Respi - Anti-asthma Drugs Flashcards Preview

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Flashcards in Respi - Anti-asthma Drugs Deck (21):
1

Asthma is characterized by (3)

1. Hyper-responsiveness of the airway
2. Recurrent reversible airway obstruction
3. Chronic airway inflammation

2

Classes of anti-asthma drugs used & examples

Controllers (anti-inflammatory)
1. Inhaled Corticosteroids (Fluticasone, Ciclesonide)
2. Leukotriene Receptor Antagonist (Montelukast)
3. Cromolyn
4. Anti-IgE Antibody (Omalizumab)

Relievers (bronchodilators)
1. β2 Agonists (SABA - Salbutamol, LABA - Salmeterol, ULABA - Indacaterol)
2. Methylxanthine (Theophylline)
3. Anti-Muscarinic (Ipratropium Bromide)

3

Mechanism of action of inhaled corticosteroids

1. Binds to steroid receptors in cell cytoplasm - forms a complex that enters nucleus - binds to glucocorticoid response element (GRE) - controls protein synthesis
2. Inhibits enzyme phospholipase A2 (arachidonic acid - inflammation) - Anti-inflammatory effects
- DECREASED T cells, mast cells, macrophages, eosinophils in the airways; shedding of epithelial cells, macrophage phagocytosis & production of cytokines & proteases, COX2, 5-LOX, iNOS & PLA2 expression
- INCREASED lipocortin, β2 receptors on airway smooth muscle
- direct vasoconstriction and decreased plasma exudation/mucus secretion

4

Uses of inhaled corticosteroids (2)

1. 1st line prophylactic Asthma therapy
2. Nocturnal Asthma

5

Toxicity of inhaled corticosteroids (7)

1. Oropharyngeal Candidiasis - immune suppression
2. Dysphonia - problem with vocal cords leading to hoarseness
3. Cough/Throat Irritation
4. Easy bruising of skin (elderly)
5. Adrenal Suppression
6. Posterior Subcapsular Cataracts
7. Osteoporosis

6

Mechanism of action of leukotriene receptor antagonist

Blocks LTD4 in the leukotriene pathway which contributes to the pathogenesis of asthma (bronchoconstriction, inflammation)

7

Uses & toxicity of leukotriene receptor antagonists (3+1)

1. Prophylaxis & chronic treatment of asthma
2. Aspirin-induced asthma
3. Exercise-induced asthma

1. Eosinophilia

8

Mechanism of action of cromolyn

1. Inhibits mast cell degradation induced by IgE-mediated FcεRI cross linking
2. Alters delayed Cl channels - inhibits cellular activation
2. Promotes secretion of Annexin A1/Lipocortin-1 - blocks histamine & eicosanoid release from mast cells
3. Blocks release of inflammatory mediators from eosinophils, neutrophils, macrophages

9

Uses of cromolyn (2)

1. Prophylactic control of Asthma
2. Prophylactic control of Allergic Rhinitis/Conjunctivitis
- prevents cold, dry air & exercise-induced bronchospasm

10

Toxicity of cromolyn (2)

1. Throat irritation, dry mouth, coughing (preventable by first inhaling β2 agonist)
2. Unpleasant, bitter taste

11

Mechanism of action of anti-IgE antibody

1. Binds to Fc portion of IgE - decreases FcεRI expression on mast cells/basophils - prevents degranulation & asthmatic reaction
2. Depletes free IgE levels in serum

12

Uses of anti-IgE antibody (2)

1. Allergic Asthma
2. Allergic Rhinitis

13

Mechanism of action of β2 agonists

1. Activates β2GPCR - activates adenylyl cyclase - increased cAMP leading to (A) decreased intracellular Ca (B) decreased MLCK (C) increased K+ conductance - leading to airway smooth muscle relaxation
2. Mast cell stabilization, reduced microvascular leakiness, increased mucociliary clearance

14

Uses of β2 agonists (3)

1. SABA - reverses constricted airways (PRN)
2. LABA - prevents exercise-induced asthma + long term maintenance of (nocturnal) asthma
3. ULABA - COPD

15

Toxicity of β2 agonists (6)

1. Fine tremor of skeletal muscle
2. Muscle cramps
3. Peripheral vasodilation
4. Palpitations & tachycardia (cross reaction with β1 receptors)
5. Hypokalemia, Hyperglycemia
6. Tolerance

16

Mechanism of action of theophylline

1. Inhibits PDE which breaks down cAMP - increased cAMP - increased ASM relaxation
2. Inhibits adenosine which causes SM constriction
- Increased epinephrine release from adrenal medulla
- Decreased microvascular leakiness
- Increased contractility of fatigued diaphragm in COPD

17

Uses of theophylline (3)

1. Adjunct/add-on therapy to inhaled β2 agonists/steroids
2. Nocturnal bronchospasm (sustained release)
3. Improve lung function in COPD

18

Toxicity of theophylline (3)

1. GIT-related (nausea, vomiting, anorexia, abdominal discomfort)
2. CNS (nervousness, tremor, anxiety, headache, seizures)
3. CVS (arrhythmias)

19

Mechanism of action of ipratropium bromide

1. Inhibits M3 receptor-mediated bronchospasm (M3R is only expressed in airways)
- reverses portion of bronchospasm & mucus secretion caused by vagal nerve
2. Inhibits M2-nerve terminal transiently - bronchodilation

20

Uses of ipratropium bromide (2)

1. Adjunct/add-on therapy to inhaled steroids/β2 agonists
2. Patients intolerant of β2 agonists
2. COPD (more bronchodilator effect)

21

Toxicity of ipratropium bromide (4)

1. Unpleasant Taste
2. Dry Mouth
3. Urinary Retention in elderly
4. Paradoxical Bronchospasm