pharmacokinetics

Question 1

ways in which drugs enter the body

Answer 1

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

Question 2

in which 2 formulations do drugs come

Answer 2

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

Question 3

name the 3 sites of administration

Answer 3

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

Question 4

why does it take up to 10 hours for the transit time of an oral drug

Answer 4

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.

Question 5

how will the drug be absorbed in the small intestine passively

Answer 5

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

Question 6

how will a drug be absorbed by facilitated diffusion

Answer 6

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

Question 7

factors affecting drug absorption

Answer 7

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

Question 8

what is first pass

Answer 8

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.

Question 9

what is oral bioavailability

Answer 9

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

Question 10

equation by oral availability

Answer 10

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?

Question 11

factors affecting the amount of drug entering the tissue or reaching the target site

Answer 11

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

Question 12

how to work out therapeutic ratio and what is it?

Answer 12

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.

Question 13

what is the therapeutic window

Answer 13

the window between where its minimum effective but the max that can be tolerated where you get unwanted side effect

Question 14

why do you need to be careful about the therapeutic window

Answer 14

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

Question 15

route which the drug takes to the site of action

Answer 15

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

Question 16

what is vd?

Answer 16

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

Question 17

how to work out vd

Answer 17

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.

Question 18

what does a low vd mean?

Answer 18

low penetration into interstitial fluid and tissues

Question 19

what does high vd mean

Answer 19

lots of penetration into interstitial fluid and tissues

Question 20

why is vd important

Answer 20

because it changes during pregnancy, in cancer patients, in paediatrics and in geriatrics

Question 21

how can we control how much drug is absorbed over a period of time

Answer 21

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

Question 22

what state is drug in when its available for elimination

Answer 22

free state. not bound to proteins.

Question 23

where are drugs eliminated

Answer 23

by the kidney or the liver

Question 24

where does excretion predominantly occur and where doe smetabolism predominantly occur

Answer 24

excreition= kidney in glomerular filtrate 
matabolism = liver

Question 25

explain and describe the phases of metabolism in the liver

Answer 25

phase 1 - drug may be activated during first pass if its oral, deactivated or unchanged by redox reactions. done by cytochrome enzymes. products have increased ionic charge
phase 2 - conjugates are added by enzymes. these are hydrophilic molecules so that can enter circulation and enter kidney. some drugs enter phase 2 directly

Question 26

how can cytochrome enzymes be affected and what does this in turn affect

Answer 26

they can be induced or inactivated by other drugs which means you need to be very careful when prescribing multiple drugs at once

Question 27

an example of drug interaction

Answer 27

cimetidine inhibits chytchrome and therefore decreases metabolism of warfarin increasing its conc= overdose

Question 28

how can a drug be activated during metabolism in the liver

Answer 28

coding can be activated to morphine in the liver by a certain mutant cytochrome eznyme

Question 29

discuss phase 2 metabolic enzymes

Answer 29

they are cytosolic and are more rapid than phase 1 drugs. they enhance renal elimination by making them hydrophilic

Question 30

what is first order kinetics

Answer 30

rate of elimination is proportional the drug level therefore it has a half life which can be seen when drawn as graph on logarithmic scale shows straight line. fairly safe because self regulating

Question 31

what is zero order kinetics

Answer 31

where rate of elimination is constant and therefore need to be much more careful. this is because enzymes are working at full max. example is alcohol. after 3 drinks tipped over edge, no more enzymes available and has much larger effect than first drink. makes straight line graph with linear scale

Question 32

when do drug interactions matter if zero order

Answer 32

with low therapeutic ratio- may cause side effects very quickly and suddenly. fly out of window and may quickly exceed vmax of enzyme and cause overdose

Question 33

how to measure rate of drug clearance

Answer 33

elimination rate/drug conc in plasma. this is (mass/time)/(mass/volume) which is measured in ml/min. volume of blood that is completely clear of drug per unit of time

Question 34

how to work out half life of drug

Answer 34

0.693xvd/clearence rate. this makes sense as higher vd means more dissolved in tissues and therefore a longer half life

Question 35

why is half life clinically relevant

Answer 35

needed to decide dosages

Question 36

how many half lives does it take to reach steady state and what is the problem with this

Answer 36

5 half lives and the problem with this is that this may take far too long before patient reaches steady state

Question 37

how to overcome the fact that you need 5 half lives to reach steady state and if these half lives are long

Answer 37

prescribe a bolus loading dose which is a high dose to get them under control quickly. after this maintenance doses are given to maintain therapeutic window.

Question 38

how do drugs enter the kidney

Answer 38

most free dugs enter via glomerular filtrate and some will be secreted into the proximal tubule by transporters.

Question 39

what is the problem with lipophilic drugs in the kidney

Answer 39

if they are lipophilic then they may be reabsorbed into the blood which means they take much longer to be eliminated. this is called passive reabsorption

Question 40

what is passive reabsorption of drugs in the kidney affected by

Answer 40

dependant on pH. pk of drug is pH at which half is ionised and excreted and half is non-ionised and not excreted because exits kidney across lipid membranes

Question 41

how weak acids affect renal excretion of drugs

Answer 41

acid increases absorption of drugs because will pass into circulation. more alkaline therefore decreases reabsorption. this means pH of urine does effect amount of excreted drug

Question 42

how weak bases will affect renal excretion of drugs

Answer 42

acid will decrease the absorption because combines with base so can’t move through membrane but more alkaline means base stays unprotonated and moves through lipid membrane.

Question 43

example of how aspirin poisoning can be controlled by pH

Answer 43

is a weak acid and usually absorbed but if overdose need to get rid of it much more quickly so bicarbonate is given to take of H+ charge forcing it to leave body

Question 44

problem with prescribing medication for those with renal disease

Answer 44

if drug is excreted by kidneys the half life will be linger if you have renal disease therefore lower maintenance doses needed but maybe also a higher bolus dose needed. it also means protein binding is altered