Pathophysiology and Drug Action Exam 2 (Set 1)

Question 1

Define pharmacology

Answer 1

science of interactions of chemical (drug) compounds with biological (receptor) systems

Question 2

Define pharmacodynamics

Answer 2

the study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of their actions and effects with their chemical structure

Question 3

Define pharmacokinetics

Answer 3

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

Question 4

Describe the characteristics of drugs

Answer 4

-are defined by their actions (whether they are agonist or antagonist)
-act on receptors
-can be endogenous or xenobiotics
-have covalent, electrostatic, and hydrophobic interactions
-drug shape/design for receptor specificity

Question 5

What do receptors mediate the actions of?

Answer 5

4 types of ligand that act by binding to a cell surface receptor (orthosteric)
1. agonists
2. antagonists
3. partial agonists
4. inverse agonists
Allosteric
1. positive (PAM)
2. negative (NAM)

Question 6

what is an agonist?

Answer 6

a ligand that binds to a receptor and produces an appropriate response

Question 7

what is an antagonist?

Answer 7

ligands which prevent an agonist from binding to a receptor and therefore prevent its effects

Question 8

what is a partial agonist?

Answer 8

an agonist that will not produce the maximal response of which the tissue is capable, even when it binds to the same number of receptors as a full agonist binds to when it produces a complete response
-may prevent the action of pother agonists, and may appear to be acting as an antagonist

Question 9

What is an inverse agonist?

Answer 9

compound that binds to a receptor and produces an effect opposite to that of its corresponding agonist

Question 10

define and name sites of drug action

Answer 10

-where the acts to initiate the chain of events leading to an effect
-extracellular
neutralization of excessive gastric acid by antacids
Cholestryramine resin in reducing cholesterol absorption
-intracellular
infections; cancer chemotherapy; hormones such as estrogen
-on the cell surface
majority of drugs
acetylcholine
catecholamines
growth factors

Question 11

What is the Concentration-Effect Relationship?

Answer 11

-measures the EC50;EC10;EC90 etc
-concentration of drug that produces 50% of the maximal response
-sigmoidal curve

Question 12

relate affinity to the law of mass action

Answer 12

the effect of a drug is directly proportional to the amount of drug-receptor complex formed
[D][R]/[DR] = k(off)/k(on)=Kd (dissociation constant)
THE LOWER THE KD THE HIGHER THE AFFINITY

Question 13

define KD

Answer 13

-KD concentration is reached when 50% of the drug is bound
-KD is the concentration of ligand that will bind half the receptors at steady state

Question 14

relate affinity to receptor occupancy

Answer 14

-the relationship between occupied receptor B and drug/ligand concentration D

Question 15

outline components in a receptor binding assay

Answer 15

-requires radiolabeled ligand
-receptor will bind to ligand
-will be filtered and just the ligands will be left (some test ligands some regular ligands)
-displays competitive binding to displace the test ligands

Question 16

What is Bmax and KD in terms of saturation binding anaylsis?

Answer 16

Bmax is the total number of receptors on given cell or tissue
KD is affinity of ligand for the receptor readily identified at 1/2 Bmax

Question 17

What is pharmacological profiling?

Answer 17

-heterologous competition testing several unlabeled compounds simultaneously
-can calculate rank affinity from it

Question 18

How is Ki calculated?

Answer 18

-using the Cheng-Preusoff equation
Cheng-Prusoff: Ki= IC50/[1+L/KD]
-Ki is indirect measure of affinity (KD)
IC50 is determined experimentally
L is radio labeled drug concentration

Question 19

What is Ki? What does it measure?

Answer 19

-dissociation constant describing the binding affinity between the inhibitor and enzyme
-measures binding affinity (potency)
-highest affinity, lowest KD found on the furthest left line on the graph

Question 20

What does IC50 measure?

Answer 20

concentration of inhibitor required to reduce the enzymatic activity to half of the uninhibited value

Question 21

WHAT IS THE CHENG PRUSOFF EQUATION?

Answer 21

Ki=IC50/[1+L/KD]

Question 22

how does receptor affinity relate to receptor selectivity

Answer 22

greatest affinity does not mean greatest selectivity
greatest selectivity will be large number ex. 50 times selective for DOR over MOR or KOR
best affinity will be low number ex.0.75

Question 23

What is Bmax?

Answer 23

-total number of receptors on a given cell or tissue
-Bmax values are independent of the ligand
-can influence downstream signaling events