Block V, Asthma And Copd Drugs

Front 1

Patient's responsibility in control of asthma.

Back 1

ADHERENCE
-medication must be taken as directed to be effective

Front 2

Asthma

Back 2

Chronic inflammatory disorder of the airways
(Nuetrophils, Eosinophils, Lymphocytes infiltation)
Epithelial cell injury and mass cell activation

Front 3

Mechanisms of Allergy in Asthma

Back 3

Allergen exposure, lympocyte IL-4 production signals b cells to product IgE, activate mass cells, mass cells degranulation release mediators (Histamine, LTs, PGs, bradykinin), leads to inflammation in late phase.

Front 4

Early Allergic Reaction

Back 4

Decease FEV1 in minutes (lasts 1.5-2 hours)
Acute airway obstruction.

Front 5

Late Allergic Reaction

Back 5

Another decrease in FEV1 about 2-8 h after exposure

Cytokines released from mast cells

Lasts days to weeks.

Front 6

MOA of Beta2 agonists

Back 6

Bind receptor, active adenylate cyclase increasing cAMP. Actives protein kinases affecting myosin light chain kinase and Ca++ dependent K+ channels... Bronchodilation

May also enhance mucociliary clearance, reduce mucosal edema, decrease mediator release, weak antiinflammatory

NO effect on late response or on airway hyperresponsiveness.

Front 7

Beta2 agonists

Back 7

Albuterol (onset within 5 min) last 3-6 hours

Salmeterol (onset 10-15 min) last 12 hours.

Formoterol (onset 2-3 min) last 12 hours.

All inhaled.

Front 8

SABA Indications

Back 8

Best agent for exercise-induced asthma

Treatment of choice for mild intermittent asthma and acute exacerbation of asthma with systemic steroids

COPD maintenace and exacerbations (often combined with anticholinergic agents)

Front 9

LOBA Indications

Back 9

(Salmeterol, Formoterol)

Maintenace treatment of asthma, COPD, and EIA.

Never use as monotherapy (add to ICS theapy)

Front 10

B2 Agoinists Adverse effects

Back 10

CNS
Nervousness, irritability, insomnia

Skeletal muscle tremor – ß2 manifestation
Tolerance develops

Heart – ß1 manifestation
Palpitations, tachycardia, arrhythmias

Paradoxical bronchospasm
Regular or too frequent dosing

Front 11

Parasympathetic effect on bronchioles

Back 11

Parasympathetic stimulation of muscarinic receptors – airway mostly M3 receptor
Increased cholinergic tone
Increased bronial smooth muscle tone and mucus secretion

Front 12

Anticholinergics for Asthma

Back 12

Ipratropium (Atrovent)

Tiotropium
-once daily doing (Atrovent 4x/day)

Combination albuterol/ipratropium.

Front 13

Anticholinergics Indications

Back 13

FDA-approved for COPD
-may be better than B2 agonists.

Non-FDA approved for asthma

Front 14

Methylxanthines

Back 14

Theophyllin (caffeine, theobromine are natural alkaloids)

Low therapeutic index

Front 15

Methylxanthine effects

Back 15

Pulmonary – theophylline > caffeine
Nonspecific phosphodiesterase inhibitor that increases intracellular cAMP
Airway smooth muscle relaxation – Bronchodilation
CNS effect – caffeine > theophylline
Increased alertness, reduced fatigue
Respiratory stimulant
Nervousness, insomnia
Cardiovascular effect
Positive inotropic & chronotropic

GI effects
Increased gastric acid secretion
Decreased LES pressure
Renal effect – Weak diuretic
Increased GFR
Decreased tubular Na+ reabsorption
Tolerance develops
Improvement of diaphragmatic contractility
May be important in COPD patients

Front 16

Theophylline Why not used

Back 16

Less effective than B2 agonists

Metabolized by CYP450.

Significant does-related side effects. >30 mcg/mL CNS stimulation & seizures

Front 17

Anti-Inflammatory Agents for Asthma

Back 17

Corticosteroids

Mass cell stabilizers

Leukotriene modifiers

Front 18

Effects of corticosteroids in asthma

Back 18

Block late-phase reation

Reduce mucus secretion

Increases B receptors

Front 19

Corticosteroids for Asthma

Back 19

Fluticason (Flovent)
Triamcinole

Front 20

Combination drugs for Asthma

Back 20

Fluticasone/Salmeterol (Advair) 1 inhal q12h

Budesonide/Formoterol (Symbicort) 2 inhal q12h.

Front 21

Cromolyn

Back 21

Mast Cell Inhibitors

Not used very often

mild potency anti-inflammatory agent, NOT a bronchodilator.

Front 22

Leukotrienes Overview

Back 22

CYSTEINYL LTs – LT C4, D4 & E4
Formerly known as slow reacting substance of anaphylaxis (SRS-A)
Very potent bronchoconstrictors & inflammatory mediators
1000 x > bronchospasm potency as histamine

ACTIONS OF LTS
Contract airway smooth muscle
Increase vascular permeability (edema)
Increase mucus secretions
Decrease mucociliary clearance
Recruit & activate eosinophils and basophils into airway
Proliferation of smooth muscle

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Zileuton

Back 23

5-lipooxygenase inhibitor

Front 24

Montelukast and Zafirlukast

Back 24

Cysteinyl LT receptor antagonists)

Montelukast (Singulair)

Alternative, not preferred, treatment. Modest improvement in lung function as monotherapy.

Front 25

Omalizumab

Back 25

Monoclonal Ab that binds IgE
-decrease free IgE in serum

Allergy should be established by skin or blood test.

Consider for severe persistent asthma (very expensive)

Front 26

Asthma Classification

Back 26

Front 27

COPD

Back 27

4th leading cause of death in US

Pharmacotherapy has not improved mortality, but does reduce symptoms and complications

Smoking cessation and O2 most helpful to improve mortality.

Front 28

Therapy for COPD

Back 28

Smoking cessation
Bronchodilator therapy
Inhaled are preferred
Methylxanthines
Corticosteroids
Treatment of Alpha-1 antitrypsin deficiency
Influenza and pneumonia vaccination
Oxygen supplementation
Pulmonary rehabilitation
Lung volume reduction surgery

Front 29

COPD Management

Back 29