MCQ4
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
a. Bradykinin
b. Histamine
c. Leukotrienes
d. Phospholipase A2
e. Prostaglandin F2
Answer The answer is e. (Cotran, 6/e, pp 70–72.) Certain drugs are important
in the control of acute inflammation because they inhibit portions of the
metabolic pathways involving arachidonic acid. For example, corticosteroids
induce the synthesis of lipocortins, 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 important
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
arteriosus open. At birth, breathing decreases pulmonary resistance and
reverses the flow of blood through the ductus arteriosus. The oxygenated
blood flowing from the aorta into the ductus inhibits prostaglandin production
and closes the ductus arteriosus. Therefore prostaglandin E2 can be
given clinically to keep the ductus arteriosus 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 part 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 arterioles and increased
vascular permeability of venules.
