Pharmacological hypotheses: Is acetaminophen selective in its cyclooxygenase inhibition?

Esh, Christopher J.; Chrismas, Bryna C. R.; Mauger, Alexis R.; Taylor, Lee

doi:10.1002/prp2.835

Cited by 22 publications

(17 citation statements)

References 105 publications

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“…The major inconveniences of NSAIDs are related to their cardiovascular, nephrotoxic, and gastrointestinal adverse effects; thus, pharmacological guidelines for the management of OA recommend paracetamol intake of only up to 4 g/day [37]. It is an over-the-counter analgesic and antipyretic but the specific mechanism of its action is not fully elucidated [38]. Taken in therapeutic doses, paracetamol is remarkably well tolerated and metabolized, and the metabolic products are excreted in the urine [39].…”

Section: Nonsteroidal Anti-inflammatory Drugs (Nsaids)mentioning

confidence: 99%

Overview of First-Line and Second-Line Pharmacotherapies for Osteoarthritis with Special Focus on Intra-Articular Treatment

Nowaczyk

Szwedowski

Dallo³

et al. 2022

IJMS

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Osteoarthritis (OA) can be defined as the result of pathological processes of various etiologies leading to damage to the articular structures. Although the mechanism of degenerative changes has become better understood due to the plethora of biochemical and genetic studies, the drug that could stop the degenerative cascade is still unknown. All available forms of OA therapy are based on symptomatic treatment. According to actual guidelines, comprehensive treatment of OA should always include a combination of various therapeutic options aimed at common goals, which are pain relief in the first place, and then the improvement of function. Local treatment has become more common practice, which takes place between rehabilitation and pharmacological treatment in the hierarchy of procedures. Only in the case of no improvement and the presence of advanced lesions visible in imaging tests, should surgery be considered. Currently, an increasing number of studies are being published suggesting that intra-articular injections may be as effective or even more effective than non-steroidal anti-inflammatory drugs (NSAIDs) and result in fewer systemic adverse events. The most commonly used preparations are hyaluronic acid (HA), glucocorticosteroids (GS), and also platelet-rich plasma (PRP) in recent years. This review aims to present the mechanism of action and clinical effectiveness of different pharmacological options in relieving pain and improving functions in OA as well as the emerging approach in intra-articular treatment with PRP.

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Section: Nonsteroidal Anti-inflammatory Drugs (Nsaids)mentioning

confidence: 99%

Overview of First-Line and Second-Line Pharmacotherapies for Osteoarthritis with Special Focus on Intra-Articular Treatment

Nowaczyk

Szwedowski

Dallo³

et al. 2022

IJMS

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“…Acetaminophen exerts its effects by blocking the synthesis of prostaglandins from arachidonic acid and via actions of its metabolite AM404 ( Flower and Vane, 1972 ; Ghanem et al, 2016 ). Inhibition of prostaglandin synthesis is achieved by hampering the activity of COX-1 and COX-2 ( Esh et al, 2021 ). COX-1 is expressed in most tissues and regulates basal levels of prostaglandins which control platelet activation and protect the lining of the gastrointestinal tract ( Crofford, 1997 ).…”

Section: Reactive Oxygen Species Modulation By Approved Drugsmentioning

confidence: 99%

Modulation of Reactive Oxygen Species Homeostasis as a Pleiotropic Effect of Commonly Used Drugs

et al. 2022

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Age-associated diseases represent a growing burden for global health systems in our aging society. Consequently, we urgently need innovative strategies to counteract these pathological disturbances. Overwhelming generation of reactive oxygen species (ROS) is associated with age-related damage, leading to cellular dysfunction and, ultimately, diseases. However, low-dose ROS act as crucial signaling molecules and inducers of a vaccination-like response to boost antioxidant defense mechanisms, known as mitohormesis. Consequently, modulation of ROS homeostasis by nutrition, exercise, or pharmacological interventions is critical in aging. Numerous nutrients and approved drugs exhibit pleiotropic effects on ROS homeostasis. In the current review, we provide an overview of drugs affecting ROS generation and ROS detoxification and evaluate the potential of these effects to counteract the development and progression of age-related diseases. In case of inflammation-related dysfunctions, cardiovascular- and neurodegenerative diseases, it might be essential to strengthen antioxidant defense mechanisms in advance by low ROS level rises to boost the individual ROS defense mechanisms. In contrast, induction of overwhelming ROS production might be helpful to fight pathogens and kill cancer cells. While we outline the potential of ROS manipulation to counteract age-related dysfunction and diseases, we also raise the question about the proper intervention time and dosage.

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“…7 Indeed, ACE has a higher affinity for COX-2 than COX-1 (4.4-fold). 8,9 ACE also affects central sites of action that differ from NSAIDs. 10 While the primary uses of ACE are to alleviate pain and reduce fever, research indicates that the physiological effects may influence musculoskeletal adaptations.…”

Section: Introductionmentioning

confidence: 99%

Acetaminophen influences musculoskeletal signaling but not adaptations to endurance exercise training

Roberts,

Geddis,

Ciuciu

et al. 2024

The FASEB Journal

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Acetaminophen (ACE) is a widely used analgesic and antipyretic drug with various applications, from pain relief to fever reduction. Recent studies have reported equivocal effects of habitual ACE intake on exercise performance, muscle growth, and risks to bone health. Thus, this study aimed to assess the impact of a 6‐week, low‐dose ACE regimen on muscle and bone adaptations in exercising and non‐exercising rats. Nine‐week‐old Wistar rats (n = 40) were randomized to an exercise or control (no exercise) condition with ACE or without (placebo). For the exercise condition, rats ran 5 days per week for 6 weeks at a 5% incline for 2 min at 15 cm/s, 2 min at 20 cm/s, and 26 min at 25 cm/s. A human equivalent dose of ACE was administered (379 mg/kg body weight) in drinking water and adjusted each week based on body weight. Food, water intake, and body weight were measured daily. At the beginning of week 6, animals in the exercise group completed a maximal treadmill test. At the end of week 6, rats were euthanized, and muscle cross‐sectional area (CSA), fiber type, and signaling pathways were measured. Additionally, three‐point bending and microcomputer tomography were measured in the femur. Follow‐up experiments in human primary muscle cells were used to explore supra‐physiological effects of ACE. Data were analyzed using a two‐way ANOVA for treatment (ACE or placebo) and condition (exercise or non‐exercise) for all animal outcomes. Data for cell culture experiments were analyzed via ANOVA. If omnibus significance was found in either ANOVA, a post hoc analysis was completed, and a Tukey's adjustment was used. ACE did not alter body weight, water intake, food intake, or treadmill performance (p > .05). There was a treatment‐by‐condition effect for Young's Modulus where placebo exercise was significantly lower than placebo control (p < .05). There was no treatment by condition effects for microCT measures, muscle CSA, fiber type, or mRNA expression. Phosphorylated‐AMPK was significantly increased with exercise (p < .05) and this was attenuated with ACE treatment. Furthermore, phospho‐4EBP1 was depressed in the exercise group compared to the control (p < .05) and increased in the ACE control and ACE exercise group compared to placebo exercise (p < .05). A low dose of ACE did not influence chronic musculoskeletal adaptations in exercising rodents but acutely attenuated AMPK phosphorylation and 4EBP1 dephosphorylation post‐exercise.

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Pharmacological hypotheses: Is acetaminophen selective in its cyclooxygenase inhibition?

Cited by 22 publications

References 105 publications

Overview of First-Line and Second-Line Pharmacotherapies for Osteoarthritis with Special Focus on Intra-Articular Treatment

Overview of First-Line and Second-Line Pharmacotherapies for Osteoarthritis with Special Focus on Intra-Articular Treatment

Modulation of Reactive Oxygen Species Homeostasis as a Pleiotropic Effect of Commonly Used Drugs

Acetaminophen influences musculoskeletal signaling but not adaptations to endurance exercise training

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