MCMP 824: Lecture 4 Flashcards
drugs bind receptors with
stereoselectivity
priorities are assigned to atoms attached to a chiral center based on
atomic number
different stereoisomers have different properties why?
the more active isomer of a drug makes contact with more interacting groups in the receptor binding pocket
Easson-Stedman hypothesis states that
the more potent enantiomer must be involved in a minimum of 3 intramolecular interactions with the receptor
LESS POTENT ONLY INTERACTS WITH (easson-stedman hypothesis)
only interacts with 2 sites
different stereoisomers have different
potencies
____ drug enantiomers will have different affinities but ____ drugs will have the same
- BETA
- ALPHA
enantiomers are
complete mirror images of each other
are diastereomers mirror images?
no
many drugs are sold as a racemic mixture with the assumption that the _____ enantiomer is inert
inactive
phases that a drug can encounter prior to reaching the biologic target? (6)
1) drug dose
2) membrane selectivity
3) selective metabolism
4) nonspecific receptors, site of loss
5) drug receptor
6) desired response
not all differences in activity of isomers ar due to differences in _____ with the ______
- interactions
- receptor
____ ____ ____ ____ can affect a drug’s pharmacokinetics and thus biological activity
non-specific protein binding
many drugs bind to ___ ___ via ___ or ____ interactions
- plasma proteins
- ionic
- hydrophobic
a drug cannot partition to the target receptor unless it is?
free in the plasma
protein binding can : (3)
1) prevent rapid drug excretion
2) limit the amount of free drug available at any given time
3) act as a sink for prolonged drug release
interactions can be
stereospecific
plasma is really good at binding ______ molecules
hydrophobic
take home message: drug distribution throughout the body is complex and highly dependent on a drug’s relative (3)
1) lipid/water solubility
2) degree of ionization
3) tendency to bind proteins
different stereoisomers can differ in terms of (3)
1) pharmacokinetics
2) bioavailability
3) toxicity
many drug formations are ____ ___
racemic mixture = 50:50 mixtures of two enantiomers
one of the enantiomers may differ from the other in terms of
absorption, serum protein binding, metabolism
an inactive enantiomer may selectively trigger ______
toxicity
bottom line: in general it would be preferable to administer drugs as
pure enantiomers
enantiomers are ____ molecules that are ___ ___ of one another. Furthermore the molecules are ____ ____ on one another.
- chiral
- mirror images
- non-superimposable
diastereomers are stereoisomers that are not ___ ___ of one another and are _____ _______. Stereoisomers with two or more ____ can be diastereomers
- mirror images
- non-superimposable
- stereocenters (chiral centers)
priorities ____ > _____> _____> _____> ____> _____> ______> ______>
I>Br>Cl>S>O>N>C>H
