Gold Compounds Chemische Eigenschaften,Einsatz,Produktion Methoden
Indications
Gold compounds (chrysotherapy) are the oldest of the
DMARDs in use to treat rheumatoid arthritis. Parentally
administered gold is generally believed to be
somewhat less effective than methotrexate; oral gold is
less effective than parenteral preparations. Gold compounds
take several months to produce a measurable
effect. Among patients who can tolerate this therapy,
some benefit will be obtained in about 80%, and complete
remission will be induced in 20% of cases. Remissions are
maintained for varying periods after discontinuing therapy,
with a relapse rate as high as 80%. Relapse is usually
less severe in such patients, and a second course of gold
therapy usually produces beneficial effects.
Pharmakologie
The gold preparations available in the United States include
two preparations administered via intramuscular
injection: gold sodium thiomalate (GSTM, Myochrysine,
Aurolate) and aurothioglucose (gold sodium thioglucose,
GSTG, Solganal), and an oral preparation, auranofin
(Ridaura). Although called gold salts, these compounds
contain monovalent gold bound to sulfur, a
bond that is at least partly covalent.
The mechanism by which gold compounds produce
their antiarthritic effects is not known. Since gold therapy
can suppress the increased phagocytic activity that
occurs in rheumatoid arthritis, the antirheumatic activity
of gold preparations may involve the inhibition of either
antigen processing by macrophages or lysosomal
enzyme release in the joint. Gold preparations also directly
inhibit certain lysosomal enzymes found in polymorphonuclear
leukocytes and macrophages.
Generally, 2 months of multiple dosing of gold
compounds is required to reach steady-state levels.
Auranofin therapy produces lower steady-state blood
gold concentrations than does treatment with parenteral
gold compounds, but it also produces a lower incidence
of adverse effects.
Nebenwirkungen
Toxic manifestations of gold therapy are most common
after a minimal total amount (200–300 mg) of gold has
been administered. Serious reactions necessitating discontinuance
of therapy or antidotal therapy are encountered
in perhaps 5% of the patients.
Both oral and parenteral gold therapy frequently
produces dermatitis, usually preceded and accompanied
by pruritus. Stomatitis may accompany dermatitis,
which may be preceded by a metallic taste in the mouth
of the patient. Blue or gray skin discoloration can arise
from gold deposition in that tissue, and photosensitivity
may also occur. Unlike parenteral gold compounds, auranofin
does not accumulate appreciably in the skin.
Auranofin, but not the parenteral gold preparations,
most frequently causes diarrhea (about 50%), abdominal
pain, nausea, and anorexia.
Mild proteinuria is fairly common and does not always
require discontinuance of therapy; however, severe
proteinuria may indicate a toxic nephritis.The proteinuria
is usually reversible when gold administration
is stopped. Hepatotoxicity has also been reported.
Fatalities from gold therapy have been reported, usually
a consequence of a blood dyscrasia. The most common
hematological abnormality is eosinophilia. Serious
blood dyscrasias, such as thrombocytopenia, agranulocytosis,
and hypoplastic or aplastic anemia, are rare.
To complement steroidal and other measures used
in treating gold toxicity, it may be necessary to hasten
the elimination of gold from the body.
Vorsichtsma?nahmen
Gold compounds are contraindicated for use in patientswith systemic lupus erythematosus, Sj?gren’s syndrome,severe debilitation, or uncontrolled congestive heartfailure or hypertension. Caution must be used in administeringgold compounds to individuals who haveconditions that might increase their susceptibility togold toxicity: blood dyscrasias, immunosuppression, renaldisease, hepatic disease, skin diseases, or inflammatorybowel disease.Animal studies have shown adverseeffects on reproduction; gold compounds may distributeto breast milk and are therefore contraindicated forwomen who are breast-feeding.
Gold should be used cautiously in patients receivingdrugs that can also cause nephrotoxicity. Interactionsbetween gold compounds and penicillamine may resultin severe hematological and renal side effects.
Gold Compounds Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
