Ammonia is a compound made up of nitrogen and hydrogen with the chemical formula NH3. In the body, ammonia is produced as a byproduct of protein metabolism. Normally, the liver efficiently converts ammonia into urea which is then excreted in urine. However, when the liver’s ability to convert ammonia to urea is impaired, ammonia accumulates in the blood. This condition is known as hyperammonemia.
Elevated levels of ammonia in the blood (hyperammonemia) can have toxic effects on the brain and central nervous system. That’s why it’s important to treat and prevent hyperammonemia. One way to do this is by using medications called ammonia scavengers. These work by binding to ammonia in the gastrointestinal tract, allowing it to be eliminated from the body before it can be absorbed into the bloodstream.
Some ammonia scavengers also have anticoagulant effects. Anticoagulants prevent blood clotting. This article will explore the mechanisms and uses of common ammonia scavengers that also serve as anticoagulants.
Lactulose
Lactulose is a non-absorbable synthetic disaccharide commonly used to treat hyperammonemia. Here is a summary of how lactulose works as an ammonia scavenger and anticoagulant:
Mechanism as ammonia scavenger
– Lactulose works in the colon to trap ammonia. It causes osmotic retention of water which acidifies the colonic contents.
– The acidic environment converts ammonia (NH3) into ammonium (NH4+).
– Ammonium is trapped and unable to be reabsorbed into the bloodstream. It is eventually excreted in feces.
Mechanism as anticoagulant
– Lactulose enhances antithrombin III activity which inhibits the coagulation cascade.
– It also decreases levels of factors VII, IX, X and prothrombin.
– The result is reduced blood clotting activity.
Clinical uses
– Treatment of hepatic encephalopathy and hyperammonemia
– Constipation relief
– Potential anticoagulant in patients with cirrhosis and coagulopathy
Rifaximin
Rifaximin is a non-absorbable antibiotic that acts as an ammonia scavenger in the gastrointestinal tract. Here are key points about its mechanisms and uses:
Mechanism as ammonia scavenger
– Rifaximin alters gut flora to reduce ammonia producing bacteria.
– It also directly binds to ammonia within the gastrointestinal tract.
Mechanism as anticoagulant
– Rifaximin has minimal systemic absorption and no clinically relevant anticoagulant effects.
Clinical uses
– Treatment of hepatic encephalopathy
– Adjunctive treatment of hyperammonemia
– Not used as an anticoagulant due to lack of systemic absorption
AST-120 (Spherical carbon adsorbent)
AST-120 is an oral adsorbent used to reduce blood ammonia levels by binding ammonia in the GI tract. Here are key details:
Mechanism as ammonia scavenger
– AST-120 consists of tiny spherical carbon particles that adsorb molecules via surface interactions.
– It has a high affinity for ammonia and binds ammonia in the gastrointestinal tract, preventing absorption.
Mechanism as anticoagulant
– AST-120 itself does not have anticoagulant effects.
– However, it can bind to orally administered anticoagulants like warfarin in the GI tract, reducing their absorption and anticoagulant effect.
Clinical uses
– Treatment of hyperammonemia
– Not used as an anticoagulant itself, but can interact with oral anticoagulants
Neomycin
Neomycin is an aminoglycoside antibiotic that has some activity as an ammonia scavenger. Here are key details:
Mechanism as ammonia scavenger
– Neomycin alters gut flora, suppressing ammonia-producing bacteria
– Directly binds some ammonia in the gastrointestinal tract
Mechanism as anticoagulant
– Neomycin has no direct anticoagulant activity
Clinical uses
– Occasionally used as adjunctive treatment for hyperammonemia
– Not used clinically as an anticoagulant
– Major limiting factor is antibiotic side effects with long-term use
Comparison of Key Features
Here is a table summarizing and comparing the key features of the ammonia scavengers discussed:
| Medication | Mechanism as Ammonia Scavenger | Mechanism as Anticoagulant | Clinical Uses |
|---|---|---|---|
| Lactulose | – Acidifies colon, converts NH3 to NH4+ – Traps NH4+ so not absorbed |
– Enhances antithrombin III – Reduces clotting factors |
– Hepatic encephalopathy – Hyperammonemia – Potential anticoagulant |
| Rifaximin | – Alters gut flora – Binds ammonia |
– Minimal systemic absorption – No anticoagulant effect |
– Hepatic encephalopathy – Hyperammonemia |
| AST-120 | – Adsorbent binds ammonia | – No direct anticoagulant effect | – Hyperammonemia |
| Neomycin | – Alters gut flora – Binds some ammonia |
– No direct anticoagulant effect | – Adjunct for hyperammonemia |
Using Anticoagulants in Hyperammonemia
Hyperammonemia is sometimes accompanied by abnormalities in blood clotting. Patients may develop coagulopathies for several reasons:
– Impaired liver synthesis of clotting factors
– Reduced levels of natural anticoagulants like protein C, S and antithrombin
– Increased fibrinolysis
– Low platelet counts (thrombocytopenia)
This puts patients at higher risk of bleeding events. However, the coagulation abnormalities can also paradoxically increase risk of thrombosis like portal vein thrombosis.
For these reasons, anticoagulation may be considered in hyperammonemia patients. The ammonia scavengers lactulose and rifaximin have little to no anticoagulant activity clinically. However, lactulose does have some anticoagulant properties that may be beneficial.
The non-absorbable nature of lactulose makes it unlikely to cause systemic bleeding. But it may help decrease thrombotic risk in the portal circulation while also reducing ammonia levels. More research is needed to establish clinical guidelines on anticoagulation in the setting of hyperammonemia.
Conclusion
In summary, the ammonia scavengers lactulose, rifaximin, AST-120 and neomycin can all reduce ammonia levels through various mechanisms. Of these, only lactulose has the additional effect of acting as a mild anticoagulant.
Lactulose works by enhancing antithrombin III activity and reducing clotting factors in the blood. The localized anticoagulant activity may be beneficial in hyperammonemia patients with coagulation abnormalities at higher risk of bleeding or thrombosis. More studies are needed to confirm the risk/benefit profile of targeted anticoagulation therapy in hyperammonemia patients.
