Lead intoxication: effects on cytochrome P-450-mediated hepatic oxidations.

Acute administration of lead to rats caused significant decreases in cytochrome P=450, ethylmorphine N-demethylase, and aniline hydroxylase activities and prolonged hexobarbital-induced sleeping times. However, chronic administration of lead to weanling rats caused no significant changes in hepatic cytochrome P-450 levels or in the microsomal oxidative enzymes over a 12-wk period. Eight patients exposed to lead in the process of burning through lead-painted steel structures for at least 3 mo showed marked effects of chronic lead intoxication on the erythropoietic system: inhibition of erythrocyte delta-aminolevulinic acid dehydratase, increased erythrocyte protoporphyrin levels, and increased urinary excretion of delta-aminolevulinic acid. Chelation therapy greatly alleviated the inhibitory effects on dehydratase activity and decreased urinary delta-aminolevulinic acid excretion. The plasma elimination rate of antipyrine, a drug primarily metabolized by hepatic microsomal enzymes, was determined in the 8 subjects prior to and following chelation therapy. In 7 of 8 subjects, chelation therapy shortened the antipyrine half-lives, but the effect was minimal. These studies show that chronic lead exposure results in significant hematopoietic inhibition of the heme biosynthetic pathway without causing significant changes in hepatic cytochrome P-450-associated enzymic activities.     

Lead intoxication due to ayurvedic medications as a cause of abdominal pain in adults

Background: Though a majority of cases of lead intoxication come from occupational exposures, traditional and folk remedies have also been reported to contain toxic amounts of lead. We present a large series of patients with lead poisoning due to intake of Ayurvedic medicines, all of whom presented with unexplained abdominal pain.

Methodology: This was a retrospective, observational case series from a tertiary care center in India. The charts of patients who underwent blood lead level (BLL) testing as a part of workup for unexplained abdominal pain between 2005 and 2013 were reviewed. The patients with lead intoxication (BLLs?>25?μg/dl) were identified and demographics, history, possible risk factors, clinical presentation and investigations were reviewed. Treatment details, duration, time to symptomatic recovery, laboratory follow-up and adverse events during therapy were recorded.

Results: BLLs were tested in 786 patients with unexplained abdominal pain and high levels were identified in 75 (9.5%) patients, of which a majority (73 patients, 9.3%) had history of Ayurvedic medication intake and only two had occupational exposure. Five randomly chosen Ayurvedic medications were analyzed and lead levels were impermissibly high (14–34,950?ppm) in all of them. Besides pain in abdomen, other presenting complaints were constipation, hypertension, neurological symptoms and acute kidney injury. Anemia and abnormal liver biochemical tests were observed in all the 73 patients. Discontinuing the Ayurvedic medicines and chelation with d-penicillamine led to improvement in symptoms and reduction in BLLs in all patients within 3–4 months.

Conclusion: The patients presenting with severe recurrent abdominal pain, anemia and history of use of Ayurvedic medicines should be evaluated for lead toxicity. Early diagnosis in such cases can prevent unnecessary investigations and interventions, and permits early commencement of the treatment.     

Phenytoin intoxication

We studied the clinical features of 85 cases of phenytoin toxicity in 76 patients treated at a general hospital. Serum levels of phenytoin on admission ranged from 30.3 to 95.0 micrograms/mL (median, 46.5). Iatrogenic causes of intoxication were common and included increased daily dosage and intravenous loading in the emergency room for single seizures in patients with subtherapeutic serum phenytoin levels. The most frequent neurologic findings were nystagmus (95%), ataxia (88%), lethargy (22%), and seizures (19%). Outcome was usually good, but three patients had serious complications.     

Cocaine intoxication

Cocaine intoxication can be manifested by a multitude of chief presenting complaints. Although cardiovascular and central nervous system stimulation is common, patients may present with a broad array of symptoms. Thus, whenever the underlying cause of a set of symptoms is unexplained, the primary care physician needs to consider the possibility of cocaine abuse.     

Acute intoxication

Acute alcohol intoxication is a commonly encountered clinical presentation in Emergency Medicine. Its role should be considered in many Emergency Department presentations, specifically in major and minor trauma, and in gastrointestinal, metabolic, neurologic, and psychiatric disorders. The differential diagnosis of change in mental status must be considered in all intoxicated patients. Management of intoxicated patients is generally supportive although complications of chronic alcoholism should be considered. Management should consist of correction of complications resultant from intoxication, as well as observation and the provision of a safe environment for the patient during the recovery phase of acute intoxication.     

Acute arsenic intoxication

The diagnosis of acute arsenic poisoning should be considered in any patient presenting with severe gastrointestinal complaints. Signs and symptoms include nausea, vomiting, colicky abdominal pain and profuse, watery diarrhea. Hypotension, fluid and electrolyte disturbances, mental status changes, electrocardiographic abnormalities, respiratory failure and death can result. Quantitative measurement of 24-hour urinary arsenic excretion is the only reliable laboratory test to confirm arsenic poisoning. Treatment includes gastric emesis or lavage, chelation therapy, electrolyte and fluid replacement, and cardiorespiratory support.     

Acute acetaminophen intoxication

Acetaminophen is a readily available, widely used drug which has been thought safer than aspirin. Overdosage which may result in fatal hepatic necrosis is commonly seen in the United Kingdom but is rarely reported in the United States. In a two-month period, three patients were admitted to a general hospital because of acetaminophen overdose, suggesting that this problem may occur more commonly than expected. They were successfully treated with N-acetylcysteine. Our experience in management of these three patients is presented and the pertinent literature concerning diagnosis and treatment of acute acetaminophen intoxication in briefly reviewed.     

Barium carbonate intoxication

A 22-year-old man attempted to commit suicide by swallowing an unknown amount of barium carbonate dissolved in hydrochloric acid. Shortly after ingestion, he developed crampy abdominal pain and generalized muscle weakness. About 2 h later, respiratory failure ensued necessitating orotracheal intubation and mechanical ventilation. Concomitantly, life-threatening arrhythmias including ventricular fibrillation occurred, and he had to be resuscitated for 45 min. After correction of severe hypokalemia (serum potassium 1.5 mmol/l), cardiac rhythm stabilized. In an attempt to accelerate removal of barium from the circulation hemodialysis was begun. During hemodialysis muscle strength returned. Pharmacokinetic analysis of serum barium levels suggest that hemodialysis shortened the serum half-life of barium. Subsequently, the patient made a complete and uneventful recovery. Our case demonstrates that severe barium poisoning can be survived provided that early aggressive therapeutic measures are undertaken. Hemodialysis seems to be efficacious in the therapy of barium intoxication.