Principles Flashcards
(41 cards)
define pharmacodynamics
what a drug does to the body
define pharmacokinetics
what the body does to a drug
ADME
adsorption, distribution, metabolism and excretion
goal of drug metabolism
inactivate and excrete xenobiotics
phase 1 function
introduce of reveal a functional group for phase 2
phase 2 function
conjugate to a polar molecule
where drug metabolism occurs
primarily liver, then GI, kidney and lungs
functions of metabolism
want to take a non-polar compound and make it more polar - so add functional group and then conjugate it to make it more polar, as non-polar molecules cannot pass out of the renal tubule
phase 1 type of reaction
usually oxidation (most common)
types of phase 1 enzymes
monooxygenases (specific enzymes) eg. alcohol dehydrogenase and MAO
mixed function oxidase (general enzyme family) eg. cytochrome P450, will oxygenate any unknown compound
process of oxidative deamination
Monoamine oxidase
Acts on molecules such as catecholamines (common neurotransmitter)
removes amine group, produces an aldehyde and ammonia
cytochrome P450 action
replaces C-H with C-O(at physiological pH and temp)
aliphatic hydroxylation from saturated hydrocarbon to an alcohol and water, uses NADPH as electron donor
can also do aromatic hydroxylation to oxidise benzene
what is cytochrome P450
superfamily of enzymes with overlapping specificities, however the largest group of enzymes is to oxidise large non-polar molecules
mixed-function oxidases
case study - toxicity in paracetamol metabolism
metabolism in overdose makes paracetamol toxic
can be oxidised by offing glucuronate or sulphate to make it more soluble
if in excess, 10% can be metabolism by a cP450 enzyme, can make a quinoneimine (very reactive) and result in cell death - hepatotoxicity
shows that drug metabolites may be toxic
another action of cP450
inducible in the liver, eg. can increase or decrease transcription if consuming lots of specific metabolites
phase 2 metabolism action
addition of polar groups
eg. glucuronic acid, glycine, glutathione, sulphate
incorporated by oxidation/ reduction reactions to increase solubility
alcohol metabolism process
ethanol -> acetaldehyde -> acetic acid
aldehydes are very toxic, can cross-link proteins
alcohol dehydrogenase and aldehyde dehydrogenase enzymes
(aldehyde dehydrogenase deficiency associated with asian flushing syndrome)
what does chemical modification do?
usually abolishes activity
another reaction of drug metabolism
hydrolysis, eg. acetylcholinesterase
glomerular filtration of drugs
most filtered freely, unless bound to serum proteins
filtered drugs either passively reabsorbed to trapped in urine depending on lipid solubility and tendency to ionise
other form of renal excretion
tubular secretion and reabsorption, eg. the active secretion of penicillin
drug-drug interactions
drugs can alter the pharmacokinetics of another drug
enzymes can be induced by different compounds
eg. ethanol can induce cP450 systems to increase metabolism and potential toxicity of other compounds
other actions of phase 1
can activate pro-drugs
can transform innocuous substrate into chemically reactive, toxic metabolite
factors affecting alcohol metabolism
conc, of alcohol blood flow at site of absorption irritant properties of alcohol rate of ingestion fed/ fasted state
