This document summarizes the pathophysiology and treatment of respiratory conditions like asthma, COPD, and pulmonary hypertension. It describes asthma as widespread reversible narrowing of airways due to increased bronchial responsiveness and inflammation. Treatment depends on timing and includes short-acting beta-agonists for acute relief and inhaled corticosteroids for chronic inflammation reduction. Beta-agonists, methylxanthines, anti-muscarinics, leukotriene inhibitors, and corticosteroids are discussed as primary asthma therapies. COPD treatment focuses on bronchodilators and corticosteroids for severe cases. Pulmonary hypertension can be treated with prostanoids, endothelin receptor antagonists, or phosphodiesterase

1. Respiratory
Pharmacology Review

2. Asthma
Widespread reversible narrowing of
bronchial airways
Increased bronchial responsiveness to inhaled stimuli
Lymphocytic, eosinophilic inflammation of bronchial
mucosa

3. Physiology of Asthma

4. Asthma treatment by timing of
presentation
Short Term Treatment:
Goal = relax airway smooth muscle
(Short Acting Beta Agonists most
common, also can use
Methyxanthines or anti-muscarinics)
Chronic Treatment:
Goal = reduce airway inflammation
(Inhaled corticosteroids most
effective, can also use cromolyn or
nedocromil)

5. Beta 2 agonists- most widely
used for treatment for asthma!
 Short Acting: Albuterol, piralbuterol, metaproterenol and levalbuterol
 Long Acting: Salmeterol, Formeterol, Arformeterol
 Multiple Mechanisms of Beta 2 activation:



Relaxes airway smooth muscle
Inhibits mediator release
Activates the Na/K pump
 Side Effects



Tachycardia, tremor (flight or flight!)
Hypokalemia
Transiently decreases PaO2 as they may increase perfusion to poorly ventilated
areas supplemental oxygen helpful
 Important note: DO NOT use long acting beta agonists by themselves, as they
do not have an effect on inflammation. Combine them with corticosteroids
 Long Acting Beta Agonists have a BLACK BOX WARNING: can cause
increased risk of death or near-death from asthma attack, especially in African
American population

6. Mechanism of Beta 2 agonists

7. Directly relax
airway smooth
muscle
(sympathomim
etic agents,
theophylline)

8. Mechanism of Methylxanthines
(Theophylline)

9. Methylxanthines
(theophylline)
 Multiple other mechanisms
 Inhibition of PDE4 on inflammatory cells reduces
cytokine and chemokine release
 Enhancement of histone deacetylation  decreased
inflammatory cell gene transcription
 Narrow therapeutic window!
 Toxicity: anorexia, N/V, abdominal discomfort, HA,
anxiety
 More severe toxicity: seizures and arrhythmias

10. Inhibit the effect
of acetylcholine
from vagal motor
nerves
(muscarinic
antagonists)

11. Anti-Muscarinics
 Ipratropium: primarlily M3 receptor
 Tiotropium (longer acting): primarily M1 and M3
receptors
 Treatment of COPD, potential use in asthma but not
approved
 SE: dry mouth, exacerbation of narrow angle glaucoma
and myasthenia gravis

12. Pathophysiology of Asthma
Widespread reversible narrowing of
bronchial airways
Increased bronchial responsiveness to inhaled stimuli
Lymphocytic, eosinophilic inflammation of bronchial
mucosa

13. Omaluzimab, cromolyn and nedocromil
Reduce amount of
IgE bound to mast
cells (anti-IgE
antibodyomaluzimab)
OR
Prevent mast cell
degranulation
(cromolyn or
nedocromil)

14. Cromolyn sodium and Nedocromil
sodium (insoluble salts)
 Alter delayed chloride channels in cell membrane (inhibits
activation):
 Airway nerves  inhibits cough
 Mast cells  inhibits early response to antigens (degranulation)
 Eosinophils  inhibits inflammation
 NO effect on smooth muscle tone
 ONLY useful for prophylaxis of asthma
 Also has some benefit in allergic rhinoconjunctivitis
 SE: throat irritation, cough, dry mouth, wheezing
prevented by pre-treatment of beta agonist

15. Omalizumab: IgG monoclonal
antibody
 Inhibits IgE from binding to IgE receptor on mast cells
and basophils
 Used for refractory asthma
 BLACK BOX WARNING: anaphylaxis! (2-24 hours after
administration)

16. Decrease airway
inflammation that is
linked with increased
airway responsiveness
(inhaled corticosteroids)

17. Inhaled Corticosteroids
 Budesonide, Triamcinolone, Fluticasone, Mometasone,
Flunisolide, Beclomethasone, Ciclesonide
 *First line treatment for asthma!* (except exercise induced asthma)
 Reduce bronchial reactivity and reduce frequency of asthma
exacerbations when taken regularly
 Used as ‘controller’ asthma medications- not curative
 Inhibit infiltration of airways by lymphocytes, eosinophils and mast
cells
 UNIQUE SIDE EFFECT of Inhaled Corticosteroids!!!
 Oropharyngeal candidiasis- prevented by gargling and spitting
water after use

18. Leukotriene inhibitors
 Leukotriene B4: neutrophil chomoattractant
 Leukotriene C4 and D4: cause bronchoconstriction, increased bronchial
reactivity, mucosal edema and mucous hypersecretion
 Leukotriene D4 receptor antagonists inhibit these effects: zafirlukast and
montelukast
 5-lipoxegenase is the enzyme involved in leukotriene synthesis: inhibition by
zileuton inhibits the above effects
 These agents are less effective than inhaled corticosteroids, but similar
efficacy in reducing frequency of asthma exacerbations
 Shown to be particularly effective in aspirin-induced asthma
 *Zileuton MAJOR SE: LIVER TOXICITY!!! (less often used)- zafirlukast has
some hepatotoxicity, but less than zileuton
 Monteleukast UNIQUE SE: eosinophilia and Churg Strauss Syndrome

19. COPD
 Differences from asthma:
 NOT reversible with bronchodilator treatment
 Occurs in older patients
 Neutrophil mediated
 Less responsive to inhaled corticosteroid treatment
 Acute symptoms SABA, anti-cholinergic (ipratropium) or both
 Persistent symptoms  LABA or tiotropium (long acting)
 Severe airflow obstruction  inhaled corticosteroid
 Theophylline is also useful (improves contractility of the diaphragm
 improved ventilatory capacity)
 Oxygen is needed with progression

20. Protease inhibitors

21. Protease inhibitors
 Helpful in patients with emphysema caused by alpha 1
anti-trypsin deficiency
 SE: anaphylaxis and low grade fever (especially in
patients with IgA deficiency)

22. Pulmonary Hypertension
Treatment
 Epoprostenol: FIRST LINE for severe pulmonary hypertension


Mechanism: vasodilation and inhibition of clotting
SE: Jaw pain, chest pain, weakness, shortness of breath, arrhythmias, flushing,
hypotension
 Treprostinil: prostanoid- pulmonary and systemic vasodilation; inhibits
platelet aggregation
 Iloprost: Prostaglandin- vasodilation, suppression of vascular smooth muscle
proliferation, inhibition of platelet aggregation
 Bosentan: non-selective endothelin receptor antagonist

SE: hepatotoxicity
 Ambrisentan: selective type A endothelin-1 receptor antagonist
 Sildenafil and Tadalafil: cGMP phosphodiesterase inhibitor (prolongs nitric
oxygen  prolonged vasodilation)