Week 14 Pharmacology - Respiratory Drugs

Question 1

What are the major categories of drugs used in the treatment of asthma? (Short term)

Answer 1

Sympathomimetics
Anti-muscarinics
Methylxanthine agents

Question 2

What are the major categories of drugs used in the treatment of asthma? (Long term)

Answer 2

LABA
Corticosteroids
Leukotriene pathway inhibitors (montelukast)

Question 3

What is the mechanism of action of adrenergic agonists in management of asthma?

Answer 3

Mediated through B2 receptors: agonist bind and cause airway smooth muscle relaxation (adenylyl cyclase, increased cAMP levels) and inhibit release of bronchoconstrictive agents from mast cells

Question 4

Describe pharmokinetics of salbutamol:

Answer 4

A: Inhaled, 10% reaches bronchial tree (spacer > neb with adequate respiratory effort)

D: Maximal within 15 mins, duration 3-4 hours, crosses placenta

M: hepatic metabolism

E: 30% unchanged in urine, remained in faeces and metabolites in urine

Question 5

What are adverse effects of salbutamol?

Answer 5

Hypotension (vasodilation)
Hypokalaemia (stimulation of Na+/K+ ATPase pump)
Tremor
Tachycardia
Lactic acidosis

Question 6

What is the duration of action of LABA salmeterol or formoterol?

Answer 6

12hr duration of action
Highly lipid soluble, therefore large Vd and T/12

Question 7

What is the mechanism of ipratropium?

Answer 7

Muscarinic antagonist –> competitively inhibits ACh at M3 muscarinic receptors on bronchial smooth muscle

**Main action is to antagonise vagal input to the bronchial smooth muscle, reducing bronchoconstriction and mucus production

Question 8

Describe pharmacokinetics of ipratropium:

Answer 8

A: poor systemic absorption when inhaled, 5% bioavailability

D: Doesn’t cross BBB, onset 3-5 mins, duration 4-6 hours

M: inactive metabolites

E: 50/50 urine and faeces

Question 9

What are LAMA and their duration of action?

Answer 9

Tiotropium: 24 hours, OD dosing
Aclidinium: 12 hrs, BD dosing

Question 10

What are two common types of methylanthines?

Answer 10

Theophylline
Caffeine

Question 11

What is the mechanism of action of theophylline?

Answer 11

PDE inhibition, therefore decreased metabolism of cAMP –> increased cAMP availability, leading to bronchodilation (main mechanism)

Also inhibits adenosine receptor, and can affect transcription of inflammatory genes to promote anti-inflammatory response

Question 12

What are the pharmacokinetics of theophylline?

Answer 12

A: Good oral absorption

D: Vd 0.5L/kg

M: Liver: initially first order/concentration dependent, but becomes zero order when saturated

E: Metabolites excreted in urine

Question 13

What are the pharmacodynamic effects of theophylline? (Think caffeine!)

Answer 13

Resp: bronchodilation, inhibition off antigen induced histamine release
CNS: cortical alertness, nervousness, tremor
CVS: positive chronotropic, inotropic, therefore increased CO
Renal: diuresis, increased GFR

Question 14

What is the major drawback that limits theophylline usage in clinical practice?

Answer 14

Narrow therapeutic window, therefore serum monitoring required.

**N+V, arrhythmia, tremor, seizure, hypokalaemia, hyperglycaemia

Question 15

What is sodium cromoglycate?

Answer 15

Mast cell degranulation inhibitor

Regular use can reduce symptom severity and regular bronchodilator medications, but no intrinsic bronchodilator activity itself

Question 16

What is the mechanism of inhaled corticosteroids?

Answer 16

Broad anti-inflammatory effect through inhibition of pro-inflammatory cytokine production mediated by downregulation of gene transcription –> reduce bronchial hyperactivity and reduce frequency of asthma exacerbations, potentiate action of B-agonists

Question 17

What are the pharmacokinetics of corticosteroids?

Answer 17

A: Usually PO in acute exacerbations, 70% bioavailability, first pass metabolism

D: Wide distribution

M: Liver

Question 18

As per steroid use for other purposes, what are the adverse effects?

Answer 18

Osteoporosis
Adrenal insufficiency
Immunosuppression
Cataracts

Question 19

What are the benefits, and the adverse effects of ICS?

Answer 19

Benefits: little systemic absorption, therefore limited chronic steroid effect

Adverse: oral candidiasis

Question 20

What is the mechanism of action of leukotriene inhibitors (montelukast)?

Answer 20

1. Inhibition of 5-lipo-oxygenase (preventing leukotriene synthesis from arachidonic acid
2. Inhibition of LTD4 binding to its receptor, preventing bronchoconstriction, bronchial reactivity, mucosal oedema

Question 21

What is the main clinical utility of montelukast?

Answer 21

Reduction of frequency of asthma exacerbations and improved symptom control in long term management, approved >1 yr old

Particularly beneficial in NSAID induced and exercise induced asthma.

(NSAIDs shunt AA pathway to leukotriene production)

Question 22

What is the role of ketamine in asthma?

Answer 22

NMDA receptor antagonist

Causes transient hypoventilation, hypercapnia, bronchial smooth muscle relaxation

Question 23

What is the theory as to the efficacy of heliox?

Answer 23

Combination of helium + oxygen (usually 80/20 or 70/30)

Density of gas is reduced, improving laminar flow and oxygen delivery to acinus.

Can be used in lower airway (asthma, COPD, bronchiolitis, bronchiectasis) as well as tracheal obstruction (croup, epiglottitis, FB, tumour)