Pro-Slugger Sporting Goods Prostaglandins, Prostacyclin, Bosentan, PDE-5 Inhibitors

1.3 – “Pro “Pro--Slugger Sp Sporting orting Good Goods”: s”: Prostag Prostaglandins, landins, prostac prostacyclin, yclin, bosentan, PDE -5 inhibitors • Prostaglandin R is an important mediator of vasoconstriction & inflammation. Recall arachidonic acid pathways, produced by Cox-1 & COX-2 (coaches in the back). Numerous prostaglandins are synthesized endogenously, and may be administered exogenously in certain clinical scenarios with effects on smooth muscle of GI,, vascular, genitourinary tracts. • PGE1 & PGE2 (Extreme Sports) o Alprostadil = synthetic PGE1 (dill pickle themed board). ▪ Acts as a vasodilator ▪ Indications • ED therapy (erect pro-slugger bat). Second line treatment, either monotherapy or in combination therapy. Works because PGE1 is a vasodilator with potent smooth muscle relation effects. • Maintains patency of fetal ductus arteriosus (knocking air duct open with bat). PGE2 acts locally in the womb on fetal vasodilatory receptors. After birth, PGE2 levels fall, causing closure of the PDA. In conditions where maintaining patency is important (as in certain congenital heart diseases), may administer PGE1 via continuous infusion. o This closure is why NSAID/prostaglandin use is not recommended in third trimester o when PDA doesn’t close after birth, which may induce respiratory failure in preemies, can give indomethacin – an NSAID – to promote closure. o Misoprostol = synthetic PGE1 analog (kid in front missing the ball) ▪ Indications • Cytoprotective in the GI tract at low doses, ↑secretion of gastric mucosa. Protects against NSAID-induced peptic ulcers (kid knocking over fire extinguisher) • Potent oxytocic actions. Used to increase uterine smooth muscle tone to facility labor or terminate pregnancy (uterus shaped bags expelling contents). Hence is a pregnancy category X drug. ▪ Adverse effects • Abdominal discomfort, diarrhea (flooded bathroom) o Dinoprostone = PGE2 analog (kid in a dino helmet) ▪ Stimulates contraction of uterus throughout pregnancy. May be used to induce abortion. ( open uterus bag) ▪ Directly affects cervix, promoting softening. May be applied locally for cervical ripening in preparation for labor induction • PGF2a (footwear section) o Carboprost = PGF2a analog (cardboard box) ▪ Used in obstetrics to increase uterine tone. May be used to induce abortion or to control refractory post-partum hemorrhage (uterus bags) o Latanoprost & travoprost (La Tan Sandals, Traveler boots) ▪ Stable, long-acting prostaglandin agents used in the management of glaucoma (leaky eyeball containers). Increase aqueous humor outflow → ↓IOP (cleaner flowing off of glasses) ▪ Causes increased iris pigmentation. Most commonly seen in green-brown eyes (brown sunglasses) Pulmonary hyp hypertension ertension manage management ment • Narrow and fibrosed pulmonary arteries result from long-term untreated HTN. Idiopathic pulmonary HTN specific classically manifests as dyspnea & exercise intolerance in women aged 20-40. All treatments have direct vasodilatory effects on pulmonary vasculature (high tension lung-shaped rackets). For most patients with pulmonary HTN, treat underlying conditions. • Prostacyclin (PGI2) analogs o Prostacyclin is a potent vasodilator and platelet inhibitor produced by COX-2 at the vascular endothelium (pro-cycler pitching machine) o Epoprostenol & iloprost (iLOW – ePRO setting). Epoprostenol is first line as has been shown to improve symptoms, prolong survival, & delay need for lung transplant. However, must be given as continuous IV infusion. o Major adverse effects include flushing, headache, hypotension (fainted girl) • Endothelin R antagonists o Bosentan (boss man stan) o Endothelin is a potent vasoconstrictor & promotes endothelial proliferation (end o’ the line). Bosentan inhibits endothelin → vasodilation (untucked shirt) o Adverse effects ▪ Associated with fatal hepatotoxicity (liver shaped spot). Calls for monthly LFTs. ▪ Can cause hypotension. (fainted girl) • PDE-5 inhibitors o Sildenafil, tadalafil (ball FILL) o Potent vasodilation o Inhibit PDE breakdown of cGMP, increasing intracellular levels (Don’t Phoster Disinterest = inhibiting phosphodiesterase; grumpy employee). ↑cGMP → dephosphorylation of myosin light chains → vasodilation. o Also used to treat ED (erect bat in photo)