Liver

Question 1

Functions of liver

Answer 1

• Production of bile
• Synthetic function- Production of proteins/clotting factors, metabolism of carbs/cholesterol
• Metabolism
• Storage- e.g. Fe
• Detoxification

Question 2

Detoxification

Answer 2

• Hormones
• Meds
• Waste products of demaination of amino acids

Question 3

First pass metabolism

Answer 3

• When drugs are absorbed orally they travel via the portal vein to the liver prior to entering the rest of the systemic circulation
• Alot of drugs undergo initial metabolism here usually via Cytochrome P450 enzymes
• % that enters systemic circulation to have an affect is called bioavailability
• NB- often will reduce active drug concentrations but for pro-drugs will be a necessary step for activation into active compound e.g. clopidogrel

Question 5

Biotransformation (drug metabolism)

Answer 5

• Occurs in 2 stages
• Phase 1- oxidation/reduction/hydrolysis into metabolite
• Phase 2- conjugation (e.g. glucaronidation/phosphorylation)- usually to make more water soluble for excretion via the kidney

Question 6

Affects of liver disease on Pharmacokinetics

Answer 6

• Liver disease can lead to altered metabolism (reduced) of meds
• Hypoalbuminaemia can lead to increased free serum concentration of drugs increasing risk of toxicity (e.g. phenytoin)
• Shunting of blood flow in chronic liver disease can reduce hepatic excration ratio
• Compounds excreted in bile via the enterohepatic circulation may reach high concentrations resulting in hepatoxicity e.g phenytoin and some antibiotics.
• When dosing in chronic liver disease it is a good rule of thumb to start low and go slow