Metabolism and Excretion

Question 1

what is the main site of metabolism?

Answer 1

the liver

Question 2

where else in the body are drugs metabolised?

Answer 2

the GI tract, skin, lungs, kidneys and the neurones and the blood

Question 3

what are the two main effects of metabolism?

Answer 3

increases water solubility and reduces pharmacological activity

Question 4

what property does a drug need to have to be excreted through urine?

Answer 4

water soluble

Question 5

why can’t a lipophilic drug be excreted via urine?

Answer 5

the drug will be filtered through the glomerulus but will be passively absorbed back into the blood stream

Question 6

what occurs in phase I metabolism?

Answer 6

functionalization

Question 7

what is functionalization?

Answer 7

when a reactive group is added to a molecule to increase its reactivity

Question 8

what type of reactions can functionalization occur in?

Answer 8

oxidation, reduction and hydrolysis

Question 9

what is conjugation?

Answer 9

a reaction in which the drug or its metabolites are coupled with another molecule

Question 10

how can conjugation produce a polar molecule?

Answer 10

a polar molecule is added at the reactive site on the metabolite to produce a water soluble product

Question 11

how does CYP450 metabolise drugs?

Answer 11

oxidises the drug by adding a molecule of oxygen to the drug to form an OH group

Question 12

where is CYP450 found?

Answer 12

In hepatocytes of the liver

Question 13

what occurs in phase II metabolism?

Answer 13

the polar metabolites that are produced via conjugation are catalysed by specific transferases

Question 14

where are transferases found?

Answer 14

in the ER and cytoplasm of hepatocytes

Question 15

what is different about metabolites from phase I and metabolites from phase II?

Answer 15

phase II metabolites usually have lower pharmacological activity or toxicity

Question 16

what are examples of polar molecules that phase I metabolites can be linked to?

Answer 16

glucoronic acid, glycine, sulphate, acetate, methyl or glutathione

Question 17

what are active drug metabolites?

Answer 17

when the metabolites produced are not less toxic or less pharmacologically active

Question 18

what are some examples of drugs that have active metabolites?

Answer 18

codeine when converted to morphine, imipramine to desipramine, enalapril to enalapriat

Question 19

what drug has toxic metabolites?

Answer 19

paracetamol

Question 20

what is paracetamol conjugated as at normal therapeutic doses?

Answer 20

glucoronide or sulphate

Question 21

how can paracetamol be potentially toxic?

Answer 21

because a small amount is converted to a potentially toxic intermediate in phase I via an oxidation reaction

Question 22

at normal doses, why does the toxic intermediate of paracetamol cause no damage?

Answer 22

because the intermediate quickly reacts with a scavenger molecule called glutathione and further converted to a non-toxic form and excreted via the kidney

Question 23

how does an overdose of paracetamol cause damage to the body?

Answer 23

when high doses of paracetamol are ingested this depletes the levels of glutathione in the body and so the toxic intermediate causes hepatic and renal damage

Question 24

what is the antidote for paracetamol overdose? how does it work?

Answer 24

N-acetyl cysteine (NAC) as it is a precursor to glutathione

Question 25

how is a graph used to determine the toxicity of the drug dosage?

Answer 25

plot the drug concentration against the hours post ingestion and use this to determine what treatment should be given

Question 26

what kind of substances are excreted through urine?

Answer 26

low molecular weight substances

Question 27

what kind of substances are excreted through bile?

Answer 27

high molecular weight substances that are often conjugates

Question 28

what kind of substances is excreted through faeces?

Answer 28

compounds that are excreted through bile and materials that have not been absorbed by the gut

Question 29

what kind of substances are excreted through sweat?

Answer 29

water-soluble drug products

Question 30

what kind of substances are excreted through breath and saliva?

Answer 30

breath excretes volatile substances such as gases and solvents and saliva I slow molecular weight substances

Question 31

what kind of substances are excreted through breast milk?

Answer 31

lipid soluble and water-soluble products

Question 32

what is the the relationship between rate of elimination and drug concentration?

Answer 32

the higher the concentration, the higher the rate of elimination, in most cases

Question 33

what is first order kinetics?

Answer 33

rate of elimination is proportional to drug concentration

Question 34

what is the half life of a drug?

Answer 34

the time taken to reduce the plasma concentration of the drug by half

Question 35

what is the equation of half life and what does it tell us?

Answer 35

half life=0.693xVd/clearance, shows that the higher the Vd, the longer the half life will be

Question 36

what is clearance?

Answer 36

volume of blood that is cleared of the drug per unit of time

Question 37

what is zero order kinetics?

Answer 37

elimination is independent of drug concentration as the rate is unaffected by the increases of drug concentration

Question 38

what kind of drugs show zero order kinetics?

Answer 38

alcohol, phenytoin, warfarin at high doses, aspirin

Question 39

what causes a drug to show zero order kinetics?

Answer 39

when the enzyme system that is responsible for metabolism is fully saturated