Isoniazid overdose

Isoniazid Isoniazid is incompatible with sugars. Isoniazid overdose may be severe to fatal, and treatment is symptomatic and supportive, including stomach wash for control of convulsions and treating metabolic acidosis. Administration of pyridoxine and hemodialysis may be needed. Isoniazid interacts with carba-mazepine, phenytoin, diazepam, triazolam, chlorzoxazone, theophylline, ethosux-imide, enflurane, cycloserine, and warfarin. 

Urinary retention is a rare complication of isoniazid overdose (35). 

Wason S, Lacouture PG, and Lovejoy PH (1981) Single high-dose pyridoxine treatment for isoniazid overdose. Journal of the American Medical Association 246 1102-1104. 

Isoniazid (INH), a hydrazide derivative of isonicotinic acid, is the bactericidal drug of choice for tuberculosis. INH is well known for its propensity to cause hepatitis with chronic use. Acute isoniazid overdose is a common cause of drug-indued seizures and metabolic acidosis. 

The significance of the metabolic acidosis which occurs following ingestion of large amounts of isoniazid is emphasized in a paper by Bear et al. in which the point is made that the diagnosis of isoniazid overdose should always be considered in patients presenting with unexplained seizures together with a metabolic acidosis (10 -). 

Low antiepileptic drug levels, drug overdose (e.g., cocaine, isoniazid, theophylline, phenothiazine), ethanol-related, and drug withdrawal... 

When taken or administered in overdose to dogs, isoniazid produces seizures, metabolic acidosis, and, if untreated, death. 

Vitamin B complex is the collective term for a number of water-soluble vitamins found particularly in dairy products, cereals and liver.Vitamin B (thiamine) is used by mouth for dietary supplement purposes and by injection in emergency treatment of Wernicke-Korsakoff syndrome. Vitamin B2 (riboflavin) is a constituent of the coenzyme FAD (flavine adenine dinucleotide) and FMN (flavine mononucleotide) and is therefore important in cellular respiration. Vitamin Be (pyridoxine) is a coenzyme for decarboxylases and transamination, and is concerned with many metabolic processes. Overdose causes peripheral neuropathy. It may be used medically for vomiting and radiation sickness and for premenstrual tension. Pyridoxine has a negative interaction with the therapeutic use of levodopa in parkinsonism by enhancing levodopa decarboxylation to dopamine in the periphery, which does not then reach the brain. The antitubercular drug isoniazid interferes with pyridoxine, and causes a deficiency leading to peripheral neuritis that may need to be corrected with dietary supplements. Vitamin B ... 

Transient elevations of the serum transaminases occur in 12% to 15% of patients receiving isoniazid and usually occur within the first 8 to 12 weeks of therapy. Overt hep ato toxicity, however, occurs in only 1% of cases. Risk factors for hepatotoxicity include patient age, preexisting liver disease, excessive alcohol intake, pregnancy, and the postpartum state. Isoniazid also may result in neurotoxicity, most frequently presenting as peripheral neuropathy or, in overdose, as seizures and coma. Patients with pyridox-ine deficiency, such as pregnant women, alcoholics, children, and the malnourished, are at increased risk. Isoniazid may inhibit the metabolism of phenytoin, carbamazepine, primidone, and warfarin." Patients who are being treated with these agents should be monitored closely, and appropriate dose adjustments should be made when necessary. 

Hepafotoxicity from chronic paracetamol (acetaminophen) therapy in adults have been reported in the literature, but compared to the acute toxicity seen with deliberate or accidental overdoses, these are very few. The majorify of fhese are associafed wifh chronic efhanol intake, smoking, isoniazid, rifampin, phenobarbifal and phenyfoin (inducers of the cytochrome P450 system). Short-term fasting and... 

A. Acute overdose. Isoniazid produces acute toxic effects by reducing brain pyridoxal 5-phosphate, which is the active form of vitamin Bg and an essential cofactor for the enzyme glutamic acid decarboxylase. This results in lower CNS levels of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, which leads to uninhibited electrical activity manifested as seizures. INH may also Inhibit the hepatic conversion of lactate to pyruvate, exacerbating the lactic acidosis from seizures. 

A. Specific levels. Isoniazid Is not usually detected in routine toxicology screening. Specific levels may be obtained but are rarely available or helpful for management of acute overdoses. A 5 mg/kg dose produces a peak INH concentration of 3 mg/L at 1 hour (1-7 mg/L is considered antitubercular). Semm levels higher than 30 mg/L are associated with acute toxicity. 

Panganiban LR et al Rhabdomyolysis in isoniazid poisoning. J Toxicol Clin 7bx/co/2001 39(2) 143-151. [PMID 11407500] (Retrospective review of 270 iNH overdoses seen over 5-year period at Philippine General Hospital. Good review of symptoms, lab findings, and Incidence of rhabdomyolysis with INH poisoning.)... 

This report is consistent with another much earlier report of two patients who also developed peripheral neurotoxicity when they were given vincristine after starting to take isoniazid and pyridoxine, the cumulative doses of vincristine being 11 mg and 11.2 mg, respectively, and of a case of severe neurotoxicity with an overdose of isoniazid and high-dose vincristine. ... 

These predictions are as yet unconfirmed, but it would certainly be prudent to monitor tacrolimus levels closely if any of these drugs (with the possible exception of isoniazid) are used concurrently. The manufacturers also note that in animal studies, tacrolimus has been shown to decrease the clearance and increase the half-life of pentobarbital, and a report also describes the use of a phenobarbital infusion to treat a tacrolimus overdose. ... 

Drag overdose A 14-year-old girl was inadvertently immunized intracutaneously with 1.0 ml instead of 0.1 ml of BCG-Connaught vaccine and a few hours later developed a subcutaneous fluctuant tender lump at the injection site [3 ]. This was excised and she was treated with isoniazid and rifampidn for 6 weeks in order to prevent severe local and systemic complications that are often associated with BCG overdose. She had no complications, other than a minor scar. 

Six cases of isoniazid-induced convulsions were described by Coyer and Nicholson (9 ), in patients who had taken overdoses. The value of vitamin Be in the prevention and treatment of acute isoniazid poisoning was emphasized in this paper. In one of the cases reported, a single large intravenous dose of Be resulted in a dramatic cessation of seizures. These authors suggest that the dose of Be given over the first few hours after ingestion of the isoniazid should approach in weight the total amount of the latter estimated to have been taken. 

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