Respiratory System Drugs

Asst. Prof. Levent HACISÜLEYMAN

• Asthma is a disease characterized by
airway inflammation and episodic,
reversible bronchospasm with severe
shortness of breath.
• Drugs useful in asthma include
bronchodilators (smooth muscle
relaxants) and anti-inflammatory drugs.
• Chronic obstructive pulmonary disease
(COPD) is characterized by airflow
limitation that is less reversible than in
asthma and by a progressive course.
However, many of the same drugs are
used.
PATHOPHYSIOLOGY OF ASTHMA AND COPD

• The immediate cause of asthmatic bronchoconstriction is the

release of several mediators from IgE-sensitized mast cells and
other cells involved in immunologic responses.
• These mediators include the leukotrienes LTC4 and LTD4. In
addition, chemotactic mediators such as LTB4 attract
inflammatory cells to the airways.
• Finally, several cytokines and some enzymes are released,
leading to chronic inflammation.
• Chronic inflammation leads to marked bronchial hyperreactivity
to various inhaled substances, including antigens, irritants and
cold air.
• COPD is characterized by some degree of permanent structural
damage to the airways and parenchyma; exacerbation of
symptoms (wheezing, shortness of breath, cough) is often
triggered by upper respiratory infection (like asthma) but
occurs in older patients (usually long-term smokers) and is
poorly reversible with bronchodilators.
 STRATEGIES OF ASTHMA THERAPY
• Acute bronchospasm must be treated promptly and effectively with
bronchodilators (“reliever” drugs). Beta2 agonists, muscarinic
antagonists, and theophylline.
• Long-term preventive treatment requires control of the inflammatory
process in the airways (“controller” drugs) by corticosteroids. Long-
acting β2 agonists as bronchodilators. The leukotriene antagonists
have effects on both bronchoconstriction and inflammation but are
used only for prophylaxis.
• Nasal oxygen is basic therapy for acute bronchospasm of any cause.
BETA-ADRENOCEPTOR AGONISTS
• Albuterol, terbutaline, and metaproterenol are short-acting β2 agonists for
acute episodes of bronchospasm. Salmeterol and formoterol are long-acting
β2 agonists used for prophylaxis.
• Beta agonists are given almost exclusively by inhalation.
• The inhalational route decreases the systemic dose (and adverse effects) while
delivering an effective dose locally to the airway smooth muscle.
• Beta-adrenoceptor agonists stimulate adenylyl cyclase (via the β2-
adrenoceptor–Gs-coupling protein-adenylyl cyclase pathway) and increase
cyclic adenosine monophosphate (cAMP) in smooth muscle cells. The increase
in cAMP results in a powerful bronchodilator response.
• Skeletal muscle tremor is a common adverse β2 effect. Beta2 selectivity is
relative. At high clinical dosage, these agents have significant β1 effects. Even
when they are given by inhalation, some cardiac effect (tachycardia) is
common.
• Patients with COPD often have concurrent cardiac disease and may have
arrhythmias even at normal dosage.
METHYLXANTHINES
• Three major methylxanthines are found in plants: caffeine (in coffee),
theophylline (tea), and theobromine (cocoa).
• Theophylline is the only member of this group that is important in
the treatment of asthma.
• The methylxanthines inhibit phosphodiesterase (PDE), the enzyme
that degrades cAMP to AMP, and thus increase cAMP which leads to
bronchodilation.
• Other effects of therapeutic doses include CNS stimulation, cardiac
stimulation, vasodilation, a slight increase in blood pressure (probably
caused by the release of norepinephrine from adrenergic nerves) and
diuresis.
• Aminophylline is a salt of theophylline that is sometimes prescribed.
MUSCARINIC ANTAGONISTS
• ipratropium, a quaternary antimuscarinic agent, is delivered to the
airways by pressurized aerosol.
• Tiotropium and aclidinium are longer-acting analogs approved for
use in COPD.
• Because these agents are delivered directly to the airway and are
minimally absorbed, systemic effects are small.
• When given in excessive dosage, minor atropine-like toxic effects may
occur.
• In contrast to the β2 agonists, muscarinic antagonists do not cause
tremor or arrhythmias.
CORTICOSTEROIDS
• Local inhaled aerosol corticosteroids (eg,
beclomethasone, budesonide, dexamethasone,
fluticasone, mometasone) are relatively safe,
and have become common first-line therapy for
individuals with moderate to severe asthma.
• Important intravenous corticosteroids for status
asthmaticus include prednisolone (the active
metabolite of prednisone) and hydrocortisone
(cortisol).
• systemic (oral) corticosteroids (usually
prednisone) are used chronically only when
other therapies are unsuccessful.
• Corticosteroids reduce the synthesis of
arachidonic acid by phospholipase A2.
Concentrations of prostaglandins and
leukotrienes (extremely potent
bronchoconstrictors) are reduced.
 LEUKOTRIENE ANTAGONISTS
• These drugs interfere with the synthesis or the action of the
leukotrienes.
• Although their value has been established, they are not as
effective as corticosteroids in severe asthma.
• These drugs are orally active and have been shown to be effective
in preventing exercise-, antigen-, and aspirin-induced
bronchospasm.
• They are not recommended for acute episodes of asthma.
1. Leukotriene Receptor Blockers:
• Montelukast and zafirlukast are antagonists at the
LTD4 and LTE4 leukotriene receptors.
2. Lipoxygenase Inhibitor:
• Zileuton is an orally active drug that selectively
inhibits 5-lipoxygenase, a key enzyme in the
conversion of arachidonic acid to leukotrienes.