Gold salts
Encyclopedia
Chemical compound
A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...
s of gold
Gold
Gold is a chemical element with the symbol Au and an atomic number of 79. Gold is a dense, soft, shiny, malleable and ductile metal. Pure gold has a bright yellow color and luster traditionally considered attractive, which it maintains without oxidizing in air or water. Chemically, gold is a...
. The term, which is a misnomer, has evolved into a synonym for the gold compounds used in medicine
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
. The application of gold compounds to medicine is called "chrysotherapy" and "aurotherapy." The first reports of research in this area appeared in 1935, primarily to reduce inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
and to slow disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
progression in patients with rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
. Most chemical compounds of gold, including some of the drugs discussed below, are not in fact salts. Gold compounds find wide use in electroplating
Electroplating
Electroplating is a plating process in which metal ions in a solution are moved by an electric field to coat an electrode. The process uses electrical current to reduce cations of a desired material from a solution and coat a conductive object with a thin layer of the material, such as a metal...
, and as reagent
Reagent
A reagent is a "substance or compound that is added to a system in order to bring about a chemical reaction, or added to see if a reaction occurs." Although the terms reactant and reagent are often used interchangeably, a reactant is less specifically a "substance that is consumed in the course of...
s in organic chemistry
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...
.
Medical uses
Investigation of medical applications of gold salts began at the end of the 19th century, when gold cyanide demonstrated effectiveness against Mycobacterium tuberculosisMycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
.
Indications
Gold compounds, which accumulate slowly in the body and, over time, reduce inflammation, especially related to rheumatoid arthritisRheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
, inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
, psoriatic arthritis
Psoriatic arthritis
Psoriatic arthritis is a type of inflammatory arthritis that, according to the National Psoriasis Foundation, will develop in up to 30 percent of people who have the chronic skin condition psoriasis...
, membranous nephritis, lupus erythematosus
Lupus erythematosus
Lupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
and, infrequently, juvenile rheumatoid arthritis (JRA).
At present, gold salts are infrequently used to treat children with juvenile idiopathic arthritis
Juvenile idiopathic arthritis
Juvenile idiopathic arthritis is the most common form of persistent arthritis in children. JIA is a subset of arthritis seen in childhood, which may be transient and...
(previously termed Juvenile Rheumatoid Arthritis), as methotrexate
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
is the convention. Gold salts are sometimes used for children with progressive polyarthritis who are unresponsive to non-steroidal anti-inflammatory drugs, methotrexate, and other medications. This treatment is expensive requiring frequent visits to the doctor and numerous lab tests.
Mechanism in arthritis
The mechanism by which gold drugs operate to treat arthritis is a matter of scientific debate. Of the various mechanisms that have been suggested for the transportation of the drugs to their sites of action in the synoviumSynovium
Synovial membrane is the soft tissue found between the articular capsule and the joint cavity of synovial joints....
, it is thought that in the blood stream the gold attaches to albumin
Albumin
Albumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...
. The thiol
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...
groups on the gold drug being exchanged for the cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
cysteine-34 of this protein. After arrival at the synovium, the Au(I) again undergoes a second thiol exchange reaction at cell membrane transport proteins and enters the cell via the shuttle thiol mechanism. Once absorbed into the cell, gold is proposed to be linked to anti-mitochrondrial activity and induced cell apoptosis. The myriad of side effects associated with this class of prodrugs is ascribed to the nonspecific absorption and pharmacological action, thus many cells not linked with the rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
immune response are affected. Some assert that gold drugs merely inhibit the function of the various components of the immune response associated with rheumatoid arthritis, rather than acting in a disease curing fashion. It is thought that gold affects the entire immune response (phagocytes, leukocytes, T-Cells...) and reduce its potency and limit its oxidizing nature, ending the cycle of joint inflammation and erosion.
Administration
Gold drugs can be administered orally or by intramuscular injection, in which case it is administered weekly for approximately three to five months before less-frequent doses begin. AuranofinAuranofin
Auranofin is a gold complex classified by the World Health Organization as an antirheumatic agent.It has the brand name Ridaura.-Use in HIV infection:...
, in capsule form for oral administration, is marketed under the brand name Ridaura. Sodium aurothiomalate
Sodium aurothiomalate
Sodium aurothiomalate is a gold compound with the chemical formula C4H4AuNaO4S and is used for its antirheumatic effects to treat rheumatoid arthritis...
(Gold sodium thiomalate as brands Myocrisin UK, Aurolateor or Myochrysine U.S.) and aurothioglucose
Aurothioglucose
Aurothioglucose, also known as gold thioglucose, is a chemical compound with the formula AuSC6H11O5. This derivative of the sugar glucose is used to treat rheumatoid arthritis.-History:...
(Solganal in U.S.) are administered by injection. Regular urine tests to check for protein
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
(indicating kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
damage) and blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s are needed.
Efficacy
A 2005 review (Suarez-Almazor ME et al.) reports that treatment with intramuscular gold (parenteral gold) reduces disease activity and joint inflammation. Gold salts taken by mouth are less effective than by injection. Three to six months are often required before gold treatment noticeably improves symptoms.A 2002 paper (Richards et al.) chronicles the neurological side effects of gold salts reported in the medical literature. "[T]here are reports pointing to a possible involvement of naturally-occurring gold in the nervous
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
and gland
Gland
A gland is an organ in an animal's body that synthesizes a substance for release of substances such as hormones or breast milk, often into the bloodstream or into cavities inside the body or its outer surface .- Types :...
ular systems, and evidence from historical sources of a possible efficacy of gold in therapy for neurological disorders," according to the study authors. "This research has the potential for re-establishing gold as a significant therapeutic agent in a much wider range of disorders than those for which it is currently used. And it could help in sorting out valid from invalid claims of benefits from supplementation."
Side effects
Side effectsAdverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
may develop after a significant accumulation of gold in the body. Gold compounds require up to two months to reach a steady state, and have a fairly long half life. In 10 days, only 70% is excreted, exacerbating toxicity problems. The potential benefits for patients with inflammatory bowel disease, skin rash or a history of bone marrow depression should be weighed against the potential risks of gold toxicity on previously compromised organ systems or with decreased reserve. Potential problems with detection and correct attribution of toxic effects must also be considered.
Orally administered gold has fewer side effects than intramuscular injections. Common side effects of oral gold include decreased appetite
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...
, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, hair thinning
Alopecia
Alopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...
and diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, as well as problems affecting skin, blood (thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
), kidneys, eyes, or lungs. Common side effects of injected gold include an itchy skin rash or mouth sores, with rare instances of kidney problems or suppression of blood cell production.
Potential future uses
Research continued to examine the potential of gold salts as anti-cancer agents. This research stemmed from the discovery that auranofinAuranofin
Auranofin is a gold complex classified by the World Health Organization as an antirheumatic agent.It has the brand name Ridaura.-Use in HIV infection:...
was toxic towards leukemia cells. It is also noted that a wide variety of the salts currently being researched are effective against cisplatin
Cisplatin
Cisplatin, cisplatinum, or cis-diamminedichloroplatinum is a chemotherapy drug. It is used to treat various types of cancers, including sarcomas, some carcinomas , lymphomas, and germ cell tumors...
resistant cancer cells, highlighting their different but at present unknown modes of operation.
Gold salts combined with Chloroquine
Chloroquine
Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-History:Chloroquine , N'--N,N-diethyl-pentane-1,4-diamine, was discovered in 1934 by Hans Andersag and co-workers at the Bayer laboratories who named it "Resochin". It was ignored for a decade because it was...
, an anti-malarial, show potential at treating resistant strains of malaria.
It has been suggested in Japan that gold salts used for the treatment of rheumatoid arthritis particularly gold thioglucose, may also be used for the treatment of bronchial asthma.
Types of gold salts
Medical use:- AuranofinAuranofinAuranofin is a gold complex classified by the World Health Organization as an antirheumatic agent.It has the brand name Ridaura.-Use in HIV infection:...
(UK & U.S.) - AurothioglucoseAurothioglucoseAurothioglucose, also known as gold thioglucose, is a chemical compound with the formula AuSC6H11O5. This derivative of the sugar glucose is used to treat rheumatoid arthritis.-History:...
(Gold thioglucose) (U.S.) - Disodium aurothiomalateDisodium aurothiomalateDisodium aurothiomalate is a chemical compound with the formula AuSCHCH2CO2Na. In conjunction with its monoprotonated derivative, this coordination complex or closely related species are used to treat rheumatoid arthritis, under the tradename Myochrysine. The thiomalate is racemic in most...
- Sodium aurothiosulfateSodium aurothiosulfateSodium aurothiosulfate is the inorganic compound with the formula Na3Au2·2H2O, although a formule more accurate picturing this compound would be: Na3[Au2]. This salt contains an anionic linear coordination complex of gold bound to two thiosulfate ligands. Like several other gold compounds, this...
(Gold sodium thiosulfateThiosulfateThiosulfate is an oxyanion of sulfur. The prefix thio indicates that thiosulfate ion is a sulfate ion with one oxygen replaced by a sulfur. Thiosulfate occurs naturally and is produced by certain biochemical processes...
) - Sodium aurothiomalateSodium aurothiomalateSodium aurothiomalate is a gold compound with the chemical formula C4H4AuNaO4S and is used for its antirheumatic effects to treat rheumatoid arthritis...
(Gold sodium thiomalate) (UK)
Industrial use:
- PotassiumPotassiumPotassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
gold cyanide (KAu(CN)2), containing 68.2% by weight of gold, is sometimes used for industrial purposes such as electro-plating; potential risks include occupational contact eczemaEczemaEczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...
.
External links
- "Gold salts for juvenile rheumatoid arthritis". BCHealthGuide.org
- "Gold salts information". DiseasesDatabase.com
- "HMS researchers find how gold fights arthritis: Sheds light on how medicinal metal function against rheumatoid arthritis and other autoimmune diseases." Harvard University Gazette (2006)
- "Mineral Therapy and the Use of Gold". Mark Sircus Ac, OMD, International Medical Veritas Association
- "Aurothioglucose is a gold salt used in treating inflammatory arthritis". MedicineNet.com
- "About gold treatment: What is it? Gold treatment includes different forms of gold salts used to treat arthritis." Washington.edu University of WashingtonUniversity of WashingtonUniversity of Washington is a public research university, founded in 1861 in Seattle, Washington, United States. The UW is the largest university in the Northwest and the oldest public university on the West Coast. The university has three campuses, with its largest campus in the University...
(December 30, 2004)