development and regulation of drugs

Question 1

how are drugs discovered

Answer 1

1. Discovery or synthesis of a potential new drug
2. Rational design of a new molecule based on an understanding of biologic mechanism and drug receptor structure
3. Random screening of the biologicalproducts
4. Chemical modification of known active molecule resulting in a me-too analog

Question 2

• Process of testing a drug candidate which involves a sequence of experimentation and characterization to be able to define the pharmacologic profile of the drug at the molecular, cellular, organ, system and organism levels

Answer 2

DRUG SCREENING

Question 3

Leading candidate for a successful new drug

Answer 3

• Lead compound

Question 4

• Quantitative estimates

maximum dose at which a specific toxic effect is not seen

Answer 4

No-effect-dose

Question 5

• Quantitative estimates

smallest dose that is observed to kill any experimental animal

Answer 5

Minimum lethal dose-

Question 6

• Quantitative estimates
if necessary only, dose that kills approximately 50% of the animals. This is usually estimated from the smallest number of animals possible

Answer 6

Median lethal dose(LD50)-

Question 7

SAFETY TESTS
 Administration of single doses to the lethal doses
 2 species, 2 routes

Answer 7

1. ACUTE TOXICITY

Question 8

SAFETY TESTS

 Induction of malignant characteristics in cells

Answer 8

6. CARCINOGENICITY

Question 9

SAFETY TESTS

 E doses, 2 species
 2 weeks to 3 months
 Determine biochemical and physiologic effects

Answer 9

2. SUBACUTE

Question 10

SAFETY TESTS

 Rodent and nonrodent
 6-24 months
 2 and 3 tests are conducted for at least the length of time proposed for human

Answer 10

3. CHRONIC TOXICITY

Question 11

SAFETY TESTS

 Induction of developmental defects in somatic tissues of the fetus

Answer 11

4. TERRATOGENICITY

Question 12

SAFETY TESTS

 Induction of changes in the genetic material of animals of any age inducing heritable abnormalities

Answer 12

5. MUTAGENICITY

Question 13

 Standard in vitro test for mutagenicity
 Uses a special strain of Salmonella bacteria that naturally depends on specific nutrients in the culture medium
 Loss of this dependence during exposure to the test drug signals mutation

Answer 13

AMES TEST

Question 14

 Administrative body that oversees the drug evaluation in the Philippines
 Submit evidence of safety and effectiveness of the drug to this body

Answer 14

BUREAU OF FOOD AND DRUG (BFAD) (FDA- USA)

Question 15

• 2 groups of patients
• One group is given the standard
• One group the placebo prep (control) and the standard treatment (positive control) if any

Answer 15

 Cross-over design

Question 16

PHASE ___
 Careful evaluation of the dose-response relationship in a small number of normal
healthy human volunteers (20-100)

Answer 16

1

Question 17

PHASE ___
Determine the maximum tolerated dose, designed to prevent severe toxicity
 Except for trials of chemotherapeutic drugs (cancer and AIDS)and other highly toxic drugs carried by administering to patients with target disease

Answer 17

1

Question 18

PHASE ___

Performed in research centers

Answer 18

1

Question 19

PHASE ___

 Studied in patients with the target disease (100-200)

Answer 19

2

Question 20

PHASE ___

Determine its efficacy or therapeutic effects (“proof of concept”) and the doses for follow-on trials

Answer 20

2

Question 21

PHASE ___

Placebo or positive control is included in a single-blind or double-blind study

Answer 21

2

Question 22

PHASE ___

Done in special clinical centers under carefully controlled conditions and very closely monitored

Answer 22

2

Question 23

PHASE ___

Highest rate of drug failures

Answer 23

2

Question 24

PHASE _
 Large design involving many patients (1000-5000) or more in many centers and many clinicians/specialists who are using the drug in the manner proposed for itsgeneral use

Answer 24

3

Question 25

PHASE ___

Further establish and confirm safety and efficacy

Answer 25

3

Question 26

PHASE ___

Drug is formulated as intended for the market

Answer 26

3

Question 27

PHASE ___

Placebo, double-blind crossover trial

Answer 27

3

Question 28

PHASE ___

Discover toxicities

Answer 28

3

Question 29

PHASE ___

Explore the spectrum of beneficial actions of the new drug, compare with older therapies

Answer 29

3

Question 30

Drug’s proprietary name and is usually registered, it is legally protected al long as it is used

Answer 30

Trademark

Question 31

PHASE ___
 Toxicities that occur very infrequently will be detected and reported early enough to prevent a major therapeutic disasters

Answer 31

4

Question 32

PHASE ___

 Begins once approval to market a drug has been obtained

Answer 32

4

Question 33

PHASE ___

 Post marketing surveillance

Answer 33

4

Question 34

PHASE ____

 Not rigidly regulated by the Bureau of Food and Drugs (BFAD)

Answer 34

4

Question 35

design that consists of alternating periods of administration of a test drug: placebo preparation (control), and the standard treatment (positive control)

Answer 35

cross over design

Question 36

design used to quantitate and measure subject bias effects
design which involves use of a placebo, administered to the same subjects in a crossover design, if possible, or to a separate control group of well-matched subjects

Answer 36

single-blind

Question 37

design used to take into account observer bias
involves disguising the identity of the medication being used from both subjects and personnel evaluating subjects’ responses

Answer 37

double-blind

Question 38

in this design, a 3rd party holds the code identifying each medication packet, and the code is not broken until all the clinical data have been collected

Answer 38

double-blind

Question 39

factors in clinical trials

Answer 39

 Natural variable history of the diseases
 Presence of other disease and risk factors
 Proper selection and assignment of the patients to each of the study groups
 Subject and observer bias

Question 40

goals of preclinical safety and testing

Answer 40

• Identifies potential human toxicities
• Designs tests to further define the toxic mechanisms
• Predicts the most relevant toxicities to be monitored in clinical trials

Question 41

 Drugs for rare diseases

 Difficult to research, develop and market

Answer 41

ORPHAN DRUGS

Question 42

 Adverse drug event (ADE)

 Harmful or unintended response

Answer 42

ADVERSE DRUG REACTIONS (ADRs)