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Gastrointestinal pathophysiology > Drugs and the liver > Flashcards

Drugs and the liver Flashcards

1
Q

What is the definition of metabolism?

A

All chemical reactions involved in maintaining the living state of the cells and the organism

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2
Q

What is intrinsic clearance?

A

Theoretical unrestricted maximum clearance of unbound drug by an eliminating organ, in absence of blood flow or plasma protein binding limitations

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3
Q

What is conjugation?

A

Addition of chemical groups to drugs during metabolism

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4
Q

What is hydrolysis?

A

The chemical breakdown of a compound due to reaction with water

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5
Q

What is reduction?

A

The loss of oxygen (gain of electrons) within a chemical reaction

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6
Q

What is oxidation?

A

The gain of oxygen (loss of electrons) within a chemical reaction

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7
Q

Which nutrients are metabolised by the liver?

A

Carbohydrates
Protein
Lipids

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8
Q

Which proteins are synthesised by the liver?

A
  1. Albumin
  2. Coagulation factors (vit K)
  3. Complement factors
  4. Haptoglobin
  5. Ceruloplasmin
  6. Transferrin
  7. Protease inhibitors
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9
Q

Which molecules are stored in the liver?

A
  1. Iron
  2. Copper
  3. Vitamins A, D and B12
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10
Q

What does the liver secrete?

A

Bile salts

Bilirubin

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11
Q

The sinusoids contain 2 regions, what are they?

A

Perivenal region (low O2 conc) - glucoronidation occurs here

Periportal region (high O2 conc) - Ox phos and gluconeogenesis occur here

  • This creates an oxygen gradient within the sinusoid
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12
Q

What are the 2 ways that drugs enter into the hepatocyte?

A
  1. Via the hepatic artery as circulating drugs

2. Via the hepatic portal vein as absorbed drugs

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13
Q

How are the metabolites excreted from the hepatocyte?

A
  1. Hepatic vein (to undergo excretion via the kidney)

2. Bile salts

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14
Q

What does hepatic clearance of drugs depend on?

A
  1. Liver blood flow
  2. Intrinsic clearance
  3. Protein binding
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15
Q

What is the extraction ratio?

A

A way to characterise your drugs

- The ratio of hepatic clearance of a drug:flow of hepatic blood

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16
Q

There are 3 classes of extraction ratio, what are they?

A
  1. High extraction ratio
  2. Low extraction ratio
  3. Intermediate extraction ratio
17
Q

High extraction ratio drugs are rapidly cleared from the blood by the liver, true or false?

18
Q

For high extraction ratio drugs, what is clearance dependent on?

A

Primarily dependent on hepatic blood flow

19
Q

Examples of high extraction ratio drugs

A
  1. Verapamil
  2. Morphine
  3. Propanolol
20
Q

What is clearance of low extraction ratio drugs dependent on?

A
  • It is dependent on the intrinsic metabolising capacity of the liver and by the free drug fraction
21
Q

Examples of low extraction ratio drugs

A

Warfarin

Phenytoin

22
Q

What is clearance of intermediate extraction ratio drugs dependent on?

A

Both hepatic blood flor, intrinsic metabolising capacity of the liver an the free drug fraction

23
Q

Examples of intermediate extraction ratio drugs

A

Aspirin

Codeine

24
Q

Which types of enzyme mediate the phase 1 (hydrolysis/oxidation) reactions in the liver?

A

Esterases

Oxidoreductases such as CYP450

25
What do the phase 2 conjugation (sulphonation/glucoronidation) reactions do to the drug?
Make the metabolites less reactive, less toxic and more polar - CONJUGATING ENZYMES carry these out
26
The main purpose of drug metabolism is to do what?
Make the drug non-reactive, non-toxic and easy as possible to excrete preferentially via the kidney
27
The phase 2 reaction in the liver involves the addition of which substances to a toxic chemical or drug?
Cysteine, glycine, sulphur molecule
28
What is the most common phase 2 reaction in the liver?
Glucoronidation
29
What are the other conjugation reactions in the liver?
Amino acid conjugation and sulfoconjugation
30
Aspirin is hydrolysed into which substance?
Salicylic acid
31
How does paracetamol cause toxicity in a normal situation?
Paracetamol is metabolised to two metabolites 1) Formation of sulfur/glucaronide metabolites - which are secreted by urine (95% of paracetamol is metabolised via this mechanism) 2) The other 5% is metabolised into an intermediate called NAPQI. This is a toxic metabolite which is removed by addition of glutathione and excreted via the urine. IF THIS IS NOT REMOVED EFFECTIVELY, HEPATOTOXICITY WILL OCCUR
32
What happens during a paracetamol overdose?
The majority of paracetamol is now metabolised into NAPQI due to the levels of glutathione being exhausted by the excess paracetamol - The >NAPQI levels cause liver damage, potentially ending with transplant requirement
33
Paracetamol toxicity cannot be seen for the first how many hours?
48hrs
34
Treatment for paracetamol overdose
IV infusion of acetylcholine

Gastrointestinal pathophysiology (22 decks)

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