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 (SRS-A)

Autonomic Control of the Respiratory Tract

• Bronchiolar smooth muscle is relaxed by beta-2 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 beta-2 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 antigen-antibody 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 preparationsTo induce sedation, dry secretions

Prevent the symptoms of

–severe bronchial asthma

–exercise-induced bronchospasm

–allergic rhinitis

–mastocytosis

Clinical Indication of Antiallergic Drugs

Types of Drugs in this Class

Antihistamineschlorpheniramine (Chlor-Trimeton), diphenhydramine (Benadryl), fexofenadine (Allegra), loratidine (Claritin), desloratidine (Clarinex) Antiallergics cromolyn sodium (Intal)

Action of HistamineHistamine interacts with two types of histamin receptors

• H1 receptors: Produceblood pressure decrease hypotension

blood vessels dilate headache capillaries skin dilate, leak redness, itching, edemabronchioles constriction breathing difficulty intestines contraction constipationurinary sphincter constriction urine retention

• H2

heart increase heart rate tachycardia conduction impaired dysrhythmia

stomach acid secretion heart burn

HistamineHistamine 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

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)

Pharmacological Effects

Antihistamine Adverse Effects• Drowsiness• Mental confusion• Sedation• Dry mouth• Anorexia• Epigastric distress• Hypotension• Tachycardia • Urinary retention• Dysrhythmias

Antiallergic DrugsAntiallergic drugs inhibit the physiolgical effects of histamine by attaching to mast cellmembranes and inhibiting the release of histamine

Antiallergic drugs have no effect on thehistamine receptors and have the bestresults before large amounts of histaminehave been released (prophylactic)

Cautions and ContraindicationsBecause 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