Download Clinical Pharmacology of Drugs Acting on the Respiratory Organs

CLINICAL PHARMACY IN
PULMONOLOGY
Introduction

Symptom of respiratory system:
no sputum---antitussives

Cough
sputum --- expectorants

Asthma ----- antiasthmatic drugs
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.
Asthma

Pathophysiology:


Asthma is a disease characterized by airway
inflammation and episodic, reversible
bronchospasm
Two characteristic features:
1)
2)

Inflammatory changes in the airway;
Bronchial hyperreactivity to stimuli.
Important mediators: histamine, LTC4, LTD4,
etc.
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. Risk factors include self or
family history of eczema, allergies or family history of
asthma. Bronchial asthma causes cough, shortness of
breath, and wheezing. Bronchial asthma is an allergic
condition, in which the airways (bronchi) are hyper-reactive
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 asneeded 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
Bronchodilators
I.
1.
2.
3.
β receptor agonists
Theophylline
Muscarinic antagonists
Anti-inflammatory agents
II.
1.
2.
Steroids
Anti-leukotriene agents
Anti-allergic agents
III.
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
Sympathomimetics
 The sympathomimetics, also called beta agonists or adrenergic agents,
can be thought of as rescue medications because they provide rapid
relief of labored breathing during an asthma episode. Derivatives of
adrenaline, or epinephrine, they are chemically altered to maximize this
natural compound’s airway muscle relaxing effect while minimizing the
heart, muscle, and nervous system side effects of the parent compound.
All of the currently available beta agonists are superior to both adrenaline
and ephedrine for duration of action and less-pronounced side effects.
 These potent , when inhaled, provide rapid relief of bronchial obstruction.
Duration of action varies from four to six hours. An exception is
salmeterol (Serevent®) which works for up to twelve hours but has a
slower onset of action of about an hour. These agents are excellent for
the prevention of wheezing triggered by exercise or cold air if taken
before the activity or exposure. A number of products are available.
Individuals may prefer one agent to another for reasons of taste, cost, or
personal preference. Generic agents are now available for albuterol.
Users of generic substitutes should be aware of the potential problem of
dosage variability.
 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.
Maxair® is thought to cause less heart stimulation while metaproterenol
may cause a little more. There is considerable individual variation.
• 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.
• Salmeterol inhalation may also be used for conditions other than those
listed in this medication guide.

Adverse Reactions of β2 agonists:
1)
Skeletal muscle tremor
2)
Cardiac effect: tachycardia, arrhymias
3)
Metabolism disturbance: ketone bodies↑,
acidosis, [K+]o↓
BRONCHODILATORS Theophylline
 This drug is so similar to caffeine that they share the same chemical




formula. Their three-dimensional structures are slightly different. As small
changes in molecular shape often result in major changes in function,
theophylline is 100 times as potent a bronchodilator as caffeine. That
means you would have to drink several pots of coffee or several six-packs
of cola to get the same beneficial effect of a theophylline tablet.
Upset stomach, nausea, rapid or irregular heartbeat, insomnia, hyperactive
behavior, and headaches are all adverse effects that caffeine and
theophylline share. Theophylline has a narrow therapeutic range meaning
that such adverse effects occur commonly The belief that theophylline
hinders learning is unfounded. In fact, most tests demonstrate enhanced
school performance in children taking theophylline. Like caffeine,
theophylline is a diuretic. Many patients taking this agent note increased
urine production and may awaken at night to answer nature’s call.
No longer the mainstay of therapy as it was a decade ago, theophylline still
has a role to play in the treatment of asthma. Once a day dosing makes it
useful in treating nocturnal asthma (asthma occurring during sleep). It
serves an ancillary role in severe cases of asthma. There are also a few
patients who respond better to theophylline than to inhaled
corticosteroids. Some studies suggest that theophylline may have a mild
anti-inflammatory effect but this is far from established.
Both theophylline and caffeine are rapidly absorbed from the
gastrointestinal tract. Modern
theophylline products use specially-formulated tablets or capsules which
delay absorption to produce relatively constant blood levels of
theophylline throughout the day and night with once daily (Theo24® ,
Unidor®, Uniphyll®) or twice daily (Slobid® , Theodur®) use.
Theophylline


Methylxanthine derivatives.
Mechanism of Action:
1.
2.
3.
4.
5.
Inhibit phosphdiesterase (PDE);
Block adenosine receptors;
Increase endogenous catecholamine (CA)
releasing;
Interfere with receptor-operated Ca2+
channels → [Ca2+]i↓;
Anti-inflammatory action

Clinical Use:
1.
2.
3.

Asthma: maintenance treatment
Chronic obstructive pulmonary disease
(COPD)
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
acetylcholine-mediated 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.
Atrovent® should be inhaled four 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.
Anticholinergic Drugs
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 anti-inflammatory 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 down-regulate
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.
The Cromones: Cromolyn &
Nedocromil
 These agents act primarily to stabilize mast cells. They
have an extraordinary safety record but high cost and
the need for frequent dosing (four times daily for
cromolyn, three times for nedocromil) limit their use.
Cromolyn may require administration for up to a month
before its protective effect is fully noted. Nedocromil is
usually helpful within a few days. Neither drug is as
potent as the inhaled corticosteroids. Another limiting
factor of nedocromil (Tilade®) is its unpleasant
aftertaste. Rinsing the mouth with water helps.
 Both drugs are good preventers of exercise-induced
asthma when taken before activity. Because of their
safety record, they are the drugs of first choice for
children. Both are available as multidose inhalers.
Cromolyn (Intal®) is approved for children as young as
two years and is available in unit dose ampoules for
nebulizer use.
Disodium Cromoglycate (SCG)

Mechanism of Action:
1.
2.
3.
Stabilizer of mass cell membrane: decrease
the release of mediators from mast cells.
Inhibit the function of sensory nerve ending
and neurogenic inflammation in airway.
Decrease bronchial hyperreactivity.
Ketotifen
 H1 receptor blocker.
 Prevent and inverse down-regulation of β2-
receptor.
Leukotriene Antagonists



When mast cells become activated, they release a host of preformed
chemical mediators which initiate an asthma attack consisting of
increasing cough, wheeze, and difficulty breathing. The job of the
mast cells is not complete with this act. Mast cells begin to produce
a different mixture of chemical messengers even more potent than
the first. This mix includes prostaglandins, thromboxanes, and
leukotrienes. These biochemical messengers intensify and prolong
the asthma episode. Leukotrienes are responsible for the
intensification of the asthma episode, called the late phase, which
often begins six to twelve hours after the onset of wheezing.
A new class of anti-inflammatory drug, the leukotriene antagonists,
consists of two subclasses, the leutins and the lukasts. Leutin-type
drugs block the creation of leukotrienes. Lukast-type drugs attach to
receptors for leukotrienes on cells thus blocking attachment and
consequently preventing the effect of these potent asthma
accelerators. Available agents in the United States include the
leutin, zileutin (Zyflo®), and the lukasts zafirlukast (Accolate®) and
montelukast (Singulair®). These agents are about as effective as
the cromones and about half as effective as moderate doses of
inhaled corticosteroids in controlling the symptoms of asthma.
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. Churge-Strauss Syndrome has been reported
in some patients with severe asthma requiring daily oral
corticosteroids whose chronic symptoms initially responded to
zafirlukast and, in a few cases, to montelukast. Churge-Strauss
Syndrome is a complex of symptoms that occur only in patients with
severe asthma. When present, patients experience increasing
symptoms of asthma as well as skin rash, bruising, and injury to
internal organs that may include the kidney, liver, and heart. Because
the treatment of this disorder is oral prednisone and its appearance in
patients using lukasts is associated with intentionally reduced
dosages of prednisone, it remains unclear whether the leukotriene
antagonists cause Churge-Strauss or that the disorder, already
present, is "unmasked" by reduction in daily prednisone use. Although
the answer remains elusive, the former explanation seems the more
plausable given the number of new cases of Churge-Strauss reported
with Accolate® use. Prior to the introduction of the lukasts for the
treatment of asthma this was a very rare disorder.
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. Singulair® is approved for adults and
children six years of age or older. Accolate® and Zyflo® are not
approved for children under twelve years of age.
Anti-leukotriene agents

Cysteinyl leukotrienes is a important
inflammatory mediator:


Bronchoconstriction, increased bronchial
reactivity, mucosal edema, mucus
hypersecretion, etc.
Leukotrienes resulte from the action of 5lipoxygenase on arachidonic acid.
Common agents:

I.
zafirlukast and montelukast: LTD4-
receptor antagonists
II.
zileuton: 5-lipoxygenase inhibitor
Glucocorticoids (GCs)

Mechanism of Action:
1.
Broad anti-inflammatory efficacy
①
②
2.
Block the synthesis of arachidonic acid by
phospholipase A2.
Reduce bronchial reactivity.
Increase the responsiveness of βadrenoceptors in the airway.
Corticosteroids

Routes of administration:



Systemic administration: including oral and
injection. More severe toxicity.
Inhalation:
Common inhalant GCs:

FP, BDP, BUD, TAA, FNS
Corticosteroids
 Continued use of inhaled corticosteroids reduces bronchial
hyperreactivity. This means that for many patients asthma
symptoms will disappear as will the need to use additional
asthma medications. Use of these medications in children with
asthma has been found to restore or preserve normal lung
growth. Children with moderate asthma who don’t receive
inhaled corticosteroids may reach adulthood with significantly
smaller lungs. In adults with asthma, use of inhaled
corticosteroids reduces the rate of lung tissue loss over time.
 A variety of agents are available for use. All are effective on a
twice-daily routine. Azmacort® comes with its own built-in
spacer but its small volume is not optimal. Aerobid® has a taste
that some users find unpleasant. A menthol form, Aerobid-M®
tastes better. Budesonide (Pulmicort®) is marketed as a
multidose, dry powder inhaler that provides precision dosing
without a Freon® propellant.
Step-wise approach to the treatment of asthma according to recent guidelines.
LTRA, leukotriene receptor antagonist; SR, slow release. The dose of inhaled
corticosteroids refers to beclomethasone dipropionate
Bronchitis

1) Inflammation of the mucous membrane of the bronchial
tubes
2) asthmatic bronchitis, bronchitis which causes or aggravates
bronchospasm.
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.
4) 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.
Pathology

The top left illustration shows the
normal pulmonary tree, while the
lower right illustration at the
bottom shows what happens during
an attack of bronchitis. The
inflammation of the bronchi and
bronchial tubes produces a buildup
of mucus. The thickened mucus
forms a plug that can block
bronchial tubes, the passages that
carry air from the trachea
(windpipe) to the alveoli (air sacs)
of the lungs. This results in the
difficult breathing characteristic of
bronchitis
Bronchitis
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
Bronchitis
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.
There are a number of differences between the
two.
Symptoms

Pneumonia manifests itself in the
 Bronchitis manifests itself
form of high fever, cough and
as a cough with headache,
chills. It is accompanied by rapid
breathing and a certain amount of
chills and a slight fever. A
wheezing. The patient often
patient may also
complains of chest pain. Some
experience a shortness of
patients also feel extremely
breath.
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.
Reasons

Pneumonia and bronchitis are
caused by different factors.
Bronchitis occurs when there is
an inflammation of the
bronchial tubes. It may be
caused by a number of factors,
including a bacterial or viral
infection. It is also caused by
irritation originating from
pollution and smoke. Bronchitis
may be chronic or acute in
nature. Chronic bronchitis
occurs over a period of time.
Acute bronchitis may last for a
few days. However, it is usually
cured with the help of
antibiotics.

Pneumonia is caused by an
infection of the lungs. It may be
caused by bacteria, fungi or by a
virus. It usually affects people
over the age of 65, or people
who have had their immune
systems compromised.
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.
In determining the appropriate antibiotic, the
physician must first answer a number of
questions:


How severe is the pneumonia? Mild-to-moderate cases
can be treated at home with oral antibiotics. Severe
pneumonia usually needs intravenous antibiotics
administered in the hospital.
If the organism causing the pneumonia is not known,
was the disorder community- or hospital-acquired?
Different organisms are usually involved in each setting,
and the physician can use this information to guess the
most likely organism causing the pneumonia.


If the organism is known, is it typical or atypical?
Community-acquired pneumonias, for example, are
usually caused by the typical bacteria Streptococcus
pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis,
which were previously treated with related antibiotics.
These antibiotics do not treat organisms such as
legionella, mycoplasma, or chlamydia. These organisms
are generally treated with a macrolide or possibly a
newer quinolone.
Does the patient have an impaired immune system?
Antibiotics used to treat such patients may differ from
those used in patients with healthy immune systems.
Antibiotic Treatments for
Community-Acquired Pneumonia



Joint guidelines issued in 2007 by the Infectious Disease
Society of America and the American Thoracic Society
(ITSA/ATS) recommend that mild CAP in otherwise
healthy patients be treated with oral macrolide antibiotics
(azithromycin, clarithromycin, or erythromycin).
Many patients with heart disease, kidney disease, diabetes,
or other co-existing conditions may still be treated as
outpatients. However, they should be given a
fluoroquinolone (moxifloxacin, gemifloxacin, or
levofloxacin) or a beta-lactam (preferably high-dose
amoxicillin or amoxicillin-clavulanate), plus a macrolide,
unless they live in an area with high S. pneumoniae
resistance to macrolides.
Antibiotic Treatments for
Community-Acquired Pneumonia

Current recommendations call for 7 - 10 days of
treatment for S. pneumoniae and 10 - 14 days for
Mycoplasma pneumoniae and Chlamydia pneumoniae.
However, some research suggests that patients with
mild-to-moderate community-acquired pneumonia may
be successfully treated with 7 days or less of antibiotics.
The shorter treatment may increase patient tolerance,
and improve the likelihood that patients will stick to the
treatment regimen. It will also help limit the growing
problem of antibiotic resistance.
Antibiotic Treatments for
Community-Acquired Pneumonia


Many cases of community-acquired pneumonia are caused by S.
pneumoniae -- Gram-positive bacteria that usually respond to
antibiotics known as beta-lactams (which include penicillin), and
to macrolides. However, resistant strains of S. pneumoniae are
increasingly common. Most resistant strains respond to
fluoroquinolines such as levofloxacin (Levaquin), gemifloxacin
(Factive), or moxifloxacin (Avelox). Another common cause of
community-acquired pneumonia is H. influenzae.
In addition, other important causes of CAP, particularly in
younger people, are atypical bacteria, which respond to
macrolides (erythromycin, clarithromycin, or azithromycin),
ketolides, or newer fluoroquinolones.
Antibiotic treatment for CAP is
determined by a number of factors,
including:
 The patient's history of antibiotic therapy




Co-existing diseases (such as COPD, diabetes, and heart failure)
Whether the patient is well enough to be treated at home or
requires hospitalization or nursing home care.
Treatment options can include a single drug, such as levofloxacin
or doxycycline, or combination treatment, such as a macrolide
administered with a beta-lactam.
Antibiotics taken by mouth are generally enough for patients
whose CAP is mild enough to be treated at home. Intravenous
antibiotics are required for hospitalized patients with CAP.
Antibiotic therapy should be given for a minimum of 5 days -longer if the patient still has a fever and more than one sign of
continuing severe illness.
Treatment of Viral Infections

There are not as many choices for treating viral
pneumonia. Oseltamivir (Tamiflu) and zanamivir
(Relenza) have been the recommended drugs for
influenza A or B infections, but many strains of
influenza A have become resistant. Their use is only
recommended if they are started in the first 48 hours
of symptoms. Taken early, these medications may be
effective in reducing symptoms and duration of illness.
Treatment of Viral Infections




Patients with viral pneumonias are at risk for what are called
"superinfections," which generally refers to a secondary bacterial infection,
usually caused by S. pneumoniae, S. aureus, or H. influenzae. Doctors most
commonly recommend treatment with amoxicillin-clavulanate, cefpodoxime,
cefprozil, cefuroxime, or a respiratory fluoroquinolone if these secondary
infections occur.
Patients with pneumonia caused by varicella-zoster and herpes simplex
viruses are usually admitted to the hospital and treated with intravenous
acyclovir for 7 days.
No antiviral drugs have been proven effective in adults with RSV,
parainfluenza virus, adenovirus, metapneumovirus, the SARS coronavirus, or
hantavirus. Treatment is largely supportive, with patients receiving oxygen and
ventilator therapy as needed.
Treatment of RSV in Children. Ribavarin is the first treatment approved for
RSV pneumonia, although it has only modest benefits. The American
Academy of Pediatrics recommends this drug for children who are at high
risk for serious complications of RSV.
Chronic Bronchitis. The irregular
bronchovascular structures
Chronic Bronchitis. Chest film and magnified view from right
middle/upper lung field. Irregular contours of
bronchovascular structures with irregular diameters.
A segmental pneumonia of s9 of
right lower lobe shows alveolar
densities.
Lobar pneumonia
in the right upper lobe
EXPECTORANTS AND ANTITUSSIVES
Expectorants, more accurately known as bronchomucotropic agents, are drugs used to assist in
the removal of secretions or exudate from the
trachea, bronchi, or lungs. They act by liquifying viscid
mucus or mucopurulent exudates, i.e., they
are decongestants. Therefore, they are used in the
treatment of coughs to help expel these exudates
and secretions.
Antitussives are agents that specifically inhibit or su
ppress the act of coughing. They should not be used
to suppress productive cough ing. Expectorants and
antitussives are most commonly used in the
symptomatic treatment of the
common cold or bronchitis.
ANTITUSSIVES

Coughing is the forceful expulsion of air from the lungs. A
cough may be productive or nonproductive. With a
productive cough, secretions from the lower
respiratory tract are expelled. A nonproductive cough is a
dry, hacking one that produces no secretions. An antitussive
is a drug used to relieve coughing. Many antitussive drugs
are combined with another drug, such as an antihistamine
or expectorant, and sold as nonprescription cough medicine.
Other antitussives, either alone or in combination with other
drugs, are available by prescription only.
ACTIONS
Some antitussives depress the cough center located in the
medulla and are called centrally acting drugs. Codeine and
dextromethorphan are examples of centrally acting antitussives. Other antitussives are peripherally acting drugs,
which act by anesthetizing stretch receptors in the
respiratory passages, thereby decreasing coughing. An
example of
a peripherally acting antitussive is benzonatate (Tessalon),
libexin.
ANTITUSSIVES (cont’d)
USES
Antitussives are used to relieve a nonproductive cough.When the cough
is productive of sputum, it should be treated by the primary health care
provider who, based on a physical examination, may or may not
prescribe or recommend an antitussive.
ADVERSE REACTIONS
Use of codeine may result in respiratory depression, euphoria, lightheadedness, sedation, nausea, vomiting,and hypersensitivity reactions.
The more common adverse reactions associated with the antitussives
When used as directed, nonprescription cough medicines containing two
or more ingredients have few adverse reactions. However, those that
contain an antihistamine may cause drowsiness.
CONTRAINDICATIONS
Antitussives are contraindicated in patients with known hypersensitivity
to the drugs. The narcotic antitussives (those with codeine) are
contraindicated in premature infants or during labor when delivery of a
premature infant is anticipated. Codeine is a Pregnancy Category C drug
except in the pregnant woman at term
or when taken for extended periods, when it is considered a Pregnancy
Category D drug.
ANTITUSSIVES

Classification:
一．
1.
2.
二．
Central antitussives
Dependent central antitussives
Independent central antitussives
Peripheral antitussives
Dependent Central Antitussives



Opioid alkaloids.
Morphine is the most effective drug for the
suppression of cough, but have addiction.
Mechanism: suppressing of cough center
Codeine


Selectively suppress cough center in
medulla oblongata
Potency:



Suppression of cough: ≈1/10 of morphine
Analgesia: ≈1/7 of morphine
Respiratory depression, constipation,
tolerance, dependence ＜ that of morphine

Pharmacokinetics:



Clinical Uses:


Well absorbed from oral and injection.
10% converted to morphine through demethylation
Dry cough
Adverse Reactions:



Respiratory suppression in high dose;
Tolerance and physical dependence with frequently
repeated administration;
Suppress secretion of bronchial gland and movement
of cilia.
Independent Central Antitussives


Stereoisomers of opioid molecules that are
devoid of analgesic effects and addiction liability.
Classification:
1)
2)
3)
4)
5)
-orphan-antitussives : dextromethorphan
amido-antitussives: pentoxyverine, clofedanol
piperidine-antitussives: cloperastine
morpholine-antitussives: promolate, fominoben;
others: eprazinone, zipeprol.
Dextromethorphan


Dextrorotatory stereoisomers of a
methylated derivative of levorphanol
Clinical Use:

Dry cough. Often + Antihistamine drug
Pentoxyverine



Suppression of cough: ≈1/3 of codeine.
Direct suppression of cough center
Atropine-like action and local anesthesia
action.
Cloperastine



Derivative of diphenhydramine
Suppression of cough center
Blocking H1-receptor
Peripheral Antitussives

Inhibiting receptor, afferent nerve,
efferent nerve of cough reflex arc →
cough suppression.
1.
2.
local anesthesia action: narcotine,
benzonatate;
Alleviative action: extractum glycyrrhizae
liquidum, Syrup
Expectorants
Mucokinetic drugs
Classification:
By the mechanism of action:


I.
1.
2.
Mucus secretagogue drugs: stimulating gastric
mucosa → reflex secretion of bronchial gland↑ →
dilution of sputum: ammonium chloride.
Mucolytic drugs:
1)
2)
3)
4)
break acid mucin: bromhexine
drug-SH
S-S of mucin → Fragmentation:
acetylcysteine
Enzymolysis: α-chymotrypsin
Surfactant: tyloxapol----Fog inhalation
By route of administration：
II.
1.
Oral drugs:
2.
Fog inhalation drugs: 1.8%NaCl,
2%~7.5%NaHCO3.