Week 4

Question 1

What is the collective name for metabolism and excretion of drugs?

Answer 1

Elimination

Question 2

What is the main site of drug metabolism in the body?

Answer 2

Liver

Question 3

Name some areas of the body that have metabolic activity.

Answer 3

Liver
Gastrointestinal tract
Skin
Lungs
Kidneys
Neurones
Blood

Question 4

What are the 2 main effects of metabolism on drugs?

Answer 4

Increased water solubility

Reduced pharmacological activity

Question 5

What is the purpose of increasing water solubilityof a drug?

Answer 5

Enables urinary excretion

Question 6

What must happen to a drug for it to be excreted from the body?

Answer 6

Its lipid solubility must decrease and its water solubility must increase

Question 7

Why will a drug which is lipid soluble not be excreted?

Answer 7

It will move by simple diffusion from the renal tubule of the nephron of the kidney to the peritubular capillaries surrounding the kidney and reach the heart via the circulation. It will continue to re-enter the circulation.

Question 8

What is the main property of a drug required for it to be absorbed and distributed around the body?

Answer 8

Must be lipid soluble

Question 9

What is the purpose of Phase 1 metabolism?

Answer 9

Functionalizing.

Question 10

How is a drug caused to become active in phase 1 metabolism?

Answer 10

A chemically reactive, polar molecule is added to the drug, usually via an oxidation reaction

Question 11

What type of reaction is used to make drugs chemically active in phase 1 metabolism?

Answer 11

Usually oxidation reaction

Question 12

What enzymes are used in phase 1 of drug metabolism?

Answer 12

CYP450

Question 13

What are the overall effects of phase 1 of drug metabolism?

Answer 13

Used to reduce toxicity and pharmacological effects of a drug

Question 14

Where does phase 1 of drug metabolism occur?

Answer 14

Liver

Question 15

What is the overall purpose of phase 2 of drug metabolism?

Answer 15

Forming a water soluble drug from a chemically active drug.

Question 16

Where does phase 2 of drug metabolism occur?

Answer 16

In the liver

Question 17

What is the overall process which occurs during phase 2 of drug metabolism?

Answer 17

Conjugation

Question 18

What chemically happens during phase 2 of drug metabolism?

Answer 18

A polar reactive molecule is attached to the drug to result in a water soluble product

Question 19

What are xenobiotic compounds?

Answer 19

Compounds which are foreign to the body but can be found in the biosphere.

Question 20

What type of enzymes have the ability to break down Xenobiotics?

Answer 20

CYP450

Question 21

How can Xenobiotics enter the body?

Answer 21

Frequently enter via the food.

Question 22

What are CYP450 enzymes?

Answer 22

A large number of relative oxidative enzymes which are responsible for the metabolism of thousands of endogenous and exogenous drugs

Question 23

Where are P450 enzymes mainly found?

Answer 23

In the membranes of the small endoplasmic reituclum and mitochondria of hepatocytes

Question 24

What are hepatocytes?

Answer 24

A cell of the main parenchymal tissue of the liver.

Question 25

How do P450 enzymes oxidise drugs?

Answer 25

They add an oxygen atom to form a hydroxyl group on the drug which can then be reacted in phase 2 of metabolism.

Question 26

What type of enzymes metabolise phase 2 of drug metabolism?

Answer 26

Specific transferase enzymes

Question 27

Where are the transferase enzymes used for phase 2 of drug metabolism found?

Answer 27

Bound to the endoplasmic reticulum or free in the cytoplasm of hepatocytes

Question 28

What is the overall objective of phase 2 of drug metabolism?

Answer 28

To reduce the toxicity and pharmaceutical effects of a drug.

Question 29

What are endogenous molecules?

Answer 29

Molecules which originate inside the body

Question 30

What are exogenous molecules

Answer 30

Molecules which originate outside the body

Question 31

Outline the negative effects that can occur due to metabolism of codeine.

Answer 31

A small proportion of codeine can be metabolised into morphine which is more pharmaceutically active than codeine

Question 32

What is an analgesic?

Answer 32

A drug used to relieve pain

Question 33

What is meant by the term 'potency'?

Answer 33

The ability of a drug to cause a pharmaceutical effect.

Question 34

Which isomer of warfarin is the most potent?

Answer 34

S isomer

Question 35

What are the 2 isomers of warfarin?

Answer 35

S and R

Question 36

What are the effects of having too much CYP2D6 on metabolism of codeine?

Answer 36

Too much - rapid metabolism of codeine to morphine. Can reach toxic levels of morphine in the body. Too little - insufficient metabolism of codeine to morphine. Anagelsic effects or morphine not felt.

Question 37

What enzyme is used to metabolise codeine into morphine?

Answer 37

CYP2D6

Question 38

In normal therapeutic doses, what is Paracetamol conjugated into?

Answer 38

Glucoronide and Sulphate

Question 39

What is the toxic product that can be formed in phase 1 metabolism of paracetamol?

Answer 39

NAPQI

Question 40

In what phase of metabolism can paracetamol be metabolised into a toxic intermediate?

Answer 40

Phase 1

Question 41

What reaction type causes paracetamol to form a toxic NAPQI intermediate during metabolism?

Answer 41

Oxidation using P450 enzymes

Question 42

Why are the toxic effects of metabolism of paracetamol into NAPQI often not felt by the body?

Answer 42

NAPQI quickly reacts with Glutathione and is further converted to non-toxic conjugates which are excreted via the kidney.

Question 43

What happens if Glutathione levels are low in the body and alot of paracetamol has been converted to NAPQI in phase 1 of metabolism?

Answer 43

The toxic NAPQI will build up in the body and cause severe damage to the kidney which can lead to liver failure.

Question 44

What happens when someone overdoses on paracetamol?

Answer 44

Glutathione levels are rapidly depleted and so toxic levels of NAPQI metabolite cause hepatic and renal damage which can cause death by liver failure.

Question 45

What antidote is used for paracetamol overdose?

Answer 45

N-acetylene cysteine

Question 46

How does N-acetylene cysteine acts as an antidote for paracetamol overdose?

Answer 46

Absorbs NAPQI and therefore reduces its toxic effects in the body

Question 47

What is used to determine when an individual should be given an antidote to a drug?

Answer 47

A treatment nomogram

Question 48

What does a treatment nomogram show?

Answer 48

The concentration of a drug in the body against time and at what concenetration it will move out of the therapeutic range.

Question 49

Outline the routes of drug excretion.

Answer 49

``` Urine Bile Faeces Sweat Breath Saliva Milk Hair ```

Question 50

What type of drugs are excreted via urine?

Answer 50

Drugs with a low molecular weight

Question 51

What type of drugs are excreted via bile?

Answer 51

Larger, high molecular weight substances which are often conjugated.

Question 52

What type of drugs are excreted via faeces?

Answer 52

Compounds excreted through bile and materials which have not been absorbed by the gut.

Question 53

What type of drugs are excreted via sweat?

Answer 53

Water soluble drug products

Question 54

What is 'the gut'?

Answer 54

The full digestive tract

Question 55

What type of drugs are excreted via breath?

Answer 55

Volatile substances

Question 56

What type of drugs are excreted via saliva?

Answer 56

Low molecular weight compounds

Question 57

What type of drugs are excreted via lactation (milk)?

Answer 57

Lipid and water soluble products

Question 58

What are the negatives of drug elimination via the hair?

Answer 58

Very slow

Question 59

What is rate of elimination of a drug proportional to in a first orderreaction?

Answer 59

Concentration of drug in the body

Question 60

How does an increased concentration of drug in the body affect rate of elimination in a first order reaction?

Answer 60

Increased concentration= increased rate

Question 61

Outline the shape of a first order kinetics graph of drug concentration against time.

Answer 61

(

Question 62

What is a first order reaction in terms of drug elimination?

Answer 62

Rate of elimination is directly proportional to concentration of drug.

Question 63

Define 'half life' of a drug.

Answer 63

The time taken for the concentration of a drug in the plasma to decrease by half its initial concentration

Question 64

What is the calculation for determining half life of a drug?

Answer 64

(0.693 x volume of distribution)/ clearance

Question 65

What is 'clearance' of drug?

Answer 65

The volume of blood cleared of drug per unit of time

Question 66

What is a zero order reaction in terms of drug elimination?

Answer 66

Elimination of drug is independent of the concentration of drug in the body.

Question 67

Give examples of drugs which have a zero order reaction.

Answer 67

Alcohol, phenytoin, warfarin, aspirin

Question 68

What is the approximate elimination rate of alcohol from the body?

Answer 68

10ml per hour

Question 69

What causes zero order elimination of drugs from the body?

Answer 69

When all enzymes become saturated, zero order reactions occur.

Question 70

Draw the shape of a zero order reaction graph.

Answer 70

\

Question 71

What enzyme enables to conversion of codeine to morphine?

Answer 71

CYP2D6

Question 72

Where does drug metabolism mainly occur?

Answer 72

Liver

Question 73

Which enzymes are involved with Phase 1 metabolism and where are they located?

Answer 73

CYP450 - found in the hepatocytes of the smooth endoplasmic reticulum and mitochondria.

Question 74

What factors can affect metabolism?

Answer 74

``` Age Muscle mass Gende Genetics Body size Physical activity Hormonal balance Environmental factors Diet Drugs ```

Question 75

Which enzyme converts codeine to morphine?

Answer 75

CYP2D6

Question 76

How is paracetamol metabolised at normal doses?

Answer 76

It is conjugated by glucoronide or sulphate via phase 2 metabolism.

Question 77

What % of drugs are first order?

Answer 77

95%

Question 78

Name some drugs which are zero order.

Answer 78

Alcohol, ethanol, phenytoin, salicylates, cisplatin, fluoxetine, omeprazole