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Prostaglandins
Indications
Prostaglandin analogs are synthetic medications that bind to specific prostaglandin receptors.[1] Their clinical indications vary depending on the target tissue.
FDA-Approved Indications
- Latanoprost, bimatoprost, travoprost, tafluprost, and latanoprostene bunod are prostaglandin F2α (PGF2α) analogs approved by the US Food and Drug Administration (FDA) for reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.[2][3]
- Bimatoprost is also approved by the FDA for the treatment of hypotrichosis of the eyelashes.[4]
- Misoprostol, a PGE1 analog, is approved by the FDA to reduce the risk of nonsteroidal anti-inflammatory drug (NSAID)–induced gastric ulcers in patients at high risk for complications.[5]
- Carboprost, a PGF2α analog, is approved by the FDA for the treatment of postpartum hemorrhage [6] and, under specific conditions, for the induction of abortion.[7]
- Dinoprostone, a PGE2 analog, is approved by the FDA for initiating or maintaining cervical ripening during labor induction.[8]
- Alprostadil, a PGE1 analog, is approved by the FDA for the treatment of erectile dysfunction and for maintaining a patent ductus arteriosus in neonates with congenital heart defects.[9][10]
- Epoprostenol and treprostinil, which are prostacyclin PGI2 analogs, are approved by the FDA for the treatment of pulmonary arterial hypertension.[11]
- Iloprost, a prostacyclin PGI2 analog, is approved by the FDA for the treatment of pulmonary arterial hypertension and severe frostbite in adults to reduce the risk of digit amputations.[12][13]
Off-Label Indications
- Misoprostol is used off-label for cervical ripening, labor induction, pregnancy termination, and treatment of postpartum hemorrhage.[14]
Mechanism of Action
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Mechanism of Action
Prostaglandins are synthesized in the body through a multistep process.[15] Phospholipase A2 enzymes in the plasma membrane release arachidonic acid, which is then converted by cyclooxygenase enzymes (COX-1 and COX-2) into prostaglandin H2 (PGH2), an unstable intermediate.[16][17] Tissue-specific isomerases and synthases subsequently convert PGH2 into prostanoids, including thromboxane A2 (TXA2) and various stable prostaglandins, such as PGE2, PGI2, PGD2, and PGF2.[16] Prostaglandins exert their effects locally at the site of synthesis rather than traveling to distant target tissues.[18]
COX-1 and COX-2 differ in their expression patterns and biological roles.[19] COX-1 is constitutively expressed in many tissues and produces prostaglandins that maintain physiological “housekeeping” functions.[20] Examples include mediating platelet aggregation, regulating renal water homeostasis, and protecting the gastric mucosa.[21] In contrast, COX-2 is an inducible enzyme, with levels increasing in response to inflammatory stimuli, such as cytokines, certain growth factors, and mechanical stress.[21] This upregulation leads to elevated prostaglandin production, resulting in inflammation, swelling, and pain.
Prostaglandin analogs are synthetic agents that bind to specific prostaglandin receptors,[1] which are G protein–coupled receptors (GPCRs).[16] A total of 9 types of prostaglandin GPCRs are expressed on various cell surfaces, and each prostaglandin binds selectively to its receptor subtype.[2] For example, PGD2 binds to DP1 and DP2 receptors; PGE2 binds to EP1, EP2, EP3, and EP4 receptors; PGF2 binds to FP receptors; and TXA2 binds to TP receptors.[22]
The PGF2α analogs latanoprost, bimatoprost, travoprost, and tafluprost lower intraocular pressure by increasing uveoscleral outflow through extracellular matrix remodeling and ciliary muscle relaxation. This mechanism results in a reduction of intraocular pressure.[2][3]
Latanoprostene bunod is a prodrug metabolized into 2 active compounds—latanoprost acid and nitric oxide. These exert independent intraocular pressure-lowering effects.[3] Nitric oxide enhances aqueous humor outflow, contributing to the reduction in intraocular pressure.
The mechanism by which bimatoprost promotes eyelash growth is not fully understood, although it is thought to involve stimulation of melanogenesis.[23]
Latanoprost, travoprost, and tafluprost also promote eyelash growth; however, they are not FDA-approved for this indication due to insufficient clinical trials evaluating this outcome.
The PGE1 analog misoprostol inhibits gastric acid secretion, thereby protecting gastric cells from acid-related damage.[24] Misoprostol also increases the secretion of gastric mucus and bicarbonate, which provide a protective barrier to the gastric mucosa.[5]
Misoprostol's mechanism of action has led to several off-label uses in obstetrics and gynecology.[25] The drug selectively binds to EP2 and EP3 receptors, leading to uterine muscle contractions. As a result, it is used for cervical ripening and labor induction.[25] As misoprostol induces uterine contractions, it is also used for the termination of intrauterine pregnancy in the first trimester and for the treatment of postpartum hemorrhage.[26][14]
Carboprost, a PGF2α analog, has potent uterotonic effects, compresses blood vessels, and stops bleeding.[6]
Dinoprostone, a PGE2 analog, stimulates the release of PGF2α, thereby increasing the sensitivity of uterine muscles to both endogenous and exogenous oxytocin.[8]
Alprostadil relaxes smooth muscles in the corpus cavernosum and dilates the cavernous arteries, producing an erection.[27] Alprostadil also relaxes the smooth muscles of the ductus arteriosus in neonates.[28]
Zeng et al identified FDA-approved and off-label indications for various prostaglandin analogs based on their receptor subtypes and mechanisms of action.[11] In addition, PGI2 inhibits platelet aggregation, reduces inflammation, and limits smooth muscle proliferation.
Administration
Available Dosage Forms and Strengths
Prostaglandin analogs are available in various dosage forms and are administered via different routes, depending on the desired therapeutic effect. The following prostaglandins are formulated as ophthalmic drops.
- Latanoprost 0.005%
- Travoprost 0.04%
- Bimatoprost 0.01% or 0.03%
- Tafluprost 0.0015%
- Latanoprostene bunod 0.024% [22]
As intraocular pressure peaks at night, the long-acting properties of these agents allow once-daily dosing at bedtime to provide effective coverage during this period.[3]
Bimatoprost for eyelash growth is applied topically to the skin. This drug is available as a 0.03% kit containing an ophthalmic solution and sterile, single-use applicators for each eye.[4] Patients should use a sterile applicator to apply one drop per eye at night to the skin at the base of the upper eyelid margin.[23]
Misoprostol is marketed exclusively as an oral tablet, and it is administered orally to prevent and treat NSAID-induced gastric ulcers. [29] Off-label, the tablet can be administered via buccal, vaginal, sublingual, or rectal routes. Vaginal administration of misoprostol induces cervical ripening and uterine contractions.[29] Rectal administration, in combination with oxytocin, is used to treat postpartum hemorrhage.[14]
Carboprost, indicated for the treatment of postpartum hemorrhage or for abortion induction, is administered via intramuscular injection.[6][7]
Dinoprostone is available as a retrievable vaginal insert that releases the drug over 12 hours.[8] A healthcare professional should insert and remove it at the onset of labor or after 12 hours, whichever occurs first.
Alprostadil is administered either intracavernosally or intraurethrally for the treatment of erectile dysfunction.[9] This drug is also administered as an intravenous infusion to maintain patent ductus arteriosus.[30]
Epoprostenol is administered as a continuous intravenous infusion.[11][31]
Treprostinil can be administered orally, intravenously, subcutaneously, or by inhalation.[11]
Iloprost is administered via inhalation.[11]
Adverse Effects
The route of administration can influence the adverse effects experienced by patients with prostaglandin analogs.
Topical ophthalmic prostaglandin analogs, including latanoprost, bimatoprost, travoprost, tafluprost, and latanoprostene bunod, generally have limited systemic adverse effects. Headaches or migraines may occur but are typically reversible upon drug discontinuation.[32]
Topical latanoprost may also cause ocular adverse effects over time, such as iris darkening, eyelash thickening, periocular skin pigmentation, and conjunctival hyperemia.[33]
Bimatoprost is associated with increased eyelash prominence.[23]
Misoprostol may cause nausea, vomiting, diarrhea, abdominal pain, chills, shivering, and fever.[14]
Carboprost may cause nausea, vomiting, diarrhea, and bronchospasm.[6]
Dinoprostone is generally well tolerated but may carry a risk of uterine hyperstimulation due to its mechanism of action.[8]
Alprostadil may cause transient penile pain and urethral bleeding.[34][27]
Epoprostenol is associated with dose-limiting adverse effects, such as nausea, vomiting, headache, hypotension, flushing, chest pain, anxiety, dizziness, bradycardia, dyspnea, abdominal pain, musculoskeletal pain, and tachycardia.[31] Treprostinil is generally better tolerated than epoprostenol. Adverse effects associated with epoprostenol, including high cardiac output symptoms (such as fatigue and palpitations), ascites with long-term use, and thrombocytopenia, often resolve when patients switch to treprostinil.[35]
Iloprost has been associated with thrombocytopenia,[35] and may also cause hypotension, peripheral edema, cough, flushing, nausea, dizziness, and headache.[36] Right heart failure is a severe but reported adverse effect of iloprost.
Contraindications
Contraindications to prostaglandin therapy vary depending on the specific agent and indication, but a major contraindication is hypersensitivity to the drug.
Misoprostol is teratogenic [29] and is contraindicated for the treatment of gastric ulcers during pregnancy, as it can induce cervical ripening and potentially cause abortion.[5]
Carboprost is contraindicated in patients with acute pelvic inflammatory disease or active cardiac, pulmonary, renal, or hepatic disease.
Alprostadil, when used for erectile dysfunction, is contraindicated in patients with sickle cell disease, polycythemia vera, thrombocytosis, or multiple myeloma, as these conditions increase the risk of priapism.[37] Clinicians should also exercise caution when using alprostadil in patients with Peyronie disease, as alprostadil may increase the risk of penile fibrosis.
Monitoring
Monitoring requirements vary depending on the treatment indication.
In glaucoma, intraocular pressure should be monitored to assess the efficacy of latanoprost, travoprost, bimatoprost, tafluprost, and latanoprostene bunod.[38] For safety, monitoring should include conjunctival hyperemia, iris pigmentation changes, eyelash alterations, and ocular discomfort.[38]
When misoprostol is used for labor induction, monitoring should include the onset and progression of uterine contractions and cervical ripening.[39] When used for postpartum hemorrhage, monitoring should focus on excessive vaginal or uterine bleeding.
With carboprost therapy, monitoring should include uterine tone and bleeding control.[40]
When alprostadil is used for the treatment of erectile dysfunction, monitoring should include patient-reported improvement in erectile function.[41] When used to maintain ductal patency, monitoring should assess improvement or preservation of ductal patency. Please see StatPearls' companion resource, "Alprostadil," for more information.
With epoprostenol, treprostinil, and iloprost, monitoring should include mean arterial pressure, pulmonary vascular resistance, blood pressure, and heart rate.[31][42][36]
Toxicity
In general, most prostaglandins are well tolerated and associated with limited toxicity. No specific antidote exists for prostaglandin analogs. In the event of overdose, therapy should be discontinued, and supportive treatment should be initiated.[43]
Overdose with topical ophthalmic prostaglandin drops is extremely rare and usually resolves upon drug discontinuation.[44] A case report of accidental travoprost overdose described severe abdominal cramps and sudden, heavy menstrual bleeding.[45]
A case report described a self-administered overdose involving 12 mg of misoprostol for abortion induction, which resulted in multiorgan failure, acute abdominal signs, hemodynamic instability, and ultimately death.[43]
A case report of carboprost overdose in a newborn described tachypnea, hypertension, bronchospasm, dystonic movements, and seizure activity in the upper extremities.[46]
A case report of treprostinil overdose described excessive hypotension and cardiac arrhythmias, and the patient was successfully stabilized within 24 hours.[47]
Overdose of epoprostenol has been reported to cause severe ascites associated with high cardiac output.[35]
Enhancing Healthcare Team Outcomes
The safe and effective use of prostaglandin analogs requires a collaborative, interprofessional approach to optimize therapeutic outcomes and minimize preventable adverse effects. These agents are utilized across multiple specialties, including ophthalmology, obstetrics, cardiology, pulmonology, gastroenterology, and urology, each with distinct administration routes, monitoring requirements, and safety considerations. Several agents have off-label indications, and misoprostol may be administered via off-label routes of administration. Coordinated care and clear communication among interprofessional healthcare team members are therefore essential to ensure safe, evidence-based, and patient-centered therapy.
Physicians and advanced practice healthcare professionals play a central role in selecting the appropriate prostaglandin analog based on clinical indication, patient comorbidities, and evidence-based guidelines. They are also responsible for initiating therapy and monitoring the patient’s response to treatment.
Pharmacists play a vital role in reviewing dosing regimens, screening for drug interactions and contraindications, and providing education on proper administration and expected effects. Their involvement is particularly critical in high-risk situations, such as labor induction, abortion induction, or treatment of pulmonary hypertension, to promote medication safety.
Nurses are often responsible for administering prostaglandin analogs and monitoring for adverse effects. Their role is essential in assessing therapeutic response, particularly during labor induction or continuous infusion therapies.
By leveraging the unique expertise of each healthcare professional and fostering open communication, the team can optimize the use of prostaglandin analogs, enhance safety and adherence, and ultimately improve clinical outcomes and patient satisfaction.
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