Drug used for Respiratory

Tract Disorders

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 Pharmacotherapy of Asthma
 Asthma is an inflammatory condition in which there is
reversible airway obstruction in response to irritant stimuli
that are too weak to affect non asthmatic patient.
 Clinical feature: coughing, shortness of breath with difficulty,
chest tightness & wheezing.
 Characterized by:
1. Reversible air way obstruction
2. Inflammation of air way
3. Bronchial hyperactivity/ Hyper responsiveness to stimuli
such as irritant chemical, cold air, stimulant drug in w/c all
result Broncho-constriction

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 Pathogenesis of Asthma
 Allergen cause production of IgE in mast cell. Then the binding of
allergen with the IgE on the surface of mast cell trigger the release
of mediator stored as well as synthesis of other mediator like
histamine, Leukotriene (LC4, LD4), PD2.
 Early Asthmatic response: due to contraction of bronchial
smooth muscle due to spasmogen. E.g histamine, LB4,
prostaglandin D2( PD2).
 Late Asthmatic response: progressive inflammatory reaction ,
due to inflammatory cell, Eosinophil release cystinyl leukotriene,
interleukin, Eosinophil major basic protein (EMBP), Eosinophil
cationic protein(ECP)

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 Contd...
Airway Obstruction
 Factors that contribute to airway obstruction in asthma
 Contraction of the smooth muscle that surrounds the
airways
 Excessive secretion of mucus and in some, secretion of
thick, tenacious mucus that adheres to the walls of the
airways

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 Airway Inflammation
 Antigens, such as pollen, sensitize individuals by eliciting the
production of antibodies of the IgE type. These antibodies
attach themselves to the surface of mast cells and basophils.
 If the individual is re-exposed to the same antigen days to
months later, the resulting Ag–Ab rxn on lung mast cells
triggers the release of histamine and the cysteinyl
leukotrienes, chemotactic mediators (such as leukotriene B4
and cytokines).
Cont,,,,,,
 Regulation of airway muscle, blood vessels and glands
 The parasympathetic nerves mediate bronchial constriction
and mucus secretion (M3-mediated)

 Circulating adrenaline acts on β2-adrenoceptors to relax

airway smooth muscle.
 Main neurotransmitter causing relaxation of airway smooth
muscle is thought to be nitric oxide.
 Types of Asthma
1. Asthma associated with specific allergic reaction
 Are extrinsic/ classical, the commonest type of asthma.
 Occur in patient who develop allergy to inhaled antigenic
substance.
 Allergen avoidance is relevant to manage this type of asthma.
2. Asthma not associated with known allergy
 Intrinsic/ less common
 Caused by chronic or recurrent respiratory infection, emotional
upset, exercise, & cold air stimulate bronchial spasm
 Patient experience wheezing, breathlessness in the absence of
allergen.
 Allergen avoidance have no value in the management.

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 Cont….

• In both type of asthma there is airway inflammation. Once asthma

attack established it triggered by various stimuli such as viral
infection, exercise, atmospheric pollutant.
Acute sever asthma(status Asthmatics)
 Is not easily reversed, cause hypoxemia
 Require hospitalization, oxygen therapy.

Exercise induced Asthma

 Some patient develop wheeze within few minutes of exercise similar
response occur during cold air.
 It appear due to air way drying.

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 Drug used in Asthma
• Drugs used in the treatment of bronchial asthma can be
grouped into three main categories:
1. Bronchodilators
2. Anti-inflammatory agents: corticosteroids
3. Mast Cell Stabilizers : Chromones

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Strategies for asthma management
 Avoid allergen exposure
 Reduce amount of IgE production bound to mast cell( Anti IgE).

 Prevent mast cell degranulation( cromolyn, nedocromolyn.

 Block the action of release mediator( Leukotriene receptor
antagonist).
 Inhibit the effect of Acetylcholine ( Muscarinic antagonist)

 Direct relax air way smooth muscle( symptomatic agent).

 Anti inflammatory agent( Inhaled corticosteroid)

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 1. Bronchodilators
A. -agonists (sympathomimetic agents)
MOA:- stimulation of B2- receptor in the bronchial smooth
muscle cell activate Adenyl cyclase w/c increase cytosolic
cAMP .

The increase cytosolic cAMP result:

 relaxation of Bronchial smooth muscle.
 inhibit the release of inflammatory mediator in
inflammatory cell .

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  -agonist…….

• Non-selective -agonists
– Epinephrine, ephedrine, isoprotenerol
• Selective 2-agonists
– Salbutamol (albuterol), pirbuterol, terbutaline,
metaproterenol, salmeterol, formaterol and etc
Short acting Long acting
B2- agonist B2-agonist

terbutaline
B2- agonist salmeterol
Albuterol/
Short Long Salbutamol
acting acting formoterol

Metaproterenol
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 2- Selective agonists
– They are largely replace non-selective 2- agonists

– are available as inhaled & oral administration

– they have a shorter or longer duration of action

– They are the most widely used sympathomimetic
– Commonly used drugs both by oral and inhalation are
Salbutamol, terbutaline, metaproterenol, pirbuterol and
bitolterol
– Salmeterol and formeterol are new generation, long acting
2- selective agonists (with DOA 12 hrs or more)
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 Short Acting B2- agonist
 Have rapid onset of action within 5 minute, max effect 30 min.
 Used for acute Tt of Bronchospasm, most of them are
inhalational, some are oral( Albuterol, Metaproterenol).
 Have short duration of action (3-5 hr).
 used only for symptomatic relief of asthma
 Inhalation drugs has rapid onset of bronchodialation (1-5
min) which lasts for about 2 to 6 hours.
 Are the preferred treatment for rapid symptomatic relief of
dyspnea associated with asthmatic bronchoconstriction.
 Used as required base (PRN)
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Long Acting B2 agonist

• Have slow onset of action but longer duration of action

• Their high lipophilicity result extended(longer) effect.

• Given regularly (BID), as adjunctive therapy in patients whose

Asthma controlled inadequately by Glucocorticoid.

– with inhaled corticosteroids to improve asthma control

• Delivery of adreno-receptor agonists through inhalation results in

the greatest local effect on airway smooth muscle with least
systemic toxicity
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 • Contraindications:

– Sympathomimetics are contraindicated in patients with

known hypersensitivity to the drugs
• Precautions:
– They should be used cautiously in patients with
hyperthyroidism, glaucoma, diabetes, pregnancy.

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 B. Methylxanthines
• The three important methylxanthines are theophylline,
theobromine, and caffeine
• Of the three natural xanthines agents

– Theophylline is most selective in its smooth muscle effect

– Caffeine has the most marked central effect

 Theophylline: Not frequently used nowadays, due to the greater

effectiveness of 2-agonists and glucocorticoids.

 Its lower cost is the main reason behind its use in some settings.

 The theophylline preparation most commonly used for therapeutic

purposes is Aminophylline (theophylline plus ethylenediamine)
 Cont…..
MOA: inhibit phosphodiesterase enzyme( PDE) result cytosolic
level of cAMP & cGMP cause
– relaxation of bronchial smooth muscle,

– Cardiac stimulation,
– Decreased release of inflammatory mediators from mast cells
• They competitively inhibit the action of adenosine on adenosine
(A1 and A2) receptors
– Which cause contraction of isolated airway smooth muscle
and to provoke histamine release from airway mast cells
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Pharmacological effects
 On GIT : Stimulation of secretion of both gastric acid and
digestive enzymes
 Effects on kidney(Weak diuretics) :-Increased glomerular
filtration and Reduced tubular sodium reabsorption
 Effects on Smooth Muscle : Bronchodilation:
Pharmacokinetics
 Most preparations are well absorbed from the GIT and are
metabolized by liver
 Doses should be decreased in cases of liver disease and
heart failure 19
Adverse Effects:
It has a narrow therapeutic window
 5–20 mg/L is associated with improvement in pulmonary
function ,
 15 mg/L: N,V,A, abdominal discomfort, headache, and anxiety
in some patients and become common at concentrations
greater than 20 mg/L.
 Higher levels (> 40 mg/L) may cause seizures or arrhythmias

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C. Muscarinic Receptor Antagonists
• Mechanism of Action
– Muscarinic antagonist competitively inhibit the effect of
ACh at muscarinic receptors –block
• the contraction of air way smooth muscle and
• the increased secretion of mucus that occurs in response
to vagal activity
– E.g. Atropine sulphate
– Systemic adverse effects as a result of rapid absorption
include:
• urinary retention; tachycardia; loss of accommodation
and agitation; and, other local effects like excessive
dryness of mouth →this limits the quantity of atropine
used
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• Ipratropium bromide is poorly absorbed and does not readily
enter the CNS
• Antimuscarinic antagonist drugs appear to be slightly less
effective than - agonists agents
– But the addition of ipratropium enhances the bronchodilation
produced by nebulized   albuterol in acute severe asthma
• The anti-muscarinic agents appear to be of significant value in
chronic OPD – perhaps more than asthma
• These agents are useful as alternative therapies for patients
intolerant of - agonists
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2. Anti-inflammatory agents: Corticosteroids

: Available in oral, parenteral & inhalational

MOA: 1. Inhibition of Eicosanoid synthesis.
2. inhibition of release of inflammatory mediator.
 Used both for treatment and prophylactic purposes
 Inhaled corticosteroid are not curative that’s way
manifestation of Asthma return after some week of treatment.
• Effects on airway
– Decreases bronchial reactivity
– Increases airway caliber/width
– Decreases frequency of asthma exacerbation and severity
of symptoms
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 Cont…..

• The commonly used corticosteroids are: hydrocortisone;

prednisolone; beclomethasone; triamcinolone; and, etc.
• The drugs can be taken by inhalation as aerosol, oral, or an IV
administration
• Oral corticosteroids such as prednisone and methylprednisolone
lower swelling in airways.
• Because of severe ADR, oral and parenteral corticosteroids are
reserved for patient who need urgent treatment
• Aerosol treatment is the most effective way to decrease the
systemic adverse effect
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 Cont……
 Inhaled corticosteroid are 1st choice in any degree of Asthma(mild,
moderate & sever).
 Systemic corticosteroid are used for short term for Asthma
exacerbation that don’t respond to B2- agonist & Aerosol
Corticosteroid.
 For patient with sever symptom & air flow obstruction, initial
treatment with inhaled & oral corticosteroid treatment is
appropriate ,
 when it improved discontinue oral dose in tapering way.
 Abrupt discontinuation should be discouraged because of the fear
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Clinical uses in bronchial asthma
• Urgent treatment of severe asthma not improved with bronchodilator
– IV, inhalation or oral
• Nocturnal asthma prevention
– Oral or inhalation
• Chronic asthma
– Regular aerosol corticosteroids
Side Effects:
– Osteoporosis - bone loss

– Sodium retention and hypertension (B/C of mineralocorticosteroids)

– Impairment of growth in children

– Susceptibility to infection like oral candidiasis, tuberculosis

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3. MAST CELL STABILIZERS
e.g. Cromolyn sodium and Nedocromil sodium
Mechanism of action
– Inhibit(Stabilize) mast cell degranulation then prevent
release of inflammatory mediator.
– It has no role once mediator is released and is used for casual
prophylaxis
– Poorly absorbed (administered by inhalation so side effects
are minimal, making them particularly useful in treating
children.
Clinical uses
– Exercise & antigen induced asthma, Occupational asthma
Side effects -
– Throat irritation, cough, dryness of mouth, chest tightness
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 Leukotriene(L) Inhibiter
Leukotriene Inhibiter L-synthesis Inhibiter
• inhibit 5-lipooxygenase. eg. Zeliuton
• Their effect on inflammation < corticosteroid
L-Receptor Inhibiter
• Have better oral administration. eg. Zafirlukast,
• Used for Aspirin induced Asthma Montelukast
Biologics( Anti-Ig E) :prevent airway inflammation.
– include benralizumab, dupilumab, mepolizumab omalizumab
and reslizumab.
 Indicated for patient > 12 yrs with allergies & moderate to sever
Persistent Asthma e.g. Nasal & food allergy

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Classification Bronchoco Long term control Quick relief
nstriction of Symptom
episodes

Mild < 2 per No daily medication Short acting

intermittent week B2- agonist

Mild persistent > 2 per Low dose inhaled Short acting

week corticosteroid(ICS) B2- agonist

Moderate Daily Low to moderate Short acting

persistent dose ICS) & long B2- agonist
actin B2- agonist

Sever persistent continual High dose ICS) & Short acting

long actin B2- B2- agonist
agonist
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TREATMENT OF STATUS ASTHMATICS
Status asthmatics
 This is a very severe and sustained attack of asthma which
fails to respond to treatment with usual measures
 Management includes:
– Administration of oxygen
– Frequent or continuous administration of aerosolized β2-
agonists like salbutamol
– Systemic corticosteroid like methyl prednisolone or
hydrocortisone IV
– Aminophylline IV infusion
– IV fluid to avoid dehydration
– Antibiotics in the presence of evidence of infection
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 BRONCHITIS
• Bronchitis & bronchiolitis are inflammatory conditions of
the large & small elements of the tracheo-bronchial tree
respectively.
• It is classified as acute or chronic.
• Acute bronchitis occurs in individuals of all ages, whereas
chronic bronchitis primarily affects adults.
• Bronchiolitis is a disease of infancy.
Acute bronchitis.
Clinical Presentation
• Cough is the hallmark of acute bronchitis and occurs
early.
– Cough persisting >5 days to weeks
– Initially is nonproductive but then progresses,
yielding mucopurulent sputum.
– Coryza, sore throat, malaise, headache
– Fever rarely >39°C
 Etiology
Cause: Cold, damp climates and irritating substances
(e.g., air pollution, cigarette smoke) may precipitate
attacks.
• Respiratory viruses are the most common infectious
agents associated with acute bronchitis.
• The common cold viruses (rhinovirus and corona virus)
and LRT pathogens (influenza virus and adenovirus)
• Mycoplasma pneumoniae & Chlamydia pneumoniae
 Cont…..

• Bacteria, including Streptococcus pneumoniae,

Streptococcus species, Staphylococcus species, and
Haemophilus species, may be isolated from throat or
sputum culture
• Although a primary bacterial etiology for acute
bronchitis appears rare, secondary bacterial infection
may be involved.
TREATMENT
Acute Bronchitis
• Acute bronchitis almost always is self-limiting.
• The goals of therapy
– provide comfort to the patient and,
– in severe case, to treat associated dehydration and
respiratory compromise.
• Treatment of acute bronchitis is symptomatic & supportive.
• Get plenty of rest
• encouraged Patients to drink fluids to prevent dehydration
and to decrease the viscosity of respiratory secretions.
• Avoid lung irritant: don’t smoke, wear mask
• Use humidifier: warm, moist air relieve cough and loosen
mucus in airway
 PHARMACOLOGIC THERAPY
• Most case of bronchitis is due to viral infection so
antibiotics are not effective. However if bacterial infection
suspected Antibiotics given (Azithromycin, Amoxicillin,
Augmentin)
• In some cases other medication recommended like:
• Mild analgesic–antipyretic therapy often is helpful in
relieving the associated lethargy, malaise, and fever.
– Aspirin, NSAID or acetaminophen (Paracetamol)
– In children, aspirin should be avoided and acetaminophen
used as the preferred agent – due to Reye syndrome
• Antitussives should be used cautiously when the cough is
productive.
 Cont…..
• Cough suppressant not recommended for routine use : if
cough is bother the patient
– (for persistent, mild cough, dextromethorphan & for
more severe coughs may require intermittent codeine).
• If the patient have allergy, Asthma or COPD:
– Anti-allergy drug (Anti-histamines
– Bronchodilator (inhaler
 CHRONIC BRONCHITIS
• It is a disease of the bronchi that is manifested by cough
and excessive sputum expectoration
• Occurs on most days of the week for a min of 3 months/
year for at least 2 consecutive years that is unrelated to
other pulmonary or cardiac disease.
• Cause: Similar to acute bronchitis
• The most prominent include
– Cigarette smoking (predominant factor) ,
– Exposure to occupational dusts, fumes, & environmental
pollution
– Host factors (e.g. genetic factors )and
– Bacterial [and possibly viral] infections).
 TREATMENT
The goals of therapy
• to reduce the severity of chronic symptoms
• to ameliorate acute exacerbations and achieve
prolonged infection-free intervals.
GENERAL APPROACH TO TREATMENT
• reduce the patient’s exposure to known bronchial irritants
• humidification of inspired air may promote the hydration
(liquefaction) of tenacious secretions
• Mucolytics in patients with moderate or severe COPD
who are not receiving inhaled corticosteroids.
 PHARMACOLOGIC THERAPY
• β2-agonist bronchodilators (e.g., as albuterol aerosol)
should be considered
Baseline Status Criteria or Risk Usual Pathogens Initial Treatment Options
Factors

Class I No underlying Usually a virus 1. None unless symptoms

Acute structural disease persist
tracheobronchitis 2. Amoxicillin; Augmentin;
macrolide- if bacterial
infection is suspected
Class II increased H. influenzae 1. Same as Class I, no. 2, or a
Chronic sputum volume Haemophilus fluoroquinolone if
bronchitis and purulence species, Moraxella prevalence of H. influenzae
catarrhalis, Strept. resistance to amoxicillin is
pneumoniae >20%
(β-lactam resistance 2. Fluoroquinolone,
possible) amoxicillin–clavulanate,
azithromycin, or
cotrimoxazole
Baseline Status Criteria or Risk Usual Pathogens Initial Treatment Options
Factors
Class-III increased Same as class 1. Fluoroquinolone
Chronic sputum II; also E. coli, 2. Extended spectrum
bronchitis volume and Klebsiella, cephalosporin,
with purulence, Enterobacter amoxicillin–
complication advanced species, clavulanate,
s age, or P.aeruginosa or azithromycin
significant (β-lactam
comorbidity resistance
common)
Class IV Same as for Same as class 1. Oral or parenteral
Chronic class III plus III fluoroquinolone,
bronchial yearlong carbapenem, or
infection production of extended spectrum
purulent cephalosporin
sputum
 Drug for Upper Respiratory tract
infection
Pharyngitis
• is an acute infection of the oropharynx or
nasopharynx.
• Viruses cause the majority of acute pharyngitis
– include rhinovirus (20%), coronavirus (≥5%),
adenovirus (5%), herpes simplex (4%), influenza
virus (2%)
• A bacterial etiology for acute pharyngitis is rare
– group A β-hemolytic Streptococcus, or S.
pyogenes, is the primary bacterial cause
TREATMENT
• The goals of treatment
– are to improve clinical signs and symptoms,
– minimize adverse drug reactions,
– prevent transmission to close contacts, and prevent acute
rheumatic fever and suppurative complications
• Viral pharyngitis goes away on its own with salt water
gargles,
• pain relievers and extra fluids help alleviate the symptoms.
• Bacterial pharyngitis is treated with antibiotics; and fungal
pharyngitis, with antifungal medications
 Tonsillitis
• Tonsils are the two lymph nodes located on each side of the back of your
throat.
• They function as a defense mechanism and help prevent our body from
getting an infection.
• When tonsils become infected, the condition is called tonsillitis.
• There are 3 types of tonsillitis: acute, chronic, and recurrent.
Possible symptoms of tonsillitis include:
• a very sore throat, difficulty or pain while swallowing
• a scratchy-sounding voice, fever, chills, earaches
• Stomachaches, headaches, a stiff neck
• jaw and neck tenderness from swollen lymph nodes
• tonsils that appear red and swollen
• tonsils that have white or yellow spots
• In very young children, you may also notice increased irritability, poor
appetite, or excessive drooling
 Cont,,,,,
• Acute tonsillitis: common in children.
•  last around 10 days or less.
• If symptoms last longer, or if tonsillitis comes back
multiple times during the year, it may be chronic or
recurrent tonsillitis.
• Acute tonsillitis will improve with home treatments, but in
some cases may require other treatments, like antibiotics.
Causes
• Tonsillitis can be caused by a virus, such as the 
common cold, or by a bacterial infection, such as strep
throat.
• Viral tonsillitis: rhinovirus, EBV, hepatitis A…
 Cont….
• Antibiotics won’t work for viruses, but symptoms treated
by staying hydrated, taking OTC Analgesucs, and
resting to help body heal.
Tonsillitis treatment
• A mild case of tonsillitis doesn’t necessarily require
treatment, especially if a virus, such as a cold, causes it.
• Treatments for more severe cases of tonsillitis may
include antibiotics or a tonsillectomy.
• If a person becomes dehydrated they may need IV fluids.
• Pain medicines to relieve the sore throat can also help
while the throat is healing.
 Cont…..
• Tonsillectomy: only recommended for people
– who experience chronic or recurrent tonsillitis, or
– tonsillitis causes complications or symptoms don’t improve.
Tonsillitis home remedies
• drink plenty of fluids, get lots of rest
• gargle with warm salt water several times a day
• use throat lozenges
• eat frozen foods
• use a humidifier to moisten the air in home
• avoid smoke
• take acetaminophen or ibuprofen to reduce pain and
inflammation
Cont….
• Penicillin taken by mouth for 10 days is the most
common antibiotic treatment prescribed for tonsillitis
caused by group A streptococcus.
•  If the child is allergic to penicillin, use an alternative
antibiotic.
• Azithromycin used for pharyngitis and tonsillitis
 Thanks!

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