Details About Overdose or Poisoning Generic Salt ::  Unithiol, DMPS

Unithiol (DMPS)

    

Drug Pharmacology ::

I. Pharmacology.Unithiol (DMPS; 2,3-dimercaptopropanol-sulfonic acid), a dimercaptochelating agent that is a water-soluble analog of BAL (see BAL[Dimercaprol]), is used in the treatment of poisoning by several heavymetals, principally mercury, arsenic, and lead. Available on theofficial formularies of Russia and former Soviet countries since 1958and in Germany since 1976, unithiol has been legally available fromcompounding pharmacists in the United States since 1999. The drug canbe administered orally and parenterally. Oral bioavailability isapproximately 50%, with peak blood concentrations occurring inapproximately 3.7 hours. It is bound extensively to plasma proteins,mainly albumin. More than 80% of an intravenous dose is excreted in theurine, 10% as unaltered unithiol and 90% as transformed products,predominantly cyclic DMPS sulfides. The elimination half-life for totalunithiol is approximately 20 hours. Unithiol and/or its in vivobiotransformation products form complexes with a variety of inorganicand organic metal compounds, increasing excretion of the metal in theurine and decreasing its concentration in various organs, particularlythe kidney. Unlike BAL, unithiol does not redistribute mercury to thebrain.

Drug Indications ::

Indications

   

. Unithiol has been used primarily in the treatment of intoxication by mercury, arsenic, and lead.In animal models, unithiol has averted or reduced the acute toxiceffects of inorganic mercury salts and inorganic arsenic whenadministered promptly (minutes to hours) after exposure. Unithiol isassociated with a reduction in tissue levels of mercury, arsenic, andlead in experimental animals, and it increases the excretion of thosemetals in humans. However, randomized, double-blind, placebo-controlledclinical trials demonstrating therapeutic efficacy in acute or chronicheavy metal poisoning have not been reported.

. Animal studies and a few case reports suggest that unithiol may have utility in the treatment of poisoning by bismuth compounds.

Drug Contra-Indications ::

III. Contraindications./b>

   

. History of allergy to the drug.

.Because renal excretion is the predominant route of elimination ofunithiol and its metal complexes, caution is warranted in administeringunithiol to patients with severe renal insufficiency. Use of unithiolas an adjunct to hemodialysis or hemofiltration in patients with anuricrenal failure caused by mercury salts and bismuth has been reported.

Drug Adverse Effects ::

IV. Adverse effects

   

The German manufacturer (Heyl) notes a low overall incidence (< 4%) of adverse side effects.

Self-limited, reversible allergic dermatologic reactions such asexanthems and urticaria have been the most commonly reported adverseeffect. Isolated cases of major allergic reactions, including erythemamultiforme and Stevens-Johnson syndrome, have been reported.

Becauserapid intravenous administration may be associated with vasodilationand transient hypotension, intravenous injections of unithiol should beadministered slowly, over a 15- to 20-minute interval.

Unithiol increases the urinary excretion of copper and zinc, an effectthat is not anticipated to be clinically significant in patientswithout preexisting deficiency of these trace elements.

E. Use in pregnancy.Unithiol did not exhibit teratogenicity or other developmental toxicityin animal studies. Although protection against the adverse reproductiveeffects of selected toxic metals has been demonstrated in pregnantanimals, there is insufficient clinical experience with the use ofunithiol in human pregnancy.

Drug Lab Interactions ::

Drug or laboratory interactions.

   

A.Aqueous solutions of unithiol for intravenous injection should not bemixed with other drugs or minerals. Oral preparations should not beconsumed simultaneously with mineral supplements.

B. Unithiol has been shown to form a complex with an arsenic metabolite (MMAIII),which then is excreted in the urine. Laboratory techniques that usehydride reduction to measure urinary arsenic and its metabolites(“speciation”) may not detect this complex. However, the complex willcontribute to measurement of “total urinary arsenic.”

Drug Dose Management ::

Dosage and method of administration. Unithiolmay be administered by the oral, intramuscular, and intravenous routes.The intravenous route should be reserved for treatment of severe acuteintoxication by inorganic mercury salts or arsenic when compromised GIor cardiovascular status may interfere with rapid or efficientabsorption from the GI tract. In animal models, oral unithiol did notincrease the GI absorption of mercuric chloride.

   

Severe acute poisoning by inorganic mercury or arsenic.Administer 3–5 mg/kg every 4 hours by slow intravenous infusion over 20minutes. If, after several days, the patient’s GI and cardiovascularstatus have stabilized, consider changing to oral unithiol, 4–8 mg/kgevery 6–8 hours.

Symptomatic poisoning by lead (without encephalopathy). Oral unithiol, 4–8 mg/kg orally every 6–8 hours, may be considered an alternative to succimer (see Succimer [DMSA]). Note:Parenteral therapy with EDTA (see Digoxin-Specific Antibodies) ispreferable for the treatment of severe lead intoxication (leadencephalopathy or lead colic) and for patients with extremely highblood lead concentrations (eg, blood lead >150 mcg/dL).

Mobilization or “chelation challenge” tests measuring an increase inurinary excretion of mercury and arsenic after a single dose ofunithiol have been described, but their diagnostic or prognostic valuehas not been established.

Drug Chemical Formulations ::

Formulations

   

In the United States, compounding pharmacists (including hospitalinpatient pharmacies) may obtain bulk quantities ofpharmaceutical-grade unithiol and dispense it as injection solutionsfor infusion (usually 50 mg/mL in sterile water). Capsules (typicallyin 100- or 300-mg sizes) may also be prepared in an oral dose form.Note that bulk unithiol must be obtained outside the United States, andsuch supplies should have a certificate of analysis to assure productpurity.

The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is 2100 mg.

Disclaimer ::

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