GI IV- Hepatic Faliure Flashcards
What are the steps of drug metabolism in the liver
Phase 1 –> Catabolic (oxidation, reduction or hydrolysis)
Phase 2 –> Anabolic “conjugation rxn” that produces inactive/ excretable metabolite
Metabolism of Paracetamol at normal dose
Metabolism of Paracetamol after overdose
1) conjugation with glucuronide/sulphate becomes saturated,
2) shift to CYP450 enzyme.
3) Glutathione rescue becomes depleted = subsequent hepatotoxicity.
Antidote used to reverse side effects of paracetamol overdose?
N-acetyl cystine
Explain how N-acetyl Cysteine reverses Paracetamol overdose Side effects
Replenishes Glutathione (GSH) stores -> restores NAPBQI
AE of Paracetamol toxicity?
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
when should N-acytel Cysteine be administered ?
Up to (within) 8h post-ingestion of paracetamol overdose
clinical uses of Charcol
Paracetamol overdose 1h post-ingestion
Common causes of liver failure
1) alcohol abuse,
2) viral hepatitis,
3) non-alcoholic fatty liver disease.
Complications of liver failure
1) Hepatic encephalopathy,
2) ascites,
3) variceal bleeding,
4) spontaneous bacterial peritonitis,
5) hepatocellular carcinoma
Tx approach for Ascites
- salt restriction,
- diuretics (spironolactone and furosemide),
- paracentesis
Tx approach for Spontaneous Bacterial peritonitis
Abx
Tx approach for Hepatic encephalopathy
Lactulose and Rifaximin
Tx approach for Oesophageal varices?
Prophylaxis: Propranolol.
Acute Tx: Terlipressin, Octreotide, Fluids & variceal ligation once stable.
Drugs to avoid in liver failure
1) Opiates & Diuretics (increased risk of hepatic encephalopathy),
2) oral hypoglycaemic (loss of glucose homeostasis),
3) warfarin (effects enhanced)
opiates –> Morphine, Codeine , Heroin
Drugs that cause abnormal LFTs (liver function tests)
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.
Class of Terlipressin
Vasopressin agonist
Clinical uses of Terlipressin
Tx in Acute variceal bleeding caused by Esophageal varices
Class of Octreotide
Somatostatin analogue
MoA of Octreotide
Constricts splanchnic blood vessels
Clinical uses of Octreotide
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
Class of Lactulose
osmotic laxative
Clinical uses of Lactulose
Used to Tx hepatic encephalopathy
(since it traps NH3 into the lumen, NH3 becomes then NH4)
MoA of Lactulose
Entrapment of NH3 in the gut lumen, NH3 becomes NH4. It also alters NH3 metabolism by microbial flora
