drug distribution Flashcards
what must a drug do after it has been absorbed?
it must be available for biological action and distribution to tissues
what conditions must be met for a drug to become active?
drug must leave the bloodstream and enter the inter or intracellular spaces
what factors affect the way that a drug is distributed throughout tissues?
plasma protein binding tissue perfusion membrane characteristics transport mechanisms diseases other drugs elimination
what membrane characteristics can affect tissue distribution?
the blood-brain barrier
blood-testes/ovary barrier
whether the drug is lipid soluble
whether the drug is actively transported or not
what are some examples of plasma proteins that drugs bind to?
albumin
alpha 1 glycoprotein
what form of the drug is biologically active?
the unbound form
is binding reversible or irreversible?
reversible
what can change the amount of bound drug?
renal failure hypoalbuminaemia pregnancy other drugs saturability of binding
what percentage of the drug has to be bound for protein binding to be an important factor?
more than 90%
does tissue distribution have to be large or small in order for protein binding to be an important factor?
small
what is the apparent volume of distribution? (Vd)
the volume in which a drug seems to distribute within the body
what does a higher volume of distribution indicate?
a greater ability of the drug to diffuse into and through membranes
what should the the theoretical volume of distribution be?
40L
what would the Vd be if the drug stays in the extracellular fluid but cannot penetrate cells?
12L
what would the Vd be in a drug that is highly protein bound?
3L
what would the Vd be if the drug was sequestered in the extravascular lipid compartment?
> 40L
what is clearance defined as?
the theoretical volume of fluid from which a drug is completely removed over a period of time?
what is clearance a measure of?
elimination
what is renal clearance dependent on?
concentration of drug and urine flow rate
what is hepatic clearance dependent on?
metabolism and biliary excretion
what is the half life of a drug?
the time taken for the drug concentration in the blood to decline to half of the current value
how is the half life calculated?
o.693Vd/Cl
what does the half life of a drug depend on?
volume of distribution and rate of clearance
what effect does prolongation of the half life of a drug have?
increases the toxicity of the drug due to a reduction in clearance or due to a large volume of distribution
what clinical application does knowledge of a drugs half life have?
allows us to figure out how often a drug needs to be administered
how many doses of a drug does it usually take for plasma levels of said drug to stabilise? (steady state)
4-5
what is drug elimination?
removal of active drug from the body
what does drug elimination determine?
length of action of the drug
what 2 parts is drug elimination made up of?
metabolism (usually in the liver)
excretion (usually in the kidney but also the biliary system/gut and lung)
what are the 3 principal mechanisms employed by the kidney with regards to drug excretion?
glomerular filtration
passive tubular reabsorption
active tubular secretion
when would an unbound drug NOT be filtered at the glomerulus?
if the molecular size, charge or shape is excessively large
what happens if the glomerular filtration rate is decreased?
clearance is reduced
what happens to the concentration of a drug as the filtrate moves down the renal tubule?
it increases
where does passive diffusion occur in the kidney?
the distal tubule and collecting duct
what are the only drugs that are reabsorbed in passive tubular reabsorption?
un ionised drugs
what kinds of drugs are actively secreted into the proximal tubule?
acidic and basic compounds
what kinds of drugs is active tubular secretion most important in eliminating?
protein bound cationic and anionic drugs
what is the term given for when drugs are reabsorbed from the bile into the circulation?
entero-hepatic circulation
when does entero-hepatic circulation continue until?
until the drug is metabolised in the liver or excreted by the kidneys
