Exam 4 Study Guide Flashcards
what is a lead compound
structure that had some activity against the chosen target, but not yet good enough to be the drug itself
what is meant by SAR
Structure-Activity-Relationships
pharmacophore definition
the structural features directly responsible for activity
pharmacodynamics vs pharmacokinetics
- pharmacodynamics = explores what a drug does to the body
- pharmacokinetics = explores what the body does to the drug
how do most pharmaceutical companies choose the disease of interest
big market, developed countries
what is the orphan drug act of 1983
encourage pharmaceutical companies to develop drugs to treat diseases which affect fewer than 200k people in the US
how has human genome mapping helped with drug development
people can work with a specific enzyme or receptor to discover its structure and biological function
in vitro definition
in an artificial environment
in vivo definition
in the living body
ex vivo definition
doing test on tissue taken from a living organism
in vitro advantages and disadvantages
- advantages: speed and small amount needed
- disadvantages: may not translate into living animal
in vivo advantages and disadvantages
- advantages: can be translated to living organism
- disadvantages: more expensive, can cause suffering/side effects
ways for companies to find lead compounds
- screening natural products
- screening synthetic banks
- using someone else’s lead
once the lead is discovered, why is studying the SAR important
to identify the pharmacophore, or exactly what is responsible for the biological activity; can enable a more precise and active molecule
what is the ADME of drugs
Absorption
Distribution
Metabolism
Excretion
what is Phase I of metabolism
small chemical changes that make the compound more hydrophilic so it can be eliminated by kidneys; detoxify or toxify
what is cytochrome P450
responsible for most Phase I metabolism reactions
what is Phase II of metabolism
links drug to more polar molecules to make it even easier to excrete; commonly detoxify
what is Phase III of metabolism
uses drug transporters to move drug across cellular barriers
what are some of the key issues for a company when manufacturing a new drug
toxicity, drug must be able to be “scaled up” in quantity to be sold at a profit, efficient synthetic route needed
thalidomide tragedy
prescribed for morning sickness, caused malformities, led to laws requiring safety tests for during pregnancy before approval
Type A vs Type B ADRs
Type A: known but undesirable, dose-related
Type B: unknown, rare, unpredictable
detoxification vs toxification
Detox: make less toxic
Toxify: make toxic
6 mechanisms of toxicology
- allergic responses
- receptor, ion channel, and enzyme-mediated toxicity
- biochemical pathways
- organ-directed toxicity
- mutagenesis and carcinogenesis
- teratogenicity