Drugs to Treat Respiratory
Disorders
Bronchoconstriction
• Result from release ACH, histamine and
inflammatory mediators
• Vagus nerve releases ACH
• ACH triggers release of pulmonary
secretions
• Treated with sympathomimetics
Chronic Inflammation
• Prolonged exposure to airway irritants
• Inflammation causes same factors
contributing to bronchoconstriction
– (e.g. histamine, cytokines)
• Treated with corticosteroids
– Side effects and expensive
Loss of Lung Elasticity
• Lung tissue typically elastic
• Conditions such as smoking cause loss of
the tissue contributing to elasticity
• Can collapse, lose compliance or become
chronically inflamed
Reactive Airway Disease (Asthma)
Chronic Obstructive Pulmonary
Disease (COPD)
Asthma Drugs
Common Diseases Affecting the
Respiratory Tract
• Chronic bronchitis – condition caused by chronic
respiratory irritation, inflammation, and
characterized by increased secretions and infection
• Emphysema – disease characterized by destruction of
alveoli, labored respiratory gas exchange, and
shortness of breath
• Asthma – inflammatory disease of the respiratory
passageways characterized by bronchoconstriction
and shortness of breath
Inflammatory Mediators
of the Respiratory Tract
• Histamine
• Eosinophilic chemotactic factor of anaphylaxis
(ECF-A)
• Prostaglandins and leukotrienes
• Slow-reacting substance of anaphylaxis (SRSA)
Autonomic Control
of the Respiratory Tract
• Bronchiolar smooth muscle is relaxed by beta2 adrenergic receptor stimulation
• Bronchiolar smooth muscle is contracted by
cholinergic receptor stimulation
• Respiratory secretions are increased by
cholinergic stimulation
• Drugs that increase intracellular levels of
cyclic AMP produce bronchodilation
Bronchodilator Drugs
• Sympathomimetics – drugs that stimulate beta2 adrenergic receptors
• Xanthine derivatives – theophylline
• Parasympatholytics – drugs that block
cholinergic receptors (anticholinergic drugs)
Beta Adrenergic Drugs
• Epinephrine and isoproterenol are nonselective
beta-1 and beta-2 agonists
• Albuterol, terbutaline, and salmeterol are selective
beta-2 agonists that do not cause excessive cardiac
stimulation
• Selective beta-2 drugs are preferred for the control
of asthma
• Epinephrine SC is the drug of choice to treat an
acute attack of asthma
Theophylline
• Increases cyclic AMP levels to cause
bronchodilation and inhibition of chemical
mediator release from mast cells
• Theophylline is usually administered orally
• In COPD theophylline decreases secretions
and stimulates respiration
• Overdosage produces cardiac and CNS
stimulation, and may cause seizures
Anticholinergic Drugs
• Ipratropium bromide is the only drug
currently available
• By blocking cholinergic receptors
ipratropium produces bronchodilation and
decreased respiratory secretions
• The drug is administered by oral inhalation
Corticosteroids
• Adrenal gland hormone derivatives used in
inflammatory and allergic conditions
• Administered orally or parenterally in acute
asthmatic and inflammatory diseases
• Administered by oral inhalation for the
chronic control of asthma and related
inflammatory conditions
• Inhalation limits systemic toxicity
Leukotriene Inhibitors
• Antiinflammatory drugs that interfere with
the inflammatory actions of the leukotrienes
• Zafirukast and montelukast block
leukotriene receptors
• Zileutron blocks the enzyme required for
the formation of leukotrienes
• Drugs are indicated for the chronic
treatment and control of asthma
Antiallergic Drugs
• Cromolyn and nedocromil inhibit the antigenantibody reaction on mast cells that triggers
allergic reactions
• Administration is by oral inhalation
• Drugs are used on a daily basis and are intended to
prevent or decrease allergic reactions
• Several weeks are usually required for the full
therapeutic effect
Mucolytics
• Mucolytics are intended to break apart and
liquefy thick respiratory secretions to
facilitate easier removal
• Acetylcysteine is the most widely used
mucolytic and is inhaled by nebulization
• Administration is usually followed by
postural drainage and tracheal suction
Antihistamines
Clinical Indication of Antihistaminic
Drugs
Prevent or interrupt the symptoms of seasonal allergy,
rhinitis, cold or flu
Acute allergic reactions-urticaria, hay fever, insect bites, rhinitis
and dermatitis
Adjunct medication pre-, post-anesthesia
To induce sedation, minimize irritability
Active ingredient in cough/cold preparations
To induce sedation, dry secretions
Clinical Indication
of Antiallergic Drugs
Prevent the symptoms of
–severe bronchial asthma
–exercise-induced bronchospasm
–allergic rhinitis
–mastocytosis
Types of Drugs in this Class
Antihistamines
chlorpheniramine (Chlor-Trimeton),
diphenhydramine (Benadryl),
fexofenadine (Allegra), loratidine (Claritin),
desloratidine (Clarinex)
Antiallergics
cromolyn sodium (Intal)
Action
of
Histamine
Histamine interacts with two types of histamin receptors
•
•
H1 receptors:
blood pressure
blood vessels
capillaries skin
bronchioles
intestines
urinary sphincter
H2
heart
stomach
decrease
dilate
dilate, leak
constriction
contraction
constriction
Produce
hypotension
headache
redness, itching, edema
breathing difficulty
constipation
urine retention
increase heart rate tachycardia
conduction impaired dysrhythmia
acid secretion
heart burn
Histamine
Histamine is naturally found in the body
within mast cells or basophils. Mast cells are
found predominately in the lungs, gastrointestinal
tract, circulatory system
Environmental, bacterial or viral proteins
(allergens) attach to mast cells membranes
and cause histamine release
The greater the allergen challenge, the
greater the histamine release
Mechanism of Action
Antihistamines block the physiological effects of
histamine by selectively acting on receptors to prevent
histamine from stimulating the receptor and inducing
the common effects observed during an allergic
reaction:
•Redness, edema, itching
•Allergy headache
•Breathing difficulty
Pharmacological Effects
The pharmacological effects of antihistamines are
the result of blocking the physiological effects of
histamine (histamine antagonists)
and
occupying acetylcholine receptors to inhibit the
action of acetylcholine (anticholinergic)
Antihistamine Adverse Effects
•
•
•
•
•
•
•
•
•
•
Drowsiness
Mental confusion
Sedation
Dry mouth
Anorexia
Epigastric distress
Hypotension
Tachycardia
Urinary retention
Dysrhythmias
Antiallergic Drugs
Antiallergic drugs inhibit the physiolgical
effects of histamine by attaching to mast cell
membranes and inhibiting the release of
histamine
Antiallergic drugs have no effect on the
histamine receptors and have the best
results before large amounts of histamine
have been released (prophylactic)
Cautions
and
Contraindications
Because of their anticholinergic activity, antihistamines
should be used with caution in patients with:
• Cardiovascular disease
• Hypertension
• Increased intraocular pressure
• Urinary retention
• Stenosing peptic ulcer
• A history of sensitivity to this class
• CNS depression
Used with caution in elderly patients
Not used by nursing mothers, dehydrated children
Drug Interactions
Increase drowsiness of antihistamines
• CNS depressants- sedatives, tranquilizers,
alcohol
Elevate plasma levels of antihistamines
• Macrolide antibiotics- erythromycin,
clarithromycin, troleandomycin
• Antifungal drugs