What is the mechanism of action (MOA) of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and corticosteroids?

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From the Guidelines

NSAIDs and steroids have distinct mechanisms of action, with NSAIDs inhibiting cyclooxygenase (COX) enzymes to reduce prostaglandins, and steroids binding to glucocorticoid receptors to suppress inflammatory pathways, making them suitable for different conditions and severity levels. The mechanism of action of NSAIDs involves the inhibition of COX-1 and COX-2 enzymes, which are responsible for producing prostaglandins that cause pain, inflammation, and fever 1. By blocking these enzymes, NSAIDs like ibuprofen, naproxen, and diclofenac reduce the production of prostaglandins, thereby reducing inflammation and pain. Selective COX-2 inhibitors, such as celecoxib, target primarily the COX-2 enzyme, which is involved in inflammation, while sparing the COX-1 enzyme, which is responsible for protecting the stomach lining 1. On the other hand, steroids, such as prednisone, methylprednisolone, and dexamethasone, work by binding to intracellular glucocorticoid receptors, which then regulate gene expression, broadly suppressing multiple inflammatory pathways. This more comprehensive anti-inflammatory effect explains why steroids are more potent than NSAIDs but also carry greater risks with long-term use, including immunosuppression, metabolic effects, and bone density loss. The choice between these medications depends on the condition being treated, with NSAIDs typically used for mild to moderate pain and inflammation, while steroids are reserved for more severe inflammatory conditions or when NSAIDs are insufficient. Key considerations in choosing between NSAIDs and steroids include the severity of the condition, the potential risks and benefits of each medication, and the individual patient's medical history and comorbidities. In general, NSAIDs are preferred for mild to moderate pain and inflammation, while steroids are reserved for more severe conditions, such as autoimmune disorders or severe inflammatory reactions. However, the decision to use NSAIDs or steroids should always be made on a case-by-case basis, taking into account the individual patient's needs and circumstances. It is also important to consider the potential interactions between NSAIDs and other medications, such as aspirin, and to monitor patients closely for signs of gastrointestinal toxicity or other adverse effects. Ultimately, the goal of treatment is to reduce inflammation and pain while minimizing the risk of adverse effects, and the choice of medication should be guided by this principle. In terms of specific dosing recommendations, NSAIDs such as ibuprofen and naproxen are typically used at doses of 400-800mg every 6-8 hours, while selective COX-2 inhibitors like celecoxib are used at doses of 100-200mg daily 1. Steroids, such as prednisone and methylprednisolone, are typically used at doses of 5-60mg daily, depending on the condition being treated and the individual patient's response to treatment. It is essential to follow established dosing guidelines and to monitor patients closely for signs of adverse effects, such as gastrointestinal toxicity or immunosuppression. By carefully considering the mechanisms of action, potential risks and benefits, and individual patient needs, healthcare providers can make informed decisions about the use of NSAIDs and steroids in clinical practice.

From the FDA Drug Label

The mechanism of action of the naproxen anion, like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition

The mechanism of action of NSAIDs, such as naproxen, is believed to be related to prostaglandin synthetase inhibition.

  • NSAIDs work by inhibiting the production of prostaglandins, which are hormone-like substances that cause pain and inflammation.
  • The exact mechanism is not completely understood. There is no information about the mechanism of action of steroids in the provided drug label. 2

From the Research

Mechanism of Action of NSAIDs

  • The primary mechanism of action of NSAIDs is the inhibition of cyclooxygenase (COX) enzymes, which are involved in the production of prostaglandins 3, 4.
  • There are two isoforms of COX: COX-1 and COX-2, with COX-1 being constitutively expressed in normal cells and COX-2 being induced in inflammatory cells 3, 4.
  • Inhibition of COX-2 is thought to be the primary mechanism of action for NSAID-mediated analgesia, while inhibition of COX-1 is associated with adverse effects such as gastrointestinal toxicity 3, 4.
  • NSAIDs may also exert their effects through other mechanisms, including inhibition of the lipoxygenase pathway, interference with G-protein-mediated signal transduction, and central mechanisms involving the formation of prostaglandins within the CNS or the release of endogenous opioid peptides 4.

Mechanism of Action of Steroids

  • No information is available on the mechanism of action of steroids in the provided evidence.

Comparison of NSAIDs and Steroids

  • No direct comparison of the mechanisms of action of NSAIDs and steroids is available in the provided evidence.

Additional Mechanisms of NSAIDs

  • NSAIDs have been shown to inhibit TRPM7 channels by cytosolic acidification, which may be a novel mechanism of action unrelated to COX enzyme inhibition 5.
  • NSAIDs may also affect ion channels and cellular calcium homeostasis, and influence neutrophil function and lymphocyte proliferation 5, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Nonsteroidal antiinflammatory drugs and their effects.

Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 1996

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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