1
Q
- what is the prevelance of asthma: (in children)?
- what is the amount of clinical visits?
- ER visits?
- asthma prescriptions?
A
- Children (under 18 years): more than 6 million children
- 3 million clinic visits annually
- 570 thousand (over half a million)
- 8.7 million asthma related scripts
2
Q
Epidemiology
1• Ethnicity: Outcomes in African American children are (better or worse)?
2• Prevalence in black children is__%__ than whites?
3• disability & hospitalizations?
4• mortality of black children (—X higher)?
A
1• Ethnicity: Outcomes much worse in African American children
2• Prevalence is 26% higher
3• More severe disability; More frequent hospitalizations
4• 4-6 times more likely to die of asthma
3
Q
Asthma factoids:
- what can albuterol cause? how is it reversed?
- chloro-flourocarbons which are bad for ASA are in inhalers, what does getting rid of it do to price?
A
- Beta 2 receptor desensitization may occur with albuterol and can be reversed or prevented with steroids
- CFC being eliminated as propellant in inhalers-may increase cost since generics not available
4
Q
- what does ICS stand for?
2. what is important regarding treatment of asthma with ICS?
A
- Inhaled Cortico Steroids
2. ICS is the preferred single controller regimen (lower cost and visits than single LMT or combined controllers)
5
Q
- Pathophysiology: what is the definition of asthma?
2. what are characteristics?
A
- A clinical syndrome characterized by episodes of hyper-responsive airways with asymptomatic periods
- • Bronchoconstriction
• Inflammation
• Airway remodeling
6
Q
- is asthma obstructive or restrictive?
2. why?
A
- restrictive
2. because it doesnt block the bronchus, it shrinks the bronchus
7
Q
- what is atopy?
2. what does that have to do with asthma?
A
- persons that are very reactive (skin etc).
2. atopic persons (children especially) are at high risk for asthma
8
Q
risk factors for asthma:
- what is the Strongest predisposing factor?
- what are genetic risks (%) with having 1 parent with asthma?
- 2 parents?
A
- Genetic predisposition to developing IgE response to common allergens (family Hx:).
- One parent with asthma: up to 25% risk for child
3• Two parents with asthma: up to 50% risk for child
9
Q
• Uncontrolled asthma in pregnancy is associated with…
A
congenital malformations
10
Q
- what is the preferred single controller medication for asthma?
- why?
A
1• ICS (inhaled cortico steroids)
2. lower cost and visits than single LMT or combined controllers
11
Q
Pathophysiology of asthma:
A
A clinical syndrome characterized by episodes of hyper-responsive airways with asymptomatic periods
12
Q
Characteristics of asthma (3)
A
- Bronchoconstriction
- Inflammation
- Airway remodeling
13
Q
what is the Hallmark of Asthma?
A
Bronchial wall Hyper-responsiveness
14
Q
What happens in the Early Phase Asthma Reaction:
A
Bronchoconstriction caused by: Antigenic Stimulation of bronchial wall & Mast Cell Degranulation which releases: --• Histamine --• Chemotactics Proteolytics --• Heparin
15
Q
Late Phase Asthma Reaction a:
-what is happens in this phase?
A
- Bronchial Inflammation & Inflammatory Cells Recruited
16
Q
Late Phase Asthma Reaction b:
- what cells are recruited?
A
- Neutrophils• Monocytes• Eosinophils
17
Q
.Late Phase Asthma Reaction c:
- what inflammatory mediators are released?
A
- Release Cytokines, Vasoactives, Arachidonic acid• Release of Interleukin 3-6, Interferon-gamma
18
Q
.Late Phase Asthma Reaction d:
- what tissues become inflammed?
A
-Epithelial and Endothelial Cell inflammation
19
Q
asthma is usually evaluated as:
A
a decreased FEV1 (forced expiratory volume) and/or FEV1/FVC (forced vital capacity)ratio
20
Q
Definition of Asthma:
A
Asthma
• Reversible airway obstruction
• Airway inflammation
• Increased bronchial hyper responsiveness
21
Q
what is Status Asthmaticus?
A
• Severe airway obstruction developing over days-week
22
Q
Types of Asthma (14 different types)
A
1• Extrinsic Asthma (Allergic)
2• Intrinsic Asthma (Non-allergic)
3• Mixed Asthma (Extrinsic and Intrinsic)
4• Occupational Asthma
5• Chemical dusts (isocyanates from polyurethane)
6• Organic dusts (grains)
7• Animal dander
8• Metals (nickel, chromium)
9• Healthcare worker exposures (latex, gluteraldehyde, etc)
10• Drug Induced Asthma
11- Aspirin-induced Asthma
12- NSAID-induced Asthma
13• Exercise Induced Asthma
14• Cough Variant Asthma -Very common! (Especially in children)
23
Q
how is cough and wheeze differentiated between asthma and just cold symptoms
A
recurrence is usually asthma, but not all asthma wheezes.
24
Q
Upper airway disease that may be confused as asthma:
A
• Allergic rhinitis • Sinusitis • Large airway obstruction
• Foreign body • Vocal cord dysfunction • Laryngotracheomalacia
• Tracheobronchial-stenosis • Enlarged lymph node or tumor
• Small Airway obstruction • Viral bronchiolitis
• Bronchiolitis obliterans • Cystic fibrosis • Bronchopulmonary dysplasia • Heart disease
Other Causes
• Psychogenic cough (uncertain or non-identifiable cause)
• GERD
• ACE inhibitor induced bronchospasm
• Malingering if secondary gain (missed school)
25
confirming asthma, how is it done?
PFTs every 3-6 month
26
who is at additional risk for asthma?
```
o Elderly
o Pregnancy
o History of early life injury to airways
o Bronchopulmonary Dysplasia
o Parental smoking
```
27
• what is the asthma "Classic Triad"?
Asthma, Nasal Polyps, Aspirin allergy
28
when assessing present management and response, what should be looked at?
o Frequency of systemic steroid need
o History steroid-induced complications
o Co morbid conditions
29
symptoms of asthma:
* Recurrent wheezing
* Dyspnea
* Productive or paroxysmal cough (especially at night)
* Chest tightness
30
signs of asthma:
* Expiratory Rhonchi
* Wheezing may or may not be heard
* Prolonged Inspiratory to Expiratory ratio
* Hyperexpansion of thorax and accessory muscle use
* Diminished chest excursion
* Nasal mucosal swelling or polyps
* Atopic dermatitis, eczema, urticaria
* Respiratory Distress
* Tachypnea
* Dyspnea
* Anxiety
* Accessory Muscle Use
* Intercostal muscle, Sternocleidomastoid
* Respiratory Distress
* Cyanosis in severe cases (lips)
* Tachycardia
31
other aspects of diagnosing asthma: why it may be difficult-
1. what might patients do to make dx hard?
2. what in the patient history may prove they have asthma?
1• Patient may underplay symptoms
--• Symptom accommodators (10% of patients) -Patients who do not recognize severe Symptoms of their asthma
2• Age of onset and asthma diagnosis
--• Past history of respiratory failure or Intubation
32
making the diagnosis:
| what about family history?
```
• Family History of:
o Asthma
o Allergic rhinitis
o sinusitis
o Nasal polyps
```
33
```
what makes the diagnosis:
social history (about the home):
```
```
• Social History
o Home characteristics
o Heating and cooling system
o Wood burning stove
o Humidifier
```
34
making the history of asthma:
1. current management and response?
2. what other conditions may contribute:
1• Present management and response
o Frequency of systemic steroid need
o History steroid-induced complications
2. Co morbid conditions
35
what factors provoke asthma symptoms:
```
Provocative factors
• Exercise
• Viral infection
• Animals with fur or feathers
• House dust mites
• Mold
• Smoke
• Airborne irritants (Pollen, chemicals, dusts)
• Weather changes
• Emotional stress
• ANESTHESIA
```
36
What are implications for a chest xray?
```
Indications
• Initial diagnosis
• Status asthmaticus or no acute asthma improvement
• Excludes other diagnoses
• Excludes complications
```
37
what will be the cxr findings in asthmatics?
Chest X-ray Findings
• Increased bronchial wall markings (MOST characteristic)
----Associated with thicker bronchial wall, inflammation
• Flattening of diaphragm
---- Associated with chronic inflammation
---- Associated with accessory muscle use
• Hyperinflation (variably present)
• patchy infiltrates (variably present) from atelectasis
38
What are labs that are indicated ; and what are the findings?
Labs
• ABGs
----o Hypoxemia
----o Hypercarbia (or normal CO2) with decompensation • CBC
----o Eosinophelia may be present
• Increased Levels of IgE may be present
• Other markers include fraction of exhaled NO (FENO) and pH of exhaled
breath condensate (EBC) (expensive tests- no more effective)
• Sputum sample
----o May show casts of small airways
----o Thick mucoid sputum
39
1. what will PFTs show?
2. what type of "challenge" may be done as part of PFTs?
3. what does this challenge do?
PFTs
1• Obstructive pattern
2• + methacholine challenge
3. methacoline is a short acting acetylcholine derived and causes severe bronchoconstriction; asthmatics will not have enough reserve to do adequate PFT (will cause decreased forced inspiratory volume).
40
Pharmacologic management: NIH Categories for Severity
| Mild intermittent:
Mild intermittent
• Occasional exacerbations (twice or less per week)
• Exacerbations are brief, but can be intense
• FEV1 or PEFR (peak exp Flow rate) > 80%
41
Pharmacologic management: NIH Categories for Severity
| Mild persistent:
```
Mild persistent
• Frequent exacerbations (> twice weekly, but not daily)
• May affect activity
• Nighttime symptoms > 2/month
• FEV1 or PEFR > 80%
```
42
Pharmacologic management: NIH Categories for Severity
| Moderate persistent:
Moderate persistent
• Daily symptoms with daily Beta Agonist use
• Exacerbations that affect activity at least twice/week and may last for days
• Nighttime symptoms > 1/week
• FEV1 or PEFR 60-80% of predicted value
43
Pharmacologic management: NIH Categories for Severity
| Severe persistent:
```
Severe persistent
• Continuous Symptoms and frequent exacerbations
• Frequent nighttime symptoms
• Limited physical activity
• FEV1 or PEFR < 60% of predicted value
```
44
what is the rule of 2s?
```
established how well the asthma is controlled
Rule of 2s
• Uses rescue inhaler:
> 2 times per week during the day
> 2 times per month at night
>2 inhalers per year
If any are present control is inadequate
```
45
what is the general management strategy pharmacologically?
a. Long term use of inhaled corticosteroids
- --• Decreased inflammation
b. Intermittent and cautious use of beta agonists
- --• Avoid more than 4 puffs per day (increases chance of MI)
c. Treat other possible confounding factors:
- --• GERD, chronic sinusitis, allergic rhinitus
d. Prevent exercise and cold induced asthma
46
meds to control asthma: corticosteroids:
1. what is good about inhaled corticosteroids?
2. should be what treatment for persistent asthma?
3. what doesnt it do?
Inhaled corticosteroids
1• Most important agents in reactive airway disease
2• Should be first-line agent in all persistent asthma
3• Controls but DOES NOT MODIFY the underlying disease
47
meds to control asthma: Mast Cell Stabilizers: Cromolyn Sodium (Intal), Nedocromil (Tilade)-
• Indications:
Mast Cell Stabilizers
• Alternative anti-inflammatory drug for young patients
• Prophylactic agent for exercise and cold induced asthma
48
meds to control asthma:Beta Adrenergic Agonist
Beta Adrenergic Agonist
• Short acting Rescue Inhaler (e.g. Albuterol)
• Long acting scheduled inhaler (e.g. Serevent)
• Indicated for moderate to severe asthma
49
meds to control asthma: Anticholinergics: Ipratropium Bromide (Atrovent)
block bronchoconstrictive action of acetylcholine
50
meds to control asthma: Leukotriene Receptor Antagonists (aka leukotriene modifiers)(e.g. Montelukast):
--indications:
Leukotriene Receptor Antagonists
| • Indicated for moderate to severe asthma
51
meds to control asthma: Theophyllines
1. is it used alot?
2. what type of use (primary or adjunct)?
3. what must you do with theophylline?
Theophyllines
1. (infrequent use)
2• Adjunct
3• Requires close monitoring of levels
52
meds to control asthma: Systemic corticosteroids
1. how often used?
2. what symptoms would solicit its use?
Systemic corticosteroids
• Not often needed
• Used for severe/moderate exacerbations to speed recovery and avoid recurrence
53
meds to control asthma: Immunomodulators
1. MOA?
2. what is Xolair?
3. what are other examples of immunomodulators used for asthma?
Immunomodulators (a new approach)
1• Various MOAs
--• Thought to provide long term control and/or reduce steroid effects
2• Anti Ig-E therapy-omalizumab (xolair)
--• Xolair recommended by expert panel as possible adjunt therapy. It binds to Fc portion of IgE antibody to prevent binding to receptors on mast cells etc.
3• Other examples are methotrexate, interleukin, antibiotics,
54
what is the emergency management of asthma?
| what did you give in the ER???
1. albuterol/ atrovent (or combined as duoneb):
• Inhaled, nebulized short acting beta agonist
----o One dose up to every 20 minutes for one hour
----o Equally effective as IV EPI
• Anticholinergic (Ipratropium bromide or Atrovent)
----o Add to nebulized albuterol (Indication: FEV1 or PEF <50% predicted)
--• No immediate response to nebulizer or beta agonist
--• PO recently taken by patient
55
Short Acting Beta Agonists-
1. brand name?
2. what are adverse effects?
3. what are the indications?
```
Short Acting Beta Agonists-
1. Albuterol (either nebulized or MDI)
2• Adverse Effects
--o Tachycardia
3• Indications
--o Short acting agents for rescue use only
```
56
what are the Adverse Effects of SCHEDULED short acting MDI beta agonist use?
Adverse Effects of scheduled short acting MDI beta agonist use
• Loss of indicator for worsening of asthma (patient stays tachy)
• Delays use of inhaled steroid (by using these first)
• Increases airway hyper-reactivity
• Treats only acute phase reaction (doesnt decrease inflamm.)
• Regular use associated with increased mortality
• Acute coronary syndrome risk in those with CAD risk
57
Long Acting Beta Agonists-
1. names?
2. indications?
3. precautions?
Long Acting Beta Agonists-
1. Salmeterol (Serevent), Formoterol (Foradil)
2• Indications
--• Moderate and severe persistent asthma
--.Supplement, may allow lower dose of ICS
3• Precautions
--o Not a substitute for inhaled corticosteroids
--o May increase severity of asthma episodes
--o Do NOT exceed dosing schedule ( tolerance may develop over
time to protective effect)
58
```
Inhaled Corticosteroids (ICS)
1. name some:
```
* Flovent (fluticasone) • Vanceril • Pulmicort
* Beclovent • Azmacort
* Aerobid • Asthmanex
59
Inhaled Corticosteroids (ICS)
1. Indications:
2. Efficacy:
3. which are the strongest 2 and which is the weakest of them?
1. Indications: Most important agent
2. Efficacy
--• ICS reduce asthma related death
--• Mortality risk decreases with steroid inhalers/year
--• Benefits in COPD and asthma persist for >5 years
3• Testing indicates that most potent are Vanceril DS and Flovent - other agents i.e. Azmacort may have 25% less potency
60
```
Inhaled Corticosteroids (ICS)
Adverse Effects:
```
Adverse Effects
• Dysphonia
• Oral and esophageal candidiasis
• Glaucoma risk of high dosed ICS increased 44% over non steroid users
(not associated with nasal steroids)
• Cataract risk slightly increased
• Bone: minimal risk of osteoporosis, no effect on pediatric bone density by scanning studies
61
1. what does uncontrolled asthma cause in the skeletal system?
2. what might some studies say is the culprit? which one in particular?
1• Uncontrolled asthma reduces linear growth!
2• Some studies show no effect on growth velocity, other studies show agent specific growth delay (Fluticasone (flovent) appears to have least growth effect )
62
Leukotriene Receptor Antagonists (LTM)
| name them:
Leukotriene Receptor Antagonists (LTM)
• Montelukast (Singulair)
• Zafirluzast (Accolate)
• Zileuton (Zyflo)
63
Leukotriene Receptor Antagonists (LTM)
| mechanism:
Mechanism
• leukotriene receptor antagonist (part of inflammation cascade)
• Attenuates bronchoconstriction and inflammation
64
Leukotriene Receptor Antagonists (LTM)
| indication:
Indication
| • Mild to moderate asthma, allergic rhinitis
65
Leukotriene Receptor Antagonists (LTM)
| efficacy:
Efficacy
• Modestly effective- but, ICS are preferred over leukotriene agents
• used as adjunctive therapy
66
Leukotriene Receptor Antagonists (LTM)
| Adverse Effects:
Adverse Effects
• Multiple P450 drug interactions
• Potentiates Warfarin, Theophylline, Inderal
• Some association with Churg-Strauss Syndrome (which is...)
----- Systemic eosinophic vasculitis, vasculitic rash, Pulmonary and cardiac conditions
• Hepatotoxicity with Zileuton (Zyflo)
67
what to do???
| if Bronchspasm During Anesthesia:
```
Bronchspasm During Anesthesia
• 100% O2
• Remove aggravating factor
----o Light anesthesia (get them deeper_
----o Allergen
----o Volatile agent? (is it Des?)
----o secretions
• initiate Bronchodilation (epi)
• give Beta agonist (albterol)
• Volatile agent? (are you using desflurane--irritating)
```
68
```
what to do?
what meds to give when Managing Bronchospasm?
1. first Beta agonists drug?
2. sq dose?
3. iv dose?
4. nebulized dose?
5. pediatric dose?
```
1• Epinephrine for Bronchospasm
2• SQ - (1:1000) 0.1mg-0.5mg (may repeat 10-15 minutes as needed)
3• IV - 0.1-0.25 mg (Single dose max=1mg)
4• Nebulized
5• Peds (infants/children) – 10 mcg/kg SQ
69
what to do?
what meds to give when Managing Bronchospasm?
2. what is the second beta agonist drug?
Beta agonists (*Beta 2 selective agents)
o Albuterol- multiple puffs (4-12) via ETT (2 in an awake patient)
o Each MDI puff = 90mcg
o Available as Ventolin, Proventil, Accuneb or Albuterol
70
what to do?
what meds to give when Managing Bronchospasm?
what is the third Beta agonists medication?
1. dose
2. onset
3. gtt for whom? what dose?
4. what other uses?
1• Terbutaline- 0.25 mg SQ, may repeat x 1 (0.5mg/4hours)
2• Onset 5-15 minutes SQ
3• For status asthmaticus- GTT @10mcg/kg over2-3 minutes
4• Also used for premature labor
71
what to do?
what meds to give when Managing Bronchospasm?
1. what is the next (fourth) Beta agonists med?
2. what is MDI dose per puff? how many puffs? what is onset?
3. nebulized concentration? how many ml in 2.5 ns?
4. what is the caveat with this medication?
Beta agonists:
1. Isoproterenol
2• MDI- 120mcg/puff 1-2 puffs, onset 2-5 minutes
3• Nebulizer 1:200 solution 0.5ml in 2.5ml NS
4. LESS beta selective, therefore more beta 1 effects, increased risk of untoward (unfavorable) cardiac response
72
what to do?
what meds to give when Managing Bronchospasm?
1. what is the 5th beta agonist drug?what class?
2. why not often used?
3. what is MOA?
Theophyline (Aminophylline)
1• Methylxanthine class
2• Not often used due to availability of ICS, beta agonists as well as it’s low margin of safety, required monitoring of blood levels and potential for side effects
3• Several MOAs exist for effects but bronchodilation MOA is unclear
----• Inhibits phosphodieserase leads to increased cAMP possible smooth muscle relaxation
73
what to do?
what meds to give when Managing Bronchospasm?
Last considerations/questionable benefit:
1. medication #5; name? action? efficacy?
2. medication #6; name? action?
Last considerations/questionable benefit:
1• Magnesium Sulfate
---o May inhibit smooth muscle contraction, decrease histamine release and inhibit ach release
---o Effectiveness is controversial
2• Heliox
---o Mixture of helium and oxygen to drive albuterol into the lungs
---o Could improve exchange during bronchospasm due to low density of helium.
74
IV Steroids:
1. what do IV steroids do?
2. what is the dose and time interval; how is it discontinued?
3. what is a major concern with steroids?
4. what about patients on steroids already?
IV Steroids:
1• Decrease airway reactivity and inflammation
2• Dose- 1mg/kg methylprednisolone IV Q 6 hours, with gradual decrease (weaned over days)
3• Major concern is dose dependent adrenal suppression
4• May/should be given as prophylaxis in steroid dependent patients
75
Adrenal steroids consist of:
name some types
3 main branches and their products
```
Adrenal steroids consist of:
1. Glucocorticoids
• Hydrocortisone
• Cortisone
2. Mineral Corticoids
• Aldosterone (the main mineral corticoid)
3. Sex steroids
• Androgen
• estrogen
```
76
Glucocorticoid Pharmacologic Actions
| 10 things that glucocorticoids do:
Glucocorticoid Actions:
1• Regulatory
2• Negative feedback effects on pituitary and hypothalamus
3• Prolonged therapy can atrophy adrenal cortex
4• Metabolic
5• Decreased uptake of glucose, gluconeogenesis, hyperglycemia
6• Decreased protein synthesis
7• Anti-inflammatory/immunosuppressive
8• Reduced activity of mediators such as eicosanoids, platelet activating factor interleukins and Nitric Oxide
9• Reduction of chronic inflammation and allergic response
10• Decreased healing diminished protective response to inflammation and immune response to infection
77
Clinical Uses of Glucocorticoids:
| 7 uses for glucosorticoids:
Clinical Uses of Glucocorticoids
1• Anti-inflammatory and immunosuppressant therapy
2• Asthma
3• Diseases with autoimmune inflammatory response (rheumatoid arthritis)
4• Topical for skin inflammations
5• To prevent host versus graft response after organ or bone marrow transplant
6• PONV
7• Replacement therapy for adrenal failure
78
Unwanted Effects of Glucocorticoid Therapy:
| 6 things
Unwanted Effects of Glucocorticoid Therapy
1• Suppression of response to infection
2• Suppression of endogenous GC synthesis (negative feedback effect) can lead to adrenal insufficiency
3• Hyperglycemia
4• Iatrogenic Cushing's syndrome
5• Growth suppression in children
6• Osteoporosis (long term therapy)
79
Mechanism of Action of Glucocorticoids
1. how are most effects mediated (what receptors)?
2. inflammation is decreased by the suppression of what and the reversal of what?
Mechanism of Action of Glucocorticoids
1• Most effects are mediated by widely distributed GC receptors
2• Decreased inflammation by suppression of migration of
polymorphonuclear leukocytes and reversal of increased capillary permeability
80
Hydrocortisone-Dosing:
1. what should be given for patients that are adrenally suppressed or on chronic steroids
2. what is does for minor surgery?
3. moderate surgery?
4. major surgery?
Hydrocortisone-Dosing
1• Stress dosing (replacement) for known adrenal suppressed or on chronic steroids:
---o Minor surgery-25 mg/day x 1
---o Moderate surgery- 50-75mg/day for 1-2 days
---o Major surgery- 100-150 mg/day for 2-3 days
81
Hydrocortisone-Dosing:
what are doses for:
• Anti-inflammatory?
• Status asthmaticus?
* Anti-inflammatory 15-240mg q 12
| * Status asthmaticus 1-2 mg/kg q 6h x 24h
c. pharm exam 3 (w13)
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