Respiratory

Question 1

1. Define asthma.

Answer 1

Reversible airway obstruction as a result of bronchial hyper-reactivity, airway inflammation, mucous plugging, and SM hypertrophy. [The airway obstruction is due to inflammation of the bronchial wall, constriction of the bronchiolar SM and increased mucous secretion.]

Question 2

2. What endogenous products play an important role in asthma?

Answer 2

1. Prostaglandins
2. ACh
3. B2-adrenergics
4. Histamine
5. Adenosine

Question 3

3. What are the major triggers of an asthma attack?

Answer 3

1. Allergens – induce mast cells
2. Infections – viral upper respiratory tract infection
3. Pharmacological factors – B-blockers, cholinergics, adenosine, aspirin
4. Exercise and Stress – vagal and adrenergic influence

Question 4

4. What are the different categories of drugs used to treat Asthma?

Answer 4

1. bronchodilators → B2 receptor agonists, antimuscarinic drugs, methylxanthines [control bronchoconstriction and symptoms]
2. Anti-inflammatory agents → corticosteroids, leukotriene inhibitors, mast cell stabilizers, anti-IgE antibodies [control bronchial hyperreactivity]

Question 5

5. What are the different short and long acting B2 adrenergic agonists? How do B2 adrenergic agonists tx asthma?

Answer 5

Short acting B2 agonists (SABAs) → Albuterol, Pirbuterol, Terbutaline [used for acute relief of bronchospasm]
Long acting B2 agonists (LABAs) → Salmeterol, Formoterol
*B2 agonists increase intracellular cAMP resulting in relaxation of the bronchial smooth muscle and subsequent bronchodilation. When administering these drugs they are inhaled minimizing their systemic effects b/c B2 agonists are poorly absorbed into the circulation via the lungs. [available via MDI (metered-dose inhalers), spaces of VHC (valved holding chambers)]

Question 6

6. What is a concern in regards to using long acting beta agonists?

Answer 6

A small percentage of the population may have a genetic predisposition (polymorphism at the b2 receptor) that causes worsened asthma → exacerbations → death. ??

Question 7

7. When should LABAs be used clinically?

Answer 7

1. do not take as rescue medication
2. use in conjunction with inhaled steroid
3. if asthma worsens after starting LABAs – seek medical help
4. if you take LABAs and suffer asthmatic exacerbations that does not respond normally to quick-relief – seek medical help

Question 8

8. How do you treat exercise induced bronchoconstriction (EIB)?

Answer 8

1. SABAs prior to exercise will prevent up to 2-4 hrs
2. LABAs prior to exercise will prevent up to 12 hrs
3. Montelukast will decreased EIB in 50% of pts up to 24 hrs

Question 9

9. What are adverse effects of inhaled B2 adrenergic agonist bronchodilators?

Answer 9

Tremors, tachycardia arrhythmias, hyperglycemia, tolerance, paradoxical bronchospasm

Question 10

10. Which anticholinergics are used as bronchodilators?

Answer 10

1. Ipratropium – short acting inhaled anticholinergic that can be used in asthma to prevent vagal mediated bronchoconstriction and drug induced bronchospasm (ex. B-blocker)
2. Tiotropium – long acting anticholinergic used once a day for COPD

Question 11

11. What is the mechanism of how anticholinergics are used as bronchodilators?

Answer 11

Parasympathetic stimulation causes bronchial constriction and mucous secretion. Anticholinergics are used to block the muscarinic receptors in the smooth muscles and maintain bronchial dilation of the airway.

Question 12

12. What are adverse effects of Ipratropium?

Answer 12

1. Dry mouth

2. Use with caution in pts with Glaucoma, BPH, bladder neck obstruction

Question 13

13. What Methylxanthine drugs are used to treat asthma? What is the mechanism of action of these drugs?

Answer 13

1. Theophylline – limited role in asthma due to small therapeutic window
2. Aminophylline
   * These methylxanthine derivates inhibit phosphodiesterase (enzyme responsible for metabolism of cAMP → AMP) allowing for increased levels of cAMP resulting in bronchodilation. These drugs also block adenosine receptors. An increase in caffeine or tea may have similar effects to theophylline with increased CNS and cardiac effects.

Question 14

14. What drugs interact to increase and decrease theophylline levels?

Answer 14

Increase levels → Cimetidine, erythromycin, ciprofloxacin

Decrease levels → phenytoin, phenobarbitone, carbamazepine

Question 15

15. What are complications of theophylline overdoses?

Answer 15

Tremor, insomnia, GI distress, nausea, hypokalemia, hyperglycemia, seizures, arrhythmias

Question 16

16. Give examples of corticosteroids used in asthma. What is the MOA of corticosteroids in the tx of asthma?

Answer 16

1. Beclomethasone
2. Dexamethasone
3. Fluticasone
4. Budesonide
5. Flunisolide
6. Prednisolone
   * Corticosteroids inhibit synthesis of arachidonic acid by phospholipase A2 thereby decreasing leukotrienes, cytokines, and prostaglandins. Steroids bind to intracellular receptors and activate glucocorticoid response elements (GREs) in the nucleus resulting in the synthesis of substances that inhibit expression of inflammation and allergy. They also increase B2 responsiveness in respiratory tract thereby reducing need for B2 agonists as well as prevent remodeling with severe, progressive inflammation of chronic asthma.

Question 17

17. What is the different dosing of corticosteroids in asthma management?

Answer 17

Acute exacerbations → systemic steroids when attack is severe
Maintenance therapy → low dose inhalation corticosteroids suppress inflammation and reduce the risk of exacerbation
*use in both acute and maintenance asthma management. Most inhaled corticosteroid goes in to the stomach to be metabolized.

Question 18

18. When pts are not responsive to normal asthma tx or for uncontrolled allergic asthma, what should be administered to the pt?

Answer 18

Omalizumab – this is an anti-IgE antibody that is administered parenterally. It binds to IgE on sensitized mast cells and prevents their activation and thus release of LTs and other mediators. It is used in the prophylactic management in asthmatic patients of inadequate control above the age of 12. There is a slim risk of the development of anaphylaxis.

Question 19

19. What are adverse effects of inhaled corticosteroids?

Answer 19

Cough, oral thrush, dysphonia

Question 20

20. What are the different systemic corticosteroids and what are their adverse effects?

Answer 20

Dexamethasone and prednisone → life saving steroid in status asthmaticus
Oral glucocorticoids → used in exacerbations with incomplete response to B2 agonists
*Adverse effects → abnormal glucose metabolism, increased appetite, weight gain, HTN, adrenal suppression [minimize systemic corticosteroid use to a few days]

Question 21

21. What are the specific leukotriene inhibitors used to treat asthma? What is the clinical use of leukotriene inhibitors in the tx of asthma?

Answer 21

1. Zileuton – inhibits 5-lipoxygenase which catalyzes the formation of leukotrienes from arachidonic acid
2. Zafirlukast – LTD4 receptor antagonist
3. Montelukast – LTD4 receptor antagonist
   * These medications are given orally and useful in exercise, antigen and aspirin induced asthma. They prevent bronchoconstriction and airway inflammation. These drugs are used in chronic maintenance, NOT acute bronchospasm.

Question 22

22. What are the adverse effects of leukotriene inhibitors?

Answer 22

Zileuton – elevated liver enzymes
Zafirlukast and Montelukast – development of vasculitis and systemic eosinophilia similar to Churg-Strauss syndrome (p-anca)

Question 23

23. Give examples of drugs used as release inhibitors in the treatment of asthma. What are these drugs MOA?

Answer 23

1. Cromolyn
2. Nedocromil
   * The exact mechanism of these drugs is unknown, but they are thought to be mast cell stabilizes that reduce the release of inflammatory and bronchoconstrictor mediators from sensitized mast cells. Cromolyn can be used as an inhaled aerosol for asthma, but it is rarely used. It is more commonly used for ophthalmic nasopharyngeal and GI allergies.

Question 24

24. What are adverse effects of Cromolyn and Nedocromil?

Answer 24

Infrequent laryngeal edema, cough, wheezing and Nedocromil may cause an unpleasant taste

Question 25

25. What is the mnemonic used to remember medications for asthma exacerbations?

Answer 25

ASTHMA A – albuterol/pirbuterol/terbutaline S – steroids T – theophylline H – humidifier O2 M – magnesium (severe exacerbations only when B2 agonists and anti-cholinergics are unsuccessful) A – anticholinergics [more of a preferred tx for COPD]

Question 26

26. What is the mnemonic used to remember treatment for COPD exacerbations?

Answer 26

``` COPD C – corticosteroids O – oxygen P – prevention D – dilators (anticholinergics, B2 agonists) *B2 agonists – Albuterol, Salmeterol **DO NOT use B-blockers or cholinergic ***Mucolytics (NAC) – liquefies mucus in COPD pts by disrupting disulfide bonds ```

Question 27

27. What drugs may cause pulmonary fibrosis and breathing difficulties? What are the general symptoms?

Answer 27

Drugs → Amiodarone, Busulfan, Bleomycin, Carmustine, Methotrexate, Nitrofurantoin Signs and Symptoms → shortness of breath, cough, fatigue, weakness, chest pain

Question 28

28. What are examples of opioids used as cough mediations (antitussives)? What is the MOA of these drugs?

Answer 28

1. Codeine 2. Dextrometorphan * MOA →acts on GPCR leading to closure of presynaptic nerve voltage operated Ca2+ channels or open K+ channels inhibiting postsynaptic neurons. These are used to relieve acute debilitating cough or reduce cough reflexes.

Question 29

29. What is rhinitis?

Answer 29

Inflammation of the mucous membranes of the nose most commonly caused by viruses or HSN responses to airborne allergens. Treatment generally includes avoidance therapy , antihistamines, nasal corticosteroids, a-adrenergic agonists or cromolyn sodium (mast cell stabilizers).

Question 30

30. Give examples of 1st and 2nd generation H1 antagonists.

Answer 30

1st generation → Diphenhydramine, chlorpheniramine | 2nd generation → Loratadine, Fexofenadine, Cetirizine

Question 31

31. What is the mechanism of action, use and AE of 1st generation H1 blockers?

Answer 31

Diphenhydramine, chlorpheniramine MOA → competitive pharmacologic block of peripheral and CNS H1 receptors plus a- and M- receptor block. It also has an anti-motion sickness effect Uses → hay fever, angioedema, motion sickness, OTC for sleep aid, parenterally for dystonias AE → sedation and anticholinergic effects

Question 32

32. What is the mechanism of action, use and AE of 2nd generation H1 blockers?

Answer 32

Loratadine, Fexofenadine, Cetirizine MOA → competitive pharmacologic block of peripheral H1 receptors [no CNS involvement so no autonomic or anti-motion sickness effects] Uses → hay fever, angioedema

Question 33

33. What corticosteroids are used to treat chronic rhinitis? What is its MOA, use and AE?

Answer 33

Beclomethasone, Flunisolide MOA → inhibition of PLA2, reduction of COX Use → chronic rhinitis but does not show improvement until 1-2 weeks after start of therapy AE → pharyngeal candidiasis

Question 34

34. What is the MOA, use, duration of action, and AE for the use of phenylephrine with rhinitis?

Answer 34

MOA → a1, a2 agonist Use → decongestant, mydriatic, neurogenic hypotension – given via oral, inhalant, topical or parenteral Duration of action → 10-15 minutes AE → HTN, stroke, MI

Question 35

35. When does surfactant synthesis begin and when is maturation complete?

Answer 35

Begins at week 26 | Ends around week 35

Question 36

36. What should be administered before birth to prevent ARDS?

Answer 36

Dexamethasone

Question 37

37. Daptomycin? – should not be used for pneumonia as it avidly binds to and is inactivated by surfactant

Answer 37

??