Pharm - S2B2 - 12 Asthma

Front 1

What are the 2 physiologic features of Asthma?

Back 1

1. increased bronchial and tracheal responses to stimuli

2. widespread narrowing of airway passages

Front 2

What are the pathologic features associated with Asthma?

Back 2

1. Contraction of airway smooth muscles
2. Mucosal thickening from edema and cellular infiltration
3. thickening in the airway lumen of viscid mucus plugs

Front 3

Bronchoconstriction from smooth muscle contraction is most easily reversed by __1__ drugs, while reversal of edema and cellular infiltration requires sustained treatment with __2__ drugs

Back 3

1. Bronchodilator

2. Anti-inflammatory

Front 4

Antiasthmatic drugs classified as "short-term releivers"? "Long-term" controllers?

Back 4

Short-term = Bronchodilators

Long-term = Anti-inflammatory agents

Front 5

Explain the Immunopathogenesis of the Early Rxn of Asthma (occurs within 2 hrs)

Back 5

1. initial allergen exposure
2. production of IgE that bind to mast cells of airway mucosa
3. Re-exposure to allergen cross-links Ag-Ab complexes
4. Mast cell degranulation of Anaphylatoxins
5. Smooth muscle contraction
6. Bronchoconstriction and immediate fall in FEV1

Front 6

The early reaction of Asthma is mediated by these factors

Back 6

Histamine
Tryptase
PGD2
LTC4
PAF

Front 7

Explain the immunopathogenesis of the late reaction of Asthma (occurs 2-8 hrs later)

Back 7

1. release of cytokines, IL's, and various factors from T cell and Mast cells
2. Activate Eosinophils and Neutrophils that release proteins and PAF
3. Edema, mucus hypersecretion, Smooth muscle contractions
4. Bronchoconstriction and increased bronchial reactivity with late fall in FEV1

Front 8

Describe the Reflex response causing Bronchoconstriction

Back 8

1. Afferent vagal pathway sends signal to CNS upon irritant stimulation
2. Efferent vagal pathway goes to Autonomic ganglia
3. Postganglionic fibers release ACh which binds to Muscarinic receptors on bronchial smooth muscle -> Bronchoconstriction

Front 9

What are the 2 separate ways in which inhaled irritants can cause Bronchoconstriction?

Back 9

1. releasing chemical mediators from Mast cells

2. stimulating Afferent Vagal receptors to initiate reflex bronchoconstriction

Front 10

What 2 things does Bronchospasm in Asthma result from?

Back 10

1. Mediator release

2. Bronchial hyperreactivity

Front 11

Class of antiasthmatic drugs that relax smooth muscles, but will not relieve mucosal edema, cellular infiltration, or mucus formation

Back 11

Bronchodilators

Front 12

List the 5 B2-adrenergic agonist Bronchodilators

Back 12

Albu-terol
Bitol-terol
Pirbu-terol
Meta-proter-enol
Terbut-aline

Front 13

List the 2 Long-acting B2-adrenergic agonist Bronchodilators

Back 13

Salme-terol

Formo-terol

Front 14

List the 3 Sympathomimetic Bronchodilators

Back 14

Epinephrine

Ephedrine

Iso-proter-enol

Front 15

List the 4 Methylxanthine Bronchodilators

Back 15

Amino-phylline

Theo-phylline

Dy-phylline

Pentoxi-fylline

Front 16

List the 3 Muscarinic Antagonist Bronchodilators

Back 16

Ipra-tropium

Tio-tropium

Atropine

Front 17

Class of Antiasthmatic drugs that reduce bronchial responsiveness

Back 17

Anti-inflammatory

Front 18

List the 6 Glucocorticoids used as anti-inflammatories to treat Asthma

Back 18

Beclo-methasone
Bud-eso-nide
Dexa-meth-asone
Flu-nisolide
Flu-tic-asone
Momet-asone

Front 19

List the 2 Leukotriene antagonists used as Anti-inflammatories to treat Asthma

Back 19

Monte-lukast

Zafir-lukast

Front 20

Anti-IgE Antibody used as anti-inflammatory to treat Asthma

Back 20

Omalizumab

Front 21

What is the mechanism of action of prophylactics used to prevent asthma?

Back 21

prevent Mast cell degranulation

Front 22

Name the 2 prophylactic anti-asthmatic drugs

Back 22

Cromolyn sodium

Nedo-cromil sodium

Front 23

What is the theoretical goal of the Aerosol delivery of antiasthmatic drugs?

Back 23

-producing high local drug concentration in the lungs

-LOW systemic absorption

Front 24

Aerosol delivery to the lungs with low systemic absorption is especially important for these 2 groups of antiasthmatic drugs

Back 24

B2-adrenergic agonists

Glucocorticoids

**have potentially serious side-effects when absorbed systematically

Front 25

Even under ideal conditions, only __1__% of the aerosolized drug is deposited in the lungs and most of the remainder is __2__

Back 25

1. 2-10%

2. Swallowed

Front 26

In order to have minimal systemic effects, Aerosolized drugs should have one of these 2 properties

Back 26

1. poor absorption from GI tract

2. rapidly inactivated by first-pass hepatic metabolism

Front 27

The ratio of inhaled to swallowed drug can be improved by these 2 things

Back 27

1. Large-volume 'spacer'

2. proper technique

Front 28

What is Bronchodilation promoted by?

What 2 things can cause this and how?

Back 28

cAMP

1. B2-adrenergic agonists = increase cAMP synthesis by activating Adenylyl Cyclase

2. Phosphodiesterase inhibitors (Theophylline) to slow cAMP degradation

Front 29

What 2 things can inhibit Bronchoconstriction?

Back 29

1. Muscarinic antagonists (Ipratropium)

2. Adenosine antagonists (Theophylline)

Front 30

What are each of the following Methylxanthines found in?
1. Theophylline
2. Theobromine
3. Caffeine

Back 30

1. Tea
2. Cocoa
3. Coffee

Front 31

How are aminophylline, dyphylline, pentoxifylline, and theophylline administered?

Back 31

Oral sustained-release or Parenteral preps

Front 32

The Methylxanthines are declining in use b/c of greater effectiveness of other drugs except one...which one and why?

Back 32

Theophylline b/c it is cheap

Front 33

What is Theophylline's mechanism of action? (2)

Back 33

1. inhibits Phosphodiesterase that usually degrades cAMP = causes increase intracellular cAMP = Cardiac stimulation and Smooth Muscle relaxation

2. acts partly as Adenosine Antagonist

Front 34

What is the main therapeutic action of Theophylline (Methylxanthine)?

Back 34

Bronchodilation

Front 35

List the Pharmacodynamics of the Methylxanthines

Back 35

1. CNS stimulation results in alertness and deferred fatigue
-side effects = nervousness, insomnia, tremors, convulsions

2. Positive Inotropic and Chronotropic effects with increased Cardiac Output may produce Arrhythmias and increase BP

3. Stimulate secretion of Gastric Acid and Digestive enzymes

4. are weak Diuretics due to increased GFR and diminished tubular Na+ reabsorption

5. Improve contractility of Skeletal muscle and the diaphragm; improved diaphragmatic fxn will diminish dyspnea

**think of Caffeine's effects

Front 36

What is the most effective Methylxanthine bronchodilator?

Back 36

Theophylline

Front 37

Theophylline relieves airflow obstruction in __1__ and reduces symptom severity in __2__

Back 37

1. acute asthma

2. chronic asthma

Front 38

Sustained-release oral tablets of Theophylline produce therapeutic blood levels for how long?

Back 38

12 hours or more

Front 39

When should Theophylline only be used? Why?

Back 39

When blood levels can be measured

b/c Therapeutic and Toxic effects are related to plasma levels

Front 40

What may toxic doses of Theophylline cause?

Back 40

Insomnia
Anorexia
NVD
Heachache
Anxiety
Arrhythmias
Seizures

***Neurotoxicity and Cardiotoxicity

Front 41

Would Theophylline toxicity be increased in Liver or Renal disease? Why?

What 3 drugs increase the toxicity of Theophylline?

Back 41

Liver b/c that is what metabolizes it = toxicity may increase in liver disease...beware!!!

Cimetidine, Fluoroquinilone (-floxacin's), & Macrolides (Erythromycin)

Front 42

What is the mechanism of action of the Beta-2-Adrenergic agonists?

Back 42

stimulate Adenylyl Cyclase -> increase cAMP -> Smooth muscle relaxation and bronchodilation

Front 43

What is the drug of choice for Acute Asthmatic attacks?

Back 43

β2-adrenergic agonists
-Albuterol
-Terbutaline
-Metaproterenol
-Pirbuterol
-Bitolterol

Front 44

Which β2-adrenergic agonists are used for Prophylaxis?

Back 44

Longer acting
= Sal-met-erol & Formo-terol

Front 45

β2-adrenergic agonists have a longer duration of action than _______ when given orally or by inhalation

Back 45

Epinephrine

Front 46

The bronchodilation with β2-adrenergic agonists is maximal by __1__ and lasts for __2__

Back 46

1. 30 min

2. 3-4 hrs

Front 47

What are the common adverse effects of β2-adrenergic agonists?

Back 47

Skeletal muscle tremor

Nervousness

Occasional weakness

**generally safe and effective when given in doses that avoid adverse systemic effects

Front 48

What are the 2 Sympathomimetics used as Bronchodilators?

Back 48

Ephedrine

Epinephrine

Front 49

What is the downside of the Sympathomimetics?

Back 49

by stimulating β1-adrenergic receptors they cause more cardiac side-effects = tachycardia, arrhythmia, worsening of angina

**also stimulate β2-adrenergic receptors to cause Bronchodilation

Front 50

Sympathomimetic that is administered by inhalation or SubQ injection, is effective and rapid acting for Acute Asthmatic attacks

Back 50

Epinephrine

Front 51

Mechanism of action of Muscarinic Antagonists?

Back 51

block Acetycholine at muscarinic receptors = prevent Bronchoconstriction

Front 52

What 2 effects do Muscarinic Antagonists ultimately cause?

Back 52

1. inhibit vagal stimulation to relax bronchial smooth muscle = prevent bronchoconstriction

2. decrease mucus secretion

**but do so without affecting those to NONMUSCARINIC stimuli

Front 53

Why do Muscarinic Antagonists not always work?

Back 53

Parasympathetic involvement in bronchospastic responses varies widely

Front 54

Muscarinic Antagonist that is given by IV or by Inhalation and produces Bronchodilation lasting for 5 hours, but may cause dry mouth, urinary retention, tachycardia, loss of visual accomidation, and agitation

Back 54

Atropine

Front 55

Muscarinic antagonist that is given by Aerosol or Nasal spray and allows delivery of large doses because it is poorly absorbed and therefore has minimal CNS effects

Back 55

Ipra-tropium bromide

Front 56

Muscarinic antagonist that has a longer duration of 24 hours

Back 56

Tio-tropium

Front 57

List the 6 Corticosteroids used to treat Asthma

Back 57

1. Beclo-methasone
2. Budes-onide
3. Flu-niso-lide
4. Flu-tica-sone
5. Mo-metasone
6. Triam-cino-lone

Front 58

What is the mechanism of Corticosteroids in treating Asthma?

Back 58

Inhibit the production of Inflammatory cytokines
1. reduce bronchial reactivity
2. increase airway caliber
3. reduce frequency of asthmatic attacks

Front 59

By what modes of administration are the Glucocorticoids given?

Back 59

Orally

Injection

Aerosol

Front 60

Which routes of administration of Glucocorticoids may produce severe adverse effects?

Back 60

Oral or Parenteral

Front 61

When is systemic administration of Glucocorticoids only given?

Back 61

patients requiring urgent treatment

Front 62

Inhaled preparation of Corticosteroids may cause what 2 adverse effects?

Back 62

1. Oropharyngeal candidiasis

2. Hoarseness from vocal cord irritation

Front 63

What 2 Leukotrienes are potent Bronchoconstrictors secreted in Asthma and Anaphylaxis?

Back 63

LTC4 & LTD4

Front 64

What 2 drugs are LTD4-receptor antagonists?

Back 64

Monte-lukast

Zafir-lukast

Front 65

How are Monte-lukast and Zafir-lukast administered? Who are they especially useful for? What type of asthma are they especially good for?

Back 65

Orally

children unable to comply with inhalation therapy

Aspirin-induced asthma

Front 66

Antileukotriene that inhibits 5-lipoxygenase to reduce leukotriene formation but has been withdrawn due to Liver toxicity

Back 66

Zi-leu-ton

Front 67

What is the mechanism of action of Omalizumab?

Back 67

Monoclonal Ab that inhibits binding of IgE to mast cells

***does NOT inactivate already bound IgE

Front 68

Antiasthmatic that lessens the severity of asthma and reduces corticosteroid requirement

Back 68

Omalizumab

Front 69

Lowers plasma IgE levels and reduces bronchospastic antigen responses

Back 69

Omalizumab

Front 70

2 antiasthmatic drugs that are only effective when given prophylactically

Back 70

Cromolyn

Nedocromil

Front 71

Cromolyn and Nedocromil have an acute protective effect when given before these 2 things

Back 71

1. Exercise

2. Allergen exposure

Front 72

Cromolyn and Nedocromil inhibit bronchial hyper-reactivity in these 2 things

Back 72

Antigen- & allergen-induced asthma

Front 73

Cromolyn and Nedocromil do not affect these 2 things

Back 73

Bronchial smooth muscles

Asthmatic bronchospasm

Front 74

What is the mechanism of action of Cromolyn and Nedocromil?

Back 74

Alter delayed chloride channels in cell membranes to:
1. inhibit mast cell activation
2. reduce release of histamine and other mediators

Front 75

How are Cromolyn and Nedocromil administered? Why?

Back 75

Aerosols b/c of poor GI absorption

Front 76

Cromolyn and Nedocromil are less potent or effective when compared to _________

Back 76

inhaled Corticosteroids

Front 77

What are the characteristics of Mild Asthma?

Back 77

Occasional symptoms occuring on exposure to allergens or pollutants, after exercise or Upper Respiratory viral infection

Front 78

What are the characteristics of Severe Asthma?

Back 78

Frequent attacks of wheezing dyspnea especially at NIGHT, resulting in limitation of activity