Drugs used in Respiratory Disease

Question 1

Name the drugs used as an appropriate management for life-threatening acute exacerbation of asthma [6]

Answer 1

1. High flow oxygen
2. Nebulised bronchodilators
3. Oral prednisolone 40 mg
4. Oral doxycycline 200 mg
5. IV magnesium 2g
6. Consider IV aminophylline infusion

Question 2

Why is high flow oxygen used in the management of a life-threatening acute exacerbation of asthma? [1]

Answer 2

to maintain SpO₂

Question 3

Why is oral prednisolone used in the management of a life-threatening acute exacerbation of asthma? [1]

Answer 3

to reduce bronchial inflammation

Question 4

When is oral doxycycline used in the management of a life-threatening acute exacerbation of asthma? [1]

Answer 4

if chest infection suspected

Question 5

Why is IV magnesium used in the management of a life-threatening acute exacerbation of asthma (mechanism of action? [3]

Answer 5

1. relaxation of smooth muscle;
2. blocks histamine release from mast cells;
3. diminishes acetylcholine release from nerve endings

Question 6

Why is IV aminophylline infusion considered in the management of a life-threatening acute exacerbation of asthma (mechanism of action)? [2]

Answer 6

• phosphodiesterase inhibitor, raises cAMP, activates PKA
  
  • reduces inflammation/innate immune response

Question 7

Name the respiratory antibiotics used for bacterial infection [4]

Answer 7

1. amoxicillin
2. co-amoxiclav
3. clarithomycin
4. doxycycline

Question 8

Describe the pharmacology of amoxicillin under the following headings:

1. mechanism of action incl. what family it’s in [3]
2. resistance [2]
3. excretion [1]

Answer 8

1. Mechanism of action:
   
   • Amino-penicillin family
   • Inhibits bacterial cell wall synthesis
   • Kills dividing bacteria
2. Resistance:
   
   • Production of β-lactamase by the bacteria is the most common mechanism of resistance
   • This breaks down β-lactam ring of penicillins
3. Excretion:
   
   • Predominantly renally excreted

Question 9

Describe the pharmacology of co-amoxiclav under the following headings:

1. mechanism of action [2]
2. excretion [1]
3. caution: when should you reduce dose? [1]

Answer 9

1. Mechanism of action:
   
   • Co-amoxiclav = amoxicillin + clavulanic acid
   • Clavulanic acid is an irreversible inhibitor of β-lactamases so it prevents cleavage of amoxicillin
2. Excretion:
   
   • Predominantly renally excreted
3. Reduce dose in:
   
   • severe renal impairment

Question 10

Describe the pharmacology of clarithromycin under the following headings:

1. mechanism of action [2]
2. administration [2]
3. when to be cautious & side effects [4]

Answer 10

1. Mechanism of action
   
   • Broad-spectrum bacteriostatic macrolide antibiotic
   • Inhibits bacterial protein synthesis (prokaryote ribosome, 50S subunit)
2. Administration
   
   • Rapidly absorbed orally
   • (can cause phlebitis [inflammation of vein] intravenously so avoid if possible)
3. Caution:
   
   • Undergoes hepatic mechanism
     
     • Caution in liver failure
   • Reduce dose in significant renal impairment
   • Inhibits CYP450
     
     • Risk of adverse drug interactions
   • QT prolongation → increased risk of arrhythmia

Question 11

Describe the pharmacology of doxycycline under the following headings:

1. mechanism of action [3]
2. resistance mechanisms [2]
3. side effects [2]

Answer 11

1. Mechanism of action:
   
   • Tetracycline - long half-life and broad spectrum
   • Bacteriostatic drug
   • Inhibits addition of amino acids to growing peptide by binding to prokaryotic ribosome
2. Resistance mechanisms:
   
   • efflux via ABC-transporters,
   • ribosome protection proteins (RPPs) preventing tetracycline binding
3. Side effects:
   
   • Avoid/caution in patients with hepatic impairment
   • Chelates calcium (avoid in young children and pregnancy)

Question 12

Describe the pharmacology of corticosteroids under the following headings:

1. mechanism of action [2]
2. indications [3]
3. side effects [13]

Answer 12

1. Mechanism of Action:
   
   • Bind to activated glucocorticoid receptors to suppress multiple pro-inflammatory genes that are activated in asthmatic airways by reversing histone acetylation
2. Indications:
   
   • Asthma
   • COPD with recurrent exacerbations
   • Exacerbations of asthma/COPD
3. Side Effects: MULTIPLE! NOT VERY SPECIFIC AGENTS
   
   • diabetes,
   • osteoporosis,
   • hypertension
   • muscle wasting,
   • peptic ulceration,
   • cataracts,
   • Cushing’s syndrome,
   • Adrenal suppression,
   • acute pancreatitis
   • hyperlipidaemia,
   • increased appetite,
   • salt and water retention,
   • immune suppression

Question 13

Describe the pharmacology of bronchodilators β₂ agonists under the following headings:

1. mechanism of action [2]
2. indications [2]
3. side effects [9]
4. important pharamcokinetics/pharmacodynamics [4]
   
   • examples of short-acting and long-acting?
   • administration options?

Answer 13

1. Mechanism of Action:
   
   • Higher specificity for pulmonary (ß2) receptors vs. cardiac (ß1) receptors
   • Stimulate adenyl cyclase to increase intracellular cAMP -5 relaxation of bronchial smooth muscle
2. Indications:
   
   • Treatment of asthma
   • Treatment of COPD
3. Side Effects:
   
   • tremor,
   • hypokalaemia,
   • hyperglycaemia,
   • hypomagnesaemia
   • flushing,
   • tachycardia,
   • arrhythmias,
   • headache,
   • muscle cramps
4. Important Pharmacokinetics/Pharmacodynamics:
   
   • Short-acting — salbutamol, terbutaline (elimination half-life: 3-5 hours)
   • Long-acting — salmeterol, formoterol, vilanterol, indacaterol
   • Salbutamol can be given via inhaled, nebulised, oral, intravenous routes
   • Inhalational route preferable/nebulised if severe

Question 14

Describe the pharmacology of bronchodilators antimuscarinics under the following headings:

1. mechanism of action [3]
2. indications [2]
3. side effects [6]
4. important pharamcokinetics/pharmacodynamics [3]
   
   • examples of short-acting & long-acting
   • excretion

Answer 14

1. Mechanism of Action
   
   • Antagonist of cholinergic M1 and M3 (muscarinic) receptors in the lung,
   • countering the direct bronchoconstriction of muscarinic receptor activation, which is coupled to Gq G-proteins and hence to Phospholipase P, IP3 production and intracellular Ca2+
   • On vasculature, M3 activation increases NO production, causing vasodilation
2. Indications
   
   • Treatment of asthma
   • Treatment of COPD
3. Side Effects
   
   • blurred vision,
   • dry mouth,
   • urinary retention,
   • nausea,
   • constipation
   • Nebulised ipratropium may precipitate acute angle closure glaucoma — use a mouthpiece not a mask (keep it out of the eyes!)
4. Important Pharmacokinetics/Pharmacodynamics
   
   • Short-acting — ipratropium bromide
   • Long-acting — tiotropium, glycopyrronium, umeclidinium
   • Renally excreted

Question 15

Describe the pharmacology of bronchodilators: methylxanthines (aminophylline/theophylline) under the following headings:

1. mechanism of action [2]
2. indications [2]
3. side effects [6]
4. what is unique about the composition of aminophylline and what does this allow? [3]
5. Important Pharmacokinetics/Pharmacodynamics [14]
   
   • time to steady state?
   • therapeutic window?
   • toxicity?
   • cautions?
   • effect of smoking?

Answer 15

1. Mechanism of action:
   
   • Non-selective inhibition of phosphodiesterase → increased intracellular cAMP → bronchial smooth muscle relaxation
   • Immunomodulatory action - improved mucociliary clearance and anti-inflammatory effect (inhibits synthesis of leukotrienes and TNFα)
2. Indications
   
   • Adjunct to inhaled therapy in asthma/intravenous infusion in severe exacerbations of asthma
3. Side Effects
   
   • GI upset,
   • palpitations,
   • tachycardia/arrhythmias,
   • headache,
   • insomnia,
   • hypokalaemia
4. Composition of Aminophylline
   
   • a mixture of theophylline and ethylenediamine (ratio 2:1)
   • This formulation improves solubility and is preferred for IV administration;
   • also non-selective adenosine receptor antagonist
5. Important Pharmacokinetics/Pharmacodynamics
   
   • Time to steady state: 2-3 days
   • Narrow therapeutic window: 10-20 mg/L
     
     • Drug monitoring: 4-6 hours post-dose
   • Toxicity:
     
     • severe vomiting,
     • hypokalaemia/hypocalcaemia,
     • seizures,
     • arrhythmias,
     • hypotension
6. Metabolised in the liver
   
   • caution in liver disease and with concomitant use of some antibiotics including rifampicin, clarithromycin, ciprofloxacin
7. Smoking increases theophylline clearance
   
   • dose may need adjusted following smoking cessation

Question 16

Give examples of combination inhalers [9]

Answer 16

1. LABA/LAMA
   
   • Anoro Ellipta → umeclidinium/vilanterol
   • Ultibro Breezhaler → glycopyrronium/indacaterol
   • Duaklir Genuair → aclidinium/formoterol
2. LABA/ICS
   
   • Relvar Ellipta → fluticasone/vilanterol
   • Seretide Accuhaler/Evohaler → fluticasone/salmeterol
   • Symbicort Turbohaler → budesonide/formoterol
   • Fostair MDI → beclometasone/formoterol

Question 17

Name the 3 maintenance drugs used for asthma [3]

Answer 17

1. Leukotriene receptor antagonists (Montelukast and Zafirlukast)
2. Omalizumab
3. Mepolizumab

Question 18

Describe the pharmacology of leukotriene receptor antagonists (Montelukast & Zafirlukast) under the following headings:

1. indications [2]
2. administration [1]
3. mechanism of action [3]
4. half-life? [1]

Answer 18

1. Indications:
   
   • For asthma maintenance; not to be used for treatment of acute attacks.
   • Useful for prophylaxis of exercise-induced asthma, allergic rhinitis
2. Administration:
   
   • Taken orally
3. Mechanism of action;
   
   • High affinity antagonist of cysteinyl leukotriene receptor (CysLT1) inhibiting the action of LT-D4 in smooth muscle cells of the airway and airway macrophages → reduces airway oedema and smooth muscle contraction
4. Short half-life

Question 19

Describe the pharmacology of omalizumab under the following headings:

1. type of drug [1]
2. indications [1]
3. administration [1]
4. risk? [1]

Answer 19

1. monoclonal anti-IgE antibody
2. severe persistent allergic asthma
3. subcutaneous injection every 4 weeks
4. risk of severe hypersensitivity reaction

Question 20

Describe the pharmacology of mepolizumab under the following headings:

1. type of drug? [1]
2. mechanism of action [1]
3. indication [1]
4. administration [1]
5. side effects [1]

Answer 20

1. anti-IL5 monoclonal antibody
2. reduces circulating eosinophils
3. severe refractory eosinophilic asthma
4. subcutaneous injection every 4 weeks
5. headaches commonly reported

Question 21

Name the 3 drugs used to reduce exacerbations in COPD [3]

Answer 21

1. Roflumilast
2. Azithromycin
3. Carbocysteine