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Flashcards in Drug Metabolism Deck (28):
0

What is the difference between pharmacodynamics and pharmacokinetics?

Pharmacodynamics is how drugs work
Pharmacokinetics is the fate of drugs in the body

1

What happens during phase I of drug metabolism?

A reactive group is exposed on the parent molecule or a reactive group is added

2

What are the common types of chemical reaction in phase I?

Hydrolysis, oxidation, reduction

3

What does phase I require?

A complex enzyme system - cytochrome P450 (CYP)
NADPH

4

What happens in phase II of drug metabolism?

The reactive intermediate is conjugated with a polar molecule to form a water-soluble complex

5

Name three common conjugates

Glucuronic acid
Glutathione
Sulphate ions

6

What does phase II require?

Enzymes
UDPGA (a high energy cofactor)

7

Why do drugs need to be made water soluble?

Most are lipid soluble, so would be reabsorbed from the urine in the renal tubules.

8

What are pro drugs?

Drugs which are metabolised in the body to their active form

9

List some of the main sites of drug metabolism

Liver
Lungs
Kidneys
Plasma
GI tract

10

Why is there variation in drug metabolism within the population?

People have different levels of enzymes and may even be lacking in some enzymes.

11

Name three well known enzyme inducors

Nicotine, ethanol, barbiturates

12

When would a drug go straight into phase II of drug metabolism?

When it already has a reactive group

13

What do enzyme inducers do?

Increase the metabolism of other drugs

14

What is the first pass effect?

Substances absorbed from the lumen of the ileum drain into the hepatic portal vein which goes straight to the liver - the site of metabolism of drugs.
Drug is extensively metabolised during its first pass so a higher dose is required.

15

What is alcohol converted to in the body and what enzymes are involved?

Alcohol oxidised to acetaldehyde - alcohol dehydrogenase

Acetaldehyde oxidised to acetate - acetaldehyde dehydrogenase

Acetate to acetyl CoA

16

Which product of alcohol metabolism is extremely toxic to cells and how is its concentration kept to a minimum?

Acetaldehyde
Acetaldehyde dehydrogenase has a very low Km so removes it as soon as it is formed.

17

How does prolonged alcohol consumption affect the liver?

Acetaldehyde builds up - damage

Decreased NAD+/NADH ratio
Increased acetyl CoA - affects liver metabolism

18

What is NAD+ used for?

Beta oxidation of fatty acids
Conversion of lactate to pyruvate
Metabolism of glycerol

19

How can excessive alcohol consumption lead to lactic acidosis?

Less NAD+
Lactate cannot be converted to pyruvate
Lactate accumulates in the blood

20

How can excessive alcohol consumption lead to gout?

Increased lactate on blood
Decreases kidneys' ability to excrete uric acid
Crystals of urate accumulate in tissues -> gout

21

How can excessive alcohol consumption cause hypoglycaemia?

Low NAD+
Liver cannot use lactate or glycerol
Gluconeogenesis cannot be activated

22

What are the effects of high amounts of acetyl CoA in the liver?

Acetyl CoA is converted to fatty acids and ketone bodies - no NAD+ so cannot be oxidised

Fatty acids are converted to triacylglycerols which cannot be transported away from the liver due to a lack of lipoproteins. They accumulate in the liver - fatty liver

Ketone bodies could cause ketoacidosis.

23

What enzymes are used to test for liver function and why?

Transaminases and gamma glutyl transpeptidase
Damaged liver cells have leaky plasma membranes - enzymes lost into the blood

24

List some effects of a damaged liver

Hyperbilirubinaemia -> jaundice
Increased clotting time
Hyperammonaemia
Oedema due to low serum albumin
Fatty liver

25

What drug is used to treat alcohol dependence and what does it do?

Disulphiram
Inhibits acetaldehyde dehydrogenase causing symptoms of a hangover when alcohol is consumed

26

What happens when someone takes an overdose of paracetamol?

Normally metabolised by phase II pathway. This becomes saturated so phase I instead, producing the toxic metabolite NAPQI.
NAPQI is then metabolised in phase II, conjugation with glutathione. Depletes cells of glutathione, an important antioxidant.
Destruction of liver cells and leads to liver failure.

27

What can be given to a patient with an overdose of paracetamol?

N-acetylcysteine (an anti-oxidant)