Respiratory: Pharmacology - Muscarinic antagonists, steroids, disodium cromoglycate and other agents in respiratory disease

Question 1

Describe the pharmacokinetics of ipratropium

Answer 1

Absorption: poor oral absorption when inhaled (less systemic side effects)
Distribution: VD 340L/kg, 0.9% protein bound
Metabolism: onset within 15mins, peak serum levels 1-3hrs, duration of action 3-4hrs, metabolised in liver, t1/2 = 2hrs
Elimination: 50% renal

Question 2

Describe the pharmacodynamics of ipratropium

Answer 2

Inhibits vagally-mediated action of ACh at muscarinic receptors
Inhibits bronchial smooth muscle contraction and mucus secretion

Question 3

Describe the pharmacodynamics of tiotropium and umeclidinium

Answer 3

Long-acting muscarinic antagonists
Act at M1, M2 and M3 receptors but dissociate rapidly from M2 receptors

Question 4

Three mechanisms of action of corticosteroids in asthma

Answer 4

1. Inhibition of inflammatory cytokine production
2. Contraction of engorged bronchial mucosal vessels
3. Potentiation of B agonist effects

Question 5

Four examples of inhaled corticosteroids used in asthma

Answer 5

Budesonide
Fluticasone
Beclomethasone
Ciclesonide

Question 6

Two adverse effects of ICS

Answer 6

Oral candidiasis
Systemic glucocorticoid effects with long-term use of high-dose (including OP, cataracts)

Question 7

Mechanism of action of sodium cromoglycate in asthma

Answer 7

Inhibits mast cell degranulation (no direct bronchodilator effect)

Question 8

Pharmacokinetics of sodium cromoglycate

Answer 8

Poorly absorbed
Little toxicity

Question 9

Three clinical uses of sodium cromoglycate

Answer 9

1. Systemic mastocytosis
2. Allergic rhinoconjunctivitis (topical)
3. Asthma (historic)

Question 10

Which leukotrienes play a role in asthma?

Answer 10

LTB4: chemoattractant
LTC4 and LTD4: bronchoconstriction, bronchial hyperreactivity, mucus hypersecretion, mucosal oedema

Question 11

Mechanism of action of montelukast

Answer 11

LTD4 receptor antagonist

Question 12

Two clinical uses of montelukast

Answer 12

Asthma (especially where concerns re ICS toxicity)
Specific role in treatment of aspirin-exacerbated respiratory disease (5-10% of asthma patients)

Question 13

What proportion of asthma patients does AERD represent?

Answer 13

5-10%

Question 14

Two types of monoclonal antibodies available for the treatment of asthma

Answer 14

1. Anti-IgE
2. Anti-IL-5

Question 15

Mechanism of action of omalizumab

Answer 15

Anti-IgE monoclonal Ab (inhibits IgE binding but does not activate already-bound IgE, so does not cause mast cell degranulation)

Question 16

Three clinical uses of omalizumab

Answer 16

Severe asthma, especially with allergic component
Chronic recurrent urticaria
Peanut allergy

Question 17

Clinical use of mepolizumab

Answer 17

Eosinophilic asthma

Question 18

Role of IL-5 in asthma

Answer 18

Released by TH2 cells as pro-eosinophilic cytokine

Question 19

When should low-dose ICS be added in asthma management?

Answer 19

If reliever use >2/week, nocturnal symptoms >2/month, or FEV1 <80% predicted

Question 20

When should high-dose ICS and LABA be added in asthma management?

Answer 20

If severe symptoms or if FEV1 <50%

Question 21

Why are ICS not typically used in COPD unless severe or frequent exacerbation?

Answer 21

Increased risk of bacterial pneumonia

Question 22

What are the main drug classes used in management of COPD?

Answer 22

SABA and/or SAMA
Add LABA and/or LAMA if more severe disease
May be a role for theophylline