drug metabolism

Question 1

pH equation

Answer 1

-log10[H+]

Question 2

physiological pH

Answer 2

7.4

Question 3

what happens to amino acids at physiological pH?

Answer 3

protonated at the amine group

Question 4

what proteins can the kidney filter out?

Answer 4

xenobiotics

Question 5

xenobiotics definition

Answer 5

proteins found in plants that the kidney can filter out

Question 6

metabolism function

Answer 6

inactive and excrete xenobiotics

go from non polar molecules to polar ones

tag molecules so that the body can recognise them

Question 7

what occurs in phase 1?

Answer 7

introduce or reveal a functional group by hydroxylation, oxidation, reduction or hydrolysis

Question 8

what occurs in phase 2?

Answer 8

conjugate to a polar molecule such as glucuronate, sulfate, glycine and glutathione

allows a point of attack for conjugating systems

Question 9

where does phase 2 take place?

Answer 9

liver primarily

GI, kidney and lungs

Question 10

why are nonpolar drugs not excreted?

Answer 10

able to diffuse across the bilayer of the nephron epithelia, so they become reabsorbed easily

Question 11

problem with phase 1 reactions?

Answer 11

products are often more chemically active and thus are more toxic

Question 12

oxidation reaction definition

Answer 12

adding oxygen which results in a change within the chemical substance

Question 13

reduction reaction definition

Answer 13

removal of oxygen

Question 14

what may the activation of xenobiotics result in?

Answer 14

formation of carcinogens

Question 15

prodrug definition

Answer 15

medication that becomes active once metabolised

Question 16

important enzymes in phase 1

Answer 16

cytochrome P450 and monoamine oxidase

Question 17

explain cytochrome P450 action

Answer 17

aliphatic hydroxylation, replacing CH with CO

oxidises hydrocarbons to form an alcohol and water

mixed function oxidase, will oxidise any tagged molecule

Question 18

explain monoamine oxidase action

Answer 18

oxidise nitrogen on the monoamines to form aldehyde intermediates and ammonia

oxidative deamination

Question 19

phase II general product properties

Answer 19

increased molecular weight

less active than substrates

polar metabolites- water soluble

Question 20

where is alcohol metabolised in the body? + why

Answer 20

liver

has a high concentration of enzymes

Question 21

brief stages of alcohol breakdown

Answer 21

ethanol–> acetaldehyde –> acetic acid and acetyl- CoA

Question 22

phase I in alcohol metabolism

Answer 22

ethanol is oxidised to acetaldehyde using NAD+ and alcohol dehydrogenase

Question 23

how is alcohol metabolised in a fetus + why?

Answer 23

alcohol dehydrogenase is not yet fully developed

alcohol metabolism depends on cytochrome P450

Question 24

phase II in alcohol metabolism

Answer 24

acetaldehyde dehydrogenase catalyses the oxidation of acetaldehyde to acetic acid

Question 25

why is phase II important?

Answer 25

aldehydes are highly unstable compounds that form free radical structures which are highly toxic lead to the damage of neural crest cells and can cause severe birth defects can cause severe liver and kidney disease

Question 26

alcohol side effects

Answer 26

hypoglycaemia, lactic acidosis, hyperuricaemia

Question 27

hypoglycaemia explained

Answer 27

alcohol contains sugars, leading to an increase in insulin secretion, which leads to low blood glucose also impairs gluconeogenesis

Question 28

lactic acidosis explained

Answer 28

ethanol is metabolised using NAD to form NADH high levels of NADH inhibit the glycolysis pathway, to prevent too much glucose being broken down this diverts the pyruvate metabolism towards lactate

Question 29

hyperuricaemia definition

Answer 29

excess uric acid in the blood

Question 30

what does the amount of urate depend upon?

Answer 30

balance between the amount of purines eaten in food, and urate synthesised by the body and the amount of urate excreted in urine or through the GI tract

Question 31

explain alcoholic hyperuricaemia

Answer 31

ethanol increases uric acid by increasing lactic acid production

Question 32

how may alcohol cause paracetamol toxicity?

Answer 32

1. alcohol presence induces transcription of more cytochrome P450 2. more cytochrome P450 will oxidise paracetamol 3. 10% of the products are quinoneimine which is a hot electrophile which can cause cell death and organ failure

Question 33

explain metabolism of paracetamol

Answer 33

1. paracetamol does not undergo phase I, as it already has a polar hydroxyl group 2. tagged with glucuronate or sulfate which is then urinated out 3. 10% is oxidised by CYP2E1 to form an electrophile

Question 34

why is paracetamol overdose dangerous?

Answer 34

large quantity of quinoneimine in the liver will link sulfhydryls, crosslinking proteins resulting in coagulation