Salbutamol

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

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.

Target receptor

Beta-2 receptor; less selective for beta-1

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

Literature reference

Sandoz product monograph

CICM details of understanding Level 2
Mentioned around Deranged Physiology
Related SAQs

Question 10 from the first paper of 2023, as a stand-alone, but also many others obliquely.