Chapter 29: Drugs For Respi System

Question 1

SHORT-ACTING b2 ADRENERGIC AGONISTS

Answer 1

Albuterol PROAIR, PROVENTIL, VENTOLIN
Levalbuterol XOPENEX

Question 2

LONG-ACTING b2 ADRENERGIC AGONISTS

Answer 2

Arformoterol BROVANA
-copd
Formoterol FORADIL, PERFOROMIST
Indacaterol ARCAPTA
- copd
Salmeterol SEREVENT

Question 3

INHALED CORTICOSTEROIDS

Answer 3

Beclomethasone BECONASE AQ, QVAR
-Allergic rhinitis, Asthma, COPD
Budesonide PULMICORT, RHINOCORT
-Allergic rhinitis, Asthma, COPD
Ciclesonide ALVESCO, OMNARIS, ZETONNA
- Allergic rhinitis
Fluticasone FLONASE, FLOVENT
- Allergic rhinitis, Asthma, COPD
Mometasone ASMANEX, NASONEX
-Allergic rhinitis , asthma
Triamcinolone NASACORT AQ- Allergic rhinitis

Question 4

LONG-ACTING b2 ADRENERGIC AGONIST/CORTICOSTEROID COMBINATION

Answer 4

Formoterol/budesonide SYMBICORT
-Asthma, COPD
Formoterol/mometasone DULERA
-Asthma, COPD
Salmeterol/fluticasone ADVAIR
-Asthma, COPD
Vilanterol/fluticasone BREO ELLIPTA-copd

Question 5

SHORT-ACTING ANTICHOLINERGIC

Answer 5

Ipratropium ATROVENT- Allergic rhinitis, copd

Question 6

LONG-ACTING ANTICHOLINERGIC

Answer 6

Aclidinium bromide TUDORZA PRESSAIR-copd
Tiotropium SPIRIVA-copd

Question 7

LEUKOTRIENE MODIFIERS

Answer 7

Montelukast SINGULAIR
-Asthma, allergic rhinitis
Zafirlukast ACCOLATE
-Asthma
Zileuton ZYFLO CR- Asthma

Question 8

ANTIHISTAMINES (H1-RECEPTOR BLOCKERS)

Answer 8

Azelastine ASTELIN, ASTEPRO
Cetirizine ZYRTEC
Desloratadine CLARINEX
Fexofenadine ALLEGRA
Loratadine CLARITIN

*All for allergic rhinitis

Question 9

α-ADRENERGIC AGONISTS

Answer 9

Oxymetazoline AFRIN, DRISTAN
Phenylephrine NEOSYNEPHRINE, SUDAFED PE
Pseudoephedrine SUDAFED

*All for allergic rhinitis

Question 10

AGENTS FOR COUGH

Answer 10

Benzonatate TESSALON PERLES
- Cough suppressant
Codeine (with guaifenesin) VARIOUS
-Cough suppressant/expectorant
Dextromethorphan VARIOUS
- Cough suppressant
Dextromethorphan (with guaifenesin) VARIOUS
- Cough suppressant/expectorant
Guaifenesin VARIOUS- Expectorant

Question 11

OTHER AGENTS

Answer 11

Cromolyn NASALCROM
-asthma, allergic rhinitis
Omalizumab XOLAIR
-asthma
Roflumilast DALIRESP
-copd
Theophylline ELIXOPHYLLIN, THEO-24, UNIPHYL-asthma

Question 12

Intermittent

Answer 12

Less than 2 days
per week
Near normal* spirometry/peak flow
Long term:no daily meds
Acute relief of symptoms: Short-acting β2 agonist

Question 13

Mild persistent

Answer 13

More than 2
days per week,
not daily
Near normal peak flow or spirometry
Long term control: Low-dose ICS
Acute relief: Short-acting β2 agonist

Question 14

Moderate persistent

Answer 14

Daily
60% to 80% of
normal peak flow/spirometry
Long term: Low-dose ICS + LABA
OR
Medium-dose ICS
Acute relief: Short-acting β2 agonist

Question 15

Severe persistent

Answer 15

Continually
Less than 60% of
normal
Long term control: Medium-dose ICS + LABA
OR
High-dose ICS + LABA
Acute relief: Short-acting β2 agonist

Question 16

Guidelines for the pharmacologic therapy of stable COPD.

Type A
Low risk
Less symptoms

Answer 16

1st choice: Short-acting anticholinergic when necessary
or
Short-acting β2 agonist when necessary

Alternative: Long-acting anticholinergic
or
Long-acting β2 agonist
or
Short-acting β2 agonist and short-acting anticholinergic

Question 17

Type B
Low risk
More symptoms

Answer 17

1st choice: Long-acting anticholinergic
or
Long-acting β2 agonist

Alternative: Long-acting anticholinergic and long-acting β2 agonist

Question 18

Type C
High risk
Less symptoms

Answer 18

1st choice: Inhaled corticosteroid + long-acting β2 agonist
or
Long-acting anticholinergic

Alternative: Long-acting anticholinergic and long-acting β2 agonist
or
Long-acting anticholinergic and PDE-4 inhibitor
or
Long-acting β2 agonist and PDE-4 inhibitor

Question 19

Type D

High risk
More symptoms

Answer 19

1st choice: ICS + long-acting β2 agonist
and/or
Long-acting anticholinergic

Alternative: ICS + long-acting β2 agonist and long-acting anticholinergic
or
ICS + long-acting β2 agonist and PDE-4 inhibitor
or
Long-acting anticholinergic and long-acting β2 agonist or
Long-acting anticholinergic and PDE-4 inhibitor

Question 20

Preferred Drug to treat Asthma

Answer 20

C. β2
-Adrenergic agonists
Inhaled β2
-adrenergic agonists directly relax airway smooth muscle.
They are used for the quick relief of asthma symptoms, as well as
adjunctive therapy for long-term control of the disease.
1. Quick relief: Short-acting β2
agonists (SABAs) have a rapid onset
of action (5 to 30 minutes) and provide relief for 4 to 6 hours. They
are used for symptomatic treatment of bronchospasm, providing
quick relief of acute bronchoconstriction. All patients with asthma
should be prescribed a SABA inhaler. β2
agonists have no anti-
inflammatory effects, and they should never be used as the sole
therapeutic agents for patients with persistent asthma. However,
monotherapy with SABAs may be appropriate for patients with
intermittent asthma or exercise-induced bronchospasm. Direct-
acting β2
-selective agonists include albuterol [al-BYOO-ter-all]
and levalbuterol [leh-val-BYOO-ter-all]. These agents provide sig-
nificant bronchodilation with little of the undesired effect of α or β1
stimulation (see Chapter 6). Adverse effects, such as tachycardia,
hyperglycemia, hypokalemia, and hypomagnesemia, are mini-
mized with inhaled delivery versus systemic administration. These
agents can cause β2
-mediated skeletal muscle tremors.
2. Long-term control: Salmeterol [sal-MEE-ter-all] and formoterol
[for-MOE-ter-all] are long-acting β2
agonists (LABAs) and chemical
analogs of albuterol. Salmeterol and formoterol have a long dura-
tion of action, providing bronchodilation for at least 12 hours. Neither
salmeterol nor formoterol should be used for quick relief of an acute
asthma attack. Use of LABA monotherapy is contraindicated, and
LABAs should be used only in combination with an asthma control-
ler medication. Inhaled corticosteroids (ICS) remain the long-term
controllers of choice in asthma, and LABAs are considered to be
useful adjunctive therapy for attaining asthma control. Some LABAs
are available as a combination product with an ICS (Figure 29.1).
Adverse effects of LABAs are similar to quick-relief β2
agonists.

Corticosteroids
ICS are the drugs of choice for long-term control in patients with any
degree of persistent asthma (Figure 29.3). Corticosteroids inhibit
the release of arachidonic acid through phospholipase A2
inhibition,
thereby producing direct anti-inflammatory properties in the airways
(Figure 29.4). A full discussion of the mechanism of action of cortico-
steroids is found in Chapter 27. No other medications are as effec-
tive as ICS in the long-term control of asthma in children and adults.
To be effective in controlling inflammation, glucocorticoids must be
used regularly. Severe persistent asthma may require the addition of
a short course of oral glucocorticoid treatment.
1. Actions on lung: ICS do not directly affect the airway smooth
muscle. Instead, ICS therapy directly targets underlying airway
inflammation by decreasing the inflammatory cascade (eosino-
phils, macrophages, and T lymphocytes), reversing mucosal
edema, decreasing the permeability of capillaries, and inhibiting
the release of leukotrienes. After several months of regular use,
ICS reduce the hyperresponsiveness of the airway smooth muscle
to a variety of bronchoconstrictor stimuli, such as allergens, irri-
tants, cold air, and exercise.

Question 21

ALTERNATIVE DRUGS USED TO TREAT ASTHMA

Leukotriene modifiers

Answer 21

A. Leukotriene modifiers
Leukotrienes (LT) B4 and the cysteinyl leukotrienes, LTC4, LTD4,
and LTE4, are products of the 5-lipoxygenase pathway of ara-
chidonic acid metabolism and part of the inflammatory cascade.
5-Lipoxygenase is found in cells of myeloid origin, such as mast
cells, basophils, eosinophils, and neutrophils. LTB4 is a potent che-
moattractant for neutrophils and eosinophils, whereas the cyste-
inyl leukotrienes constrict bronchiolar smooth muscle, increase
endothelial permeability, and promote mucus secretion. Zileuton
[zye-LOO-ton] is a selective and specific inhibitor of 5-lipoxygen-
ase, preventing the formation of both LTB4 and the cysteinyl leu-
kotrienes. Because zafirlukast [za-FIR-loo-kast] and montelukast
[mon-te-LOO-kast] are selective antagonists of the cysteinyl leu-
kotriene-1 receptor, they block the effects of cysteinyl leukotrienes
(Figure 29.4). All three drugs are approved for the prevention of
asthma symptoms. They should not be used in situations where
immediate bronchodilation is required. Leukotriene receptor antag-
onists have also shown efficacy for the prevention of exercise-
induced bronchospasm.
1. Pharmacokinetics: All three drugs are orally active and highly
protein bound. Food impairs the absorption of zafirlukast. The
drugs are metabolized extensively by the liver. Zileuton and its
metabolites are excreted in urine, whereas zafirlukast, montelu-
kast, and their metabolites undergo biliary excretion.
2. Adverse effects: Elevations in serum hepatic enzymes have
occurred with all three agents, requiring periodic monitoring and
discontinuation when enzymes exceed three to five times the upper
limit of normal. Other effects include headache and dyspepsia

Zafirlukast is an inhibitor of cytochrome P450 (CYP) isoenzymes
2C8, 2C9, and 3A4, and zileuton inhibits CYP1A2.

Question 22

Alternative drug to treat Asthma
Cromolyn

Answer 22

Cromolyn
Cromolyn [KRO-moe-lin] is a prophylactic anti-inflammatory agent
that inhibits mast cell degranulation and release of histamine. It is
an alternative therapy for mild persistent asthma. However, it is not
useful in managing an acute asthma attack, because it is not a bron-
chodilator. Cromolyn is available as a nebulized solution for use in
asthma. Due to its short duration of action, this agent requires dosing
three or four times daily, which affects adherence and limits its use.
Adverse effects are minor and include cough, irritation, and unpleas-
ant taste.

Question 23

Alternative drug to treat Asthma , cholinergic antagonist

Answer 23

C. Cholinergic antagonists
The anticholinergic agents block vagally mediated contraction
of airway smooth muscle and mucus secretion (see Chapter 5).
Inhaled ipratropium [IP-ra-TROE-pee-um], a quaternary derivative
of atropine, is not recommended for the routine treatment of acute
bronchospasm in asthma, as its onset is much slower than inhaled
SABAs. However, it may be useful in patients who are unable to tol-
erate a SABA or patients with concomitant COPD. Ipratropium also
offers additional benefit when used with a SABA for the treatment of
acute asthma exacerbations in the emergency department. Adverse
effects such as xerostomia and bitter taste are related to local anti-
cholinergic effects

Question 24

Alternative drug to treat Asthma:: Theophylline

Answer 24

Theophylline
Theophylline [thee-OFF-i-lin] is a bronchodilator that relieves airflow
obstruction in chronic asthma and decreases its symptoms. It may also
possess anti-inflammatory activity, although the mechanism of action
is unclear. Previously, the mainstay of asthma therapy, theophylline
has been largely replaced with β2
agonists and corticosteroids due to
its narrow therapeutic window, adverse effect profile, and potential for
drug interactions. Overdose may cause seizures or potentially fatal
arrhythmias. Theophylline is metabolized in the liver and is a CYP1A2
and 3A4 substrate. It is subject to numerous drug interactions. Serum
concentration monitoring should be performed when theophylline is
used chronically

Question 25

Alternative drug to treat Asthma Omalizumab

Answer 25

Omalizumab Omalizumab [OH-ma-LIZ-oo-mab] is a recombinant DNA-derived monoclonal antibody that selectively binds to human immunoglobulin E (IgE). This leads to decreased binding of IgE to its receptor on the surface of mast cells and basophils. Reduction in surface-bound IgE limits the release of mediators of the allergic response. Omalizumab is indicated for the treatment of moderate to severe persistent asthma in patients who are poorly controlled with conventional therapy. Its use is limited by the high cost, route of administration (subcutaneous), and adverse effect profile. Adverse effects include serious anaphylac- tic reaction (rare), arthralgias, fever, and rash. Secondary malignan- cies have been reported.

Question 26

DRUGS USED TO TREAT CHRONIC OBSTRUCTIVE PULMONARY DISEASE Bronchodilators

Answer 26

Inhaled bronchodilators, including the β2 -adrenergic agonists and anticholinergic agents (ipratropium and tiotropium [tye-oh-TROE- pee-um]), are the foundation of therapy for COPD (Figure 29.5). These drugs increase airflow, alleviate symptoms, and decrease exacerbation rates. The long-acting agents, LABAs and tiotropium, are preferred as first-line treatment of COPD for all patients except those who are at low risk with less symptoms. Combination of both an anticholinergic and a β2 agonist may be helpful in patients who have inadequate response to a single inhaled bronchodilator.

Question 27

Drugs to treat copd Corticosteroids

Answer 27

Corticosteroids The addition of an ICS to a long-acting bronchodilator may improve symptoms, lung function and quality of life in COPD patients with FEV1 of less than 60% predicted. However, the use of an ICS is asso- ciated with an increased risk of pneumonia, and therefore, use should be restricted to these patients. Although often used for acute exac- erbations, oral corticosteroids are not recommended for long-term treatment.

Question 28

DRUGS USED TO TREAT ALLERGIC RHINITIS Antihistamines (H1 -receptor blockers)

Answer 28

Antihistamines are useful for the management of symptoms of aller- gic rhinitis caused by histamine release (sneezing, watery rhinorrhea, itchy eyes/nose). However, they are more effective for prevention of symptoms, rather than treatment once symptoms have begun. Ophthalmic and nasal antihistamine delivery devices are available for more targeted tissue delivery. First-generation antihistamines, such as diphenhydramine and chlorpheniramine, are usually not preferred due to adverse effects, such as sedation, performance impairment, and other anticholinergic effects (see Chapter 30). The second- generation antihistamines (for example, fexofenadine, loratadine, desloratadine, cetirizine, and intranasal azelastine) are generally better tolerated. Combinations of antihistamines with decongestants (see below) are effective when congestion is a feature of rhinitis.

Question 29

Drugs to treat allergic rhinitis Corticosteroid

Answer 29

Corticosteroids Intranasal corticosteroids, such as beclomethasone, budesonide, flutica- sone, ciclesonide, mometasone, and triamcinolone, are the most effec- tive medications for treatment of allergic rhinitis. They improve sneezing, itching, rhinorrhea, and nasal congestion. Systemic absorption is mini- mal, and side effects of intranasal corticosteroid treatment are localized. These include nasal irritation, nosebleed, sore throat, and, rarely, candi- diasis. To avoid systemic absorption, patients should be instructed not to inhale deeply while administering these drugs because the target tissue is the nose, not the lungs or the throat. For patients with chronic rhinitis, improvement may not be seen until 1 to 2 weeks after starting therapy.

Question 30

Drugs for allergic rhinitis Alpha-adrenergic agonist

Answer 30

α-Adrenergic agonists Short-acting α-adrenergic agonists (“nasal decongestants”), such as phenylephrine, constrict dilated arterioles in the nasal mucosa and reduce airway resistance. Longer-acting oxymetazoline [OX-i-me-TAZ- oh-leen] is also available. When administered as an aerosol, these drugs have a rapid onset of action and show few systemic effects. Unfortunately, the α-adrenergic agonist intranasal formulations should be used no longer than 3 days due to the risk of rebound nasal con- gestion (rhinitis medicamentosa). For this reason, the α-adrenergic agents have no place in the long-term treatment of allergic rhini- tis. Administration of oral α-adrenergic agonist formulations results in a longer duration of action but also increased systemic effects.

Question 31

Drugs to treat allergic rhinitis - other agents

Answer 31

Other agents Intranasal cromolyn may be useful in allergic rhinitis, particularly when administered before contact with an allergen. To optimize the thera- peutic effect, dosing should begin at least 1 to 2 weeks prior to allergen exposure. A nonprescription (over-the-counter) nasal formulation of cromolyn is available. Although potentially inferior to other treatments, some LT antagonists are effective for allergic rhinitis as monotherapy or in combination with other agents. They may be a reasonable option in patients who also have asthma. An intranasal formulation of ipratro- pium is available to treat rhinorrhea associated with allergic rhinitis or the common cold. It does not relieve sneezing or nasal congestion.

Question 32

Drugs to treat cough Opiods

Answer 32

Opioids Codeine [KOE-deen], an opioid, decreases the sensitivity of cough cen- ters in the central nervous system to peripheral stimuli and decreases mucosal secretion. These therapeutic effects occur at doses lower than those required for analgesia. However, common side effects, such as constipation, dysphoria, and fatigue, still occur. In addition, it has addictive potential (see Chapter 14). Dextromethorphan [dex- troe-meth-OR-fan] is a synthetic derivative of morphine that has no analgesic effects in antitussive doses. In low doses, it has a low addic- tive profile. However, it is a potential drug of abuse, since it may cause dysphoria at high doses. Dextromethorphan has a significantly safer side effect profile than codeine and is equally effective for cough sup- pression. Guaifenesin [gwye-FEN-e-sin], an expectorant, is available as a single-ingredient formulation and is also a common ingredient in combination products with codeine or dextromethorphan.

Question 33

Drugs for cough Benzonatate

Answer 33

Benzonatate Unlike the opioids, benzonatate [ben-ZOE-na-tate] suppresses the cough reflex through peripheral action. It anesthetizes the stretch receptors located in the respiratory passages, lungs, and pleura. Side effects include dizziness, numbness of the tongue, mouth, and throat. These localized side effects may be particularly problematic if the capsules are broken or chewed and the medication comes in direct contact with the oral mucosa.

Question 34

H1 receptors

Answer 34

Exocrine excretion Increased production of nasal and bronchial mucus, resulting in respiratory symptoms. Bronchial smooth muscles Constriction of bronchioles results in symptoms of asthma and decreased lung capacity. Intestinal smooth muscle Constriction results in intestinal cramps and diarrhea.