Drug development and regulation

Question 1

Pure food and drug act (PFDA)

Answer 1

Prohibits mislabeling and adultering drugs

Question 2

Amendment to PFDA

Answer 2

Prohibits false/fraudulent advertising claims

Question 3

Harrison narcotics act**

Answer 3

Established regulations for use of opium, opiates, cocaine and later marijuana

Question 4

Controlled substances act of 1970***

Answer 4

Outlines strict controls in the manufacture, distribution and prescribing of habit-forming drugs;
Establish program to prevent and treat addiction***

Question 5

Drug Price Competition and Patent Restoration act

Answer 5

Abbreviates new drug applications for generic drugs
Required bioequivalence data.
Patent life extended by time it spends under FDA review

Question 6

Orphan Drug Ammendment**

Answer 6

Ammends FDCA, provides incentives for development of drugs that treat disease with less than 200,000 pt’s in the USA

Question 7

Major Legislation pertaining to PR: Ley 11 del 23 de junio del 1976

Answer 7

Creates a board for Bioequivalent for Medications, named by the Secretary of health of PR

Question 8

Drug development and approval process

Answer 8

Safety tests include: 
Acute toxicity
Subacute toxicity
Chronic Toxicity
Effect on reproduction
Carcinogenic potential
Mutagenic potential
Investigative toxicology

Question 9

U.S. Pharmacopeia and Nation al Formulary

Answer 9

Establishes and regulates reference standards

Established by the Food and Drug Act of 1906 (Wiley/Heyburn Act)

Question 10

Comprehensive drug abuse prevention and control act of 1970

Answer 10

Established the DEA
Established 5 schedules for drugs of abuse
Established penalties for misuse
Established quotas for manufacturing narcotics

Question 11

Amendment that established the practice of pharmacy

Answer 11

Durham Humphrey Amedment of 1951

• also established pharmacist physician relationship
• Separate class for narcotics and physician registration numbers
• Deals with legen drugs: prescription drugs

Question 12

Act responsible for premarket clearance for safety and efficacy as well as establishing modern drug review and approval procedures

Answer 12

Kefauver-Harris act

• Requires animal data to be submitted before beginning human trials
• **3 phases of clinical testing

Question 13

Act that caused review time to be sped up

Answer 13

Prescription Drug User Fee Act: Industry provides FDA funds in the form of fees to pay for positions and resources to review new drug applications

Question 14

Molecular profile test of a drug

Answer 14

Receptor binding
Enzyme activity
Biotransformation enzymes

Question 15

Cellular profile tests of a drug

Answer 15

cell culture systems

isolated organ prep

Question 16

Systems/Disease model systems of a new drug

Answer 16

Blood Pressure
Blood coagulation
Diuretic activity
Cardiac effects
CNS model systems

Question 17

Screening of drugs

Answer 17

How most new drugs are discovered
Specific set of procedures (in vivo and in vitro)
Bioassay (quantitative analysis) is used to establish relationship between dose and response

Question 18

How to make a new drug?

Answer 18

Synthesis de novo
Modifying the structure of an existing drug (SAR)
Purification of drugs from natural sources
Exploration of side effects of existing drugs

Question 19

Bioassay parameter EC50:

Answer 19

Concentration of an agonist where 50% of its max agonistic effect is observed

Question 20

Bioassay parameter IC50:

Answer 20

Concentration of an antagonist compound where 50% of its maximal antagonistic effect is observed

Question 21

Bioassay parameters ED50

Answer 21

Minimum required dose to show desired activity of drug in half the members of a tested population after a specific duration of time

Question 22

Bioassay parameters LD50

Answer 22

Represents the dose required to kill half the members of a tested population after a specific duration of time

Question 23

Therapeutic index (bioassay parameters)
****Safety parameter in Experimental animals

Answer 23

Represents the ration of LD50 to ED50:

LD50/ED50=therapeutic index

Question 24

Therapeutic index in clinical medicine

Answer 24

Ratio between median toxic dose and median effective dose:

TD50/ED50=therapeutic index

Question 25

Animal studies: acute toxicity tests

Answer 25

One administration to each animal Generation of dose-response curves Appropriate pharm testing to determine ED50 Develop ways to determine absorption, excretion, distribution, and metabolism of chem

Question 26

Animal studies: Chronic toxicity tests

Answer 26

2 to 5 years | Multiple administrators or continuous exposure via food or water

Question 27

How to judge a drug?

Answer 27

Efficacy Safety Convenience Cost

Question 28

What are possible drug reactions/toxicities/side effects?

Answer 28

``` Allergic reactions Blood dyscrasias Hepatotoxicity and nephrotoxicity Teratogenic effects Behavioural toxicity Drug dependence and abuse Carcinogenesis Pharmacogenetic toxicities ```

Question 29

Blood dyscrasias as side effects:

Answer 29

``` Agranulocytosis Aplastic Anemia** Hemolytic anemia Thrombocytopenia Clotting factors ```

Question 30

Behavioural toxicity examples

Answer 30

Suppression of normal anxiety Reduced motivation Adverse effects of moods

Question 31

Carcinogenesis

Answer 31

Delayed type of toxicity with latency of many YEARS***

Question 32

Pharmacogenic toxicities example

Answer 32

Malignant hyperthermia and anesthetics

Question 33

Controlled drugs (narcotics): Schedules

Answer 33

``` I. No medical use II. High potential for abuse (used medically with severe restrictions) III. Medium potential for abuse IV. Low potential for abuse V. Low (still some) potential for abuse ```

Question 34

Schedule I drug

Answer 34

NO medical use Considered highly addictive 78 opioids, 29 hallucinogens, depressants/stimulants (7) Heroin, LSD, marijuana, quaaludes

Question 35

Class II drugs

Answer 35

Highly addictive with medical use Morphine, cocaine, pentobarbital, methylphenidate NO REFILLS, must have a DEA liscense HIGHLY regulated

Question 36

Schedule III

Answer 36

Moderately addictive Acetaminophen combos, codeine, nalorphine No more than 5 refills/6mo's

Question 37

Schedule IV

Answer 37

Drugs with limited addiction potential Phenobarbital, benzo's, chloral hydrate NO refilling more than 5 times/6mo's

Question 38

Schedule V

Answer 38

Drugs w/low addiction potential Diphenoxylate (opioid) May be sold w/out prescription by pharmacist

Question 39

Role of institutional review board (IRB)

Answer 39

1. Ensures ethical acceptability of proposed research 2. Reviews and approves research protocols involving humans 3. Ensures the appropriateness of the informed consent document 4. Reviews and approves the company's/investigator's IND document