MOA Rheumatoid arthritis is an autoimmune disease in which the body's immune system mistakenly attacks the lining of various skeletal bone joints of the body [A32325, L1956]. These attacks are facilitated by various pro-inflammatory immune cells and agents like cytokines, histamines, mast cells, macrophages, monocytes, lymphocytes, leukocytes, and many others [A32325]. The longterm result of this unwanted immune response is chronic inflammation and painful tissue damage [A32325, L1956]. The cause of the malfunctioning immune system in rheumatoid arthritis is unknown and there is no definitive cure for the condition [A32325, L1956].; ; Similarly, the mechanism of action of aurothioglucose is also not well elucidated. Nevertheless, some studies have suggested that the combination of both the sulfhydryl ligand and aureus cation present in aurothioglucose elicits an inhibitory effect on adenylyl cyclase activity in human lymphocyte membranes and in membranes of T and B lymphocyte subsets [A32325]. In particular, such inhibition of the activity of adenylyl cyclase and its various isoforms would theoretically also limit the cyclases' ability to induce mast cell degranulation and histamine release, to enhance respiratory burst effects, to stimulate the action of resting macrophages, to induce and activate phagocytes, to induce neutrophil chemotaxis, etc. - all of which are pro-inflammatory actions [A32325].

INDICATION Aurothioglucose is indicated for the adjunctive treatment of early active adult and juvenile type rheumatoid arthritis that is not adequately controlled by other anti-inflammatory agents and conservative measures like salicylate, glucocorticoids, etc. [L1925, L1937]. In chronic, advanced cases of rheumatoid arthritis, such gold therapy is not demonstrated to be as valuable [L1937].; ; Antirheumatic measures such as salicylate and other anti-inflammatory drugs (both steroidal and non steroidal) may be continued after initiation of gold therapy [L1937]. After improvement commences, these measures may be discontinued slowly as symptoms permit [L1937].

ABSORPTION In general, aurothioglucose is administered via intramuscular injection - preferably intragluteally [L1947] - after which the resultant absorption is typically slow and erratic [T149].; ; Gold is absorbed from injection sites, reaching peak concentration in blood in about 4 to 6 hours [L1937]. After a single intramuscular injection of 50 mg of aurothioglucose suspension in two subjects, peak serum levels were observed at approximately 235 g/dL and 450 g/dL [L1937].; ; Storage of gold in human tissues depends upon organ mass as well as the concentration of gold [L1937].Subsequently, tissues having the highest gold levels (w/w) may not necessarily have the largest total amounts of gold [L1937]. The highest concentrations of gold are generally found in the lymph nodes, adrenal glands, liver, kidneys, bone marrow, and spleen [L1937]. Relatively small concentrations are actually found in the articular structures [L1937]. In particular, following the administration of aurothioglucose doses, about 85% of the resultant plasma gold will be stored in the major bodily gold depots, which in decreasing order of total gold content are, the lymph nodes, bone marrow, liver, skin, and bone [L1937, L1947].

TOXICITY Overdose as a result of too rapid increases in dosing with aurothioglucose will be manifested by rapid appearance of toxic reactions, including those that are particular to renal damage, like hematuria and proteinuria, while hematologic effects include thrombocytopenia and granulocytopenia [L1937].; ; Other toxic effects, including fever, nausea, vomiting, diarrhea, and various skin disorders like papulovesicular lesions, urticaria, and exfoliative dermatitis, each of which are typically combined with severe pruritus can also develop [L1937].; ; The intramuscular TDLo for males is reported to be approximately 3.357 mg/kg when considering sense organs and special senses like eye vision and about 5.5 mg/kg for affects on the lungs, thorax, or respiration [L1940]. For women, the intramuscular TDLo for effects on the liver, gastrointestinal tract, and cholestatic jaundice is between 2.6-2.7 mg/kg while the value for effects on the kidney, ureter, bladder, and acute renal failure, acute tubular necrosis, and other changes in urine composition is about 14.402 mg/kg [L1940].