Disulfiram Toxicity: Symptoms, Diagnosis, and Treatment

What Is Disulfiram Toxicity?

Disulfiram is a medication that helps people stop drinking alcohol. It works by causing an unpleasant reaction when alcohol is consumed, discouraging its use. This reaction occurs due to the buildup of a substance called acetaldehyde in the body, leading to unpleasant symptoms. However, disulfiram itself can also have toxic effects on the body, affecting organs such as the liver, skin, and nervous system. These toxic effects, collectively known as disulfiram toxicity, can occur both from the reaction with alcohol and from the direct actions of the medication. It is important to be aware of these potential risks and complications associated with disulfiram use to ensure safe and effective treatment.

What Are the Signs and Symptoms of a Disulfiram Reaction?

The signs and symptoms of disulfiram toxicity can include

• Neurological Symptoms: Disulfiram toxicity can cause problems with the nerves in both the central and peripheral nervous systems. This may result in issues such as weakness, numbness, or tingling in the limbs; changes in mental state like confusion or psychosis, involuntary movements like twitching or jerking; and problems with coordination and balance.

• Dermatological Symptoms: Some people may develop skin-related issues due to disulfiram toxicity. This can include acne-like eruptions on the skin and allergic reactions that cause itching, redness, or a rash.

• Gastrointestinal Symptoms: Disulfiram toxicity can affect the digestive system and lead to symptoms such as a bad smell on the breath (often described as a rotten-egg odor), a metallic or garlic taste in the mouth, stomach pain, nausea, vomiting, and yellowing of the skin and eyes (jaundice).

• Hematologic Symptoms: Disulfiram toxicity can also affect the blood. It may cause problems such as a decrease in the number of certain blood cells, leading to a higher risk of infections, easy bruising or bleeding, and a condition called methemoglobinemia, where the blood is unable to carry oxygen effectively.

• Signs and Symptoms of Acute Disulfiram Overdose: It includes hypotension, tachycardia, dyspnea, abdominal pain, nausea, vomiting, sulfur or garlic odor on breath, agitation, dysarthria, chorea, hallucinations, lethargy, coma, seizures, Parkinson-like syndrome, polyneuropathy, hypersensitive hepatitis, and hepatic failure.

It is important to note that the symptoms may vary depending on the individual, the dosage and duration of disulfiram therapy, and other factors.

Is Disulfiram Neurotoxic?

Yes, disulfiram can be neurotoxic. It can cause neurotoxicity, including peripheral neuropathy (damage to the peripheral nerves), encephalopathy (brain damage), basal ganglia lesions (disorders affecting the ganglia of the brain), extrapyramidal disorders (movement disorders caused by defects in basal ganglia), and optic neuropathy (damage to the optic nerve of the eye). MRI (magnetic resonance imaging) of the brain typically shows lesions in the basal ganglia, striatum, or putamen. This neurotoxicity occurs when an affected individual receives disulfiram for several months and develops symptoms including distal weakness, sensory loss, and an unsteady gait.

How Is Disulfiram Toxicity Diagnosed?

The diagnosis of disulfiram toxicity involves conducting various laboratory studies. These tests help evaluate different aspects of the patient's health and determine if disulfiram is causing any adverse effects. The following laboratory studies are typically performed:

• Glucose Level: This test measures the amount of glucose (sugar) in the blood and helps assess if there are any abnormalities related to disulfiram toxicity.

• Electrolyte Levels: Electrolytes, such as sodium, potassium, and chloride, play a vital role in maintaining the body's balance. Testing electrolyte levels helps identify any imbalances caused by disulfiram toxicity.

• Renal Function Tests: These tests assess the functioning of the kidneys and evaluate if disulfiram toxicity has affected kidney function.

• Liver Function Tests: Liver function tests measure different markers that indicate the liver's health. Disulfiram toxicity can impact liver function, and these tests help detect any abnormalities.

• Ethanol Level: Measuring the level of ethanol (alcohol) in the blood helps determine if the patient has recently consumed alcohol, as disulfiram can cause a severe reaction when combined with alcohol.

• Acetaminophen Level: Acetaminophen is a common medication, and testing its level can help rule out any potential interactions with disulfiram.

• Arterial Blood Gas Analysis: This test measures the levels of oxygen, carbon dioxide, and other gases in the blood, providing information about respiratory function.

• Methemoglobin Level: Methemoglobin is a form of hemoglobin that cannot carry oxygen effectively. Testing methemoglobin levels helps identify a specific type of blood disorder that may be related to disulfiram toxicity.

Additional specific laboratory tests that may be considered include:

• Acetaldehyde Level Test: This test measures the level of acetaldehyde, a toxic byproduct of alcohol metabolism, in the blood. Elevated levels can indicate disulfiram toxicity.

• DDC Level Test: DDC refers to diethyldithiocarbamate, a metabolite of disulfiram. Measuring DDC levels can help confirm disulfiram exposure.

• CS2 Level Test: CS2 (carbon disulfide) is another metabolite of disulfiram. Its measurement can provide further evidence of disulfiram toxicity.

• Tetraethylthiuram Level (Disulfiram Level) Test: This test directly measures the level of disulfiram in the blood, confirming its presence.

In addition to laboratory studies, imaging techniques like CT (computed tomography) scans or MRIs of the head may be conducted. These imaging studies are helpful in assessing the involvement of the central nervous system (CNS) and identifying any specific brain abnormalities, such as basal ganglia ischemia or infarction. They also aid in ruling out other potential causes of altered mental status. Brain MRI typically shows lesions in the basal ganglia, striatum, or putamen suggestive of disulfiram neurotoxicity.

How Does Disulfiram Toxicity Affect Children?

Disulfiram toxicity is primarily used in adults as a treatment for alcohol dependency. Though disulfiram toxicity is uncommon in children and only a few cases have been documented in the literature, it can occur in children who have ingested an overdose of the drug due to careless and unsafe storage. Disulfiram inhibits the enzyme aldehyde dehydrogenase and can lead to elevated levels of acetaldehyde in the body, causing an unpleasant reaction. the rare occurrence of disulfiram poisoning in children, which typically happens when the drug is carelessly stored, and large amounts are ingested.

Overdose symptoms include vomiting, a skin rash, aggressive behavior, and, in severe cases, coma and paralysis. There is no specific antidote for disulfiram toxicity, and treatment involves supportive care, airway protection, oxygen, and intravenous fluids.

Also, if a child who was healthy before has unexplained brain dysfunction (encephalopathy) with extrapyramidal symptoms (a group of movement disorders caused by dysfunction of the basal ganglia) and an MRI brain scan shows signal changes in the basal ganglia (a group of brain nuclei involved in controlling movement), acute disulfiram poisoning should be considered as a possible cause.

The exact cause of disulfiram-mediated encephalopathy is not known, but it is thought that the drug may damage cells by causing excitotoxicity, which is when cells die because of the harmful effects of excitatory amino acids, and by making it harder for cells to get rid of free oxygen radicals. The recommended treatment for disulfiram poisoning in children is mainly supportive care, including airway protection, oxygen therapy, and administering dextrose-containing intravenous fluids.

How Can Disulfiram Toxicity Be Prevented?

Patients using disulfiram should be instructed to keep a medical alert card with them, which includes information about their medication-assisted treatment, possible side effects such as symptoms of a disulfiram-alcohol reaction, and contact details of their healthcare provider or hospital for emergencies. Additionally, patients should be informed to promptly inform their physician if they experience any initial signs of hepatitis, such as fatigue, weakness, malaise, loss of appetite, nausea, vomiting, jaundice, or dark urine.

What Is the Treatment for Disulfiram Toxicity?

The treatment of disulfiram toxicity involves several approaches:

• Supportive Care: Providing supportive measures to manage symptoms and stabilize vital signs. This includes maintaining a clear airway, ensuring proper oxygenation, and administering fluids and medications as needed.

• Symptom Management: Addressing specific symptoms such as nausea, vomiting, or headache with appropriate medications.

• Discontinuation of Disulfiram: If disulfiram toxicity is confirmed, discontinuing the medication is necessary to prevent further adverse effects.

• Monitoring and Observation: Close monitoring of vital signs, organ function, and overall clinical status to assess improvement and detect any complications.

In severe cases or when complications arise, hospitalization may be required for intensive monitoring and management. It is important to seek medical attention promptly if disulfiram toxicity is suspected or if severe symptoms occur.

Conclusion

To conclude, while disulfiram can be beneficial in helping people overcome alcoholism, it is essential to be aware of the potential risks and complications associated with its use. Prompt recognition and appropriate management of disulfiram toxicity are crucial for ensuring patient safety and well-being.