Introduction to Pharmacodynamics

Question 1

therapeutic index

Answer 1

• ratio of TD50 to the ED50
• provides indication of drug safety
• larger the index the safer the drug

Question 2

what is ED50?

Answer 2

effective dose in 50% of population

Question 3

what is TD50?

Answer 3

toxic dose in 50% of population

Question 4

how does a drug work?

Answer 4

• binds to receptor
• change in physical property of cell
• chemical or metabolic changes
• do not create new cell effects/actions

Question 5

drug receptor

Answer 5

• proteins on or within cell surface/cytoplasm

Question 6

ligand

Answer 6

• something that binds to a receptor
• signal molecule: endogenous substance or drug

Question 7

tachyphylaxis

Answer 7

• acute tolerance
• rapidly decreasing response to drug after only a few doses - need a drug free period to reset

Question 8

tolerance

Answer 8

• decreasing response to repeated constant doses of a drug
• may be pharmacokinetic or dynamic
• ex: opioids - if stop and restart must start at low dose or may OD

Question 9

affinity

Answer 9

• force of attraction between drug and receptor
• higher affinity drugs are harder to displace

Question 10

selectivity

Answer 10

• specificity of drug for target receptor binding
• SNS receptors
• makes fewer effects on unwanted receptors

Question 11

potency

Answer 11

• comparative term to describe concentrations of different drugs necessary to induce same magnitude of response
• a more potent drug is not necessarily a better drug

Question 12

efficacy (intrinsic activity)

Answer 12

• ability of drug to have response
• complex relationship (drug conc., receptor activation, cellular response)

Question 13

what are the 4 types of efficacy responses?

Answer 13

• agonist
• antagonist
• partial agonist
• inverse agonist

Question 14

agonist

Answer 14

• receptor interaction results in activation
• occupation theory: magnitude of response is proportional to # of receptors occupied

Question 15

partial agonists

Answer 15

• binds to receptor
• activates receptor
• only results in partial response - maximal response not observed (lower efficacy)

Question 16

antagonist

Answer 16

• drug interacts selectively with receptors, lacks intrinsic efficacy
• blocks or reduces the action of an agonist at the receptor

Question 17

2 types of antagonists

Answer 17

• competitive
• non-competitive

Question 18

competitive antagonist

Answer 18

• looks like drug, binds same site

Question 19

non-competitive

Answer 19

• binds somewhere else (allosteric site)
• changes receptor conformation so agonist cannot bind

Question 20

reversible antagonist

Answer 20

• bind to receptor (affinity) but can easily dissociate from the receptor (weak bonds like H-bonds and van der waals)
• agonist present at sufficiently high conc. can displace an antagonist
• decreases potency bc a higher conc. is now necessary to induce same response

Question 21

irreversible antagonists

Answer 21

• binds and stays
• covalent bonds
• agonist response cannot occur until receptor is replaced and any remaining unbound antagonist has been removed from body
• decreases efficacy preventing maximal possible response

Question 22

inverse agonists

Answer 22

• bind and have negative response
• receptors that have constitutive activity
• shut off cell activity

Question 23

chemical antagonism

Answer 23

• direct chemical interaction between two drugs

Question 24

physiologic antagonism

Answer 24

• two drugs act in same physiologic system but act on different receptors or pathways

Question 25

pharmacokinetic antagonism

Answer 25

- one drug alters the response to another drug through changes in disposition

Question 26

drug characteristics affecting concentration at receptor

Answer 26

- molecular weight - lipid solubility - pKa - protein binding - concentration gradient

Question 27

increased drug transfer

Answer 27

- smaller MW - higher lipid sol. - unionized - lower protein binding - higher concentration gradient