drug-target pharmacodynamics part 1

Question 1

what is a drug

Answer 1

molecules that interact with a biological system to produce a biological response

Question 2

what is the MW of drugs

Answer 2

under 600

Question 3

are drugs endogenous

Answer 3

no

Question 4

examples of biologics

Answer 4

antibodies and proteins

Question 5

what is drug safety dependent on

Answer 5

therapeutic index

Question 6

how do you make drugs safe

Answer 6

keep it between the therapeutic window from efficacy vs toxicity

Question 7

why are drugs administered

Answer 7

to achieve a biological response that alleviates the symptoms or cause of an illness

Question 8

what is a biological process responsible for

Answer 8

producing the symptoms or causing the illness

Question 9

at the molecular level what is a drug target

Answer 9

usually a biomacromolecule (enzyme, receptor, ion channel) that’s involved in the biological process

Question 11

what are they key intermolecular interactions that promote association between the drug and the amino acid target proteins binding site

Answer 11

hydrogen bonding, VDW or LDF, ionic/electrostatic, pi-pi bonding and dipole interactions

Question 12

what determines the types of interactions available for drug molecules

Answer 12

the functional groups it contains

Question 13

what determines physiochemical properties such as water solubility and membrane permeability

Answer 13

the functional groups present

Question 14

how do drugs with non polar, aliphatic side groups bind to targets

Answer 14

short range vdw forces

Question 15

how do drugs with aromatic side groups bind to targets

Answer 15

short range vdw forces

Question 16

how do drugs with polar uncharged side groups bind to targets

Answer 16

midrange H-bonds

Question 17

how do drugs with positive and negatively charged side groups bind to targets

Answer 17

long range ionic

Question 18

what does the tertiary structure allow the enzyme to do

Answer 18

perform its function and maintain the integrity of the active site where catalysis is performed

Question 19

what do the amino acids that border the active site do

Answer 19

produce a particular 3D shape that maximises interactions between the enzyme and the substrate which ensure that the substrate is in the correct position

Question 20

how does the movement of the active site lower the activation energy

Answer 20

by forcing the substrate into a transition-state confirmation which is why it is catalytic

Question 21

what are the types of interactions between the amino acids that border the active site and the substrate

Answer 21

a mixture of H-bonds which are directional and specific for H-bonding groups on the substrate

and short range vdW interactions

Question 22

what is a competitive inhibitor of cox

Answer 22

flurbiprofen

Question 23

how does flurbiprofen work

Answer 23

it binds in preference to arachidonic acid and blocks prostaglandin synthesis which reduces the inflammatory response

Question 24

how do competitive inhibitors compete with substrates

Answer 24

• must have some structural resemblance so that it can match the 3D shape of the active site
• must form stronger interactions with the active site so that it binds in preference to the substrate
• need to stay in longer than the substrate as usually the binding process is dynamic and molecules will associate and dissociate

Question 25

what type of interactions happen between the enzymes that border the active site and an inhibtor/drug

Answer 25

the same as the interactions between the substrate and the active site