Professional Documents
Culture Documents
Learning Objectives
Treatment of Asthma and COPD
1. The indications, mechanism of action, adverse effects and contraindications for
the different anti-asthmatics including the preference for certain drugs in certain
situations.
2. The pharmacokinetics of anti-asthmatics and the rapidity of their onset of
action.
3. Describe the strategies of drug treatment of asthma and COPD.
4. List the major classes of drugs used in asthma and COPD.
5. Describe the mechanisms of action of these drug groups.
6. List the major adverse effects of the prototype drugs used in airways disease.
2
Marc Imhotep Cray, M.D.
Learning Objective cont.
7. To provide a global overview of the drugs affecting the respiratory system
as a prerequisite to deeper layered discussions and case-based learning in
subsequent lectures, including:
Classification and class prototype/s
Mechanism of action
Indications (therapeutic use)
Side effects (adverse effects)
Drug-drug interactions and contraindications
Pharmacokinetic properties and drug-disease (patient) interactions
Toxicities and antidotes (or) treatment
3
Marc Imhotep Cray, M.D.
Learning Objectives cont.
8. Histamine and its Antagonists
The physiological and pathophysiological role of histamine
The pharmacology of histamine receptors
The mechanisms of histamine release
The indications, mechanism of action, adverse effects and contraindications
of histamine H1 and H2 receptor antagonists.
4
Marc Imhotep Cray, M.D.
Organization of the Nervous System
CENTRAL
BRAIN & SPINAL CORD NERVOUS
SYSTEM (CNS)
AFFERENT EFFERENT
(Sensory) (Motor)
NERVES NERVES
PERIPHERAL
NERVOUS
EXTEROCEPTORS INTEROCEPTORS SOMATIC AUTONOMIC SYSTEM (PNS)
SMOOTH MUSCLE,
EFFECTOR SKELETAL
CARDIAC MUSCLES
ORGANS MUSCLES
AND GLANDS
VOLUNTARY
INVOLUNTARY
Monosynaptic
Marc Imhotep Cray, M.D. Pre & Post Ganglionic Fiber
Classes of Chemical Messengers
1. Autocrine chemical messengers An autocrine chemical messenger
stimulates the cell that originally secreted it
Examples are those secreted by white blood cells during an infection
o Several types WBCs can stimulate their own replication, so that
total number of white blood cells increases rapidly
8
Marc Imhotep Cray, M.D.
Summary of drugs affecting the respiratory
system
MEDICATION INDICATION
SHORT-ACTING β2 ADRENERGIC AGONISTS
Albuterol PROAIR, PROVENTIL, VENTOLIN Asthma, COPD
Levalbuterol XOPENEX Asthma, COPD
LONG-ACTING β2 ADRENERGIC AGONISTS
Arformoterol BROVANA COPD
Formoterol FORADIL, PERFOROMIST Asthma, COPD
Indacaterol ARCAPTA COPD
Salmeterol SEREVENT Asthma, COPD
9
Marc Imhotep Cray, M.D.
Summary of drugs affecting respiratory
system (2)
MEDICATION INDICATION
INHALED CORTICOSTEROIDS
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
10
Marc Imhotep Cray, M.D.
Summary of drugs affecting respiratory
system (3)
MEDICATION INDICATION
LONG-ACTING β2 ADRENERGIC AGONIST
/CORTICOSTEROID COMBINATION
Formoterol/budesonide SYMBICORT Asthma, COPD
Formoterol/mometasone DULERA Asthma, COPD
Salmeterol/futicasone ADVAIR Asthma, COPD
Vilanterol/futicasone BREO ELLIPTA COPD
SHORT-ACTING ANTICHOLINERGIC
Ipratropium ATROVENT Allergic rhinitis, COPD
LONG-ACTING ANTICHOLINERGIC
Aclidinium bromide TUDORZA PRESSAIR COPD
Tiotropium SPIRIVA COPD
11
Marc Imhotep Cray, M.D.
Summary of drugs affecting respiratory
system (4)
MEDICATION INDICATION
LEUKOTRIENE MODIFIERS
Montelukast SINGULAIR Asthma, Allergic rhinitis
Zafirlukast ACCOLATE Asthma
Zileuton ZYFLO CR Asthma
ANTIHISTAMINES (H1-RECEPTOR BLOCKERS)
Azelastine ASTELIN, ASTEPRO Allergic rhinitis
Cetirizine ZYRTEC Allergic rhinitis
Desloratadine CLARINEX Allergic rhinitis
Fexofenadine ALLEGRA Allergic rhinitis
Loratadine CLARITIN Allergic rhinitis
12
Marc Imhotep Cray, M.D.
Summary of drugs affecting respiratory
system (5)
MEDICATION INDICATION
α-ADRENERGIC AGONISTS
Oxymetazoline AFRIN, DRISTAN Allergic rhinitis
Phenylephrine NEOSYNEPHRINE, SUDAFED PE Allergic rhinitis
Pseudoephedrine SUDAFED Allergic rhinitis
AGENTS FOR COUGH
Benzonatate TESSALON PERLES
Codeine (with guaifenesin) VARIOUS
Dextromethorphan VARIOUS
Dextromethorphan (with guaifenesin) VARIOUS
Guaifenesin VARIOUS
13
Marc Imhotep Cray, M.D.
Summary of drugs affecting respiratory
system (6)
MEDICATION INDICATION
OTHER AGENTS
Cromolyn NASALCROM Asthma, Allergic rhinitis
Omalizumab XOLAIR Asthma
Roflumilast DALIRESP COPD
Theophylline ELIXOPHYLLIN, THEO-24, UNIPHYL Asthma
14
Marc Imhotep Cray, M.D.
Overview
Common respiratory diseases include:
Asthma
chronic obstructive pulmonary disease(COPD includes emphysema
and chronic bronchitis)
acute bronchitis
dyspnea(difficult breathing) and
pneumonia
Drugs for treating respiratory system are used primarily to open bronchial
tubes, either
By reversing effects of histamines (which are released by body when
exposed to substances that cause allergic reactions) or
By relaxing muscle bundles surrounding bronchial tubes
15
Marc Imhotep Cray, M.D.
Overview (2)
Asthma, which involves constriction of pulmonary passages and secretion
of excess mucus, is characterized by
Dyspnea
Coughing and
wheezing
Asthma is precipitated by triggers such as
Allergens
cold air
viral infections
bacterial infections and
Exercise
Anti-IgE antibodies, mast cell degranulation blockers, smooth muscle
relaxants, and antiinflammatory agents are major drug classes used for
asthma
16
Marc Imhotep Cray, M.D.
Overview (3)
Emphysema results from breakdown of alveolar walls, which leads to
reduced alveolar surface area and impaired cellular respiration and gas
exchange
Acute bronchitis results from inflammation of bronchial passages and has
causes similar to those of asthma
Chronic bronchitis is characterized by persistent production of excess
mucus in bronchial tubes
Cough, shortness of breath, and lung damage are typical of chronic
bronchitis
Medications for COPD include short-acting β2 agonists and other
bronchodilators
Pneumonia is an acute lung inflammation that results in collapse of lung
tissue and can be treated with antibiotics only when cause is bacterial
17
Marc Imhotep Cray, M.D.
Respiration: Introduction to
Physiology and Pathology
18
Marc Imhotep Cray, M.D.
Respiration Overview
Respiration means ventilation, or breathing
2 phases of breathing are inspiration (inhalation) and expiration (exhalation)
21
Marc Imhotep Cray, M.D.
Allergy
Term allergy, from Greek allos (altered state) and ergon
(reactivity), was first used to describe patients who had
reactions caused by effect of external factors, or allergens, on
body’s immune system
Often defined as hypersensitive reactions of immune system
to substances (allergens) that are usually innocuous in most
people food, animal dander, pollen, bee stings, mold,
ragweed, and drugs
22
Marc Imhotep Cray, M.D.
Allergy (2)
Allergic person’s immune system recognizes something as foreign
mounts a specific reaction to identify allergen and destroy it via
inflammation
Thus, a sensitivity to a material that causes a symptom is allergic only
if it has an identifiable mechanism
23
Marc Imhotep Cray, M.D.
Mechanism of Type 1 (Immediate) Hypersensitivity
24
Marc Imhotep Cray, M.D.
Leukocyte Function
Humans have a special immune system to combat infectious and toxic
agents (eg, bacteria and viruses)
Major cells involved in defense against foreign substances are leukocytes
(WBCs)
Like all blood cells synthesized in bone marrow
26
Marc Imhotep Cray, M.D.
Leukocyte Function (3)
27
Marc Imhotep Cray, M.D.
Leukocyte Function (4)
28
Marc Imhotep Cray, M.D.
Allergic Rhinitis
Allergic rhinitis (hay fever), an inflammation or irritation of mucous
membranes lining nose initiated when allergens cause body to defend
itself by producing antibodies
allergen-antibody combination prompts histamine release and allergic
response
Symptoms are
o sneezing
o stuffy or runny nose
o itchy eyes
o noisy breathing
o chronic fatigue
o poor appetite and
o nausea
seasonal disorder is caused by pollen and normally wanes during winter
perennial disorder occurs year-round and is caused by indoor allergens(eg,
animal dander, mold spores, dust mites)
29
Marc Imhotep Cray, M.D.
Allergic Rhinitis (2)
Treatments are:
Antihistamines (H1 antagonist) (Treatment of choice; blocks histamine
action but can cause drowsiness)
o Diphenhydramine (1st Gen.), Loratadine (2nd Gen.= less sedation)
o See: Histamine and Antihistamines in Autocoids, Ergots, Anti-inflammatory and
Immunosuppressive Agents Notes
Nasal decongestants (relieve nasal stuffiness but can increase histamine
release and worsen congestion)
o Short-acting α-adrenergic agonists, such as phenylephrine, constrict dilated
arterioles in nasal mucosa and reduce airway resistance
o Longer-acting oxymetazoline
corticosteroids (desensitize cellular response to histamine and
minimize allergic reaction) and
cromolyn sodium (inhibits histamine release, which reduces or stops
allergic response)
30
Marc Imhotep Cray, M.D.
General Management Principles for Allergic Rhinitis
31
Marc Imhotep Cray, M.D.
Asthma
Asthma is a chronic disease characterized by hyperresponsive
airways, affecting over 25 million patients in U.S , and resulting in 2
million emergency room visits and 500,000 hospitalizations annually.
32
Marc Imhotep Cray, M.D.
Introduction to Asthma
Bronchial asthma, known simply as asthma, is a chronic lung
disease characterized by inflammation and obstruction of lower
airways
Affects approximately 10% of the US population, or 25 million
people
Most common symptoms are
o acute constriction of bronchial smooth muscle
o cough
o chest tightness High-Yield Tip: Chronic cough in a young
o wheezing and adult, particularly a cough that worsens at
night and is associated with dyspnea and
o rapid breathing chest tightness, is classic for asthma.
33
Marc Imhotep Cray, M.D.
Types of Asthma
Older classification: Extrinsic and Intrinsic Asthma
Nonallergic asthma
o Epidemiology: Occurs more frequently in adults
o Mechanism of nonallergic asthma: Not type I hypersensitivity
reaction; IgE levels are normal
o Causes: Exercise, cold air, drugs, gastroesophageal reflux, viral
infections 35
Marc Imhotep Cray, M.D.
Clinical presentation of asthma
Symptoms:
Classic triad is persistent wheezing, chronic episodic dyspnea,
and chronic nonproductive cough
Symptoms may be worse, or only present at night, due to
physiologic drop in cortisol secretion
Night-time cough, which may be only symptom, is a classic
symptom of asthma
Dark rings under the eyes (“allergic shiners”) and a dark
transverse crease on nose (“allergic salute”) are often seen,
especially in children
Status asthmaticus is a prolonged asthmatic attack, which can be
fatal Otherwise deaths caused by asthma are infrequent
36
Marc Imhotep Cray, M.D.
Clinical presentation of asthma (2)
Laboratory studies:
Low peak expiratory flow (PEF)
38
Marc Imhotep Cray, M.D.
Extrinsic and Intrinsic Asthma
Pharmacotherapy of asthma depends on understanding disease pathogenesis
extrinsic (allergic, type I) or intrinsic (nonallergic, type II) asthma
In immunologic, or antigen challenge, model IgE antibodies produced by
airway mucosa mast cells mediate asthma
Intrinsic asthma develops later in life, has unclear causes, is associated with
a worse prognosis, and is less responsive to treatment than extrinsic asthma
40
Marc Imhotep Cray, M.D.
Extrinsic Allergic Asthma:
Clinical Features
Features common to both extrinsic
allergic and intrinsic asthma:
respiratory distress
dyspnea
wheezing
flushing
cyanosis
cough
flaring of alae
use of accessory respiratory muscles
apprehension
tachycardia
perspiration
hyperresonance
distant breath sounds and rhonchi
eosinophilia
41
Marc Imhotep Cray, M.D.
Intrinsic Asthma:
Clinical Features
Features common to both extrinsic
allergic and intrinsic asthma:
respiratory distress
dyspnea
wheezing
flushing
cyanosis
cough
flaring of alae
use of accessory respiratory muscles
apprehension
tachycardia
perspiration
hyperresonance
distant breath sounds and rhonchi
eosinophilia
42
Marc Imhotep Cray, M.D.
Asthma Pharmacotherapy
Major classes of drugs for asthma:
I. Anti-lgE Antibodies
II. Mast Cell Degranulation Blockers
III. Bronchodilators
IV. Methylxanthine
V. β-Adrenergic Agonists:
o Nonselective
o Selective
VI. Antimuscurinic Antagonists
VII. Anti-inflammatory Agents:
o Corticosteroids
o Leukotriene Antagonists
43
Marc Imhotep Cray, M.D.
Asthma
Pharmacotherapy
Capsule
44
Marc Imhotep Cray, M.D.
Asthma Pharmacotherapy (2)
When exposure to allergens cannot be avoided, drug therapy is needed
Major goals being to reverse asthmatic symptoms and prevent recurrent
episodes by disrupting actions of endogenous agents that worsen
bronchospasm and inflammation
45
Marc Imhotep Cray, M.D.
Asthma Pharmacotherapy (3)
Now, antiinflammatory agents are first-line therapy [(Inhaled
corticosteroids (ICS)] for patients who have more than occasional
symptoms
46
Marc Imhotep Cray, M.D.
Guidelines for Treatment of Asthma
Classification Bronchoconstrictive Results of Peak Flow Long-term Quick Relief of
Episodes or Spirometry Control Symptoms
Intermittent Less than 2 days per Near normal* No daily Short-acting β2
week medication agonist
Mild More than 2 days per Near normal* Low-dose ICS Short-acting β2
persistent week, not daily agonist
Moderate Daily 60% to 80% of normal Low-dose ICS + Short-acting β2
persistent LABA agonist
OR Med-dose
ICS
Severe Continual Less than 60% of Med-dose ICS + Short-acting β2
persistent normal LABA OR High- agonist
dose ICS + LABA
ICS = inhaled corticosteroid. LABA = long-acting β2 agonist. *Eighty percent or more of predicted function.
Redrawn from: Whalen K. Lippincott Illustrated Reviews: Pharmacology Sixth Ed., 2015.
N.B. In all asthmatic patients, quick relief (“rescue” therapy) is provided by a SABA as needed for
symptoms.
Marc Imhotep Cray, M.D. 47
I. Anti-lgE Antibodies
One of the more novel therapies is use of anti-IgE antibodies
In theory, drugs acting as anti-IgE antibodies would prevent IgE binding to
mast cell surfaces
48
Marc Imhotep Cray, M.D.
Immunologic basis of anti-IgE antibodies MOA
49
Marc Imhotep Cray, M.D. Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Saunders, 2014. Figure 7-9
Anti-lgE Antibodies (2)
Most notable anti-IgE antibody, omalizumab, is a recombinant
humanized monoclonal antibody to human immunoglobulin E
(IgE)
By binding to circulating IgE in blood, omalizumab blocks
release of inflammatory mediators by keeping IgE from binding
to mast cells and basophils
Reduction in surface-bound IgE limits release of mediators of
allergic response
Indicated for treatment of moderate to severe persistent asthma
in patients who are poorly controlled with conventional therapy
50
Marc Imhotep Cray, M.D.
Anti-lgE Antibodies (3)
Rhumab-E25 (Omalizumab) blocks release of inflammatory mediators by
keeping IgE from binding to mast cells
51
Marc Imhotep Cray, M.D.
Anti-lgE Antibodies (4)
Omalizumab use is limited by high cost, route of administration
(subcutaneous), and adverse effect profile
Adverse effects include:
o serious immediate- or delayed-onset anaphylactic
reactions pose the greatest risk (rare)
o arthralgias
o fever, and rash
o secondary malignancies have been reported
High-Yield Pearl: Anaphylaxis or less severe untoward
immunologic reactions have been reported 24 hours or longer
post administration, so patient should have an epinephrine
autoinjector (self-injector) (prescribed by physician) handy for
at least several days after an omalizumab dose. 52
Marc Imhotep Cray, M.D.
II. Mast Cell Degranulation Blockers
(Chromones)
Cromolyn block mast cell degranulation by suppressing release of
mediators of immediate bronchoconstriction (early response) and
reduce eosinophil recruitment that causes airway inflammation
Does not directly alters smooth muscle tone or reverses
bronchospasm
53
Marc Imhotep Cray, M.D.
Mast Cell Degranulation Blockers (2)
Poorly absorbed, so adverse effects are restricted to deposition
site
Cromolyn (nasal spray) is preferred for young patients
Cromolyn alter Cl− channel function, which
1) on airway neurons underlies cough inhibition
2) on mast cells delays antigen-evoked bronchoconstriction
and
3) on eosinophils prevents inflammatory responses to
antigens
NB: Cromolyn and related compounds do not
posses bronchodilator activity and are therefore
not useful in acute asthma attacks.
Neither cromolyn and nedocromil, is available in
Marc Imhotep Cray, M.D.
the USA. 54
Mast Cell
Degranulation
Blockers MOA
55
Marc Imhotep Cray, M.D. Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Saunders, 2014
III. Bronchodilators (smooth muscle relaxants)
Drugs that expand pulmonary airways (bronchi)-bronchodilators-block
early response by inhibiting immediate bronchoconstriction
These drugs are usually used when a persistent cough and bronchial
constriction are present
Agents are usually given via inhalation, but some can be given orally or
parenterally (intravenous, intramuscular, or subcutaneous route)
56
Marc Imhotep Cray, M.D.
Bronchodilators (2)
Most drugs have a rapid onset of action (within minutes), but
effect usually wanes in 5 to 7 hours (short duration of action)
57
Marc Imhotep Cray, M.D.
G protein linked 2nd messenger mechanism
(β2-Receptor)
Receptor G-Protein Class Major Function
Beta 2 Gs Vasodilation, Bronchodilation, Increase Heart Rate,
Increase Contractility, Increase Lipolysis, Increase
Insulin release, Decrease Uterine Muscle tone
Le T and Bhushan V. First Aid for the USMLE Step 1 2015 (McGraw-Hill 2015)
58
Marc Imhotep Cray, M.D.
59
Marc Imhotep Cray, M.D. Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Saunders, 2014.
IV. Methylxanthines
The methylxanthines theophylline, caffeine, and theobromine, found in
cola, tea, and coffee, are bronchodilators that reduce bronchial smooth
muscle activity by causing increase intracellular cAMP levels
62
Marc Imhotep Cray, M.D. Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Saunders, 2014.
Methylxanthine: Adverse Effects
Methylxanthine doses and bld levels must be closely watched
Low therapeutic index Serum concentration monitoring should be
performed when theophylline is used chronically
Low doses have little effect, if any, whereas high doses can affect central
nervous (seizures), cardiovascular (arrhythmias), skeletal muscle, GI, and
renal system
Theophylline is most selective at sm. mm.; caffeine induces most marked CNS
effects
Even at low to moderate doses, they enhance cortical arousal & alertness &
defer fatigue
In hypersensitive patients, insomnia and nervousness may occur
It has a longer duration of action, lower potency, and greater oral activity
than epinephrine
However, has marked adverse effects, particularly in CNS, and is
rarely administered
68
Marc Imhotep Cray, M.D.
β-Adrenergic Agonists MOA
69
Marc Imhotep Cray, M.D. Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Saunders, 2014.
Selective β-Adrenergic Agonists
Selective β2-adrenoceptor activators are most widely prescribed
sympathomimetic drugs because of their…
β2 selectivity
oral activity
rapid onset and long duration of action (4 hours)
Inhalation route allows greatest local effects with fewest adverse effects
Inhaled agents cause bronchodilation equal to isoproterenol and
persists for 4 hours (metaproterenol, terbutaline, albuterol)
70
Marc Imhotep Cray, M.D.
Selective β-Adrenergic Agonists (2)
Terbutaline, metaproterenol, and albuterol can be given orally as tablets
Terbutaline, the only drug that can be used subcutaneously, is given for
severe asthma attacks or if insensitivity to inhaled agents exists
71
Marc Imhotep Cray, M.D.
Catecholamine Action on α and β Receptors
of Heart and Bronchial Tree
72
Marc Imhotep Cray, M.D. Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Saunders, 2014.
VI. Antimuscarinic Agents (Muscarinic Antagonists)
Acetylcholine mediates its physiologic effects via 2 types of
receptors:
muscarinic and nicotinic
Muscarinic receptors are GPCRs that are densely expressed in
airways
When stimulated AChM receptors cause muscle contraction
leads to narrowing of airways bronchoconstriction
Muscarinic antagonists, or anticholinergics, prevent
acetylcholine from producing smooth muscle contractions &
excess mucus in bronchi
73
Marc Imhotep Cray, M.D.
Antimuscarinic Agents (2)
Ipratropium bromide and atropine are most commonly used
74
Marc Imhotep Cray, M.D.
Antimuscarinic Agents
MOA
75
Marc Imhotep Cray, M.D.
Leukotriene Modulators (LTMs)
Leukotrienes (LTs) are potent
inflammatory mediators
generated from metabolism of
arachidonic acid through the 5-
lipoxygenase (5-LOX) pathway
Le T and Bhushan V. First Aid for the USMLE Step 1 2015 (McGraw-Hill 2015)
78
Marc Imhotep Cray, M.D.
Corticosteroids (2)
Corticosteroids taken regularly have the following effects:
reduce bronchial reactivity
enhance airway quality
decrease severity & frequency of asthma attacks
o However, corticosteroids do not directly relax smooth muscle
o They would be only agents needed to treat asthma if their adverse
effects were not so pronounced
79
Marc Imhotep Cray, M.D.
Corticosteroids: Clinical Uses
Corticosteroids have marked adverse effects on nonrespiratory systems,
so inhalation (maintenance therapy in asthma, via inhaler) or intranasal (in
allergy, as nasal spray) route is preferred
Intranasal corticosteroids relieve stuffy nose, nasal irritation, and other
discomforts
Corticosteroids inhaled by mouth effectively prevent asthma attacks
Regular doses of aerosol agents are smaller than doses used in pill form
Smaller, regular doses reduce side effect risk and may eliminate a need for oral
steroids
Oral prednisone or IV methylprednisone is used only when pts are
insensitive to inhaled drugs or need urgent treatment for severe asthma
attacks
80
Marc Imhotep Cray, M.D.
Corticosteroids:
Clinical Uses (2)
Spacers (chambers) can be
attached to metered-dose
inhalers to reduce velocity &
particle size of drug amount
of drug reaching lungs
maximized, quantity of drug
deposited in mouth is
minimized
82
Marc Imhotep Cray, M.D. Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Saunders, 2014.
Corticosteroids: Adverse Effects
Taking corticosteroids orally (prednisone) and intravenously
(methylprednisone) can cause unwanted side effects
85
Marc Imhotep Cray, M.D. Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Saunders, 2014.
Leukotrienes
Leukotrienes are arachidonic acid derivatives involved in inflammatory
processes including asthma and anaphylaxis
See Eicosanoids in Autocoids, Ergots, Anti-inflammatory Agents, and Immunosuppressive Agents Notes
86
Marc Imhotep Cray, M.D.
Leukotriene (2)
Evidence that inhaled leukotrienes increase bronchial reactivity
and that antigen challenge in sensitized airways augments
leukotriene synthesis supports a role for these mediators in
asthma and a rationale for development of drugs that block
leukotriene or 5-lipoxygenase action
87
Marc Imhotep Cray, M.D.
Newly generated lipid mast cell mediators
depicting sites of action of LTMs
Inhibitory actions of LTMs are shown in red
89
Marc Imhotep Cray, M.D. Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Saunders, 2014.
Anti-inflammatory Agents: Leukotriene
Antagonists
Efforts to develop drugs that disrupt proinflammatory actions of
leukotrienes produced 2 types of drugs:
1) 5-lipoxygenase inhibitors and
2) leukotriene antagonists
These drugs are effective and safe when taken orally, an advantage
compared with inhaled corticosteroids
Strong safety profile and excellent oral activity account for popularity of
leukotriene antagonists for children
92
Marc Imhotep Cray, M.D. Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Saunders, 2014.
Question
A woman who has asthma and is recovering from a myocardial infarction is on
several medications including a baby aspirin a day. She complains of large
bruises on her arms and legs and some fatigue. A standard blood panel reveals
markedly elevated alanine aminotransferase (ALT). Which of the following is
most likely responsible for the increase in liver enzymes?
(A)Heparin
(B)Zileuton
(C)Zafirlukast
(D)Albuterol
(E)Aspirin
93
Marc Imhotep Cray, M.D.
Management of Acute Asthmatic Attack
94
Marc Imhotep Cray, M.D. Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Saunders, 2014.
The National Asthma Education and
Prevention Program 1997 Guidelines (Updated)
RECOMMENDATIONS FOR PHARMACOLOGIC MANAGEMENT OF ASTHMA IN ADULTS AND CHILDREN
OLDER THAN 5
Asthma Severity Symptom Medications
Frequency
Mild intermittent <2 days/week, No regular therapy; short-acting β2 –agonists as needed for
<2 nights/month symptom relief
Mild persistent >2 per week but Low-dose inhaled glucocorticoids. Alternate: cromolyn,
<once per day nedocromil, leukotriene modifier, or sustained release
>2 nights/month theophylline
Moderate Daily, Low- to medium-dose glucocorticoids and long-acting inhaled
persistent >1 night/week β2 -agonists. Alternate: leukotriene modifier or theophylline
Severe persistent Continual during High-dose glucocorticoids and long-acting inhaled β2 -agonist
day, frequent at and (if needed) systemic glucocorticoids. Consider
night omalizumab for allergy sufferers
Ressel GW, Centers for Disease Control and Prevention, National Asthma Education and Prevention Program. NAEPP
updates guidelines for the diagnosis and management of asthma. Am Fam Physician . 2003;68:169–70.
95
Marc Imhotep Cray, M.D.
Respiratory Drugs Summary
Short-Acting β2-Adrenoceptor Agonists
Albuterol Levalbuterol Metaproterenol
Long-Acting β2-Adrenoceptor Agonists
Salmeterol Formoterol Terbutaline
Other Adrenoceptor Agonists for Asthma
Epinephrine Isoproterenol Ephedrine
Methylxanthines
Theophylline
Muscarinic Antagonists
Ipratropium bromide Tiotropium Atropine
Chromones
Cromolyn sodium Nedocromil sodium
Inhaled Glucocorticoids
Beclomethasone Triamcinolone acetate Budesonide Flunisolide Fluticasone
propionate
96
Marc Imhotep Cray, M.D.
Respiratory Drug Summary cont.
Leukotriene Inhibitors
Zafirlukast Montelukast Zileuton
Enzyme Inhibitors
α1-Proteinase inhibitor
Anti-IgE Antibody
Omalizumab
Antihistamines (selected H1-receptor antagonists
Diphenhydramine Loratadine Chlorpheniramine Brompheniramine
α-Adrenoceptor Agonists (selected)
Oxymetazoline Phenylephrine Pseudoephedrine
Antitussives
Codeine Hydrocodone Hydromorphone Dextromethorphan Benzonatate
Expectorants
Guaifenesin
Mucolytics
Acetylcysteine
97
Marc Imhotep Cray, M.D.
98
Marc Imhotep Cray, M.D.
Further study:
eLearning:
Unit 7: Drugs Used In Disorders Of The Respiratory System. In: Digital Guidebook 2015
Integrated Scientific and Clinical Pharmacology
IVMS MedPharm Cloud Folder
Notes:
Drugs Used In Disorders Of The Respiratory System Notes
Autacoids, Ergots, Anti-inflammatory Agents, and Immunosuppressive Agents Notes
o Histamine and its Antagonists
o Eicosanoids
99
Marc Imhotep Cray, M.D.
e-Medicine (Medscape) Articles
Obstructive Airway Diseases
Alpha1-Antitrypsin Deficiency
Asthma
Bronchiectasis
Bronchiolitis
Bronchitis
Chronic Bronchitis
Chronic Obstructive Pulmonary Disease
Emphysema
Status Asthmaticus
100
Marc Imhotep Cray, M.D.