Pharmacology of drugs used for

treatment of common diseases

of the Bronchi

Asthma Bronchitis
 Introduction
When a person breathes, the air travels through
the nose or mouth and into the larynx.
From the larynx, air moves into the trachea,
which divides into a left and right bronchus, large tubes that
supply the air to the lungs.
Each bronchus further divides into smaller airways,
called bronchi.
The bronchi continue to divide into bronchioles, which
are the smallest airways of the lungs
Bronchial diseases are those that affect these
airways and result in breathing difficulties.
 Asthma
Asthma is an inflammatory disease of the airways
characterized by episodes of acute
bronchoconstriction causing
shortness of breath, cough, chest tightness, wheezing, and
rapid respiration
The bronchoconstriction results from
1. Contraction of bronchial smooth muscle,
2. Inflammation of the bronchial wall, and
3. Increased mucous secretion
The symptoms of asthma may be effectively
treated by several drugs,
but no agent provides a cure for this obstructive
lung disease.
 Adrenergic agonists
2 agonists are potent bronchodilators that relax
airway smooth muscle.
Most clinically useful 2 agonists have a rapid onset
of action (<30 minutes) and provide relief for 4 to 6
hours
2 Agonists have no anti-inflammatory effects, and
They should never be used as the sole therapeutic
agents for patients with persistent asthma
What is the advantage of dosing via inhalation?
Adverse effects, such as tachycardia and hyperglycemia,
can be minimized
 Adrenergic agonists
Pirbuterol, terbutaline, and albuterol are used for
quick relief
Salmeterol and formoterol are long-acting 2 agonist
bronchodilators
provide bronchodilation for at least 12 hours
analogs of albuterol but differ by having a
lipophilic side chain, increasing the affinity of the
drug for the 2-adrenoceptor
Quiz
Isoprenaline and salbutamol are similar in efficacy
but why we choose salbutamol for asthma???
 Corticosteroids
Inhaled corticosteroids (ICS) are the drugs of first
choice in patients with any degree of persistent
asthma (mild, moderate, or severe)
No other medications are as effective as ICS in the
long-term control of asthma

Inhaled steroids used in the mgt of chronic asthma

Beclomethasone
Flunisolide
Triamcinolone
Fluticasone
Budesonide
 Corticosteroids
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
(eosinophils, macrophages, and T lymphocytes),
reversing mucosal edema, decreasing the
permeability of capillaries, and inhibiting the
release of leukotrienes
 Drugs used to treat respiratory conditions can be
delivered
Topically to the nasal mucosa,
Inhaled into the lungs, or
Given orally or parenterally for systemic
absorption.
Topical delivery methods, such as nasal sprays or
inhalers, are preferred so as to target affected tissues
while minimizing systemic side effects
 Inhalation therapy deposits
asthma medications directly,
but not exclusively, in the
lungs.
Distribution of inhaled drug
between lungs and esophagus
depends on particle size and
efficiency of delivery to lungs.
Most material, approximately
90%, will be swallowed and
absorbed, entering the
systemic circulation.
Some drug also will be
absorbed from the lungs.
Optimal particle size for
deposition in small airways is 1
to 5 m.
The critical determinant of the
delivery of any particulate matter
to the lungs is the size of the
particles
 Leukotriene antagonists
Leukotriene (LT) B4 and the cysteinyl leukotrienes,
LTC4, LTD4, and LTE4, are products of the 5-lipoxygenase
pathway of arachidonic acid metabolism and part of the
inflammatory cascade
Zileuton is a selective and specific inhibitor of 5-
lipoxygenase,
prevent the formation of both LTB4 and the cysteinyl
leukotrienes.
Zafirlukast and montelukast are selective, reversible
inhibitors of the cysteinyl leukotriene-1 receptor
blocking the effects of cysteinyl leukotrienes
 Clinical role
Used for prophylaxis of asthma
They prevent bronchoconstriction and airway
inflammation
Used for chronic maintenance therapy
Not effective in situations where immediate
bronchodilation is required
They should not be used for acute bronchospasm
 Cromolyn and nedocromil
are effective prophylactic agents
That stabilize the membranes of mast cells and
prevent mediator release
Not used for treating acute attacks of asthma
Pre-treatment with cromolyn or nedocromil blocks
allergen-induced and exercise induced
bronchoconstriction
 Cholinergic antagonists
They block the vagally mediated contraction
of airway smooth muscle and mucus
secretion.
Inhaled ipratropium, a quaternary derivative
of atropine, is useful in patients who are
unable to tolerate adrenergic agonists.
 Theophylline
Methylxantine that increase cAMP by inhibiting the
enzyme phosphodiesterase
Results in bronchodilation
narrow therapeutic window,
high side-effect profile,
potential for drug interactions.
Overdose may cause seizures or potentially fatal
arrhythmias.
Theophylline is metabolized in the liver, is a CYP1A2
and 3A4 substrate, and interacts adversely with many
drugs.
 Bronchitis
Bronchitis -is an inflammation of the bronchi.
Caused by irritants, such as cigarette smoke, air
pollution, or infections (bacterial or viral).
The inflammation results in
swelling of the mucous membrane lining the bronchi,
increased mucus production, and
decreased movement of mucus by cilia.
Consequently, the diameter of the bronchi is
decreased, and ventilation is impaired.
Bronchitis can progress to emphysema.
Bronchitis ---STG For General Hosp of Eth
1. For Dry Cough
First line
Dextromethorphan hydrobromide
Alternative
Codeine phosphate
2. For productive cough
Guaifenesin
3. For infection
Antibiotic treatment is indicated when bronchitis is complicated by
bacterial Infections
First line
Amoxicillin
Alternatives
Ampicillin OR
Sulfamethoxazole+trimethoprim OR
Erythomycin OR
Tetracycline
 Antibiotics
When bronchitis is complicated by bacterial
Infections, antibiotics can be used

Classification of antibiotics based on their proposed

mechanism of action
Cell wall synthesis inhibitors
Protein synthesis inhibitors
Plasma membrane-injuring agents
Nucleic acid inhibitors
Metabolic/enzyme inhibitors
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 Aminopenicillins
Have greater activity than pen G against gram-negative
bacteria
Enhanced ability to penetrate the gram-negative outer
membrane
Are inactivated by -lactamases
Are acid resistant & can be used orally
Includes: ampicillin & amoxicillin
Both have good oral bioavailability; ampicillin is also
bioavailable after intramuscular injection

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 Aminopenicillins
Concomitant ingestion of food decreases the
bioavailability of ampicillin but not amoxicillin
Consequently, oral doses of ampicillin should be given
before meals
Ampicillin achieves therapeutic concentrations in the CSF
only during inflammation
Ampicillin is effective treatment for meningitis caused by
Listeria monocytogenes
Other indications for ampicillin include serious infections
like:
Enterococcal endocarditis
Pneumonia caused by -lactamase negative H. influenzae
UTIs, lower respiratory tract infections
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 -Lactamase Inhibitor Combinations
Several formulations combine a -lactam antibiotic
with a -lactamase inhibitor

Clavulanic acid
o It is combined with amoxicillin for oral administration
o AUGMENTIN
o and with ticarcillin for parenteral administrition
o TIMENTIN
Sulbactam
combined with ampicillin for IV or IM use
UNASYN
Tazobactam
It has been combined with piperacillin as a parenteral preparation
ZOSYN
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 Adverse effects of penicillins
Penicillins are remarkably nontoxic & safest of the
antibiotics
Most of the serious adverse effects are due to
hypersensitivity
Allergic reactions include:
Anaphylactic shock, urticaria, pruritus bronchospasm,
angioedema, laryngeal edema, and hypotension
Late onset immune-mediated reactions to -lactam antibiotics
may manifest as eosinophilia, hemolytic anemia, interstitial
nephritis, or serum sickness
All penicillins are cross-sensitizing
In general, patients with a history of allergic reaction to one -
lactam antibiotic should avoid all other -lactam antibiotics
except aztreonam

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 2. Protein synthesis inhibitors
Bacteria have two ribosomal subunits
30S and 50S
The 30S subunit binds mRNA in initiation and
holds growing peptide chain.
The 50S subunit accepts / translocates charged
tRNAs.
are divided into two groups: bacteriostatic and
bactericidal.
Chloramphenicol, macrolides, clindamycin
(Lincosamides), and tetracyclines are
bacteriostatic
Aminoglycosides are bactericidal
 Macrolides
group of antibiotics which have a large lactone ring
to which one or more deoxy sugars are attached.
Includes:
erythromycin ..parent drug
azithromycin & clarithromycin semisynthetic
derivatives
These structural modifications improve acid stability
and tissue penetration and broaden the spectrum of
activity

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 Mechanism of Action

are bacteriostatic agents that inhibit protein synthesis

by binding reversibly to 50S ribosomal subunits of
sensitive microorganisms
Are bacteriostatic but can be bactericidal at higher
concentrations for susceptible microbes
Resistance to Macrolides can occur:
Efflux pumps
Metabolizing enzymes
Modification of the 50s ribosomal subunit

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 Pharmacokinetics
Erythromycin base
is incompletely but adequately absorbed from the upper
small intestine
administered as enteric-coated tablets or as capsules to
prevent inactivation by gastric acid
Food may delay absorption by increases gastric acidity
IV erythromycin related with high incidence of
thrombophlebitis

Clarithromycin
is absorbed rapidly from the GIT after oral administration
first-pass metabolism reduces its bioavailability to 50% to
55% & Can be given with or without food
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 Foliate Antagonists
Folic acid coenzymes:
are required for the synthesis of purines and pyrimidines
(precursors of RNA and DNA) and other compounds
required for cellular growth and replication.
In the absence of folic acid, cells cannot grow or divide.

Sulfonamides and Trimethoprim are inhibitors of folic

acid synthesis

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 Sulfonamides
Are the 1st effective chemotherapeutic agents to be
employed systemically for the prevention and cure of
bacterial infections in humans

Use of sulphonamides was declining due to:

emergence of resistant strains
development of patient allergies and
advent of penicillins

but after the synergistic effect of sulfamethoxazole with

trimetoprim ( co-trimoxazole), there has been renewed
interest with sulfonamides

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 Mechanism of action
Mechanism of cotrimoxazole

Sulfonamides do not affect mammalian cells??? 42

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