Flashcards in Exam 1: Drug Development & Testing Deck (71):
Drugs are chemical substances that are used for the _______, ________ or ________ of disease, and for the prevention of ________.
diagnosis, prevention or treatment....pregnancy
What was the first SPECIFIC drug used to treat an infectious disease (malaria) that was taken from nature?
One of the first drugs was also called 'the magic bullet' which was SYNTHESIZED by adding ______ to carbon. It was used to treat syphilis.
What is the drug from a plant that is still the best treatment for congestive heart failure? What plant is it from?
Digitalis from the Foxglove plant.
The isolation of _______ lead the way to techniques for the isolation of caffeine (thank God!), atropine, strychnine.
Atropine (to dilate the pupils) and Scopolamine (for motion sickness) are both derived from this plant....
The SINGLE MOST IMPORTANT drug discovery in medicine.
ASA-Acetyl Salicyclic Acid (Aspirin)
What was the first hormone isolated? (Happened at Johns Hopkins)
Penicillin was derived from this plant _______ and inhibited the growth of _______.
Penicillium Notatum......S. Aureus
What were the drugs that pre-date penicillin?
Sulfa Drugs are still used today to treat ______.
________ was the antibiotic used in WWII.
Time necessary to develop a drug is approximately ____ years
Cost of developing a drug approximates $____ million, but may cost significantly more.
Only about ___ in 10 new compounds successfully reach the market
2 out of 10
How long is the patent on a NEW DRUG, when does that patent start?
17 years!! Clock starts at Phase 1 clinical testing (generally 8 year process!)
What are the 5 steps for Drug development? (Simplified!)
1.Discovery of a new drug 2.Safety evaluation 3. Effective in humans 4.New Drug Application 5.Post-market surveillance
Is Short-term toxicity testing done in humans or animals?
animals (generally mice)
The _______ is the dose of a drug that kills 50% of the total numbers of mice that received it.
Leathal Dose (LD50)
The _______ is the dose of a drug that causes an effect in 50% of the total numbers of mice that received it.
Effective Dose (ED50)
The margin of safety= ______ divided by ______.
LD50 / ED50
What is the margin of safety if LD50=10mg and ED50 = 2mg?
Margin of safety= 10mg (LD50) / 2mg (ED50) = 5
If a margin of safety is 5, that means the _______ is only 5 times the _______.
lethal dose is only 5x the effective dose
What is an ACCEPTABLE margin of safety for a drug?
2000 or MORE!!!
Long-term toxicity-aka ______ toxicity studies-give daily dosing to _____ or _____ from ___ months to ___ years.
chronic....rats or dogs....3months to 2 years
In long-term toxicity, many toxic effects appear only after repeated dosing over many ______ or ______. Also they _______ the animals to look at any histopathology.
months or years....sacrifice :(
Drugs that cause birth defects are termed ________.
Studies for carcinogenicity of a drug typically rate over ____ months.
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????
(IND)- Investigational New Drug Application
The _____ is when the company releases information on the drug, including the chemical structure.
IND-Investigational New Drug Application
When does Phase I clinical studies begin?
Immediately after IND(investigative new drug application) is approved
Which testing Phase evaluates the drug in HUMANS for the first time?
Phase I...18-24 year old men (poor bastards)
Phase I trials on healthy young men study the _____ profile, and determine the Pharmo______. It also establishes the dose at which ______ appears.
safety....pharmokinetics...toxicity (poor bastards!)
Which Phase of testing do we give to patients with the condition for which the drug was intended?
About how many subjects are in Phase II trials? What time frame is this Phase studying? long-term or short-term?
100-300 subjects, studies SHORT-term effectiveness
Which Phase studies adverse drug events?
Phase II, Phase III, Phase IV
Which Phase establishes therapeutic efficacy, dose- response and dose range, kinetics, and metabolism.
Which Phase has 1000 to 3000 subjects?
Which Phase is checking long-term efficacy?
In Phase III-Trial design is always a ________, _______ control. So there are 2 groups, one receives the _____ and one receives the ______.
randomized, double-blind....drug, palcebo
What is the MOST EFFECTIVE design for avoiding bias and distributing unknown variables between the treatment and control groups?
Randomized, double-blind control
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
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.
1 in 1000 exposures...millions!
The _________ is submitted after 8 years of testing.
(NDA)-New Drug Application
Phase IV is also known as _______.
Phase IV can have the drug pulled off the market if new ______ are uncovered. Often problems in Phase IV result in _____ of the drug.
The use of investigational drugs occurs during the review of _____. These are in rare situations and are considered "_______ use protocols"
NDA-new drug application (post/during? Phase III)..compassionate
Who oversees OTC drugs?
________– 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 _____.
Chemical Name...letters and numbers
_______ – before any drug is marketed, it is given a this which becomes the “official” name of the drug (e.g. cola)
All drugs have one _______ name, but can have many ______ names
generic names are NOT _______. ex. _______ is the generic name and Coumadin is the trade name.
_______ - 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)
Trade name = _____ name = Proprietary name
The 1984 – Drug Price Competition and Patent Term Restoration Act Allows ______ drugs to receive expedited approval.
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.
The 1984 – Drug Price Competition and Patent Term Restoration Act: _______ drugs are frequently more affordable and provide cost-savings to the patient
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.
How was the FDA created?
the 1906 Pure Food & Drug Act
The 1906 Pure Food & Drug Act said that drugs must meet _______ of purity and quality AND manufacturers must provide correct and truthful ______.
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.
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
Durham-Humphrey Act of 1952 Grants the FDA authority to determine which drugs may be sold without a ________.
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.
efficacy as well as safety
For dietary supplements, the FDA must demonstrate that a supplement is _____ before taking action against it.
________ cannot make therapeutic claims and must have the disclaimer: "this product is not intended to diagnose, treat, cure, or prevent any disease."
An _____ disease is a disease that affects <200,000 people, there are incentives for manufacturers to develop drugs.
Haha, before the Harrison Narcotic act of 1914 and Maryjane in 1937, these drugs were sold _____.
Which government agency administers Controlled Substances?
The _________ is an agreement between the FDA and the manufacturer so that the drug is presented in a way that is marketable