Acetohydroxamic acid

Absorption

Well absorbed from the GI tract following oral administration.

Toxicity

Oral, rat: LD50 = 4.8gm/kg. Symptoms of overdose include anorexia, malaise, lethargy, diminished sense of wellbeing, tremor, anxiety, nausea, and vomiting.

Description

Acetohydroxamic acid is a potent, non-competitive and irreversible inhibitor of bacterial urease (Ki≈lO^-7M). This enzyme, which is widely distributed in plants and bacteria, but not in mammalian cells, catalyzes the decomposition of urea to ammonia. Elevated urinary ammonia levels can reduce the antibacterial effectiveness of a number of agents. Thus, acetohydroxamic acid is useful as adjunctive therapy to decrease urinary ammonia and alkalinity in patients with chronic urea-splitting urinary infection. Such infections are a leading cause of recurring complications and death in paraplegics.

Chemical properties

White Crystalline Solid

Originator

Research Organics; Baylor Unk. (USA)

The Uses of Acetohydroxamic acid

Acetohydroxamic acid is a potent inhibitor of bacterial urease activity and reduces urinary ammonia levels. 2-Acetohydroxamic acid loaded floating microspheres forms an efficient drug delivery system for the treatment of Helicobacter pylori.
Acetohydroxamic acid was used:
to study the mechanism of complexation of iron (III) with acetohydroxamic acid.
to study the inhibitory mechanism of lansoprazole and omeprazole on Helicobacter pyloni.
in urease inhibition studies.
for in situ generation of nitrosocarbonylmethane as a Diels-Alder dienophile.
Used in urease inhibition studies and for in situ generation of nitrosocarbonylmethane as a Diels-Alder dienophile.

The Uses of Acetohydroxamic acid

A urease inhibitor. Used in the synthesis

The Uses of Acetohydroxamic acid

Urease inhibitorAcetohydroxamic acid acts as a drug, as an inhibitor of bacterial and plant urease, which is used for urinary tract infections. It is also used in organic synthesis. It acts as an antiurolithic and antibacterial agent. It is involved in the study of complexation of iron(III) with acetohydroxamic acid as well as in the inhibition study of lansoprazole and omeprazole on Helicobacter pyloni. It plays an important role in the insitu generation of nitrosocarbonylmethane as a Diels-Alder dienophile. In addition to this, it is used in the treatment of kidney stones and urinary tract infections.

What are the applications of Application

Acetohydroxamic Acid is An inhibitor of urease.

Indications

Used, in addition to antibiotics or medical procedures, to treat chronic urea-splitting urinary infections.

Background

Acetohydroxamic Acid, a synthetic drug derived from hydroxylamine and ethyl acetate, is similar in structure to urea. In the urine, it acts as an antagonist of the bacterial enzyme urease. Acetohydroxamic Acid has no direct antimicrobial action and does not acidify urine directly. It is used, in addition to antibiotics or medical procedures, to treat chronic urea-splitting urinary infections.

Definition

ChEBI: Acetohydroxamic acid is a member of the class of acetohydroxamic acids that is acetamide in which one of the amino hydrogens has been replaced by a hydroxy group. It has a role as an EC 3.5.1.5 (urease) inhibitor and an algal metabolite. It is functionally related to an acetamide. It is a tautomer of a N-hydroxyacetimidic acid.

Manufacturing Process

3 Methods of producing of acetohydroxamic acid:
1. Ethyl acetic acid ether was treated with hydroxylamine and acetohydroxamic acid was obtained.
2. Acetohydroxamic acid was obtained in the result of reaction of acetamide with hydroxylamine.
3. Acetohydroxamic acid was obtained by treatment of acetaldehyde with nitrohydroxylamine.

brand name

Lithostat (Mission).

Therapeutic Function

Urease inhibitor

General Description

Acetohydroxamic acid is a potent inhibitor of bacterial urease activity and reduces urinary ammonia levels. 2-Acetohydroxamic acid loaded floating microspheres forms an efficient drug delivery system for the treatment of Helicobacter pylori.

Pharmacokinetics

Acetohydroxamic Acid, a synthetic drug derived from hydroxylamine and ethyl acetate, is similar in structure to urea. In the urine, it acts as an antagonist of the bacterial enzyme urease. Acetohydroxamic Acid has no direct antimicrobial action and does not acidify urine directly.

Side Effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have:
pounding heartbeats or fluttering in your chest;
signs of a blood clot in your leg --pain, swelling, warmth, or redness in one or both legs;
signs of a red blood cell disorder --pale or yellowed skin, dark colored urine, fever, confusion or weakness.
Common side effects may include:
headache during the first 2 days of treatment;
skin rash, warmth, tingling or redness (especially if you drink alcohol while taking acetohydroxamic acid);
upset stomach, nausea, loss of appetite;
depressed mood;
anxiety, tremors, nervousness;
hair loss.

Safety Profile

Moderately toxic by intraperitonealroute. An experimental teratogen. Other experimentalreproductive effects. Mutation data reported. When heatedto decomposition it emits toxic fumes of NOx.

Veterinary Drugs and Treatments

Acetohydroxamic acid can be used in dogs as adjunctive therapy in some cases of recurrent urolithiasis or in the treatment of persistent urinary tract infections caused by the following bacteria: E. coli, Klebsiella, Morganella morganii, Staphylococci spp., and Pseudomonas aeruginosa. Adverse effects limit its usefulness.

Metabolism

35-65% of oral dose excreted unchanged in urine (which provides the drug's therapeutic effect).