SEMESTRAL

• Fieldworkersexposedtoaplanttoxindeveloppainfulfluid- filled blisters. Analysis of the blister fluid reveals high concen- trations of a peptide. Which of the following is a peptide that causes increased capillary permeability and edema?

  (A) Angiotensin II

  (B) Bradykinin

  (C) Captopril

  (D) Histamine

  (E) Sacubitril

  Histamine and bradykinin both cause a marked increase in capillary permeability that is often associated with edema, but histamine is not a peptide. The answer is B.
• In a laboratory study of several peptides, one is found that decreases peripheral resistance but constricts veins. Which of the following causes arteriolar vasodilation and venoconstriction?

  (A) Atrial natriuretic peptide (ANP)

  (B) Bradykinin

  (C) Endothelin-1

  (D) Substance P

  (E) Vasoactive intestinal peptide

  Substance P is a potent arterial vasodilator and venoconstrictor. The answer is D.
• Which of the following endogenous molecules is elevated in heart failure and when given as a drug is a vasodilator with significant renal toxicity?

  (A) Angiotensin I

  (B) Angiotensin II

  (C) BNP(nesiritide)

  (D) Histamine

  (E) Vasoactive intestinal peptide

  BNP is an atrial and brain peptide found in increased amounts in patients with heart failure. The commercial for- mulation (nesiritide) is approved for use in severe acute heart failure but has significant renal toxicity. The answer is C.
• Which drug binds endothelin receptors and is approved for use in pulmonary hypertension?

  • Macitentan
• What is Aliskiren used for?

  Primary hypertension
• What is Capsaicin known for?

  It is the molecule responsible for the release of substance P.
• What is Conivaptan used to treat?

  Hyponatremia
• What type of antagonist is Sacubitril?

  Neprilysin antagonist
• What is the primary use of Macitentan?

  Treatment of pulmonary hypertension
• A 60-year-old financial consultant presents with severe pain in a neuronal dermatome region of her chest. This area was previously affected by a herpes zoster rash. Which of the following might be of benefit in controlling this post- herpetic pain?

  (A) Aliskiren (B) Aprepitant (C) Bosentan (D) Capsaicin (E) Captopril (F) Losartan (G) Macitentan

  Substance P is an important pain-mediating neurotransmitter peptide and appears to be involved in post-herpetic pain as well as arthritic pain. Capsaicin can be used topically to deplete substance P stores from sensory nerves. The answer is D.
• What was found to increase in the blood of hypertensive patients treated with large doses of diuretics in a phase 2 clinical trial?

  An endogenous octapeptide vasoconstrictor
• Why does angiotensin II increase when blood volume decreases?

  Because the compensatory response causes an increase in renin secretion
• What is the structure of angiotensin II?

  It is an octapeptide
• How many amino acids are in angiotensin I?

  It is a decapeptide
• Which endogenous peptide is most likely to increase in the blood of patients treated with large doses of diuretics?

  Angiotensin II
• What are the characteristics of angiotensin II and angiotensin I?

  • Angiotensin II:
  • Octapeptide
  • Increases with decreased blood volume
  • Angiotensin I:
  • Decapeptide
  • Precursor to angiotensin II
• Which of the following is a vasodilator that increases in the blood or tissues of patients treated with captopril?

  (A) Angiotensin II

  (B) Bradykinin

  (C) Brainnatriureticpeptide

  (D) Calcitonin gene-related peptide

  (E) Endothelin

  (F) Neuropeptide Y

  (G) Vasopressin (AVP)


  Bradykinin increases because the enzyme inhibited by cap- topril, angiotensin converting enzyme, degrades kinins in addition to synthesizing angiotensin II (see Figure 11–3). The answer is B.
• Which of the following is an antagonist at NK1 receptors and is used to prevent or reduce chemotherapy-induced nausea and vomiting?

  (A) Angiotensin I

  (B) Aprepitant

  (C) Bosentan

  (D) Bradykinin

  (E) Brain natriuretic peptide

  (F) Enalapril

  (G) Ondansetron

  Aprepitant and ondansetron are both used to reduce or pre- vent chemotherapy-induced nausea and vomiting. Ondanse- tron is an antagonist at 5-HT3 receptors. The answer is B.
• What type of medication has the woman been treated with for her arthritis?

  Nonsteroidal anti-inflammatory drugs (NSAIDs)
• How long has the woman been treated with NSAIDs?


  6 months
• Which drug is most likely associated with increased gastrointestinal motility and uterine cramping?

  • Misoprostol
  • It is a PGE1 analog
  • Increases gastrointestinal and uterine motility
  • Sometimes used as part of an abortifacient
• Which of the following drugs is known to rarely cause diarrhea?

  Aspirin and zileuton
• What type of drug is famotidine?


  H2 blocker
• Does famotidine cause diarrhea?


  No, it does not cause diarrhea
• What is leukotriene LTB4 known for?


  It is a chemotactic factor
• What mechanism explains aspirin’s inhibition of thromboxane synthesis?


  Blocks cyclooxygenase
• How do hydrocortisone and other corticosteroids affect phospholipase?


  They inhibit phospholipase
• What is the effect of ibuprofen and indomethacin on cyclooxygenase?


  They inhibit cyclooxygenase reversibly
• What does zileuton inhibit?


  It inhibits lipoxygenase
• Why is aspirin's action more effective in platelets than in the endothelium?


  Because platelets lack the ability to synthesize new enzyme
• Does aspirin block prostaglandin receptors?


  No, aspirin does not block prostaglandin receptors
• How does the irreversible inhibition of cyclooxygenase by aspirin differ from the reversible inhibition by ibuprofen and indomethacin?


  Aspirin's irreversible inhibition is more effective in platelets
• What are the differences in the inhibition mechanisms of aspirin, ibuprofen, indomethacin, and zileuton?


  • Aspirin: Irreversibly inhibits cyclooxygenase
  • Ibuprofen: Reversibly inhibits cyclooxygenase
  • Indomethacin: Reversibly inhibits cyclooxygenase
  • Zileuton: Inhibits lipoxygenase
• 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?

  (A) Acetylcholine

  (B) Bradykinin

  (C) ProstaglandinPGF2α

  (D) Prostacyclin

  (E) Thromboxane


  Prostacyclin(PGI2)isaverypotentvasodilator.Acetylcholine and bradykinin cause generalized vasodilation and many other undesirable effects; they are not useful in pulmonary or systemic hypertension. PGF2α and thromboxane are vasocon- strictors. The answer is D.
• A 19-year-old woman complains of severe dysmenorrhea. A uterine stimulant derived from membrane lipid in the endo- metrium is

  (A) Angiotensin II

  (B) Oxytocin

  (C) Prostacyclin (PGI2)

  (D) Prostaglandin PGF2α

  (E) Serotonin


  Although serotonin and, in some species, histamine may cause uterine stimulation, these amines are not derived from membrane lipid. Similarly, oxytocin causes uterine contrac- tion, but it is a peptide hormone released from the poste- rior pituitary. Prostacyclin relaxes the uterus (Table 18–1). The answer is D.
• What substances are released during inflammation?

  Cytokines, leukotrienes, prostaglandins, and peptides are released.
• Which enzyme is responsible for producing leukotrienes from arachidonic acid?


  Lipoxygenase is responsible for producing leukotrienes.
• What does Phospholipase A2 do in the inflammatory process?


  It converts membrane phospholipid to arachidonic acid.
• What is the role of cyclooxygenases in inflammation?


  Cyclooxygenases convert arachidonic acid to prostaglandins.
• 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?

  (A) Cyclooxygenase-1

  (B) Cyclooxygenase-2

  (C) Glutathione-S-transferase

  (D) Lipoxygenase

  (E) Phospholipase A2

  (D) Lipoxygenase