excretion Flashcards
some of the molecules that are released into the bile are..
absorbed again in the small intestine and returned to the liver
what are the molecules that are absorbed in the small intestine and liver part of?
enterohepatic circulation
transfer of drug or drug metabolites from the plasma to the bile through the hepatocytes (biliary excretion) is…
irreversible
transfer of drug or drug metabolites from the plasma to the bile through the hepatocytes (biliary excretion) is followed by
intestinal reabsorption of the active drug (enterohepatic cycle).
how can active drug be regenerated after it has been through phase one and 2
Concentrated in bile and given back into intestines – into interstines and hydrolysed - be deivered back into the circulatory system – known as enterohepatic circulation
Excretion
Combination of mechanisms by which a drug is irreversibly transferred from the systemic circulation into extracorporal fluids (e.g. urine or bile).”
how are the majority of drugs removed form the body?
renal excretion in the urine
clearance is
the volume of plasma from which a substance is completely removed in a given amount of time.
For example, the clearance for urea is 65 ml/min. This means that the all of the urea in 65 ml of plasma is removed in one minute.
what is the maximum renal clearance
700ml/min, which is the renal blood flow
what are some other routes of elimination?
saliva, sweat, tears faeces (especially in renal impairment) and lungs (e.g. volatile anaesthetics)
what sort of compounds would concentrate in breast milk?
basic compounds because breast milk is more acidic than blood plasma
renal clearance equation
Clren = (Cu x Vu) / Cp
what are the 3 fundamental processes which account for renal drug excretion?
- glomerular filtration
- active tubular secretion
- passive reabsorption (diffusion from the concentrated tubular fluid back across tubular epithelium).
why should you consider renal function when dosing a drug?
- work out whether the drug will accumilate in body or all be excreted
Varies massively per drug
if a drug was going to reabsorbed in the kidney where would this be?
proximal convoluted tubule
how are the drugs eliminated in the urine
as whole or metabolites
how much plasma(blood) is filtered through the glomerulus?
20%
what would secrete drugs into the tubules for excretion?
peritubular capilaries
what is the difference in glomeruli filtration and peritubular elimination?
glomerulus will only remove free drug, where as peritubular will also remove protein bound drug (polarity and ionised would affect whether bound or not)
how would penicillin be removed from the plasma
completely through peritubular secretion
how does most peritubular secretion occur?
via OAT (organic anion transporter) or OCT (organic cation transporter). These use co-transportation of ions into/out of cell.
what size of molecule will the glomerulus allow to cross
20 kilo dalton
albumin - 68kD
how much drug excretion goes through organic anionic and cationic transporters?
80%
why are OAT and OCTs important
removing drugs that are bound to plasma proteins and drugs that are too large in molecular weight to remove through glomerulus
what is the range of pH in urine?
4.5-8
pH is lower in the morning than in the evening
if you overdosed on a weak acidic drug what would happen to the urine/
would make the urine more alkali – from pKa the drug wont be ionised will stay in compartment and be excreted
if you overdosed on a basic drug what would happen to the urine/
make the urine more acidic – from pKa the drug wont be ionised will stay in compartment and be excreted
is it more common for drugs to be excreted through the kidney unchanged or as metabolites
as metabolites
how do free drugs pass into the glomeruli filtrate
freely
20% of renal plasma flow
how are 80% or weak acid/basic drugs secreted into the renal tubule for excretion?
actively through peritubular capilaries
how are lipid soluble drugs (uncharged) reabsorbed
by diffusion drag in the renal tubules
what happens to charged molecules in the urine
they are trapped and held back
Absorption
Speed, route, bioavailability, effect of GI pH
Distribution
Final equilibrium volumes of distribution
Equilibration in/out of ‘compartments’ with differing speeds
Plasma protein binding
Metabolism
First order, zero order, saturating first order
Individual/ethnic differences in CYP450
Excretion
Entero-hepatic circulation
pH of urine
