Flashcards in Topic 1 Deck (23):
What is a drug?
Any chemical, other than food that affects living organisms. In medicine, a chemical agent used in treatment, cure, prevention, or diagnosis of disease.
Study of actions and mechanisms of drugs. Determines the effect of a certain concentration of a drug at site.
Study of absorption, distribution, localization in tissues, excretion, and metabolism of drugs. Determines concentration of drug at site.
Study of the clinical or therapeutic use of drugs to diagnose, treat, prevent, cure diseases
Concerned with adverse effects of drugs and poisonous substances.
Generic name. Assigned by AMA, USAN, etc.
Pure Food and Drug Act
1906. Governed labeling of drugs.
Food Drug and Cosmetic Act
1938. Sulfanimide in Diethylene Glycol. New Drug Application (NDA) required. Proof of safety.
1962. Thalidomide. Research in animals before humans (investigation new drug (IND)). 3 phases before NDA. Proof of efficacy.
Orphan Drug Amendments
1983. Incentives for developing drugs treating <200,000.
Expedited Drug Approval Act
1992. Accelerated approval if medical need high. Company pays extra.
Approaches to identify New Drug candidates
1.Chemical modification of known molecule-Thiazide Diuretics
2. Random Screening-Antibiotics, cyclosporine
3. Rational drug design, make a drug to fit in receptor-H2 Antagonists
4. Biotechnology and cloning genes-Recombinant tissue plasminogen activator.
Start with receptor then to disease state then to drug instead of starting with disease state.
Limitations of Pre-clinical testing
Time consuming expensive; lots of animals; animal to human doesn't extrapolate; rare adverse effects not detected.
Info on composition, source of drug; manufacturing info; animal studies data; clinical plans/protocols; names and credentials of physicians
Normal volunteers (20-200); mainly safety; months
Selected patients (up to several hundred). Short term safety, dosage, effectiveness; months to 2 years.
Selected patients (hundreds to thousands); safety, dosage, effectiveness; 1-4 years; gets really expensive at this phase.
FDA course of action on NDA
Not approvable, approvable, approval
Confounding Factors in clinical trials
Variable natural history of diseases; presence of other diseases/risk factors; subject and observer bias.
Controlled Substance Schedules
I-Highly addictive, no medical use.
II-Highly addictive, known medical use
III-V. Less addictive, known medical use.