L4- Respiratory Pharmacology

Question 1

list the 3 main characteristics of Asthma

Answer 1

• chronic inflammation of the airways
• bronchial hyper-responsiveness
• airflow obstruction

Question 2

in asthma, inflammation of the airway leads to the following 4 changes, (1), which will all lead to (2)

Answer 2

• bronchial smooth muscle spasm
• airway hyper-responsiveness
• airway edema
• inc mucus secretion

all => Airflow Obstruction

Question 3

list and define the classifications of Asthma (hint- 4)

Answer 3

Intermittent:

• <2 Sxs per wk
• <2 nighttime awakenings/mo

Mild Persistent:

• > 2 Sxs but not daily
• 3-4 awakenings/mo

Moderate Persistent:

• daily Sxs
• > 1 awakening/wk

Severe Persistent:

• Sxs throughout the day
• 4-7 awakenings/wk

Question 4

describe the MOA of inhaled β-agonists

Answer 4

1) binds β2 receptors (Gs) on airway smooth muscle cells
2) stimulation of adenylyl cyclase –> inc cAMP
3) cAMP activates protein kinase A –> phosphorylates / inactivates MLCK (myosin light chain kinase)
4) => relaxation of SM cells => bronchodilation

Question 5

SABAs are the drug of choice for…..

Answer 5

• relief of acute asthma symptoms

- prevent exercise induced asthma (use before exercise)

Question 6

LABAs are used for (1) therapy. They are almost always used with (2) because monotherapy with LABAs may cause (3). LABAs are also never used for (4).

Answer 6

1- long-term asthma therapy for moderate to severe asthma
2- ICS (inhaled corticosteroid)
3- inc risk of serious asthma-related events
4- acute Sxs or exacerbation

Question 7

The main adverse effects of SABAs and LABAs is (1). There is really only one contraindication for LABAs, which is (2).

Answer 7

1- tachycardia, tremor, hypokalemia

2- monotherapy: inc risk for serious asthma-related events

Question 8

describe the MOA of inhaled anticholinergics

Answer 8

1) blocks muscarinic (M3- Gq) receptors
2) dec IP3 and intracellular Ca++
3a) => bronchodilation
3b) => dec respiratory secretions

Question 9

(SABAs/SAMAs) are more efficacious

Answer 9

SABAs are more efficacious

Question 10

The main use of Ipratropium is (1). It is the drug of choice for (2).

The main use of tiotropium is (3).

Answer 10

(SAMA)
1- in adjunct with SABAs for moderate to severe asthma exacerbations
2- β-blocker induced bronchospasm

(LAMA)
3- adjunct with ICS for long-term control of severe persistent asthma

Question 11

SAMAs and LAMAs are compounds in the (1) form, therefore their adverse effects are limited to (2). The common adverse effects are (3). It is also pertinent that SAMAs are used over SABAs in (4) situations.

Answer 11

1- quaternary ammonium (lipophobic)
2- systemic circulation
3- xerostomia (mild anticholinergic effects)
4- Pts with CVD, SAMAs are safer than SABAs

Question 12

The main methylxanthine is (1), which functions to inhibit (2) in order to increase (3) levels intracellularly and induce (4).

Answer 12

1- theophylline
2- phosphodiesterase (normal function is cAMP –> AMP)
3- cAMP
4- bronchodilation

Question 13

Theophylline is administered in (1) fashion and is only used for (2) situations because of (3).

Answer 13

1- oral, IV
2- alternate therapy for persistent asthma
3- β2 agonists and corticosteroids are safer: theophylline has narrower therapeutic window, more AEs and drug interactions

Question 14

The most common adverse effects of theophylline is (1). At high concentrations, (2) are critical side effects that can occur.

Answer 14

1- HA, n/v, abdominal discomfort, restlessness

2- cardiac arrhythmias, seizures

Question 15

Glucocorticoids function to inhibit (1) and (2) in order to reduce (3). This is most effective for (4) while used in adjunct with SABAs.

Answer 15

1- phospholipase A2
2- COX2
3- LT and PG formation
4- prevents or reverses β2 desensitization with prolonged use of SABAs

Question 16

The most effective long-term control medication for persistent asthma is (1). (2) maybe added to (1) in (3) or used alone adjunct to other medications in (4) situations.

Answer 16

1- ICS
2- oral/systemic corticosteroid
3- long-term control of severe persistent asthma
4- short course for moderate to severe acute (=> speedy recovery and to prevent recurrence of exacerbation)

Question 17

(ICS/systemic) corticosteroids have more adverse effects.

• local AEs for ICS are (2)
• long-term AEs for ICS are (3)
• long-term AEs for systemic corticosteroids are (4)

Answer 17

1- systemic (ICS has less F)
2- oropharyngeal candidiasis, dysphonia, reflex cough, bronchospasm
3- osteoporosis, cataracts (+ deceleration of vertical growth in children)
4- hypercortisolism / Cushing’s syndrome

Question 18

Cromolyn and Nedocromil function to inhibit (1) in order to prevent (2) and (3) in asthmatic patients. They are not as useful for (4) in asthmatics.

Answer 18

1- mast cell degranulation
2- Ag induced bronchospasm
3- exercise induced bronchospasm
4- acute asthma attacks (b/c not bronchodilators)

Question 19

Cromolyn and Nedocromil are mainly used for (1) and (2)

Answer 19

1- alternative for mild persistent asthma
2- prevent exercise induced bronchospasm

Note- once widely used, now replaced by other therapies

Question 20

Cromolyn and Nedocromil:

• (1) common AEs
• (2) rare AEs
• (3) rare side effect syndromes

Answer 20

1- throat irritation, cough, mouth dryness
2- chest tightness, wheezing
3- reversible dermatitis, myositis, gastroenteritis, pulmonary infiltration with eosinophilia / anaphylaxis

Question 21

(1) is the main immunomodulator used for asthmatics. It is described as a (2) structure, used in order to bind (3) to prevent (4).

Answer 21

1- omalizumab
2- monoclonal Ab
3- IgE
4- binding / activation / degranulation of basophils and mast cells

Question 22

Omalizumab is mainly used for….

Answer 22

management of severe persistent asthma with evidence of allergy

Question 23

the main AE for omalizumab is (1), therefore it is only used in (2)

Answer 23

anaphylaxis- only administered in hospitals

Question 24

LTMAs, aka (1), function to interfere with (2), in order to reduce release from (3).

Answer 24

1- leukotriene modifying agents
2- pathway of leukotriene mediators
3- mast cells, eosinophils, basophils

Question 25

LTMAs are mostly used in (1) fashion. They are also used to prevent (2) and manage (3- a drug induced side-effect).

Answer 25

1- alternative therapy for asthmatics
2- exercise induced bronchospasm
3- NSAID exacerbated respiratory disease (NERD)

Question 26

describe the pathogenesis of NERD

Answer 26

(NSAID exacerbated respiratory disease)

1) NSAIDs inhibit COX1/2
2a) dec PG, TX synthesis
2b) inc LT synthesis
3) LTs => asthma-like Sxs and persistent bronchoconstriction

Question 27

Montelukast has the following AEs….

Answer 27

insomnia
anxiety
depression
suicidal thinking

Question 28

Zileuton has the following AEs….

Answer 28

hepatotoxicity

Question 29

COPD is a (acute/chronic) (sporadic/progressive) (ir-/reversible) obstruction of airflow. (4) is the main important risk factor. The three cardinal symptoms of COPD are (5).

Answer 29

1/2/3- chronic, progressive, irreversible obstruction to airflow
4- smoking
5- dyspnea, chronic cough, sputum production

Question 30

Oxygen therapy is indicated for COPD in……

Answer 30

• Pts w/ severe hypoxemia, O2 therapy will inc survival

- key component of hospital Tx for COPD exacerbation

Question 31

LAMAs and or LABAs are recommended to be used in (1) patients in order to improve (2) and reduce (3).

Answer 31

1- Pts with moderate to severe dyspnea (COPD)
2- lung function
3- COPD Sxs and exacerbation rates

Question 32

what is the key difference in LABA therapy for Asthmatics and COPD patients

Answer 32

Asthma: contraindicated to be used in monotherapy b/c of inc risk of asthma related death

COPD: no such evidence, monotherapy is appropriate

Question 33

SAMAs and SABAs are used in COPD for….

Answer 33

• Sx relief

- management of acute exacerbations

Question 34

ICS are used (more/less) in COPD patients than in asthmatics. This is because of (2), therefore it is appropriate to use ICS is (3) fashion.

Answer 34

1- less
2- ICS doesn’t slow COPD progression or reduce mortality + LABAs are more effective (therefore not used in monotherapy)
3- adjunct with LABA to improve lung function and reduce exacerbations

Question 35

the main mucolytic agent is (1), which functions to (2) and is used in treatment of (3)

Answer 35

1- N-acetlycysteine
2- breaks disulfide linkages in mucus => dec viscosity
3- COPD

Question 36

(1) are often used in COPD patients because exacerbations commonly involve (2). (2) is usually indicated by (3) and (4) changes, and therefore (1) therapy is usually prescribed.

Answer 36

1- antibiotics
2- bacterial infections in lower airways
3- increasing dyspnea
4- change in phlegm quantity or color

Question 37

Allergic rhinitis is the result of (1) due to various allergens. (1) will induce (2) symptoms. Treatment for allergic rhinitis consists of (3) and (4).

Answer 37

1- inflammation nasal mucosa
2- nasal pruritus, sneezing, rhinorrhea, nasal congestion
3- allergen avoidance
4- pharmacotherapy

Question 38

_____ is the first line treatment for allergic rhinitis

Answer 38

glucocorticoid nasal sprays

Question 39

list the AEs for glucocorticoid sprays

Answer 39

• local irritation of nasal mucosa
• nosebleed
• nasal septal perforation
• nasopharyngeal candidiasis

Question 40

compare the AEs for 1st and 2nd generation oral antihistamines

Answer 40

1st (diphenhydramine, chlorpheniramine): lipophilic –> sedation central effect

• anticholinergic effects
• orthostatic hypotension (α blocker)

2nd (loratadine, fexofenadine, cetirizine): hydrophilic –> no central effects

• minor anticholinergic effects
• little or no orthostatic hypotension (less likely to block α-receptors)

Question 41

(1) and (2) are the major nasal decongestants that work on (3) receptors in order to induce (4). (5) is the main risk of (1) and (2) if used in (6) fashion.

Answer 41

1/2- phenylephrine, pseudoephedrine
3- α-receptors
4- vasoconstriction of arterioles in nasal mucosa
5- rebound nasal congestion
6- longer than 3 days

Question 42

(1) and (2) are the main cough suppressors by directly acting on (3). (1/2) is preferred because of (4). (5) are the main adverse effects for (1) and (2).

Answer 42

1- codeine
2- dextromethorphan** (preferred b/c safer and lower abuse potential)
3- cough center in medulla –> suppress cough reflex
4- constipation, drowsiness