Salbutamol Practical Class

Question 1

Complete the diagram on the mechanism of action

Answer 1

Question 2

What is the mechanism of action of salbutamol-mediated relaxtion?

Answer 2

• Salbutamol activates the ß2 adrenoreceptor
• The ß2 receptor is a metabotropic receptor meaning it is connected to a G protein
• Once activated the ß2 receptor causes an increase in the activity of the enzyme adenylate cyclase
• Adenylate cyclase catalyses the formation of cAMP from ATP
• cAMP activates the enzyme protein kinase A (PKA)
• PKA phosphorylates two proteins involved in smooth muscle contraction to INHIBIT their activity:
• Inositol 1,4,5-triphosphate (IP3) Receptor which stimulates Ca2+ release from the endoplasmic reticulum
• Myosin light chain kinase (MLCK) which phosphorylates myosin to facilitate its interaction with actin and cause contraction.

Question 3

Complete the diagram

Answer 3

Question 4

What is the mechanism of action for Methacholine- and histamine-mediated contraction?

Answer 4

• Methacholine activates muscarinic 3 (M3) receptors on smooth muscle cells
• Histamine activates H1 receptors on smooth muscle cells
• Both M3 and H1 receptors are metabotropic and activate G proteins
• The 2nd messenger system is same for both receptors
• Phospholipase C is activated catalyzing the conversion of Phosphatidylinositol 4,5-bisphosphate (PIP2) to Inositol 1,4,5-triphosphate (IP3) and Diacyl glycerol (DAG)
• IP3 activates the IP3 receptor on the endoplasmic reticulum increasing Ca2+ release which when in association with calmodulin stimulates Myosin light chain kinase (MLCK) which phosphorylates myosin to facilitate its interaction with actin and cause contraction
• DAG activates protein kinase C (PKC) which phosphorylates Myosin Light Chain Phosphatase (MLCP) to INHIBIT its action. MLCP is responsible for dephosphorylating myosin so it can no longer interact with actin so causing relaxation.
• Therefore the activation of these receptors both promotes contraction, while inhibiting relaxation

Question 5

•Common side effects of salbutamol include?

Answer 5

• Increased heart rate
• Increased tremor

Question 6

•In addition to asthma what other conditions can salbutamol be used to treat?

Answer 6

•Premature labour between 22 and 37 weeks of pregnancy-both oral and IV preparations can be used.