Title 8.4 Clinical symptoms and management of chronic poisoning of Heavy metals - Iron - Clinical Toxicology - Pharma Dost.pdf ✅

Cl.Toxicology Clinical symptoms and management of chronic poisoning Pharma Dost | www.PharmaDost.info 1 Heavy metals Iron Metallic iron is silvery white in colour, occurring naturally as haematite, magnetite, etc. and usually causes no problems. In fact it is an essential element and deficiency results in anaemia. Even if there is more than the required intake daily, the excess is excreted. But in some individuals with inborn errors, even normal dietary iron can cause toxic effects due to accumulation, e.g. haemochromatosis. Toxicity levels: This may be done using clinical state, dose ingested and/or iron concentrations. The usual fatal dose corresponds to about 200 to 250 mg of elemental iron per kg of body weight. In practice, this can be as low as 60 mg of elemental iron/kg. Hence just a handful of these tablets (15 to 20 in number), can be lethal Fig 9.19: Ferrous sulfate to a young child. Mechanism: Iron toxicity develops when serum iron concentrations exceed the iron binding capacity of transferrin in blood. The free circulating iron damages many organs by direct cellular toxicity, effects on vasculature and the release of vasodilating mediators. The mechanism of toxicity involves  Direct corrosive effect on the GIT, Metabolic acidosis
Cl.Toxicology Clinical symptoms and management of chronic poisoning Pharma Dost | www.PharmaDost.info 2  Metabolic acidosis: Conversion of Fe++ to Fe+++, binding to -OH and release of H+, Inhibition of mitochondrial respiration and lactic acid production.  Cell death following lipid peroxidation due to production of free radicals.  Coagulopathy - Initially due to direct iron inhibition of thrombin, then. Secondary to hepatotoxicity and reduced production of factors II, VII, IX and X. Clinical (Toxic) Symptoms: A severe iron poisoning leads to multiorgan failure however, there are two preceding phases: o Gastrointestinal toxicity o Window period  Gastrointestinal effects: A severe haemorrhagic gastroenteritis occurs within a few hours of ingestion. Vomiting occurs in virtually all patients with severe poisoning but is not a specific sign. If fluid loss is significant there may be hypotension, acidosis and central nervous system signs. Other symptoms include Lethargy, coma and convulsions.  Cardiovascular effects: Intractable hypotension and pulmonary oedema.  Renal toxicity - renal failure and acute tubular necrosis.  Metabolic acidosis - severe lactic acidosis is common.  Hepatotoxicity - severe hepatic necrosis may occur with peak ALT/AST occurring 1-4 days post ingestion. Complicated by hypoglycaemia and coagulopathy.
Cl.Toxicology Clinical symptoms and management of chronic poisoning Pharma Dost | www.PharmaDost.info 3 Investigations/Diagnosis: Patients should have the following investigations done urgently:  Iron concentration  Full blood count and coagulation studies  Electrolytes Glucose  Abdominal X-ray Iron concentrations are used to determine the need for specific treatment. Abdominal X-rays may identify radio-opaque tablets however their absence does not exclude iron overdose. A raised white cell count and hyperglycaemia commonly occur early in poisoning. Other tests serve as a baseline with which to determine subsequent toxicity. These tests need to be repeated regularly in patients who develop gastrointestinal or other toxicity. Management:  Decontamination - Iron is well known to form drug concretions (pharmacobezoar) and/or become adherent to the gastric wall due to its corrosive effect. Activated charcoal is not effective.  Whole bowel irrigation, gastroscopic removal and gastrotomy will enhance decontamination.  Patients with confirmed exposure to a potentially toxic dose should have gastric lavage and polyethylene glycol whole bowel irrigation if they present within 4 hours.  Magnesium hydroxide solution (1%) administered orally may help reduce absorption of iron by precipitating the formation of ferrous hydroxide. Magnesium hydroxide and calcium