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What is the Difference Between COX 1 and COX 2 Inhibitors

December 3, 2021 Posted by Dr.Samanthi

The key difference between COX 1 and COX 2 inhibitors is that COX 1 inhibitor is a non-steroidal anti-inflammatory drug that inhibits cyclooxygenase-1 enzyme expressed constitutively in most tissues while COX 2 inhibitor is a non-steroidal anti-inflammatory drug that inhibits cyclooxygenase-2 enzyme expressed in areas of inflammation.

Non-steroidal anti-inflammatory drugs (NSAIDS) usually provide anti-inflammatory, analgesic, and antipyretic effects. They are used in the treatment of a variety of diseases. Non-steroidal anti-inflammatory drugs inhibit a particular rate-limiting enzyme called cyclooxygenase (COX) involved in the production of prostaglandins. Two isoforms of this enzyme have been identified: COX 1 and COX 2.  COX 1 inhibitor and COX 2 inhibitor are two non-steroidal anti-inflammatory drugs involved in the inhibition of cyclooxygenase 1 (COX 1) and cyclooxygenase 2 (COX 2), respectively.

CONTENTS

1. Overview and Key Difference
2. What are COX 1 Inhibitors
3. What are COX 2 Inhibitors
4. Similarities – COX 1 and COX 2 Inhibitors
5. COX 1 vs COX 2 Inhibitors in Tabular Form
6. Summary – COX 1 vs COX 2 Inhibitors

What are COX 1 Inhibitors?

COX 1 inhibitor is a non-steroidal anti-inflammatory drug that inhibits the cyclooxygenase-1 enzyme. This enzyme is constitutively expressed in most tissues. Cyclooxygenase-1 (COX 1) isoform normally produces cytoprotective prostaglandins. This enzyme is present in tissues, including gastrointestinal tract mucosa, kidneys, and platelets. Cyclooxygenase-1 isoform maintains the normal lining of the stomach and intestines. This isoform also protects the stomach from digestive juices. Moreover, Cyclooxygenase-1 isoform is involved in kidney and platelet function. Cyclooxygenase-1 enzyme produces prostaglandins that contribute to pain, fever, and inflammation. Therefore, COX 1 inhibitor is used to inhibit cyclooxygenase-1 isoform. Since the main role of cyclooxygenase-1 is to protect the stomach and intestine and contribute to blood clotting, the use of COX 1 inhibitor drugs can lead to unwanted side effects.

COX 1 vs COX 2 Inhibitors in Tabular Form

Figure 01: COX 1 Inhibitor

Traditional non-steroidal anti-inflammatory drugs such as ibuprofen, aspirin, and naproxen are inhibitors of both COX 1 and COX 2 isoforms as they are non-selective in their action. Traditional non-steroidal anti-inflammatory drugs are used to treat conditions like arthritis. Modern selective COX 1 inhibitors selectively inhibit only COX 1 isoform. Some examples of modern selective COX 1 inhibitors include ketorolac, flurbiprofen, ketoprofen, indomethacin, tolmetin, piroxicam, and meclofenamate. However, the inhibition of the COX 1 isoform can lead to side effects such as gastrointestinal ulcers and uncontrolled bleeding.

What are COX 2 Inhibitors?

COX 2 inhibitor is a non-steroidal anti-inflammatory drug that inhibits the cyclooxygenase-2 enzyme that is expressed in areas of inflammation. Selective COX 2 inhibitor drugs possess a bulky side chain that is too large to orient into the binding site of the cyclooxygenase-1 enzyme. But they are enabled to align and bind to the cyclooxygenase-2 isoform. Cyclooxygenase-2 enzyme plays a major role in maintaining vascular integrity.

COX 1 and COX 2 Inhibitors - Side by Side Comparison

Figure 02: COX 2 Inhibitor

The inhibition of the cyclooxygenase-2 isoform leads to decreased production of vasodilator prostaglandins from endothelial cells. However, thromboxane from platelets is not inhibited by COX inhibitor due to the lack of COX 2 isoform present on mature platelets. Furthermore, COX inhibitor is thought to be a contributing factor to the increased risk of developing myocardial infarction, congestive heart failure, stroke, pulmonary and systemic hypertension. Some examples include COX 2 inhibitors are sulindac, diclofenac, celecoxib, meloxicam, etodolac, etoricoxib, and lumiracoxib.

What are the Similarities Between COX 1 and COX 2 Inhibitors?

  • COX 1 inhibitor and COX 2 inhibitor are two non-steroidal anti-inflammatory drugs.
  • They are involved in the inhibition of cyclooxygenase 1 (COX 1) and cyclooxygenase 2 (COX 2) enzymes that produce prostaglandins.
  • Both COX 1 and COX 2 inhibitors can cause serious side effects.
  • COX 1 and COX 2 inhibitors are selective in action than traditional non-steroidal anti-inflammatory drugs.

What is the Difference Between COX 1 and COX 2 Inhibitors?

COX 1 inhibitor is a non-steroidal anti-inflammatory drug that inhibits the cyclooxygenase-1 enzyme, which is constitutively expressed in most tissues, while COX 2 inhibitor is a non-steroidal anti-inflammatory drug that inhibits the cyclooxygenase-2 enzyme, which is expressed in areas of inflammation. Thus, this is the key difference between COX 1 and COX 2 inhibitors. Furthermore, the side effects of the COX 1 inhibitor include gastrointestinal ulcers and uncontrolled bleeding, while the side effects of the COX 2 inhibitor include developing myocardial infarction, congestive heart failure, stroke, pulmonary and systemic hypertension.

The below infographic presents the differences between COX 1 and COX 2 inhibitors in tabular form for side by side comparison.

Summary – COX 1 vs COX 2 Inhibitors

COX 1 inhibitor and COX 2 inhibitor are two non-steroidal anti-inflammatory drugs. They are selective than traditional non-steroidal anti-inflammatory drugs such as ibuprofen, aspirin, and naproxen. COX 1 inhibitor is a drug that inhibits cyclooxygenase-1 enzyme. COX 2 inhibitor is a drug that inhibits cyclooxygenase-2. So, this is the key difference between COX 1 inhibitor and COX 2 inhibitor.

Reference:

1. “Cyclooxygenase 1 Inhibitor.” An Overview | ScienceDirect Topics.
2. Annette (Gbemudu) Ogbru, PharmD. “COX-2 Inhibitors: Drug List, Uses, Side Effects, Interactions.” RxList, 8 Apr. 2021.

Image Courtesy:

1. “Flurbiprofen in COX-2” By Ppruks – Own work (CC0) via Commons Wikimedia
2. “Etoricoxib molecule spacefill” By Jynto (more from this user) – Own work.  created with Discovery Studio Visualizer. (CC0) via Commons Wikimedia

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Filed Under: Biochemistry

About the Author: Dr.Samanthi

Dr.Samanthi Udayangani holds a B.Sc. Degree in Plant Science, M.Sc. in Molecular and Applied Microbiology, and PhD in Applied Microbiology. Her research interests include Bio-fertilizers, Plant-Microbe Interactions, Molecular Microbiology, Soil Fungi, and Fungal Ecology.

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