pharmacokinetics Flashcards
ways in which drugs enter the body
via oral which will go through the go tract and the liver or intravenously which will be put straight into the blood stream. As a free drug it will then diffuse into the tissue which is the site of drug action
in which 2 formulations do drugs come
tablet or liquid. rate of dissolution changes the rate of reaction therefore you can change the formulation to suit how quickly you need an effect. E.g in a MI then need quick solution and therefore is required to soluble
name the 3 sites of administration
focal-at the site of action e.g eye, skin or inhilation
enteral- oral, sublingual or rectal. All goes into GI tract
parenteral- intravenous, intramuscular and all other routes
why does it take up to 10 hours for the transit time of an oral drug
there is very little absorption of the drug in the stomach but a lot in the small intestine which is where most of it is absorbed.
how will the drug be absorbed in the small intestine passively
as the pH changes going from the stomach into the small intestine the charges of small molecules change and become more or less deprotonated. When they are uncharged they are able to simply cross the GI epithelia and be absorbed into the blood. this is a passive process
how will a drug be absorbed by facilitated diffusion
using a solute carrier transport which carries ions across GI epithelia down electrochemical gradient. Have organic anion transporters and organic cation transporters. some may be transported using secondary active transport
factors affecting drug absorption
GI surface area, drug lipophility, blood flow(greater after meal meaning better uptake), GI motility(slow after meal), pH(if too low may destroy the drug) and first pass
what is first pass
in the liver there are 2 drugs which metabolise drugs reducing their availability called cytochrome p450 and conjugating to. this only happens when the drug is administered orally.
what is oral bioavailability
fraction which defines the dose of drug which has reached circulation unchanged. IV=100% and is used as a reference. the oral route is therefore affected by first pass and how fast gut absorption is
equation by oral availability
oral(reaching circulation)/total drug given by IV. this helps inform which route should be take for prescriptions. is there enough of an effect using oral?
factors affecting the amount of drug entering the tissue or reaching the target site
drug lipophilicity - if more lipophilic then can move freely and also capillary permeability e.g if there are OAT’s or OCT’s. also affected by rate of binding of drug to plasma/tissue proteins because must be free to bind to target site therefore the drug that is bound acts as a resevior and is released when conc of drug is reduced
how to work out therapeutic ratio and what is it?
max tolerated/min effective. The therapeutic index is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity.
what is the therapeutic window
the window between where its minimum effective but the max that can be tolerated where you get unwanted side effect
why do you need to be careful about the therapeutic window
need to be careful because if the drug is fast release because they are soluble then may go over toxic conc and if they are slow release because are tablets then may never reach effective conc
route which the drug takes to the site of action
moves out of plasma into interstitial fluid and then into intracellular space where it can act. however less and less of the due grill move that far
what is vd?
drug distribution volume. the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma. theoretical volume if it went straight where it needed to go
how to work out vd
extrapolate the graph to find t=0 and then divide the total amount of drug dose by the t=0. if lots stays in plasma then will be low vd.
what does a low vd mean?
low penetration into interstitial fluid and tissues
what does high vd mean
lots of penetration into interstitial fluid and tissues
why is vd important
because it changes during pregnancy, in cancer patients, in paediatrics and in geriatrics
how can we control how much drug is absorbed over a period of time
when a large amount of it is deprotonated and charged at the certain pH there may only be a little bit of drug which is able to diffuse into the tissue however to keep reestablishing equilibrium it will keep shifting so actually lot of drug will be absorbed over a long period of time
what state is drug in when its available for elimination
free state. not bound to proteins.
where are drugs eliminated
by the kidney or the liver
where does excretion predominantly occur and where doe smetabolism predominantly occur
excreition= kidney in glomerular filtrate matabolism = liver
