Drug elimination 1 (L6)

Question 1

what is ADME?

Answer 1

absorption
distribution
metabolism
excretion

Question 2

what is first pass metabolism?

Answer 2

the concentration of a drug is greatly reduced before it reaches the systemic circulation

Question 3

what is enterohepatic recirculation (HER)?

Answer 3

drugs that are eliminated in the bile can be reabsorbed in the GI tract

secreted into bile which is then stored in the gall bladder and released into the duodenum

allows a gradual decrease - only a small amount gets recirculated
• increases half-life

Question 4

process of enterohepatic recirculation (HER)?

Answer 4

1) drug given orally
2) moves through the gut and absorbed into blood
3) transported to liver
4) transferred to gall bladder in bile
5) secreted into small intestine
6) back to beginning

Question 5

factors that affect distribution?

Answer 5

ability to cross a cell membrane

blood perfusion of the tissue or organ

plasma protein binding ability

Question 6

how are drugs distributed to the tissues?

Answer 6

through slit junctions - fairly big gaps in between cells

Question 7

what do slit junctions do?

Answer 7

act as a sieve

allows drug to get into the interstitium

drug then gets into active tissue cells either by simple or active transport

Question 8

what is the plasma compartment?

Answer 8

is the drug being in the blood at that time

Question 9

what is plasma and how are drugs affected by it?

Answer 9

plasma is an aqueous environment and the drug will either be happy or unhappy in that environment depending on whether it is hydrophilic or lipophilic

Question 10

what happens if a drug has a high molecular weight?

Answer 10

it will get bound to plasma proteins really well meaning it will sty in the the blood stream and not be distributed well

Question 11

what happens to unbound drugs?

Answer 11

only unbound drugs can leave the blood stream and get into the tissues

Question 12

2 examples of plasma proteins that are important in pharmacokinetics

Answer 12

AAG - alpha1 acid glycoprotein

HSA - human serum albumin

Question 13

what is AAG?

Answer 13

alpha1 acid glycoprotein
• it is an acute phase protein
• a natural response to inflammation and stress
also gets rid of drugs

person with high amounts of AAG may need a higher dosage to compensate for the amount of plasma binding that occurs

Question 14

what is HSA?

Answer 14

human serum albumin
• binds acidic drugs

when a person is malnourished, they don’t have free amino acids to build anabolic compounds so one of the first things lost is HSA - energy go into building more important things

Question 15

what happens if you have little HSA?

Answer 15

a person with less HSA has less free drug bound so it is distributed more effectively

would need a lower dose

albumin levels are often measured before drug is administered to make sure malnourished people don’t overdose

Question 16

what is volume of distribution?

Answer 16

a volume that would contain all of the drug at the concentration it would be seen in the blood

= total amount of drug administered (dose) / plasma drug concentration

the higher the Vd, the better the drug is distributed

Question 17

stages of drug metabolism

Answer 17

phase I - occurs in the liver and mainly mediated by CYPs

phase II - mediated by bigger enzymes such as UGTs and are anabolic (add molecules onto a drug)

Question 18

goal of drug metabolism

Answer 18

the goal of these processes is to make a drug more water soluble so its easier to excrete

Question 19

what are prodrugs?

Answer 19

when metabolism activates a drug

they undergo phase I and then the drug becomes active

they are made more useful instead of more excretable

Question 20

mechanisms of elimination

Answer 20

volatile gases - exhaled amor

water soluble - filtered out in kidney –> urine

mass transport in gut - faeces

secretion into glands - breast milk and sweat

Question 21

what is clearance (CL)?

Answer 21

the volume of plasma (or blood) cleared of the compound per unit of time

= sum of all organ CL processes

= IV dose / IV AUC
= (oral dose x F) / oral AUC

Question 22

what is the elimination rate constant (Kel)?

Answer 22

the fraction of drug in the body that is removed per unit of time

is a gradient
change in y over x

Question 23

what does half-life tell us?

Answer 23

how long a drug lasts in the body

time taken for plasma concentration to reduce by half

t(1/2) = ln2 / Kel

Question 24

what does fenestrated mean?

Answer 24

contained windows or perforated

Question 25

what is enterohepatic circulation?

Answer 25

cycling of drug between gut and liver

Question 26

what is partioning?

Answer 26

used to describe the movement of unbound drug from the plasma into tissues