Describe the pharmacology of salbutamol (70% of Marks), including the principles
and efficacy of methods of delivery (30% of Marks).
Good candidates answered this question in 4 parts; pharmaceutics, pharmacokinetics, pharmacodynamics and delivery devices. The most common reason for not passing this question was providing vague statements without explanation or the specific information required. Candidates were expected to comment on importance of particle size and drug delivery, patient compliance, the effect of a spacer and systemic effects of different routes of administration. Whilst some candidates did make reference to this it lacked the detail required to demonstrate that they understood the concepts.
| Class | Bronchodilator |
| Chemistry | Synthetic sympathomimetic amine, structurally analogous to catecholamines |
| Routes of administration | IV, nebulised |
| Absorption | Poor oral bioavailability; but it is still somehow available as a syrup. When given as a nebuliser, approximately 10% of an inhaled salbutamol dose is deposited in the lungs. |
| Solubility | Alkaline drug with two ionisable groups, phenolic hydroxyl group (pKa = 9.3) and the secondary amine group (pKa 10.3). Freely soluble in acidic solutions. |
| Distribution | VOD is 1.3L/kg; minimally protein bound |
| Target receptor | Beta-2 receptor; less selective for beta-1 |
| Metabolism | Metabolised in the liver (extensive first-pass metabolism); The main metablite is the biologically inective salbutamol-o-sulphate. It can also be de-aminated by oxidative deamination or conjugated with glucuronide. |
| Elimination | The elimination half-life of salbutamol is 118 minutes (range 69 to 162 minutes); unchanged drug and metabolite are 72% excreted in the urine within the first 24 hours. |
| Time course of action | Airway resistance decreases within 5 to 15 minutes after inhalation of salbutamol; maximum effect is seen at 60 to 90 minutes, and some level of activity persists for 3 to 6 hours. |
| Mechanism of action | Beta-adrenoceptors are coupled to Gs-proteins, which activate adenylyl cyclase to form cAMP from ATP. This results in increased protein kinase A activity, which results in the inhibition of phosphoinositol hydrolysis, which in turn results in decreased intracellular Ca2+ levels. With less intracellular calcium, the bronchial smooth muscle tone decreases. |
| Clinical effects | Bronchodilation, tachycardia, hypokalemia, hyperlactataemia, insomina, muscle cramps |
| Single best reference for further information | Sandoz product monograph |
Methods of delivery:
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Harding, Erika K., Samuel Wanchi Fung, and Robert P. Bonin. "Insights into spinal dorsal horn circuit function and dysfunction using optical approaches." Frontiers in Neural Circuits 14 (2020): 31.