Drug distribution Flashcards
when is a drug biologically active- bound or unbound to plasma protein
unbound
what can affect amount of unbound drugs
renal failure, hypoalbuminaemia, pregnancy, other drugs
when does protein binding matter
when the drug is more than 90% bound and the tissue distribution small. if the drug works best at 96% bound (4% unbound) then it decreases binding to 94% this could lead to toxicity
apparent volume of distribution (Vd)
volume of plasma that would be necessary to account for the total amount of drug in a patients body. greater the Vd, the greater the ability of the drug to diffuse into and through lipid membrane
ideal Vd
42L
clearance (Cl)
theoretical volume from which a drug is completely removed over a period of time (ml/min)
what is clearance dependent on
urine flow rate for renal clearance, drug conc, metabolism, biliary excretion for hepatic clearance, disease states and age
half life (t1/2)
time taken for the drug conc in blood to decline to half of the current value
chemical properties of drug
lipophilicity, ability of body to metabolise and excrete the drug, degree of ionisation
what does knowledge of half life help us to work out
how often the drug needs administered
loading dose
dose that gets the drug levels in the therapeutic range (steady state) as plasma levels of drug may take many doses before they stabilise, usually 4-5 half lives
factors that lead to an increase half life of drug resulting in increased blood drug levels
age, obesity, liver disease, renal disease, congestive cardiac failure, other drugs, malnourishment, hypoproteinaemia
primary organ for drug excretion
kidney
three principle mechanisms used for excretion
glomerular filtration, passive tubular reabsorption, active tubular secretion
what does metabolism in liver lead to
conjugation of drug so it is more water soluble. this makes it not reabsorbed from the intestine.
