Ch 18 - Prostaglandins and other Eicosanoids

what are the two cylcooxygenase isoforms?

• cycloxygenase 1 (COX1)

• cyclooxyrgenase 2 (COX2)

what is Cyclooxygenase 1?

• COX1

• found in normal cells, platelets (constitutive)

• found in many tissues

what is Cyclooxgygenase 2?

• COX2

• found in inflammatory cells

• also found in kidney and endothelial of vasculature

  • responsible for synthesis of prostacyclin and of prostaglandins important in normal renal function

what is PGE1?

protects gastric mucosa, increased secretion of bicarbonate and mucus, decreases acid secretion (inhibits histamine activity)

• used for allergies

• MOA: relaxes smooth muscle in ductus arteriosus

• transportation of great verses, to maintain patent ductus until surgery

• toxicity: hypotension

what is PGE2?

• maintains opening of ductus arteriosus during fetal development

• involved in the physiological ripening of the cervix

what is PGE2 and PGF2 alpha?

released from the endometrium during menstruation and may be important in labor

what is thromboxane A2?

platelet aggregation

what is PGF2alpha?

reduces intraocular pressure

what is dinoprostone?

• PGE2

• ripens the cervix (intravaginal administration)

• MOA: low concentrations contract; higher concentrations relax uterine and cervical smooth muscle

• abortifacient

• toxicity: cramping, fetal trauma

what are dinoprostone and carboprost tromethamine (PGF2a analog) used for?

• have been used in abortions

• PGE1 analog (misoprostol) with RU486, a progesterone antagonist

• carboprost tromethamine employed to control postpartum bleeding

what is alprostadil (PGE1)?

• PGE1

• infusion keeps ductus arteriosus patent

• injectable and suppository form for erectile dysfunction

• injection into the carvernosa to treat impotence

what is epoprostenol?

• PGI2, prostacyclin

• used in pulmonary hypertension and prevention of platelet aggregation

• MOA: activates IP receptors, causes vasodilation, reduced platelet aggregatiion

• used as a vasodilator in pulmonary hypertension, anti platelet agent in extravorporeal dialysis

• toxicity: hypotension, flushing, headache

what is misoprostol?

• PGE1 analog

• used to prevention of peptic ulcers (combined in a single pill with a NSAID, Arthrotec)

• MOA: activates EP receptors, causes increased HCO3^- and mucus secretion in stomach and uterine contract

• protective agent in peptic ulcer disease, abortifacient

• toxicity: diarrhea, uterine cramping

what is latanoprost?

• PGF2a used for the treatment of glaucoma (increased aqueous humor)

• bimatoprost increases eyelash length

• toxicity for these drugs is change iris pigmentation to brown and also eyelashes and skin

• MOA: increase outflow of aqueous humor, reduce intraocular pressure

• toxicity: color change in Irish