Respiratory-Pharmacology (USMLE)

Chronic inflammatory reversible disease of tracheobronchial airways characterized by airflow obstruction and increased responsiveness to a variety of stimuli
asthma

– inflammation of bronchial wall
– increased mucus secretion
– bronchiolar smooth muscle constriction

List 3 s/s of bronchoconstriction.
chest tightness

shortness of breath

wheezing

rapid respirations

use of accessory muscles of respiration

cough

Review bronchoconstriction and drugs
Review bronchoconstriction and drugs

What class of drugs inhibit phospholipase A2?
What class of drugs inhibit phospholipase A2?
corticosteroids

List 3 classes of drugs that can be used to treat acute asthmatic attack.
beta-agonists

muscarinic antagonists

theophylline

List the 2 most important types of drugs used for long-term preventive treatment of asthma.
corticosteroids (most important)

release inhibitors (e.g. cromolyn)

Acute bronchial asthma treatment of choice
short-acting beta2-agonists

Are long-acting beta2-agonists used in acute asthma or prophylaxis?
prophylaxis

List 3 bronchodilators used to treat asthma.
beta2-agonists

muscarinic antagonists

methylxanthines

List 3 anti-inflammatory agents used to treat asthma.
steroids

anti-IgE antibodies

release inhibitors

List 2 leukotriene antagonists (based on mechanism) used to treat asthma.
lipoxygenase inhibitors

leukotriene receptor blockers

List 3/4 short-acting beta2-agonists used to treat asthma.
albuterol (prototype)

terbutaline

metaproterenol

pirbuterol

List 2 long-acting beta2-agonists used to treat asthma.
salmeterol

formoterol

List 2 methylxanthines used to treat asthma.
theophylline

aminophylline

List 2 muscarinic antagonists used to treat asthma.
ipratropium

tiotropium

List 2 mediator inhibitors used to treat asthma.
cromolyn

nedocromil

List 2 I.V. corticosteroids used to treat asthma.
prednisolone (active metabolite of prednisone)

hydrocortisone

List 3 leukotriene antagonists used to treat asthma.
zafirlukast, montelukast

zileuton

List a monoclonal anti-IgE antibody used to treat asthma.
omalizumab

Why do beta2-agonists in higher doses cause tachycardia, arrhythmias, and tremors.
activate beta1-adrenoceptors at high levls

Are beta1- or beta2-agonists associated with tolerance?
beta2-agonists

What non-specific beta-agonist is used in the treatment of asthma?
isoproterenol

– primary use is for bradycardia or heart block

Methylxanthines MOA
inhibits PDE

*PDE degrades cAMP to AMP
*narrow therapeutic index

List 3 adverse effects of methylxanthines.
CNS (tremors, insomnia, convulsions)

cardiac stimulation (arrhythmias)

increased GI motility

*erythromycin, coffee, tea, cigarette-smoking can affect the effects of the drug
*beta-blockers can be useful in undoing CVS toxicity from theophylline

What derivative of theophylline is used in intermittent claudication to decrease the viscosity of blood?
pentoxifylline

Is ipratropium or tiotroipoium longer-acting?
tiotropium

Ipatropium and tiotropium MOA
competitive blockers of muscarinic receptors

What drug (based on mechanism) is preferred over beta2-agonists in COPD (associated with bronchospasm)?
antimuscarinic agents (ipratropium and tiotropium)

Cromolyn and nedocromil adverse effects (2)
cough and irritation of respiratory tract may occur with aerosol

List 2 IV steroids used in life-saving treatment of status asthmaticus.
hydrocortisone

prednisolone

List 3/5 surface-active corticosteroids used to treat moderate to severe asthma.
beclomethasone

dexamethasone

fluticasone

budesonide

flunisolide

How do corticosteroids affect beta-adrenoceptor responsiveness in the respiratory tract?
increase responsiveness

What drugs bind to intracellular receptors and activate glucocorticoid response elements in the nucleus?
steroids

– synthesis of substances that inhibit expression of inflammation and allergy

What drug class is a 1st line treatment for asthma in patients who are not responding well to beta2-agonists?
corticosteroids

– prevent modeling of respiratory tract, which may occur in severe, progressive inflammation of chronic asthma

Corticosteroids adverse effects (3/4)
oropharyngeal candidiasis

mild growth retardation may occur in children, but eventually reach full recovery of growth as adult

small degree of adrenal suppression may occur

major systemic toxicities (reduced with alternate day therapy)

What is the preferred drug in a case of bradycardia or heart block with a history of bronchial asthma?
isoproteronol

What 2 drug classes are used in antigen-, exercise-, and aspirin-induced asthma, but not in acute asthma?
antileukotrienes
– zafirlukast, montelukast

lipoxygenase pathway inhibitor
– zileuton

What 2 disorders are associated with antileukotriene use?
very rarely may produce Churg-Strauss syndrome and allergic granulomatous angiitis

What organ damage is associated with zileuton use?
liver

– elevation of liver enzymes

Omalizumab MOA and use
binds to IGE on sensitized mast cells and prevents activation by triggers

– prevents release of leukotrienes and other mediators

prophylactic management in asthmatic patients

Long-term treatment for patient with less than 2 bronchoconstrictive episodes per week with near normal spirometry
Long-term treatment for patient with less than 2 bronchoconstrictive episodes per week with near normal spirometry

Long-term treatment for patient with more than 2 bronchoconstrictive episodes per week with near normal spirometry
Long-term treatment for patient with more than 2 bronchoconstrictive episodes per week with near normal spirometry

Long-term treatment for patient with daily bronchoconstrictive episodes with 60-80% of normal spirometry
Long-term treatment for patient with daily bronchoconstrictive episodes with 60-80% of normal spirometry

Long-term treatment for patient with continual bronchoconstriction with less than 60% of normal spirometry
Long-term treatment for patient with continual bronchoconstriction with less than 60% of normal spirometry

Mild COPD FEV1% predicted and treatment
Mild COPD FEV1% predicted and treatment

Moderate COPD FEV1% predicted and treatment
Moderate COPD FEV1% predicted and treatment

Severe COPD FEV1% predicted and treatment
Severe COPD FEV1% predicted and treatment

Very severe COPD FEV1% predicted and treatment
Very severe COPD FEV1% predicted and treatment

List 2 uses of N-acetylcysteine in cystic fibrosis and drug overdose.
breaks disulfide bonds in mucus and liquefies it, making it easier to cough out

management of acetaminophen overdose

Which asthma drugs block the actions of adenosine?
methyxanthines (theophylline)

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