Pharm 101: Salbutamol

Class

Bronchodilator

Pharmacodynamics

• Selective beta-2 adrenergic receptor agonist (abundant on airway smooth muscle cells)
• Binding increases formation of intracellular cAMP via stimulation of adenylyl cyclase, which:
  • Relaxes airway smooth muscle (bronchodilation)
  • Inhibits release of bronchoconstricting mediators from mast cells
  • Inhibits microvascular leakage
  • Increases mucociliary transport

Pharmacokinetics

• Principle routes of administration are either inhaled or IV. Less commonly can be given PO, SC or IM.
• Rapid absorption in both GIT and lungs
• Via inhaled route, effects are maximal at 15-30 minutes post administration and persist for 3-4 hours
• Metabolism:
  • No lung metabolism
  • 50% first pass metabolism
  • Sulphated in the liver to inactive metabolites
  • Urinary elimination of active (30%) drug and inactive metabolites
  • Half life is 3-6 hours

Clinical uses

• Acute exacerbation of asthma or COPD
• Hyperkalaemia
• Previously used as a tocolytic in obstetric medicine to relax uterine smooth muscle to delay premature labour

Formulations

• Nebulised salbutamol
  • Advantages: no patient education required, no first pass metabolism
  • Disadvantages: larger particles and hence dose required, higher incidence of systemic side effects
• Spacer/inhaler
  • Advantages: as effective as nebulised salbutamol when used properly, can be used at lower dose, fewer side effects, no first pass metabolism
  • Disadvantages: patient education required
• IV salbutamol:
  • Advantages: no first pass metabolism, potentially efficacious in severe asthma
  • Disadvantages: requires IV access (can be problematic in young children), more systemic side effects, expensive
• Oral salbutamol:
  • Advantages: longer half-life, easier administration in disabled/very young patients
  • Disadvantages: larger dose required, 50% first pass metabolism, higher side effect profile, no advantages over inhaled route

Adverse effects

• Adverse effects relate to stimulation of beta-2 receptors, which are located in skeletal vascular and bronchial smooth muscle, the liver, and on cell membranes
• Musculoskeletal:
  • Tremor due to stimulation of beta-2 receptors in skeletal muscle
• Cardiovascular:
  • Tachycardia/palpitations/arrhythmias
  • Direct stimulating action of atrial beta-2 receptors
  • Peripheral vasodilation causes reflex cardiac stimulation
• Respiratory:
  • V/Q mismatch and transient decrease in PaO2
  • Vasodilatory action of beta-2 agonist causes transient decrease in PaO2 due to increased perfusion of poorly ventilated lung units
• Metabolic:
  • Hypokalaemia due to potassium entry into skeletal muscle
  • Other systemic metabolic effects, such as increase in FFA, insulin, glucose, pyruvate and lactate are generally only seen after large systemic doses
  • Lactic acidosis is rare
• Gastrointestinal:
  • Vomiting

Precautions/contraindications

• Arrhythmias
• Hypokalaemia

Further Reading

• Nickson C. Hyperkalaemia Management
• Nickson C. Acute Severe Asthma