Respiratory Drugs

Question 1

Beta-2 Agonist Examples

Answer 1

Salbutamol
Salmeterol
Formoterol
Terbutaline

Question 2

Beta-2 Agonist Indications

Answer 2

1. Asthma
2. COPD
3. Hyperkalaemia

Question 3

Beta-2 Agonist mechanism of action

Answer 3

Beta-2 receptors found in smooth muscle of bronchi, GIT, uterus and blood vessels.

Agonisation leads to smooth muscle relaxation - improves airflow.

Stimulates Na+/K+ pumps on cell surface membranes, causing K+ to move into cell

Question 4

Beta-2 agonist contraindications

Answer 4

May cause tachycardia - caution in cardiac disease as can promote angina / arrhythmias

Question 5

Beta-2 agonist side effects

Answer 5

Stimulates sympathetic “fight or flight response” = tachycardia, palpitations, anxiety, tremor. Promote glycolysis = increased glucose.

Long-acting can produce muscle cramps.

Question 6

Beta-2 agonist interactions

Answer 6

Beta-blockers: efficacy reduced

Corticosteroids: hypokalaemia

Question 7

Antimuscarinic examples

Answer 7

Tiotropium, Ipratopium

Question 8

Antimuscarinic indications

Answer 8

1. COPD: short-acting relieves SOB, long-acting prevents SOB and exacerbations.
2. Asthma: short-acting adjunct during acute exacerbation, long-acting added to high-dose inhaled corticosteroids and beta-2 agonists in step 4 of treatment ladder

Question 9

Antimuscarinic mechanism of action

Answer 9

Competitively inhibit acetylcholine at muscarinic receptor. Muscarinic receptors stimulate parasympathetic system. Receptor blockade =

• increased heart rate
• smooth muscle relaxation (bronchodilation)
• reduce glandular secretions in resp and GI tracts
• relax pupillary constrictor = dilated pupils
• relax ciliary muscles = prevents accomodation reflex

Question 10

Antimuscarinincs contraindications

Answer 10

Caution in patients with:

1. Angle-closure glaucoma: increase IOP
2. Arrhythmias

Question 11

Antimuscarinics side effects

Answer 11

Dry mouth

Question 12

Antimuscarinics interactions

Answer 12

None as have low systemic absorption

Question 13

Corticosteroids examples

Answer 13

Prednisolone, hydrocortisone, dexamethasone

Question 14

Corticosteroids indications

Answer 14

1. Allergic / inflammatory disorders: asthma, anaphylaxis
2. Suppression of autoimmune disease: IBD, arthritis
3. Cancer treatment - as part of chemo or to reduce tumour swelling
4. Hormone replacement in adrenal insufficiency or hypopituartism

Question 15

Coricosteroid mechanism of action

Answer 15

• Mostly glucocorticoid effects:
• Modify the immune response
• Up-regulate anti-inflammatory genes
• Down-regulate pro-inflammatory genes e.g. cytokines, TNF-alpha
• Suppress eosinophils and monocytes
• Increase gluconeogenesis

Some mineralocorticoid effects:

• Stimulate Na+ and water retention
• Promote K+ and H+ excretion

Question 16

Corticosteroid administration

Answer 16

Systemic: oral, IV, IM

Acute asthma: oral, 40mg daily

Question 17

Corticosteroids Contraindications

Answer 17

Caution in:

• Infection
• Children - suppress growth

Question 18

Corticosteroids side effects

Answer 18

1. Immunosuppression: risk and severity of infection and alters host response
2. Metabolic effects: DM, osteoporosis
3. Increased catabolism: proximal muscle weakness, skin thinning, easy bruising, gastritis
4. Mood changes: insomnia, confusion, psychosis, suicidal ideation
5. Mineralocorticoid: hypertension, hypokalaemia, oedema
6. Adrenal atrophy as suppresses ACTH secretion, switching off stimulus for normal adrenal cortisol production.
7. Sudden withdrawal = Addisonian crisis with cardiovascular collapse.
8. Symptoms of chronic glucocorticoid withdrawal include fatigue, weight loss and arthralgia.
9. Cushing’s sydnrome

Question 19

Corticosteroid interactions

Answer 19

1. NSAIDs: Increase risk of peptic ulceration and GI bleed
2. Enhance hypokalaemia: beta-2 agonists, theophylline, loop or thiazide diuretics.
3. Cytochrome P450 inducers may reduce efficacy
4. Reduce immune response to vaccines

Question 20

Corticosteroids patient information

Answer 20

Take in morning to mimic circadian rhythm.

Question 21

Mucolytics examples

Answer 21

Carbocisteine

Question 22

Mucolytics indications

Answer 22

COPD and Bronchiectasis - reduction of sputum viscosity

Question 23

Mucolytics MOA

Answer 23

Reduces goblet cel hyperplasia therefore reducing amount and viscosity of mucus glycoprotein secreted by respiratory tract

Question 24

Mucolytics adminisatration

Answer 24

Oral

Question 25

Mucolytics contraindications

Answer 25

1. History of peptic ulcer, as may disrupt gastric mucosal barrier 2. First trimester of pregnancy

Question 26

Mucolytics side effects

Answer 26

Mostly rare. 1. GI bleed 2. Eryhtmea multiforme 3. Stevens-Johnson syndrome

Question 27

Mucolytics interactions

Answer 27

Should not be used with antitussives (cough suppressants) or medicines that dry up bronchial secretions

Question 28

Theophylline indications

Answer 28

Asthma and COPD - treatment of symptoms

Question 29

Theophylline MOA

Answer 29

1. Relaxes smooth muscle of bronchial airways: inhibits enzyme responsible for breaking down cAMP --> muscle relaxation = bronchodilation 2. Reduces airway response to hisatmine / methacholine / adenosine and allergens. Prevents bronchoconstriction.

Question 30

Theophylline administration

Answer 30

Oral

Question 31

Theophylline contraindications

Answer 31

Narrow therapeutic index. Caution in cardiac and hepatic failure and viral infections as concentration increased. Concentration decreased in smokers and alcohol consumption.

Question 32

Theophylline side effects

Answer 32

Arrhythmias, tachycardia + palpitations, CNS stimulation, convulsions, GI upset, headache, insomnia

Question 33

Theophylline interactions

Answer 33

1. Metabolised by CP450 enzymes - concentration increased by inhibitors and decreased by inducers. Narrow therapeutic index. 2. Hypokalaemia if combined with Beta-2 agonists, so caution required in severe asthma.

Question 34

Oxygen indications

Answer 34

1. Increase tissue oxygen delivery in states of hypoxaemia. 2. Accelerate reabsorption of pleural gas in pneumothorax 3. Reduce half-life of carboxyhaemoglobin in carbon monoxide poisoning

Question 35

Oxygen MOA

Answer 35

1. Hypoxaemia: increases Pao2 in alveolar gas, so more o2 diffuses into blood, allowing more o2 to be delivered to tissues while underlying cause corrected. 2. Pneumothorax: reduces fraction on nitrogen in alveolar gas - accelerates diffusion of nitrogen out of body. Pleural air composed mainly of nitrogen, meaning it is reabsorbed faster. 3. CO poisoning: oxygen competes CO to bind haemoglobin - shortens half life of carboxyhaemoglobin

Question 36

Oxygen administration

Answer 36

1. Reservoir / non-rebreathe mask: bag continuously filled at 15L/min. Critical illness with sats <85%. 2. Venturi mask: blends oxygen with air at fixed ratio, used for COPD patients 3. Nasal cannulae: variable concentration (24-50%), at a flow of 2-6L/ min. 4. Simple facemask - few advantages

Question 37

Oxygen Side effects

Answer 37

``` Mask discomfort Dry throat (lack of water vapour) - improved by using humidification system ```

Question 38

Oxygen contraindications

Answer 38

In chronic type 2 respiratory failure (severe COPD), there are adaptive changes to persistent hypoxaemia and hypercapnia. If exposed to high O2 concentrations, adaptive state disturbed, causing rise in blood Co2. This leads to respiratory acidosis, depressed consciousness and worsened hypoxia. Aim for 88-92% saturations in these patients.