Eicosinoids

• 1. Dinoprostone (PGE2 synthetic)
• 2. Misoprostol (PGE1 analog)
• 3. Alprostadil (PGE1 synthetic)
• 4. Epoprostenol/Treprostinil/Iloprost (PGI2 synthetic)
• 5. Lubiprostone (PGE1 derivative)
• 6. Latanoprost/Bimaprost/Travoprost (PGF2a analog/ester prodrug)

Mechanism: stimluates EP1 and/or EP3 receptors causing SM contraction

Indications: midtrimester abortion, cervical ripening

Adverse Effects: nausea, diarrhea, hypotension, fever

Mechanism: stimulates EP3 receptors causing decreased gastric acid secretion, increased mucous and HCO3- secretion/stimulates EP1 receptors causing SM contraction

Indications: NSAID-induced ulcer prophylaxis, termination of early pregnancy

Adverse Effects: nausea, diarrhea, headache

Mechanism: stimulates EP2 and/or EP4 receptors causing vasodilation

Indications: ED, maintenance of patent ductus arteriosus in neonates prior to corrective surgery

Adverse Effects: local reactions, hypotension, apnea

Mechanism: stimulates IP receptors on vascular SM causing vasodilation

Indications: pulmonary hypertension

Adverse Effects: nausea, diarrhea, headache

Mechanism: stimulate EP4 receptors on GI epithelial cells causing increase in chloride channels and increased fluid and electrolyte secretion

Indications: chronic constipation, IBS with constipation in women

Adverse Effects: nausea, diarrhea, headache

Mechanism: Stimulate FP receptors causing increased drainage of aqueous humor

Indications: chronic open-angle glaucoma

Adverse Effects: darkening/discoloration of the iris, eyelashes and eyelids (permanent)

Mechanism: inhibit Cox, causing antipyretic, analgesic and anti-inflammatory effects

Indications: mild to severe pain, fever, osteoarthritis, RA, dysmenorrhea, migraine, cardioprotection (low dose aspirin)

Adverse Effects: gastric or intestinal ulcers, increased renal blood flow and filtration in renal problems, stimulates gestation?, hypersensitivity reactions

Other: aspirin irreversibly binds COX

Mechanism: inhibits COX causing antipyretic, analgesic effects

Indications: mild to severe pain, fever, osteoarthritis

Adverse Effects: hepatotoxicity

Other: minimal anti inflammatory effects

Celecoxib (celebrex)

Mechanism: inhibits COX-2 causing antipyretic, analgesic and anti-inflammatory effects

Indications: moderate to severe pain, osteoarthritis, RA

Adverse Effects: GI side effects but less than with tNSAIDS

Other: potential risk of thromboembolic events due to inhibiton of COX2 in endothelial cells (decrease PGI2 synthesis)

Zileuton

Mechansim: inhibits 5-LOX

Indications: asthma

Adverse Effects: Hepatotoxicity

Other: prophylactic ONLY

• 'lukasts'
• Zafirlukast
• Montelukast (singulair)

Mechansim: block CysLT1 receptors

Indications: Asthma, allergic rhinitis

Other: prophylactic use ONLY

Mechanism: induces synthesis of annexins (inhibit PLA2, decrease synthesis of eicosanoids), down regulate COX-2 expression, decrease synthesis and relase of cytokines, decrease extravasation of leukocytes

Indications: asthma, RA, acute inflammatory reactions

Adverse Effects: susceptibility to infections, osteporosis, diabetes, weight gain

Other: long term use leads to adrenal suppression so withdrawal must be gradual, inhalation administration for asthma can decrease side effects