Introduction to Respiratory Pharmacology Flashcards
A 26-year-old man suffering with an upper respiratory viral infection asked the pharmacist for a drug in order to alleviate his dry, raspy cough that was very disturbing and prevented him to sleep. The pharmacist suggested an oral over-the-counter antitussive preparation. Which of the following drugs was most included in that preparation? A) Codeine B) Albuterol C) Dextromethorphan D) Fluticasone E) Ipratropium F) Zileuton
The cough must be treated when it is nonproductive and disturbing, as in the present case. Dextromethorphan is a drug found in many over-the-counter antitussive medications usually (and incorrectly) combined with several other drugs. The reason for this is that the drug is considered safe and effective for consumer use without medical supervision.
A) Codeine is an effective antitussive, but is not available as an over-the counter preparation, because of its addiction liability.
B, D, E, F) These drugs are not antitussives.
A 42-year-old man, who has been suffering from chronic obstructive pulmonary disease for four years, had recently oral theophylline added to her current therapy. The inhibition of which of the following enzymes most likely contributed to the bronchodilating effect of theophylline in this patient? A) Phospholipase B) Phosphodiesterase C) 5-lipoxygenase D) Cyclooxygenase E) Adenylyl cyclase F) Protein kinase
Answer: B
The molecular basis for the antiasthmatic action of methylxanthines is still uncertain, but the primary mechanism of bronchodilating effect most likely involves the inhibition of phosphodiesterase the enzyme that catalyzes the metabolism of cAMP. This inhibition increases the availability of cAMP which causes two actions in bronchial smooth muscle: a) stimulation of Ca2+ efflux; b) decreased phosphorylation of myosin light chain. Both actions contribute to the bronchodilating effect of the drug.
A, E, C, D, F) Theophylline does not inhibit these enzymes.
A 7-year-old boy recently diagnosed with bronchial asthma started a treatment with inhaled albuterol “as needed”. Which of the following molecular actions most likely mediated the therapeutic effect of the drug in this patient?
A) Increased synthesis of IP3 and DAG
B) Increased synthesis of cAMP
C) Blockade of ligand-gated K+ channels
D) Opening of voltage-gated Ca2+ channels
E) Increased synthesis of eicosanoids
Answer: B
Albuterol is a β2-adrenoceptor agonist. Activation of β2-adrenoceptors in smooth muscle cells increases the synthesis of cAMP which in turn accelerates the inactivation of myosin light chain kinase. The decreased availability of this enzyme decreases the phosphorylation of myosin light chain which is a needed step for smooth muscle contraction.
A 55-year-old woman had been suffering from chronic obstructive pulmonary disease that was not adequately controlled in spite of her current inhalation therapy. Her physician decided to add another drug, given orally, that is thought to have both bronchodilating and anti-inflammatory actions. Which of the following drugs was most likely added to the patient’s therapeutic regimen? A) Ipratropium B) Albuterol C) Zileuton D) Fluticasone E) Theophylline
Answer: E
The added drug was most likely theophylline. The antiasthmatic effect of theophylline seems to result from both bronchodilating and antiinflammatory actions. The inhibition of phosphodiesterase 4 in smooth muscle most likely explains the direct bronchodilating activity. Proposed antiinflammatory mechanisms include reduced release of inflammatory cytokines and enhancement of histone deacetylation (acetylation of histone is needed for activation of inflammatory gene transcription).
A, B) These drugs are bronchodilators but are devoid of antiinflammatory actions.
C, D) These drugs have antiinflammatory actions but are devoid of significant bronchodilating activity.
A 52-year-old man complained to his physician that his chronic cough had got worse and he had an increasing breathing difficulty. The man had a long smoking history and currently he was smoking one pack of cigarettes daily. The physician decided to start a therapy with a drug that can block the acetylcholine-mediated increase in Ca2+ availability in bronchial smooth muscle. Which of the following drugs was most likely administered? A) Fluticasone B) Ipratropium C)Theophylline D) Albuterol E) Zileuton F) Zafirlukast
Answer: B
The patient was most likely suffering from COPD, the classic disease of heavy smokers. Ipratropium is an antimuscarinic drugs. By blocking M3 cholinergic receptors in bronchial tree these drugs prevent the increased synthesis of inositol triphosphate which in turn triggers the release of CA++ from storage vesicles. In COPD anticholinergic drugs may be as effective as or even superior to β2-adrenoceptor agonists.
A, C, D, E, F) These drugs do not block muscarinic receptors
A 14-year-old girl, suffering from persistent asthma, had recently fluticasone added to her therapeutic regimen. Which of the following molecular actions most likely mediated the therapeutic effect of the drug in the patient’s disease?
A) Increased synthesis of TNF alpha
B) Increased synthesis of antiinflammatory cytokines
C) Increased distribution of peripheral lymphocytes
D) Opening of Ca2+ channels in smooth muscle cell membranes
E) Activation of phospholipase A2
Answer: B
Fluticasone is a glucocorticoid drug. It has been consistently shown that inhaled glucocorticoids can exert long-term control of asthma because of their potent antiinflammatory action that is mediated, in part, by the increased transcription of genes coding for synthesis of antiinflammatory cytokines.
A, C, D, E) Glucocorticoids have actions opposite to those listed.
A 9-year-old girl recently diagnosed with allergic asthma started a treatment with inhaled albuterol as needed. Which of the following parts of the pulmonary system was most likely the primary site of action of the drug in this patient? A) Epiglottis B) Trachea C) Main bronchi D) Bronchioles E) Pulmonary alveoli
Answer: D
Albuterol is a β2-adrenoceptor agonist. Activation of β2-adrenoceptors on smooth muscles (wherever they are) causes a smooth muscle relaxation. Therefore the primary site of action of the drug in the pulmonary system is related primarily to the amount of smooth muscle present in the lungs. Bronchiole walls have a very large amount of smooth muscle and they do not contain cartilage that would oppose to any variation in bronchial caliber. Therefore albuterol action will be primarily on bronchioles.
A 17-year-old boy suffering from moderate persistent asthma complained to his physician of pain on swallowing. His asthma was completely controlled by inhaled fluticasone, 6 puffs daily. Which of the following would be the most appropriate change in his asthma therapy?
A) Switch to inhaled albuterol
B) Use the drug inhaler with a spacer chamber
C) Add ipratropium to his present regimen
D) Switch to oral zafirlukast
E) Add theophylline to his present regimen
Answer: B
The typical burst of inhaled medicine directly against the mouth can irritate the inside walls of the mouth and throat and cause infection, as in the present case. In fact the patient’s pain on swallowing was most likely due to throat irritation. The white spots on his oral mucosa likely indicate oral candidiasis, a common adverse effect of inhaled glucocorticoids. The spacer inhaler is a chamber that holds the aerosol produced by a metered dose inhaler (MDI) before it is inhaled into the lungs. This chamber performs two major functions:
(1) The aerosol remains inside the device for some time, hence the larger particles emitted by the MDI settle down on the walls of the chamber and do not unnecessarily go into the mouth or throat; therefore throat irritation and infections are reduced.
(2) The distance between the MDI emission nozzle and the mouth of the patient is increased, whereby the finer particles of the mist can be inhaled better and can penetrate into the distal airways. Because of this, the therapeutic effect of a given dose is increased.
A, C, D, E) Since the therapy was quite effective there is no reason to change treatment.
A 55-year-old woman, who had been suffering from chronic obstructive pulmonary disease for two years, had recently zafirlukast added to her therapeutic regimen. Which of the following molecular actions most likely mediated the therapeutic effect of the drug in this patient? A) Blockade of adenosine receptors B) Inhibition of phospholipase A2 C) Activation of β2-adrenoceptors D) Blockade of M3 cholinergic receptors E) Blockade of leukotriene receptors
Answer: E
Zafirlukast is a leukotriene receptors antagonist. Leukotrienes are endogenous compounds that have been consistently implicated in the pathogenesis of inflammation, especially in chronic diseases such as asthma and inflammatory bowel disease. They activate specific receptors located mainly on the membrane of vascular endothelial cells and smooth muscle cells of lungs and intestine. This activation can increase vascular permeability and cause a strong bronchoconstricting effect. Blockade of leukotriene receptors in patients with bronchospastic disorders can lead to antiinflammatory activity and bronchodilation.
A) This would be a mechanism of action of theophylline
B) This would be a mechanism of action of glucocorticoids
C) This would be the mechanism of action of β2-adrenoceptor agonists
D) This would be the mechanism of action of muscarinic antagonists.
A 10-year-old boy recently diagnosed with allergic asthma started a treatment with inhaled albuterol. Which of the following is most likely the primary advantage of inhalatory versus oral administration of drugs in bronchospastic disorders? A) Better systemic absorption B) Slower onset of action C) Better drug elimination D) Increased drug accumulation E) Lower risk of adverse effects
Answer: E
The inhalatory route of administration is used to produce local effects. An oral dose is much higher than the inhaled dose required to achieve the same therapeutic effect (typically by a ratio of 20:1). Since most adverse effects of drugs are dose-dependent the inhalatory administration can get the same therapeutic effect with lower risk of adverse effects. Not every drug can be administered by inhalatory route but when there is a choice of inhaled or oral route for a drug in the treatment of respiratory disorders, the inhaled route is always preferable.
A) Systemic absorption is actually minimized with inhalatory administration.
B) The onset of action is actually faster, not slower with inhalatory administration.
C, D) drug elimination and accumulation refer to the absorbed drug. Systemic absorption is minimized with inhalatory administration.
A. Mechanism of action of theophylline
B. Mechanism of action of glucocorticoids
C. Mechanism of action of β2-adrenoceptor agonists
D. Mechanism of action of muscarinic antagonists.
E. Mechanism of Zafirlukast
A) Blockade of adenosine receptors - the inhibition of phosphodiesterase is most likely the main molecular mechanism of the bronchodilating action
B) Inhibition of phospholipase A2 & leukotriene - Mechanisms of anti-inflammatory action
C) Activation of β2-adrenoceptors - increases the synthesis of cAMP - Enhanced mucociliary clearance & decrease SM contractio
D) Blockade of M3 cholinergic receptors - counteract ACh - leading to bronchodilation - Bronchodilation in patients with COPD is equally or more intense than that of β2-agonists - no mucous clearance
E) Blockade of leukotriene receptors - in patients with bronchospastic disorders can lead to antiinflammatory activity and bronchodilation
Purpose of space chamber
to achieve sufficient therapeutic efficacy while preventing emergence of serious toxicity
