Introduction Flashcards
Pharmacodynamics
What the drug does to the body
Pharmacokinetics
What the body does to the drug
What types of toxic studies are done?
- Acute
- Subacute
- Chronic
- Reproductive
- Carcinogenics
- Mutagenic
Acute studies
2 species, 2 routes
Determine minimal lethal dose
Subacute studies
2 species, 3 doses
Note biochemical and physiological effects
Chronic
Note biochemical and physiological effects
With both subacute and chronic studies, what do we want to know
What doses
If anything causes toxicity
Reproduction
Find out if fertility is affected by the drug
Carcinogenicity
Note gross and histologic pathology
Phase 1 clinical testing
Primary purpose: to determine pharmacokinetics - how is it metabolized
- new side effects?
- NON BLIND
Phase 2 clinical testing
Determining effectiveness
- cross over
- single blind
Phase 3 clinical testing
- double blind
- cross over
Phase 4 clinical testing
Postmarketing surveillance
-report unexpected side effects
Pure Food and Drug Act
Insures purity and proper labeling
Federal Food, Drug, and Cosmetic Act
Requires toxicity studies to determine safety
Kefauver-Harris Amendment
Mandated teratology testing
Requires proof of efficacy
FDA Modernization Act
Expedited review for drugs for serious diseases
What components make a drug lipophilic?
ring systems
aliphatic groups (e.g. -CH3)
carbon chains
What components make a drug lipophobic?
amines aldehydes alcohols carboxylic acids phenols
What is P-glycoprotein? Why is it important?
P-glycoprotein is a transporter. It can carry drugs across lipid membranes (uses ATP).
What are some examples of P-glycoprotein importance?
- pumps certain drugs/toxins actively back into GI lumen
- proximal kidney tubules can pump drugs into lumen
- pump some drugs into bile
- transports some drugs/toxins out of brain, placenta
- protects hematopoietic stem cells from toxins
- protects organs of reproduction (ovaries, testes)
What does a low Vd mean?
the molecule is lipid soluble - so it will penetrate to all tissues of the body and will be low in the plasma
Why do levels of enzymes vary in different patients?
polymorphisms
What is the main route of drug excretion?
the kidney
