Hepatic Dysfunction

Question 1

Should you continue or discontinue NSAIDs in severe liver disease? [1]

Expalin your answer

Answer 1

Discontinue: can worse liver and renal function in severe liver disease

Renal blood flow is reliant to some extent on prostacyclins; there NSAIDs reduce this and deterioate renal function

Question 2

Should you continue or discontinue spironolactone in severe liver disease? [1]

Expalin your answer

Answer 2

Discontinue: causes hyperkalaemia and renal dysfunction. Stop and correct serum potassium

Question 3

Should you continue or discontinue ACEins in severe liver disease? [1]

Expalin your answer

Answer 3

Discontinue: need RAAS to maintain peripheral vascular resistance in severe liver disease.

ACE inhibitors can lead to rapid drop in BP and cause renal failure

Question 4

Which variables are used in the Child-Pugh score? [5]

Answer 4

Ascites
Bilirubin
INR
Hepatic Enceph
Serum Albumin

Question 5

Name two antibiotics that can cause hepatitis and cholestatic jaundice [1]

Describe the onset [1]

Answer 5

Flucoxacillin: onset may be delayed by up to two months

co-amoxiclav

Question 6

Name & describe 5 drugs that may cause liver damage

Answer 6

Paracetamol

NSAIDs

Methotrexate: severe fibrosis & cirrhosis

Amiodarone: cause steoto-hepatitis

Question 7

Question 9

How do you determine the need for NAC treatment via the paracetamol overdose treatment normogram?

Answer 9

plot the measured plasma paracetamol level (in mg/L) against the time since ingestion

If plasma level falls above the line then give acetylcysteine as per the management protocols above..

Question 10

When is normogram for paracetamol treatment unreliable? [2]

Answer 10

After 15 hrs
If overdose is staggered (ingested over >1hr)

Question 11

Describe the basic principles of drug metabolism in the liver [2]

Answer 11

Phase 1:
- Drug becomes more polar by oxidation, reduction or methylation: so can combine with another molecule
- Due to cytochrome P450 enzymes
- phase I reactions convert a parent drug to more polar (water soluble) ACTIVE metabolites by unmasking or inserting a polar functional group (-OH, -SH, -NH2)

Phase 2:
- conjugation occurs: resulting in water soluble molecule that is inactive and excreted in urine or bile
- phase II reactions convert a parent drug to more polar (water soluble) INACTIVE metabolites by conjugation of subgroups to -OH, -SH, -NH2 functional groups on drug
- renally excreted

Question 12

Name 3 drugs that may need altered dosing in liver dysfunction

Answer 12

Fluoxetine:
- extensively metabolised in the liver

Nifedipine

Phenytoin: - extensively metabolised in the liver

Question 13

Describe the changes to drug metabolism can occur with cirrhosis in first pass metabolism? [3]

Answer 13

Decrease in first pass metabolism:
- collaterals develop, enabling blood to bypass the liver
- therefore, ptx with cirrhosis will have higher serum concentration of drugs that normally undergo first pass metabolism
- therefore their oral bioavailablity increases
- therefore need to reduce doses

Question 14

Answer 14

She has cirrhosis: may develop porto-systemic shunts

Oral bioavail of morphine is normally 30%: may approach 100% due to shunts

Initially: prescribe low and titrate up if necessary

ALSO

Morphine can cause constipation; increases risk of H.E

Question 15

Which drug reduces the concentration of the combined oral pill? [1]

Why? [1]

Answer 15

Carbamazapine: induces drug metabolising enzymes causing less O & P concentration

Question 16

Erythromycine & which drug combined causes acute renal failure due to the inhibition of cP450 enzymes? [1]

Answer 16

erythomycin and tacrolimus: increases serum tacrolimus levels

Question 17

Which side effects of drugs do you need to consider in patients with cirrhosis regarding clotting abnormalities? [2]

Answer 17

Those that cause:

• Thrombocytopenia: e.g. sodium valproate
• Increase risk of of bleeding: anticoagulants & antiplatelets

Question 18

Which side effects of drugs do you need to consider in patients with cirrhosis regarding H.E.? [4]

Answer 18

Question 19

Which side effects of drugs do you need to consider in patients with cirrhosis regarding gastric & oesphageal varices? [2]

Answer 19

• NSAIDS: cause irratation of GI tract
• Anticoagulants: increase risk of bleeding

Question 20

Which side effects of drugs do you need to consider in patients with cirrhosis regarding ascites.? [2]

Answer 20

NSAIDS: cause fluid retention
NaCl: increase body Na

Question 21

Answer 21

Question 22

How may protein binding and drug concentration change in hepatic dysfunction? [1]

Answer 22