drugs used in treatment of asthma and COPD

lecture given 4/14/2026

asthma

chronic inflammatory disease characterized by hyperresponsive airways and episodes of acute bronchoconstriction that cause shortness of breath, cough, chest tightness, wheezing, and rapid respiration

affects 341 million pt worldwide

COPD

group of diseases (including emphysema and chronic bronchitis) characterized by progressive, irreversible airflow obstruction

symptoms include cough, excess, mucus production, chest tightness, breathlessness, difficulty sleeping, and fatigue

affects 251 million pt worldwide

4th most common cause of death in the world

t/f drugs used to treat asthma and COPD can be administered locally into the lung, or orally and parenterally for systemic absorption

true

what is the pathophysiology of asthma?

caused by release of inflammatory mediators from IgE sensitized mast cells and other cells involved in immunologic responses

mediators include inflammatory cytokines and leukotriens (LTC and LTD) and chemotactic factors (LTB) that attract inflammatory cells to the airways activating a chronic inflammatory response

characterized by activation of mast cells, infiltration of eosinophils and T helper 2 cells, and increased numbers of mast cells in airway smooth muscle

mast cell activation by allergens and physical stimuli release mediators which cause bronchoconstriction, microvascular leakage, and plasma exudation

what do the mediators of asthma lead to?

bronchoconstriction, plasma exudation, edema, vasodilation, mucus hypersecretion, and activation fo sensory nerves

chronic inflammation may be initiated by…

allergen exposure- activates dendritic cells which upregulate TH2 cells and eosinophilic inflammation and stimulates IgE formation by B lymphocytes which activate mast cells and release of mediators that activate neutrophils

chronic inflammation in the airway leads to…

structural changes in the airways- increased number and size of smooth muscle, blood vessels, and mucus secreting cells

collagen deposition (fibrosis) below the basement membrane of the airway epithelium (eosinophilic inflammation)

airway smooth muscle hypertrophy and hyperplasia

causes bronchial hyperreactivity to histamine and inhaled substances such as antigens, muscarinic agonists, sulfur dioxide, and cold air

what is the pathophysiology of COPD?

triggered by upper respiratory infections (older pts, usually long term smokers)

inflammation located primarily in small airways, results in progressive airway narrowing and fibrosis (chronic obstructive bronchiolitis), and destruction of lung parenchyma and alveolar walls

structural changes cause airway closure on expiration, air trapping and hyperinflation

characteristic symptoms are shortness of breath on exertion and exercise limitation

t/f bronchodilators are good for reversing COPD

false- poorly reversible with bronchodilators

how is COPD characterized?

predominance of neutrophils, macrophages, and cytotoxic T lymphocytes

t/f glucocorticoids are effective in treating asthma, but not COPD

true

what does cigarette smoke do?

activate epithelial cells and macrophage in the lung to release mediators that attract circulating inflammatory cells like monocytes, neutrophils, and T lymphocytes

fibrogenic factors released from epithelial cells and macrophages lead to fibrosis of small airways

release of proteases results in alveolar wall destruction (emphysema) and mucus hypersecretion (chronic bronchitis)

what are the categories of bronchodilators used to treat asthma and COPD?

b2 agonists- albuterol, formoterol

anticholinergics- ipratropium

methylxanthines- theophylline

what are the categories of anti-inflammatory agents used to treat asthma and COPD?

glucocorticoids- budesonide

asthma only: cromones- cromolyn

asthma only: anti-IgE antibody- omalizumab

what are the categories of leukotriene modifiers used to treat asthma?

leukotriene cysterinyl receptor antagonist- montelukast

lipoxygenase inhibitor- cysteinyl, zileuton

what antibiotics are used to treat COPD?

azithromycin, erythomycin

how are bronchodilators and anti inflammatory agents usually administered and why?

pressurized aerosol canisters or occasionally by nebulizer

decreases the systemic dose/adverse effects, and provides the active agent directly to the airway smooth muscle

what is the mechanism of action of b2 selective agonists?

stimulate adenylyl cyclase and increase intracellular cAMP in smooth muscle cells

cAMP activates protein kinase A (PKA) that phosphorylates may protein targets that relax smooth muscle and cause bronchodilation

albuterol

b2 selective agonist, short acting (6hr or less duration of action)

formoterol

b2 selective agonist, long acting (12-24hr duration of action)

what are the therapeutic uses of b2 selective agonists?

first line therapy in acute asthma, may provide benefit in COPD pts, risk of toxicity is greater in COPD

what are the therapeutic uses of albuterol?

used for symptomatic treatment of acute bronchospasm (reliever)

used for exercise-induced bronchospasm (reliever)

duration of effect 3-6 hr

has no anti inflammatory effect (controller) and should NOT be used as monotherapy in asthma

what are the therapeutic uses of formoterol?

used for prophylaxis

rapid onset of action (1-3 min) and a 12 hr duration

suitable for both maintenance (controller) and rescue (reliever) therapy

always used in combination with glucocorticoids to improve safety and control of symptoms

what are adverse effects of b2 selective agents?

most common is skeletal muscle tremor

b1 effects at high clinical doses (tachycardia, possible arrhythmias)

loss of response (tolerance, tachyphylaxis) with excessive use of short-acting agents

COPD pts often have concurrent cardiac disease and may have arrhythmias at normal doses

what are the therapeutic uses of glucocorticoids?

local administration of inhaled aerosol glucorticoids is safe and first line therapy for moderate to severe asthma control

used in combination with long acting b2 selective agonist

oral glucocorticoids are used when other therapies are unsuccessful due to their toxicity

severe asthma attacks can be treated IV

COPD pts are more reistant to the beneficial effects of glucocortioids

what are adverse effects of glucocorticoids?

local administration occassionally results in a very small degree of adrenal suppression (rarely significant0

changes in oropharyngeal flora results in candidiasis (more common)

most important to dentistry: infection, impaired wound healing, osteoporosis

systemic toxicities occur with prolonged (>2 weeks) systemic administration required for severe refractory asthma