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Respiratory System Pharmacology: Asthma and COPD

Autonomic control of airway smooth muscle tone

Corticosteroids and control of airway inflammation in asthma

Drugs that can exacerbate asthma

Histamine and histamine receptor blockers

Immunoglobulin antibodies for asthma

Leukotrienes and leukotriene modifiers in asthma

Methylxanthine roles in asthma therapy

Questions

292. A 27-year-old patient is seen in the outpatient clinic for a routine checkup. She’s just moved to your town, and this is the first time you’ve met her. She has asthma and says she’s been using her inhaler (albuterol) most days each week (sometimes twice a day) as her only therapy. “I breathe a lot easier after I take several puffs,” she says. She feels well otherwise. Which statement applies to this patient or her treatment plan?

a. Her treatment plan is inappropriate and needs to be modified

b. If pulmonary function tests performed at your hospital today are normal, it is likely that the diagnosis is incorrect: she does not have asthma

c. She is likely to enjoy activities, such as skiing and skating, in which she breathes cold, clear air

d. She is most likely to have trouble with her breathing when in a warm, humid atmosphere

e. She is probably slightly bradycardic and hypertensive from the drug’s expected actions on the heart and peripheral vasculature

293. Certain adrenergic agonists clearly play a role in managing some patients with asthma, whether for prophylaxis (control medication) or for rescue therapy. Which drug is classified as an adrenergic agonist, but has no physiologically relevant or clinically useful effects on airway smooth muscle tone?

a. Albuterol

b. Epinephrine

c. Norepinephrine

d. Salmeterol

e. Terbutaline

f. Theophylline

294. A patient with asthma has moderate bronchospasm and wheezing about twice a week. Current medications are inhaled albuterol (mainly for acute symptom control) and inhaled beclomethasone as a “control medication.” The patient continues to have occasional and generally mild flare-ups of his asthma. If the physician wishes to make salmeterol part of the treatment plan, how best should it be used for this patient?

a. A replacement for the albuterol

b. A replacement for the corticosteroid

c. An add-on to current medications for additional prophylactic benefits

d. Primary (sole) therapy, replacing both albuterol and the steroid

e. The preferred agent for acute symptom control (rescue therapy)

295. The attending in the outpatient pulmonary clinic states she is going to start omalizumab therapy for a 19-year-old with refractory asthma. What most accurately describes the actions, uses, or adverse effects of this drug?

a. Antibody that binds and therefore inactivates endogenous ACh and histamine

b. Contraindicated if patient is taking an oral or orally inhaled corticosteroid

c. Good alternative to albuterol or similar adrenergic bronchodilators for rescue therapy

d. Immediate- or delayed-onset anaphylactic reactions pose the greatest risk

e. Novel agent likely to become first-line therapy as a control medication for mild but recurrent asthma

296. A 19-year-old moves from a small town to your city, and is now your patient. He has a history of asthma, and his previous primary care physician was managing it with oral theophylline. What best summarizes the efficacy or current status of theophylline in particular, or methylxanthines in general, in such patients as this?

a. Dosing is simple and convenient, rarely needs to be adjusted

b. Excellent alternative to an inhaled steroid for “rescue” therapy

c. Is, at best, a second- or third-line agent for long-term asthma control

d. Possesses strong and clinically useful anti-inflammatory activity

e. Sedation is a major side effect, even with therapeutic doses or blood levels

297. An elderly man with COPD is being managed with several drugs, one of which is inhaled ipratropium. What is the main mechanism that accounts for the beneficial effects of this drug?

a. Blocks receptors upon which an endogenous bronchoconstrictor mediator acts

b. Enhances epinephrine release from the adrenal medulla

c. Inhibits cAMP breakdown via phosphodiesterase inhibition

d. Prevents antigen-antibody reactions that lead to mast cell mediator release

e. Stimulates ventilatory rates (CNS effect in brain’s medulla)

f. Suppresses synthesis and release of inflammatory mediators

298. A 16-year-old girl treated for asthma develops drug-induced skeletal muscle tremors. What was the most likely cause?

a. Albuterol

b. Beclomethasone

c. Cromolyn

d. Ipratropium

e. Montelukast

299. A 26-year-old patient with asthma is being treated with montelukast. What is the main mechanism by which this drug works?

a. Blocks receptors for certain proinflammatory and bronchoconstrictor arachidonic acid metabolites

b. Enhances release of epinephrine from the adrenal (suprarenal) medulla

c. Increases airway β-adrenergic receptor responsiveness to endogenous norepinephrine

d. Inhibits cAMP breakdown via phosphodiesterase inhibition

e. Prevents antigen-antibody reactions that lead to mast cell mediator release

f. Stimulates ventilatory rates (CNS effect in brain’s medulla)

300. An elderly man, in obvious respiratory distress due to exacerbation of his emphysema and chronic bronchitis (COPD), presents in the emergency department. One drug ordered by the physician, to be administered by the respiratory therapist, is N-acetylcysteine. What is the main action or purpose of this drug?

a. Blocks receptors for the cysteinyl leukotrienes

b. Inhibits metabolic inactivation of epinephrine or β₂ agonists that were administered

c. Inhibits leukotriene synthesis

d. Promptly suppresses airway inflammation

e. Reverses ACh-mediated bronchoconstriction

f. Thins airway mucus secretions for easier removal by suctioning or postural drainage

301. A 23-year-old woman with asthma has what is described as “aspirin (hyper)sensitivity” (triad asthma) and experiences severe bronchospasm in response to even small doses of the drug. What is the most likely mechanism by which the aspirin provoked her pulmonary problems?

a. Blocked synthesis of endogenous prostaglandins that have bronchodilator activity

b. Induced formation of antibodies directed against the salicylate on airway mast cells

c. Induced hypersensitivity of H₁ receptors on airway smooth muscles

d. Induced hypersensitivity of muscarinic receptors on airway smooth muscles

e. Prevented epinephrine binding to β₂-adrenergic receptors (airways and elsewhere)

302. A young boy is diagnosed with asthma. His primary symptom is frequent cough, not bronchospasm or wheezing. Other asthma medications are started, but until their effects develop fully we wish to suppress the cough without running a risk of suppressing ventilatory drive or causing sedation or other unwanted effects. Which drug would meet these needs the best?

a. Codeine

b. Dextromethorphan

c. Diphenhydramine

d. Hydrocodone

e. Promethazine

303. A mother brings her 10-year-old son, who has a longstanding history of poorly controlled asthma, to the Emergency Department (ED). He is in a relatively early stage of what will prove to be a severe asthma attack. Arterial blood gases have not been analyzed yet, but it is obvious that the lad is in great distress. He is panting with great effort at a rate of about 60/min.

Given the boy’s history and the likely diagnosis of acute asthma, the health care team administers all the drugs listed below by the stated routes, and with the purposes noted. The child’s condition quickly improves, and the team leaves the boy with his mother while they go to care for other ED patients. Within a couple of minutes, the mother comes out of her son’s cubicle frantically screaming “he’s stopped breathing!” Which drug most likely precipitated the ventilatory arrest?

a. Albuterol, inhaled, given by nebulizer for prompt bronchodilation

b. Atropine, nebulized and inhaled

c. Midazolam, IV, to normalize ventilatory rate and allay anxiety

d. Methylprednisolone (glucocorticosteroid), IV, for prompt suppression of airway inflammation

e. Normal saline, nebulized and inhaled, to hydrate the airway mucosae

304. You prescribe an orally inhaled corticosteroid for a patient with asthma. Previously she was using only a rapidly acting adrenergic bronchodilator for both prophylaxis and treatment of acute attacks. She used the steroid as directed for 5 days, and then stopped taking it. What is the most likely reason why the patient quit using the drug?

a. Disturbing tachycardia and palpitations occurred

b. Relentless diarrhea developed after just 1 day of using the steroid

c. She experienced little or no obvious improvement in breathing

d. The drug caused extreme drowsiness that interfered with daytime activities

e. The drug caused her to retain fluid and gain weight

305. A patient consumes an excessive dose of theophylline and develops toxicity in response to the drug. What is the expected sign, symptom, or other consequence of this overdose?

a. Bradycardia

b. Drowsiness progressing to sleep and then coma

c. Hepatotoxicity

d. Paradoxical bronchospasm

e. Seizures

306. Acetylcholinesterase inhibitors, muscarinic agonists such as pilocarpine, and β-blockers are among the drugs used to manage patients with glaucoma. They also share properties that are particularly relevant to patients with asthma. Which statement summarizes best what that relevance is?

a. Contraindicated, or pose great risks, for people with asthma

b. Degranulate mast cells, cause bronchoconstriction

c. Tend to raise intraocular pressure in patients who have both glaucoma and asthma

d. Trigger bronchoconstriction by directly activating H₁ histamine receptors on airway smooth muscle cells

e. Useful for acute asthma, not for ambulatory patients

307. A patient suffering status asthmaticus presents in the emergency department. Blood gases reveal severe respiratory acidosis and hypoxia. Even large parenteral doses of a selective β₂ agonist fail to dilate the airways adequately; rather, they cause dangerous degrees of tachycardia. Which pharmacologic intervention or approach is most likely to control the acute symptoms and restore the bronchodilator efficacy of the adrenergic drug?

a. Give a lipoxygenase inhibitor (eg, montelukast)

b. Give a parenteral corticosteroid

c. Give parenteral diphenhydramine

d. Switch to epinephrine

e. Switch to isoproterenol (β₁/β₂ agonist)

308. The FDA has mandated a warning about the increased risk of death in asthma patients taking recommended doses of salmeterol (or other slow-/long-acting adrenergic asthma control medications) for too long a period of time. What is the most likely mechanism or phenomenon by which this fatal adverse response, or other severe airway responses, occur?

a. Anaphylaxis due to gradual formation of antibodies against the drug

b. Hypertensive crisis

c. Inhibited synthesis, release, and anti-inflammatory actions of endogenous cortisol

d. Plugging of the bronchioles with viscous mucus, due to the drug’s antimuscarinic actions

e. Tolerance of airway smooth muscle cells to the effects of adrenergic bronchodilators

309. A hungry 8-year-old is visiting his grandparents’ house and sees grandpa sprinkle some powder from a small foil pack onto his applesauce. Grandpa smiles and says “Mmmm, tastes good.” The packet contains a theophylline salt that was prescribed for his COPD. Liking applesauce, and thinking the drug packets contain candy, the lad opens the applesauce jar, finds grandpa’s stash of dozens of theophylline packets, and sprinkles on lots of drug before eating the whole thing. Toxicity ensues. What is this child most likely to experience, and do so before anything else significant and untoward develops?

a. Acute urinary retention

b. Bradycardia and hypotension

c. Irritability, other signs/symptoms of CNS stimulation, possibly seizures

d. Ischemic stroke from drug-induced platelet aggregation

e. Ventilatory suppression (centrally mediated) leading to respiratory acidosis and apnea

Respiratory System Pharmacology: Asthma and COPD

Answers

292. The answer is a. (Brunton, pp 302, 1035-1040; Katzung, pp 144, 339-357.) This patient certainly seems to have recurrent episodes of asthma. Even if they are “mild” and ostensibly responsive to an inhaled β₂

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