Eicosanoids: prostaglandins, thromboxanes and leukotrienes as drug targets
The lipid messengers made from arachidonic acid, and the anti-inflammatories, antiplatelet drugs, asthma drugs and prostaglandin analogues that act on them.
Eicosanoids are short-lived signals made on demand from arachidonic acid released from cell membranes. Cyclooxygenase (COX) makes prostaglandins and thromboxane; 5-lipoxygenase makes leukotrienes. The chemistry of these pathways is on the Biochemistry page «Eicosanoids»; this page covers the drugs that block or copy them.
The pathway in brief
Arachidonic acid can go down two main roads. The COX road gives prostaglandins (PGE2, PGF2α, PGD2), prostacyclin (PGI2, made by vessel walls; it dilates vessels and stops platelets) and thromboxane A2 (made by platelets; it constricts vessels and makes platelets clump). The lipoxygenase road gives leukotrienes: LTB4 attracts neutrophils, and the cysteinyl leukotrienes (LTC4, LTD4, LTE4) constrict airways and make vessels leak.
Blocking prostaglandins: NSAIDs and coxibs
COX-1 is present in most tissues all the time (stomach, kidney, platelets); COX-2 is induced by inflammation but also has normal roles in the kidney and vessel wall. Non-selective NSAIDs block both, which relieves pain, fever and inflammation but brings stomach ulcers, bleeding and kidney effects. COX-2 selective drugs (celecoxib) spare the stomach somewhat, but they reduce vascular prostacyclin more than platelet thromboxane, which fits with their raised cardiovascular risk.
- Aspirin: irreversible; at low doses mainly antiplatelet
- Indometacin and ibuprofen can close a patent ductus arteriosus in newborns, because prostaglandins keep it open
- Late in pregnancy NSAIDs can narrow the fetal ductus
Copying prostaglandins: analogues
- Misoprostol (PGE1 analogue): protects the stomach from NSAIDs; it also contracts the uterus, so it is dangerous in pregnancy unless used for an obstetric purpose
- Carboprost (PGF2α analogue) and misoprostol: uterine contraction in postpartum haemorrhage
- Latanoprost (PGF2α analogue): eye drops that increase aqueous outflow in glaucoma
- Alprostadil (PGE1): keeps the ductus arteriosus open in some newborn heart defects
- Epoprostenol (prostacyclin): vasodilator for pulmonary arterial hypertension
Leukotrienes and asthma
Montelukast blocks the cysteinyl leukotriene receptor (CysLT1); zileuton blocks 5-lipoxygenase. Both help in asthma, especially aspirin-exacerbated respiratory disease, in which blocking COX shunts arachidonic acid toward leukotrienes. Montelukast carries a warning about neuropsychiatric effects.
Test yourself
Think of the answer, then tap the question to see it.
Why does one dose of aspirin affect platelets for days?
Aspirin acetylates COX irreversibly, and platelets have no nucleus to make new enzyme, so thromboxane A2 stays low until new platelets are released.
Why can NSAIDs trigger asthma attacks in some patients?
Blocking COX diverts arachidonic acid toward the lipoxygenase pathway, raising bronchoconstricting cysteinyl leukotrienes.
What are two clinical uses of prostaglandin analogues?
Any two of: protecting the stomach (misoprostol), postpartum haemorrhage (carboprost, misoprostol), glaucoma (latanoprost), keeping the ductus arteriosus open (alprostadil), pulmonary arterial hypertension (epoprostenol).
Why do NSAIDs threaten the kidney in dehydration or heart failure?
In these states kidney blood flow depends on vasodilating prostaglandins; blocking them can lower filtration and cause acute kidney injury.
Example drugs
- Acetylsalicylic acid
- Ibuprofen
- Celecoxib
- Indometacin
- Misoprostol
- Carboprost
- Montelukast
- Latanoprost
- Alprostadil
- Epoprostenol
Connections
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Misoprostol: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Montelukast: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026).
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Representative model, for educational purposes only.