Bronchodilator/Pharm Martin

Question 1

inflammatory illness that results in bronchial hyperreactivity and bronchospasm

Answer 1

asthma

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 2

presence of airflow obstruction due to chronic bronchitis or emphysema

may be accompanied by airway hyperreactivity and may be partially reversible

Answer 2

COPD

Question 3

what does allergen-specific IgE bind to

Answer 3

Fc receptors on mast cells

Question 4

<10 um size particle

Answer 4

deposit in mouth and oropharynx

Question 5

<0.5 um particle

Answer 5

inhaled and then exhaled

Question 6

1-5 um

Answer 6

deposit in small airways are the most effective

Question 7

in order to minimize systemic side effects of an inhaled drug, it should be….

Answer 7

poorly absorbed from the GI tract or rapidly inactivated by first pass metabolism

Question 8

only agents shown to be immediately effective for relieving bronchoconstriction during acute, severe asthma

Answer 8

b2 agonist

Question 9

what molecule increases with b2 agonists

Answer 9

stimulate adenylyl cyclase to increase intracellular cyclic AMP

Question 10

increases in cAMP (induced by B2 agonists) is associated with …

Answer 10

decreased intracellular calcium, bronchial smooth muscle relaxation, and inhibition of mediator release from mast cells

Question 11

albuterol

Answer 11

B2 short acting agonist

Question 12

duration of action of albuterol

Answer 12

2-6 hrs

onset in <15 min

Question 13

used as a nebulizer solution to treat bronchospasm in infants and children

drug of choice for the emergency treatment of anaphylactic reactions in general

Answer 13

epinephrine

Question 14

mechanism of action of epi in the treatment of anaphylaxis

Answer 14

causes vasoconstriction that limits edema and swelling of the upper airways, produces bronchodilation, and inhibits mediator release from mast cells.

Question 15

useful for prevention of nighttime asthma attacks and prophylactic bronchodilation.

Answer 15

Salmeterol
long acting (12 hrs)
selective B2 agonist
slower onset of action

not suitable for the treatment of acute bronchospasm

Question 16

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).

Answer 16

Formoterol

not for the treatment of acute attacks

long acting B2 agonist

Question 17

what is the problem with continued use of long=acting B2 agonists

Answer 17

down regulate beta 2 receptors with loss of the bronchoprotective effect from rescue therapy

Overall the meta-analysis showed that the use of a long-acting beta-2 agonist was associated with an increased risk of a composite endpoint of asthma-related death, intubation or hospitalization; the highest risk was in children 4-11 years old. There was no significant increase in risk when a long-acting beta-2 agonist was used with an inhaled corticosteroid.

Question 18

the most effective long-term treatment for control of symptoms in patients with persistent asthma.

Answer 18

inhaled corticosteroids

Question 19

inhaled corticosteroids plus what other compound are useful in the treatment of asthma (reduces symptoms and exacerbations)

Answer 19

addition of salmeterol or formoterol

Question 20

what are the reccomendations of use of long term beta 2 agonists

Answer 20

Long-acting beta-2 agonists should not be used as monotherapy for asthma, especially in children. For maintenance treatment of persistent asthma, long-acting beta-2 agonists should be used for asthma only in combination with an inhaled corticosteroid, preferably in a fixed-dose combination in the same inhaler. How the fixed-dose combinations of fluticasone/salmeterol and budesonide/ formoterol compare with each other remains to be determined. Now the FDA has issued new Safe Use Requirements and labeling requirements for long-acting beta-2 agonists that include the following: “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 21

oral administration of b- agonists is not widely used b/c of what risks?

Answer 21

skeletal muscle tremor

muscle cramps

cardiac tachyarrhythmias

metabolic disturbances

hypokalemia (especially pt’s on diuretics)

elevation in serum glucose

Question 22

what are the 2 situations where oral therapy with B agonists are appropriate?

Answer 22

1) In young children (<5 years old) who cannot manipulate metered dose inhalers yet have occasional wheezing with upper respiratory tract infections, Brief courses of oral albuterol or metaproterenol syrups are well tolerated and effective.
2) In some patients with severe asthma exacerbations, any aerosol, nebulizer or MDI, can be irritating and cause a worsening of cough and bronchospasm. Albuterol tablets can be an effective oral therapy in these circumstances.

Question 23

true or false….The frequency of adverse systemic side effects is greater with oral therapy and greater in adults than in children. (oral therapy with beta agonists)

Answer 23

true

Question 24

what are the most common adverse effects of B-adrenergic agonists

Answer 24

skeletal muscle tremor

CNS stimulation –> restlessness, apprehension, anxiety, tremors

CVS stimulation–> tachycardia, dysrhymthmias, hyper or hypotension

hypokalemia

hyperglycemia

drug interactions–> potentiation of cardiotoxicity of thyroid, digitalis and methylxanthines

Question 25

ipratropium bromide

Answer 25

anticholinergic agent

used exclusively as an inhaled aerosol

Question 26

tiotropium

Answer 26

anticholinergic agent

Question 27

principal use of anticholinergic agents

Answer 27

COPD

Question 28

why do ipratropium and tiotropium have little or no effect in change of heart rate, blood pressure, bladder function, intraocular pressure or pupillary diameter

Answer 28

poor absorption from the lung or GI tract due to the quaternary amine structure (permanately charged)

Question 29

if given parenterally, what effect would the anticholinergic agents have ….

Answer 29

tachycardia, bronchodilation, urinary retention, dry mouth

no significant CNS effects b/c of quaternary ammonium structure

Question 30

how long does ipratropium last?

Answer 30

6 hours

Question 31

ipratropium last how long

Answer 31

usually dosed once per day

Question 32

combined treatment with ipratropium and what other agents results in a greater and more prolonged bronchodilation than therapy with either agent alone

Answer 32

Ipratropium + B2 adrenergic agonist

Combivent = albuterol + ipratropium bromide and is the treatment of choice for COPD patients

Question 33

what is the use of intranasal ipratropium

Answer 33

reduce secretion in both the upper and lower respiratory tract in allergic rhinitis and chronic postnasal drip syndrome (vasomotor rhinitis).

Question 34

what is Theophylline

Answer 34

A methylxanthine (Bronchodilator= smooth muscle relaxation)

Question 35

what are the cellular actions of methylxanthines

Answer 35

adenosine receptor antagonists
(adenosine can cause bronchospasm)

Inhibit cyclic nucleotide (cyclic AMP and cyclic GMP) phosphodiesterases and thereby elevate the cellular concentrations of these second messengers. However, the concentrations required to inhibit these enzymes is probably not achieved with therapeutic doses.

b. Lower intracellular calcium ion concentrations.
c. Hyperpolarize cell membranes

Question 36

is theophylline used as a first line therapy for asthma?

Answer 36

no

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.

Question 37

what is a therapeutic use of theophylline

Answer 37

nocturnal asthma

with slow release theophylline

less effective than inhaled corticosteroids or salmeterol

Question 38

romflumilast

Answer 38

bronchodilator - PDE4 inhibitor

Question 39

when is an asthma patient a candidate for inhaled corticosteroid?

Answer 39

those who require inhaled B adrenergic agonists four or more times weekly

Early regular use of low-dose inhaled corticosteroids in patients with mild persistent asthma of recent onset decrease the risk of severe exacerbations and improves control of symptoms.

Question 40

how long does it take for improvement in asthma symptoms with inhaled corticosteroids?

Answer 40

Asthmatic patients maintained on inhaled corticosteroids show improvement of symptoms and lowered requirements for “rescue” with β-adrenergic agonists. Improvement may be seen within one week, may continue for up 2 years or longer, and reductions in dose over time are often possible.

Question 41

what is the MOA of corticosteroids

Answer 41

Mechanism of Action:

a. Corticosteroids bind to intracellular cortisol receptors that translocate to nucleus and positively or negatively regulate gene transcription.
b. These drugs inhibit 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 effect.

Question 42

what is an adverse effect of local deposition of oral corticosteroids

Answer 42

Oral candidiasis and dysphonia can occur due to local deposition of the drug, particularly with MDIs.

Question 43

what are the adverse effects of corticosteroids

effects on bone
skin
growth?

Answer 43

a. Hypothalamic-pituitary-adrenal axis suppression - low risks until high dosages are used.
b. Bone resorption - modest risks
c. Effects on carbohydrate and lipid metabolism - minor risks
d. Cataracts and skin thinning - dose-related-
e. Purpura - dose-related
f. Dysphonia - usually resolves with no consequences
g. Candidiasis - incidence reduced with use of a spacer device and rinsing mouth after dosing.
h. Growth retardation may be a concern when high doses used in children.

Question 44

what are some adverse effects with longer term daily use of oral corticosteroids

Answer 44

glucose intolerance 
weight gain
increased BP
osteoporosis
cataracts
immunosuppression 
mood disorder (psychosis)

Question 45

cromolyn sodium MOA

Anti-inflammatory

Answer 45

Cromolyn sodium inhibits the release of histamine and other autocoids from sensitized mast cells and indirectly inhibits antigen-induced bronchospasm.

2. Cromolyn may suppress the activating effects of chemoattractant peptides on eosinophils, neutrophils, and monocytes.
3. Cromolyn does not directly relax smooth muscle but after long-term therapy bronchial hyperreactivity to allergens, histamine, and exercise is significantly diminished.

Question 46

what is the primary therapeutic use of cromolyn sodium?

Answer 46

prophylaxis - prevent asthma attacks

NOT effective in treating 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 47

Monteleukast? what is it and what is its MOA

Answer 47

Anti-inflammatory - Anti-leukotriene drug

selective LTD4 receptor antagonist

Question 48

what are the role of leukotrienes in asthma

Answer 48

neutrophil chemoattractants

bronchoconstriction

increased bronchial reactivity

mucosal edema

mucus hypersecretion

Question 49

therapeutic use of monteleukast

Answer 49

can be taken long term

not recommended for acute asthma attacks

clinical trials have shown that leukotriene inhibitors are especially useful for patients who experience aspirin-induced asthma attacks. Aspirin in these patients shifts arachidonic acid metabolism from prostaglandin production to leukotriene production.

Question 50

what are the adverse effects of leukotrienes

Answer 50

dyspepsia

liver toxicity - contraindicated in pt’s with abnormal liver function

Question 51

Omalizumab

Answer 51

Anti IgE antibody

Question 52

what is the standard treatment for allergic rhinitis

Answer 52

topical corticosteroids- fluticasone (nasal spray) or cromolyn sodium

alpha agonist (phenylephrine, pseudoephedrine) - rebound congestion is a problem with these

Question 53

chronic obstructive pulmonary disease

how do you prevent?
how do you treat COPD pt’s with active inflammation, bronchospasm, and excessive mucus production?

Answer 53

stop smoking!!!

treat–>
inhaled ipratropium or tiotropium combined with B2 agonist (albuterol)

monotherapy with inhaled corticosteroids is NOT approved for use in COPD

Question 54

triple therapy in COPD

Answer 54

Recent clinical trials have shown that triple therapy (tiotropium, formoterol or salmeterol, and fluticasone or budesonide) was superior to treatment with 1 or 2 agents in relieving symptoms such as dyspnea and in improving lung function.

Question 55

what is a cough a sign of

Answer 55

Cough is a nonspecific sign of upper or lower airway irritation or inflammation and is mediated through reflex vagal pathways. Nonproductive cough that is irritating to the throat and self perpetuating or exhausting to the patient is an indication for antitussive therapy.

Question 56

how do opioids work?

Answer 56

believe to act at the CNS level by suppression of the cough reflex

Question 57

what is the MOA of expectorants and mucolytic agents?

Answer 57

The mechanism of action of expectorants is unknown whereas the mucolytic agent is thought to act by facilitating the depolymerization of mucopolysaccharides in dried airway secretions.

Question 58

guaifenesin

Answer 58

expectorant

is claimed to enhance the output of respiratory tract fluid by reducing adhesiveness and surface tension facilitating the removal of viscous mucus. As a result, nonproductive coughs become more productive and less frequent. There is a lack of convincing studies to document efficacy.

Question 59

what drug is used in cystic fibrosis patients to aid in clearing of secretions

Answer 59

recombinant DNAse (Dornase alpha)

a recombinant DNAse has become available as a nebulizer solution for treatment of cystic fibrosis. Inspissated secretions containing large numbers of inflammatory cells lodge in the smaller airways causing obstruction in cystic fibrosis. A substantial portion of the purulent material is due to the DNA from the nuclei of lysed cells. Inhaled DNAse has been shown to aid in clearing these secretions.