Session 10.1: Pharmacodynamics 3

Question 1

how do drugs work in therapeutic treatment of ashma

Answer 1

functional antagonism of contraction - can target beta 2 adrenoreceptors to inhibit contraction and activate relaxation

Question 2

why do therapeutic drugs need to be specific/selective

Answer 2

if also bind to beta 1 adrenoreceptor can increase force and rate of contraction when trying to treat ashma - causing side effects (angina)

Question 3

how do we achieve selectivity

Answer 3

low Kd - to preferentially bind
high selective efficacy - when bound more likely to activate and cause conformational change
route of administration - quick and direct

Question 4

how do salbutamol and salmeterol differ

Answer 4

salmeterol - long acting, no selective effiacy, very low Kd - all about affinity

Question 5

potency is determined by

Answer 5

affinity and efficacy as well as other variables such as the number of receptors

Question 6

why might the response be unchanged

Answer 6

even if more receptors filled, for example a muscle can only contract so much and a gland can only secrete so much = there is a limit…not always need to bind to all receptos so will be spare receptors…biological response curve shifts to left, eg: 90% spare in muscarinic receptors for maximal contraction

Question 7

why might there be spare receptors to generate the same response

Answer 7

eg: in tyrosine kinase or GPCR

due to amplification of signal transduction pathway, or response limited by post -receptor event

Question 8

difference between values of Kd and EC50 reflect

Answer 8

amplification and spare receptors

Question 9

what does spare receptors do

Answer 9

increase potency of ligands..more sensitive to allow responses at low concentrations of agonist. as more receptos so more opporunity for the needed amount of receptors to be activated with same kd…maximal response with low conc of ligand…reduction in conc required to give 50%

Question 10

the number of receptors…

Answer 10

increase with low activity = up regulated

decrease with high activity = down regulated - removed from cell surface….receptor number fluctuates

Question 11

what can down regulation of receptors cause in response to drugs

Answer 11

tolerance/tachyphylaxis and withdrawal symptoms

as drug stimulates receptors causing them to downregulate, decrease, tissue becomes less sensitive

Question 12

if chronic heart failure

Answer 12

force of contracrtion curve shifts to right as less receptors, and potency of NA decreased as higher conc of drug required to evoke a maximal response