Drug Development & Testing Exam 1

Question 1

Discuss the history of drug development and use.

Answer 1

● Mixture of religion and use of plant substances

● Chinese in 2700 B.C = “Doctrine of Signatures”

● If a plant looked like something of medicinal value, then it probably was a medicine.

● Drug discovery took two paths:

1) Isolation & use of nature substances from botanical, mineral & animal sources.
2) Later years- chemical synthesis of compounds having biological activity.

Question 2

1630- Quinine isolated from ____________?

Answer 2

from tree bark is used to treat malaria and it is the first specific drug to treat an infectious disease.

Question 3

1760- (Magic Bullet) Synthesis of ____________ ?

Answer 3

arsenicals by attaching an arsenic atom to a carbon atom. This led to Paul Ehrlich’s use of arsphenamine to treat syphilis.

Question 4

1783- Foxglove to treat what?

Answer 4

“dropsy” (congestive heart failure). -William Withering’s use of purple foxglove lead to the isolation of digitalis. (Today, drug is still isolated from plants b/c expensive to synthesize chemically)

Question 5

1807- Morphine was isolated from what? Explain.

Answer 5

Opium, this led to techniques to isolates caffeine, atropine, and strychnine.

-Source of opium is poppy plant

Question 6

1897- Aspirin first synthesized by ______________?

Converted salicylic acid into____________

Acetylsalicylic acid aka__________?

Single most important ___________?

Answer 6

Felix Hoffman, working for Bayer.

●-Converted salicylic acid to the acetyl derivative

●-Acetylsalicylic acid = also known as aspirin
● -Single most important drug discovery in medicine

Question 7

1901- Epinephrine was the first _____________?

Answer 7

hormone isolated

Question 8

In 1927- Alexander Fleming accidentally _______________?

Answer 8

discovered “penicillin”

Question 9

1935- Sulfonamides (“sulfa drugs”)- used to treat ______________?

Answer 9

infections of the urinary tract -Pre-dated the clinical use of penicillin

Question 10

In 1941- First clinical use of _____________used in WWII

Answer 10

Penicillin

Question 11

Discuss issues related to drug development in terms of time and cost.

Answer 11

● Takes 15 years to develop
● Cost of developing a drug approximates $360 million, but may cost more
● Only about 2 in 10 new compounds successfully reach the market
● Only 3 out of 10 that reach the market actually return on the investment
● Patent for new drug= 17 years

Question 12

Describe the 1st phase of drug development and testing.

Answer 12

● Clinical studies- Phase 1:

○ Begins immediately after IND approval
○ Evaluates drug in humans for first time
○ 20 to 80 healthy volunteers (usually healthy males)
○ Study safety profile, determine pharmacokinetics
○ Establishes does at which toxicity appears

Question 13

Describe the 2nd phase of drug development and testing.

Answer 13

● Clinical studies- Phase 2:

○ Given to patients having condition for which drug is intended
○ Approximately 100-300 subjects
○ Study of short-term effectiveness
○ Establishes therapeutic efficacy, dose response and dose range, kinetics, and metabolism
○ Also studies adverse drug events

Question 14

Describe the 3rd phase of drug development and testing.

Answer 14

Phase 3 (several thousand people):

• Safety, dosage & effectiveness
• Verify drug efficacy
• Initiated only after effective dose range established in phase 2
• Numbers range from 2000 to 3000 subjects
• Try to detect effects undetected in prior studies
• Trial design always a randomized, double-blind control
• 2 groups: active drug versus control “placebo”
• Subjects are randomly assigned either drug or placebo (neither subject or investigator knows which subject is taking = double-blind)
• This is MOST effective design for avoiding bias & distributing unknown variables between treatment & control groups

Question 15

Describe the 4th phase of drug development and testing.

Answer 15

● Clinical studies- Phase 4:

○ Occurs after FDA approval
○ Drug is used by greater numbers of people than in previous studies
○ Collect additional data to define side effects
○ Drug can be pulled off market in new toxicities are uncovered
○ Often, problems result in relabeling of the drug with new warnings or precautions

Question 16

Briefly describe the summary of phases of drug development and testing.

Answer 16

○ Phase 1 (20-80 people)
■ Test for safety in “normals”

○ Phase 2 (several hundred people)
■ Safety & effectiveness

○ Phase 3 (several thousand people)
■ Safety, dosage, effectiveness, adverse events

○ Phase 4
■ Post-marketing surveillance for adverse event monitoring

Question 17

Differentiate between the chemical/scientific names for drugs.

Answer 17

● Chemical name- 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 letters and numbers

Question 18

Differentiate between the Generic name for drugs.

Answer 18

● Generic name- before any drug is marketed, it is given a generic name that becomes the “official” name of the drug
○ All drugs have one generic name, but can have many brand names (trade name)

■ listed in the official pharmacopoeia
○ generic names are NOT capitalized

■ e.g. warfarin is the generic name; Coumadin is the trade name

Question 19

Differentiate between the Trade name for drugs.

Answer 19

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

○ Trade name = brand name = proprietary name
○ Trade name is registered as a trademark
○ Copyrighted name = restricts the name of the drug for use only by the manufacturer

● After 17 years, patent expires allowing other companies to market generic drug under a trade name of choosing

Question 20

Discuss the determination and significance of the “margin of safety.”

Answer 20

● The margin of safety is LD50 (lethal dose) divided by the ED50 (efficacious dose)

● If LD50=10 mg and ED50 = 2mg, then the margin of safety is only 5

● This means that the lethal dose is only 5 times the effective dose

● May be predictive of a low margin of safety in humans

● Acceptable margin of safety is 2000 or more

Question 21

Identify & describe important pieces of legislation that regulate drug marketing and safety. (Pure Food & Drug Act and Cometic Act)

Answer 21

● 1906 - Pure Food and Drug Act
○ Created the FDA:
■ Drugs must meet standards of purity and quality
■ Manufacturers must provide correct & truthful labeling

● 1938 Food, Drug & Cosmetic Act of 1938

○ Mandated that manufacturers obtain pre-market approval from FDA contingent on demonstrated safety
○ This act was updated as the FDA Modernization Act of 1997

Question 22

Identify & describe important pieces of legislation that regulate drug marketing and safety. (Modernization Act)

Answer 22

● FDA Modernization Act of 1997:

○ Allows drugs manufacturers to discuss unapproved or “off label” indications with practitioners
■ supposed to be for one thing but prescribed for different condition (YAZ birthcontrol used for acne)

Question 23

Identify & describe important pieces of legislation that regulate drug marketing and safety. (Durham-Humphrey Act)

Answer 23

● Durham-Humphrey Act of 1952:

○ Grants the FDA authority to determine which drugs may be sold without a prescription
○ OTC drugs sold in lower doses than their prescription counterparts

Question 24

Identify & describe important pieces of legislation that regulate drug marketing and safety. (Kefauver-Harris Amendments to the Food, Drug & Cosmetic Act)

Answer 24

● 1962 Kefauver-Harris Amendments to the Food, Drug and Cosmetic Act:

○ Requires proof of efficacy as well as safety for new drugs and drugs approved since 1938

Question 25

Identify & describe important pieces of legislation that regulate drug marketing and safety. (Dietary Supplement Health & Education Act)

Answer 25

● Dietary Supplement Health and Education Act of 1994:

○ Dietary supplements
■ vitamins, minerals, herbs..
○ FDA must demonstrate that a supplement is unsafe before taking action against it

Question 26

Discuss the authority that the FDA has over OTC drugs and dietary supplements.

Answer 26

● Dietary supplements cannot make therapeutic claims

● Required to have the disclaimer: “this product is not intended to diagnose, treat, cure, or prevent any disease.”

● FDA reviews OTC drugs for misbranding & adulteration

● FDA sets guidelines to which OTC drugs are safe and effective

● FDA has authority to prevent sale & to withdraw OTCs from market