THERAPEUTICS L12 EX1 (ASTHMA) (MARSH)

T/F: Non-allergic asthma is typically not responsive to ICS therapy.

True

Protective environmental factors in regards to asthma development?

1. Healthy diet

2. Low pollution rates

3. Exercise

Simple 3 step pathophys of asthma?

1. Inflammatory cells and mediators

2. Airway narrowing

3. Expiratory airflow limitation

Medications that can exacerbate asthma?

1. Non-steroidal anti-inflammatory drugs (NSAIDs)

2. Aspirin

3. Beta-blockers

Spirometric presentation of asthma?

Demonstrates obstruction (reduced FEV1/FVC) w/ reversibility following inhaled B2-agonist administration.

^ "Reversibility" defined as an FEV1 increase of more than 12% and 200mL

Clinical signs of asthma? (four)

1. Wheezing on auscultation

2. Prolonged expiratory phase on auscultation

3. Dry hacking cough

4. Signs of atopy

Clinical symptoms of asthma? (four)

1. Episodes of SOB

2. Chest tightness

3. Coughing (HS)

4. Wheezing

Two big diagnostic criteria for patients aged 6+ ?

1. History of typical variable respiratory symptoms (wheeze, SOB, cough, chest tightness)

2. Confirmed variable expiratory airflow limitation

T/F: Separate diagnostic criteria exists for asthma patients already taking inhaled corticosteroid-containing treatment.

True

Adverse effects associated with SABAs? (four)

1. Tachycardia

2. Muscle tremors

3. Hypokalemia

4. Hyperglycemia

Criteria for "uncontrolled asthma" involves one or both of the following: (two criteria)

1. Poor symptom control (frequent symptoms or reliever use, activity limited by asthma, night waking)

2. History of one or more exacerbations in the previous year, poor adherence, incorrect inhaler technique, chronic sinusitis, smoking

Describe "difficult-to-treat" asthma severity classification (two criteria)

Uncontrolled despite prescribing of medium- or high-dose ICS with a second controller (usually LABA) or with maintenance OCS

Requires high-dose treatment to maintain good symptom control and reduce risk of exacerbations

Describe "severe" asthma severity classification

Subset of difficult-to-treat asthma that is uncontrolled despite adherence with maximal optimized high-dose ICS-LABA treatment and management of contributory factors.

Describe "mild" asthma severity classification

Well controlled with low intensity treatment

(As-needed low-dose ICS-formoterol)

(Low-dose ICS + as-needed SABA)

Treatment goals in asthma? (two big ones)

1. Long-term asthma symptoms control

2. Long-term asthma risk minimization

Describe SMART asthma therapy

Single-inhaler

Maintenance

And

Reliever

Therapy

Use of ICS-formoterol as both maintenance and reliever inhaler

T/F: Formoterol is both long-acting and short-acting (in terms of onset).

True, that is why it works for SMART therapy

Adverse effects associated with LABAs? (three)

1. Hypokalemia

2. Tachycardia

3. Boxed warning (NO MONOTHERAPY!)

T/F: SAMAs can be used in exacerbations.

True

Adverse effects associated with muscarinic antagonists? (four)

1. Dry mouth

2. Nausea

3. Metallic taste

4. Narrow-angle glaucoma

T/F: LAMAs can be used as monotherapy in COPD.

True

Adverse effects associated with systemic corticosteroids? (seven)

1. Adrenal suppression

2. Osteoporosis

3. Fracture

4. Gastrointestinal bleeding

5. Infection

6. Venous thromboembolism

7. Edema

Potential adverse effects of inhaled corticosteroids? (nine in red just look at em)

1. Dysphonia

2. Thrush

3. Growth retardation

4. Osteoporosis

5. Fractures

6. Glaucoma

7. Adrenal suppression, immunosuppression

8. Impaired wound healing, easy bruising

9. Hyperglycemia/hypokalemia

Airsupra is a(n) ______________

A. ICS

B. ICS + SABA

C. ICS + LAMA + :ABA

D. SABA

B. ICS + SABA

(budesonide + albuterol)

Symbicort HFA is a(n) ____________

A. ICS

B. ICS + SABA

C. ICS + LAMA + ABA

D. ICS + LABA

D. ICS + LABA

(budesonide + formoterol)

Adverse effects associated with leukotriene modifiers? (two)

1. Neuropsychiatric events

2. Eosinophilic granulomatosis w/ polyangitis

T/F: Oral bronchodilators are recommended by GINA.

False; oral bronchodilators are NOT recommended by GINA.

T/F: Theophylline is a methylxanthine.

True

MOA of omalizumab (Xolair)

Binds to Fc portion of IgE, preventing binding of IgE to its high-affinity receptor on mast cells and basophils (decreases the release of mediators in response to allergen exposure)

Eligibility criteria for omalizumab therapy? (three)

1. Sensitization to inhaled allergen(s) on skin prick testing or specific IgE

2. Total serum IgE and body weight within local dosing range

3. More than a specific number of exacerbations within the last year

Adverse effects associated with omalizumab? (two)

1. Local injection site reactions

2. Anaphylaxis

Anti-IL-5 biologic examples? (three)

1. Mepolizumab

2. Reslizumab

3. Benralizumab

MOA of mepolizumab, reslizumab?

Target IL-5, which regulates the terminal differentiation of eosinophils + eosinophil activation and recruitment to the airway

MOA of benralizumab?

Binds alpha subunit of IL-5 receptor of eosinophils, prevents binding of IL-5, thus mitigating downstream eosinophilic inflammation

T/F: ICS therapy are less effective than leukotriene modulators.

False; ICS more effective.

In regards to what adverse effect of montelukast did the FDA most recently issue a warning?

Neuropsychiatric events

MOA of dupilumab (Dupixent)

Targets IL-4a receptor (blocking IL4 and IL13 signaling) which are key cytokines that promote IgE synthesis and inflammatory cell recruitment

General eligibility criteria for ages 6+ for dupilumab therapy? (two points)

1. More than a specified number of severe exacerbations in the last year

2. Type 2 biomarkers above a specified level OR requirement for maintenance OCS

Major adverse effects of dupilumab (Dupixent)? (three)

1. Injection site reactions

2. Eosinophilia

3. Vasculitic-appearing rashes

MOA of tezepelumab (Tezspire)?

Binds circulating TSLP, a bronchial epithelial cell-derived alarmin

Define "clinical remission" of asthma

No asthma symptoms or exacerbations for a specific period

Define "complete (or pathophysiological) remission" of asthma

No asthma symptoms/exacerbations for a specific period, normal lung function, airway responsiveness, and/or inflammatory markers.

NAEPP Stepwise Approach for patients 12+

(steps 1-6)

Step 1 (intermittent asthma): PRN SABA

Step 2 (management of persistent asthma): Daily low-dose ICS + PRN SABA or PRN concomitant ICS and SABA

Step 3 (mgmt): Daily and PRN combination low-dose ICS-formoterol

Step 4 (mgmt): Daily and PRN combination medium-dose ICS-formoterol

Step 5 (mgmt): Daily medium-high dose ICS-LABA + LAMA and PRN SABA

Step 6 (mgmt): Daily high dose ICS- LABA + oral systemic corticosteroids + PRN SABA

According to GINA, the "alternative" reliever is what?

PRN ICS-SABA

According to GINA, the "preferred" reliever is what?

PRN low-dose ICS-formoterol

At what step in asthma therapy do we typically recommend the addition of a LAMA?

Step 5

In steps 3 and 4 of "alternative" asthma therapy (per GINA), the maintenance therapy constitutes a low or medium/high dose (respectively) what?

ICS-LABA

In steps 3 through 5 of "preferred" asthma therapy (per GINA), the maintenance therapy constitutes a low, medium, or high dose (respectively) of what?

ICS-formoterol

Steps 1-2 of "preferred" asthma therapy (per GINA) recommend what therapy?

PRN-only low dose ICS-formoterol

T/F: The small increase in potential risk of harms from a LAMA may outweigh its benefits in some individuals.

True

T/F: Black patients are more susceptible to harmful side effects when a LAMA is added to asthma maintenance therapy.

True

T/F: LAMAs have a more preferrable benefit-harm profile as opposed to LABA in add-on ICS therapy.

False; LABAs are preferred.

In ages 5-11, the NAEPP recommends what treatment in step 1 (intermittent asthma) therapy?

PRN SABA

For children 6-11, in patients with asthma symptoms <2 days a week (Step 1 asthma therapy), what is the recommended maintenance therapy?

Low dose ICS whenever SABA is taken

T/F: According to NAEPP's Stepwise Approach for patients 0-4 years of age, the addition of a short course of ICS is recommended at the start of a respiratory tract infection.

True

T/F: Per GINA's recommendations, in patients younger than 5, for step 1 asthma management therapy, only a PRN SABA is recommended.

True

Maximum dose (in adults) for budesonide-formoterol DPI?

12 doses

Maximum dose (in children) for budesonide-formoterol DPI?

8 doses

T/F: A benefit of budesonide-formoterol formulations is that there exists no necessary wait time before reliever doses.

True

Describe a "short-term" step up for asthma therapy?

Short term = 1-2 weeks

For viral infections, seasonal allergen exposure

Per asthma action plan or by provider

Describe a "sustained" step up for asthma therapy?

Assess adherence and technique

Considered a therapeutic trial with referral if no improvement