Lungs

A 17-year-old patient is brought to your allergy practice complaining of chronic cough that gets quite severe at times. The condition occurs about twice a week and is beginning to interfere with his studies. Which of the following would be the most appropriate treatment for this patient? (A) Oral prednisone (B) Omalizumab (C) Diphenhydramine (D) Inhaled budesonide (E) Theophylline

The answer is D. This is a fairly classical presentation of asthma, which should be con- firmed with further pulmonary testing. Mild persistent asthma can be treated in several ways (Table 9.1), but inhaled glucocorticoids are very effective. Oral prednisone has many side effects, especially in a young person. Omalizumab is for patients who are refractory to other treatments and those with allergies. Antihistamines such as diphenhydramine are poorly effective in asthma, and theophylline is only moderately effective.

Slow-release of salt-version of theophylline

Aminophylline

A asthmatic children who cannot tolerate adrenergic agonist can be given what as an alternative?

Anticholinergics like ipratropium

Foundation of therapy to treat COPD (emphysema and chronic bronchitis) by increasing airflow, alleviate symptoms and decreasing exacerbation of disease

Anticholinergics like ipratropium and tiotropium β2 agonists like albuterol Inhaled corticosteroids if FEV1 < 50% Long-acting β2 agonists can also be used

DOC bronchospasm caused by β blockers

Anticholinergics like ipratropium or tiotropium

Tx COPD patient suffering from acute episodes of bronchospasm

Anticholinergics like ipratropium or tiotropium

Nearly free from side effects without causing arrhythmias except from minor atropine-like effects like dry mouth, cough and urinary retention

Anticholinergics like ipratropium or tiotropium (safe to use in P with heart disorder)

Modere-to-severe intermittent and mild persistent allergic rhinitis should be treated with?

Antihistamines and/or oral decongestants/intranasal corticosteroids/leukotriene-receptor antagonists

Benzonatate

Antitussive agent

Butamirate

Antitussive agent

Codeine

Antitussive agent

Dextrometorphan

Antitussive agent

Levodropropizine

Antitussive agent

Pholcodine

Antitussive agent

Which of these is not indicated for treatment of allergic rhinitis? A. α-adrenergic agonists like phenylephrine and oxymetazoline B. H2 blockers C. Cromolyn D. Corticosteroids E. Montelukast

B - H1 blockers (antihistamines)

Gold-standard treatment for cough suppression by decreasing sensitivity of cough center in CNS to peripheral stimuli and decreasing mucosal secretion

Codeine (opioid)

Risk of addictive potential, fatigue, respiratory depression and constipation

Codeine (opioid)

1st line therapy by aerosol administration as prophylaxis and treatment of chronic (persistent) asthma

Corticosteroids

Block phospholipase A2 to reduce immune response (inhibition of COX and reduction of LTs)

Corticosteroids

Tx of chronic rhinitis by not-deep-inhaled nasal administration of a drug that takes 1-2 weeks for full effect

Corticosteroids like budesonide (prednisone or dexamethasone can be given orally)

Discontinuance of IV administration of this drug if P has shown improvement without suppressing HPA axis

Corticosteroids like prednisolone and hydrocortisone

Inhibition of chronic inflammation of airways without having a direct bronchodilator (contractile) response

Corticosteroids like prednisone

Tx status asthmaticus that can be given IV

Corticosteroids like prednisone

Tx allergic rhinitis by intranasal administration, preferably 1-2 weeks before exposure to allergen to optimize the effect

Cromolyn

Mast-cell stabilizer by blocking the initiation of immediate and delayed asthmatic reactions (Prevent degranulation of pulmonary mast cells, ↓histamine, PAF and LTC4 from inflammatory cells which mediate bronchoconstriction)

Cromolyn Nedocromil

Lack of analgesic effect in antitussive doses and low addictive profile, but at high doses it can cause dysphoria giving itself a potential cause of abuse

Dextrometorphan

Synthetic derivative of morphine that suppress the response of the central cough center

Dextrometorphan

Act centrally to decrease sensitivity of cough center to afferents (antitussive)

Diphenhydramine (H1 blocker)

Tx allergic rhinitis with no CNS entry

Diphenhydramine (H1 blockers) Promethazine Cetirizine Loratidine

Indirect-acting sympathomimetic that release stored catecholamines used in treatment of asthma

Ephedrine (DOA 6-8h)

DOC acute anaphylaxis and status asthmaticus

Epinephrine Isoproterenol

Leukotriene antagonists can be used to treat?

Exercise-, antigen- and aspirin-induced asthma Allergic rhinitis

Guaifenesin

Expectorant/mucolytic drug that affect CN X in GI to produce watery, less-viscous mucus to aid in clearance of mucus

Which of these is not a side effect of theophylline? A. Insomnia and seizures B. Cardiac arrhythmias C. GI distress D. Skeletal muscle tremors E. Drug interactions F. Dry mouth

F - this is seen with anticholinergics like ipratropium

Risk of antimuscarinic effects like dry eyes/mouth, urinary retention or constipation

H1 blockers (antihistamines)

Cetirizine

H1 blockers (antihistamines) with anticholinergic activity

Chlorpheniramine

H1 blockers (antihistamines) with anticholinergic activity

Diphenhydramine

H1 blockers (antihistamines) with anticholinergic activity

Loratidine Fexofenadine

H1 blockers (antihistamines) with anticholinergic activity

Promethazine

H1 blockers (antihistamines) with anticholinergic activity

What is not an established prophylactic strategy for asthma because it does not play a significant role in asthma?

Histamine

Long-acting β2 agonist only approved for COPD by ↓air trapping and exacerbations (often combined with corticosteroids or anticholinergics)

Indacaterol

Smallest risk of systemic adverse effects with?

Inhaled fluticasone which gives minimal systemic steroid toxicity associated with inhibition of ACTH and cortisol

Moderate to severe persistent allergic rhinitis should be treated with?

Intranasal corticosteroids like budesonide Oral antihistamines or leukotriene-receptor antagonists

Anticholinergics in the airway by reversing bronchoconstriction and decreasing mucus secretion

Ipratropium Tiotropium (longer-acting)

Purpose of a spacer attached to metered-dose inhaler (MDIs)?

It is a large-volume chamber that decrease deposition of drug in the mouth resulting in smaller, high-velocity drug particles (especially useful in children and elderly with improper inhaler technique)

Approved for prophylaxis of asthma given orally

Leukotriene antagonists like zafirlukast and zileuton

Prophylaxis of exercise, antigen- and aspirin-induced bronchospasm (not recommended for acute episodes)

Leukotriene antagonists like zafirlukast and zileuton

Slow and deep inhalation with metered-dose inhaler (MDIs)

Local aerosol administration of corticosteroids

Risk of skeletal muscle tremors and tachycardia

Long-acting β2 agonists

Slow onset of action with direct, long-acting duration of 12-24h

Long-acting β2 agonists LT antagonists also have 12h DOA

Potentiate corticosteroid action in chronic asthma to help attain asthma control

Long-acting β2 agonists like salmeterol or formeterol

Tx prophylaxis of asthma, especially night-time attacks

Long-acting β2 agonists like salmeterol or formeterol

Formeterol

Long-acting β2 full-agonist

Indacaterol

Long-acting β2 full-agonist

Salmeterol

Long-acting β2 partial-agonist

Risk of administration of α-adrenergic agonists as nasal decongestant?

Longer duration of action with increased systemic effects

Prophylaxis of asthma, especially in children or pregnant women

Mast-cell stabilizers like cromolyn and nedocromil

Topical administration wth only local effects due to lack of absorption from site of application (risk of irritation in airway and cough)

Mast-cell stabilizers like cromolyn and nedocromil (short duration of action of 3-6h)

Caffeine (coffee) Theophylline (tea) Theobromine (cocoa)

Methylxanthines (purine derivatives)

Bromhexine

Mucolytic

Gefitinib Erlotinib

Mucolytic agents that reduce viscosity by inhibiting EGFR used to treat mucus hypersecretion in patients with COPD

DNAse like dornase α

Mucolytic agents that reduce viscosity of mucus

N-acetylcysteine

Mucolytic agents that reduce viscosity of mucus and sputum used to decrease COPD exacerbations

Cleave disulfide bonds

N-acetylcysteine

Parenteral administration as prophylactic management of severe, refractory asthma that is not responsive to all drugs and allergic rhinitis

Omalizumab (monoclonal antibody)

Selectively bind IgE receptors on mast cells and basophils to decrease IgE binding (↓reaction of inhaled antigen)

Omalizumab (monoclonal antibody)

1st line therapy of allergic rhinitis

Oral antihistamines (H1 blockers) α-adrenergic agonists (decongestants)

Risk associated with inhalation of corticosteroids?

Oropharyngeal candidiasis Hoarseness

Long-acting nasal decongestant

Oxymetazoline

Tx intermittent claudication by decreasing blood viscosity

Pentoxifylline (methylxanthine)

Not used in long-term treatment of allergic rhinitis

Phenylephrine Oxymetazoline

Oral/systemic administration with an alternate-day therapy is preferred because it interferes with normal growth in children with risk of retardation of its vertical bone growth (osteoporosis)

Prednisone (can be given orally in severe asthma)

Phosphodiesterase type IV inhibitor with anti-inflammatory activity used in COPD to decrease exacerbations

Roflumilast

Albuterol

Short-acting β2 agonist

Terbutaline

Short-acting β2 agonist

DOC acute asthma attack by bronchodilation

Short-acting β2 agonists like albuterol, metaproterenol or terbutaline

DOC mild asthma

Short-acting β2 agonists like albuterol, metaproterenol or terbutaline

Inhalation from pressurized aerosol canisters or nebulizer to decrease systemic dose and adverse effects

Short-acting β2 agonists like albuterol, metaproterenol or terbutaline

Rapid onset of action within minutes with short duration of action for up to 4h

Short-acting β2 agonists like albuterol, metaproterenol or terbutaline

Zileuton is useful in the treatment of asthma because it (A) Inhibits prostaglandin biosynthesis (B) Inhibits leukotriene synthesis (C) Inhibits leukotriene receptors (D) Inhibits 12-lipoxygenase

The answer is B. By inhibiting 5-lipoxygenase, zileuton reduces leukotriene biosynthesis; it does not inhibit (and in fact it might increase) prostaglandin synthesis.

Which of the following statements about the mechanism of action of ipratropium is correct? (A) It acts centrally to decrease vagal acetylcholine (ACh) release (B) It inhibits pulmonary ACh receptors (C) It decreases mast cell release of histamine (D) It blocks the action of histamine at H1 receptors

The answer is B. Ipratropium is an acetylcholine (ACh) muscarinic receptor antagonist; it is poorly absorbed, so most of its effect is in the lung. It does not cross the blood-brain barrier and does not block mediator release or H1-receptors.

A 49-year-old man with a 15-year history of 2-pack a day smoking come to your office complaining of difficulty in breathing. You immediately notice a wheezing when he breathes. Following pulmonary function tests and lung dif- fusion studies, you and a pulmonolo- gist colleague diagnose his condition as chronic obstructive pulmonary disease (COPD) and prescribe inhaled tiopro- pium twice a day. He returns 6 months later, pleased that he has quit smoking, but complaining he is having about 1 episode of serious shortness of breath per day. Which of the following might you add to his treatment? (A) Oral dexamethasone (B) Roflumilast (C) Inhaled beclomethasone (D) Zileuton

The answer is B. Roflumilast is a fairly specific PDE4 inhibitor, useful to decrease exacerbations in patients with chronic obstructive pulmonary disease (COPD). Oral glucocorticoids such as dexamethasone pose serious risks when used chronically and inhaled glucocor- ticoids are not recommended in early-stage COPD although they might be of benefit in patients with severe disease. Zileuton is ineffective in COPD.

Which of the following statements regard- ing the pharmacokinetics of theophylline is correct? (A) It is primarily metabolized by the kidney (B) Its metabolism depends on age (C) It is poorly absorbed after oral administration (D) It has a wide therapeutic index

The answer is B. The metabolism of theophylline depends on age; the half-life of the drug in children is much shorter than in adults. The methylxanthines are all well absorbed and are metabolized in the liver.

Which of the following statements correctly describes the action of theophylline? (A) It stimulates cyclic adenosine mono- phosphate (AMP) phosphodiesterase (B) It is an adenosine-receptor antagonist (C) It does not cross the blood-brain barrier (D) It blocks the release of acetylcholine (ACh) in the bronchial tree

The answer is B. Theophylline may have several mechanisms of action, but its adenosine-receptor antagonist activity and the inhibition of phosphodiesterase are the best understood.

A woman who has asthma and is recover- ing from a myocardial infarction is on sev- eral medications including a baby aspirin a day. She complains of large bruises on her arms and legs and some fatigue. A standard blood panel reveals markedly elevated ala- nine aminotransferase (ALT). Which of the following is most likely responsible for the increase in liver enzymes? (A) Heparin (B) Zileuton (C) Zafirlukast (D) Albuterol (E) Aspirin

The answer is B. Zileuton is a leukotriene synthesis inhibitor that can cause increases in hepatic enzymes and altered liver function. It decreases the rate of heparin metabolism, leaving patients prone to easy bruising. Zafirlukast and albuterol are antiasthmatic agents but do not alter liver enzymes. Aspirin might cause bleeding disorders, but the low dose this patient is taking is unlikely to be responsible for the liver enzyme abnormalities.

A 20-year-old college student participates in several intramural athletic programs but is complaining that his asthma, which you have been treating with inhaled glucocorti- coids for 5 years, is getting worse. In the last month, he has used his albuterol inhaler at least 20 times following baseball practice, but he has not been waking much at night. You elect to change his treatment regimen. Which of the following would be the best change in treatment for this patient? (A) Oral triamcinolone (B) Zileuton (C) Salmeterol (D) Etanercept

The answer is C. The patient's asthma is worsening, especially in response to exercise or increased allergen exposure, and the excess of short-acting β2-agonists requires a change in medication. The best choice would be a long-acting β2-agonist like salmeterol. Oral glucocorticoids have many adverse effects, and zileuton is unlikely to be sufficiently efficacious in the worsening asthma. Etanercept is an anti-inflammatory used in rheuma- toid arthritis.

Which of the following statements regarding opiate action is correct? (A) It triggers a vagal reflex to suppress cough (B) It can cause diarrhea (C) Its expectorant action is caused by stimulation of mucus production (D) It acts centrally to suppress the medullary cough center

The answer is D. Opioids such as codeine act centrally to decrease the sensitivity of the cough center; they also decrease propulsion in the bowel.

Adenosine antagonist in the CNS that prevent bronchoconstriction

Theophylline

Inhibit phosphodiesterase (PDE) → ↑cAMP → bronchodilation

Theophylline

Risk of fatal cardiac arrhythmias

Theophylline

Risk of fatal insomnia and seizures

Theophylline

Used in acute/chronic asthma, especially prophylactic against nocturnal attacks (often combined with corticosteroids)

Theophylline

Oral administration

Theophylline Cortiosteroids

Individualization of this drug dosage is required because clearance varies with age, smoking status and concurrent use of other drugs that can cause drug interactions (shorter half-life in young people and smokers)

Theophylline (half-life of 8-9h)

Prevent bronchoconstriction

Theophylline via inhibition of adenosine Anticholinergics via inhibition of ACh Zafirlukast and zileuton via antagonizing LTs

Sodium salicylate

Used in P with aspirin-induced asthma

Leukotriene antagonists that are selective and reversible inhibitors at LTD4 and LTE4 receptors

Zafirlukast Montelukast

Risk of Churg Strauss syndrome (eosinophilic vasculitis) or allergic granulomatous angiitis

Zafirlukast and -lukasts

Risk of elevation of liver enzymes with liver toxicity

Zileuton

Selective inhibition of 5-lipooxygenase enzyme to prevent formation of leukotrienes

Zileuton

Constrict dilated arterioles in nasal mucosa to reduce airway resistance

α-adrenergic agonists like phenylephrine and oxymetazoline

Tx emphysema by inhibiting elastase which destroy lung parenchyma

α-proteinase inhibitors like prolastin and aralast

Powerful bronchodilator response via ↑cAMP ↑Mucociliary production and clearance Anti-inflammatory

β2 agonists

Stimulate adenylyl cyclase to ↑cAMP

β2 agonists

Aerosol administration

β2 agonists Ipratropium and tioptropium (anticholinergics) Cromolyn and nedocromil (mast-cell stabilizer) Corticosteroids

Promote bronchodilation

β2 agonists by stimulating adenylyl cyclase to increase cAMP Theophylline by inhibiting PDE to increase cAMP