Respiratory Pharmacology

Question 1

Airway Drugs

Answer 1

Bronchodilators: Adrenergic agonists (beta 2 agonists - salbutamol, salmeterol, formeterol); muscarinic antagonists/anticholinergics - tiotropium = long acting muscarinic antagonist (LAMA); ipratropium-short acting anti-muscarinic (SAMA); methylxanthines (aminophylline)
Anti-inflammatory: steroids (prednisolone = oral, beclomethasone = inhaled corticosteroid (ICS); leuotriene receptor antagonist

Question 2

Inhaled Drug Devices

Answer 2

Pressurised metered dose inhalers (pMDIs): deep exhale/inhale and puff/hold breath for slow ten count/exhale slowly/wait one minute before second puff, use spacer/aerochamber, HCFC-carbon footprint
Dry powdered inhalers: usually one inhalation, not a puff
Multitude of new devices
Ask patients specifically about inhalers when taking a drug history - otherwise they may forget

Question 3

Salbutamol

Answer 3

Duration: short acting (begin immediately, 3-5 hour duration)
Routes: inhaled or nebuliser (higher dose), intravenous (very rarely used)
Mechanism of Action: binding to beta 2 receptors in the lungs results in relaxation of bronchial smooth muscles - it is believed that salbutamol increases cAMP production by activating adenylate cyclase, and the action of salbutamol are mediated by cAMP; short acting beta agonist (SABA)
Use: asthma and COPD, another SABA

Question 4

Sameterol

Answer 4

Duration: long acting (begins 2-30 min, 10-12 hour duration.
Routes: inhaled.
Mechanism of action: ling acting beta-adrenoceptor agonist (LABA) .
Use: asthma - in patients requiring long term regular bronchodilator therapy on ICS; not PRN and always used with ICS in asthma; COPD - persistent symptoms; either LABA/LAMA combination or ICS/LABA combination - FEV1 < 50%

Question 5

Formeterol

Answer 5

Duration: long acting (with short onset similar to salbutamol, but with prolonged duration - 10-12 hours)
Routes: inhaled
Mechanism of action: long acting beta adrenoceptor agonist
Use: asthma and COPD, combined with ICS (always) for asthma

Question 6

Tiotropium

Answer 6

Duration: long acting (24hr) use once daily
Routes: inhaled (dry powder handinhaler/mist Respimat)
Mechanism of Action: long acting muscarinic antagonist (it has a similar affinity to the subtypes of muscarinic receptors M1-M5. In the airways it exhibits pharmacological effects through inhibition of M3-receptors at the smooth muscle leading to bronchodilation).
Indication: stable COPD (symptoms despite SABA); asthma: in not improving despite ICS/LABA)

Question 7

Ipratropium

Answer 7

Short acting antimuscarinic agent
Onset 30 mins, duration - 6 hrs
Nebulised for acute presentations of COPD and sometimes asthma

Question 8

Theophylline

Answer 8

Duration: half life around 5 hours healthy adults
Routes: oral/iv
Mechanism of action: phosphodiesterase inhibitor - requires monitoring of level (blood test)
Indication: oral for COPD and asthma (persistent symptoms); iv for COPD and asthma in medical emergencies

Question 9

Adverse Events - bronchodilators

Answer 9

Tachycardia
Nervousness, irratibility, tremor
Inhaled preparations - less common
Oral preparations and IV - more side effects common - tachyarrhythmias/angina usually dose related

Question 10

Glucocorticoids

Answer 10

Systemic: IV/oral, stronger effects at high dose, action unaffected by inspiratory effect/inhaler tecnhique, more side effects.
Inhaled (beclamethasone, fluticasone, budesonide): localised action, few side effects, disease may prevent penetration of drug to affected areas.
Airway effects: DECREASE release of inflammatory mediator, infiltration and action of wbcs, airway oedema, airway mucus production; INCREASE number and sensitivity of beta 2 receptors

Question 11

Adverse events of glucocorticoids

Answer 11

Inhaled: gargle and use spacer - oral candidiasis, dysphonia
General: adrenal suppression, bone loss (exercise, vit D, calcium), slow growth in children, increase risk of cataracts/glaucoma/infection, gastric ulceration, hypertension and diabetes, mood disturbance

Question 12

Combination Inhalers

Answer 12

Know the principle and classes of drugs
ICS/LABA: formoterol/budesonide, formoterol/beclomethasone, salmeterol/fluticasone
LAMA/LABA: tiotropium/olodaterol
ICS/LABA/LAMA: beclomethasone/formoterol/glycopyronium

Question 13

Allergic Rhinitis Medications

Answer 13

Antihistamines (certirizine, chlorpheniramine; H1 antagonists; side effects: drowsiness/dry mouth/dry eyes/confusion)
Intranasal glucocorticoids (inhibit leukotriene receptors; decreased inflammation, bronchoconstriction, oedema, mucus, recruitement of eosinophils)
Sympathomimetics (decongestants) (pseudoephedrine, alpha antagonist - problems with abuse and MAOI)