Introduction:
Isoniazid, when taken accidentally by kids or taken in large doses in suicide attempt cases, and patients taking additional tablets than the prescribed number causes Isoniazid toxicity (harmful effects).
What Is Isoniazid?
Isoniazid is an antibacterial agent used in the treatment plan for tuberculosis and prevents the disease from occurring again. Isoniazid is given along with other medications like Rifampicin, Streptomycin, or Ethambutol (other types of antibiotics) while treating a tuberculosis patient. The medication alone is given for the prevention of tuberculosis.
What Is Tuberculosis?
Tuberculosis is a serious lung infection caused by mycobacterium tuberculosis. It is usually spread from an infected person through a cough or while sneezing. These droplets from coughing or sneezing travel in the air, and when a healthy person comes in contact with these droplets, they acquire tuberculosis.
What Does Isoniazid Do to the Body?
Isoniazid is an antibacterial medication that fights a specific organism called mycobacterium that causes tuberculosis. This medication acts by preventing mycolic acid synthesis (a long-chain fatty acid present in the cell wall of mycobacterium). Mycolic acid helps the mycobacterium to survive and helps in creating harmful effects on the body. The bactericidal (killing the bacteria) effects of Isoniazid are achieved by preventing the mycolic acid production, which in turn prevents the cell wall synthesis of the organism (bacteria).
What Is the Recommended Dose of Isoniazid?
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For Prevention of Return of Tuberculosis:
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Adults: 300 mg total dose once daily.
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Children: Dosage for children usually depends on the weight of the child. It is 10 mg per kilogram (kg) of body weight up to 300 mg total dose once daily.
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For Treatment of Tuberculosis:
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Adults: 300 mg total one time a day or 15 mg per kg, up to 900 mg total dose, two times or three times per week.
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Children: Dosage depends on the body weight of the child. Generally, 10 mg to 20 mg per kg body weight, up to 300 mg total dose one time a day; or 20 mg to 40 mg per kg body weight, up to 900 mg total body weight, two times or three times a week will be recommended.
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These recommendations are for a period of about 6 to 9 months.
When Does Isoniazid Dose Become Toxic?
When a dosage of 30 mg per kg body weight causes seizures and doses exceeding 80 to 150 mg per kg body weight can be fatal. Also, when the patient takes a double dose or takes beyond the extended time, Isoniazid toxicity occurs.
What Are the Types of Isoniazid Toxicity?
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Acute Toxicity: Acute toxicity is caused by consuming 2g of Isoniazid and causes neurological symptoms (seizure, muscle weakness, or loss of sensation). The symptoms appear in less than 30 minutes of tablet intake.
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Chronic Toxicity: Chronic toxicity causes hepatotoxicity (harmful effects on the liver) and peripheral neuropathy (damage to nerves present outside the brain and spinal cord). Chronic toxicity occurs rarely and cannot be predicted. It is not because of the high dose of isoniazid but can occur due to some drug interactions like idiosyncratic reactions (the unexpected effects of drugs that do not depend on the dose or duration of the drug).
What Are the Symptoms of Isoniazid Toxicity?
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Nausea and vomiting.
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Slurred speech.
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Dizziness.
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Fever.
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Weakness or numbness in the legs and hands (peripheral neuritis).
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Increased heart rate.
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Urinary retention (unable to empty bladder).
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Metabolic acidosis (accumulation of acid in the body due to kidney dysfunction).
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Grand mal seizure (becoming unconscious and developing vigorous muscular contractions).
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Stupor (state of being unresponsive or unable to think clearly).
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Coma (state of unconsciousness for a long period).
What Are the Tests to Find Isoniazid Toxicity?
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Symptoms: Symptoms like refractory seizures (when the seizures are not controlled with anti-seizure medications) are typical of Isoniazid toxicity.
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Past Medical History: Thorough medical history of the patient, if the patient is undergoing treatment for tuberculosis or if the patient has any psychiatric problems.
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Purified Protein Derivative (PPD) Test: This test is done by injecting 0.5 ml of 5 TU (tuberculin units) of PPD on the uppermost layer of the skin in the forearms. The fraction of purified protein from the mycobacterium tuberculosis is tuberculin. A pale color elevation in the skin between 6 mm (millimeter) to 10 mm in diameter appears. This is a confirmatory test to detect tuberculosis.
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Complete Blood Count: Complete blood test screens all the components in the blood like red blood cells, white blood cells, hemoglobin, eosinophils, basophils, and platelets. The drop in levels of platelets, hemoglobin, and higher levels of eosinophils suggest liver damage due to Isoniazid toxicity.
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Metabolic Acidosis: The test is done by measuring the serum electrolytes and arterial blood gasses (ABGs). The results are positive for metabolic acidosis if the pH (measurement of acidity/basic of water), PaCO2 (partial pressure of carbon dioxide in the blood), and HCO3 (body's metabolic waste called bicarbonate) are low.
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Liver Function Tests: Liver function tests involve screening of liver enzymes like alanine aspartate (ASP), alkaline phosphatase (ALP), and alanine transaminase (ALT) and proteins like albumin and globulin. Elevated levels of alanine transaminase and alkaline phosphatase suggest liver injury.
What Are Treatments for Isoniazid Toxicity?
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Activated Charcoal: Administering activated charcoal in acute isoniazid toxicity before the seizure occurs will prevent further absorption of Isoniazid.
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Pyridoxine: Pyridoxine is vitamin B6 which is a water-soluble vitamin. It is administered through veins in a 1g Pyridoxine to 1g Isoniazid ingested. If the doctor is not aware of the Isoniazid dose ingested, a standard protocol of giving 5 g of Pyridoxine is given intravenously. A repeated dose of 5 g Pyridoxine should be given every 30 minutes till the seizures stop.
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Benzodiazepine: Benzodiazepine 5 mg to 10 mg is administered as an alternative when the required dose of Pyridoxine is not available. Benzodiazepine is an antidepressant that causes sedation and relaxation. It is used in controlling seizures.
What Are the Side Effects of Isoniazid?
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Unsteadiness.
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Dark-color urine.
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Numbness, tingling sensation, and burning sensation in the hands and feet.
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Nausea and vomiting.
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Unusual weakness.
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Yellowish discoloration of the skin and eyes (jaundice).
Is Patient Education Needed For Patients Receiving Isoniazid?
Yes, patients should be informed about liver damage and the harmful effects of Isoniazid overdose.
What Are the Complications of Isoniazid Toxicity?
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Repeated seizures.
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Metabolic acidosis.
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Coma.
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Death.
What Is the Prognosis of Isoniazid Toxicity?
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Acute Toxicity: The prognosis depends on the dosage ingested. If the dose ingested is 15 g, the prognosis is poor if not treated properly.
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Chronic Toxicity: The prognosis depends on the extent of the liver damage. If the liver damage is detected early and appropriate treatments are done, there will be a moderate prognosis. Elderly patients with seizure disorders, severe metabolic acidosis (accumulation of acids in the body due to kidney disease), and poor kidney functions show poor prognosis.
Can Isoniazid Toxicity be Prevented?
Yes, Isoniazid toxicity can be prevented if the protocols below are followed:
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Patients who receive isoniazid should be screened for depression.
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If the patient is positive for depression, a two-week supply prescription should be given to avoid misusing the medication.
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Avoid consuming too much alcohol while in Isoniazid therapy.
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Avoid using other medications that cause liver damage like Pyrazinamide (an antibiotic used to treat tuberculosis) along with Isoniazid.
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If the side effects of the medication do not resolve, visit the doctor immediately.
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If the patient is negative for depression screening, one month's supply of the medication can be prescribed to prevent the availability of a large dosage and misuse of the drug.
Conclusion:
Isoniazid is an antibacterial medication used in the treatment of tuberculosis. Taking a high dose of Isoniazid beyond the prescribed dose or time will result in serious health problems. Some people misuse this medication as it gives a relaxed feeling, and psychiatrically affected patients with suicidal tendencies use this medication to attempt suicide. Possible side effects should be discussed while prescribing this medication. The toxic effects of these medications lead to liver damage, coma, and death if not detected and treated early. Patients need to be educated on the toxic effects of the medication if consumed beyond the recommended dose or misuse of the medication. The patients need to be monitored every month to check for any adverse reaction or if it needs medical attention. Though Isoniazid toxicity is serious and life-threatening, taking the medications for the prescribed period and checking with the doctor if any adverse reactions occur will reduce the complications and increase the lifespan of the patient.
