Martin Bronchodilator DSA

Question 1

Corticosteroids

Inhaled

Answer 1

Budesonide
Fluticasone

(anti-inflammatory)

Question 2

corticosteroids- oral

Answer 2

prednisone
methylprednisolone
prednisolone

(anti-inflammatory)

Question 3

Cromolyn compounds

Answer 3

cromolyn sodium

anti-inflammatory

Question 4

Leukotriene Inhibitors

Answer 4

Montelukast

anti-inflammatory

Question 5

Bronchodilators- beta 2 selective adrenergic agonists

Answer 5

Short-Acting beta 2-selective adrenergic agonists
Albuterol

Long-Acting beta 2-selective adrenergic agonists
Salmeterol
Formoterol

Others:
Epinephrine
Racemic Epinephrine

Question 6

Muscarinic antagonists

Answer 6

Ipratropium bromide

Tiotropium

Question 7

Combinations

Answer 7

Albuterol + Ipratropium bromide (Combivent)

Question 8

Bronchodilators:

Methylxanthines

Answer 8

Theophylline

Question 9

Decongestants

Answer 9

Sympathomimetic Agents
(alpha-agonists)
Phenylephrine
Oxymetazoline

Question 10

Asthma

Answer 10

currently viewed primarily as an inflammatory illness that results in bronchial hyperreactivity and bronchospasm. The recommendations for prevention and treatment of asthma emphasize control of the inflammatory component as the underlying problem and reserving bronchodilators primarily for symptomatic use. The inflammatory component and the airway narrowing of asthma are largely reversible, and thus, drug therapy plays a significant role in the management of the disease.

Question 11

chronic obstructive pulmonary disease (COPD)

Answer 11

disease state characterized by the presence of airflow obstruction due to chronic bronchitis or emphysema; the airflow obstruction is generally progressive, may be accompanied by airway hyperreactivity, and may be partially reversible. Drug therapy is useful in addressing the reversible component of COPD to induce bronchodilation, decrease inflammatory reaction, and facilitate expectoration.

Question 12

Allergen-specific IgE binds to

Answer 12

Fc receptors on mast cell.

When allergen comes in contact with IgE, the mast cell is activated and releases a large number of mediators.

t an enormous variety of mediators is released, each having more than one potent effect on airway inflammation. Thus, a pharmacological blocker of any one mediator, e.g. antihistamine, is ineffective in alleviating the symptoms or progression of asthma or the inflammatory component of other respiratory diseases. Corticosteroids, which can block many of the key steps in the inflammatory process, come closest to this ideal therapy.

Question 13

KEY FEATURES OF ASTHMA

Answer 13

1. Mast cell activation associated with early bronchospasm
2. Inflammatory cell infiltration with subsequently mediator release
3. Epithelial cell damage
4. Increased responsiveness of the airways to a variety of non specific stimuli

Question 14

Benefits of Aerosol Delivery

Answer 14

Consider Ipratroprium *

The pathophysiology of asthma appears to involve the respiratory tract alone. So, ideally, effective treatment could be achieved if drug administration was restricted to the lungs.

2. Aerosol application of drugs to the lungs can produce a high local concentration in the lungs with a low systemic absorption, thereby significantly improving the therapeutic ratio by minimizing side effects.
3. Both 2-agonists and corticosteroids have potentially serious side effects when delivered systemically.
4. Probably more than 90% of asthmatic patients who are capable of manipulating inhaler devices can be managed by aerosol treatments alone.
5. Factors that determine effective deposition of drug in the lung
   a. Particle size: >10 m deposit in mouth and oropharynx; <0.5 m are inhaled and then exhaled; 1-5 m deposit in small airway and are most effective.
   b. Rate of breathing and breath holding are important.
   c. The recommendation technique is that a slow, deep breath be taken and held for 5 - 10 sec.
6. Even under ideal conditions only 2 - 10 % of drug is deposited in lungs; most of the remainder is swallowed. Therefore, to have minimal systemic side effects, an aerosolized drug should be either poorly absorbed from the GI tract or be rapidly inactivated by first-pass liver metabolism. Consider Ipratropium

Question 15

Devices for Aerosol Delivery

Answer 15

Metered-dose inhalers (MDI)- Advantages of MDIs are low cost and portability; disadvantages include need for hand-lung coordination making it more difficult for young children and the elderly to use. Spacer devices that attach to the MDI markedly improve the ratio of inhaled to swallowed drug and reduce need for coordination.

Nebulizers: preferred for severe asthma exacerbations with poor inspiratory ability; do not require hand-lung coordination.

Dry powder inhalers:  require relatively high air flow to suspend the powder and can be irritating when inhaled.

Question 16

Use of beta agonists in asthma

Answer 16

preferred therapy for bronchoconstriction per se. These are the only agents shown to be immediately effective for relieving bronchoconstriction during acute, severe asthma. Beta 2-selective agonists are more potent at Beta 2 compared to Beta-11-adrenergic receptors.

Inhalation usually produces excellent bronchodilation

Question 17

Mechanism of Action of beta-Adrenergic Agonists

Answer 17

stimulate adenylyl cyclase and an increase in intracellular cyclic AMP.
–> decreased intracellular calcium, bronchial smooth muscle relaxation, and inhibition of mediator release from mast cells

Question 18

beta 2 selective

Answer 18

albuterol

Question 19

nonselective

Answer 19

epinephrine

Epinephrine is the drug of choice for the emergency treatment of anaphylactic reactions in general. Typically, epinephrine is administered by SQ injection

Question 20

LABA

Answer 20

Salmeterol is useful for prevention of nighttime asthma attacks and prophylactic bronchodilation.

Formoterol (Foradil Aerolizer) is a long-acting, dry powder inhaler for maintenance therapy of asthma or prevention of bronchospasm in COPD and exercise-induced asthma. It was recently approved as a solution for nebulization (Perforomist). Not for treatment of acute attacks***

Question 21

LABA recommendation

Answer 21

“Stop use of the LABA, if possible, once asthma control is achieved and maintain the use of an asthma-controller medication such as an inhaled corticosteroid.”

Question 22

Adverse Effects of beta-Adrenergic Agonists

Answer 22

Skeletal muscle tremor is the most common adverse effect.

Question 23

Corticosteroids

Answer 23

In asthma (and some COPD) an inflammatory response is responsible for the underlying disease process.
So many inflammatory mediators are involved that a blocker of any given autocoid or cytokine, e.g., antihistamine, is ineffective in alleviating the symptoms of asthma.
Corticosteroids block many of the steps involved in the inflammatory cascade.

Mechanism of Action
corticosteroids are steroid receptor agonists that bind to intracellular receptors that translocate to the cell nucleus and positively or negatively regulate gene transcription. This takes time.*

corticosteroids inhibit the production and release of cytokines, vasoactive and chemoattractive factors, lipolytic and proteolytic enzymes, decrease mobilization of leukocytes to areas of injury, and decrease fibrosis.

***General anti-inflammatory response.

Question 24

Anticholinergic Agents

Answer 24

The principal clinical use of ipratropium and tiotropium is in the treatment of COPD.

Ipratropium is used exclusively as an inhaled aerosol.

less intense than that produced by beta -agonists.

A useful bronchodilation response may last up to 6 hours with ipratropium while tiotropium is usually dosed once-per-day.

Combined treatment with ipratropium and beta 2-adrenergic agonists results in a slightly greater and more prolonged bronchodilation than therapy with either agent alone. Combined therapy can be considered if severe asthma or COPD exacerbations exist.
Albuterol + ipratropium bromide combination = Combivent and is a treatment of choice for COPD patients.

Ipratropium is also used intranasally to reduce secretion in both the upper and lower respiratory tract in allergic rhinitis and chronic postnasal drip syndrome (vasomotor rhinitis).

Question 25

Combination drug containing a corticosteroid and a long-acting beta 2-agonist for inhalation are now widely available are

Answer 25

Fluticasone + Salmeterol (Advair Diskus)

Question 26

theophylline

Answer 26

Bronchodilation (smooth muscle relaxation) is a clinically relevant effect

Theophylline was formerly a first-line therapy for asthma. It now has a far less prominent role in therapy because its benefits are modest, it has a narrow therapeutic index, there is considerable variation in absorption and elimination between patients, and monitoring of plasma drug levels is often required. Slow-release formulations of theophylline are preferred to avoid large swings in plasma concentrations of the drug.

Nocturnal asthma can be improved

Question 27

corticosteroids general purpose and ADRs

Answer 27

general anti-inflammatory effect

Growth retardation may be a concern when high doses used in children.
i. Adverse effects with long-term daily use of oral corticosteroids is associated with glucose intolerance, weight gain, increased blood pressure, osteoporosis, cataracts, immunosuppression, and mood disorder (including psychosis). Alternate day use can decrease the incidence of these adverse effects, except osteoporosis.

Question 28

cromlyn is not effective for

Answer 28

ongoing bronchospasm

When inhaled several times daily, cromolyn will inhibit both the immediate and the late asthmatic responses to antigenic challenge or exercise. This drug is less effective than inhaled corticosteroids, but is frequently used as an alternative to inhaled corticosteroid in children

Question 29

Zafirlukast and montelukast

Answer 29

are selective LTD4 receptor antagonists

Montelukast is considered safe for long-term use.

Question 30

Treatment of allergic rhinitis

Answer 30

similar to that for asthma. Topical corticosteroids delivered as an aqueous nasal spray

cromolyn sodium can be highly effective with minimal side effects.
C. Unlike in asthma, antihistamines (H1 histamine receptor antagonists) produce considerable, though incomplete, symptom relief.

Question 31

nasal decongestants

Answer 31

alpha agonists

Pseudoephedrine (Sudafed) access restricted in most states because of diversion to manufacture methamphetamine.

Question 32

COPD treatment

Answer 32

cease smoking tobacco

inhaled ipratropium or tiotropium combined with a beta 2-adrenergic agonist. Ipratropium bromide + albuterol is available as a combination (Combivent).

. Monotherapy with inhaled corticosteroids is not approved for use in COPD.

Question 33

anti-tussives

Answer 33

codeine: often used for in-patient treatment.
2. dextromethorphan: has no analgesic or addictive properties and does not act through opioid receptors. Nearly as potent as codeine and produces fewer subjective and GI side effects. Available in many over-the-counter preparations.

Question 34

Expectorants and a Mucolytic Agent

Answer 34

Stimulation of secretion in the respiratory tract is of theoretic value in the treatment of chronic irritating cough.