Watts Set 1

Question 1

what is pharmacology?

Answer 1

science of interactions of chemical compounds with biological systems

Question 2

what is pharmacodynamics?

Answer 2

the study of biochemical and physiological effects of drugs and the mechanisms of their actions

Question 3

what is pharmacokinetics?

Answer 3

the study of absorption, distribution, biotransformation, and elimination of xenobiotics

Question 4

what are the many characteristics of drugs?

Answer 4

• Defined by actions
• Most act on receptors
• Endogenous drugs or xenobiotics
• Includes poison/toxin
  solids/liquids/gasses
• Covalent, electrostatic, and hydrophobic interactions
• Ions to larger proteins/antibodies/vaccines, majority are small molecules
• Drug shape and rational drug design for receptor specificity

Question 5

what are the sites of drug action?

Answer 5

extracellular, intracellular, on the cell target

Question 6

describe the extracellular site?

Answer 6

• Neutralization of excessive gastric acid by antacids
• Ex: cholestyramine resin in reducing cholesterol absorption

Question 7

describe the intracellular site?

Answer 7

• Drugs used to treat infections
• Drugs used for cancer therapy
• Ex: hormones such as estrogen

Question 8

describe the on cell target site?

Answer 8

• Comprises cell-membrane receptors
• Many drugs act by combining with receptors on the surface of the cell
• Examples
  — Acetylcholine and muscarinic or nicotinic receptors
  — Growth factors (EGF/FGF) and GF receptors
  — Monoclonal antibodies (mABs)

Question 9

how can we relay affinity to the law of mass action and receptor occupancy?

Answer 9

• Effect of a drug is directly proportional to the amount of drug-receptor complex formed
• Lower Kd (d*r/dr) → higher affinity
• Higher affinity → more drug receptor complex and receptor occupancy → more intense drug effect
• Based on koff and kon rates of drugs

Question 10

what are the components in a receptor binding assay?

Answer 10

• orthosteric: agonist/antagonist, partial agonist, inverse agonist
• allosteric: PAMS, NAMS
• each receptor has one orthosteric site and can have many other allosteric sites

Question 11

what are the principles of receptor bindng assays that measure affinity?

Answer 11

• affinity is the ability to interact with the receptor
• kD is a measure of affinity
  – low= tight
  – high= loose
• affinites can differ from drug to drug
• affinity = potency

Question 12

what is pharmacologic profiling?

Answer 12

heterologous competition testing several unlabeled compounds simultaneously

Question 13

how can we use the graphical data for pharmacologic profiling?

Answer 13

• cheng-prusoff equation
  – has IC50 value and from that we can determine the Ki
• Ki is a measure of kD
• Ki for each can be computed and compared and affinity rank can be calculated

Question 14

how can we apply affinity to receptor selectivity?

Answer 14

• the log 3 rule
  – 10%, 50%, 90%
  —> one log above and one log below

Question 15

what is Bmax?

Answer 15

total number of receptors on a given cell or tissue

Question 16

how can we use bmax with drug action?

Answer 16

it is the max affect of a drug
– it is the concentration of all receptors where they are all occupied and reach max conc.