Better MedChem Exam 2 studying

aromatic hydroxylation (phase ONE)

adds an OH to a ring

cofactor = CYP

aliphatic hydroxylation (phase ONE)

adds an OH to a CH or an H (can be chain or off of a ring!)

cofactor = CYP

alkene epoxidation (phase ONE)

turns a double bond into a <O

cofactor = CYP

alkyne epoxidation (phase ONE)

turns a triple bond into a <|O

cofactor = CYP

N-dealkylation (phase ONE)

takes a CH from an amide and replaces it with an H

cofactor = CYP

O-dealkylation (phase ONE)

takes a CHx and replaces it with an H

cofactor = CYP

S-oxidation (phase ONE)

turns R-S-R into S=O

cofactorS = FMO or CYP

N-oxidation (phase ONE)

takes R-N-R and adds an O- to it

oxidative deamination (phase ONE)

takes an amine (NH2) and turns it into an aldehyde

cofactor = MAO

alcohol oxidation (phase ONE)

takes an alcohol and turns it into an acteylaldehyde [h-=O]

cofactorS = alcohol dehydrogenase or CYP

aldehyde oxidation (phase ONE)

turns an aldehyde into a carboxylic acid

cofactor = alcohol dehydrogenase

reductive dehalogenation (phase ONE)

takes RX and turns it into RH

X = Cl and Br

cofactor = CYP

nitro reduction (phase ONE)

can lead to toxicity

takes R-N=O-O- and turns it into an amine (NH2)

cofactorS = nitroreductase or CYP

azo reduction (phase ONE)

turns N=N into an amine (NH2)

cofactorS = azoreductases or CYP

carbonyl reduction (phase ONE)

turns carbonyl into an OH

cofactorS = CRs [carbonyl reductases] or AKRs [aldo-keto reductases]

ester hydrolysis (phase ONE)

turns ester into ester and alcohol

cofactor = esterases

amide hydrolysis (phase ONE)

amide to ester + amine

cofactor = amidases

epoxide hydrolysis (phase ONE)

turns <O into OH - OH - R

cofactor = epoxide hydrolases

glucuronidation (phase TWO)

adds UDP-glucuronic acid onto an O, S, NH, COO

enzyme = UGT (udp-glucuronic acid transferase)

cofactor = UDP-glucuronic acid

acetylation (phase TWO)

adds an acetyl group

enzyme = NAT (N-acetyltransferase)

cofactor = acetyl CoA

sulfation (phase TWO)

adds SO3 group to O or NH

enzyme = SULT (sulfotranferase)

cofactor = PAPS

amino acid conjugation (phase TWO)

takes a carboxylic acid and eventually adds an amino acid on the end

enzyme = ATP-dependent acid-CoA synthetase

cofactor = acetyl CoA

methylation (phase TWO)

adds a CH3 to an O, S, or NH

enzyme = methyltransferase

cofactor = SAM (s-adenosylmethionine)

glutathione conjugation (phase TWO)

takes r-<O-r and unravels it and adds GSH to it

enzyme = GST (glutathione s tranferase)

cofactor = GSH (glutathione)

what molecules does CYP1A2 like in its active site

planar rings!

lipophilic

what molecules does CYP2D6 like in its active site

basic Nitrogen

beta blockers and CNS drugs (psych drugs)

what molecules does CYP2C9 like in its active site

weak acids

which CYPs are highly polymorhpic?

CYP2D6 —> codeine/morphine

CYP2C9 —> warfarin

what molecules does CYP3A4 like in its active site

large drugs

lipophilic [Phe groups]

can bind more than one molecule!! very versatile

what are the main classes of carriers involved in phase THREE metabolism?

SLCs and ABS transporters

(soluble carriers) (ATP-binding cassette)

what do SLCs do? (phase THREE)

[influx] carry drugs INTO the cell (no ATP required)

(OATP, OAT, OCT, PEPT)

what do ABC transporters do (phase THREE)

carry drugs OUT of the cell [efflux]

(MDR1, MRP, BCRP, MDR)

usually ATP DEPENDENT

what is an Augmented ADR

a toxic, unintended response to a drug at doses normally used in humans

*dose dependent

*can be solved with dose adjustments

*usu detected in animal models

what is a Bizarre ADR

an unexpected response in a drug

*often not detected until drug has been exposed to a high population of patients

*can occur at different doses in different patients

*potentially caused by bioactivation

urinary pH and drug excretion

drugs are excreted when they aren’t absorbed

when a drug is ionized, it doesn’t get absorbed —> gets excreted in the urine

weak acids get excreted more in high pHs (because high pH = more H+, which = charged acid)

weak bases get excreted in low pHs