MCMP 824: Lecture 1 Flashcards
Log D will never be ______ log P
above
Challenges associated with drug design and administration (5)
1) a drug must have the correct molecular structure
2) a drug must have chemical properties that favor absorption into the circulatory system
3) drug chemistry or dosage must account for metabolism
4) drug chemistry or dosage must account for non-specific protein binding
a drug must have the correct molecular structure which is critical for?
activation of the receptor AND ONLY the receptor
the drug will bind to its receptor and
alter it’s activity with selectivity
drug chemistry or dosage must account for metabolism why?
body has enzymes that attack these “drugs” which often happen in the liver. We have to account for those properties to create an effective drug
drug chemistry or dosage must account for non-specific protein binding why?
a lot of proteins exist within your systemic circulation and and the serum protein can act like a sink that can affect the effective concentration of your drug
often drugs inhibit the activity of _______ and often bind ______ with substrates.
- enzymes
- competitively
what is a drug? (4)
- molecular entity
- organic functional groups
- characteristic 3D pattern
- elicits a biological response
Ideal structural properties of drugs (4)
1) log P between -0.4 and 5.6
2) molecular weight between 160 and 480 Da
3) total number of atoms between 20 and 70
4) some combination of functional groups
what are 4 of these combiational functional groups?
1) aliphatic or aromatic rings
2) carboxamide group
3) aliphatic amine (tertiary)
4) alcoholic hydroxy group, carboxy ester, or keto group
why do we care about the ideal properties of a drug?
these properties ensure movement through lipid membrane and the ability to present functional groups in an arrangement able to bind drug receptors
in general, functional groups contribute ?
polarity
aerol groups and aliphatic hydrocarbon groups contribute
lipophilicity
the actions of drugs result from their
chemical structures
a drug can be thought of as a 3D collection of
specific groups - generally polar
functional groups are attached to a _____ ____ that is generally
- carbon skeleton
- non-polar
the following parameters play a role in linking molecular structure to a specific pharmacological activity (6)
1) molecular size
2) molecular shape
3) functional group distribution
4) stereochemistry
5) electronic effects
6) chemical reactivity
drugs with ____ __ ____ typically elicit similar pharmacological activites
similar chemical structures
how can we identify critical aspects or motifs AKA critical functional groups that we need to keep a drugs activity
use the simplest structures to identify minimal motifs (functional groups) involved in receptor binding
small structural differences can lead to major differences in (2)
potency and pharmacological activity
two drugs with the same molecular formula and core carbon framework but with a different ____ ____ of _____ _____, are likely to have different biological activites
- 3D arrangement of functional groups
what is the example of 3D arrangements and subtle differences that we talked about?
cocaine + atropine
pharmacodynamics is the study of
how a drug modifies an organism
pharmacokinetics is the study of how
the organism modifies a drug
_______ ( ) - drugs that are poorly solvated by water or are water hating and typically non-polar
hydrophobic (lipophilic)
_____ ( ) - molecules that are readily solvated by water or are water loving, typically polar
hydrophilic (lipophobic)
what are some examples of hydrophilic molecules
- OH
- COO-
- NH3+
these are molecules that contain both hydrophobic and hydrophilic groups (also known as ______)
- surface active agents
- detergents
how does the structure of a drug affect its transport in the body is an example of
pharmacokinetics
the ______ and ____ ____ of a drug to the site of action are critical parameters for therapy
- absorption
- effective distribution
orally administered drug: GI tract and other biologic ____ act like lipid barriers
membranes
most drugs are absorbed through membranes by
passive diffusion
the absorption rate of a drug is related to the drug’s _____
lipophilicity
in general, more ____ ____ are absorbed more efficiently
Hydrophobic (lipophilic)
the _______ form of an acidic or basic drug is preferentially absorbed
unionized
things that have _____ are really disfavored and cannot be absorbed through the lipid bilayer
charged
major route of drug administration: ________ drug must be absorbed to enter ______
- extravascular
- circulation
binding of drug molecule to the surface of the skin or mucosa / “on the surface”
adsorption
movement of a drug into deep layers of the skin without reaching the bloodstream
penetration
permeation of a drug through capillary walls into the circulatory system
absorption
drug must be in ___ ___ to be absorbed
aqueous solution
most drugs reach their target through ____ ____ through the lipid bilayer where the drug is dissolved in ___ ___ and then has to dissolve in the _____ inside that bilayer.
the extent to which that happens is dependent on ____ and also on _____ state because ____ things are extremely ___ and not very ___ at all within that bilayer
- passive diffusion
- aqueous solution
- lipophilic
- lipophilicity
- ionization
- charged
- polar
- soluble
transport through a semipermeable membrane =
passive diffusion
drug dissolves in the ____ part of the membrane, then redissolves in the ___ ___ on the opposite side
- lipid
- aqueous medium
extent to which the drug dissolves in the membrane depends on the drug ____ and on the ____ at the absorption site: drug must be _____ to be absorbed
- pKa
- pH
- unionized
as drug on the other side of the membrane is swept away by the ____ ___, more drug is absorbed from the ____ so that in the end ALL of the drug is absorbed
- circulatory system
- outside
partition coefficient is the measure of
“how well” a drug can move through the lipid bilayer
a drug’s lipophilicity is determined quantitatively by calculating its
partition coefficient, Log P
the higher the P value, the more
lipophilic (hydrophobic) a drug
organic layer is on?
aqueous layer is on?
- top
- bottom
if log P = 0, which phase contains more of the drug?
they contain equal amounts of drug
more negative (like -2) Log P will be
hydrophilic (lipophobic)
more positive (2) a Log P will be or more in organic layer
hydrophobic (lipophilic)
log p ranges from ______ to _____ for typical drugs
-1 to 4
