USMLE Step 2 Review 19 06 Drugs of Choice Asthma 1

USMLE Step 2 Review 19 06 Drugs of Choice Asthma 1

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Begin 19 06 Drugs of Choice Asthma 1 Transcription

The following section on asthma is long, but you’ll see this on the boards, and I guarantee you will see it all the time on rotations. Most of it is on emergency treatment because once you’ve got that, understanding chronic management is easy. Here we go.

What is the primary non-drug strategy that should be considered in the management of asthma first?

  • Avoidance of environmental irritants.

And what are the 4 categories of environmental irritants that often trigger asthma?

  • Cold air, dust, mold, animal dander.

What drug must always be given first in treating acute asthma?

  • Humidified oxygen.

What 2 categories of drugs are absolutely contraindicated in the acute asthmatic, even if the patient is extremely anxious and agitated?

  • Sedatives and tranquilizers.

Why?

  • They may precipitate respiratory arrest.

What class of drug often used for respiratory therapy is also contraindicated during an acute asthmatic attack?

  • Mucolytic agents.

Why?

  • By causing coughing up of sputum, they may precipitate bronchiospasm if a large bolus of sputum comes up at once.

Now, when mucolytic therapy IS indicated, in a less acute situation of asthma, what is the mucolytic agent of choice?

  • Acetylcysteine.

And the trade name for Acetylcysteine?

  • Mucomyst.

What is a strategy additional to oxygen, in acute asthma, that often should precede direct treatment with a specific drug?

  • Hydration IV saline.

Now, what 2 common conditions of the acute asthma patient indicate hydration with IV saline?

  • Dehydration and thick mucus plugging.

Why is using hydration to dissolve thick mucus in the lungs not contraindicated in the acute phase, even though Acetylcysteine/Mucomyst is?

  • Hydration thins the mucus much more gradually, and evenly.

Finally, what class of cardiac drugs must not be used to treat cardiac arrhythmias, hypertension, or angina when acute asthma is present?

  • Beta adrenergic blockers, even selective agents.

What is the reason for this?

  • Bronchodilation, which is what you need to achieve in treating acute asthma, is mediated by beta-2 adrenergic receptors.

What enzyme is stimulated by binding of a lung beta-2 adrenergic receptor?

  • Adenylyl cyclase.

And what conversion does adenylyl cyclase perform?

  • ATP to cyclic AMP.

What effect does this conversion of ATP to cyclic AMP have on intracellular calcium in the smooth muscle cells?

  • It causes the intracellular calcium to bind to cell membranes.

And what effect does the binding of the intracellular calcium to the cell membranes have?

  • It reduces the myoplasmic calcium concentration.

And the effect of reducing myoplasmic calcium concentration?

  • Relaxation of bronchiole smooth muscle.

What class of drug, then, is the first-line strategy for achieving bronchodilation in the emergency treatment of acute asthma?

  • Beta-2 adrenergic agonists.

And what other class of drug is the cornerstone of emergency treatment in conjunction with beta-2 agonists?

  • Corticosteroids.

There are 2 benefits that corticosteroids are thought to provide by being used along with bronchodilators, what are they?

  • Reduction of inflammation and restoration of beta receptor activity.

We’ll come back to the corticosteroids later. Right now, we’re going to go through the use of bronchodilators. The older bronchodilators were non-specific catecholamine beta adrenergic agonists, and had a short duration of action. What were the 2 most commonly used in the past? Isoproterenol and epinephrine.

And the trade name for Isopreterenol?

  • Isuprel.

And the trade name for epinephrine?

  • Adrenalin.

What are 4 side effects with using these older catecholemines?

  • Agitation, tachycardia, arrhythmias, hypertension.

The new drugs are much more beta-2 specific, so they tend to avoid cardiac effects. What is the preferred route of administration except in certain cases with children?

Aerosol delivery.

And what is the alternative route of administration?

  • Subcutaneous injection.

In the emergency room, for treating acute asthma and bronchospasm, only 2 beta-2 agonists are available for use with a compressor driven nebulizer, and they are both alternatives for drug of choice via this route.

What are they?

  • Isoetharine Mesylate and Metaproterenol Sulfate.

Again, beta-2 agonists for use with compressor driven nebulizers in the hospital setting?

  • Isoetharine and Metaproterenol.

And the trade name for Isoetharine?

  • Bronkometer.

And the trade name for Metaproterenol in forms suitable for aerosol?

  • Alupent.

There are 3 other beta-2 agonists which can be used, but are available only in metered-dose inhalers. Which of the 3 is most commonly used?

  • Albuterol.

And 3 trade names for Albuterol?

  • Proventil, Ventolin, Volmax.

And what are the other 2 also used?

Terbutaline, Ditalberol.

And the 3 trade names for Terbutaline?

  • Brethaire, Brethine, Bricanyl.

And the trade name for Bitolterol?

  • Tornalate.

Now, Bitolterol/Tornalate is a new concept in beta-2 agonists. It’s a pro-drug, which is inactive until hydrolyzed by esterases in the lung.

What is it converted into in the lung?

  • Colterol.

And what type of agonist is Colterol?

  • A beta-2 agonist.

What other factor increases its beta-2 agonist specificity for the lungs and not the heart? 

  • The hydrolyzing esterases are in the lung, and not in the heart.

Many emergency rooms still give beta agonist by subcutaneous injection, but Tintinalli, the bible of emergency medicine, discourages this practice, except for children when needed, stating that subcutaneous injection “is no more effective and is associated with more systemic side effects”.

What is the non-selective beta agonist still being given by subcutaneous injection in some places?

  • Epinephrine.

And the trade name?

  • Adrenalin.

And what is the beta-2 agonist given by subcutaneous injection?

  • Terbutaline.

And 2 trade names for Terbutaline in injectable form?

  • Brethine, Bricanyl.

Finally, there’s 1 more beta-2 agonist we should talk about. What is the long-acting beta-2 agonist (at least 12 hours) that binds more strongly to the beta 2 receptor, and which is more appropriate for maintenance therapy than for emergency use?

  • Salmeterol.

And the trade name for Salmeterol?

  • Serevent.

How is Salmeterol/Serevent administered?

  • Via a metered-dose inhaler.


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