Asthma & COPD pharm

Question 1

What is the hygiene hypothesis?

Answer 1

The immune system of the newborn infant is skewed toward Th2 cells and needs timely and appropriate environmental stimuli to create a balanced immune response

Question 2

What are the preformed mast cell mediators?

Answer 2

Histamine, TNF-alpha and proteases

Question 3

What are the Lipid-derived mast cell mediators?

Answer 3

LTC-4 (leukotrieneC-4) and LTD-4- bronchoconstriction, vasoconstriction
• LTB-4-leukocyte chemotaxis
• PGD-2 (prostaglandinD-2)-vasodilation, bronchoconstriction, mucus secretion, vasopermeability
• PAF (platelet activating factor)- bronchoconstriction, leukocyte chemotaxis

Question 4

What are the cytokine mast cell mediators?

Answer 4

IL-l (Interleukin-l)-broad promotion of inflammation
• IL-3-mast cell division
• IL-5-eosinophil differentiation and chemotaxis
• IL-6-lymphocyte growth and differentiation
• IL 4 and 13-activation of Th2 pathway activation
• GM-CSF stimulates PMNs, eosinophils and macrophages

Question 5

What are some extrinsic precipitants of asthma

Answer 5

Aspirin, NSAIDs, Beta blockers, cholinesterase inhibitors,

Question 6

What are the 10 approaches to treating asthma?

Answer 6

1. Increase cyclic AMP—Beta2 agonists
2. Block adenosine receptors—theophylline
3. Decrease cGMP—tiotropium
4. Prevent mediator release—beta2 agonists
5. Block mediator effects—antihistamines, LT receptor antagonists
6. Inhibit mediator synthesis—lipoxygenase inhibitors
7. Inhibit phosphodiesterase4 –roflumilast
8. Bind serum free lgE–omalizumab
9. Multiple antiinflammatory mechanisms of corticosteroids
10. Bind interleukin-5 –mepolizumab

Question 7

Name 3 beta agonists

Answer 7

Albuterol (short acting), Salmeterol (long acting), Levalbuterol

Question 8

Discuss the PKs of albuterol and salmeterol

Answer 8

Albuterol Onset-5 min; peak at 30-60 min; duration 4-6 h

Salmeterol • Onset-15-20 min; peak at 3-4 h; duration 12 h

Question 9

What are the side effects of beta agonists

Answer 9

Skeletal muscle tremor 
• Anxiety 
• Restlessness 
• Tachycardia and palpitations 
• Hypokalemia

Question 10

Discuss the Leukotriene receptor antagonists

Answer 10

Montelukast; Competitive antagonists of leukotrienes

1. Prevent but NOT reverse bronchorestriction
2. Used for exercise induced bronchorestriction
3. Not as effective as steriods

Question 11

Discuss the Cholinergic Muscarinic Antagonists

Answer 11

Tiotropium; Ipratropium is short acting

1. Given as a dry powder
2. Dry mouth is the SE
3. Used for COPD
4. Combined with albuterol as Combivent

Question 12

How does corticosteroids help with asthma?

Answer 12

1. Up-regulate beta-adrenergic receptors
2. Decrease vascular permeability
3. Decrease leukotriene synthesis
4. Decrease late-phase inflammatory response

Question 13

SEs of inhaled corticosteroids

Answer 13

1. Dysphonia
2. Candidasis (thrush)
3. Cataracts

Question 14

Discuss Theophylline

Answer 14

1. alpha blocker in bronchial smooth muscle

2. Treats COPD

Question 15

MOA of Theophylline

Answer 15

1. Relaxes bronchial smooth muscle and increases mucociliary clearance
2. Increases diaphragmatic contractility and decreases its fatigue
3. Dilates arterioles and venules and increases CO
4. Increases GFR and diuresis
5. Increases gastric acid secretion
6. Decreases lower esophageal sphincter tone

Question 16

SEs of Theophylline

Answer 16

1. Headaches, N/V, Gastric discomfort (PDE4 inhibition)
2. Diuresis (alpha blocker)
3. Tachycardia and Seizures (alpha blocker)

Question 17

Discuss the selective phosphodiesterase 4 inhibitors

Answer 17

Roflumilast;

1. NOT a bronchodilator
2. Reduces risk of COPD exacerbation with bronchitis

Question 18

SE of Roflumilast

Answer 18

N/V, weight loss and psychiatric symptoms

Question 19

Discuss Omalizumab

Answer 19

Monoclonal antibody against IgE; Binds free IgE

Question 20

PKs of Omalizumab

Answer 20

1. Administered sc every 2 or 4 weeks
2. Peak plasma concentrations occur in 7-8 days. Elimination half-life is about 26 days
3. Approved for treatment of moderate to severe persistent asthma in patients with reactions to allergens and not controlled with inhaled corticosteroids