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Transcript
PHARMACOTHERAPY OF
RESPIRATORY DISEASES
Bronchial asthma
Bronchial asthma is a disease caused by increased
responsiveness of the tracheobronchial tree to various
stimuli. The result is paroxysmal constriction of the bronchial
airways. Bronchial asthma is the more correct name for the
common form of asthma. The term 'bronchial' is used to
differentiate it from 'cardiac' asthma, which is a separate
condition that is caused by heart failure. Although the two
types of asthma have similar symptoms, including wheezing
(a whistling sound in the chest) and shortness of breath,
they have quite different causes.
Bronchial asthma (cont’d)
Bronchial asthma is a disease of the lungs in which an
obstructive ventilation disturbance of the respiratory
passages evokes a feeling of shortness of breath. The
cause is a sharply elevated resistance to airflow in the
airways. Despite its most strenuous efforts, the respiratory
musculature is unable to provide sufficient gas exchange.
The result is a characteristic asthma attack, with spasms of
the bronchial musculature, edematous swelling of the
bronchial wall and increased mucus secretion.
Bronchial asthma
• Symptoms can occur spontaneously or can be triggered by
respiratory infections, exercise, cold air, tobacco smoke or other
pollutants, stress or anxiety, or by food allergies or drug allergies.
The muscles of the bronchial tree become tight and the lining of the
air passages become swollen, reducing airflow and producing the
wheezing sound. Mucus production is increased.
• Typically, the individual usually breathes relatively normally, and will
have periodic attacks of wheezing. Asthma attacks can last minutes
to days, and can become dangerous if the airflow becomes severely
restricted. Asthma affects 1 in 20 of the overall population, but the
incidence is 1 in 10 in children. Asthma can develop at any age, but
some children seem to outgrow the illness. Bronchial asthma causes
cough, shortness of breath, and wheezing. Bronchial asthma is an
allergic condition, in which the airways (bronchi) are hyperreactive
and constrict abnormally when exposed to allergens, cold or
exercise.
Bronchial asthma
• Treatment is aimed at avoiding known allergens and
controlling symptoms through medication. A variety of
medications for treatment of asthma are available. People
with mild asthma (infrequent attacks) may use inhalers on
an as-needed basis. Persons with significant asthma
(symptoms occur at least every week) should be treated
with anti-inflammatory medications, preferably inhaled
corticosteroids, and then with bronchodilators such as
inhaled Alupent or Vanceril. Acute severe asthma may
require hospitalization, oxygen, and intravenous
medications.
Antiasthmatic Drugs
I.
Bronchodilators
1.
2.
3.
II.
β receptor agonists
Theophylline
Muscarinic antagonists
Anti-inflammatory agents
1.
2.
III.
Steroids
Anti-leukotriene agents
Anti-allergic agents
1.
2.
Stabilizer of inflammatory cell membrane
H1 receptor blocker
Beta Adrenoceptor Agonists
•
•
•
•
Adrenaline: α,β agonist
Ephedrine: α,β agonist
Isoprenaline:β1 ,β2 agonist
β2-selective agonists
• Salbutamol:
• Terbutaline :
• Clenbuterol:
• Formoterol:
• Salmeterol:
• Bambuterol:
intermediateacting
long-acting
BRONCHODILATORS. sympathomimetic
• Side effects are mild affecting less than 10%
of users. They include rapid heart rate,
palpitations, restlessness, anxiety, and
muscle tremors. Some children may become
"revved up" especially when the oral form is
given or sometimes after receiving an aerosol
treatment from a nebulizer.
• Salmeterol is a bronchodilator. It works by relaxing muscles in the
airways to improve breathing.
• Salmeterol inhalation is used to prevent asthma attacks. It will not treat
an asthma attack that has already begun. Salmeterol inhalation is also
used to treat chronic obstructive pulmonary disease (COPD) including
emphysema and chronic bronchitis.
SALBUTAMOL
•
Adverse Reactions of β2 agonists:
1) Skeletal muscle tremor
2) Cardiac effect: tachycardia, arrhymias
3) Metabolism disturbance: ketone bodies↑, acidosis,
[K+]↓
Theophylline
•
•
Methylxanthine derivatives.
Mechanism of Action:
1. Inhibit phosphodiesterase (PDE);
2. Block adenosine receptors;
3. Increase endogenous catecholamine (CA)
releasing;
4. Interfere with receptor-operated Ca2+ channels →
[Ca2+]i↓;
5. Anti-inflammatory action
•
Clinical Use:
1. Asthma: maintenance treatment
2. Chronic obstructive pulmonary disease (COPD)
3. Central sleep apnea (CSA)
•
Adverse Reactions:
•
•
•
Narrow margin of safety. Toxic effects are
related to its plasma concentrations.
Gastrointestinal distress, tremor, and insomnia.
Cardiac arrhythmias, convulsions → lethal.
Muscarinic Antagonists
• There are M1, M2, M3 receptor subtype in the
airway.
• Selectively blocking M1, M3 receptor is resulted in
bronchodilating effect.
• Ipratropium bromide binds to all M-R subtypes
(M1, M2 and M3 ), and inhibits acetylcholinemediated bronchospasm.
BRONCHODILATORS Anticholinergic
Drugs
• In the treatment of asthma, anticholinergic drugs are both old and
new. One hundred years ago, atropine, the parent drug of this class,
was smoked as a cigarette for asthma. Its usefulness was limited by
unacceptable side effects of rapid heart rate, hot skin, and dry mucous
membranes. Excessive doses could even provoke delusions and
irrational behavior.
• Ipratropium (Atrovent®) preserves the bronchodilator effects while
eliminating these adverse effects. Atrovent® is not as potent as the
sympathomimetics and is not considered a first choice medication. It
has an additive effect when beta agonists are insufficient for symptom
relief. It can serve as an acceptable alternate when sympathomimetics
aren’t tolerated.
Anticholinergic Drugs
• Atrovent® should be
inhaled 4 times daily for
maximum effectiveness.
It's available in multidose
inhaler form and in unit
dose ampoules for
nebulizer use. The only
common side effect is dry
mouth. Combivent® is a
convenient, combination
product composed of
albuterol and ipratropium.
Anti-inflammatory Agents
Asthma medications may be divided into two broad
categories, bronchodilators and anti-inflammatory
agents. Within each category are several subclasses
and variety of products. While bronchodilators relieve the
symptoms of coughing and wheezing, the antiinflammatory agents treat the underlying cause of
asthma. The asthmatic state involves fundamental
changes in the way the bronchi regulate their internal
diameter. When the cells lining the inner surface of the
bronchial tubes are injured, forces designed to control
airway size become unbalanced. Bronchoconstriction
(airway narrowing) becomes predominant.
• Anti-inflammatory agents act at several points in this process.
Cromolyn and nedocromil stabilize mast cells and nerve endings
preventing initiation of the inflammatory process. Leukotriene antagonists
block the production of leukotrienes, a potent mast cell messenger
chemical, or block the transmission of their message to receptor cells.
Corticosteroids stabilize blood vessels reducing vascular leakiness. They
also restore sensitivity of receptor cells to beta-agonists and downregulate the production and release of inflammatory chemicals. This
results in decreased numbers of eosinophils in the airway walls.
Corticosteroids have considerably greater anti-inflammatory activity than
any of the other drugs. The result is a gradual resolution of the asthmatic
condition.
• Since these drugs do not relax bronchial muscle, they don’t provide the
immediate relief characteristic of bronchodilators. With regular and
continued use of anti-inflammatory agents however, the need for
bronchodilators is gradually reduced. Inhaled corticosteroids may trigger
cough during an acute asthma attack. Oral prednisone may be
substituted at such times.
Anti-allergic Agents
• Madiators release inhibitors.
• No bronchodialator action but can prevent
bronchoconstriction caused by a challenge with
antigen to which the patient is allergic.
Disodium Cromoglycate (SCG)
•
Mechanism of Action:
1. Stabilizer of mass cell membrane: decrease the
release of mediators from mast cells.
2. Inhibit the function of sensory nerve ending and
neurogenic inflammation in airway.
3. Decrease bronchial hyperreactivity.
Ketotifen
• H1 receptor blocker.
• Prevent and inverse down-regulation of β2receptor.
•
Common agents:
I.
zafirlukast and montelukast: LTD4-receptor
antagonists
II.
zileuton: 5-lipoxygenase inhibitor
Leukotriene Antagonists
• Montelukast may be taken once daily while
zafirlukast must be taken twice a day. Moreover,
administration of zafirlukast with food may affect its
absorption from the gastrointestinal tract. Initially,
zileutin must be taken four times a day. This may be
decreased to three or even two times a day after a
period of demonstrated effectiveness.
• For this class of medication, minor side-effects have been
reported infrequently; major ones rarely. Both zileutin and
zafirlukast may cause mild, reversible injury to the liver.
Patients taking these medications should have liver function
tests prior to initiating therapy and periodically thereafter.
They should not be used in the presence of preexisting liver
disease.
Leukotriene Antagonists
• Of the three agents, montelukast is by far the
most convenient to use as it is administered
once daily and can be taken with food or on
an empty stomach. Zafirlukast taken twice
daily should be taken at least one hour before
or two hours after meals. Zileutin may be
taken without regard to stomach contents but
the need to dose four times a day makes
compliance difficult.
Glucocorticoids (GCs)
•
Mechanism of Action:
1. Broad anti-inflammatory efficacy
① Block the synthesis of arachidonic acid by
phospholipase A2.
② Reduce bronchial reactivity.
2. Increase the responsiveness of β-adrenoceptors in
the airway.
Corticosteroids
Corticosteroids
• With the recognition that airway inflammation is present
even in patients with mild asthma, therapy with inhaled
glucocorticoids is now recommended at a much earlier
stage
• Routes of administration:
• Systemic administration: including oral and injection. More severe
toxicity.
• Inhalation:
• Common inhalant GCs:
• Fluticasone propionate , Beclomethasone dipropionate ,
Budesonide , Triamcinolone acetonide , Flunisolide
The goal of all inhaled corticosteroids to (1) produce long-lasting
therapeutic effects at the pulmonary target site, (2) minimize oral
bioavailability, and (3) minimize systemic side effects by rapid
clearance of absorbed drug.
Local Side Effects
• Inhaled glucocorticoids have oropharyngeal side
effects whose rate of appearance depends on the
dose, the frequency of administration, and the
delivery system used:
Dysphonia (hoarseness)
Oropharyngeal Candidiasis
Cough and throat irritation
Step-wise approach to the treatment of asthma
LTRA, leukotriene receptor antagonist; SR, slow release. The dose of
inhaled corticosteroids refers to beclomethasone dipropionate
Bronchitis
Inflammation of the mucous membrane of the bronchial tubes
Classification:
• 1) asthmatic bronchitis, bronchitis which causes or aggravates
bronchospasm.
2) Acute bronchitis is usually a short, severe illness that may show
up along with a cold or follow other viral infections such as
measles or whooping cough.
•
• 3) chronic bronchitis, a condition of the bronchial tree
characterized by cough, hypersecretion of mucus, and
expectoration of sputum over a long period of time, associated
with frequent bronchial infection; usually due to inhalation, over a
prolonged period, of air contaminated by dust or by noxious gases
of combustion.
Bronchitis. Treatment
• Routine antibiotic treatment of uncomplicated
acute bronchitis is not recommended, regardless
of duration of cough. If pertussis infection is
suspected (an unusual circumstance), a
diagnostic test should be performed and
antimicrobial therapy initiated
Difference Between Pneumonia and
Bronchitis
• Both bronchitis and pneumonia are serious
diseases affecting the lower respiratory tract.
They can lead to a lot of discomforts and, if left
untreated, may cause other serious conditions.
•
Symptoms
Pneumonia manifests itself in the form
of high fever, cough and chills. It is
accompanied by rapid breathing and a
certain amount of wheezing. The
patient often complains of chest pain.
Some patients also feel extremely
exhausted and nauseous. The
symptoms of viral pneumonia often
resemble those of ordinary flu. There
are chills and high fever. It is often
accompanied by chattering teeth. It
may also produce sputum that is
green, yellow or rust colored.
Pneumonia becomes apparent when
the patient experiences a shortness of
breath.
• Bronchitis manifests itself
as a cough with headache,
chills and a slight fever. A
patient may also experience
a shortness of breath.
Differences in treatment
• The treatment for bronchitis is
relatively simple. Once identified the
reasons for the infection, a course
of antibiotics will be administered.
Patient will be advised rest and will
need to avoid pollution and smoke.
• Pneumonia is more of a serious
affliction. If the patient have been
diagnosed with this disease, will be
prescribed a strong antiviral or
antibiotics. If the condition worsens,
the patient may be hospitalized
anywhere between one and three
days, depending on the seriousness
of condition.
Medications:
• Dozens of antibiotics are available
for treating pneumonia, but
selecting the best drug is
sometimes difficult. Patients with
pneumonia need an antibiotic that is
effective against the organism
causing the disease. When the
organism is unknown, "empiric
therapy" is given, meaning the
doctor chooses which antibiotic is
likely to work based on factors such
as the patient's age, health, and
severity of the illness.