Drugs affecting the Respiratory System

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By Linda Self
 Key Terms
1.
2.
3.
4.
5.
6.
Ventilation
Perfusion
Diffusion
Pulmonary Circulation
Surfactant
pneumocytes
 Asthma—inflammation, hyperreactivity,
 and
bronchoconstriction
 GERD may cause
microaspiration/resultant nighttime
cough
 Antiasthma medications can also
exacerbate GERD
 May
be triggered by viruses
 Irritants
 Allergens
 Can develop at any age
 Seen more often in children who are
exposed to airway irritants during
infancy
 Bronchoconstriction
 Inflammation
 Mucosal
edema
 Excessive mucous
 Mast
cells
 Chemical mediators such as histamine,
prostaglandins, acetylcholine, cGMP,
interleukins, leukotrienes are released
when triggered. Mobilization of
eosinophils. All cause movement of fluid
and proteins into tissues.
 Bronchoconstrictive substances
antagonized by cAMP
 Combination
of chronic bronchitis and
emphysema
 Bronchoconstriction and inflammation
are more constant, less reversibility
 Anatomic and physiologic changes occur
over years
 Leads to increasing dyspnea and activity
intolerance
 Bronchodilators
and anti-inflammatories
 Step
1-Mild Intermittent—symptoms 2
days/week or less or 2 nights/month or
less. No daily medication needed; treat
with inhaled beta2 agonist
 Step 2-Mild persistent—symptoms
>2/week but <1x/day or >2
nights/month. In those >5 years old, use
inhaled corticosteroid, leukotriene
modifier, Intal (cromolyn), or sustained
release theophylline
 Step
2—Mild persistent
 Children 5 years and younger—inhaled
corticosteroid by nebulizer of MDI with a
holding chamber. Can also use leukotriene
modifier or Intal by nebulizer
 Step 3—Moderate persistent. Symptoms
daily and > one night per week.
 Older than 5yo—low to med. Dose
corticosteroid and long acting beta 2
agonist. Alternatives p. 714
 Step 3—
 Children
< 5 yo: low dose inhaled
corticosteroid and a long acting beta 2
agonist or medium dose inhaled
corticosteroid
 Step 4—Severe persistent—symptoms
continual during daytime and frequently at
night.
 >5yo—high dose inhaled corticosteroid,
long acting beta 2 agonist; intermittent
admin. of oral corticosteroids
 Step
4—
 Children less than 5 yo—same as for
adults and older children
 Adrenergics—stimulate
beta 2 receptors
in smooth muscle of bronchi and
bronchioles
 Receptors stimulate cAMP
=bronchodilation
 Cardiac stimulation is an adverse effect
of these medications
 Cautious
use in hypertension and cardiac
disease
 Selective beta 2 agonists by inhalation
are drugs of choice
 Epinephrine sc in acute
bronchoconstriction
 Proventil
(albuterol)
 Xopenex (levalbuterol)
 Treatment
of first choice to relieve acute
asthma
 Aerosol or nebulization
 May be given by MDI
 Overuse will diminish their
bronchodilating effects>>>>tolerance
 Foradil
(formoterol) and Serevent
(salmeterol) are long acting beta 2
adrenergic agonists used only for
prophylaxis. Black box warning on
Serevent—use in deteriorating asthma
can be life-threatening
 Alupent (metaproterenol)—intermediate
acting. Useful in exercise induced
asthma, tx acute bronchospasm.
 Brethine
(terbutaline)—selective beta 2
adrenergic agonist that is a long-acting
bronchodilator
 When given subq, loses selectivity
 Also used to decrease premature uterine
contractions during pregnancy
 Block
the action of acetylcholine in
bronchial smooth muscle when given by
inhalation
 Action reduces intracellular guanosine
monophosphate (GMP) which is a
bronchoconstrictive substance
 Atrovent (ipratropium)—caution in BPH,
narrow-angle glaucoma
 Spiriva (tiotropium)
 Theophylline
 Mechanism
of action unclear
 Bronchodilate, inhibit pulmonary edema,
increase action of cilia, strengthen
diaphragmatic contractions, over-all antiinflammatory action
 Increases CO, causes peripheral
vasodilation, mild diuresis, stimulates
CNS
 Contraindicated
in acute gastritis and
PUD
 Second line
 Narrow therapeutic window—therapeutic
range is 5-15 mcg/mLh
 Multiple drug interactions
 Suppress
inflammation by inhibiting
movement of fluid and protein into
tissues; migration and function of
neutrophils and eosinophils, synthesis of
histamine in mast cells, and production of
proinflammatory substances
 Benefits: decreased mucous secretion,
decreased edema and reduced reactivity
 Second
action is to increase the number
and sensitivity of beta 2 adrenergic
receptors
 Can be given PO or IV
 Pulmonary function usually improves
within 6-8 hours
 Continue drugs for 7-10 days
 Fewer
long term side effects if inhaled
 End-stage COPD may become steroid
dependent
 In asthma, systemic steroids generally
are used only temporarily
 Taper high dose oral steroids to avoid
hypothalamic-pituitary axis suppression
 For
inhalation:
 Beclovent—beclomethasone
 Pulmicor—budesonide
 Aerobid—flunisolide
 Flovent—fluticasone
 Azmacort—triamcinolone
 Most inhaled steroids are being
reformulated with HFA
 Systemic
use: prednisone,
methylprednisolone, and hydrocortisone
 In acute, severe asthma—a systemic
corticosteroid may be indicated when
inhaled beta 2 agonists are ineffective
 Leukotrienes
are strong chemical
mediators of bronchoconstriction and
inflammation
 Increase mucous secretion and mucosal
edema
 Formed by the lipoxygenase pathway of
arachidonic acid metabolism in response
to cellular injury
 Are release more slowly than histamine
 Developed
to counteract the effects of
leukotrienes
 Indicated for long term treatment of
asthma in adults and children
 Prevent attacks induced by some
allergens, exercise, cold air,
hyperventilation, irritants and
ASA/NSAIDs
 Not useful in acute attacks
 Injured
cell
 Arachidonic acid

XXXX
 Lipooxygenase
 Leukotrienes

XXXX
 Bronchi, WBCs
 Bronchoconstriction
 Singulair
(montelukast) and Accolate
(zafirlukast) are leukotriene receptor
antagonists
 Can be used in combination with
bronchodilators and corticosteroids
 Less effective than low doses of inhaled
steroids
 Should not be used during lactation
 Can cause HA, nausea, diarrhea, other
 Intal
(cromolyn)
 Tilade (nedocromil)
 Prevent release of bronchoconstrictive
and inflammatory substances when mast
cells are confronted with allergens and
other stimuli
 Prophylaxis only
 Inhalation, nebulizer or MDI, nasal spray
as well
 Xolair
(omalizumab) works by binding to
IgE, blocking receptors on surfaces of
mast cells and basophils
 Prevents release of chemical mediators of
allergic reactions
 Adjunctive therapy
 Can cause life-threatening anaphylaxis
 Histamine
is the first chemical mediator
released in immune and inflammatory
responses
 Concentrated in skin, mucosal surfaces of
eyes, nose, lungs, CNS and GI tract
 Located in mast cells and basophils
 Interacts with histamine receptors on
target organs called H1 and H2
 H1
receptors are located mainly on
smooth muscle cells in blood vessels and
the respiratory and GI tracts
 H1 binding causes: pruritus, flushing,
increased mucous production, increased
permeability of veins—edema,
contraction of smooth muscle in
bronchi>>bronchoconstriction and
cough
 With
H2 receptor stimulation, main
effects are increased secretion of gastric
acid and pepsin, decreased immunologic
and proinflammatory reactions,
increased rate and force of myocardial
contraction
 Are
exaggerated responses by the
immune sysem that produce tissue injury
and possible serious disease
 Allergic reactions may result from
specific antibodies, sensitized T
lymphocytes, or both, formed durng
exposure to an antigen.
 Type
I—immediate hypersensitivity, IgE
induced response triggered by the
interaction of antigen with antigenspecific IgE bound on mast cells
 Anaphylaxis is an example
 Does not occur on first exposure to an
antigen
 Can develop profound vasodilation
resulting in hypotension, laryngeal
edema, bronchoconstriction
 Type
II—IgG or IgM mediated which
generate direct damage to cell surfaces.
Examples include: blood transfusion
reactions, hemolytic disease of
newborns, hypersensitivity reactions to
drugs such as heparin or penicillin
 Type
III is an IgG or IgM mediated
reaction characterized by formation of
antigen-antibody complexes that induce
inflammatory reaction in tissues.
Prototype is Serum Sickness.
 Immune response can occur following
antitoxin administration, pcn or sulfa
drugs
 Delayed
hypersensitivity
 Cell mediated response where sensitized
T lymphocytes react with an antigen to
cause inflammation, release of
lymphokines , direct cytotoxicity or both
 Classic examples are tuberculin test,
contact dermatitis and some graft
rejections
 IgE
mediated
 Inflammation of nasal mucosa caused by
a hypersensitivity reaction to inhaled
allergens
 Presents with itching of throat, eyes and
ears
 Seasonal and perennial
 Can lead to chronic fatigue, difficulty
sleeping, sinus infections, postnasal drip,
cough and headache
 Atrovent
nasal spray
 Beconase (beclomethasone)
 Rhinocort (budesonide)
 Flonase (fluticasone)
 Nasonex (mometasone)
 Nasalcrom (a mast cell stabilizer)
 Type
IV hypersensitivity reaction
 Poison ivy an example
 Usually occurs >24h after re-exposure
 Allergic
food reactions—result from
ingestion of a protein
 Most common food allergy is shellfish,
others include milk, eggs, peanuts
 Allergic drug reactions—unpredictable,
may occur 7-10 days after initial
exposure
 Pseudoallergic drug reactions—
resemble immune responses but do not
produce antibodies, i.e. anaphylactoid
 Inhibit
smooth muscle constriction in
blood vessels and the respiratory and GI
tracts
 Decrease capillary permeability
 Decrease salivation and tear formation
 Act by binding with the histamine
receptor
 Allergic
rhinitis
 Anaphylaxis
 Allergic conjunctivitis
 Drug allergies
 Transfusions of blood products
 Dermatologic conditions
 Nonallergic such as motion sickness,
nausea and vomiting, sleep
 Caution
in pregnancy
 BPH
 Bladder
neck obstruction
 Narrow angle glaucoma
 Bind
to central and peripheral receptors
 Can cause CNS depression or stimulation
 Have substantial anticholinergic effects
Examples:
 Chlor-Trimeton (chlorpheniramine)
 Benadryl (diphenhydramine)
 Vistaril (hydroxyzine)
 Phenergan (promethazine)
 Selective
or nonsedating
 Do not cross blood brain barrier
Examples:
 Astelin (azelastine)
 Allegra (fexofenadine)
 Claritin (loratadine)
 Clarinex (desloratadine)
 Zyrtec
 Xyzal
 Relieve
nasal obstruction and discharge
 Adrenergic
 Rebound nasal swelling called “rhinitis
medicamentosa”
 Afrin
 Sudafed (pseudoephedrine)
 Contraindicated in severe hypertension,
CAD, narrow angle glaucoma, TCAs or
MAOIs
 Suppress
cough by depressing cough
center in medulla or by increasing flow of
saliva
 For dry, hacking, non-productive cough
 Not recommended in children and
adolescents
 Codeine, hydrocodone
 dextromethorphan
 Liquefy
respiratory secretions
 Guiafenesin
 By
inhalation to liquefy mucous
 Mucomyst (acetylcysteine)
 May be used in treating acetaminophen
overdose
 Contain
antihistamine, decongestant and
an analgesic
 Chlorpheniramine, pseudoephedrine,
acetaminophen, dextromethorphan and
guiafenesin
 Decongestants can cause stasis of
secretions
 PM contains antihistamine
 Tamiflu can be used to limit spread of
virus in respiratory tract
1.
2.
3.
4.
5.
6.
7.
8.
Name two beta adrenergic bronchodilators
Name an inhaled steroid
Give an example of a leukotriene modifier
Name a mast cell stabilizer
Name a common infection after frequent
use of an inhaled steroid
Name a first generation H1 receptor
antagonist
Name a second generation H1 receptor
antagonist.
Name an H2 receptor antagonist.
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