Pharmacology: Salbutamol sulfate is a selective β2-adrenoceptor agonist with effects on smooth and skeletal muscles. These include bronchodilation, relaxation of uterine muscle and tremor. Smooth muscle relaxation is dose dependent and is thought to occur via the adenyl cyclase-cyclic adenosine monophosphate (cAMP) system, with binding of the drug to the β-adrenergic receptor in the cell membrane causing conversion of ATP to cAMP, which activates protein kinase. This leads to phosphorylation of proteins, which ultimately increase bound intracellular calcium; the consequent reduced availability of ionized intracellular calcium inhibits actin-myosin linkage thus causing relaxation of smooth muscle.
β2-agonists eg, salbutamol sulfate also have an antiallergic effect on mast cells causing inhibition of release of bronchoconstrictor mediators including histamine, neutrophil chemotactive factor (NCF) and prostaglandin D2 (PGD2).
Bronchodilation occurs after administration of salbutamol sulfate in normal subjects and in patients with asthma or chronic obstructive pulmonary disease (COPD). Other actions in the respiratory system include enhanced mucociliary clearance, which have been demonstrated in patients with COPD and in normal subjects and an antiallergic effect due to inhibition of mediator release. Stimulation of β2-receptor results in widespread metabolic effects, including rise in free fatty acid, insulin, lactate and glucose levels and a fall in serum potassium concentration.
Pharmacokinetics: Salbutamol sulfate is well absorbed from the gastrointestinal tract with between 58 and 78% of a radiolabel appearing in the urine within 24 hrs and 65-84% in 72 hrs. Presystemic metabolism is considerable. The major metabolite is a sulphate conjugate, which is probably formed in the bowel mucosa and is inactive, 34-47% of a radiolabel appears in the urine as the conjugate and approximately half of this amount as unchanged drug. The proportion of circulating drug that is protein bound is approximately 10%. Transfer of the drug across the placenta has been demonstrated both in vitro and in vivo.