GI IV- Hepatic Faliure

Question 1

What are the steps of drug metabolism in the liver

Answer 1

Phase 1 –> Catabolic (oxidation, reduction or hydrolysis)
Phase 2 –> Anabolic “conjugation rxn” that produces inactive/ excretable metabolite

Question 2

Metabolism of Paracetamol at normal dose

Answer 2

Question 3

Metabolism of Paracetamol after overdose

Answer 3

1) conjugation with glucuronide/sulphate becomes saturated,
2) shift to CYP450 enzyme.
3) Glutathione rescue becomes depleted = subsequent hepatotoxicity.

Question 4

Antidote used to reverse side effects of paracetamol overdose?

Answer 4

N-acetyl cystine

Question 5

Explain how N-acetyl Cysteine reverses Paracetamol overdose Side effects

Answer 5

Replenishes Glutathione (GSH) stores -> restores NAPBQI

Question 6

AE of Paracetamol toxicity?

Answer 6

After 24h -> nausea, pallor, abdominal pain or Asymptomatic
24-48h –> Liver dysfunction (jaundice, abdominal pain and swelling ..etc)
48-72h –> Fluminant hepatic failure
72-96h -> complete recovery or Death

Question 7

when should N-acytel Cysteine be administered ?

Answer 7

Up to (within) 8h post-ingestion of paracetamol overdose

Question 8

clinical uses of Charcol

Answer 8

Paracetamol overdose 1h post-ingestion

Question 9

Common causes of liver failure

Answer 9

1) alcohol abuse,
2) viral hepatitis,
3) non-alcoholic fatty liver disease.

Question 10

Complications of liver failure

Answer 10

1) Hepatic encephalopathy,
2) ascites,
3) variceal bleeding,
4) spontaneous bacterial peritonitis,
5) hepatocellular carcinoma

Question 11

Tx approach for Ascites

Answer 11

• salt restriction,
• diuretics (spironolactone and furosemide),
• paracentesis

Question 12

Tx approach for Spontaneous Bacterial peritonitis

Answer 12

Abx

Question 13

Tx approach for Hepatic encephalopathy

Answer 13

Lactulose and Rifaximin

Question 14

Tx approach for Oesophageal varices?

Answer 14

Prophylaxis: Propranolol.
Acute Tx: Terlipressin, Octreotide, Fluids & variceal ligation once stable.

Question 15

Drugs to avoid in liver failure

Answer 15

1) Opiates & Diuretics (increased risk of hepatic encephalopathy),
2) oral hypoglycaemic (loss of glucose homeostasis),
3) warfarin (effects enhanced)

opiates –> Morphine, Codeine , Heroin

Question 16

Drugs that cause abnormal LFTs (liver function tests)

Answer 16

1) Antiepileptics (carbamazepine, phenytoin),
2) Anti-TB drugs (except ethambutol),
3) typical antipsychotics,
4) paracetamol,
5) statins,
6) fibrates,
7) amiodarone (anti-arrythmic –> tx of tachy such as Afib),
8) contraceptive pill,
9) spironolactone,
10) NSAIDs,
11) Erythromycin,
12) Valproate,
13) Amoxicillin/Clavulanate,
14) Ketoconazole.

Question 17

Class of Terlipressin

Answer 17

Vasopressin agonist

Question 18

Clinical uses of Terlipressin

Answer 18

Tx in Acute variceal bleeding caused by Esophageal varices

Question 19

Class of Octreotide

Answer 19

Somatostatin analogue

Question 20

MoA of Octreotide

Answer 20

Constricts splanchnic blood vessels

Question 21

Clinical uses of Octreotide

Answer 21

1) Useful in Tx of oesophageal varices since there is less BF and thus less P that acts on the oesophageal vessel
2) Acromegaly

* BF –> blood flow

Question 22

Class of Lactulose

Answer 22

osmotic laxative

Question 23

Clinical uses of Lactulose

Answer 23

Used to Tx hepatic encephalopathy
(since it traps NH3 into the lumen, NH3 becomes then NH4)

Question 24

MoA of Lactulose

Answer 24

Entrapment of NH3 in the gut lumen, NH3 becomes NH4. It also alters NH3 metabolism by microbial flora