F8 Quantifying drug action - concentration-response curves, comparing agonists/antagonists in CRCs

Question 1

describe a cellular / simple bioassay

Answer 1

• second messenger response in cells expressing beta-adrenoceptors antagonist

Question 2

disadvantages of cellular / simple bioassays

Answer 2

• artificial
• cell lines may not behave as the cells in actual organs, response measured can be distant from actual function

Question 3

advantages of cellular / simple bioassays

Answer 3

• well-defined receptor types and signalling pathways

Question 4

give examples of a complex / organ / system bioassay

Answer 4

• organ: rate and force of isolated heart beats
• system: blood pressure changes in whole animal

Question 5

advantages of complex bioassays

Answer 5

• increasingly close to real physiology

Question 6

disadvantages of complex bioassays

Answer 6

• many different receptor types
• response is a composite of many effects on different cells/tissues

Question 7

what is Rmax?

Answer 7

• the point at which a conc-response curve plateaus
• the maximum response in % whereby the drug cannot have any further effect

Question 8

what is the EC50?

Answer 8

• a measure of agonist potency
• the concentration of the drug that produces half of the maximum response

Question 9

describe features of a full agonist

Answer 9

• high efficacy
• good ability to convert receptors from inactive to active

Question 10

describe features of a partial agonist

Answer 10

• lower efficacy
• lower ability to activate receptors once it has bound
• eg. number of activated receptors in the tissue is lower when exposed to salbutamol compared to adrenaline

Question 11

describe competitive and reversible antagonists

Answer 11

• competitive: receptor binding site is shared with the agonist drug
• reversible: the antagonist binds non-covalently and so can associate and dissociate from the receptor

Question 12

what happens to an agonist’s EC50 and Rmax in the presence of an antagonist?

Answer 12

• EC50 is reduced
• Rmax is unchanged
• surmountable antagonism with increasing agonist concentration

Question 13

what properties must an antagonist have for non-surmountable antagonism to occur?

Answer 13

• irreversible: forming a covalent bond with the receptor so it can’t dissociate
• non-competitive: binding at a different site on the receptor from the agonist drug