17 drug elimination Flashcards
what does metabolism refer to
enzyme mediated bio transformations that alter the pharmacological activity of compounds
what do biotransformations do
they increase the hydrophilic character to render metabolites water soluble which aids urinary excretion
do hydrophilic molecules dissolve in water
yes and they don’t cross lipid membranes
do hydrophobic molecules tend do be lipophillic
yes so they will cross lipid membranes
what functional groups do many polar drugs contain
water soluble ones
-OH, NH2, COOH
what functional groups do non polar molecule contain
non water soluble ones
- CH2, CH3 and or C5H6
what does H bonding between polar functional groups and water favour
aqueous solubility
how can water solubility of a drug be increased
- by introducing polar functional groups
- by removing non polar functional groups
what groups does metabolism work on
- removal groups with positive log P fragment values to reduce log P of parent drug
- adding groups with negative log P fragment values to reduce log P of drug
what is deamination metabolism
when NH2 is removed from an amino acid or other compound
what is O-dealkylation
when an alkyl group is removed from oxygen
commonly catalysed by CYP450
what is N-dealkylation
alkyl group is removed from Nitrogen
usually carried out by CYP450
what is racemisation
the process by which a chiral compound converts from one enantiomer to its mirror image
what do phase 1 reactions do overall
covert parent compounds into a more hydrophilic metabolite by adding or unmasking polar groups
what do phase 2 reactions do overall
conjugate with endogenous substrates to further increase water solubility
what are the two types of oxidation reactions
- oxygen is incorporated into the drug molecule
- oxidation causes the loss of part of the drug molecule
what is aromatic hydroxylation
hydroxyl group (OH) is added to aromatic ring
usually carried it by CYP450
what is aliphatic hydroxylation
a hydroxyl group (OH) is added to an aliphatic carbon chain
what type of molecule does N-dealkylation of amines usually generate
ones referred to as nor- metabolites
eg morphine to N- morphine
what type of molecules does dealkylation generation
des- metabolites
eg metoprolol to desmetoprolol
what does the flavin monoxygenase system do
OXIDISE nitrogen, sulfur and phosphorus
what do alcohol dehydrogenases do
oxidise alcohols to produce aldehydes or ketones
what do esterases do
catalyse hydrolysis of esters
what do amidases do
break down amides
what are the conjugation reactions s
- glucoronidation
- sulfation
- glutathione conjugation
what is glucuronidation
- addition of glucuronic acid backbone (6 members sugar with a COOH and OH)
looks like an aromatic ring with lots of OHs coming off it
what is sulfation
addition of sulfate SO3
what catalyses transfer of sulfur
SULTS
how to tell glutathione and acetyl cystine conjugation
has SH Group
how to calculate logP
log(V of compound in oil/V of compound in water)
formula for logD
logP + log(F unionised)
formula for F unionised acids and bases
ACID — 1 / 1+10^PH-PKA
BASES — 1 / 1+10^PKA-PH
how to calculate F ionised
F unionised - 1
