Pharm Respitory Part 2

Learning objective: describe the main adverse effects of ipratropium.
Answer: C
Dry mouth is the most common adverse effects of inhaled ipratropium. It can occur in up to 25%
of patients and is most likely due to blockade of muscarinic receptors in salivary glands.
A, B, D, E, F) With all this drugs the occurrence of dry mouth is negligible.

Learning objective: describe the main adverse effects of inhaled glucocorticoids.
Answer: F
Systemic adverse effects of inhaled corticosteroids are extremely rare. Local adverse effect are
more common and include cough, dysphonia and oral candidiasis. Candida albicans is a fungal
organism that is a normal constituent of oral flora, but can cause infection when conditions (like
compromised cellular immunity due to corticosteroids) favor fungal growth.
A, B, C, D, E) These drugs do not cause oral candidiasis.

Learning objective: describe the interaction between beta-2 agonists and glucocorticoids in
the treatment of asthma.
Answer: D
Systemic corticosteroids are given in case of severe asthma exacerbation for two main reasons:
a) they improve the responsiveness of beta-2 receptors and b) They inhibit many phases of the
inflammatory responses. The antiinflammatory activity of corticosteroids is delayed for 4-6 hours
after administration. However the restoration of responsiveness to endogenous catecholamines
as well as to exogenous beta-2 agonists occurs within one hour of administration in severe
chronic asthmatics. This restoration is therefore the main potential benefit of IV administration of
corticosteroids to a patient with severe asthma exacerbation under treatment with beta-2
agonists.
A, B, C, E) Corticosteroids do not have these effects.

Learning objective: describe the main therapeutic uses of theophylline
Answer: B
Cheyne-Stokes breathing, which occurs in various disease states including stroke, is a type of .
periodic breathing in which periods of hyperpnea alternates with periods of apnea. Theophylline
has been shown to improve Cheyne-Stokes respiration, likely because of its stimulant effect on
respiratory center.
A) Neostigmine actually can worse urge incontinence, because it increases urinary bladder
contractility.
C, D, E, F) These drugs have no effect on Cheyne-Stokes breathing, urge urinary incontinence
or limb spasticity.

Learning objective: explain the mechanism of action of cromolyn.
Answer: D
Chromone derivatives like cromolyn sodium are drugs that stabilize mast cells (but not
basophils) so inhibiting the release of chemical mediators from these cells. Intranasal cromolyn
is effective for the treatment of allergic rhinitis, even if is generally less effective than intranasal
corticosteroids.
A, B, C, E) These drugs do not inhibit mast cell degranulation.

Learning objective: describe the appropriate treatment of a persistent asthma not
controlled by theophylline and salmeterol.
Answer: B
When a moderate persistent asthma is not well controlled with a long-acting bronchodilator (like
theophylline or salmeterol) plus an antiinflammatory drug like cromolyn, an inhaled steroid
should be included in the therapeutic regimen.
A) Ipratropium is usually less effective than a beta-2 agonist in asthma.
C) Theophylline is a drug with a narrow therapeutic index. To double the dose would certainly
cause overdose toxicity .
D) Isoproterenol is non selective beta-agonist and therefore it has no advantage and many
disadvantages over albuterol.
E) Ephedrine is a mixed adrenergic agonist with no advantage over a selective beta-2 agonist.

Learning objective: describe the main adverse effects of beta-2 agonists.
Answer: B
Beta-2 agonists by inhalatory route are first line drugs for asthma. The risk of adverse effects is
increased with long-acting beta-2 agonists like salmeterol. Tremor is the most frequent adverse
effect (up to 40% of patients receiving high doses). It likely occurs because beta-2 receptor
activation accelerates the sequestration of cytosolic Ca++ (by opening Ca++ channels in the
sarcoplasmic reticulum of skeletal muscle) and increases discharge in muscle spindles. Anxiety,
the second most frequent adverse effects of these drugs can occur in up to 20% of patients.
Palpitations can occur in up to 10% of patients and is related to the cardiac effects of these
drugs (beta-2 receptors activation increases heart contractility and rate). Muscle cramping is
likely a consequence of hypokalemia (beta-2 agonists stimulate Na/K+ ATPase, so facilitating K+
entry into the cells), since K+ is needed for vasodilation in the skeletal muscle.
A, C, D, F) These drugs do not cause the pattern of adverse effects reported by the patient.
E) High doses of theophylline could cause tremors, muscle cramping palpitations and anxiety but
the drug is not usually given in case of mild allergic asthma and is never administered by
inhalatory route.

Learning objective: describe the mechanism of action of ipratropium.
Answer: D
The history and the symptoms of the patient indicate that he was most likely suffering from
chronic obstructive pulmonary disease (COPD). Ipratropium is a bronchodilator of choice in
COPD since it action in these patients is equal or superior to that achieved by beta-2 agonists.
Ipratropium is a quaternary ammonium compound that belongs to the class of antimuscarinic
drugs. Unlike tertiary amines, quaternary ammonium antimuscarinic drugs block mainly
muscarinic receptors but also have a significant blocking activity on nicotinic Nn receptors.
Therefore inhaled ipratropium can block both M3 receptors on bronchial smooth muscle, and Nn
receptors located in small parasympathetic ganglia within the bronchial tree. Bot actions can
contribute to the final bronchodilating effect of the drug.
A) This activation would cause bronchoconstriction, not bronchodilation.
B) This would be a mechanism of action of glucocorticoids. These drugs are not bronchodilators
and they are used only in patient with advanced COPD and frequent exacerbations,
C), This would be the mechanism of action of beta-2 agonists. These drugs are contraindicated
in this patient because of the history of ventricular tachycardia. Patients who have survived and
episode of sustained ventricular tachycardia or ventricular fibrillation have a extraordinary high
risk of experiencing a recurrent arrhythmia.
E) This would be the mechanism of action of cromolyn. This drug is not a bronchodilator and it is
not used in COPD

Learning objective: explain the mechanism of action of dornase alpha.
Answer: C
The principle source of DNA in the sputum of cystic fibrosis patients is from the nuclei of
degenerating neutrophils which accumulate in the lung because of the chronic bacterial
infections. The DNA is the principal factor that increases the viscosity of the sputum in these
patients. Dornase alpha is a recombinant human deoxyribonuclease that is administered by
inhalatory route. It degrades the DNA, and this has been shown to significantly decrease the
viscosity of the sputum so reducing obstruction and the severity of respiratory infections.
A, B, D, E) (See explanation above).

Learning objective: explain the likely cause of arrhythmia in an asthmatic patient under
albuterol therapy.
Answer: E
The severe asthma of the patient most likely caused hypoxemia which by itself can predispose to
arrhythmias. Moreover the patient was likely receiving a high dose of beta-agonists, since the
increased dyspnea prompted him to increase the number of puffs taken daily. Tachycardia is a
common adverse effect of beta-2 agonists, likely due to activation of beta-2 receptors in the
heart, as well as to reflex effects that stem from beta-2 receptor mediated vasodilation.
A, B, D) Ipratropium and glucocorticoids taken by inhalatory route very seldom cause systemic
effects.
C) Duodenal ulcer is not a risk factor for arrhythmias.

Learning objective: describe the main therapeutic actions of albuterol in bronchospastic
disorders.
Answer: B
A patient who is artificially ventilated cannot cleared bronchial secretions, mainly because
effective cough cannot be performed. Beta-2 agonist drugs improve mucociliary clearance and
therefore can help to remove secretions from bronchial mucosa.
A) Epinephrine, by activating beta-2 receptors, can improve mucociliary clearance but can cause
several adverse effects in this patient, due to its cardiovascular action.
C) Ipratropium has bronchodilating activity but does not improve mucociliary clearance (even if,
unlike other anticholinergic drugs, it does not reduce it).
D, E, F) Chromones, corticosteroids and leukotriene antagonists have no effect on mucociliary
clearance.

Learning objective: describe the molecular mechanism of action of beta-2 receptor
agonists.
Answer: E
A short acting beta-2 receptor agonist taken “as needed” represents the standard therapy for
mild intermittent asthma. No daily medication is required in case of non persistent asthma.
Activation of beta-2 receptors in bronchial muscle increases cAMP which in turn stimulates Ca++
efflux and decreased phosphorylation of myosin light chains. Both actions leads to smooth
muscle relaxation.
A) Beta-2 agonists can block histamine release, but histamine is stored in mast cells and
basophils, not in bronchial epithelium
B ,C) Beta-2 agonists do not have these effects.
D) Beta-2 agonists activate beta-2 receptors in bronchial vessels, but this has nothing to do with
the bronchodilating action.

Learning objective: describe the bronchodilating use of ipratropium in case of a
contraindication to beta-2 agonists.
Answer: C
Accepted guidelines for the treatment of asthma indicate a short acting beta-2 agonist as needed
in all patients. In the present case, however, the patient’s hyperthyroidism contraindicates the
use of beta-2 agonists. In general, when drugs are given by inhalatory route, only 10% to 20% of
the dose can reach the target site of action (lower airways); the rest is swallowed and can be
absorbed by the intestine so causing systemic effects. Ipratropium is an effective bronchodilator
agent and the swallowed dose is not absorbed by the intestine (the drug is a quaternary
ammonium compound). Moreover In this patient:
a) the bronchospasm was triggered by emotional upset and it has been shown that inhaled
anticholinergics can block this response.
b) the nocturnal awakening indicates that the bronchospasm is triggered by a prevalence of the
parasympathetic system (which is predominant during night)
A, E, F) These drugs are not bronchodilators and cannot be used for a relief of bronchospasm.
B) Oral sustained-releases theophylline is an effective bronchodilator, but has the potential to
cause more adverse effects, may interfere with sleep and is less effective than ipratropium.
D) (see explanation above)

Learning objective: describe the use of oral glucocorticoids in bronchospastic disorders.
Answer: A
Oral steroids are usually administered in case of severe asthma that is not controlled by other
antiasthmatic drugs. Corticosteroids have potent antiinflammatory activity and, even if they are
not direct bronchodilators, they can relieve bronchial obstruction by improving the
responsiveness of beta-2 receptors to beta-2 agonists.
A) Ipratropium is usually less effective than beta-2 agonists in asthma and its action is not
potentiated by corticosteroids.
C) The antiinflammatory effect of cromolyn is inferior to that of corticosteroids.
D) It would be useless to add another beta-2 agonist with pharmacokinetic features very close to
that of albuterol.
E) Since a leukotriene antagonist (zafirlukast) was not effective, it is unlikely that an inhibitor of
leukotriene synthesis (zileuton) would be effective.