Lecture 4 - Metabolism And excretion

Question 1

What happens to most drugs in the body?

Answer 1

Bio transformation

Question 2

What are the sites of metabolism in the body?

Answer 2

Liver (major site) Kidney Lungs Skin Intestine

Question 3

What is the major site of metabolism in the body?

Answer 3

Liver

Question 4

What is the effect of first pass metabolism on bioavailability?

Answer 4

Reduces?

Question 5

What is the aim of the process of metabolism?

Answer 5

To change a drug into more water soluble molecules

Question 6

What is the effect of metabolism of absorption?

Answer 6

Lowers

Question 7

What is the effect of metabolism on excretion in urine?

Answer 7

Aids excretion

Question 8

What is the effect of metabolism on polarity ?

Answer 8

Increases

Question 9

What is the term given to drugs activated by metabolism?

Answer 9

Pro drugs

Question 10

what are pro drugs?

Answer 10

Drugs activated by metabolism

Question 11

In what form are pro drugs administered?

Answer 11

Inactive

Question 12

Metabolism can produce more active metabolites which contribute to the action of drug. When can this occur?

Answer 12

when there is more than one step in breakdown e.g. benzo

Question 13

What does metabolism often consist of?

Answer 13

Phase I and phase II

Question 14

What is phase I metabolism?

Answer 14

A group of reactions which make an intermediate more active, increasing the ease of making something more water soluble for excretion

Question 15

What is phase II metabolism?

Answer 15

Makes drug more water soluble

Question 16

What Catalyses phase I reactions?

Answer 16

Enzymes

Question 17

What is the most important enzyme that catalyses phase I reactions?

Answer 17

Microtonal mixed function oxidase

Question 18

Where does microtonal mixed function oxidase reside?

Answer 18

Smooth endoplasmic reticulum of the liver

Question 19

What does microtonal mixed function oxidase require to catalyse phase I reactions?

Answer 19

NADPH and molecular oxygen

Question 20

What is the most important microtonal mixed function oxidase?

Answer 20

Cytochrome P450

Question 21

What type of protein is cytochrome p450?

Answer 21

Haem

Question 22

What are human CYP isoforms?

Answer 22

Substrates for inhibition

Question 23

What is the most abundant human CYP isoforms?

Answer 23

3A4

Question 24

Where do phase II reaction mainly occur?

Answer 24

Liver

Question 25

What are phase II reactions?

Answer 25

Conjugation reactions which occur at polar groups

Question 26

Are conjugated products very water soluble?

Answer 26

Yes

Question 27

How are conjugated products excreted?

Answer 27

Water and bile

Question 28

what is the main phase II reaction?

Answer 28

Glucuronidation

Question 29

What is Glucuronidation?

Answer 29

Commonest conjugation reaction Endogenous reactant, UDP glucoronic six attaches to N, O or S atoms

Question 30

Effect of Paracetamol OD?

Answer 30

Liver damage Necrosis

Question 31

What are phase II reactions for paracetamol?

Answer 31

Sulphate conjugation, and glucuronide conjugation

Question 32

Phase I reactions for paracetamol

Answer 32

Cytochrome P450

Question 33

What percentage of paracetamol occurs by conjugation?

Answer 33

90%

Question 34

How Does the remainder of paracetamol metabolism occur?

Answer 34

Remainder metabolised by oxidation to produce toxic metabolite

Question 35

What isoform is crucial in paracetamol metabolism?

Answer 35

CYP2E1 isoform

Question 36

What happens to conjugation in response to overdosing?

Answer 36

Conjugation steps are saturated and cofactors are depleted Larger % of toxic metabolite produced Usually enough to deplete all available glutathione

Question 37

Where does excretion of drugs mainly occur?

Answer 37

Kidney

Question 38

What if clearance a measure of?

Answer 38

Elimination

Question 39

What is the rate of elimination dependent on?

Answer 39

Metabolism and Excretion

Question 40

How do you calculate clearance?

Answer 40

Rate of elimination/ plasma concentration

Question 41

How can renal clearance, as a measure of elongation be defined?

Answer 41

The volume of plasma cleared of drug by the kidney per unit time (ml/min)

Question 42

If a drug has a clearance of 10mp/non, how long will it take to clear 1 litre of plasma?

Answer 42

100 Mins

Question 43

What factors influence clearance ?

Answer 43

Filtration, reabsorption, active secretion and ion trapping

Question 44

What renal factors influence clearance?

Answer 44

Filtration, Reabsorption, active secretion

Question 45

Effect of reabsorption on clearance?

Answer 45

Reduces clearance

Question 46

Effect of active secretion on clearance?

Answer 46

Increases clearance

Question 47

How does ion trapping influence clearance?

Answer 47

Urinary PH fan influence clearance Alkalinity increases clearance

Question 48

What is clearance of warfarin?

Answer 48

3ml/min

Question 49

What is clearance of propranolol ?

Answer 49

840 ml/min

Question 50

What is clearance of diazepam?

Answer 50

27 ml/min

Question 51

What is clearance of Lidocaine?

Answer 51

640 ml/min

Question 52

What is an inhibitor of cytochrome p450?

Answer 52

Ketoconazole