A 35-year-old woman with moderately severe arthritis has been treated with nonsteroidal anti-inflammatory drugs for 6 mo. Her arthritis symptoms have been well controlled. She now complains of heartburn and indigestion. A fecal blood test is positive. You give her a prescription for a drug to be taken along with the anti-inflammatory agent, but 2 d later she calls the office complaining that your last prescription has caused severe diarrhea and cramping that resembles her periods. Which of the following is most likely to be associated with increased gastrointestinal motility and uterine cramping?
Aspirin and zileuton rarely cause diarrhea. LTB4 is a chemotactic factor. Famotidine is an H2 blocker that does not cause diarrhea (Chapter 16). Misoprostol, a PGE1 analog, increases gastrointestinal and uterine motility. It is sometimes used as part of an abortifacient. The answer is D.
Which mechanism explains aspirin’s inhibition of thromboxane synthesis?
(A) Blocks cyclooxygenase
(C) Blocks phospholipase A2
(D) Blocks PGE1 receptors
(E) Blocks PGI2 receptors
Hydrocortisone and other corticosteroids inhibit phospholipase. Ibuprofen and indomethacin inhibit cyclooxygenase reversibly, whereas zileuton inhibits lipoxygenase. Because aspirin inhibits cyclooxygenase irreversibly, its action is more effective in platelets, which lack the ability to synthesize new enzyme, than in the endothelium. Aspirin does not block prostaglandin receptors. The answer is A.
A 57-year-old man has severe pulmonary hypertension and right ventricular hypertrophy. Which of the following agents causes vasodilation and may be useful in pulmonary hypertension?
Prostacyclin (PGI2) is a very potent vasodilator. Acetylcholine and bradykinin cause generalized vasodilation and many other undesirable effects; they are not useful in pulmonary or systemic hypertension. PGF2α and thromboxane are vasoconstrictors. The answer is D.
A 19-year-old woman complains of severe dysmenorrhea. A uterine stimulant derived from membrane lipid in the endometrium is
Although serotonin and, in some species, histamine may cause uterine stimulation, these amines are not derived from membrane lipid. Similarly, oxytocin causes uterine contraction, but it is a peptide hormone released from the posterior pituitary. Prostacyclin relaxes the uterus (Table 18–1). The answer is D.
Table 18–1. Effects of some important eicosanoids.
|Effect ||PGE2 ||PGF2α ||PGI2 ||TXA2 ||LTB4 ||LTC4 ||LTD4 |
|Major receptors ||EP1-4 ||FPA,B ||IP ||TPα, β ||BLT1,2 ||CysLT2 ||CysLT1 |
|Coupling protein ||Gs, Gq ||Gq ||Gs ||Gq ||Gq ||Gq ||Gq, Gi |
|Vascular tone ||↓ ||↑ or ↓ ||↓↓ ||↑↑↑ ||? ||↑ or ↓ ||↑ or ↓ |
|Bronchial tone ||↓↓ ||↑↑ ||↓ ||↑↑↑ ||? ||↑↑↑↑ ||↑↑↑↑ |
|Uterine tone ||↑, ↓a ||↑↑↑ ||↓ ||↑↑ ||? ||? ||? |
|Platelet aggregation ||↑ or ↓ || ||↓↓↓ ||↑↑↑ ||? ||? ||? |
|Leukocyte chemotaxis ||? ||? ||? ||? ||↑↑↑↑ ||↑↑ ||↑↑ |
Inflammation is a complex tissue reaction that includes the release of cytokines, leukotrienes, prostaglandins, and peptides. Leukotrienes involved in inflammatory processes are typically produced from arachidonic acid by which of the following enzymes?
See Figure 18–1. Phospholipase A2 converts membrane phospholipid to arachidonic acid. Cyclooxygenases convert arachidonic acid to prostaglandins. COX-1 products appear to be important in normal physiologic processes. Lipoxygenase is the enzyme responsible for the production of leukotrienes from arachidonic acid in inflammatory cells. The answer is D.
Figure 18–1. Synthesis of eicosanoid autacoids. Arachidonic acid is released from membrane lipids by phospholipase A2 and then converted into straight-chain derivatives by lipoxygenase or into cyclized derivatives by cyclooxygenase. Because many of these products are pathogenic, drugs that inhibit synthesis or prevent the actions of the products are clinically useful.
A newborn infant is diagnosed with transposition of the great vessels, wherein the aorta exits from the right ventricle and the pulmonary artery from the left ventricle. Which of the following drugs is likely to be used in preparation for surgical correction of this anomaly?
Infants with great vessel transposition pump venous blood to the aorta and oxygenated blood back to the lungs. Therefore, they require surgical correction as soon as they are strong enough to withstand the procedure. While awaiting surgery, they are dependent on a patent ductus arteriosus to allow some oxygenated blood to flow from the left ventricle via the pulmonary artery and ductus to the aorta. The ductus can be prevented from closing by infusing the vasodilator PGE1. The answer is D.
A patient with a positive fecal blood test is referred to the gastroenterology clinic. He is apparently taking large amounts of an unidentified drug that inhibits platelet activity. Which of the following is taken orally and directly and reversibly inhibits platelet cyclooxygenase?
Aspirin is a direct but irreversible inhibitor of cyclooxygenase. NSAIDs other than aspirin (such as ibuprofen) are reversible inhibitors of COX. Corticosteroids reduce the synthesis of cyclooxygenase. The answer is C.
Which of the following is a component of slow-reacting substance of anaphylaxis (SRS-A)?
The leukotriene C and D series are major eicosanoid components of SRS-A. Leukotriene LTB4 is a chemotactic eicosanoid. The answer is D.
A 17-year-old patient complains that he develops wheezing and severe shortness of breath whenever he takes aspirin for headache. Increased levels of which of the following may be responsible, in part, for some cases of aspirin hypersensitivity?
When cyclooxygenase is blocked, leukotrienes may be produced in increased amounts by diversion of prostaglandin precursors into the lipoxygenase pathway (Figure 18–1). In patients with aspirin hypersensitivity, this might precipitate the bronchoconstriction often observed in this condition. The answer is D.
Which of the following is a leukotriene receptor blocker?
Zileuton blocks the synthesis of leukotrienes. Montelukast and zafirlukast block LTD4 receptors. The answer is E.