1- intro to drug discovery

Question 1

the study of the source, physical and chemical properties, compounding, physiological actions, absorption, fate, and excretion, and therapeutic uses of drugs

Answer 1

Pharmacology

Question 2

substance intended for use in the diagnosis, cure, mitigation, treatment, or
prevention of disease

Answer 2

Drug

Question 3

the branch of pharmacology that studies the kinetics of drug absorption, distribution, metabolism and excretion

Answer 3

Pharmacokinetics

Question 4

the branch of pharmacology that studies the biochemical, cellular, and physiological effects of drugs and their mechanisms of action

Answer 4

Pharmacodynamics

Question 5

the branch of pharmacology that studies the undesirable effects of drugs on living systems, from individual cells to humans to complex ecosystems

Answer 5

Toxicology

Question 6

-usually 2 species, 2 routes
-determine the no effect dose & maximum tolerated dose
-in some cases, determines the dose that is lethal in approximately 50% of animals

Answer 6

Acute toxicity

Question 7

-3 doses, 2 species
-2 weeks to 3 mos of testing
-determine biochemical & physiologic effects

Answer 7

Subacute or Sub-chronic toxicity

Question 8

-rodent & at least 1 non-rodent species for -/> 6mos
-required when drug is intended to be used in humans for prolonged periods
-usually run concurrently with clinical trials
-determine the same end point as subacute toxicity tests

Answer 8

Chronic toxicity

Question 9

-2 species, usually 1 rodent & rabbits
-test effects on animal mating behavior, reproduction, parturition, progeny, birth defects, post natal development

Answer 9

effect on reproductive performance

Question 10

-2 years, 2 species
-required when drug is intended to be used in humans for a prolonged periods
-determine gross & histologic pathology

Answer 10

carcinogenic potential

Question 11

-test effects on genetic stability & mutations in bacteria (ames test) or mammalian cells in culture, dominant lethal test & clastogenicity in mice

Answer 11

mutagenic potential

Question 12

maximum dose at which a specified toxic effect is not seen

Answer 12

No-effect dose

Question 13

smallest dose observed to kill any experimental animal

Answer 13

Minimum lethal dose –

Question 14

dose that kills 50% of animals in a test group

Answer 14

Median lethal dose (LD50)

Question 15

-20-100 healthy subjects
-To determine safety and pharmacokinetic profile

Answer 15

Phase 1

Question 16

-100-200 subjects with target disease
-To determine efficacy
-Has the highest rate of drug failures, and only 25% of innovative drugs move on to phase III

Answer 16

Phase 2

Question 17

Thousands of subjects with target disease
To determine efficacy and safety
Design: Randomized Controlled Trial (RCT)

Answer 17

Phase 3

Question 18

subjects do not know the intervention received

Answer 18

single blind

Question 19

subjects & investigators do not know the intervention received/given

Answer 19

double blind

Question 20

Post-marketing surveillance
Monitoring the safety of the new drug under actual conditions of use in large
numbers of patients

Answer 20

Phase 4

Question 21

Allows one pharmaceutical company to have exclusive right to market the drug
Expires 20 years after application

Answer 21

patent

Question 22

After expiration of the 20yr patent, other pharmaceutical companies can file
Application to market generic products

Answer 22

ANDA
abbreviated new drug application

Question 23

Treatment for rare diseases
Difficult to research (small number of subjects)
Low marketing value

Answer 23

orphan drug

Question 24

drug discovery

Answer 24

the process by which a new drug is identified and brought to medical practice

Steps:
In vitro studies
Animal testing
Clinical testing
Marketing

Question 25

STARTING THE DRUG DISCOVERY PROCESS

Answer 25

1. screening for biologic activity of natural products, banks of previously discovered chemical entities, or libraries of organic molecules; 2. chemical modification of a known active molecule (“me-too” analog); 3. identification or elucidation of a new drug target (the pathophysiologic process or substrate of a disease); and 4. rational design of a new molecule based on an understanding of biologic mechanisms and drug receptor structure.

Question 26

DRUG SCREENING

Answer 26

Involves assays at the molecular, cellular, organ system, and whole animal levels Aims to define the pharmacologic profile of the compound (ie, activity, mechanism of action, and selectivity) May involve chemical modification (compound optimization) to achieve more desirable pharmacokinetic or pharmacodynamic properties Results in a lead compound (ie, a leading candidate for a successful new drug)

Question 27

INVESTIGATIONAL NEW DRUG (IND)

Answer 27

Filed with the Food and Drug Administration (FDA) before clinical testing

Question 28

NEW DRUG APPLICATION (NDA)

Answer 28

Filed with the FDA before marketing Must contain full reports of all preclinical and clinical data pertaining to the drug under review