Dimercaprol lead poisoning

Thiols have a marked ten dency to bond to mercury and the word mercaptan comes from the Latin mer curium captans which means seizing mercury The drug dimercaprol is used to treat mercury and lead poisoning It IS 2 3 dimercapto 1 propanol... 

Lead poisoning (withoutencephalopathy) IM/IV 1-1.5 g/m dailyfor 3-5 days (if blood lead concentration > 100 mc dl, calcium edetate usually given with dimercaprol.) Allow at least 2-4 days, up to 2-3 wk between courses of therapy Patients should not be given more than 2 courses of therapy... 

Lead poisoning (with encephalopathy) IM Initially, dimercaprol 4 mg/kg then give dimercaprol 4 mg/kg and calcium EDTA 250 mg/m then 4 hr later and q4h for 5 days. 

For the treatment of poisoning, a selective antidote (which antagonises the action) may be given e.g., nalorphine and naloxone in case of morphine poisoning, atropine in case of anticholinergic drugs, dimercaprol in mercury and penicillamine in lead poisoning, etc. 

Dimercaprol is FDA-approved as single-agent treatment of acute poisoning by arsenic and inorganic mercury and for the treatment of severe lead poisoning when used in conjunction with edetate calcium disodium (EDTA see below). Although studies of its metabolism in humans are limited, intramuscularly administered dimercaprol appears to be readily absorbed, metabolized, and excreted by the kidney within 4-8 hours. Animal models indicate that it may also undergo biliary excretion, but the role of this excretory route in humans and other details of its biotransformation are uncertain. 

Sodium calciumedetate is the calcium chelate of the disodium salt of ethylenediaminetetra-acetic acid (calcium EDTA). It is effective in acute lead poisoning because of its capacity to exchange calcium for lead the lead chelate is excreted in the urine, leaving behind a harmless amount of calcium. Dimercaprol may usefully be combined with sodium calciumedetate when lead poisoning is severe, e.g. with encephalopathy. 

In severe lead poisoning sodium calciumedetate is commonly used to initiate lead excretion. It chelates lead from bone and the extracellular space and urinary lead excretion of diminishes over 5 days thereafter as the extracellular store is exhausted. Subsequently symptoms (colic and encephalopathy) may worsen and this has been attributed to redistribution of lead from bone to brain. Dimercaprol is more effective than sodium calciumedetate at chelating lead from the soft tissues such as brain, which is the rationale for combined therapy with sodium calciumedetate. More recently succimer (2,3-dimercaptosuccinic acid, DMSA), a water-soluble analogue of dimercaprol, has been increasingly used instead. Succimer has a high affinity for lead, is suitable for administration by mouth and is better tolerated (has a wider therapeutic index) than dimercaprol. It is licenced for such use in the USA but not the UK. 

Intravenous administration of disodium edetate can cause renal insufficiency and acute tubular necrosis (2). In children with subclinical lead poisoning, the administration of sodium calcium edetate and dimercaprol together was associated with mild and transient biochemical evidence of renal damage in 13% of patients, whereas another 3% had acute renal insufficiency (19). 

Clinical use Dimercaprol is used in acute arsenic and mercury poisoning—and for lead poisoning when administered with edetate. It is an oily liquid that must be given parenterally. 

The name mercapto is derived from the fact that thiols were once called mercaptans. This terminology was abandoned by lUPAC several decades ago, but old habits die hard, and many chemists still refer to thiols as mercaptans. The term is derived from the Ladn mercurium captans (capturing mercury) and describes the abiUty of thiols to form complexes with mercury as well as other metals. This abihty is put to good use by the drug called dimercaprol, which is used to treat mercury and lead poisoning. 

Dimercaprol (British Anti-Lewisite or BAL) is a colorless, viscous oily compound with an offensive odor used in treating arsenic, mercury, and gold poisoning. It displaces the arsenic bound to enzymes. The enzymes are reactivated and can resume their normal biological activity. When given by injection, BAL can lead to alarming reactions that seem to pass in a few hours. 

The treatment of metal poisoning is to administer a compound that binds the metal ion more strongly than does the group in the active centre of the enzyme. These compounds are known as chelating agents. For lead, the compound ethyl-enediaminetetraacetic acid (EDTA) is used. For mercury, dimercaptopropanol (dimercaprol) is used. 

Unithiol has no FDA-approved indications, but experimental studies and its pharmacologic and pharmacodynamic profile suggest that intravenous unithiol offers advantages over intramuscular dimercaprol or oral succimer in the initial treatment of severe acute poisoning by inorganic mercury or arsenic. Aqueous preparations of unithiol (usually 50 mg/mL in sterile water) can be administered at a dose of 3-5 mg/kg every 4 hours by slow intravenous infusion over 20 minutes. If a few days of treatment are accompanied by stabilization of the patient s cardiovascular and gastrointestinal status, it may be possible to change to oral administration at a dose of 4-8 mg/kg every 6-8 hours. Oral unithiol may also be considered as an alternative to oral succimer in the treatment of lead intoxication. 

Treatment of acute mercury poisoning is by use of the dimercaprol chelating agents which leads to excretion via both bile and urine. Chronic exptisure is best treated with N-aceiyl-penicillamine. unless renal function is compromised. 

Chelation therapy often is begun with dimercaprol (3—4 mg/kg intramuscularly every 4—12 hours) until abdominal symptoms subside and charcoal (if given initially) is passed in the feces. Oral treatment with penicillamine then may be substituted for dimercaprol and continued for 4 days. Penicillamine is given in 4 divided doses to a maximum of 2 g/day. If symptoms recur after cessation of chelation therapy, a second course of penicillamine may be instituted. Succimer (2,3-dimercaptosuccinic acid), a derivative of dimercaprol, is efficacious in the treatment of arsenic poisoning but is FDA-approved only for lead chelation in children. 

I. Pharmacology. BAL (British anti-Lewisite, dimercaprol, 2,3-dimercaptopro-panol) is a dithiol chelating agent used in the treatment of poisoning by the heavy metals arsenic, mercury, lead, and gold. Because the vicinal thiol groups are unstable in aqueous solution, the drug is supplied as a 10% solution (100... 

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