Exam 2

Lipinski’s Rules states that oral drugs should be _____ than _____ g/mol.

less, 500

Lipinski’s Rules states that oral drugs should have a lipophilicity constant of ___ than __.

less, 5

Lipinski’s Rules states that oral drugs should have _ or fewer H-bond donors and __ or fewer H-bond acceptors.

5, 10

Lipinski’s Rules states that oral drugs should have __ than __ rotatable bonds

less, 10

A large pi value means ____ lipophilicity.

greater

A smaller pi value means ____ lipophilicity.

lower

A positive sigma value means electron _____ group.

withdrawing

A negative sigma value means electron _____ group.

donating

A smaller KD value means ____ affinity of the drug for the receptor.

greater

Common drug-receptor interactions include:

ionic, ion-dipole, dipole-dipole, h bonds

More intramolecular H-bonds mean more ______ (lipophilic / hydrophilic)

lipophillic

More intramolecular H-bonds mean less ______ (lipophilic / hydrophilic)

hydrophilic

Intramolecular bonding structures work like _____ rings

bicyclic

Strength of cyclic rings from greatest to least:

6, 5, 7

Halogens can act as electron ______ (donors / acceptors)

acceptors

Larger halogens make ______ (stronger/weaker) bonds

stronger

EC50 measures the concentration that produces ___ _____

50% effect

A ____ ____ binds and produces 100% response

full agonist

A ____ ____ binds and produces some degree of response

partial agonist

A ____ _____ prevents 100% of the response.

full antagonist

A ______ ______ is the most common type of antagonist.

competitive antagonist

The most common type of noncompetitive inhibitor binds to an _______ site.

allosteric

A _____ _____ behaves like both an agonist and antagonist, and brings the response either up or down to some level.

partial agonist

An ____ _____ _____ binds and produces 100% of the opposite effect.

full inverse agonist

An ____ _____ _____ binds and produces some amount of the opposite effect.

partial inverse agonist

A full agonist binds to the ______ receptor

active

A partial agonist binds preferentially to the ____ receptor but can also bind to the ____ receptor

active, inactive

A full inverse agonist can only bind to the _______ receptor

inactive

A partial inverse agonist binds preferentially to the ________ receptor but can also bind to the _____ receptor.

inactive, active

An antagonist binds to

TODO

The drug-receptor complex become ______ when a racemic drug is bound.

diastereomers

The more potent enantiomer is called the _________.

eutomer

The less potent enantiomer is called the _______.

distomer

The ratio of eutomer/distomer potentices is the ______ ratio.

eudismic

A drug with a stereocenter in the auxophore will have a _____ eudismic ratio

low

A ______ is a less-active form of a drug with extra groups added to help it get to where it needs to go without being destroyed.

prodrug

Two functional groups commonly added to drugs to make prodrugs are ____ and ____.

ethers, amides

Ethers are cleaved by ______ enzymes

esterase

Amides are cleaved by ______ enzymes

amidase

Reasons to use a prodrug:

improve absorption, improve patient acceptance, increase half-life, increase site-specificity, minimize side effects, 

A large group is linked to ampicillin via an ____ to improve absorption.

ether

Two alkyl groups are added to adrenaline via ____ to allow it to pass through the lipid layer of the eye.

ethers

Two different groups can be added to clindamycin via ethers to improve either ______ or ______

taste, pain

Adding a long chain via an amide to tolmetin increases the ____-___.

half-life

Adding an acyl group to salicylic acid reduces ___ ____ and is the more GI-safe drug aspirin.

side effects

Drug resistance can be caused by ______ ________

natural selection

List the resistance pathways

altered drug uptake, overproduction of target enzyme, altered target enzyme or active site, production of drug-destroying enzymes, deletion of produg-activating enzymes, overproduction of substrate, new formation pathways, efflux pumps

A ________ is any molecule foreign to the body

xenobiotic

Phase I of metabolism involves _____ _______ _______.

functional group modification

The three Phase I reactions are: _____, _______, and _______

oxidation, reduction, hydrolysis

Phase II of metabolism involves adding ___ ______ to the metabolite.

large groups

In the first pass effect, drugs go directly to the _____ and are metabolized. These are not effective drugs.

liver

As lipophilicity increases, metabolic rate _______.

decreases

Cytochrome p450 is a common family of liver enzymes that catalyze ____ ____ transformations.

functional group

OH groups added to a benzene ring by p450 are always in the ___ position.

para

The flavin monooxygenase enzymes are the second most common F.G. modification enzyme family, and usually add to ______.

heteroatoms

Not enough ________ in the cell leads to apoptosis

glutathione

Metabolites with epoxides are very ____ (good/bad)

bad

Metabolites with two carbonyls in the ___ or ____ positions are bad because they are magnets for nucleophiles.

ortho, para