Lecture 10: Asthma, Copd, Allergies

Front 1

asthma rx goals

Back 1

prevent chronic and troublesome s/s
require infrequent use (<= 2 days/week) of inhaled SABA
maintain near normal pulmonary function
maintain normal activity levels
meet patients' and families' expectations of and satisfaction with asthma care
prevent recurrent exacerbations of asthma and minimize the need for ED visits or hospitalizations
minimize adverse AEs of medications

Front 2

COPD rx goals

Back 2

relief of acute s/s
minimize exacerbation frequency
prevent progression of pulmonary remodeling
pt satisfaction

Front 3

asthma inflammation cells

Back 3

mast cells
eosinophils

Front 4

COPD inflammation cells

Back 4

neutrophils, macrophages (bigger role than in asthma)

Front 5

Beta Agonist MOA

Back 5

Beta agonists promote AC
adenylyl cyclase inc production of cAMP
bronchodilation by cAMP

Front 6

2 non-selective beta agonists

Back 6

epi
isoproterenol

Front 7

non-selective beta agonists AEs

Back 7

tachycardia
arrhythmias
angina, therefore, don't like to use these drugs as first line agents

Front 8

short acting beta-2-agonists most widely used for:

Back 8

asthma

Front 9

short acting beta-2-agonists make-up

Back 9

most are mixtures of R and S isomers.
Levalbuteral is R only

Front 10

short acting beta-2-agonists (3):

Back 10

albuterol (inh, tab), levalbuterol (inh), terbutaline (inh, tab, sc)

Front 11

long acting beta-2-agonists (2):

Back 11

salmeterol
formoterol

Front 12

SABA duration
LABA duration

Back 12

3-4 hrs
12 hrs

Front 13

LABA recommended use

Back 13

synergy with corticosteroids for asthma
not recommended as monotherapy
not recommended for acute use (SABA used for acute use)

Front 14

beta-2-agonists benefits and pitfalls

Back 14

benefits: rapid effect, safe
pitfalls- side effects: arrythmias, acute hypoxemia, tachyphylaxis, technique

Front 15

what to do in a severe asthma attack?

Back 15

albuterol 4 puffs q 20 min over 1 hr
if no improvement after 1st 4 puffs, take addition treatments but head to ED

Front 16

methylxanthines (3 and origins)

Back 16

tea => theophylline (aminophylline => theophylline-ethylenediamine)
cocoa => theobromide
coffee => caffeine

Front 17

methylxanthines used for

Back 17

historically used for asthma, but also have role in COPD
role has diminished with use of inhaled Beta-2-agonists

Front 18

methylxanthines MOAs

Back 18

High concentrations
-inhibit PDE
-inhibition of cell surface receptors for adenosine-involved in bronchoconstriction
low concentrations
-enhancement of histone deacetylation, which is necessary for activation of inflammatory gene transcription
-inc effectiveness of corticosteroid responsiveness in COPD pts

Front 19

methylxanthines MOA (diagram)

Back 19

inhibit PDE which inc breakdown of cAMP which promotes brochodilation

Front 20

theophylline
-drug interactions

Back 20

-narrow therapeutic window
-induction: smoking induces 3a4 therefore dec levels of theophyline
-inhibition

Front 21

theophylline effective serum concentrations

Back 21

5-20 mg/L

Front 22

serum conc > 15 mg/L. what happens?

Back 22

anorexia, N/V, abd discomfort, HA, anxiety

Front 23

serum conc > 40 mg/L

Back 23

may cause seizures or arrythmias
may not be preceded by GI or neurologic warning s/s

Front 24

3 anti-muscarinics

Back 24

atropine
ipratopium
tiotropium

Front 25

atropine s/e

Back 25

bronchodilator
dry as a bone, blind as a bat, red as a beet, mad as a hatter (anti-cholinergics, therefore not successful for asthma, COPD)

Front 26

anti-muscarinics: development of inhaled atropine analogs do what?

Back 26

competitively inhibit acetylcholine as muscarinic receptors
block vagal activity
-block contraction of airway smooth muscle
-block inc in secretion of mucus
poor systemic absorption

Front 27

info on anti-muscarinics for asthma

Back 27

slightly less effective than beta-2-agonists for bronchospasm
addition to beta-2-agonists enhances bronchodilation in acute severe asthma
addition of tiotropium to inhaled corticosteroids as effective as adding LABA in uncontrolled pts
pts intolerant of inhaled beta-2-agonists probably where you'll see this class of drugs used most commonly

Front 28

info on COPD for anti-muscarinics

Back 28

at least as effective as B-2-agonists in pts with partially reversible component
tiotropium FDA approved for rx of COPD- reduces frequency of exacerbations

Front 29

info on corticosteroids

Back 29

have been used to treat asthma since 1950
broad anti-inflammatory actions mediated in part by inhibition of production of inflammatory cytokines
inhibit infiltration by lymphocytes, eosinophils, and mast cells
reduce bronchial reactivity
reduce the frequency of asthma exacerbations if taken regularly
do not releax airway smooth muscle directly

Front 30

corticosteroids: results of clinical trials show consistent improvement in the following:

Back 30

severity of s/s
tests of airway caliber and bronchial reactivity
frequency of exacerbations
quality of life

Front 31

corticosteroids indications

Back 31

-frequent exacerbations
OR
-severe s/s / airflow obstruction
-acute treatment

Front 32

inhaled corticosteroids: role in asthma

Back 32

reduce s/s and improves pulmonary function in pts with mild asthma
-reduce or eliminates need for oral corticosteroids in pts with more severe dz
-reduce bronchial reactivity
-guidelines recommend for pts who require B-2-agonist more than occasionally
NOT curative

Front 33

4 inhaled corticosteroids and 2 combo products

Back 33

beclomethasone (QVAR)
budesonide (Pulmicort)
Fluticasone (Flovent) Triamcinolone (Azmacort)
Combo:
Fluticasone/Salmeterol (Advair)
Budesonide?Formoterol (Symbicort)

Front 34

corticosteroids: benefits and pitfalls

Back 34

benefits: effective, inexpensive
pitfalls: compliance, osteoporosis, adrenal insufficiency, hyperglycemia, psychologic effects, cataracts, thrush with inhaled

Front 35

Cromolyn and Nedocromil

Back 35

inhaled with min systemic absorption
pretreatment inhibits Ag- and exercise-induced asthma
-inhibits activation of mast cells, eosinophils in response to allergens
-ineffective in reversing bronchospasm
-chronic use QID slightly reduces the overall level of bronchial reactivity

Front 36

Cromolyn and Nedocromil benefits/ AEs:

Back 36

benefits: niche, seasonal, exercise-induced, serious AEs rare
AEs: throat irritation, cough, dry mouth

Front 37

role of leukotriene in asthma

Back 37

leukotrienes synthesized by inflammatory cells in airways:
-eosinophils
-mast cells
-macrophages
-basophils
LTB4 is potent neutrophil chemoattractant
-LTC4 and LTD4 lead to bronconstriction, inc bronchial reactivity, mucosal edema, and mucus hypersection

Front 38

leukotriene pathway inhibitors: 2 approaches

Back 38

-inhibition of 5-lipoxygenase
--Zileuton (hepatotoxicity)
-inhibition of binding of LTD4 to its receptor on target tissue
--Zafirlukast
--Montelukast

Front 39

leukotriene pathway inhibitors outcomes

Back 39

improve asthma control
reduce frequency of asthma exacerbations
effects on symptoms, airway caliber, bronchial reactivity, and airway inflammation less marked than inhaled corticosteroids
nearly equivalent to inhaled corticosteroids in reducing frequency of exacerbation

Front 40

leukotriene pathway inhibitors benefits

Back 40

PO-easy to take
compliance
well-tolerated

Front 41

Anti-IgE antibodies for Asthma (example)

Back 41

-omalizumab (Xolair)

Front 42

Anti-IgE antibodies for Asthma info

Back 42

admin sc
murine monoclonal antibody-derived from mouse. BBW for anaphylaxis
binds to FC-R1 and FC-R2 on inflammatory cells and inhibits binding to IgE
measure IgE levels at baseline and look for reduction

Front 43

Anti-IgE antibodies for Asthma
10-wk rx in asthmatics

Back 43

lowered plasma IgE to undetectable levels
significantly reduced early and late bronchospastic responses to Ag
decreased asthma severity frequency of exacerbations, and reduced corticosteroid requirement in moderate-severe dz
improved nasal and conjunctival s/s in perennial or seasonal allergic rhinitis
reduced exacerbations reqiring hospitalization by 88%

Front 44

Anti-IgE antibodies for Asthma- pts most likely to respond.

Back 44

history of repeated exacerbations
high requirement for corticosteroids
poor pulmonary function

Front 45

future directions in asthma rx

Back 45

monoclonal antibodies directed ag cytokines (IL-4, IL-5, IL-13)
antagonists of cell adhesion molcs
protease inhibitors
immunomodulators of CE4 T-cells of specific Ag
Macrolide abx
-Clarithromycin trial failed

Front 46

Stepwise approach for managing Asthma

Back 46

Step 1: SABA, PRN
Step 2: Low Dose ICS. Alt: Cromolyn, LTRA, Nedocromil, or Thophyline
Step 3: Preferred: Low-dose ICS + LABA or med-dose ICS
Alternatives: Low-dose ICS + either LTRA, Theophiline, or Zileufon
Step 4: Preferred: Med-dose ICS or LABA. Alternative: Med-dose ICS + either LTRA, Theophylline, or Zileuton
Step 5: Preferred: High-dose ICS + LABA and Consider Omalizumab for pts who have allergies
Step 6: Preferred: high-dose ICS + LABA + oral corticosteroid and consider omalizumab for pts who have allergies

Front 47

COPD: abx should be given to pts with:

Back 47

3 cardinal s/s: inc dyspnea, inc sputum volume, inc sputum purulence
who require mechanical ventilation

Front 48

info ab allergic rhinitis

Back 48

IgE mediated
common triad: nasal polyps, asthma, asa allergy

Front 49

allergic rhinitis diagnosis

Back 49

history
physical examination
-conjunctivitis
-rhinitis
-wheezing
allergen testing
blood or nasal eosinophilia suggest an allergic cause, whereas neutrophilia points to an infection cause

Front 50

oral antihistamines MOA

Back 50

block H1 receptor
-smooth muscle
-endothelium
-brain

Front 51

oral antihistamines effectiveness

Back 51

substantially reduce nasal itching and watery eyes
moderate but clinically and statistically significant effects in reducing rhinorrhea and sneezing
minimal effects on nasal congestion

Front 52

oral antihistamines 1st generation vs. 2nd generation

Back 52

1st gen: are clinically effective. use is limited by anticholinergic and sedative effects
2nd gen: lacking substantial sedative properties have largely supplanted earlier drugs- some dry mouth, sedation

Front 53

oral antihistamines

Back 53

Cetirizine (Zyrtec)
Chlorpheniramine (Chlor-Trimeton)
Clemastine (Tavist)
Desloratidine (Clarinex)
Diphenhydramine (Benadryl)
Fexofenadine (Allegra)
Levocetirizine (Xyzal)
Loratadine (Claritin, Tavist)

Cyproheptadine (used for serotonin syndrome)
Dimenhydrinate (Dramamine)
Hydroxyzine (Vistaril) (itching)
Meclizine (Antivert) (antinausea)
Promethazine (Phenergan)

Front 54

nasal corticosteroids

Back 54

first line therapy for mod-to-severe allergic rhinitis
inhibit influx of inflammatory cells
nasal congestion better relieved by nasal corticosteroids than by placebo
meta-analysis compared effects of oral antihistamines and nasal corticosteroids
-congestion and wheezing-clinically and statistically significant benefit
-ocular s/s- no significant difference
similar results were obtained in meta-analysis of nasal antihistamines and nasal corticosteroids
combination therapy oral antihistamine and nasal corticosteroid

Front 55

nasal corticosteroids examples

Back 55

Beclomethasone (Beconase)
Budesonide (Rhinocort)
Fluticasone (Flonase)
Mometasone (Nasonex)
Flunisolide (Nasalide)
Triamcinolone (Nasalcort)

Front 56

nasal corticosteroids AEs

Back 56

epistaxis
delay in attainment of normal height has been reported in children using intranasal beclomethasone- not other nasal corticosteroids
inc intraocular pressure and posterior subscapular cataracts in adults

Front 57

1 alpha-adrenergic agonists

Back 57

psuedoephedrine

Front 58

alpha-adrenergic agonists info

Back 58

conters vascular engorgement of turbinates, improving nasal air flow
psuedoephedrine + oral antihistamine significantly more effective in reducting total nasal s/s than either agent alone
pseudoephedrine + oral antihistamine at least as effective as nasal beclomethasone for nasal s/s and was superior for relief of ocular s/s

Front 59

Sudafed AEs

Back 59

arrhtymias
htn
insomina
nervousness

Front 60

alt. agents for allergic rhinitis

Back 60

Montelukast- Singulair
Inhaled cromolyn
Opthalmic agents for allergic conjunctivitis
-Cromolyn- eye drops
-Antihistamines- eye drops
-Ketorolac- eye drops (NSAID)
Systemic corticosteroids
Allergen immunotherapy