Pharmacology - Respiratory

Question 1

What are the different groups of drugs used in asthma?

Answer 1

• Sympathomimetics – beta-2 agonists e.g. Salbutamol, Salmeterol, Formoterol
• Anti-muscarinic agents e.g. Ipratropium, Tiotropium
• Corticosteroids e.g. Prednisolone, Budesonide, Fluticasone
• Anti-histamines e.g. Promethazine, Loratadine
• Methylxanthines e.g. Theophylline (PDE inhibitor and adenosine receptor blocker), Aminophylline
• Leukotriene inhibitors e.g. Montelukast (Singulair)
• Mast cell stabiliser - cromolyn

Question 2

What are the mechanisms of action of beta-2 agonists?

Answer 2

• Bronchodilation

- Inhibit mast cell release

Question 3

Compare salmeterol and salbutamol.

Answer 3

Salbutamol

• PO/IV/inhaled – fast absorption all routes
• 50% metabolism with first pass via liver, remainder excreted by kidneys
• Short acting (4 hours)

Salmeterol

• Inhaled only
• Long acting (12 hours)

Question 4

What are the side effects of beta-2 agonists?

Answer 4

• Tachycardia
• Tremors/shakes
• Hypokalaemia

Question 5

How do steroids work in asthma?

Answer 5

1) Inhibition of airway mucosal inflammation
2) Reduce bronchial reactivity
3) Local immune suppression

Question 6

How do steroids work on a cellular level in asthma?

Answer 6

• Decreased activation of lymphoid cells/eosinophils
• Decreased cytokine production and action
• Decreased production of prostaglandins
• Decreased histamine release
• Decreased production of IgE and IgG

Question 7

Which drugs are used as asthma preventers?

Answer 7

• Corticosteroid/LABA combinations e.g. Seretide, Symbicort
• Long acting antimuscarinic agents e.g. Tiotropium (Spiriva)
• Cromolyn (works by mast cell stabilisation) – common in exercise induced or allergen-induced asthma
  → only offer value if taken prophylactically

Question 8

What are the potential adverse effects of inhaled steroid therapy?

Answer 8

• Oral candidiasis
• Hoarseness
• Delayed growth in children

Question 9

What are the potential adverse effects of Theophylline?

Answer 9

non-selective phosphodiesterase inhibitor

• Narrow therapeutic window:
  o 5-20mg/mL: improvement in pulmonary function
  o 15-20mg/mL: nausea, vomiting, headaches, abdo pain
  o > 40mg/mL: seizures or arrhythmias
• CNS: tremor, nervousness, convulsions and death
• CVS: positive chronotropic and inotropic effects → tachycardia, increased CO and BP
  77
• Renal: weak diuretic
• Resp: bronchodilation
• Skeletal muscle: increased contractions, which can provide benefit in contraction and reducing fatigue in the diaphragm in patients with COPD
• Toxicity: hypomagnesaemia, hypokalaemia, hypophosphataemia, hyperglycaemia and metabolic acidosis