ADME 5 Flashcards
what is metabolism?
Overall process by which a living system acquires and utilises the free energy needed to carry out various functions
what is anabolism?
Biosynthesis•Biomolecules are synthesised from simpler components
what is catabolism?
Degradation•Nutrients are broken down to salvage components and energy•Carbohydrates, lipids, proteins are all converted to the same common intermediate•Acetyl CoA
what is the purpose of drug metabolism?
Aids elimination of drugs and foreign compounds
Detoxification process
A drug is often metabolised into many products
do most drugs emerge from a patient unchanged after matabolism?
rare- most drugs undergo a chemical change to produce metabolites
why does is the purpose of making the drug more hydrophilic functionality?
to excrete urine
how do you slow the rate of metabolism?
modify its structure
why are metabolites often eliminated quicker than the drug?
more water soluble
what 4 things influence drug metabolism
genetic/ physiological/Pharmacodynamics/ environmental factors
what happens if the rate of metabolism decreases?
increased intensity and duration of drug action
•increased accumulation of parent drug in the plasma, increased toxicity risk
what happens if the rate of metabolism increases?
decreased intensity and duration of drug action
•toxicity may increase owing to production of toxic metabolites
what are the sites of metabolism?
liver
Endoplasmic reticulum (microsomes)
Cytosol
Non-specific enzymes
what happens when you introduce polar groups to molecules?
oxidative, hydrolytic (hydrolysis/hydration), reductive, isomerisatio
why would you convert one functional group into another?
Increases a molecules polarity
May not produce metabolites for excretion
Provides a site for Phase II metabolism
what are esters hydrolised to?
alcohols, phenols and carboxylic acids
what are amides hydrolized to?
amines and carboxylic acids
what reaction is slower? amides/ester hydrolysis?
amides
what does cytochrome P450 do?
addition of oxygen
Mixed function oxidases or monooxygenases located in the liver hepatocyte endoplasmic reticulum
what is required for P450 oxidation?
require NADH or NADPH and O2as cofactors
•Cytochrome P-450 (or cytochrome b5) enzyme needed
what kind of an enzyme is cytochrom P450?
iron containing porphyrin
where does all activated chemistry occur in the pathway of P450?
occurs at the iron centre heme with oxygen transfer to the protein bound substrate
what is P450 drug-drug interaction?
involving induction or inhibition of metabolism of one drug by co-administration of another
what s involved in biotransformation of ~60% of drugs undergoing oxidative metabolism ?
CYP3A4
why is there some genetic variation with the CYP2D6 drug?
8% Caucasians, 4% African-Americans, 1% Asians are poor metabolisers through CYP2D6
what is an inducer and an inhibitor?
inducer•Activity is increased and rate of metabolism increases
Inhibitor•Activity is decreased and rate of metabolism decreases
