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Pg analogue
- 1. PROSTAGLANDIN AND ITS ANALOGUES Dr.Prerna Singh Junior Resident Department of Pharmacology, JNMC
- 2. Prostaglandins ■ Unsaturated fattyacid derivative ■ 20 carbon atoms (aka eicosanoids), cyclic ring structure ■ Produced by all organs ■ Act locally ■ Rapidly metabolized
- 3. History ■ Discovred in1930 from human semen ■ It is secreted form prostate gland ■ Hence the name prostglandin
- 4. Synthesis ■ Precursor: Arachidonicacid ■ Present as a component of phospholipid in cell membrane ■ Released by action of phospholipase A2
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- 6. Inhibitors of synthesis ■Glucocorticoids inhibit PLA2 by inducing synthesis of annexin, which modulate PLA2 activity ■ Glucocorticoids also downregulate expression on COX 2 ■ Aspirin and NSAID inhibit COX but not LOX (LTs: GI side effects) ■ Selective COX2 inhibitor: coxibs – superior due to GI safety ■ But, cardiovascular hazard COX2: PGs in inflammation, cardioprotective PGs - PGI2 COX1 : cytoprotective PGs in GIT
- 7. Degradation ■ Rapidly inactivated ■Lung kidney and liver ■ Step 1: PG specific enzymes ■ Step 2: oxidized by enzymes identical to those of fatty acid oxidation
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- 9. Receptors G protein coupledreceptors ■ PGD2: DP1 DP2 ■ PGE2: EP1 EP2 EP3 EP4 ■ PGF2⍺: FP ■ PGI2: IP
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- 11. Physiological action onCVS ■ PGE2: vasodilator, fall in BP, weak inotropic effect, Keep ductus arteriosus patent ■ PGF2⍺: vasoconstrictor, little effect on BP, weak inotropic ■ PGI2: vasodilator, decrease BP Platelets ■ PGI2: inhibit platelet aggregation ■ PGE2: Variable effect
- 12. Bronchial and trachealmuscle ■ PGE2 , PGI2 relax bronchial smooth muscle, inhibit histamine release ■ PGF2⍺, PGD2: Contract bronchial smooth muscle Uterus ■ PGF2⍺> PGE2 : Contract uterus, softening of uterus ■ Dysmenorrhoea is due to increased PGs
- 13. GI smooth muscle ■PGE2> PGI2 : inhibit acid secretion Increase mucus production, mucosal blood flow Aspirin is ulcerogenic: due to loss of cytoprotective influence ■ PGE2: contact longitudinal muscle, increase water and electrolyte secretion Side effect: diarrhea
- 14. Kidney ■ PGE2, PGI2cause natriuresis, renal vasodilation, renin release Eye ■ PGF2⍺, PGE2 lower IOP by increasing uveoscleral outflow CNS ■ PGE2: pyrogenic
- 15. Endocrine ■ PGE2 Facilitaterelease of GH, TSH, ACTH, FSH, LH prolactin ■ Analogue have no effect on release of these hormones Pain ■ PGE2 PGI2 sensitize pain receptors at afferent to mediators
- 16. Bone ■ PGE2: Rolein osteoporosis, stimulate bone resorption, mobilization of bone calcium Cancer ■ PGE2: promotes polyp formation ■ Pro oncogenic prostanoid
- 17. Prostaglandin analogues ■ NOTUSED WIDELY: cost, availability, half life, parenteral administration ■ Labor and therapeutic abortion ■ Maintain patent ductus arteriosus ■ Gastric cyto-protection ■ Impotence ■ Pulmonary hypertension ■ Glaucoma
- 18. Alprostadil ■ PGE1 Analogue ■To maintain patent ductus arteriosus –TGA ■ Ductus arteriosus is sensitive to vasodilation by PGE1 ■ PGE1 inhibit platelet aggregation ■ Also used for erectile dysfunction – Intra cavernosal injection
- 20. Lubiprostone ■ PGE1 analogue ■Use: chronic idiopathic constipation, opioid induced constipation, IBS with constipation ■ MOA: Stimulate chloride channel in luminal cell of intestinal epithelium, increase fluid secretion ■ Side effects: nausea, diarrhea
- 21. Misoprostol ■ PGE1 analogue ■Protect mucosal lining of stomach in NSAID treatment Oral: 200µg QID MOA: PG receptor on parietal cell to decrease acid secretion Stimulate mucus and bicarbonate production Enprostil: PGE2 analogue also used for NSAID induced ulcer ■ For labor induction: increase uterine contraction ■ For abortion: with mifepristone, orally ■ Side effect: diarrhea, abdominal pain, vaginally- sepsis ■ Contraindicated in pregnancy
- 22. Dinoprostone ■ PGE2 analogue ■Cervical ripening ■ Preferred over oxytocin in eclampsia pre eclampsia patients: diuretic and natriuretic effect ■ Second trimester abortion: vaginally ■ Half life: 2.5- 5 mins ■ Side effect: prolonged vaginal bleed, cramps
- 23. PGF2⍺ analogue ■ Bimatoprost ■Latanoprost ■ Tafluprost ■ Travoprost ■ Increase uveoscleral outflow : glaucoma ■ Side effects: Increase eyelash prominence Blur vision Iris color change Occular irritation, foreign body sensation ■ Carboprost: intra amniotic injection for second trimester abortion Not used : cardiovascular collapse, anaphylactic shock Control PPH
- 24. PGI2 analogue ■ Epoprostenol ■Iloprost ■ Treprostanil: IV, SC, Inhalatinal ■ Used in Pulmonary artery hypertension ■ Short half life ■ Side effects: Headache, Dizziness Flushing, Fainting Bronchospasm, Cough ■ Beraprost: oral, for PVD