3.7.2. Pharmacology of Astma

Question 1

Adrenergic agonists stimulate what?

Answer 1

Stimulate B2-adrenoreceptors, resulting in the relaxation of bronchial smooth muscle

Question 2

Adrenergic agonists inhibit what?

Answer 2

inhibit the release of mediators, stimulating mucociliary clearance

Question 3

Albuterol, levalbuterol, pirbuterol, metaproterenol are what kinds of drugs?

Answer 3

B2-selective agonists: Preferred for brochoconstriction

Question 4

With B2 selective agonists, what is their effect?

Answer 4

Enhanced B2 selectivity = Bronchodilation

Question 5

How do we administer B2 agonists and how long does it take to activate?

Answer 5

administered by inhalation, active in 1-5 minutes

Question 6

Long term effect of B2 agonists?

Answer 6

long-term use associated with diminished control of breathing, possibly due to down regulated B-receptors

Question 7

Effect of B2 agonists on specific pulmonary cells?

Answer 7

Increases surfactant by Type II pneumocyte, ciliary clearence

Question 8

B2 agonists desensitizes and downregulates a few things. What are they?

Answer 8

Desensitizes neutrophils, eosinophils, T-Cells, decreases cholinergic transmission as well as plasma exudation and mast cell releases

Question 9

Discuss isoproterenol and what it does?

Answer 9

Isoproterenol: relatively non-selective B-receptor and potent bronchodilator

Question 10

Discuss Epinephrine and what it acts on?

Answer 10

Epinephrine: available OTC inhalant, acts on B1, B2, and A1 receptors; onset in 5-10 min and duration 60-90 minutes

Question 11

Salmeterol, formoterol are examples of what?

Answer 11

Long acting B2-agonists

Question 12

Salmeterol, formoterol are administered as inhalants but with slower onset of action and longer duration. Why?

Answer 12

very lipophilic side chains that slow diffusion out of the airway (very high lipid solubility)

Question 13

Salmeterol, formoterol, which are 50x more selective than albuterol, are used in the clinical setting primarily for what?

Answer 13

use for prophylaxis of asthma

Question 14

Discuss the specificity of Terbutaline and it’s effect on the heart

Answer 14

moderately specific B2 agonist that is available as injection or tablet moderately cardiostimulatory

Question 15

Side effects of Epinephrine and isoproterenol

Answer 15

Epinephrine and isoproterenol have significant B1-receptor activity and can cause increases in cardiac effects (tachycardia, arrhythmias, angina)

Question 16

most common side-effect of B2-agonists is ____ ____.

Answer 16

most common side-effect of B2-agonists is muscle tremors (skeletal)

Question 17

A-receptor agonists may cause _____ and _____.

Answer 17

A-receptor agonists may cause vasoconstriction and hypertension

Question 18

What is the side effect “Tachyphlaxis” and how do we counter it?

Answer 18

Tachyphlaxis, blunted response due to prolonged use, cna be countered by switching to a different agonist or adding methylxanthine or a corticosteroid

Question 19

Methylxanthines cause what and how?

Answer 19

broncohdilation via action on smooth muscles of the airways

Question 20

Theophylline has _____ properties and reduces airway responsiveness to ____ and _____.

Answer 20

Theophylline has anti-inflammatory properties and reduces airway responsiveness to histamine and allergens

Question 21

Methylxanthines does what biochemically?

Answer 21

inhibits PDE (increasing cAMP) at high doses

Question 22

Methylxanthine pharmacologic effect (4)

Answer 22

1. Produce rapid relaxation of smooth muscle in bronchioles 2. decrease response to histamine 3. stimulate ciliary transport of mucus 4. improve contractility of diaphragm

Question 23

Methylxanthine has effects on other systems besides the pulmonary one. What are those effects?

Answer 23

1. chronotropic and inotropic actions on the heart 2. pulmonary and peripheral vasodilation but cerebral vasoconstriction 3. at high doses can lead to nervousness and seizures due to medullary stimulation

Question 24

Methylxanthine can be used for 3 things?

Answer 24

1. as an adjunct to inhaled corticosteroids and B-agonists to improve response 2. treat COPD and emphysema 3. treat apnea in preterm infants (specifically caffeine)

Question 25

Methylxanthine adverse effects

Answer 25

1. Physical: arrhythmias, nervousness, vomitin, and GI bleed 2. Psych: behavioral problems in children 3. Contraindications: combined use with B2 receptors is suspected for increased asthma mortality

Question 26

Ipratrpoium and atropine are what drugs?

Answer 26

Are muscarinic antagonists

Question 27

What do muscarinic antagonists do?

Answer 27

competitive antagonists of ACh

Question 28

Muscarinic antagonists do what?

Answer 28

inhibit constriction of airways and decrease vagal-stimulated mucus secretion

Question 29

Distinguish between Ipratropium and Tiotropium

Answer 29

Ipratropium is poorly absorbed and does not cross the blood brain barrier, administered as an aerosol and therefore limits its adverse effects - short acting Tiotropium is a long-acting antagonist used to treat COPD

Question 30

Side effects of atropine

Answer 30

Atropine is readily absorbed, adverse effets include drowsiness, sedation, dry mouth, blurred vision

Question 31

How does Chromlyn Sodium work?

Answer 31

precise mechanism is unclear, inhbits release of mediators from mast cells; suppresses neutrophils, eosinophils, monocytes; inhibits cough reflexes (may be due to inhibition of chloride ion channels)

Question 32

only anti-asthmatic that inhibits early AND late phase response

Answer 32

Chromlyn Sodium

Question 33

Function of gluccocorticoids

Answer 33

produce significant increase in airway diameter, probably by attenuating PG and LT synthesis via inhibition of phosphlipase A2 reaction and general inhibition of immune response

Question 34

What does Prednisone do

Answer 34

Prednisone - Used for acute and chronic asthma exacerbations

Question 35

Zafirlukast and montelukast do what biochemically?

Answer 35

agonists of the LT receptor LT1; blocks LTC4/D4/E4

Question 36

General effect and use for Zafirlukast and montelukast

Answer 36

reduces bronchoconstrion and inflammatory cell infiltration for mild persistent asthma

Question 37

Zileuton does what?

Answer 37

inhibits 5-lipoxygenase, the rate-limiting enzyme in LT biosynthesis

Question 38

Immediate effect of Zileuton

Answer 38

immediate and sustained 15% improvement in forced expiratory volume (FEV)

Question 39

Zileuton inhibits microsomal P450’s and decreases the metabolism of ____ \_\_\_\_ and \_\_\_\_.

Answer 39

inhibits microsomal P450’s and decreases the metabolism of terfenadine, warfarin, and theophylline

Question 40

Prolastin, Aralast are what?

Answer 40

A1-proteinase inhibitors (Prolastin, Aralast)

Question 41

What do we use A1-proteinase inhibitors (Prolastin, Aralast) for and how often do we give them?

Answer 41

used to treat emphysema caused by a deficiency in a1-proteinase Weekly IV injection to treat patients homozygous for the deficiency

Question 42

Omalizumab does what?

Answer 42

Omalizumab binds to human IgE’s high-affinity Fc receptor, blocking the binding of IgE to mast cells and basophils and other cells associated with allergic response reduces early phase degranulation of mast cells and late phase release of mediators

Question 43

Omalizumab lowers serum IgE concentrations, but does not block \_\_\_\_\_\_\_\_\_\_\_\_.

Answer 43

lowers serum IgE concentrations, but does not block alergen-antibody response

Question 44

Who gets Omalizumab

Answer 44

used in patients \>12 yo who are refractory to inhaled gluccocorticoids and asthmatics with allergies SubQ injection every 2-4 weeks

Question 45

Increased serum levels of IgE Allergens Infections (rhinovirus, parasites, etc) Environmental exposure to all kinds of particulates and toxins Stress, Panic Medicines Food additives, Metabisulfides These are all examples of what?

Answer 45

Extrinsic Asthma triggers

Question 46

Examples of intrinsic asthma triggers

Answer 46

Normal IgE Patho disturbances Negative responses to common antigenic challenge Cold

Question 47

Asthma anatomy changes

Answer 47

Increased smooth muscle around airway Inflammation Actual trapping, which is closing of the airway

Question 48

Cells that contribute to Asthma inflammation

Answer 48

Inflammatory cells Vascular endothelial cells Epithelial cells Smooth muscle cells

Question 49

Mast cells secrete these: To cause:

Answer 49

Mast cells secrete IgE, peroxidase, chemotactic factors, cytokines, etc. This causes leaking of the endotheial barrier, SMC contraction and inflammatory cells to infiltrate the airspaces

Question 50

Bronchial gland and mast cells release histamine. This causes:

Answer 50

Bronchial gland and mast cells - histamine. This causes more recruitment of inflammatory cells, SMC contraction and increased granular secretions

Question 51

Protease production by mast cells and eosinophils do this:

Answer 51

Protease production by mast cells and eosinophils, which increases vascular permeability, further inflammatory cell infiltration, alterations to the ECM, and contributes to the permanent remodeling we see in asthma patients

Question 52

Leukotriene C4 and D4 released by leukocytes and platelets do this:

Answer 52

Leukotriene C4 and D4 released by leukocytes and platelets, which are both chemoatractants for inflammatory cells. They also cause bronchiospasm, increased mucus production, and increased vascular permeability

Question 53

Prostaglandin and chemokine release by mast cells and lung epithelial cells do this

Answer 53

Prostaglandin and chemokine release by mast cells and lung epithelial cells, further recruiting inflammatory cells

Question 54

These 3 things are late asthma events:

Answer 54

Cytokine releases (inflammatory cell recruitment including eosinophils, CD$+T lymphocytes, monocytes, neutrophils). Persistent airflow obstruction Increased airway hyperresponsiveness, SMC growth, etc.

Question 55

Airway inflammation 3 stages and what happens during them

Answer 55

Acute - Early recruitment of cells to the airway Sub-acute - Recruited and resident cells are activated to cause a more persistent pattern of inflammation Chronic - Persistent level of cell damage and repair processes

Question 56

Histologic changes we see in asthma

Answer 56


Question 57

Discuss a metered-dose inhaler

Answer 57

Metered-dose inhaler - usually contains a large volume holding channel (or “spacer”) that fits between the inhaler and the mouth. The inhaler discharges into it and the patient inhales from it

Question 58

Discuss a nebulizer

Answer 58

Nebulizer - Not as cheap or portable but doesn’t require hand/breathing coordination (therapy can be delivered by face mask)

Question 59

Discuss a dry-powder inhaler

Answer 59

Dry Powder inhaler - Developed as alternative to chlorofluorocarbon propellants

Question 60

Two concepts for treating asthma

Answer 60

Drugs that treat symptoms only - Relievers - Bronchodilatory actions, usually rapid onset Drugs that treat underlying cause - Controllers - Antiinflammatory actions, slower acting, often prophylactic (not for emergencies)