British Anti-Lewisite, widely known by the acronym BAL, is the common name for the chemical compound Dimercaprol. This medication serves a specific purpose in medicine as a chelating agent, meaning it has the ability to bind with heavy metal ions in the body. BAL was initially developed as a defense against a chemical weapon, but it found modern utility in treating acute poisoning caused by various toxic metals. Its primary function is to neutralize the harmful effects of these substances and facilitate their removal from the body.
Historical Context and Origin
The development of Dimercaprol was a direct result of military necessity during the Second World War. British biochemists at Oxford University worked to create an effective antidote for Lewisite, an arsenic-based chemical warfare agent. Lewisite was classified as a vesicant, a blistering agent that causes tissue damage by disrupting biochemical processes in the body.
Lewisite achieved its toxicity by binding to sulfhydryl groups on specific enzymes, thereby inactivating them and causing cellular damage. The research team successfully synthesized 2,3-dimercaptopropanol, a dithiol compound that contained two sulfhydryl groups. This molecule was designed to compete with the body’s natural enzymes for binding to the arsenic in Lewisite.
The compound’s ability to form a stable, non-toxic ring structure with the arsenic neutralized the poison, leading to the name British Anti-Lewisite. This development was a significant strategic achievement, providing a crucial defense against a potential chemical attack on Allied forces. After the war, researchers realized the compound’s metal-binding properties could be applied to accidental and intentional heavy metal poisonings.
Mechanism of Action and Current Medical Applications
Dimercaprol’s function centers on a process called chelation, which involves the molecule encapsulating toxic metal ions circulating in the bloodstream and tissues. It is a dithiol, meaning it possesses two sulfhydryl (thiol) groups that have a high affinity for heavy metals.
Heavy metals like arsenic and mercury exert their toxic effects by binding to and inactivating the sulfhydryl groups found in the body’s native proteins and enzymes. Dimercaprol intervenes by binding to the metal ions more strongly than the body’s enzymes do. Once the metal is bound, a stable, water-soluble complex is formed, which effectively neutralizes the metal’s toxicity.
The newly formed metal-Dimercaprol complex is then processed by the body and excreted, primarily through the urine. This mechanism makes BAL an important treatment for acute toxicity caused by several metals. Its primary current medical applications are in the treatment of severe arsenic and inorganic mercury poisoning.
Dimercaprol is also used for acute, severe lead poisoning, especially in cases where the brain is affected, known as lead encephalopathy. In this specific application, it is often used in combination with another chelating agent, calcium disodium edetate, to enhance lead removal. It can also be used to treat poisoning from gold, which historically occurred in patients receiving gold salt injections for conditions like rheumatoid arthritis.
While other, newer chelating agents have been developed, Dimercaprol remains a standard treatment for specific, life-threatening heavy metal poisonings. However, it is not used for all metal toxicities, as it can form toxic complexes with elements like iron, cadmium, and selenium. These toxic complexes can increase harm to the patient, particularly causing damage to the kidneys, which is why its use is restricted. Its effectiveness is highest when administered as soon as possible after the exposure to the toxic metal.
Administration and Safety Considerations
The practical use of Dimercaprol is highly specific due to its chemical properties and the severe nature of the poisonings it treats. The medication is not absorbed well through the digestive system, so it must be administered by a deep intramuscular injection. Because Dimercaprol is an oily liquid, it is formulated as a suspension in peanut oil, which makes it a contraindication for any patient with a peanut allergy.
The injection itself can be quite painful, and multiple doses over several days or weeks are often necessary to ensure complete removal of the toxic metal. Peak concentrations in the blood are generally reached within 30 to 60 minutes after the injection, and the rapid elimination requires frequent dosing to maintain therapeutic levels. Healthcare providers must carefully monitor patients, as the drug has a narrow therapeutic range, meaning the dose needed for treatment is close to the dose that can cause side effects.
Many patients experience adverse effects during treatment, though most are not serious and resolve once the drug is stopped. Common side effects include pain at the injection site, nausea, and vomiting. Systemic reactions can include a temporary rise in blood pressure, rapid heart rate, and a burning sensation in the mouth, throat, or eyes.
A distinctive sulfurous odor on the breath and urine is a common occurrence, related to the chemical structure of Dimercaprol itself. Contraindications for its use include severe impairment of liver function, except in cases of liver damage caused by arsenic, and certain pre-existing conditions like G6PD deficiency. Its use must be carefully managed to balance the necessity of removing the toxic metal against the drug’s inherent side effects.