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PHRD5915 Drug Design - Winston Lectures Review
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pharmacokinetic phase of drug action
ADME
pharmacodynamic phase of drug action
pharmacological & toxicological effects (interactions w/ biological targets)
how most drugs pass through lipid membranes for absorption & distribution to occur
passive diffusion
2 requirements for most drugs to pass through lipid membranes
1) drugs must have lipophilicity
2) concentration gradient
faces outside of lipid bilayers
polar, hydrophilic heads
faces inside of lipid bilayers
nonpolar, hydrophobic fatty acid tails
saturated or unsaturated tails increase fluidity
unsaturated
4 factors controlling drug distribution
1) size
2) lipophilicity/hydrophilicity
3) polarity
4) ionic state (pKa)
imine
toxic metabolite of APAP
N-acetyl-p-benzoquinone
imine
(NAPQI)
phenol
ester
carbonyl
carboxylic acid
or
aldehyde
ether
ketone
amide
pH > pKa
deprotonated
pH < pKa
protonated
carboxylic acid + alcohol
ester + H2O
carboxylic acid + amine
amide + H2O
thiol
(important fcnal group in cysteine)
sulfide
sulfoxide
sulfone
sulfonic acid
Henderson-Hasselbalch Equation
pH = pKa - log([HA]/[A
-
])
[A
-
] > [HA]
non-ionized
e- withdrawing groups in R ____ (raise/lower) pKa
lower
(weaken the base)
e- donating groups in R ____ (raise/lower) pKa
raise
(make a stronger base)
substrate binds close to P450 heme. spectrum?
Type 1
(high @ 410nm)
substrate binds directly to P450 heme. spectrum?
Type II
(high @ 440nm)
where does P450 get its electrons?
from NADPH via CYP450 reductase
biotransformation
changes properties of a xenobiotic from lipophilic to hydrophilic
characteristics of Phase I products (2)
1) inactivation
2) conversion of active drug to another active one
example of Phase 1 conversion of an active drug to another active drug
codeine, heroine -> morphine
4 compartments alcohol detoxification takes place in
1) microsomes (CYP2E1)
2) cytosol (ADH)
3) mitochondria (ALDH)
4) peroxisomes (catalase)
products of CCl
4
breakdown (4)
1) carbon monoxide
2) carbon dioxide
3) phosgene
4) HCl
coupling of reduction of H
2
O
2
& lipid hydroperoxides to the oxidation of other substances
cooxidation
(used by peroxidases, instead of using NADPH or NADH)
universal sulfonate donor for all sulfotransferase reactions
PAPS (3'phosphoadenosine-5'phosphosulfate)
APS + ATP =
PAPS
(sulfation reaction)
sulfotransferase + PAPS =
PAP
Author
daynuhmay
ID
265403
Card Set
PHRD5915 Drug Design - Winston Lectures Review
Description
drug design
Updated
2014-03-07T09:19:43Z
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