Asthma and COPD

Question 1

Differences between Asthma and COPD

• Disease of?
• Reduced airway via?
• Inflammatory mediators?
• Symptoms?
• Reversible or Irreversible?

Answer 1

• Asthma
  
  • inflammation + allergen exposure
  • reduced airway via smooth muscle thickening that → bronchoconstriction
  • Inflamm mediators: Eosinophils, basophils, mast cells, CD₄ cells, IL-5
  • symptoms: episodic SOB, wheeze, cough, chest tightness
  • Reversible
• COPD
  
  • ​inflammation + irritation
  • reduced airway via cellular damage by external irritants
  • Inflamm mediators: neutrophils, macropages, CD₈ cells
  • Symptoms: chronic cough, excessive sputum, production
  • Irreversible

Question 2

Pathophysiology of Asthma

Answer 2

• IgE production in response to trigger
• Binds to mast cells
• Upon next exposure mast cells degranulate and leake things like leukotrienes and histamine
• 3-6 hrs later more sustained bronchoconstriction mediated by cytokines
  
  • late reponse= increased sensitivity to stimuli
    
    • inhaled GC’s
    • for early phase=SABA’s

Question 3

Pathophysiology of COPD

Answer 3

• irritants cause inflammatory cells to accumulate in the lungs
• triggers release of inflammatory mediators
  
  • TNF-alpha, IL-6, IL-8 and fibrinogen (airway inflammation)
• tissue damage and systemic effects
  
  • chronic inflammation leads to fibrosis, alveolar damage, and mucus hypersecretion (structural remodeling + mucociliary dysfunction)
    
    • loss of alveolar elasticity =poor O₂ exhange

Question 4

What is the number one cause of COPD and what is the # 1 treatment for COPD?

What does COPD meds cure the disease?

Answer 4

• smoking
  
  • smoking cessation leads to increase lung function
• No they only treat symptoms

Question 5

What is the preferred method of treatment for Asthma and COPD? Pros and Cons

Answer 5

• aeroslized delivery system pro’s
  
  • medication gets delivered directly to site (reduces systemic exposure)
  • lower dose & quicker onset
• con’s
  
  • requires proper technique (variability in diff. device techniques)
  • exspensive

Question 6

Aerosilzed Delivery Systems

• What devices do we have available?
• Advantages/ Disadvantages

Answer 6

Examples

• Metered dose inhaler (MDI)
  
  • Small, easy to use, can be used with spacer
    
    • Needs proper technique/coordination with breath being held
• Dry powder inhalers (DPI)
  
  • small, compact, cheaper, less coordination needed
    
    • patient must prepare the dose, fast deep inhalation, moisture sensitive
• Soft mist inhalers
  
  • high lung depostion-does not contain propellants
    
    • Complicated process for first dose , no spacer
• Nebulizer
  
  • minimal technique, pt doesn’t need to hold breath
    
    • $$$, requires dose preparation, bulky (not portable), 5-15 min administration, power source

Question 7

What Considerations should you keep in mind when selecting a device for your patient? (5 things)

Answer 7

• Patient-related factors
  
  • age, physical and cognitive abilities
• patient preference
• availability of the drug
• convience
  
  • portability
• cost/ reimburstment

Question 8

Short Acting Beta-2 Agonists (SABA)

1. MOA?
2. Selective for what receptor?
3. DOC for?
4. Onset of action and duration of action?
5. Administered?

Answer 8

1. MOA: stimulate adenylyl cyclase at beta-2 receptor →increase in cAMP in bronchial smooth muscle→bronchodilation
2. Selective for beta-2 receptor
3. DOC for ACUTE ASTHMA ATTACKS and exercise induced asthma
4. Onset: 5 min – Duration: 3-4 hrs
5. administered via inhalation

Question 9

1. What SABA agents do we have available?
2. ADR’s with PRN use and long term?

Answer 9

1. Albuterol and Levalbuterol
2. )

• PRN use
  
  • well tolerated maybe mouth irritation or cough
• Long term
  
  • muscle tremor
  • tachycardia
  • build up a tolerance to medication ( due to downregulation of beta receptors)

Question 10

Albuterol vs. levalbuterol

Answer 10

• albuterol is mixutre of (s)- albuterol and (r)-albuterol (levalbuterol)
  
  • (r)-albuterol is theraputically active
    
    • developed to minimize side effects
  • (s) is clinically inert w/ cardiac side effects
• in acute asthma and COPD attacks no sig difference b/w two- and no difference in HR

Question 11

1. What longacting and ultra long acting agents (LABA’s) do we have available?
2. MOA?
3. Indication?
4. Always use LABA w/ ?
5. ADR’s?

Answer 11

1.)

• long acting (LABA)
  
  • salmeterol
  • formoterol
• ultra long acting (LABA)
  
  • indacaterol
  • olodaterol
  • vilanterol

2.) same as SABA- MOA: stimulate adenylyl cyclaseat beta-2 receptor →increase in cAMPin bronchial smooth muscle→bronchodilation

3&4.)

• used in COPD-always use LABA with inhaled corticosteroid
  
  • NOT USED as monotherapy in asthma
  • Not for rescue therapy

5.) same as SABA

• PRN use
  
  • well tolerated maybe mouth irritation or cough
• Long term
  
  • muscle tremor
  • tachycardia
  • build up a tolerance to medication ( due to downregulation of beta receptors)

Question 12

1. What antimuscarinic agents are appropiate to use? WHAT IS IT THE DOC FOR?
2. Which one is short acting?
3. MOA?
4. anti-muscarinic and chronic inflammation effects
5. How long does the bronchodialating effects last?

Answer 12

1.) DOC for COPD

• Ipratropium
  
  • short acting (2.)
• Tiotropium
• Aclidinium
• Umeclidinium
• Glycopyrolate

3. ) blocks muscarinic receptors in airway- ACh cant bind- prevents vasoconstriction
4. ) no effects on chronic inflammation
5. ) bronchodilating effects last longer than beta-agonists

Question 13

• ADR’s for Antimuscarinics?
  
  • these drugs are good for what patients?

Answer 13

• dry mouth/eyes
• bitter, metallic taste
• constipation
• uriniary retention
• NO tremors or arrhythmias
  
  • DOC for elderly- b/c med is minimally absorbed, generally well tolerated

Question 14

Methylxanthine derivative

1. Agent available?
2. MOA?
3. Duration of action?

Answer 14

1. Theophylline-oral
2. Dual MOA:
   
   • non selectively inhibits PDE→ increase in cAMP→bronchodilation
   • blocks adenosine receptors →bronchodilation
3. Duration of action 12 hours

Question 15

Methylxanthine derivative

1. Agent available?
2. DDI’s?
3. Clearence mediated by what three things
4. Monitoring?

Answer 15

1. Theophylline
2. Many DDI’s via CYP 1A2
3. clearance mediated by age, smoking status, and other drugs
4. yes need to monitor due to narrow theraputic index
   
   • if you make the slightest dose change you are at risk for toxicity
   • requires higher conc. esp in adults

Question 16

What woud happen if Theophylline is given to a smoker?

What would happen overtime if patient stopped smoking and remained on theophylline?

Answer 16

• Theophylline is a CYP 1A2 substrate
  
  • smoking is an inducer of CYP 1A2
    
    • will cause theophylline to be metabolized faster
      
      • dose will be ineffective and u need to increase it
• If patient stopped smoking but stayed on theophylline then..
  
  • dose of drug needs to be REDUCED

Question 17

What are the ADR’s of Theophylline?

What are the ADR’s of Theophylline overdose?

Answer 17

• GI distress
  
  • due to enhanced gastric secretion (b/c of increase in cAMP)
• Tremor
• Insomnia
• In overdose
  
  • severe n/v
  • hypotension
  • cardiac arrest

Question 18

Roflumilast

1. Class?
2. MOA?
3. Indication?
4. Administration?

Answer 18

Roflumilast

1. PDE-4 inhibitors
2. MOA: selectively inhibits PDE-4 → increase cAMP → bronchodilation
3. Indication: severe COPD (used last-roflumiLAST)
4. Should be given with at least one LABA-oral once daily
   
   • duration of action > 10-20 hours

Question 19

Roflumilast (PDE-4 inhibitor)

• ADR’s?
• DDI’s?

Answer 19

Roflumilast (PDE-4 inhibitor)

• ADR’s
  
  • psychiatric events- need to screen prior to use
  • weight loss
• DDI’s with CYP 3A4

Question 20

Corticosteriods?

1. MOA?
2. DOC?
3. Onset of action?
4. Taper?

Answer 20

1. MOA: binds to glucocorticoid receptor to
   
   • inhibits cell inflammation/migration
   • inhibits cytokine and inflammatory mediators release
   • up-regulate Beta-2 receptors
   • Inhibit IgE
2. DOC for persistent asthma-prophylaxsis
3. Onset of action: 4-6 weeks
4. need taper don’t abruptly stop

Question 21

Corticosteroids

• Inhaled vs. IV/ORAL
  
  • agents available

Answer 21

• Inhaled
  
  • Beclomethasone
  • Budesonide
  • Fluticasone propionate (flovent)
  • Fluticasone furoate
  • Mometasone
  • Flunisolide
  • Ciclesonide
• Oral/IV
  
  • Prednisone
  • Prednisolone
  • Methylprenisolone
  • Hydrocortisone

Question 22

Corticosteroids

• Inhaled vs. IV/ORAL
  
  • ADR’s?

Answer 22

• Inhaled
  
  • Thrush
    
    • counsel patients to rinse mouth after use
• Oral
  
  • chronic use
    
    • cushings syndrome
    • infection risk
    • adrenal suppression
  • short term
    
    • mood changes
    • weight gain
    • edema

Question 23

1. What can you do for a patient that no longer uses advair b/c of recurrent thrush and nystatin is giving her no relief?
2. What inhaler causes thrush the most? examples?

Answer 23

• Ensure she is using proper technique of her advair
  
  • rinsing mouth after each use
• Mouth piece is cleaned
• consider swtiching to a spacer
  
  • reduces medication deposited in mouth
• Consider risning with alcohol based mouthwash
• Try different steroid

2.)

• DPI inhaler- dry powder inhaler
  
  • Diskus -advair
  • Handihaler
  • Twisthaler
  • Ellipta
  • Pressair
  • Flexhaler

Question 24

1. Example of Soft mist inhaler?
2. What cortico-steroid is the safest in pregnancy?

Answer 24

1. Respimat
2. Inhaled corticosteroid-Budesonide

Question 25

1. What is the DOC in children for asthma? 2. What are the potentional harms of this drug?

Answer 25

1. Corticosteroids 2. Potentional growth stunting in children

Question 26

Zileuton 1. Class? 2. MOA? 3. **ADR?** 4. C/I's?

Answer 26

1. Lipoxygenase inhibitor-adjunct asthma treatment 2. MOA: Inhibits actions of 5-lipooxygenase to inhibit the synthesis of leukotrienes 3. **ADR:Hepatotoxicity** 4. **C/I:** * **​**don't give if LFT's greater than 3x ULN * Females \>65 * those with pre-exsiting LFT elevation

Question 27

1. What **Leukotriene receptor antagonist** do we have? 2. MOA? 3. Indication? 4. **DDI's?** 5. **ADR's?**

Answer 27

1. Montelukast and Zafirlukast 2. MOA: blocks actions of leukotrienes at the LTD4 receptor 3. used for asthma, allergic symptoms (urticaria) * esp for allergic symptoms with no relief for antihistamine 4. Zafirlukast + warfarin → increase risk of bleed 5. * Generally well tolerated * **Neuropsychiatric events** * Hepatoxicity (Zafirlukast)

Question 28

Mast Cell Stabilizers 1. Agents available? 2. MOA? 3. Indicaiton? 4. Onset of action

Answer 28

1. Cromolyn sodium and Nedocromil sodium 2. MOA: block influx of Ca → prevents mast cell degranulation (stabilized) 3. **Mild cases of asthma but not DOC-NOT FOR RESCUSE SYMPTOMS** 4. **2-6 weeks**

Question 29

Omalizumab 1. Class? 2. MOA? 3. Indication? how old do you have to be? 4. formulation? onset of action? 5. ADR's? why is this ADR important

Answer 29

1. Anti-IgE agents 2. Monoclonal IgE antibody- inhibits fusion of IgE to mast cell → no release of inflamm mediators 3. **Allergic asthma not relieved with corticosteriod therapy-MUST BE GREATER THAN 12 years of age** 4. **subcutaneous injection (based on IgE and weight)- takes up to 12 weeks to work** 5. ADR's -anaphylaxsis (1.5-2 hrs post dose) so you need to monitor in office

Question 30

1. What IL-5 agents do we have? 2. MOA? 3. Indication? requirments? 4. ADR?

Answer 30

1.) * Mepolizumab * Reslizumab 2.) MOA: antagonize IL-5 to reduce circulating eosinophils **3.) maintenance of severe asthma- MUST BE GREATER THAN 18 with eosinophilic phenotype** 4.) Hypersensitivity rxn- can cause anaphylaxsis \*\*\*pt needs to stay for first dose