Drug Development & Testing Exam 1 Flashcards
Discuss the history of drug development and use.
● 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.
1630- Quinine isolated from ____________?
from tree bark is used to treat malaria and it is the first specific drug to treat an infectious disease.
1760- (Magic Bullet) Synthesis of ____________ ?
arsenicals by attaching an arsenic atom to a carbon atom. This led to Paul Ehrlich’s use of arsphenamine to treat syphilis.
1783- Foxglove to treat what?
“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)
1807- Morphine was isolated from what? Explain.
Opium, this led to techniques to isolates caffeine, atropine, and strychnine.
-Source of opium is poppy plant
1897- Aspirin first synthesized by ______________?
Converted salicylic acid into____________
Acetylsalicylic acid aka__________?
Single most important ___________?
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
1901- Epinephrine was the first _____________?
hormone isolated
In 1927- Alexander Fleming accidentally _______________?
discovered “penicillin”
1935- Sulfonamides (“sulfa drugs”)- used to treat ______________?
infections of the urinary tract -Pre-dated the clinical use of penicillin
In 1941- First clinical use of _____________used in WWII
Penicillin
Discuss issues related to drug development in terms of time and cost.
● 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
Describe the 1st phase of drug development and testing.
● 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
Describe the 2nd phase of drug development and testing.
● 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
Describe the 3rd phase of drug development and testing.
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
Describe the 4th phase of drug development and testing.
● 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
Briefly describe the summary of phases of drug development and testing.
○ 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
Differentiate between the chemical/scientific names for drugs.
● 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
Differentiate between the Generic name for drugs.
● 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
Differentiate between the Trade name for drugs.
● 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
Discuss the determination and significance of the “margin of safety.”
● 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
Identify & describe important pieces of legislation that regulate drug marketing and safety. (Pure Food & Drug Act and Cometic Act)
● 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
Identify & describe important pieces of legislation that regulate drug marketing and safety. (Modernization Act)
● 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)
Identify & describe important pieces of legislation that regulate drug marketing and safety. (Durham-Humphrey Act)
● 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
Identify & describe important pieces of legislation that regulate drug marketing and safety. (Kefauver-Harris Amendments to the Food, Drug & Cosmetic Act)
● 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
Identify & describe important pieces of legislation that regulate drug marketing and safety. (Dietary Supplement Health & Education Act)
● 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
Discuss the authority that the FDA has over OTC drugs and dietary supplements.
● 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
