Basic Pharm Principles I

Question 1

Drug action = _______, _______ response

Drug effect = ________, _______ response

Answer 1

molecular action, invisible; pharmacologic effect, visible

Question 2

Define selectivity; what is desired and what may/may not be desired?

Answer 2

Property of drug to cause a specific effect;

primary effect vs. secondary effect

Question 3

What do drug-receptor interactions cause within a cell and then tissue?

Answer 3

Molecular events in each cell leading to a change in cell function and later a change in tissue function with enough of them going on

Question 4

List the properties of receptors: (9 of them)

Answer 4

1. Macromolecules (esp proteins)
2. Could be on/in cell or free in plasma or EC fluid
3. They are specific
4. Can be ligand binder and effector
5. Natural ligand (agonist) or drug can bind receptor and modulate its activity
6. Can be stimulated or inhibited
7. Many of these contained by cell, accessible to drugs easily
8. When enough molecular events have occurred within a cell (small changes because of drug-receptor interactions), then cell function changes and tissue function is altered such that pharmacologic response can be noted/observed
9. Max response achieved: related to number of drug-receptor interactions and capacity of tissue (ie normal vs. disease)

Question 5

Which bond is irreversible? van der Waal, ionic, covalent, H?

Answer 5

Covalent

Question 6

Drug-receptor interactions last ______; activated G protein activity lasts _______

Answer 6

fractions of seconds (e.g. nanoseconds); seconds

Question 7

What do G proteins regulate? How many are there in a single cell? How long can they act once turned on?

Answer 7

They regulate distinct cellular effector proteins like enzymes, transport proteins, channels; can be multiple; a few seconds

Question 8

If a drug uses a second messenger as part of the mechanism, does the drug enter the cell? What are two examples of secondary messengers from lecture? How do second messengers impact the original drug-receptor interaction? How do G proteins influence these messengers?

Answer 8

No; cAMP and Ca; they can amplify it and convert event happening outside cell into change happening inside the cell;
can stimulate or inhibit

Question 9

What is an example of structure-activity relationships that he gives in terms of how structure of drugs influences activity?

Answer 9

Epinephrine (R isomer more effective than S isomer)

Question 10

Show equilibrium equation of drug producing an effect

Answer 10

D + R DR -> (Pharmalogical) effect

Question 11

What is effect equal to? What is the idea of receptor occupancy? What is Kd equal to?

Answer 11

Effect = Emax[D]/Kd + [D]; the intensity of response is proportional to the fraction of the receptors occupied; EC50

Question 12

What is intrinsic activity? How does it relate to efficacy?

Answer 12

ability to stimulate the receptor once bound; greater intrinsic activity = greater efficacy

Question 13

Define the ideas of spare and secondary receptors.

Answer 13

With spare receptors, it means you may not have needed all of the R’s occupied to achieve Emax (efficient agonists), and with secondary R’s, you have possible side effects if the R’s are on different cells/tissues

Question 14

Examples of receptor regulation?

Answer 14

Denervation hypersensitivity (with antagonists if you were to take someone rapidly off a beta blocker); desensitization (with agonists and you have down regulation of the receptor or fatigue/depletion of IC/tissue mech’s)

Question 15

What type of drug produces a pharmacological effect? What are the two important events?

Answer 15

Agonists; bind receptor, activate receptor after binding

Question 16

How does the log dose-response curve shift with weaker agonists? Does this mean that the weaker agonists cannot reach Emax? What would be “free” with the stronger agonist and what would be “free” with the weaker agonist?

Answer 16

To the right; no, EC50 could remain the same but higher dose required to reach Emax!!
Spare receptors vs. free drug!!

Question 17

If a drug can bind two receptors equally, but one receptor can’t reach Emax, what is different about the two?

Answer 17

Intrinsic activity (stimulated the receptor once bound)

Question 18

How can you quantify agonism?

Answer 18

Efficacy (ability of drug to activate effector portion of receptor once bound to R; depends on drug structure);
Potency (amount of drug needed for effect; depends on receptor density, efficiency of stimulus-response mech’s of tissue, affinity, and efficacy)

Question 19

What kind of relationship is observed with drugs of different potency and efficacy on a log dose-response relationship?

Answer 19

Horizontal (shift right/left) vs. vertical

Question 20

How are competitive antagonists different compared to non-competitive antagonists relative to agonists and efficacy/potency?

Answer 20

Former can be overcome with enough dosing of agonist;

potency changes with competitive agonists, efficacy changes with non-competitive agonists

Question 21

What are two ways that a non-competitive inhibitor can work?

Answer 21

Changing the binding site or effector site (non-comp I involves changing the effector site such that ligand binding leads to no response; non-comp II means the inhibitor binds at the binding site or it binds at a different site and alters the binding site)