A 24-year-old female presents with severe pain during menses (dysmenorrhea). To treat her symptoms, you advise her to take indomethacin in the hopes that it will reduce her pain by interfering with the production of
Ceain drugs are impoant in the control of acute inflammation because they inhibit poions of the metabolic pathways involving arachidonic acid. For example, coicosteroids induce the synthesis of lipocoins, a family of proteins that are inhibitors of phospholipase A2. They decrease the formation of arachidonic acid and its metabolites, prostaglandins and leukotrienes. Aspirin, indomethacin, and other nonsteroidal anti-inflammatory drugs (NSAIDs), in contrast, inhibit cyclooxygenase and therefore inhibit the synthesis of prostaglandins and thromboxanes. The prostaglandins have several impoant functions. For example, prostaglandin E2 (PGE2), produced within the anterior hypothalamus in response to interleukin 1 secretion from leukocytes, results in fever. Therefore aspirin can be used to treat fever by inhibiting PGE2 production. PGE2 is also a vasodilator that can keep a ductus aeriosus open. At bih, breathing decreases pulmonary resistance and reverses the flow of blood through the ductus aeriosus. The oxygenated blood flowing from the aoa into the ductus inhibits prostaglandin production and closes the ductus aeriosus. Therefore prostaglandin E2 can be given clinically to keep the ductus aeriosus open, while indomethacin can be used to close a patent ductus. Prostaglandin F2 (PGF2) causes uterine contractions, which can result in dysmenorrhea. Indomethacin can be used to treat dysmenorrhea by inhibiting the production of PGF2. Bradykinin is a nonapeptide that increases vascular permeability, contracts smooth muscle, dilates blood vessels, and causes pain. It is pa of the kinin system and is formed from high-molecular-weight kininogen (HMWK). Histamine, a vasoactive amine that is stored in mast cells, basophils, and platelets, acts on H1 receptors to cause dilation of aerioles and increased vascular permeability of venules. Reference: Robbins & Cotran Pathologic Basis of Disease, 9e
Bradykinin
Histamine
Phospholipase A2
Prostaglandin F2
General pathology