metabolism and excretion of drugs

Question 1

what are the mechanisms the body uses to protect itself

Answer 1

1* Prevent from entering blood or sensitive tissue (eg BBB)
2* Physical removal from the body (urine, bile, sweat, perspiration)
3* Biochemical transformation which aims to removed products faster than the should be removed faster than parent compound .

Question 2

what is biotransformation

Answer 2

this is the conversion of a drug to a form that can easily be excreted

Question 3

what is the aim of drug metabolism

Answer 3

to break down the drug in molecules that can easily be excreted.

Question 4

mechanism of biotransformation

Answer 4

making the drug more polar and thus less lipophilic and there is no absorption

Question 5

enzymes involved in phase 1 reactions

Answer 5

cytochrome p50
short chain dehydrogenases

Question 6

examples of reactions that take place in phase 1 reactions

Answer 6

reactions that aim to modify an existing drug or modifying an existing one
for example
hydrolysis
reduction
oxidation

Question 7

some of the functional groups that are involved in the phase 1 reactions

Answer 7

-OH; -NH2 ; -SH

Question 8

site for phase 1 reactions

Answer 8

liver but can take place in the lungs , small intestine and kidney

Question 9

cellular organelle that has enzymes for phase 1 reactions

Answer 9

enzymes are at the membrane of the smooth endoplasmic reticulum
some in the cytosol
some in the mitochondria

Question 10

toxicity of the intermediates that are produced

Answer 10

some of the intermediates may form adducts with other molecules such as DNA since they are electrophilic.
This may lead to bioactivation.

Question 11

examples of biological molecules that are bioactivated

Answer 11

DNA - negatively charged
Proteins - depends diff proteins with a different charge .

Question 12

examples of drugs that have a tendency of bioactivation

Answer 12

quinone and quinone analogues

Question 13

benefit of phase 1 metabolism

Answer 13

activation of prodrugs ( that is drugs that were taken in in their inactive form)

Question 14

cytochrome p450

Answer 14

an enzyme that is used in phase 1 metabolism

Question 15

cytochrome p450 strains

Answer 15

60 individual enzymes; 18
families

Question 16

factors that lead to the formation of the different strains of cytochrome p450

Answer 16

mutations and polymorphisms

Question 17

characteristics of molecules in phase 2 reactions

Answer 17

1. , larger
2. weak acids so they can possibly ionise while in the SI and they will not be absorbed.
   3.more likely to be bound to a plasma molecule such as albumin.

Question 18

phase 2 reaction

Answer 18

involves addition of a different molecule that is conjugation

Question 19

conjugation of a intermediate metabolite

Answer 19

phase 2 reaction
1.addition of co -factors and co-substrates.
2.addition of glucuronic acid which is the most common this process is known as glucuronidation.

Question 20

acetaminophen metabolism

Answer 20

1.cytochrome p450 that breaks down and there is a hydrolysis reaction that involves addition of a quinone.
2.there is addition of a glutathione in the formation of a conjugate that is taken in through renal clearance.

Question 21

cyp450 enzymes action can be increased and reduced

Answer 21

yes

Question 22

CYP2E1 action and St , Johns Wort

Answer 22

action of st john`s wort plant causes the increase of metabolism in paracetamol increasing the likelihood of toxicity.

Question 23

CYP3A4 enzyme and grapefruit juice

Answer 23

grapefruit inhibits the action of CYP3A4 therefore there is less metabolism of drugs.

Question 24

omeprazole and CYP3A4

Answer 24

may induce that is increase in the metabolic pathway of the drug.

Question 25

polymorphic variation and cyp450

Answer 25

polymorphic variation because of of DNA differences leads to difference in expression of the receptors.

Question 26

what is the mechanism of action for warfarin

Answer 26

Intrinsic and extrinsic converge on common pathway (drug target)

Question 27

excretion of drugs

Answer 27

rate of removal of a drug from the blood in relation to plasma concentration.

Question 28

clearance of a drug formula

Answer 28

rate of drug elimination / the plasma concentration ( ml/min)

Question 29

low clearance

Answer 29

means there is the most circulation most of the drug is not in the plasma

Question 30

what is meant by total clearance

Answer 30

renal hepatic lung

Question 31

clearance in the kidney

Answer 31

function of the 1. glomerular filtration 2.tubular secretion 3.reabsorption(active )

Question 32

factors that influence filtration

Answer 32

drug must be free in the plasma and this depends on the volume of distribution and protein binding, kidney perfusion the kidney must be healthy.

Question 33

clearance of the glomerular filtrate

Answer 33

that is a function of the amount that is being filtered to the rate of filtration.

Question 34

total renal clearance

Answer 34

when there is no secretion and there is no reabsorption

Question 35

measurement of glomerular filtrate

Answer 35

creatine inulin

Question 36

factors that influence the process of filtration

Answer 36

size - large molecules charge - with a charge

Question 37

where does active renal secretion take place

Answer 37

occurs in the proximal tubule

Question 38

characteristics of drugs that are pass through active secretion

Answer 38

1.Weak acid/base; Nucleoside; Pglycoprotein transporters 2.Can clear drugs too large to filter 3.Again depends on blood flow; free drug 4,Saturable becausee they depend on transporters

Question 39

transporters during secretion

Answer 39

transporters for weak acid weak bases transporters p glycoprotein transporters nucleoside transporters

Question 40

purpose of active secretion

Answer 40

there is excretion of particles that were unable to be excreted in the glomerular filtrate.

Question 41

factors that affect the process of drug secretion

Answer 41

flow of blood free drug that is unbound that can easily cross the membrane.

Question 42

what is a term for the transporters of secretion failing to transport the free material

Answer 42

they are saturable

Question 43

example of rapidly secreted drugs

Answer 43

beta lactam antibiotics frusemide ranitidine ribavirin verapamil

Question 44

passive tubular reabsorption

Answer 44

movement of the molecules back to the blood circulation

Question 45

factors that favor passive tubular reabsorption

Answer 45

1.lipid solubility 2. concentration gradient - that is movement from a high conc grad to a low conc grad. 3.dehydration that means there is more reabsorption. 4.urine flow rate -high flow rate reduces gradient and there is limited reabsorption. 5.pH and ion trapping a weak acid is more ionisation less likely to be reabsorbed.

Question 46

urinary alkalization

Answer 46

this is to enhance clearance this is done by making sure there is no ionisation of the weak acids and there is reduced reabsorption for example aspirin.

Question 47

test for a healthy kidney

Answer 47

renal clearance is proportional to GFR

Question 48

measurement of GFR

Answer 48

creatine clearance

Question 49

hepatic clearance factors

Answer 49

1.free drug 2.flow of blood

Question 50

hepatic clearance

Answer 50

the rate of clearance = extraction ratio* blood flow into the liver