Introduction to Drugs

Question 1

What does receptor mean?

Answer 1

Receptor denotes the macromolecular component of an organism with which a chemical interacts.

Any protein that binds selectively to a molecule. Drugs produce their effect through receptors.

Question 2

Central prism of pharmology

Answer 2

Drugs act through receptors to make effect

Question 3

Agonists, full agonists and partial agaonist are all…

Answer 3

Endogenous neurotransmitters, hormones,

growth factors, etc. OR synthetic molecules

Question 4

Examples of antagonists are…

Answer 4

Naturally occurring molecules (curare, snake,

frog, snail toxins, etc) OR synthetic molecules

Question 5

True or False: Antagonist + Receptor or Antagonists + Agonist + Receptor produce NO effect

Answer 5

True. Remember Agonist + Antagonist + Receptor is like sticking a trunk key into a lock and then trying to stick the real key into it. The trunk key has blocked the entry point for the real key. This inhibits agonist-induced cell signaling events

Question 6

What are four examples of protein targets for drug action?

Answer 6

1) Receptors (agonist/antagonist)
2) Ion Channels (modulators-increased or decreased opening probablity/blockers-permeation blocked)
3) Enzymes (pro-drug-active drug produced/false substrate-abnormal metabolite produced/inhibitor-normal reaction inhibited)
4) Carriers (normal transport/inhibitor-transport blocked/false substrate-unnatural compound accumulated)

Question 7

What percent of targets currently have drugs?

Answer 7

~500 drugs or 10% of targets

Question 8

Name the three side effects of drugs

Answer 8

Therapeutic effect or Mechanism based side effect- You are getting side effect but doing what you want it to do. Examples was when you block beta 1 receptor in heart with beta blocker you induce CHF. 99.99% of pt this is what you want to do to tx angina, arrythmias, etc. In small proportion of pts bradycardia occurs. (May be evenly distributed across pt population)

Off target side effect- We can predict. At some dose this will bind to beta 2 as well. It will bind to beta 1 selectively but it will bind to beta 2 as well. (May be evenly distributed across patient population)

Idiosyncratic adverse effect- We can’t predict this from the drug, from the disease, from anything. Weird things that happen in very small population that you cant predict and only can see after using it for a long time (NOT evenly distributed across patient population)

Question 9

What is Pharmokinetics?

Answer 9

How drugs are distributed in the body and how we can predict what drug level we will get at a time

Question 10

Name some factors that influence drug effect

Answer 10

medication errors
rate and extent of absorption
 body size and composition
 distribution in body fluids
 binding in plasma and tissues
 rate of metabolism
 rate of elimination
patient compliance
drug-receptor interaction
 functional state
 placebo effects

Question 11

What variables are pharmacokinetics and pharmacodynamics influenced by?

Answer 11

age
 physiological condition
 disease states
 interaction with other drugs
 development of tolerance
 genetic factors

Question 12

What is the first phase of drug development?

Answer 12

1) Discovery and Preclinical Testing
Drug discovery and optimization (1-10 years)
In vitro studies that delineate mechanism (3-6 years)
Animal testing that establish existence of mechanism-based effect and toxicities

Question 13

What is the second phase of drug development?

Answer 13

Clinical Testing (6-7 years)
Phase 1: safety, effects, metabolism, and pharmacokinetics established in 20-100 normal volunteers
Phase 2: Target small number of selected pt with the disease you are targeting. Therapeutic efficacy, dose range, pharmacokinetics, and metabolism determined in 100-500 selected patients-
Phase 3: Pt’s are treated with drug. Efficacy and safety established in a larger sample (1000-3000?) of patients

Question 14

What is the third phase of drug development?

Answer 14

NDA Review by FDA (takes 1 year)

Question 15

What is the four and final phase of drug development?

Answer 15

Postmarketing Surveillance

Adverse reactions, patterns of drug utilization, additional indications are identified

Question 16

What did the Hatch-Waxman Act do?

Answer 16

Made generic versions of brand-name drug much more available in the US.

Question 17

According to the FDA, what is the definition of a generic drug?

Answer 17

“identical or bioequivalent to a brand-name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use”

Question 18

How is equivalence of performance established?

Answer 18

Don’t memorize

Rapidity and extent of absorption of single doses of the generic formulation are similar to those of the reference brand-name drug in 24-36 adult volunteers
● blood concentrations are measured from time of ingestion until elimination is nearly complete, and pharmacokinetic values must be within 80% to 125% of the reference drug.

Question 19

Should we use generic drugs? If yes why?

Answer 19

Yes. Generic drugs are by law bioequivalent to and must pass the same quality standards as brand-name drugs—and health care costs would be reduced substantively by acceptance of this truth by all physicians