Katzung & Trevor’s Pharmacology Examination & Board Review – 10E – Part IV (Drugs With Important Actions On Smooth Muscle)

Your 37-year-old patient has been diagnosed with a rare metastatic carcinoid tumor. This neoplasm is releasing serotonin, bradykinin, and several unknown peptides. The effects of serotonin in this patient are most likely to include which one of the following?

(A) Constipation
(B) Episodes of bronchospasm
(C) Hypersecretion of gastric acid
(D) Hypotension
(E) Urinary retention

(B) Episodes of bronchospasm

Serotonin causes bronchospasm, but the other effects listed are not observed. Carcinoid is associated with diarrhea and hypertension.

A 23-year-old woman suffers from recurrent episodes of angioneurotic edema with release of histamine and other mediators. Which of the following drugs is the most effective physiologic antagonist of histamine in smooth muscle?

(A) Cetirizine
(B) Epinephrine
(C) Granisetron
(D) Ranitidine
(E) Sumatriptan

(B) Epinephrine

The smooth muscle effects of histamine are mediated mainly by H1 receptors. Cetirizine is a pharmacologic antagonist of histamine. Granisetron is a 5-HT3 antagonist. Sumatriptan is a 5-HT1D agonist. Ranitidine is a histamine antagonist but blocks the H2 receptor in the stomach and the heart, not H1 receptors in smooth muscle. Epinephrine has a physiologic antagonist action that reverses histamine’s effects on smooth muscle.

A 20-year-old woman is taking diphenhydramine for severe hay fever. Which of the following adverse effects is she most likely to report?

(A) Muscarinic increase in bladder tone
(B) Nausea
(C) Nervousness, anxiety
(D) Sedation
(E) Uterine cramps

(D) Sedation

H1 blockers do not activate muscarinic receptors, mediate vasoconstriction, or cause uterine cramping. They do not cause nervousness or anxiety. Diphenhydramine is a potent sedative.

A laboratory study of new H2 blockers is planned. Which of the following will result from blockade of H2 receptors?

(A) Increased cAMP (cyclic adenosine monophosphate) in cardiac muscle
(B) Decreased channel opening in enteric nerves
(C) Decreased cAMP in gastric mucosa
(D) Increased IP3 (inositol trisphosphate) in platelets
(E) Increased IP3 in smooth muscle

(C) Decreased cAMP in gastric mucosa

H2 receptors are Gs-protein-coupled receptors, like β adre- noceptors. Blockade of this system will cause a decrease in cAMP.

You are asked to consult on a series of cases of drug toxicities. Which of the following is a recognized adverse effect of cimetidine?

(A) Blurred vision
(B) Diarrhea
(C) Orthostatic hypotension
(D) P450 hepatic enzyme inhibition
(E) Sleepiness

(D) P450 hepatic enzyme inhibition

The older H1 blockers, not H2 blockers, cause blurred vision, orthostatic hypotension, and sleepiness. Neither group typi- cally causes diarrhea. Cimetidine (unlike other H2 blockers) is a potent CYP3A4 inhibitor.

A 40-year-old patient is about to undergo cancer chemother- apy with a highly emetogenic (nausea- and vomiting-causing) drug combination. The antiemetic drug most likely to be included in her regimen is

(A) Bromocriptine
(B) Cetirizine
(C) Cimetidine
(D) Ketanserin
(E) Ondansetron

(E) Ondansetron

Ondansetron and other 5-HT3 antagonists have significant antiemetic effects. Diphenhydramine and prednisone are also used for this purpose.

The hospital Pharmacy Committee is preparing a formulary for staff use. Which of the following is a correct application of the drug mentioned?

(A) Alosetron: for obstetric bleeding
(B) Cetirizine: for hay fever
(C) Ergonovine: for Alzheimer’s disease
(D) Ondansetron: for acute migraine headache
(E) Ranitidine: for Parkinson’s disease

(B) Cetirizine: for hay fever

Alosetron is indicated in irritable bowel syndrome. Ergonovine is used in uterine bleeding. Ondansetron is useful for chemo- therapy-induced emesis. Cetirizine is used in the treatment of hay fever.

A 26-year-old woman presents with amenorrhea and galactorrhea. Her prolactin level is grossly elevated. Which of the following is most useful in the treatment of hyperprolactinemia?

(A) Bromocriptine
(B) Cimetidine
(C) Ergotamine
(D) Ketanserin
(E) LSD
(F) Ondansetron
(G) Sumatriptan

(A) Bromocriptine

Bromocriptine is an effective dopamine agonist in the CNS with the advantage of oral activity. The drug inhibits prolactin secretion by activating pituitary dopamine receptors.

A 28-year-old office worker suffers from intense migraine headaches. Which of the following is a serotonin agonist useful for aborting an acute migraine headache?

(A) Bromocriptine
(B) Cimetidine
(C) Ephedrine
(D) Ketanserin
(E) Loratadine
(F) Ondansetron
(G) Sumatriptan

(G) Sumatriptan

Sumatriptan, an agonist at 5-HT1D receptors, is indicated for prevention or treatment of migraine and cluster headaches. Ergotamine (not on the list) is also effective for acute migraine but is produced by the fungus Claviceps purpurea.

A 33-year-old woman attempted to induce an abortion using ergotamine. Her legs became cold with absent arterial pulses. Which of the following is the most useful antidote for reversing severe ergot-induced vasospasm?

(A) Bromocriptine
(B) Cimetidine
(C) Ergotamine
(D) Ketanserin
(E) LSD
(F) Nitroprusside
(G) Sumatriptan
(H) Ondansetron

(F) Nitroprusside

A very powerful vasodilator is necessary to reverse ergot-induced vasospasm; nitroprusside is such a drug (see Chapter 11).

Field workers exposed to a plant toxin develop painful fluid- filled blisters. Analysis of the blister fluid reveals high concentrations 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) Losartan

(B) Bradykinin

Histamine and bradykinin both cause a marked increase in capillary permeability that is often associated with edema, but histamine is not a peptide.

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) Angiotensin II
(B) Bradykinin
(C) Endothelin-1
(D) Substance P
(E) Vasoactive intestinal peptide

(D) Substance P

Substance P is a potent arterial vasodilator and venoconstrictor.

Which of the following is elevated in heart failure and is a vasodilator with significant renal toxicity?

(A) Angiotensin I
(B) Angiotensin II
(C) Histamine
(D) Nesiritide
(E) Vasoactive intestinal peptide

(D) Nesiritide

BNP is an atrial and brain peptide found in increased amounts in patients with heart failure. The commercial formulation (nesiritide) is approved for use in severe acute heart failure but has significant renal toxicity.

A 45-year-old painter presents with respiratory symptoms and careful workup reveals idiopathic pulmonary hypertension. Which of the following binds endothelin receptors and is approved for use in pulmonary hypertension?

(A) Aliskiren I
(B) Bosentan
(C) Capsaicin
(D) Losartan
(E) Nesiritide

(B) Bosentan

Aliskiren, captopril, and losartan are used in primary hypertension. Bosentan, an endothelin antagonist, is used in pulmonary hypertension.

A 60-year-old woman 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) Nesiritide

(D) Capsaicin

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.

In a phase 2 clinical trial in hypertensive patients, an endogenous octapeptide vasoconstrictor was found to increase in the blood of patients treated with large doses of diuretics. Which of the following is the most likely endogenous peptide?

(A) Angiotensin I
(B) Angiotensin II
(C) Atrial natriuretic peptide
(D) Bradykinin
(E) Calcitonin gene-related peptide
(F) Endothelin
(G) Neuropeptide Y
(H) Renin
(I) Substance P
(J) Vasoactive intestinal peptide

(B) Angiotensin II

Angiotensin II, an octapeptide, increases when blood volume decreases (a diuretic effect) because the compensatory response causes an increase in renin secretion. Its precursor, angiotensin I, would also increase, but it is a decapeptide.

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) Brain natriuretic peptide
(D) Calcitonin gene-related peptide
(E) Endothelin
(F) NeuropeptideY
(G) Renin

(B) Bradykinin

Bradykinin increases because the enzyme inhibited by captopril, converting enzyme, degrades kinins in addition to synthesizing angiotensin II (see Figure 11-3).

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

(B) Aprepitant

Aprepitant and ondansetron are both used to reduce or prevent chemotherapy-induced nausea and vomiting. Ondansetron is an antagonist at 5-HT3 receptors.

You have been treating a 50-year-old woman with moderately severe arthritis with nonsteroidal anti-inflammatory drugs for 6 months. She now complains of heartburn and indigestion. You give her a prescription for a drug to be taken along with the anti-inflammatory agent, but 2 days later she calls the office complaining that your last prescription has caused severe diarrhea. Which of the following is most likely to be associated with increased gastrointestinal motility and diarrhea?
(A) Aspirin
(B) Corticosteroids
(C) Leukotriene LTB4
(D) Misoprostol
(E) Zileuton

(D) Misoprostol

Aspirin, corticosteroids, and zileuton do not cause diarrhea. LTB4 is a chemotactic factor.

Which of the following drugs inhibits thromboxane synthesis much more effectively than prostacyclin synthesis?

(A) Aspirin
(B) Hydrocortisone
(C) Ibuprofen
(D) Indomethacin
(E) Zileuton

(A) Aspirin

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.

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) Angiotensin II
(B) Ergotamine
(C) Prostaglandin PGF2α
(D) Prostacyclin
(E) Thromboxane

(D) Prostacyclin

Prostacyclin (PGI2) is a very potent vasodilator. All the other choices in the list are vasoconstrictors.

A 19-year-old woman complains of severe dysmenorrhea. A uterine stimulant derived from membrane lipid in the endometrium is:

(A) Angiotensin II
(B) Oxytocin
(C) Prostacyclin (PGI2)
(D) Prostaglandin PGE2
(E) Serotonin

(D) Prostaglandin PGE2

Although serotonin and, in some species, histamine may cause uterine stimulation, these substances are not derived from membrane lipid. Similarly, oxytocin causes uterine contraction, but it is a peptide hormone secreted by the posterior pituitary. Prostacyclin relaxes the uterus (Table 18-1).

Inflammation is a complex tissue reaction that includes the release of cytokines, leukotrienes, prostaglandins, and peptides. Prostaglandins 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

(B) Cyclooxygenase-2

See Figure 18-1. Phospholipase A2 converts membrane phospholipid to arachidonic acid. Cyclooxygenases convert arachidonic acid to prostaglandins. COX-2 is the enzyme believed to be responsible for this reaction in inflammatory cells.

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?

(A) Aspirin
(B) Leukotriene LTC4
(C) Prednisone
(D) Prostaglandin PGE2
(E) Prostaglandin PGF2α

(D) Prostaglandin PGE2

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. In the mean- time, they are dependent on a patent ductus arteriosus to allow some oxygenated blood to flow from the left ventricle via the pulmonary artery to the aorta. The ductus can be prevented from closing by infusing the vasodilator PGE2.

A patient with a bleeding tendency presents in the hematology clinic. He is apparently taking large amounts of an unidentified drug that inhibits platelet activity. Which of the following directly and reversibly inhibits platelet cyclooxygenase?

(A) Alprostadil
(B) Aspirin
(C) Ibuprofen
(D) Leukotriene LTC4
(E) Misoprostol
(F) Prednisone
(G) Prostacyclin
(H) Zafirlukast
(I) Zileuton

(C) Ibuprofen

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.

Which of the following is a component of slow-reacting substance of anaphylaxis (SRS-A)?

(A) Alprostadil
(B) Aspirin
(C) Leukotriene LTB4
(D) Leukotriene LTC4
(E) Misoprostol
(F) Prednisone
(G) Prostacyclin
(H) Zafirlukast
(I) Zileuton

(D) Leukotriene LTC4

The leukotriene C and D series are major components of SRS-A. Leukotriene LTB4 is a chemotactic eicosanoid.

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?

(A) Alprostadil
(B) Hydrocortisone
(C) Ibuprofen
(D) Leukotriene LTC4
(E) Misoprostol
(F) PGE2
(G) Prostacyclin
(H) Thromboxane
(I) Zileuton

(D) Leukotriene LTC4

When cyclooxygenase is blocked, leukotrienes may be pro- duced 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.

Which of the following is a leukotriene receptor blocker?

(A) Alprostadil
(B) Aspirin
(C) Ibuprofen
(D) Leukotriene LTC4 (E) Misoprostol
(F) Prednisone
(G) Prostacyclin
(H) Zafirlukast
(I) Zileuton

(H) Zafirlukast

Zileuton blocks the synthesis of leukotrienes. Zafirlukast and montelukast block LTD4 receptors.

Which one of the following is not a nitric oxide donor but causes it to be released from endogenous precursors, resulting in vasodilation?

(A) Acetylcholine
(B) Arginine
(C) Isosorbide mononitrate
(D) Nitroglycerin
(E) Nitroprusside

(A) Acetylcholine

Nitroprusside and organic nitrites (eg, amyl nitrite) and nitrates (eg, nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate) contain NO groups that can be released as NO. Arginine is the normal source of endogenous NO. Acetylcholine stimulates the production of NO from arginine.

A molecule that releases nitric oxide in the blood is:

(A) Citrulline
(B) Histamine
(C) Isoproterenol
(D) Nitroglycerin
(E) Nitroprusside

(E) Nitroprusside

Nitroprusside is the only molecule in this list that releases NO in the bloodstream.

The inducible isoform of nitricoxide synthase (iNOS,isoform2) is found primarily in which of the following?

(A) Cartilage
(B) Eosinophils
(C) Macrophages
(D) Platelets
(E) Vascular endothelial cells

(C) Macrophages

The inducible form of NOS is associated with inflammation, and the enzyme is found in highest concentration in macro- phages, cells that are particularly involved in inflammation.

The primary endogenous substrate for the enzyme nitric oxide synthase (NOS) is:

(A) Acetylcholine
(B) Angiotensinogen
(C) Arginine
(D) Citrulline
(E) Heme

(C) Arginine

Arginine is the substrate and citrulline and NO are the products of NOS.

5. Which of the following is a recognized effect of nitric oxide (NO)?

(A) Arrhythmia
(B) Bronchoconstriction
(C) Constipation
(D) Inhibition of acute graft rejection
(E) Pulmonary vasodilation

(E) Pulmonary vasodilation

NO does not cause arrhythmias or constipation. It causes bronchodilation and may hasten graft rejection. NO does cause pulmonary vasodilation.

Which of the following is an approved application for nitric oxide administered as a gas?

(A) Asthma
(B) Dysmenorrhea
(C) Patent ductus arteriosus
(D) Pulmonary hypertension
(E) Transposition of the great vessels in newborns

(D) Pulmonary hypertension

Thus far, NO gas has been approved for use by inhalation in neonatal hypoxic respiratory failure and adult pulmonary hypertension.

One effect that theophylline, nitroglycerin, isoproterenol, and histamine have in common is

(A) Direct stimulation of cardiac contractile force
(B) Tachycardia
(C) Bronchodilation
(D) Postural hypotension
(E) Throbbing headache

(B) Tachycardia

Theophylline does not ordinarily cause headache or postural hypotension. Nitroglycerin does not cause direct cardiac stimulation but does evoke a compensatory sympathetic reflex. Histamine does not cause bronchodilation.

A 23-year-old woman is using an albuterol inhaler for frequent acute episodes of asthma and complains of symptoms that she ascribes to the albuterol. Which of the following is not a recognized action of albuterol?

(A) Diuretic effect
(B) Positive inotropic effect
(C) Skeletal muscle tremor
(D) Smooth muscle relaxation
(E) Tachycardia

(A) Diuretic effect

Albuterol is a β2-selective receptor agonist, but in moderate to high doses it induces β1 cardiac effects as well as β2-mediated smooth and skeletal muscle effects. It does not cause diuresis.

A 10-year-old child has severe asthma and was hospitalized 5 times between the ages of 7 and 9. He is now receiving outpatient medications that have greatly reduced the frequency of severe attacks. Which of the following is most likely to have adverse effects when used daily over long periods for severe asthma?

(A) Albuterol by aerosol
(B) Beclomethasone by aerosol
(C) Cromolyn by inhaler
(D) Prednisone by mouth
(E) Theophylline in long-acting oral form

(D) Prednisone by mouth

If oral corticosteroids must be used, alternate-day therapy is preferred because it interferes less with normal growth in children.

A 16-year-old patient is in the emergency department receiving nasal oxygen. She has a heart rate of 125 bpm, a respiratory rate of 40 breaths/min, and a peak expiratory flow <50% of the predicted value. Wheezing and rales are audible without a stethoscope.
Which of the following drugs does not have a direct bronchodilator effect?(A) Epinephrine
(B) Terbutaline
(C) Prednisone
(D) Theophylline
(E) Ipratropium

(C) Prednisone

Although extremely important in severe chronic asthma and status asthmaticus, corticosteroids do not have a demonstrable direct bronchodilator action.

A 16-year-old patient is in the emergency department receiving nasal oxygen. She has a heart rate of 125 bpm, a respiratory rate of 40 breaths/min, and a peak expiratory flow <50% of the predicted value. Wheezing and rales are audible without a stethoscope.

After successful treatment of the acute attack, the patient was referred to the outpatient clinic for follow-up treatment for asthma. Which of the following is not an established prophylactic strategy for asthma?

(A) Avoidance of antigen exposure
(B) Blockade of histamine receptors
(C) Blockade of leukotriene receptors
(D) IgE antibody blockade
(E) Inhibition of phospholipase A2

(B) Blockade of histamine receptors

Histamine does not appear to play a significant role in asthma, and antihistaminic drugs, even in high doses, are of little or no value. Antigen avoidance is well established. Blockade of leukotriene receptors with montelukast; inhibition of phospholipase with corticosteroids; and inhibition of mediator release with the IgE antibody are also useful.

Mr Green is a 60-year-old former smoker with cardiac disease and severe chronic obstructive pulmonary disease (COPD) associated with frequent episodes of bronchospasm. Which of the following is a bronchodilator useful in COPD and least likely to cause cardiac arrhythmia?

(A) Aminophylline
(B) Cromolyn
(C) Epinephrine
(D) Ipratropium
(E) Metaproterenol
(F) Metoprolol
(G) Prednisone
(H) Salmeterol
(I) Zafirlukast
(J) Zileuton

(D) Ipratropium

Ipratropium is the bronchodilator that is most likely to be useful in COPD without causing arrhythmias. Tiotropium is similar.

A 22-year-old man is brought to the emergency department after suffering seizures resulting from an overdose of a drug he has been taking. His friends state that he took the drug orally and sometimes had insomnia after taking it. Which of the following is a direct bronchodilator that is most often used in asthma by the oral route and is capable of causing insomnia and seizures?

(A) Cromolyn
(B) Epinephrine
(C) Ipratropium
(D) Metaproterenol
(E) Metoprolol
(F) Prednisone
(G) Salmeterol
(H) Theophylline
(I) Zileuton

(H) Theophylline

Theophylline is a bronchodilator that is active by the oral route. It causes insomnia in therapeutic doses and seizures in overdosage.

Which of the following in its parenteral form is life-saving in severe status asthmaticus and acts, at least in part, by inhibiting phospholipase A2?

(A) Aminophylline
(B) Cromolyn
(C) Epinephrine
(D) Ipratropium
(E) Metaproterenol
(F) Metoprolol
(G) Prednisone
(H) Salmeterol
(I) Zafirlukast
(J) Zileuton

(G) Prednisone

Parenteral corticosteroids such as prednisolone (the active metabolite of prednisone) are lifesaving in status asthmaticus. They probably act by reducing production of leukotrienes (see Chapter 18).

Which of the following has a slow onset but long duration of action and is always used in combination with a corticosteroid by inhalation?

(A) Aminophylline
(B) Cromolyn
(C) Epinephrine
(D) Ipratropium
(E) Metaproterenol
(F) Metoprolol
(G) Prednisone/prednisolone
(H) Salmeterol
(I) Zafirlukast
(J) Zileuton

(H) Salmeterol

Salmeterol is a β2-selective agonist that has a slow onset and long duration of action. Used alone, it increases asthma mortality, but in combination with inhaled corticosteroids it improves asthma control.

Oral medications are popular for the treatment of asthma in children because young children may have difficulty with the proper use of aerosol inhalers. Which of the following is an orally active inhibitor of leukotriene receptors?

(A) Albuterol
(B) Aminophylline
(C) Ipratropium
(D) Montelukast
(E) Zileuton

(D) Montelukast

Zileuton is an inhibitor of the lipoxygenase enzyme involved in the synthesis of leukotrienes. Montelukast and zafirlukast are leukotriene antagonists at the leukotriene receptor.

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