Drug Metabolism and Elimination

Question 1

Which type of reactions take place in phase I metabolism?

Answer 1

Oxidation, reduction, hydrolysis

Question 2

What is achieved by phase I metabolism?

Answer 2

Introduction/revelation of functional group

More reactive products

Question 3

What type of reactions take place in phase II metabolism?

Answer 3

Synthetic, conjugative reactions

Question 4

What results from phase II metabolism?

Answer 4

Hydrophilic, inactive compounds generated

Question 5

Which type of drugs are easily excreted by the kidneys in urine?

Answer 5

Hydrophillic

Question 6

What happens to hydrophobic drugs in the liver?

Answer 6

Converted to hydrophillic metabolite

Conjugated and excreted in bile

Question 7

What happens to drugs excreted in bile?

Answer 7

Pass to intestines and out in faeces

De-conjugated and taken back up by liver

Question 8

Describe the CYP450 enzymes

Answer 8

Microsomal enzymes
Composed of CYP450, NAPDH-CYP450 reductase and lipid
Require NADPH and oxygen

Question 9

Describe the reaction of aspirin to salicyclic acid

Answer 9

Spontaneous, non-enzymatic conversion when in the plasma - rapid process (phase I metabolism)

Question 10

How is salicylic acid metabolised?

Answer 10

Oxidised (phase I)

Glucoronidation and glycination (phase II)

Question 11

Which molecules are responsible for transfer of drugs from plasma to bile?

Answer 11

Organic cation transporters (OCTs)
Organic anion transporters (OATs)
P-glycoproteins (P-GP)

Question 12

Why may oral antibiotics make the contraceptive pill less effective?

Answer 12

They disrupt the microbiota of the gut, reducing enterohepatic recirculation of oestrogen which is required to keep oestrogen levels high and prevent ovulation

Question 13

Describe enterohepatic recirculation?

Answer 13

Drug in blood is conjugated in liver and excreted into the intestines in bile
Drug is then reabsorbed into the blood from the intestine and enters the liver again to be conjugated and excreted in bile again

Question 14

When are lipophilic drugs not filtered in the glomerulus?

Answer 14

When they are bound to albumin

Question 15

Which molecules are responsible for tubular secretion of drugs in the kidney?

Answer 15

OATs and OCTs

Question 16

Describe the diffusion of different types of drugs in the renal tubule

Answer 16

Lipophillic drugs are mostly reabsorbed so poorly excreted
Polar drugs remain in the lumen so are more readily excreted
Urinary pH can affect this

Question 17

How does pH of urine affect drug excretion?

Answer 17

Weak acids are more rapidly excreted if urine is alkaline

Weak bases are more rapidly excreted if urine is acidic

Question 18

Why can bicarbonate be used in aspirin overdose?

Answer 18

Urine becomes more alkaline resulting in drugs that are weak acids to become more ionised meaning they cannot be reabsorbed and therefore are more rapidly excreted

Question 19

Give an example of a drug which exhibits 0 order kinetics

Answer 19

Alcohol - 1 unit per hour

Alcohol dehydrogenase becomes saturated

Question 20

What is zero order kinetics?

Answer 20

Rate of metabolism is constant

Rate doesn’t vary with amount of drug present

Question 21

What is first order kinetics?

Answer 21

Constant fraction of drug metabolised per unit time

Increases proportionately to drug (more drug, faster metabolism)

Question 22

What is clearance?

Answer 22

The volume of plasma cleared of the drug per hour

Question 23

What is the volume of distribution?

Answer 23

The total amount of drug in the body / blood plasma concentration of drug

Question 24

How do you calculate half life?

Answer 24

Ln2xVd/CL

Question 25

How does Vd affect half life?

Answer 25

Higher Vd, higher half life

Question 26

How does CL affect half life?

Answer 26

Higher clearance, lower half life