Prostaglandins are naturally occurring lipid compounds, often described as local hormones, synthesized from fatty acids in nearly every tissue of the human body. These substances mediate physiological processes, including inflammation, blood flow regulation, blood clot formation, and smooth muscle contraction or relaxation. Prostaglandin analogs (PGAs) are synthetic versions designed to bind to the same specific receptors as natural prostaglandins to mimic or block their effects.
How Prostaglandin Analogs Work
The function of prostaglandin analogs hinges on a precise “lock and key” mechanism involving cell surface receptors. They bind to a family of specific prostaglandin receptors (e.g., EP, FP, TP, and IP receptors) found on various cell membranes. Targeting these receptors initiates an intracellular signaling cascade that prompts a defined cellular response.
The resulting cellular effects depend on the targeted receptor and tissue location. Some PGAs cause smooth muscle relaxation, leading to vasodilation or increased fluid drainage, while others induce powerful smooth muscle contraction, particularly in the uterus. PGAs also influence the remodeling of the extracellular matrix. In the eye, this remodeling reduces resistance to fluid outflow, lowering internal pressure.
Diverse Therapeutic Uses
Ophthalmology
Prostaglandin F2α (PGF2α) analogs are the first-line treatment for managing elevated intraocular pressure in open-angle glaucoma and ocular hypertension. Medications such as Latanoprost, Travoprost, and Bimatoprost are administered as topical eye drops once daily. These analogs primarily reduce pressure by increasing the drainage of aqueous humor, the fluid inside the eye, through the uveoscleral outflow pathway. They achieve this by relaxing the ciliary muscle and modifying the surrounding connective tissue.
Gastrointestinal Protection
The prostaglandin E1 (PGE1) analog, Misoprostol, is used to prevent gastric ulcers, particularly in patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) for long periods. NSAIDs inhibit the body’s natural production of protective prostaglandins, which can lead to stomach lining damage. Misoprostol counteracts this effect by reducing the secretion of gastric acid and enhancing the production of a protective mucus layer lining the stomach and duodenum.
Obstetrics and Gynecology
PGAs are used in reproductive health due to their effects on the uterine muscle and cervix. The PGE2 analog Dinoprostone is used for cervical ripening and labor induction by causing the cervix to soften and dilate. The PGF2α analog Carboprost manages severe postpartum hemorrhage, causing intense contraction of the uterine muscle to constrict blood vessels and control bleeding. Misoprostol is also widely used for induction of labor, cervical preparation, and pregnancy termination.
Vascular and Pulmonary Hypertension
Prostacyclin analogs, which mimic PGI2, are powerful vasodilators used to treat severe pulmonary arterial hypertension (PAH). Medications like Epoprostenol, Treprostinil, and Iloprost work by relaxing the smooth muscle cells within the pulmonary artery walls. This widens the blood vessels, reducing high blood pressure and easing the workload on the right side of the heart.
Navigating Side Effects and Drug Interactions
Prostaglandin analogs often produce side effects that are extensions of their intended biological mechanism. Topical ophthalmic PGAs used for glaucoma commonly cause localized effects, such as conjunctival hyperemia and darkening of the iris and skin around the eye. They can also cause increased eyelash growth. Systemic PGAs, particularly those administered orally or intravenously, often present gastrointestinal side effects. Misoprostol frequently causes diarrhea and abdominal cramping due to smooth muscle stimulation. The vasodilatory effects of PAH treatments like Epoprostenol can lead to systemic issues such as flushing, headache, jaw pain, and hypotension.
Certain PGAs carry specific contraindications. Misoprostol has a boxed warning against use in pregnant women for ulcer prevention due to the high risk of uterine rupture, miscarriage, and fetal harm. Epoprostenol is contraindicated for chronic use in patients with severe heart failure involving left ventricular dysfunction. Drug interactions are minimal for topical forms, but systemic agents require caution. Concurrent use of Misoprostol with magnesium-containing antacids should be avoided because it increases the risk of severe diarrhea. For PAH treatments, co-administration with other blood pressure-lowering agents or antiplatelet drugs requires close monitoring due to the increased risk of profound hypotension or bleeding.