NSAIDs in the Management of Rheumatoid Arthritis: Difference between revisions

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== Overview ==
== Overview ==
NSAIDS are commonly used for antipyretic, anti-inflammatory and analgesic purposes. The main indications are pain, inflammation and infection.<ref>Sohail R, Mathew M, Patel KK, Reddy SA, Haider Z, Naria M, Habib A, Abdin ZU, Chaudhry WR, Akbar A, Patel KK. Effects of non-steroidal anti-inflammatory drugs (NSAIDs) and gastroprotective NSAIDs on the gastrointestinal tract: a narrative review. Cureus. 2023 Apr 3;15(4).</ref>
Non-steroidal anti-inflammatory drugs ([[NSAIDs]]) are the first drugs used to symptomatically treat RA.<ref>O'Dell JR. Therapeutic strategies for rheumatoid arthritis. N Engl J Med. 2004;350(25):2591-2602.</ref> While they are not as potent anti-inflammatory drugs as glucocorticoids, they tend to have fewer side effects and offer pain relief.<ref>Gotzche PC, Johansen HK. Short-term low-dose corticosteroids vs placebo and nonsteroidal antiinflammatory drugs in rheumatoid arthritis. Cochrane Databse Syst Rev. 2004;(3):CD000189. doi:10.1002/14651858.CD000189.pub2</ref><ref>Adebajo A. Non-steroidal anti-inflammatory drugs for the treatment of pain and immobility-associated osteoarthritis: consensus guidance for primary care. BMC Fam Pract. 2012;13:23. doi:10.1186/1471-2296-13-23.</ref> In addition, they may later be combined with [[DMARDs in the Management of Rheumatoid Arthritis|DMARD]]<nowiki/>s to control the disease process.<ref>Blumenauer B, Cranney A, Clinch J, Tugwell P. Quality of life in patients with rheumatoid arthritis: which drugs might make a difference. Pharmacoeconomics. 2003;21(13):927-940.</ref> The NSAIDs focused on below are ibuprofen, diclofenac, and celecoxib.
Non-steroidal anti-inflammatory drugs ([[NSAIDs]]) are the first drugs used to symptomatically treat RA.<ref>O'Dell JR. Therapeutic strategies for rheumatoid arthritis. N Engl J Med. 2004;350(25):2591-2602.</ref> While they are not as potent anti-inflammatory drugs as glucocorticoids, they tend to have fewer side effects and offer pain relief.<ref>Gotzche PC, Johansen HK. Short-term low-dose corticosteroids vs placebo and nonsteroidal antiinflammatory drugs in rheumatoid arthritis. Cochrane Databse Syst Rev. 2004;(3):CD000189. doi:10.1002/14651858.CD000189.pub2</ref><ref>Adebajo A. Non-steroidal anti-inflammatory drugs for the treatment of pain and immobility-associated osteoarthritis: consensus guidance for primary care. BMC Fam Pract. 2012;13:23. doi:10.1186/1471-2296-13-23.</ref> In addition, they may later be combined with [[DMARDs in the Management of Rheumatoid Arthritis|DMARD]]<nowiki/>s to control the disease process.<ref>Blumenauer B, Cranney A, Clinch J, Tugwell P. Quality of life in patients with rheumatoid arthritis: which drugs might make a difference. Pharmacoeconomics. 2003;21(13):927-940.</ref> The NSAIDs focused on below are ibuprofen, diclofenac, and celecoxib.


== Pharmacokinetics ==
== Pharmacokinetics ==
NSAIDS exert their effects by inhibiting the COX-1 and COX-2 forms of enzymes that synthesize prostaglandins.<ref name=":0">Vane JR, Botting RM. The mechanism of action of aspirin. Thromb Res. 2003;110(5-6):255-258.</ref> Inhibition of COX-1 blocks the production of beneficial and protective prostaglandins, whereas inhibition of COX-2 blocks the synthesis of prostaglandins in inflamed tissues. Ibuprofen and diclofenac block both forms of the enzyme (Roberts & Morrow, 2001).<ref>Roberts LJ, Morrow JD. Analgesic-antipyretic and antiinflammatory agents and drugs employed in the treatment of gout. In: Hardman JG et al, ed. The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill;2001.</ref> Celecoxib, on the other hand, selectively inhibits only COX-2.<ref name=":0" />
NSAIDS exert their effects by inhibiting the COX-1 and COX-2 forms of enzymes that synthesize prostaglandins.<ref name=":0">Vane JR, Botting RM. The mechanism of action of aspirin. Thromb Res. 2003;110(5-6):255-258.</ref> Inhibition of COX-1 blocks the production of beneficial and protective prostaglandins, whereas inhibition of COX-2 blocks the synthesis of prostaglandins in inflamed tissues. Ibuprofen and diclofenac block both forms of the enzyme (Roberts & Morrow, 2001).<ref>Roberts LJ, Morrow JD. Analgesic-antipyretic and antiinflammatory agents and drugs employed in the treatment of gout. In: Hardman JG et al, ed. The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill;2001.</ref> Celecoxib, on the other hand, selectively inhibits only COX-2.<ref name=":0" /><ref>Machado GC, Abdel-Shaheed C, Underwood M, Day RO. Non-steroidal anti-inflammatory drugs (NSAIDs) for musculoskeletal pain. Bmj. 2021 Jan 29;372.</ref>
 
To determine which NSAID should be prescribed, the pharmacokinetics of the drugs should be considered. The half-lives of NSAIDs vary, ranging from a couple of hours (ibuprofen and diclofenac) to eleven hours (celecoxib). Absorption methods also differ. Ibuprofen is primarily absorbed by the GI tract and diclofenac undergoes first-pass metabolism via the liver, resulting in 50% bioavailability. The exact absorption mechanism for celecoxib is still unknown. All three undergo metabolism via the liver and are typically excreted in urine.<ref name=":1">U.S. Food and Drug Administration. Motrin® Ibuprofen Tablets, USP. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/017463s105lbl.pdf. Last Modified January 20, 2007. Accessed November 21, 2018.</ref><ref name=":2">U.S. Food and Drug Administration. Voltaren®  (diclofenac sodium enteric-coated tablets). https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019201s046lbl.pdf. Last Modified January 20, 2007. Accessed November 21, 2018.</ref>


To determine which NSAID should be prescribed, the pharmacokinetics of the drugs should be considered. The half-lives of NSAIDs vary, ranging from a couple of hours (ibuprofen and diclofenac) to eleven hours (celecoxib). Absorption methods also differ. Ibuprofen is primarily absorbed by the GI tract and diclofenac undergoes first-pass metabolism via the liver, resulting in 50% bioavailability. The exact absorption mechanism for celecoxib is still unknown. All three undergo metabolism via the liver and are typically excreted in urine.<ref name=":1">U.S. Food and Drug Administration. Motrin® Ibuprofen Tablets, USP. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/017463s105lbl.pdf. Last Modified January 20, 2007. Accessed November 21, 2018.</ref><ref name=":2">U.S. Food and Drug Administration. Voltaren®  (diclofenac sodium enteric-coated tablets). https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019201s046lbl.pdf. Last Modified January 20, 2007. Accessed November 21, 2018.</ref><ref name=":3">U.S. Food and Drug Administration. Celebrex® celecoxib capsules. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020998s026lbl.pdf. Last Modified January 20, 2007. Accessed November 21, 2018.</ref>
== Therapeutic Effects Of NSAIDS ==
== Therapeutic Effects Of NSAIDS ==
* NSAIDs are the first line of treatment for rheumatoid arthritis which helps in symptomatic relief.
* NSAIDs are the first line of treatment for rheumatoid arthritis which helps in symptomatic relief.
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* Cardiovascular- Myocardial infarction, stroke
* Cardiovascular- Myocardial infarction, stroke
* Neuro- dizziness, confusion, seizures
* Neuro- dizziness, confusion, seizures
* Renal- water retention, hypertension, weight gain<ref>Crofford LJ. Use of NSAIDs in treating patients with arthritis. Arthritis research & therapy. 2013 Jul;15:1-0.</ref><ref name=":2" /><ref name=":3" />
* Renal- water retention, hypertension, weight gain<ref name=":2" /><ref name=":3">U.S. Food and Drug Administration. Celebrex® celecoxib capsules. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020998s026lbl.pdf. Last Modified January 20, 2007. Accessed November 21, 2018.</ref>
 
== Clinical Implications ==
 
* NSAIDS are the most common medications used in treating arthritis, CV disease  and pain.
* It has been proven that NSAIDS causes delay in ulcer healing and produce gastrointestinal ulcer.<ref>Tarnawski AS, Jones MK. Inhibition of angiogenesis by NSAIDs: molecular mechanisms and clinical implications. Journal of molecular medicine. 2003 Oct;81:627-36.</ref>
* It can even lead to intestinal obstruction , GI erosion and GI bleeding.


== References ==
== References ==

Latest revision as of 11:41, 26 June 2024

Original Editor - Kristie Nguyen Top Contributors - Nupur Smit Shah, Kristie Nguyen, Kim Jackson and Lucinda hampton

Overview[edit | edit source]

NSAIDS are commonly used for antipyretic, anti-inflammatory and analgesic purposes. The main indications are pain, inflammation and infection.[1]

Non-steroidal anti-inflammatory drugs (NSAIDs) are the first drugs used to symptomatically treat RA.[2] While they are not as potent anti-inflammatory drugs as glucocorticoids, they tend to have fewer side effects and offer pain relief.[3][4] In addition, they may later be combined with DMARDs to control the disease process.[5] The NSAIDs focused on below are ibuprofen, diclofenac, and celecoxib.

Pharmacokinetics[edit | edit source]

NSAIDS exert their effects by inhibiting the COX-1 and COX-2 forms of enzymes that synthesize prostaglandins.[6] Inhibition of COX-1 blocks the production of beneficial and protective prostaglandins, whereas inhibition of COX-2 blocks the synthesis of prostaglandins in inflamed tissues. Ibuprofen and diclofenac block both forms of the enzyme (Roberts & Morrow, 2001).[7] Celecoxib, on the other hand, selectively inhibits only COX-2.[6][8]

To determine which NSAID should be prescribed, the pharmacokinetics of the drugs should be considered. The half-lives of NSAIDs vary, ranging from a couple of hours (ibuprofen and diclofenac) to eleven hours (celecoxib). Absorption methods also differ. Ibuprofen is primarily absorbed by the GI tract and diclofenac undergoes first-pass metabolism via the liver, resulting in 50% bioavailability. The exact absorption mechanism for celecoxib is still unknown. All three undergo metabolism via the liver and are typically excreted in urine.[9][10]

Therapeutic Effects Of NSAIDS[edit | edit source]

  • NSAIDs are the first line of treatment for rheumatoid arthritis which helps in symptomatic relief.
  • It mainly reduces pain and stiffness of the affected joints. the mechanism behind this is inhibition of prostaglandin production in peripheral tissues. Prostaglandin also plays an important role in neuronal sensitization.
  • It also has an anti inflammatory effect on juvenile rheumatoid arthritis.[11]

Adverse Effects[edit | edit source]

There are various toxicities linked with NSAIDS. The effect of it varies based on the compound and dosage.

  • Gastrointestinal- ulcer, colitis, Esophagitis
  • Cardiovascular- Myocardial infarction, stroke
  • Neuro- dizziness, confusion, seizures
  • Renal- water retention, hypertension, weight gain[10][12]

Clinical Implications[edit | edit source]

  • NSAIDS are the most common medications used in treating arthritis, CV disease and pain.
  • It has been proven that NSAIDS causes delay in ulcer healing and produce gastrointestinal ulcer.[13]
  • It can even lead to intestinal obstruction , GI erosion and GI bleeding.

References[edit | edit source]

  1. ↑ Sohail R, Mathew M, Patel KK, Reddy SA, Haider Z, Naria M, Habib A, Abdin ZU, Chaudhry WR, Akbar A, Patel KK. Effects of non-steroidal anti-inflammatory drugs (NSAIDs) and gastroprotective NSAIDs on the gastrointestinal tract: a narrative review. Cureus. 2023 Apr 3;15(4).
  2. ↑ O'Dell JR. Therapeutic strategies for rheumatoid arthritis. N Engl J Med. 2004;350(25):2591-2602.
  3. ↑ Gotzche PC, Johansen HK. Short-term low-dose corticosteroids vs placebo and nonsteroidal antiinflammatory drugs in rheumatoid arthritis. Cochrane Databse Syst Rev. 2004;(3):CD000189. doi:10.1002/14651858.CD000189.pub2
  4. ↑ Adebajo A. Non-steroidal anti-inflammatory drugs for the treatment of pain and immobility-associated osteoarthritis: consensus guidance for primary care. BMC Fam Pract. 2012;13:23. doi:10.1186/1471-2296-13-23.
  5. ↑ Blumenauer B, Cranney A, Clinch J, Tugwell P. Quality of life in patients with rheumatoid arthritis: which drugs might make a difference. Pharmacoeconomics. 2003;21(13):927-940.
  6. ↑ 6.0 6.1 Vane JR, Botting RM. The mechanism of action of aspirin. Thromb Res. 2003;110(5-6):255-258.
  7. ↑ Roberts LJ, Morrow JD. Analgesic-antipyretic and antiinflammatory agents and drugs employed in the treatment of gout. In: Hardman JG et al, ed. The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill;2001.
  8. ↑ Machado GC, Abdel-Shaheed C, Underwood M, Day RO. Non-steroidal anti-inflammatory drugs (NSAIDs) for musculoskeletal pain. Bmj. 2021 Jan 29;372.
  9. ↑ U.S. Food and Drug Administration. Motrin® Ibuprofen Tablets, USP. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/017463s105lbl.pdf. Last Modified January 20, 2007. Accessed November 21, 2018.
  10. ↑ 10.0 10.1 U.S. Food and Drug Administration. Voltaren® (diclofenac sodium enteric-coated tablets). https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019201s046lbl.pdf. Last Modified January 20, 2007. Accessed November 21, 2018.
  11. ↑ Crofford LJ. Use of NSAIDs in treating patients with arthritis. Arthritis research & therapy. 2013 Jul;15:1-0.
  12. ↑ U.S. Food and Drug Administration. Celebrex® celecoxib capsules. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020998s026lbl.pdf. Last Modified January 20, 2007. Accessed November 21, 2018.
  13. ↑ Tarnawski AS, Jones MK. Inhibition of angiogenesis by NSAIDs: molecular mechanisms and clinical implications. Journal of molecular medicine. 2003 Oct;81:627-36.
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