Exam 1: Drug Development & Testing

Question 1

Drugs are chemical substances that are used for the _______, ________ or ________ of disease, and for the prevention of ________.

Answer 1

diagnosis, prevention or treatment….pregnancy

Question 2

What was the first SPECIFIC drug used to treat an infectious disease (malaria) that was taken from nature?

Answer 2

Quinine

Question 3

One of the first drugs was also called ‘the magic bullet’ which was SYNTHESIZED by adding ______ to carbon. It was used to treat syphilis.

Answer 3

arsenic

Question 4

What is the drug from a plant that is still the best treatment for congestive heart failure? What plant is it from?

Answer 4

Digitalis from the Foxglove plant.

Question 5

The isolation of _______ lead the way to techniques for the isolation of caffeine (thank God!), atropine, strychnine.

Answer 5

morphine

Question 6

Atropine (to dilate the pupils) and Scopolamine (for motion sickness) are both derived from this plant….

Answer 6

Atropa BellaDonna

Question 7

The SINGLE MOST IMPORTANT drug discovery in medicine.

Answer 7

ASA-Acetyl Salicyclic Acid (Aspirin)

Question 8

What was the first hormone isolated? (Happened at Johns Hopkins)

Answer 8

Epinephrine

Question 9

Penicillin was derived from this plant _______ and inhibited the growth of _______.

Answer 9

Penicillium Notatum……S. Aureus

Question 10

What were the drugs that pre-date penicillin?

Answer 10

Sulfa Drugs

Question 11

Sulfa Drugs are still used today to treat ______.

Answer 11

UTI’s

Question 12

________ was the antibiotic used in WWII.

Answer 12

Penicillin

Question 13

Time necessary to develop a drug is approximately ____ years

Answer 13

15 years

Question 14

Cost of developing a drug approximates $____ million, but may cost significantly more.

Answer 14

$360 million

Question 15

Only about ___ in 10 new compounds successfully reach the market

Answer 15

2 out of 10

Question 16

How long is the patent on a NEW DRUG, when does that patent start?

Answer 16

17 years!! Clock starts at Phase 1 clinical testing (generally 8 year process!)

Question 17

What are the 5 steps for Drug development? (Simplified!)

Answer 17

1.Discovery of a new drug 2.Safety evaluation 3. Effective in humans 4.New Drug Application 5.Post-market surveillance

Question 18

Is Short-term toxicity testing done in humans or animals?

Answer 18

animals (generally mice)

Question 19

The _______ is the dose of a drug that kills 50% of the total numbers of mice that received it.

Answer 19

Leathal Dose (LD50)

Question 20

The _______ is the dose of a drug that causes an effect in 50% of the total numbers of mice that received it.

Answer 20

Effective Dose (ED50)

Question 21

The margin of safety= ______ divided by ______.

Answer 21

LD50 / ED50

Question 22

What is the margin of safety if LD50=10mg and ED50 = 2mg?

Answer 22

Margin of safety= 10mg (LD50) / 2mg (ED50) = 5

Question 23

If a margin of safety is 5, that means the _______ is only 5 times the _______.

Answer 23

lethal dose is only 5x the effective dose

Question 24

What is an ACCEPTABLE margin of safety for a drug?

Answer 24

2000 or MORE!!!

Question 25

Long-term toxicity-aka ______ toxicity studies-give daily dosing to _____ or _____ from ___ months to ___ years.

Answer 25

chronic....rats or dogs....3months to 2 years

Question 26

In long-term toxicity, many toxic effects appear only after repeated dosing over many ______ or ______. Also they _______ the animals to look at any histopathology.

Answer 26

months or years....sacrifice :(

Question 27

Drugs that cause birth defects are termed ________.

Answer 27

teratogens

Question 28

Studies for carcinogenicity of a drug typically rate over ____ months.

Answer 28

6

Question 29

What is Submitted if drug has impressive margin of safety in mice, Submitted if drug lacks long-term toxicities, Submitted if drug does not cause cancer, reproductive effects or birth defects and is Usually a 30 day approval????

Answer 29

(IND)- Investigational New Drug Application

Question 30

The _____ is when the company releases information on the drug, including the chemical structure.

Answer 30

IND-Investigational New Drug Application

Question 31

When does Phase I clinical studies begin?

Answer 31

Immediately after IND(investigative new drug application) is approved

Question 32

Which testing Phase evaluates the drug in HUMANS for the first time?

Answer 32

Phase I...18-24 year old men (poor bastards)

Question 33

Phase I trials on healthy young men study the _____ profile, and determine the Pharmo______. It also establishes the dose at which ______ appears.

Answer 33

safety....pharmokinetics...toxicity (poor bastards!)

Question 34

Which Phase of testing do we give to patients with the condition for which the drug was intended?

Answer 34

Phase II

Question 35

About how many subjects are in Phase II trials? What time frame is this Phase studying? long-term or short-term?

Answer 35

100-300 subjects, studies SHORT-term effectiveness

Question 36

Which Phase studies adverse drug events?

Answer 36

Phase II, Phase III, Phase IV

Question 37

Which Phase establishes therapeutic efficacy, dose- response and dose range, kinetics, and metabolism.

Answer 37

Phase II

Question 38

Which Phase has 1000 to 3000 subjects?

Answer 38

Phase III

Question 39

Which Phase is checking long-term efficacy?

Answer 39

Phase III

Question 40

In Phase III-Trial design is always a ________, _______ control. So there are 2 groups, one receives the _____ and one receives the ______.

Answer 40

randomized, double-blind....drug, palcebo

Question 41

What is the MOST EFFECTIVE design for avoiding bias and distributing unknown variables between the treatment and control groups?

Answer 41

Randomized, double-blind control

Question 42

Phase ___ has one problem: small number of subjects taking drug for more than 3 to 6 months compared with the potential number who will take the drug long term

Answer 42

Phase III

Question 43

Phase III- Drug toxicities which occur at less than 1 in ____ exposures may not be revealed in this phase 3 trial! This is only found when ______ of people are taking the drug.

Answer 43

1 in 1000 exposures...millions!

Question 44

The _________ is submitted after 8 years of testing.

Answer 44

(NDA)-New Drug Application

Question 45

Phase IV is also known as _______.

Answer 45

Post-marketing Surveillance

Question 46

Phase IV can have the drug pulled off the market if new ______ are uncovered. Often problems in Phase IV result in _____ of the drug.

Answer 46

toxicities....relabeling

Question 47

The use of investigational drugs occurs during the review of _____. These are in rare situations and are considered "_______ use protocols"

Answer 47

NDA-new drug application (post/during? Phase III)..compassionate

Question 48

Who oversees OTC drugs?

Answer 48

FDA

Question 49

________– when a drug is being investigated by a company, it is identified by this name, which is determined by its chemical structure. If the structure is unknown, then usually a combination of ______ and _____.

Answer 49

Chemical Name...letters and numbers

Question 50

_______ – before any drug is marketed, it is given a this which becomes the “official” name of the drug (e.g. cola)

Answer 50

Generic name

Question 51

All drugs have one _______ name, but can have many ______ names

Answer 51

generic....brand

Question 52

generic names are NOT _______. ex. _______ is the generic name and Coumadin is the trade name.

Answer 52

capitalized...warfarin

Question 53

_______ - If the compound is found to be useful and will be marketed commercially, then the pharmaceutical company that discovered the drug gives the drug a this name (e.g. Coke)

Answer 53

Trade name

Question 54

Trade name = _____ name = Proprietary name

Answer 54

brand

Question 55

The 1984 – Drug Price Competition and Patent Term Restoration Act Allows ______ drugs to receive expedited approval.

Answer 55

generic (bastards!)

Question 56

The 1984 – Drug Price Competition and Patent Term Restoration Act: FDA still requires that the ________ of the generic product enter the bloodstream at the same rate as the trade name product.

Answer 56

active ingredient

Question 57

The 1984 – Drug Price Competition and Patent Term Restoration Act: _______ drugs are frequently more affordable and provide cost-savings to the patient

Answer 57

generic

Question 58

Prior to and at the start of the 20th century, tampering and mislabeling of food and drugs was common BUT! the 1906 – Pure Food and Drug Act came about, prompted by unsanitary and unsafe conditions in ______ industry.

Answer 58

meat packing

Question 59

How was the FDA created?

Answer 59

the 1906 Pure Food & Drug Act

Question 60

The 1906 Pure Food & Drug Act said that drugs must meet _______ of purity and quality AND manufacturers must provide correct and truthful ______.

Answer 60

standards...labeling

Question 61

the 1938 food, drug, and cosmetic act requiring proof of a drug's safety and purity was brought about because the Lilly corp killed people by adding anti-freeze to their _____ drugs.

Answer 61

sulfa drugs

Question 62

The FDA Modernization Act of 1997 Allows drug manufacturers to discuss unapproved or “_______” indications with practitioners.... ________ drug approvals for life- threatening medical disorders.....Makes provisions for _______ drug research, Revises communications between FDA and researchers conducting ______ trials

Answer 62

"off-label"....accelerated..pediatric...clinical

Question 63

Durham-Humphrey Act of 1952 Grants the FDA authority to determine which drugs may be sold without a ________.

Answer 63

prescription (OTC)

Question 64

1962 Kefauver-Harris Amendments to the Food, Drug and Cosmetic Act Requires proof of ______ as well as _____ for new drugs and drugs approved since 1938.

Answer 64

efficacy as well as safety

Question 65

For dietary supplements, the FDA must demonstrate that a supplement is _____ before taking action against it.

Answer 65

unsafe

Question 66

________ cannot make therapeutic claims and must have the disclaimer: "this product is not intended to diagnose, treat, cure, or prevent any disease."

Answer 66

Dietary Supplements

Question 67

An _____ disease is a disease that affects <200,000 people, there are incentives for manufacturers to develop drugs.

Answer 67

orphan

Question 68

Haha, before the Harrison Narcotic act of 1914 and Maryjane in 1937, these drugs were sold _____.

Answer 68

OTC!!

Question 69

Which government agency administers Controlled Substances?

Answer 69

DEA

Question 70

The _________ is an agreement between the FDA and the manufacturer so that the drug is presented in a way that is marketable

Answer 70

package insert

Question 71

Can the package insert for a drug contain bias?

Answer 71

YES!