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CLINICAL TOXICOLOGY

Toxicology Folder
I-CLINICAL STRATEGY FOR TREATMENT OF THE POISONED PATIENT Clinical Stabilization-[ABCs/ Vital Signs] Clinical History in the Poisoned Patient Physical Examination Laboratory Evaluation Radiographic Examination Prevention of Further Poison Absorption Enhancement of Poison Elimination Use of Antidotes in Poisoning Supportive Care of the Poisoned Patient Source: Modified from Casarett and Doulls, Toxicology-The Basic Science of Poisons CH. 32 Content Outline; McGraw-Hill 7th ed. 2008

II- DRUG POISONING


(See: BRS Pharm pg. 319 and IVMS Principles of Toxicology and Anidotes -IN Special Topics Pharmacology.pdf)

A. General management of the poisoned patient (see Table 13-1) 1. Observe vital signs. 2. Obtain history. 3. Perform a toxicologically oriented physical examination. B. Symptoms 1. More than a million cases of acute poisoning occur each year in the United States, many in children and adolescents. 2. The symptoms of most drug and chemical poisonings are extensions of their pharmacologic properties. Common causes of death include CNS depression with respiratory arrest, seizures, cardiovascular abnormalities with severe hypotension and arrhythmias, cellular hypoxia, and hypothermia. C. Treatment. Measures to support vital functions, slow drug absorption, and promote excretion are generally sufficient for treatment. If available, specific antidotes can also be used. 1. Vital function support a. In the presence of severe CNS depression, it is important to clear the airway and maintain adequate breathing and circulation (ABC). Comatose patients may die as a result of airway obstruction, respiratory arrest, or aspiration of gastric contents into the tracheobronchial tube. b. Other important supportive measures include maintaining electrolyte balance and maintaining vascular fluid volume with IV dextrose infusion.
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2. Drug absorption a. Drug absorption may be slowed or prevented by decontamination of the skin. Induction of vomiting with ipecac orally is no longer recommended for routine use at home, and is contraindicated in children under 6 years. Its use is also limited in the emergency room in favor of activated charcoal. b. Emesis is contraindicated if corrosives have been ingested (reflux may perforate the stomach or esophagus), petroleum distillates have been ingested (may induce chemical pneumonia if aspirated), the patient is comatose or delirious and may aspirate gastric contents, or CNS stimulants have been ingested (may induce seizure activity with stimulation of emesis). (1) Gastric lavage is performed only when the airway is protected by an endotracheal tube. (2) Chemical adsorption with activated charcoal (a) Activated charcoal will bind many toxins and drugs, including salicylates, acetaminophen, and antidepressants. (b) This procedure can be used in combination with gastric lavage. (3) Cathartics are used occasionally to speed removal of toxins from the GI tract. Sorbitol is a recommended agent in the absence of heart failure. Magnesium sulfate can be used in the absence of renal failure. 3. Promotion of elimination may be achieved by the following: a. Chemically enhancing urinary excretion. Urinary excretion can be enhanced by the administration of agents such as sodium bicarbonate, which raises urinary pH and decreases renal reabsorption of certain organic acids such as aspirin and phenobarbital. b. Hemodialysis is an efficient way to remove certain low molecular weight, watersoluble toxins and restore electrolyte balance. Salicylate, methanol, ethanol, ethylene glycol, paraquat, and lithium poisonings are effectively treated this way; hemoperfusion may enhance the whole-body clearance of some agents (carbamazepine, phenobarbital, phenytoin). Drugs and poisons with large volumes of distribution are not effectively removed by dialysis. 4. Antidotes (see respective agents) are available for some poisons and should be used when a specific toxin is identified. Some examples include naloxone, acetylcysteine, physostigmine, metal chelators (see above), atropine, pralidoxime, and ethanol.

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POISONED PATIENT QUESTIONS Step 1 q and a 16 Block 5 A 3-year-old boy presents to his pediatrician with irritability, an ataxic gait, and regression of speech to single words. During the interview, the patient is constantly putting objects in his mouth. Laboratory values are significant for a hemoglobin level of 8.3 g/dL. Which of the following etiologies should be suspected in this patient? (A) Acetaminophen toxicity (B) Aspirin toxicity (C) Button battery ingestion (D) Lead poisoning (E) Organophosphate absorption (F) Tricyclic antidepressant overdose 16. The correct answer is D. A diagnosis of lead poisoning should be considered in young patients living in an environment with high lead levels (such as old houses with lead paint) and with a history of pica (eating non-nutritive substances) These patients present with the findings described in this case, including irritability, anorexia, ataxia, and regression of speech. These findings are due to acute encephalopathy secondary to lead poisoning as well as a microcytic anemia from inhibition of the heme synthetic pathway by lead. Treatment should include ethylenediamine tetra-acetic acid (EDTA) or, for more severe cases, dimercaprol. Answer A is incorrect. Acetaminophen toxicity can be a time bomb because patients may initially be asymptomatic. In the first 24 hours, nausea, vomiting, and malaise are common. At 2448 hours, the patients symptoms subside with possible right upper quadrant pain. At day 34, there is onset of jaundice and hepatic failure. N-acetylcysteine (Mucomyst) should be given within 8 hours of ingestion but is useful as late as 36 hours after ingestion. Answer B is incorrect. Aspirin (salicylic acid) toxicity is associated with tinnitus, abdominal pain, vomiting, and tachypnea at low doses. At higher doses, respiratory alkalosis, metabolic acidosis, hypotension, coma, and death can occur. Urine can be alkalinized with sodium bicarbonate infusion to promote excretion of salicylate. Salicylate toxicity can be confused with diabetic ketoacidosis. Answer C is incorrect. Button battery ingestion is a concern only if the battery becomes lodged in the esophagus, because leakage of alkali can lead to perforation. If the battery is past the esophagus, the child can be sent home and the parents can be instructed to screen for the battery in the patients stool. Answer E is incorrect. Organophosphate toxicity found in insecticides and carbamates can be absorbed through the skin. Symptoms include excess cholinergic activity (due to block of anticholinesterase by the organophosphate) leading to miosis, salivation,
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lacrimation, diarrhea, urination, and sweating. Treatment includes atropine and pralidoxime. Answer F is incorrect. Tricyclic antidepressant overdose can result in anticholinergic symptoms such as hallucinations, dry mouth, fl ushing, urinary retention, and mydriasis (mad as a hatter, dry as a bone, red as a beet). However, the most severe complication of tricyclic antidepressant overdose is tachyarrhythmias, which can result in death. Step 1 q and a 48. Renal A 17-year-old girl develops severe diarrhea after eating an undercooked hamburger at a family picnic. After 3 days of experiencing diarrhea, she presents to the emergency department with moderate dehydration and orthostatic hypotension. Which of the following acid-base states is most probable in this patient?

(A) A (B) B (C) C (D) D (E) E (F) F 48. The correct answer is D. The lab values given show low pH with low plasma bicarbonate and lack of an anion gap. Anion gap can be calculated by: Na+ (Cl + HCO3 ), where normal is within 1016 mEq/L. This patient has a nonunion gap metabolic acidosis. The cause of metabolic acidosis is generally either an increase in acid (e.g., diabetic ketoacidosis, hypovolemic shock via generation of lactic acid) or a decrease in base (e.g., diarrhea, kidney failure).
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Metabolic acidosis can be further subdivided into nonanion-gap and anion-gap metabolic acidosis. If the primary cause of acidosis is a loss of HCO3 , there will be an increase in Cl and the anion gap will be normal, as seen in the case of severe diarrhea. However, in the case of high serum anion gap, the metabolic acidosis is caused by an increase of an unmeasured anion such as lactate (e.g., lactic acidosis). Answer A is incorrect. The lab values in this choice are consistent with an anion gap metabolic acidosis. However, the patients anion gap will be normal. The primary cause of her metabolic acidosis is loss in HCO3 due to her diarrhea. Increased anion-gap metabolic acidosis is caused by an increase in unmeasured anion. A useful mnemonic is MUDPILES: Methanol, Uremia, Diabetic ketoacidosis/ EtOH ketoacidosis, Paraldehyde, Isoniazid/ Iron toxicity, Lactic acidosis, Ethylene glycol, and Salicylates. Rhabdomyolysis is also a cause of metabolic acidosis but traditionally is not included in this mnemonic. Answer B is incorrect. Respiratory acidosis is the presence of low pH due to a decrease in ventilation and an increase in serum carbon dioxide. This occurs in cases of inadequate ventilation (e.g., depressed respiration by drugs or neurologic injury) or impaired gas exchange (e.g., pulmonary edema). This would not be caused by diarrhea. Answer C is incorrect. Metabolic alkalosis is the presence of high pH with increased plasma bicarbonate. This occurs with addition of alkaline compounds (antacid ingestion) or loss of acid (vomiting). This would not be caused by diarrhea. Answer E is incorrect. In severe diarrhea with significant loss of fluids and electrolytes, especially bicarbonate, it is unlikely that the patient will have a normal acid-base state. Answer F is incorrect. Respiratory alkalosis is the presence of high pH due to an increase in ventilation leading to a decrease in serum carbon dioxide. This occurs in cases of increased respiratory drive (e.g., by drugs or central nervous system disorders, anxiety, and fear). This would not be caused by diarrhea. Step 1 q and a 47. Biohem A patient presents to the emergency department with nausea, headache, and dizziness. On physical examination his lips and fingernail have a bluish tint. Arterial blood gas sampling reveals arterial partial oxygen pressure of 100 mm Hg and an arterial partial carbon dioxide pressure of 40 mm Hg. The nurse who drew blood for the gas analysis notes that the patients blood looked oddly brown in the collecting tube. Which of the following is the most appropriate treatment for this condition? (A) Hyperbaric oxygen (B) Methylene blue (C) N-Acetylcysteine (D) Protamine (E) Thiosulfate

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The correct answer is B. This patient suffers from methemoglobinemia, which is characterized by a high blood level of methemoglobin in which the oxygen-caring iron is present in the oxidized (Fe3+) state instead of the normal (Fe2+) reduced state. The oxidized form of hemoglobin (Fe3+) does not bind oxygen effectively. Thus, signs and symptoms of methemoglobinemia reflect decreased blood oxygen content and subsequent cellular hypoxia, including headache, dizziness, and nausea, and at higher levels, shortness of breath, confusion, seizures, and coma. Cyanosis that is worst in the fingernails, ears, and lips may be present on physical exam. Because oxygen diffusion is not impaired, the arterial partial pressure of oxygen will be normal. However, blood may have a characteristic muddy color secondary to the oxidization state of iron. Methemoglobinemia may occur as an adverse effect of oxidizing agents such as sulfonamides, from hereditary hemoglobin abnormalities, or secondary to a hereditary deficiency of NADH. Methylene blue has been shown to increase the conversion of Fe3+ back to Fe2+. Answer A is incorrect. Hyperbaric oxygen is used to treat carbon monoxide poisoning. Carbon monoxide binds to hemoglobin with significantly higher affinity than oxygen, thus displacing oxygen from hemoglobin and decreasing the oxygen carrying capacity of blood. Further mechanisms of carbon monoxide toxicity may include inhibition of cytochrome oxidase and binding to myoglobin. Like methemoglobinemia, signs and symptoms include headache, dizziness, and nausea, and at higher levels, confusion, seizures, and coma. Death may occur. Although the arterial partial oxygen pressure may be normal as in methemoglobinemia, carbon monoxide poisoning is characterized by cherry-red skin color due to the presence of carboxyhemoglobin. Hyperbaric oxygen aids in the displacement of carbon monoxide from hemoglobin, thus improving its elimination. Answer C is incorrect. N-Acetylcysteine is used to treat acetaminophen toxicity, most likely by reducing the effects of toxic metabolites. Signs and symptoms of acetaminophen overdose include anorexia, nausea, or vomiting, followed by elevation of aspartate aminotransferase and alanine aminotransferase within 48 hours of ingestion. Fulminant hepatic failure and death may occur. Muddy blood and cyanosis is characteristic of methemoglobinemia, not cyanide poisoning. Answer D is incorrect. Protamine is used to reverse the effects of heparin. Heparin overdose can lead to excessive anticoagulation and bleeding. Protamine is a positively charged molecule that works by binding to negatively charged heparin. Answer E is incorrect. Sodium thiosulfate and sodium and amyl nitrites are used to treat hydrogen cyanide toxicity. Cyanide is a toxic gas that binds irreversibly and inhibits the function of the enzyme cytochrome c oxidase, thus impairing the electron transport chain and aerobic respiration. Like methemoglobinemia, signs and symptoms include headache, dizziness, and nausea, and at higher levels, shortness of breath, confusion, seizures, and coma. However, muddy blood and cyanosis is characteristic of methemoglobinemia, not cyanide poisoning. The nitrites oxidize hemoglobin, inducing
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methemoglobinemia. Cyanide binds more tightly to methemoglobin than to cytochrome c oxidase, resulting in the formation of cyanmethemoglobin. Sodium thiosulfate converts this product into thiocyanate, an excretable product. Step 1 q and a 12. GI Which of the following types of hepatocellular injury is commonly seen after acetaminophen overdose? (A) Acute hepatitis (B) Centrilobular necrosis (C) Fibrosis (D) Granuloma formation (E) Microvesicular fatty change 12. The correct answer is B. Acetaminophen is known to cause centrilobular necrosis. This type of necrosis occurs immediately around the terminal hepatic vein. In addition to acetaminophen, centrilobular necrosis can be caused by carbon tetrachloride, bromobenzene, halothane, and rifampin. Diffuse hepatic necrosis has also been reported with acetaminophen toxicity. Answer A is incorrect. Drugs causing acute hepatitis include methyldopa, isoniazid, nitrofurantoin, and phenytoin. Acetaminophen is not associated with acute hepatitis. Answer C is incorrect. Hepatic fibrosis is commonly associated with drugs that cause chronic hepatitis and/or hepatocellular injury. Some of the culprits include ethanol, methotrexate, and amiodarone. Acetaminophen is not associated with fibrotic liver changes. Answer D is incorrect. Granuloma formation does not occur with acetaminophen overdose. Some of the drugs associated with granuloma formation include sulfonamides, methyldopa, quinidine, hydralazine, and allopurinol. Answer E is incorrect. Microvesicular fatty change does not occur with acetaminophen overdose. It is usually seen with tetracycline, salicylates, and ethanol use.

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