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General Description:

Ammonia, identified by CAS number 7664-41-7, is a notable compound with significant therapeutic applications. Ammonia is a naturally-occurring compound with a chemical formula NH3 and structure of trigonal pyramidal geometry. It is a colorless gas with a pungent smell, and become NH4, or ammonium ion, when in water. Although ammonia is used as a food additive in the anhydrous form and serves as a starting material in pharmaceutical and commercial products, it is caustic and hazardous when concentrated. Ammonia gas has been used in the clinical setting as a respiratory stimulant to prevent fainting. The radiolabelled form of ammonia, ammonia N 13, is intravenously administered as a radioactive diagnostic agent for Positron Emission Tomography (PET) imaging of the myocardium to evaluate myocardial perfusion. Ammonia is a natural byproduct of biological and chemical reactions, including decomposition of organic matter, including plants, animals, and animal wastes. It is present in normally present in all tissues constituting a metabolic pool, where it is mostly taken up by glutamic acid and take part in transamination and other reactions, including the synthesis of protein by the Krebs-Hanseleit cycle in the liver . It is proposed that human adults produce about 1000 mmol of ammonia daily, most of which undergoes excretion in the urine.

Indications:

This drug is primarily indicated for: - Indicated for use as a smelling salt to treat or prevent fainting. - (when radiolabelled) Indicated for diagnostic PET imaging of the myocardium under rest or pharmacologic stress conditions to evaluate myocardial perfusion in patients with suspected or existing coronary artery disease . Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Ammonia undergoes metabolic processing primarily in: Healthy hepatocytes detoxify ammonia where hepatic glutaminase, glutamine synthetase and the urea cycle enzymes act as major enzymes for ammonia metabolism. Ammonia is converted to urea in the liver and other tissues. Glutaminase and glutamine synthetase catalyze the condensation of ammonia with glutamate to glutamine, which is a common nontoxic carrier of ammonia . In case of hepatic dysfunction or impairment, detoxification capacity decreases and may cause severe pathologies from hyperammonemia, such as hepatic encephalopathy . This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Ammonia are crucial for its therapeutic efficacy: Ammonia can be absorbed via oral or inhalation route. Inhales ammonia is temporarily dissolved in the mucus of the upper respiratory tract, however the majority of the gas is released back into the air via expiration . In healthy male subjects under exposure to 500 ppm ammonia for 10-27 minutes, about 70-80% of total inspired ammonia was expired . In extrahepatic tissues such as the intestine, ammonia is incorporated into nontoxic glutamine and released into blood, where it is transported to the liver for ureagenesis . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Ammonia is an important consideration for its dosing schedule: In normal rat brain, blood-derived ammonia was rapidly converted to glutamine, indicating very short half-life of less than 3 seconds . This determines the duration of action and helps in formulating effective dosing regimens.

Route of Elimination:

The elimination of Ammonia from the body primarily occurs through: It is mainly excreted through expired air or renal elimination . Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Pharmacodynamics:

Ammonia exerts its therapeutic effects through: As a gas, ammonia is a natural byproduct and respiratory stimulant. Its renal metabolism plays a role in whole body acid-base balance. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Ammonia functions by: Renal excretion and metabolism of ammonia is critical in regulation of acid-base balance by generating bicarbonate ions and promoting renal net acid excretion, both under basal conditions and in response to acid-base disturbances . There is evidence that acute ammonia exposure activates NMDA receptor signalling pathways, and high concentrations of ammonia resulting from urea cycle enzyme deficiencies are associated with changes in astrocyte morphology due to glutamine accumulation, changes in the expression of key astrocyte proteins, and increased concentrations of neuroactive L-tryptophan metabolites . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Categories:

Ammonia is categorized under the following therapeutic classes: Gases, Nitrogen Compounds, Respiratory System Agents. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Ammonia include:

• Melting Point: -77.7
• Boiling Point: -33.4