Pharmacology II

Question 1

What are the two types of asthma?

Answer 1

Extrinsic: IgE Mediated; environmental triggers

Intrinsic: Normal IgE; physiological triggers

Question 2

What are triggers for extrinsic asthma?

Answer 2

Increased serum levels of IgE

Environmental Triggers:

Allergens

Infections

Environmental exposure to endotoxin, irritants, particulates, cockroaches, danders, floor heaters, wood fornaces

Stress, panic

Medicines: aspirin, NSAIDs, non-selective b-blockers, eye drops, steroid withdrawal

food additives

Question 3

What are triggers for intrinsic asthma

Answer 3

Normal serum levels of IgE

Pathophysiological Triggers:

Cold air

Exercise

Negative response to commone antigenic challenge

Question 4

What is the physiology of asthma?

Answer 4

Bronchospasm and Inflammation

Bronchioles are excessively sensitive to triggers

Airways becoem very narrow (bronchospasm) and lining of airways becomes inflamed

Inflammation produces swelling and excessive amounts of mucus in airways

Constant asthma attacks can lead to permanent damage to the bronchioles

Question 5

What cell types contribute to asthma?

Answer 5

• Inflammatory cells:
  Mast cells
  basophils
  eosinophils
  T lymphocytes
  macrophages
  neutrophils

- epithelial cells

- smooth muscle cells

- vascular endothelial

Question 6

What is occuring on the cellular level during an asthma attack?

Answer 6

1. Mast cell secretions: Ige, peroxidase, chemotactic factors and cytokines

• leads to leaking of endothelial barrier
• *2.** Bronchial gland and mast cells: Histamine
• more inflammatory recruitment
• *3.** Mast cells and eosinophils: protease production
• increased vascular permeability for further inflammatory infiltration
• *4.** Leukocytes and Platelets: leukotriene C4 and D4
• bronchiospasm and increased mucus production

5. Mast cells and lung epithelial cells: Prostaglandin

Question 7

What are the two concepts utilized in treating asthma?

Answer 7

1. Drugs that treat symptoms only - relievers
   Bronchodilatory actions
   rapid onset
2. Drugs that traet underlying cause - controllers
   anti-inflammatory actions
   slower acting
   often prophylactic

Question 8

What types of drugs are used as brochodilators?

Answer 8

1. B2 adrenergic agonists
Activates B2 receptors leading to bronchiole relaxation via G_s protein and adenylyl cyclase

2. Muscarinic antagonists
Block acetylcholine M₃ receptors; blocking constriction

3. Methylxanthines
Blocks adenosine A2 receptor

Question 9

What Beta 2 agonists are used to treat asthma?

Answer 9

Short acting B2-adrenergic agonists (SABA):
Albuterol
terbutaline

Long acting B2-adrenergic agonists (LABA):
Salmeterol
formoterl

Question 10

What are SABA’s and LABA’s used for?

Answer 10

SABA:
- response to acute asthma attack

LABA:

• good for nocturnal asthma attacks
• slow-onset - not for acute brochospasm

Question 11

What anticholinergics can be used to treat asthma?

Answer 11

- atropine

- ipratropium: short acting, doesn’t enter CNS

- tiotropium: long acting

Question 12

What methylxanthines are used to treat asthma?

Answer 12

• Theophylline
  * Plasma clearance varies widley and has very narrown therapeutic index: danger of toxicity
• caffeine
• theobromine

Question 13

What anti-inflammatory drug categories are used to treat asthma?

Answer 13

• Corticosteroids
• Leukotriene pathway modifiers
• Anti-IgE antibody

Question 14

What corticosteroids are used to treat asthma?

Answer 14

• prednisone
• fluticasone

- budesonide

- beclomethasone

*bold are inhaled

Question 15

What leukotriene pathway modifiers are used to treat asthma?

Answer 15

Zileuton: inhibits 5-lipoxygenase

zafirlukast and Montelukast: antagonize LTD4 receptor

Question 16

What anti-IgE drug can be used to treat astha?

Answer 16

Omalizumab:

• recombinant IgG1 monoclonal Ab
• Binds IgG and prevents its interaction with mast cells
• Useful for patients with persistent asthma