[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Inflammation](https://durgical.com/en/general-pathology/#a-inflammation) › Arachidonic acid metabolites in inflammation, and the drugs that block them

[General pathology](https://durgical.com/en/general-pathology/) · [Inflammation](https://durgical.com/en/general-pathology/#a-inflammation)

# Arachidonic acid metabolites in inflammation, and the drugs that block them

- Mechanism

Cell membranes release arachidonic acid, which enzymes turn into prostaglandins and leukotrienes; most anti-inflammatory drugs block this pathway.

Updated 2026-11-01

## Key points

- Phospholipase A2 → arachidonic acid → COX (prostaglandins, thromboxane) or 5-lipoxygenase (leukotrienes).
- Glucocorticoids act upstream (phospholipase A2, COX-2 transcription); NSAIDs block COX.
- Aspirin acetylates COX irreversibly: its antiplatelet effect lasts the life of the platelet.
- COX-2 inhibitors: fewer ulcers, more thrombosis (PGI2 falls, TXA2 does not).
- LTB4 = neutrophil chemotaxis; LTC4, LTD4, LTE4 = bronchospasm and leakage.

## What it is

When a cell is activated, phospholipase A2 frees arachidonic acid from membrane phospholipids. Cyclooxygenases turn it into prostaglandins and thromboxane, and 5-lipoxygenase into leukotrienes; together these eicosanoids drive vasodilation, pain, fever, bronchospasm and chemotaxis. The pathway explains how glucocorticoids, aspirin, NSAIDs, COX-2 inhibitors and leukotriene blockers work, and their typical side effects.

## Key facts

- PGE2: vasodilation, pain sensitisation, fever, gastric mucus and bicarbonate; keeps the ductus arteriosus open.
- PGI2 (prostacyclin, endothelium): vasodilation, blocks platelet aggregation. TXA2 (platelets): vasoconstriction, aggregation.
- PGD2 (mast cells): vasodilation, leakage, attracts eosinophils and Th2 cells.
- LTC4, LTD4 and LTE4 (once called the slow-reacting substance of anaphylaxis) cause bronchospasm and leakage.
- Lipoxins, resolvins and protectins are pro-resolving lipids that help end inflammation.

## Step by step

- A stimulus raises cytoplasmic calcium and activates phospholipase A2, which releases arachidonic acid from membrane phospholipids.
- Cyclooxygenase (COX-1, constitutive; COX-2, induced by inflammation) converts it to PGG2 and then PGH2.
- Cell-specific enzymes then make PGI2 in endothelium, TXA2 in platelets, PGD2 in mast cells and PGE2 in many cells.
- 5-lipoxygenase, helped by FLAP, converts arachidonic acid to LTA4, then to LTB4 (neutrophils) or LTC4, D4, E4 (mast cells).
- Leukocytes and platelets working together make lipoxins, which slow neutrophil entry and help resolution.
- The products act on G-protein-coupled receptors near where they are made and are quickly inactivated.

## Where the drugs act

| Drug | Target | Effects and key adverse effects |
| --- | --- | --- |
| Glucocorticoids | Reduce phospholipase A2 activity (through annexin A1) and the expression of COX-2 and cytokines | Broad anti-inflammatory effect; infections, hyperglycaemia, poor wound healing |
| Aspirin | Irreversibly acetylates COX-1 and COX-2 | Anti-inflammatory and antipyretic; lasting antiplatelet effect; gastric ulcers; Reye syndrome in children |
| Other NSAIDs (ibuprofen, naproxen, indomethacin) | Reversibly inhibit COX-1 and COX-2 | Less pain and fever; peptic ulcer, kidney injury; indomethacin closes the ductus arteriosus |
| Celecoxib (COX-2 selective) | Inhibits inducible COX-2 | Fewer gastric ulcers; higher thrombotic risk |
| Zileuton | Inhibits 5-lipoxygenase | Fewer leukotrienes; used in asthma |
| Montelukast, zafirlukast | Block the CysLT1 receptor | Less bronchospasm and leakage in asthma |
| Misoprostol | PGE1 analogue | Protects the gastric mucosa against NSAID ulcers |

## Clinical notes

- Aspirin-exacerbated respiratory disease: COX blockade shifts arachidonic acid toward leukotrienes, causing asthma attacks, nasal polyps and rhinitis.
- NSAIDs reduce prostaglandin-dependent kidney blood flow; risk is higher with dehydration, heart failure, cirrhosis, or with ACE inhibitors and diuretics.
- Loss of protective mucosal PGE2 explains NSAID-induced gastric ulcers, the second great cause of peptic ulcer after H. pylori.

## Memory aid

Prostacyclin (PGI2) keeps vessels open and platelets apart; thromboxane (TXA2) is the plug: it closes the vessel and builds the clot.

## Test yourself

Think of the answer, then tap the question to see it.

## Why do selective COX-2 inhibitors increase thrombotic risk?

They lower endothelial prostacyclin (PGI2, made partly through COX-2) while platelet thromboxane A2 (made by COX-1) is unaffected, tipping the balance toward clotting.

## Which leukotriene is chemotactic for neutrophils?

Leukotriene B4.

## Why can aspirin trigger asthma attacks in some patients?

Blocking COX diverts arachidonic acid to the 5-lipoxygenase pathway, increasing cysteinyl leukotrienes that cause bronchospasm.

## At what step of the pathway do glucocorticoids act?

Upstream: they reduce phospholipase A2 activity and the expression of COX-2 and inflammatory cytokines.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/general-pathology/arachidonic-acid-metabolites-in-inflammation-and-the-drugs-that-block-them/)

## Related

- [Mediators of inflammation: the table to know](https://durgical.com/en/general-pathology/mediators-of-inflammation-the-table-to-know/)
- [Systemic effects of inflammation: fever, acute-phase proteins, leukocytosis, sepsis](https://durgical.com/en/general-pathology/systemic-effects-of-inflammation-fever-acute-phase-proteins-leukocytosis-sepsis/)
- [Histamine, serotonin, bradykinin and the plasma protein cascades](https://durgical.com/en/general-pathology/histamine-serotonin-bradykinin-and-the-plasma-protein-cascades/)
- [Inflammation: the cardinal signs and its five steps](https://durgical.com/en/general-pathology/inflammation-the-cardinal-signs-and-its-five-steps/)

## Related conditions

- [Peptic ulcer disease](https://durgical.com/en/conditions/peptic-ulcer-disease/)
- [Asthma](https://durgical.com/en/conditions/asthma/)
- [Patent ductus arteriosus](https://durgical.com/en/conditions/patent-ductus-arteriosus/)
- [Acute kidney injury](https://durgical.com/en/conditions/acute-kidney-injury/)
- [Anaphylaxis](https://durgical.com/en/conditions/anaphylaxis/)
- [Gout](https://durgical.com/en/conditions/gout/)
- [Rheumatoid arthritis](https://durgical.com/en/conditions/rheumatoid-arthritis/)

## Elsewhere in DurgiPedia

- [Prostaglandin and thromboxane synthesis](https://durgical.com/en/biochemistry/pathways/prostaglandin-and-thromboxane-synthesis/)
- [Eicosanoids: prostaglandins, thromboxanes and leukotrienes](https://durgical.com/en/biochemistry/topics/eicosanoids-prostaglandins-thromboxanes-and-leukotrienes/)
- [Arachidonic acid](https://durgical.com/en/biochemistry/molecules/arachidonic-acid/)
- [Prostaglandin H₂ (PGH₂)](https://durgical.com/en/biochemistry/molecules/prostaglandin-h/)
- [Actions of cortisol](https://durgical.com/en/physiology/actions-of-cortisol/)
- [Fever](https://durgical.com/en/physiology/fever/)

## In Pharmacology

- [Nonsteroidal anti-inflammatory drugs (NSAIDs)](https://durgical.com/en/pharmacology/classes/nonsteroidal-anti-inflammatory-drugs/)
- [Celecoxib](https://durgical.com/en/pharmacology/celecoxib/)
- [Corticosteroids (glucocorticoids)](https://durgical.com/en/pharmacology/classes/corticosteroids/)
- [Leukotriene modifiers](https://durgical.com/en/pharmacology/classes/leukotriene-modifiers/)
- [Montelukast](https://durgical.com/en/pharmacology/montelukast/)
- [Misoprostol](https://durgical.com/en/pharmacology/misoprostol/)
- [Ibuprofen](https://durgical.com/en/pharmacology/ibuprofen/)
- [Ketorolac](https://durgical.com/en/pharmacology/ketorolac/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [Pain Relievers | Analgesics | Painkillers | MedlinePlus](https://medlineplus.gov/painrelievers.html) (MedlinePlus, US National Library of Medicine, 2026); [Peptic Ulcer Disease](https://www.ncbi.nlm.nih.gov/books/NBK534792/) (StatPearls (NCBI Bookshelf), 2024); [17.5 Inflammation and Fever](https://openstax.org/books/microbiology/pages/17-5-inflammation-and-fever) (OpenStax (Microbiology), 2016).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/arachidonic-acid-metabolites-in-inflammation-and-the-drugs-that-block-them/