Q. MOA of lactulose in hep. encephalopathy?

[sgsh]

In FA GI pharma, it's mentioned that In hepatic encephalopathy, lactulose is useful because when lactulose is given it is acted upon by gut flora converting it into lactic acid and lactic acid in turn promotes nitrogen excretion as ammonium.

But, In wikipedia and other resources it is mentioned that lactulose converts ammoina ( absorbable and toxic form) to ammonium ( not absorbable through gut and is non-toxic) and increase transit of bowel content through gut.

I am confused. which of the mechanism of action is correct ? If both is correct, Can anybody pls help me to fill up what I am missing to combine them together and give a meaningful sense to both MOA mentioned above.Thanks.

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[Keto]

Hi

there are a few proposed mechanisms...

Main proposed mechanism

• Lactulose cannot be absorbed and is trapped in the gut
• Bacterial flora: Lactulose → Lactic acid
• Lactic acid →↓ pH in colon
• ↓ pH in colon favors: NH3 → NH4+
• NH4+ is trapped in the colon and excreted
  net effect: ↓ plasma NH3

Other proposed mechanisms

1. Hyperosmolar state in colon → ↑ transit time
2. ↑ stool volume → ↑ fecal nitrogen excretion
3. Change in bacterial colonic flora; Displacement of urease-containing bacteria;
4. ...

 

[Keto]

double post

 

[sgsh]

Thanks keto for detailed explanation. You have made everything clear.