Drugs Affecting the

Respiratory System
Upper and Lower Respiratory Tracts
 Drugs Affecting the
Respiratory System

Antihistamines,
Decongestants,
Antitussives,
and
Expectorants
 Understanding the Common Cold

• Most caused by viral infection

(rhinovirus or influenza virus—the “flu”)
 Understanding the Common Cold

• Virus invades tissues (mucosa) of upper re

spiratory tract, causing upper respiratory i
nfection (URI).
• Excessive mucus production results from t
he inflammatory response to this invasion.
• Fluid drips down the pharynx into the esop
hagus and lower respiratory tract, causing
cold symptoms: sore throat, coughing
 Understanding the Common Cold

• Irritation of nasal mucosa often triggers th

e sneeze reflex.
• Mucosal irritation also causes release of se
veral inflammatory and vasoactive substan
ces, dilating small blood vessels in the nas
al sinuses and causing nasal congestion.
Treatment of the Common Cold
• Involves combined use of antihistamines,
nasal decongestants, antitussives, and exp
ectorants.
• Treatment is SYMPTOMATIC only, not cur
ative.
• Symptomatic treatment does not eliminate
the causative pathogen.
Treatment of the Common Cold
• Difficult to identify whether cause is viral o
r bacterial.
• Treatment is “empiric therapy,” treating th
e most likely cause.
• Antivirals and antibiotics may be used, but
viral or bacterial cause may not be easily i
dentified.
 Antihistamines
Drugs that directly compete with histamine
for specific receptor sites.
• Two histamine receptors:
– H1 histamine-1
– H2 histamine-2
 Antihistamines
H2 Blockers or H2 Antagonists
– Used to reduce gastric acid in PUD
– Examples: cimetidine (Tagamet),
ranitidine (Zantac), or
famotidine (Pepcid)
 Antihistamines
H1 antagonists are commonly referred to
as antihistamines
• Antihistamines have several effects:
– Antihistaminic
– Anticholinergic
– Sedative
Antihistamines: Mechanism of Action

BLOCK action of histamine at the recepto

r sites
• Compete with histamine for binding at unocc
upied receptors.
• CANNOT push histamine off the receptor if al
ready bound.
 Antihistamines: Mechanism of Action
• The binding of H1 blockers to the histamin
e receptors prevents the adverse consequ
ences of histamine stimulation:
– Vasodilation
– Increased gastrointestinal and respiratory secr
etions
– Increased capillary permeability
 Antihistamines: Mechanism of Action
• More effective in preventing the actions of
histamine rather than reversing them
• Should be given early in treatment, before

all the histamine binds to the receptors

 Histamine vs. Antihistamine Effects

Cardiovascular (small blood vessels)

• Histamine effects:
– Dilation and increased permeability
(allowing substances to leak into tissues)
• Antihistamine effects:
– Prevent dilation of blood vessels
– Prevent increased permeability
 Histamine vs. Antihistamine Effects

Smooth Muscle
• Histamine effects:
– Stimulate salivary, gastric, lacrimal, and
bronchial secretions
• Antihistamine effects:
– Prevent salivary, gastric, lacrimal, and
bronchial secretions
Histamine vs. Antihistamine Effects

Immune System
(Release of substances commonly ass
ociated with allergic reactions)
• Histamine effects:
– Mast cells release histamine and other sub
stances, resulting in allergic reactions.
• Antihistamine effect:
– Binds to histamine receptors, thus prevent
ing histamine from causing a response.
Antihistamines: Other Effects
Skin:
• Block capillary permeability, wheal-and-flare
formation, itching
Anticholinergic:
• Drying effect that reduces nasal, salivary, an
d lacrimal gland secretions (runny nose, teari
ng, and itching eyes)
Sedative:
• Some antihistamines cause drowsiness
Antihistamines: Therapeutic Uses

Management of:
• Nasal allergies
• Seasonal or perennial allergic rhinitis
(hay fever)
• Allergic reactions
• Motion sickness
• Sleep disorders
 Antihistamines
10 to 20% of general population is sensit
ive to various environmental allergies.
• Histamine-mediated disorders:
– Allergic rhinitis
(hay fever, mold and dust allergies)
– Anaphylaxis
– Angioneurotic edema
– Drug fevers
– Insect bite reactions
– Urticaria (itching)
Antihistamines: Therapeutic Uses

Also used to relieve symptoms associate

d with the common cold:
• Sneezing, runny nose
• Palliative treatment, not curative
 Antihistamines: Side effects

• Anticholinergic (drying) effects, most co

mmon:
– Dry mouth
– Constipation
– Changes in vision
• Drowsiness
– (Mild drowsiness to deep sleep)
 Antihistamines: Two Types

• 1st generation

• 2nd generation
 Antihistamines:

1st Generation
• Older
• Work both peripherally and centrally
• Have anticholinergic effects, making them more e
ffective than nonsedating agents in some cases
Examples: diphenhydramine (Benadryl)
chlorpheniramine (Chlor-Trimeton)
 Antihistamines:

2nd generation
• Developed to eliminate unwanted side effects,
mainly sedation
• Work peripherally to block the actions of histam
ine; thus, fewer CNS side effects
• Longer duration of action (increases complianc
e)
Examples: fexofenadine
loratadine
 Implications: Antihistamines

• Gather data about the condition or allergic re

action that required treatment; also, assess f
or drug allergies.
• Use with caution in increased intraocular pre
ssure, cardiac or renal disease, hypertension,
asthma, COPD, peptic ulcer disease, BPH, or
pregnancy.
 Implications: Antihistamines

• Instruct patients to report excessive se

dation, confusion, or hypotension.
• Avoid driving or operating heavy machi
nery, and do not consume alcohol or ot
her CNS depressants.
• Do not take these medications with oth
er prescribed or OTC medications witho
ut checking with prescriber.
 Implications: Antihistamines

• Best tolerated when taken with meals

—reduces GI upset.
• If dry mouth occurs, teach patient to p
erform frequent mouth care, chew gu
m, or suck on hard candy (preferably s
ugarless) to ease discomfort.
• Monitor for intended therapeutic effect
s.
Decongestants
 Nasal Congestion

• Excessive nasal secretions

• Inflamed and swollen nasal mucosa

• Primary causes:
– Allergies
– Upper respiratory infections (common col
d)
 Decongestants

Two main types are used:

• Adrenergics (largest group)
• Corticosteroids
 Decongestants

Two dosage forms:

• Oral
• Inhaled/topically applied to the nasal membr
anes
 Oral Decongestants

• Prolonged decongestant effects,

but delayed onset
• Effect less potent than topical
• No rebound congestion
• Examples: phenylephrine
pseudoephedrine
 Topical Nasal Decongestants

• Both adrenergics and steroids

• Prompt onset
• Potent
• Sustained use over several days causes
rebound congestion, making the condit
ion worse
 Topical Nasal Decongestants

• Adrenergics:
ephedrine naphazoline
oxymetazoline phenylephrine
• Intranasal Steroids:
beclomethasone dipropionate
flunisolide
Nasal Decongestants: Mechanism of Act
ion

Site of action: blood vessels surrounding

nasal sinuses
• Adrenergics
– Constrict small blood vessels that supply
URI structures
– As a result, these tissues shrink and nasal se
cretions in the swollen mucous membranes
are better able to drain
– Nasal stuffiness is relieved
Nasal Decongestants: Mechanism of Act
ion

Site of action: blood vessels surrounding

nasal sinuses
• Nasal steroids
– Anti-inflammatory effect
– Work to turn off the immune system cells i
nvolved in the inflammatory response
– Decreased inflammation results in decreased
congestion
– Nasal stuffiness is relieved
Nasal Decongestants: Drug Effects

• Shrink engorged nasal mucous membr

anes
• Relieve nasal stuffiness
 Nasal Decongestants:
Therapeutic Uses

Relief of nasal congestion associated with:

• Acute or chronic rhinitis
• Common cold
• Sinusitis
• Hay fever
• Other allergies
May also be used to reduce swelling of the nasal passag
e and facilitate visualization of the nasal/pharyngeal me
mbranes before surgery or diagnostic procedures.
Nasal Decongestants: Side Effects

Adrenergics Steroids
nervousness local mucosal dryness and irri
tation
insomnia
palpitations
tremors
(systemic effects due to adrenergic stimulation
of the heart, blood vessels, and CNS)
Implications: Nasal Decongestants

• Decongestants may cause hypertensio

n, palpitations, and CNS stimulation—a
void in patients with these conditions.
• Assess for drug allergies.
 Implications: Decongestants

• Patients should avoid caffeine and caff

eine-containing products.
• Report a fever, cough, or other sympto
ms lasting longer than a week.
• Monitor for intended therapeutic effect
s.
Antitussives
 Cough Physiology

Respiratory secretions and foreign object

s are naturally removed by the
• cough reflex
– Induces coughing and expectoration
– Initiated by irritation of sensory receptors i
n the respiratory tract
 Two Basic Types of Cough

• Productive Cough
– Congested, removes excessive secretions
• Nonproductive Cough
– Dry cough
 Coughing

Most of the time, coughing is beneficial

• Removes excessive secretions
• Removes potentially harmful foreign substan
ces
In some situations, coughing can be har
mful, such as after hernia repair surger
y
 Antitussives

Drugs used to stop or reduce coughing

• Opioid and nonopioid (narcotic a
nd non-narcotic)
Used only for NONPRODUCTIVE coughs!
Antitussives: Mechanism of Action

Opioid
• Suppress the cough reflex by direct action o
n the cough center in the medulla.
Examples: codeine, hydrocodone
Antitussives: Mechanism of Action

Nonopioid
• Suppress the cough reflex by numbing the st
retch receptors in the respiratory tract and p
reventing the cough reflex from being stimul
ated.
Examples: benzonatate
dextromethorphan
Antitussives: Therapeutic Uses

• Used to stop the cough reflex when the

cough is nonproductive and/or harmful
 Antitussives: Side Effects

Benzonatate
• Dizziness, headache, sedation

Dextromethorphan
• Dizziness, drowsiness, nausea

Opioids
• Sedation, nausea, vomiting, lightheadedness, consti
pation
Implications: Antitussive Agents

• Perform respiratory and cough assessm

ent, and assess for allergies.
• Instruct patients to avoid driving or op
erating heavy equipment due to possibl
e sedation, drowsiness, or dizziness.
Implications: Antitussive Agents

• Report any of the following symptoms to the

caregiver:
– Cough that lasts more than a week
– A persistent headache
– Fever
– Rash
• Antitussive agents are for NONPRODUCTIVE
coughs.
• Monitor for intended therapeutic effects.
Expectorants
 Expectorants

• Drugs that aid in the expectoration

(removal) of mucus
• Reduce the viscosity of secretions
• Disintegrate and thin secretions
Expectorants: Mechanisms of Action

• Direct stimulation
or
• Reflex stimulation

Final result: thinner mucus that is easier to re

move
Expectorants: Mechanism of Action

Direct stimulation:
• The secretory glands are stimulated directly to i
ncrease their production of respiratory tract flui
ds.
Examples: terpin hydrate, iodine-containing
products such as iodinated glycerol, potassi
um iodide
Expectorants: Mechanism of Action

Reflex stimulation:
• Agent causes irritation of the RI tract.
• Loosening and thinning of respiratory tract s
ecretions occur in response to this irritation.
Examples: guaifenesin, syrup of ipecac
 Expectorants: Drug Effects

• By loosening and thinning sputum and

bronchial secretions, the tendency to c
ough is indirectly diminished.
Expectorants: Therapeutic Uses

Used for the relief of productive coughs a

ssociated with:
Common cold Pertussis
Bronchitis Influenza
Laryngitis Measles
Pharyngitis
Coughs caused by chronic paranasal sinusitis
Expectorants: Common Side Effects

guaifenesin terpin hydrate

Nausea, vomiting Gastric upset
Gastric irritation (Elixir has high alcohol c
ontent)
 Implications: Expectorants

• Expectorants should be used with caution i

n the elderly, or those with asthma or respi
ratory insufficiency.
• Patients taking expectorants should receive
more fluids, if permitted, to help loosen an
d liquefy secretions.
• Report a fever, cough, or other symptoms l
asting longer than a week.
• Monitor for intended therapeutic effects.
MUCOLYTIC
Mucolytics
Acetyl cysteine

M.O.A
 Reduce viscosity of sputum by opening disulfide bond of

mucoprotein

S/E
 Nausea,vomiting,stomatitis,bronchospasm,rhinorrhea
 Dose 200mg
 Administer directly to respiratory tract
 Carbocysteine
 Liquefies viscid sputum
 Other mode of action

S/E
 G.I irritation
 Dose 250-750mg TDS
 Bromhexine
 Synthetic derivative of vasicine (Vasaka)
M.O.A
 Depolymerization of muco polysaccharide
 Increasing lysosomal enzyme activity
 ↑ volume & ↓ viscosity of sputum
S/E
 GIT upset, rhinorrhea,lacrimation
Uses

Useful where mucus plug present(tracheostomy,emphysema,CF)

Dose 30mg TDS
 Ambroxol
❖ Metabolite of bromhexine

❖ Similar properties

❖ Dose 15-30 mg TDS

Dornase alfa
❖ Human recombinant DNAse

❖ Cleaves DNA

❖ Useful in Cystic fibrosis

❖ Given by inhalation

❖ Dose 2.5mg OD
Bronchodilators and Other Respiratory
Agents
Asthmatic Response
 theophylline

Salbutamol Formoterol
Albuterol Salmeterol

Ipratropium
bromide
 Bronchodilators: Xanthine Derivatives

• Plant alkaloids: caffeine, theobromine, an

d theophylline
• Only theophylline is used as a bronchodilat
or
Examples:aminophylline
theophylline
 Bronchodilators: Xanthine Derivatives
Mechanism of Action

• Increase levels of energy-producing cAMP*

• This is done competitively inhibiting phosphodies
terase (PDE), the enzyme that breaks down cAM
P
• Result: decreased cAMP levels, smooth muscle r
elaxation, bronchodilation, and increased airflow
*cAMP = cyclic adenosine monophosphate
 Bronchodilators: Xanthine Derivatives
Drug Effects

• Cause bronchodilation by relaxing smooth muscles of

the airways.
• Result: relief of bronchospasm and greater airflow int
o and out of the lungs.
• Also causes CNS stimulation.
• Also causes cardiovascular stimulation: increased for
ce of contraction and increased HR, resulting in incre
ased cardiac output and increased blood flow to the k
idneys (diuretic effect).
 Bronchodilators: Xanthine Derivatives
Therapeutic Uses

• Dilation of airways in asthmas, chronic bronc

hitis, and emphysema
• Mild to moderate cases of asthma
• Adjunct agent in the management of COPD
• Adjunct therapy for the relief of pulmonary e
dema and paroxysmal nocturnal edema in lef
t-sided heart failure
Bronchodilators: Xanthine Derivatives
Side Effects

• Nausea, vomiting, anorexia

• Gastroesophageal reflux during sleep
• Sinus tachycardia, extrasystole, palpita
tions, ventricular dysrhythmias
• Transient increased urination
Bronchodilators: Beta-Agonists
• Large group, sympathomimetics
• Used during acute phase of asthmatic atta
cks
• Quickly reduce airway constriction and res
tore normal airflow
• Stimulate beta2 adrenergic receptors throu
ghout the lungs
 Bronchodilators: Beta-Agonists Three typ
es

• Nonselective adrenergics
– Stimulate alpha1, beta1 (cardiac), and beta2 (respiratory)
receptors.
Example: epinephrine
• Nonselective beta-adrenergics
– Stimulate both beta1 and beta2 receptors.
Example: isoproterenol
• Selective beta2 drugs
– Stimulate only beta2 receptors
Example: albuterol
Bronchodilators: Beta-Agonists Mechanis
m of Action
• Begins at the specific receptor stimulated
• Ends with the dilation of the airways

Activation of beta2 receptors activate cAMP, whic

h relaxes smooth muscles of the airway and resu
lts
in bronchial dilation and increased airflow.
Bronchodilators: Beta-Agonists Therapeu
tic Uses

• Relief of bronchospasm, bronchial asthma, bronc

hitis, and other pulmonary disease.
• Useful in treatment of acute attacks as well
as prevention.
• Hyperkalemia—stimulates potassium to shift into
the cell.
 Devices Used in Asthma Therapy

• Metered Dose Inhaler (MDI)

– Contains medication and compressed air
– Delivers a specific amount of medication with
each puff
• Spacer
– Used with MDIs to help get medication into th
e lungs instead of depositing on the back of t
he throat
 Devices Used in Asthma Therapy

• Dry powder inhalers

– Starting to replace MDIs
– The patient turns the dial and a capsule full of
powder is punctured
– The patient then inhales the powder
Bronchodilators: Implications
Xanthine Derivatives
• Contraindications: history of PUD or
GI disorders
• Cautious use: cardiac disease
• Timed-release preparations should not
be crushed or chewed (causes gastric i
rritation)
Bronchodilators: Nursing Implications
Xanthine Derivatives

Palpitations Nausea Vomiting

Weakness Dizziness Chest pain
Convulsions
Bronchodilators: Implications
Xanthine Derivatives
• Be aware of drug interactions with: ci
metidine, oral contraceptives, allopurin
ol
• Large amounts of caffeine can have de
leterious effects.
Bronchodilators: Implications
Beta-Agonist Derivatives
• Albuterol, if used too frequently, loses
its beta2-specific actions at larger dose
s.
• As a result, beta1 receptors are stimula
ted, causing nausea, increased anxiety
, palpitations, tremors, and increased
heart rate.
Bronchodilators: Nursing Implications
Beta-Agonist Derivatives

• Patients should take medications exactly

as prescribed, with no omissions or doubl
e doses.
• Patients should report insomnia, jitterines
s, restlessness, palpitations, chest pain, o
r
any change in symptoms.
 Anticholinergics:
Mechanism of Action
• Acetylcholine (ACh) causes bronchial const
riction and narrowing of the airways.
• Anticholinergics bind to the ACh receptors,
preventing ACh from binding.
• Result: bronchoconstriction is prevented, a
irways dilate.
 Anticholinergics
• Ipratropium bromide (Atrovent) is the only
anticholinergic used for respiratory disea
se.
• Slow and prolonged action

• Used to prevent bronchoconstriction

• NOT used for acute asthma exacerbations!
Anticholinergics: Side Effects

Dry mouth or throat Gastrointestinal distres

s
Headache Coughing
Anxiety

No known drug interactions

 Antileukotrienes
• Also called leukotriene receptor antagonist
s (LRTAs)
• New class of asthma medications
• Three subcategories of agents
 Antileukotrienes
Currently available agents:
• montelukast (Singulair)
• zafirlukast (Accolate)
• zileuton (Zyflo)
 Antileukotrienes:
Mechanism of Action
• Leukotrienes are substances released whe
n a trigger, such as cat hair or dust, starts
a series of chemical reactions in the body.
• Leukotrienes cause inflammation, broncho
constriction, and mucus production.
• Result: coughing, wheezing, shortness
of breath
 Antileukotrienes:
Mechanism of Action
• Antileukotriene agents prevent leukotriene
s from attaching to receptors on cells in th
e lungs and in circulation.
• Inflammation in the lungs is blocked, and
asthma symptoms are relieved.
 Antileukotrienes: Drug Effects
By blocking leukotrienes:
• Prevent smooth muscle contraction of the
bronchial airways
• Decrease mucus secretion
• Prevent vascular permeability
• Decrease neutrophil and leukocyte infiltration
to the lungs, preventing inflammation
Antileukotrienes: Therapeutic Uses

• Prophylaxis and chronic treatment of asth

ma in adults and children over age 12
• NOT meant for management of acute asth
matic attacks
• Montelukast is approved for use in childre
n age 2 and older
 Antileukotrienes: Side Effects
zileuton zafirlukast
Headache Headache
Dyspepsia Nausea
Nausea Diarrhea
Dizziness Liver dysfunction
Insomnia
Liver dysfunction

montelukast has fewer side effects

 Corticosteroids

• Anti-inflammatory
• Used for CHRONIC asthma
• Do not relieve symptoms of acute
asthmatic attacks
• Oral or inhaled forms
• Inhaled forms reduce systemic effects
• May take several weeks before full
effects are seen
 Corticosteroids:
Mechanism of Action
• Stabilize membranes of cells that release h
armful bronchoconstricting substances.
• These cells are leukocytes, or white
blood cells.
• Also increase responsiveness of bronchial
smooth muscle to beta-adrenergic stimulat
ion.
 Inhaled Corticosteroids
• beclomethasone dipropionate
(Beclovent, Vanceril)
• triamcinolone acetonide
(Azmacort)
• dexamethasone sodium phosphate (Decad
ron Phosphate Respihaler)
• flunisolide (AeroBid)
Inhaled Corticosteroids: Therapeutic Use
s
• Treatment of bronchospastic disorders
that are not controlled by conventional bro
nchodilators.
• NOT considered first-line agents for mana
gement of acute asthmatic attacks
or status asthmaticus.
 Inhaled Corticosteroids:
Side Effects
• Pharyngeal irritation
• Coughing
• Dry mouth
• Oral fungal infections
Systemic effects are rare because of the low
doses used for inhalation therapy.
 Inhaled Corticosteroids:
Implications
• Contraindicated in patients with psychosis,
fungal infections, AIDS, TB.
• Cautious use in patients with diabetes, gla
ucoma, osteoporosis, PUD, renal disease,
CHF, edema.
• Teach patients to gargle and rinse the mo
uth with water afterward to prevent the d
evelopment of oral fungal infections.
 Inhaled Corticosteroids:
Implications
• Abruptly discontinuing these medications c
an lead to serious problems.
• If discontinuing, should be weaned for a p
eriod of 1 to 2 weeks, and only if recomm
ended by physician.
• REPORT any weight gain of more than 5 p
ounds a week or the occurrence of chest p
ain.
 Mast Cell Stabilizers
• cromolyn (Nasalcrom, Intal)
• nedocromil (Tilade)
 Mast Cell Stabilizers
• Indirect-acting agents that prevent the rel
ease of the various substances that
cause bronchospasm
• Stabilize the cell membranes of
inflammatory cells (mast cells, monocytes,
macrophages), thus preventing release of
harmful cellular contents
• No direct bronchodilator activity
• Used prophylactically
 Mast Cell Stabilizers:
Therapeutic Uses
• Adjuncts to the overall management
of COPD
• Used solely for prophylaxis, NOT for
acute asthma attacks
• Used to prevent exercise-induced broncho
spasm
• Used to prevent bronchospasm associated
with exposure to known precipitating facto
rs, such as cold, dry air or allergens
 Mast Cell Stabilizers: Side Effects

Coughing Taste changes

Sore throat Dizziness
Rhinitis Headache
Bronchospasm
 Mast Cell Stabilizers:
Implications
• For prophylactic use only
• Contraindicated for acute exacerbations
• Not recommended for children under age 5
• Therapeutic effects may not be seen for up t
o 4 weeks
• Teach patients to gargle and rinse the mout
h with water afterward to minimize irritation
to the throat and oral mucosa