Intro to Pharm - Pechnick

Question 1

What are the different ways to discover a drug? (8)

Answer 1

1. Screening natural products
2. Testing herbal/traditional medicines
3. Molecular modeling
4. Combinatorial chemistry and high-throughput screening
5. “Me too” drugs
6. Son of a drug
7. Repurposing/repositioning
8. Serendipity

Question 2

Phase I drug testing

Answer 2

• Uses “normal” volunteers (≈20-80)
o Issues of risk/reward is patient selection
• Determines safety and biological effects
• Efficacy is not studied
• Assesses pharmacokinetics (absorption, distribution, metabolism and excretion)
• Time required to complete; months – 1 year

Question 3

Phase II drug testing

Answer 3

• Studies a small number of patients with the -targeted disease (≈200-300)
• Efficacy is established
• Pharmacokinetics are characterized
• Dose range is determined
• Short-term side effects and risks are assessed
• Highest rate of failure is in Phase II
• Time required to complete; 1 – 2 years

Question 4

Phase III drug testing

Answer 4

• Large, multi-site sample of patients (hundreds to thousands)
• Safety and efficacy are established
• Drug-Drug interactions are assessed
• Risk-Benefit information is generated
• Time required to complete; 3-5 years
• If successful, a New Drug Application (NDA) is filed with the FDA. FDA review can take 1-2 years.
• If approved the drug can be marketed

Question 5

Phase IV drug testing

Answer 5

This is the one all physicians are involved in
• Additional uses of the drug are discovered
• Post-Marketing Surveillance
o Identify new or unusual adverse reactions
o Incidence of adverse effects might be low
o Adverse effects might require chronic exposure
o Might occur in higher frequency in subpopulations (gender, age or ethnic)

Question 6

How long does it take to get a drug to market?

Answer 6

• Approximately 12 years

* Patents last 20 years

Question 7

How much money does it take to get a drug to market?

Answer 7

From $200 million to $5 billion

Question 8

FDA Use-in-Pregnancy Ratings: A

Answer 8

Controlled studies in humans show no risk to the fetus

Question 9

Pure food and drug act of 1906

Answer 9

• Progressive legislation signed by Teddy Roosevelt
• Proof of efficacy not required
• Proof of safety not required
• Required proper labeling
• Limited interstate transport of misbranded/adulterated drugs
• Led to the creation of the Food and Drug Administration (FDA)

Question 10

Food, drug and cosmetic act of 1938

Answer 10

• Driven by the death of more than 100 children due to a sulfanilamide medication containing diethylene glycol (Massengill Company)
• Proof of safety was required
• Toxicity testing required in animals
• Proof of efficacy not required
• A new drug application (NDA) had to be filed with the FDA prior to approval

Question 11

Harris-Kefauver amendment 1962

Answer 11

• Both efficacy and safety must be proven
• Required documentation of risk to benefit ratio
• Gave the FDA authority to regulate advertising
• Began to classify all pre-1962 drugs already on the market as effective, ineffective or needing further study.

Question 12

FDA Use-in-Pregnancy Ratings: B

Answer 12

No evidence of risk in humans. No controlled studies have been conducted in humans; animal studies show no risk to the fetus

Question 13

FDA Use-in-Pregnancy Ratings: C

Answer 13

Risk cannot be ruled out. No controlled studies have been conducted in humans and animal studies have not been conducted or have shown a risk. Benefits may outweigh risks

Question 14

FDA Use-in-Pregnancy Ratings: D

Answer 14

Evidence of risk to fetus in humans exists; however, benefits may outweigh risks in limited situations (i.e., life-threatening situations)

Question 15

FDA Use-in-Pregnancy Ratings: X

Answer 15

Controlled studies in both animals and humans demonstrate fetal abnormalities; the risk outweighs any possible benefit