibuprofen, ketoprofen, dexketoprofen, and naproxen have gained most acceptance. Combination therapy with other analgesics or adjuvants is largely accepted.
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