Pharmacology/Hazardous substances 5/18/09 98: E- upper endoscopy with biopsy The patient described in the vignette presents with iron deficiency anemia and guaiac-positive stool, which suggest the presence of inflammation and bleeding of the gastrointestinal tract. It is unlikely that she has an acute gastrointestinal hemorrhage because she is hemodynamically stable. The differential diagnosis of chronic gastrointestinal bleeding and anemia in this patient is broad and includes Helicobacter pylori infection, celiac disease, and Crohn disease. However, her chronic use of ibuprofen points toward gastritis and ulcer disease due to chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) (ibuprofen). Upper endoscopy is indicated to establish a diagnosis of NSAID gastropathy and to exclude other conditions. Abdominal ultrasonography, abdominal spiral computed tomography scan, mesenteric angiography, and radionuclide tagged red cell study may be useful in the evaluation of large-volume gastrointestinal hemorrhages, but they lack the sensitivity to identify gastric or duodenal ulcers. Ideally, the ibuprofen should be held for 3 to 5 days prior to the upper endoscopy to reduce the risk of bleeding from biopsies. If ulcers are identified on upper endoscopy, the ibuprofen should be discontinued and the patient treated with a proton pump inhibitor (eg, omeprazole, lansoprazole). NSAIDs are anti-inflammatory drugs that reduce the synthesis of prostaglandins. Nonselective NSAIDs (eg, aspirin, ibuprofen, and naproxen) work by inhibiting cyclooxygenase (COX) 1 and 2; COX2 inhibitors (eg, celecoxib) preferentially bind to COX2. The nonselective agents have a higher risk of gastrointestinal and renal toxicity, and the COX2 inhibitors have a higher risk of adverse cardiovascular events in adults. It is estimated that 1% to 4% of adults taking chronic NSAIDs develop ulcers annually. Peptic ulcer disease from NSAIDs most commonly presents with bleeding or anemia. If a patient requires chronic NSAID therapy and is at risk for gastrointestinal bleeding (eg, prior history of ulcer, taking corticosteroids or anticoagulants), medical options for ulcer prophylaxis include use of a proton pump inhibitor or the synthetic prostaglandin misoprostol. 127: D- serum sickness Adverse drug reactions can be characterized immunologically with the Gell and Coombs classification as immediate hypersensitivity (type I), cytotoxic antibody responses (type II), immune complex reactions (type III), and delayed hypersensitivity (type IV). The time of onset and type of symptoms described for the girl in the vignette strongly suggest serum sickness, a condition that previously was associated with the use of bovine serum but now is observed most commonly with penicillin. Serum sickness is a systemic type III immune complex reaction that involves antibody-antigen complex formation and complement activation. Symptoms generally begin 1 to 2 weeks after drug initiation and may include fever, rash (Item C127A), malaise, lymphadenopathy, arthralgia, and arthritis. In addition to drug discontinuation, supportive therapy is recommended with antihistamines, analgesics, and corticosteroids. Erythema multiforme may be "minor" or "major." Both forms typically present with targetoid cutaneous lesions (Item C127B).
With the major form (Stevens-Johnson syndrome), the mucosal surfaces are involved. A skin biopsy may be helpful in establishing a diagnosis. Toxic epidermal necrolysis now is considered distinct from Stevens-Johnson syndrome and is characterized by a severe blistering disease that affects more than 30% of the total surface body area (Item C127C). Lesions often demonstrate the hallmark Nikolsky sign in which skin separation occurs with slight pressure.
Red man syndrome classically is associated with vancomycin and presents as diffuse flushing during intravenous drug administration. The mechanism is believed to be nonspecific mast cell degranulation due to the rapid rate of infusion. Red man syndrome generally can be avoided by slowing the infusion. Immunoglobulin (Ig) E-mediated penicillin hypersensitivity is a type I hypersensitivity reaction characterized by urticaria (Item C127D), flushing, pruritus, or angioedema developing within a few days of drug exposure. The lack of symptoms until after completion of the course of antibiotics in the vignette argues against an IgE-mediated drug reaction.
142: A- hypercalciuria Furosemide is a loop diuretic that acts at the ascending limb of the loop of Henle (LOH). Normally, approximately 20% to 25% of filtered sodium is reclaimed at this site, so blockade of sodium reabsorption results in a brisk diuresis, with urinary losses of sodium, potassium, and chloride. The blocked transporter is the Na +-K+-2Cl- channel. In addition to direct effects on the electrolytes of this channel, loop diuretics influence calcium and magnesium transport. Calcium and magnesium are reabsorbed passively in the ascending limb of the LOH through paracellular transport as a result a gradient derived from normal sodium chloride transport. The passive reabsorption of calcium is believed to occur through a paracellular pathway that is facilitated by paracellin-1, a tight junction protein. Interruption of sodium chloride reabsorption results in impaired calcium reabsorption and consequent hypercalciuria and increased risk for nephrocalcinosis and kidney stones. Furosemide also has an effect on the composition of endolymph in the inner ear because the Na +-K+-2Cl- transporter that is in the ascending limb of the LOH also can be found in the marginal cells of the cochlear duct of the inner ear. Furosemide induces changes in ion transport in these cells, reducing endocochlear potentials in the cells, which results in hearing loss. Ototoxicity is more likely when loop diuretics are used in high doses or are used in conjunction with other ototoxic agents such as aminoglycosides. Furosemide-induced ototoxicity usually is temporary, but can be permanent in some cases. Patients receiving loop diuretics also may develop hypokalemia, metabolic alkalosis, and hypomagnesemia (from increased urinary losses). Abnormalities in serum calcium are not typical, despite hypercalciuria. Hypercalciuria can lead to nephrocalcinosis, which can be longstanding, even after discontinuation of furosemide. Patients receiving furosemide are at risk for dehydration, but this is typically hypernatremic dehydration; hyponatremic dehydration is more common with thiazide diuretics. 143: B- negative skin testing to major and minor determinants of penicillin can exclude almost all immunoglobulin (Ig) E-mediated reactions As is often the case, the patient described in the vignette can only recall what her parents remembered about her drug reaction. Although the incidence of a true immunoglobulin (Ig) E-mediated penicillin allergy is 10% or less in this scenario, most clinicians continue to avoid this drug class in such patients. The administration of a penicillin during mononucleosis often results in a nonpruritic, maculopapular rash (Item C143A) within a few days. The mechanism for the rash is unknown, but this reaction is not IgE-mediated and should not preclude future penicillin use. For patients who have experienced a suspected IgE-mediated penicillin reaction, the use of cephalosporins generally is endorsed for those whose previous reaction did not result in severe anaphylaxis. Further, the second- and third-generation cephalosporins are less likely to cross-react with penicillin than are first-generation cephalosporins. Overall, the risk for cross-reaction remains less than 10% for all cephalosporins. Although not commercially available in the United States, skin testing to both major (penicilloyl) and minor (penicillin, penilloate, penicilloate) determinants can be very helpful. Negative skin test results to both major and minor determinants virtually rule out (≥97% chance) that the patient is allergic to penicillins. On the other hand, positive skin test results are approximately 60% predictive for ruling in a penicillin allergy. Serum sickness, erythema multiforme, fixed drug reactions, and toxic epidermal necrolysis are non-IgE-mediated penicillin reactions. Such reactions are not identified with skin testing because they are not IgE-mediated. When these reactions occur after penicillin administration, future penicillin use is contraindicated. 42: B- administer parenteral hydrocortisone hemisuccinate The girl described in the vignette has adrenal insufficiency and is vomiting and febrile. She needs stress doses of glucocorticoids but cannot keep down orally administered agents. No parenteral preparation of mineralocorticoid is available. In contrast to synthetic glucocorticoids, hydrocortisone has about 1% of the mineralocorticoid effect of aldosterone (the most important natural mineralocorticoid), and a large dose of hydrocortisone can act as a mineralocorticoid. Accordingly, this child needs a rapid-acting parenteral hydrocortisone preparation. Hydrocortisone hemisuccinate administered subcutaneously, unless she has poor perfusion, which would necessitate intramuscular or intravenous administration, can stabilize her course. The girl's usual oral medication is not sufficient for the increased need of stress. Increasing the oral medication may not be sufficient because she probably will not be able to keep it down or absorb it if she is vomiting. Mineralocorticoid need generally does not increase during stress. If she is vomiting and receiving parenteral hydrocortisone, she might require intravenous 0.9% saline with glucose to maintain her sodium stores and her blood glucose in the normal range. For children who have usual febrile illnesses or require surgery, administration of glucocorticoid in doses that supply three
to six times the usual cortisol secretion rate of 3 to 7 mg/M 2 per day is reasonable treatment. However, children who have adrenal insufficiency and develop varicella because of failure or lack of immunization must be managed very carefully. There are no controlled studies, but some anecdotal data suggest that infection with varicella virus can become devastating in glucocorticoid-treated individuals. For such children, careful titration of hydrocortisone dose to only twice the usual need may provide the small amount of needed additional glucocorticoid without compromising the children's immune responses. 69: D- his school performance may be adversely affected Beta-blocking drugs have an antagonistic effect on the beta-adrenergic receptors. This diverse and widely used group of medications can have multiple and various effects on the heart and other organ systems. In the heart, they typically exhibit some degree of negative chronotropic (slowing of the heart rate), negative dromotropic (slowing of the conduction through the atrioventricular node), and negative inotropic (decrease in the ventricular force of contraction) effects. As a result, this class of medications is used in the treatment of many pediatric conditions, including hypertension, arrhythmias, hypertrophic cardiomyopathy, dilated cardiomyopathy, Marfan syndrome, and migraine prophylaxis. The adverse effects of beta-blocker drugs have been well-documented and may be divided into three broad categories based on end-organ effects (Item C69). The patient described in the vignette has been prescribed a beta blocker that has relative cardiac selectivity. Some children and adolescents experience a decrease in school performance while being treated with beta blockers, most likely related to the central nervous penetration, and it may be difficult to differentiate this effect from the known fatigue or depression that also can occur. Although bronchospasm or asthma is a contraindication to the use of some beta blockers (eg, propranolol), a family history alone is not a contraindication for their use. Some beta blockers can cause a decreased reaction to hypoglycemia, leading to a relative contraindication of their use in those who have diabetes, but their use does not increase the risk of developing diabetes mellitus. Similarly, beta blocker use typically does not lead to gynecomastia. Although reflex tachycardia may be noted when chronic beta blocker use is discontinued, these drugs are not associated with tachyphylaxis. 85: B- continuous cardiac monitoring for dysrhythmias The child described in the vignette has symptoms suggestive of tricyclic antidepressant (TCA) ingestion. This class of antidepressants is used less frequently today for treatment of depression because of the availability of selective serotonin reuptake inhibitors (SSRIs). TCAs are not the drugs of choice for treatment of depression in children and adolescents but are used occasionally in the treatment of other disorders (eg, enuresis, narcolepsy). SSRIs are much safer to use than TCAs because they have fewer adverse effects and are unlikely to result in death when overdose occurs. When TCAs are ingested in toxic amounts, they primarily affect the central nervous and cardiovascular systems. Central nervous system signs and symptoms of TCA toxicity include irritability, euphoria, seizures, and unresponsiveness. Autonomic nervous system symptoms such as mydriasis, dry skin, dry mouth, urinary retention, and tachycardia also may be evident. Among the direct effects on the cardiac system are a delay in signal conduction through the bundle of His, depression of myocardial contractile function, and prolongation of the QRS and the QT intervals. These latter cardiac effects may potentiate arrhythmia formation. Continuous cardiac monitoring for the possible occurrence of arrhythmia is essential in patients who are suspected of toxic TCA ingestion. Electrocardiography is the best tool for assessing the function of the conduction system. The voltage intervals should be measured, with particular attention to the QRS duration and the QT interval. A QRS duration of greater than 100 msec is associated with the development of seizures; a QRS duration of more than 160 msec is associated with ventricular dysrhythmias that may be particularly difficult to treat. Echocardiography is an excellent tool to evaluate cardiac structure and function but is not necessarily indicated as part of the emergency department evaluation of a child in whom toxic TCA ingestion is suspected and does not obviate the need for continuous cardiac monitoring. Similarly, chest radiography does not play a role in the acute management of such a patient. Electroencephalography has no place in the initial evaluation and management of children in whom a TCA toxic ingestion is suspected. Seizures, when they occur, usually do so early in the course and often resolve by the time anticonvulsants are administered. Measuring serum drug concentrations of TCAs is not helpful for the prognosis or management of TCA ingestion. Serum electrolyte concentrations may be measured, but they have no predictive value in the management of TCA toxicity. 163: E- tetracycline should not be taken with dairy products It is important for the clinician to recognize that the concomitant use of foods and medications may result in an undesired response to the drug, either through decreased efficacy or increased risk of toxicity. Such interactions may result from a feature of the drug or food. For example, some medications, such as isotretinoin or griseofulvin, are more bioavailable when taken with fatty foods because they are lipophilic agents. Others, such as digoxin, have lower bioavailability with high-fiber meals because the fiber binds the drug. In fact, most food-drug interactions occur because some characteristic of the food affects the bioavailability of the drug. Components in some foods and dairy products chelate a portion of the drug and reduce bioavailability, which occurs with many antibiotics. Other antibiotics are acid-labile agents, so the increased gastric acid secretion that occurs with food intake may reduce their bioavailability. For some medications, the effect is minimal unless the dose is inadequate, but for others, the risk is higher and warrants careful attention to avoid treatment failure. Item C163 (Item C163) lists some antibiotics commonly used in the pediatric population that have potential food-drug interactions. In general, for medications that should not be taken with food, the drug should be given either 1 to 2 hours before or 2 hours after the ingestion of the food in question. Many other medications should be administered with caution to ensure proper bioavailability and efficacy. Patients should
be advised to pay close attention to any instructions offered by their pharmacist to avoid adverse reactions or treatment failures.
249: C- ingestion of infant formula 3 hours ago The goal of procedural sedation is to provide anxiolysis and analgesia and minimize patient movement. Sedation should be viewed as a continuum; the American Academy of Pediatrics has defined four levels of sedation. Minimal sedation (formerly anxiolysis) is defined as a drug-induced state in which the patient retains the ability to respond normally to verbal commands, and cardiovascular and respiratory functions are unaffected. Moderate sedation (formerly conscious sedation) is a drug-induced depression of consciousness in which patients still should respond to verbal and physical stimulation. Cardiovascular status is maintained, but the clinician must be able to recognize and respond to potential airway compromise. Deep sedation is defined as further depression of the level of consciousness, with partial or complete loss of protective airway reflexes and the need for assistance with airway maintenance. General anesthesia is the deepest level of sedation that is characterized by loss of consciousness and airway protective reflexes. Impairment of respiratory and cardiovascular function is common. Provision of safe and effective sedation requires appropriate patient selection, evaluation, and preparation. Appropriate monitoring and resuscitation equipment, thorough documentation, and trained personnel are essential. A contraindication to proceeding with the planned sedation for the patient in the vignette is the ingestion of formula 3 hours ago, which increases the risk of aspiration due to potential loss of airway reflexes. Children should not ingest formula or food within 6 hours or human milk within 4 hours of sedation. Clear liquids such as juice are allowed up to 2 hours prior to a planned elective sedation and may help reduce gastric contents. Neither the history of birth at 36 weeks estimated gestational age nor the lack of previous anesthetic administration are contraindications, but the preanesthetic history should explore any complications at birth as well as any family history of difficulty with sedation or anesthesia. Because preterm infants are at increased risk of apnea and bradycardia following sedation until they have achieved a postconceptual age of 52 weeks, they deserve additional monitoring. Pediatric sedations frequently are achieved with oral medications, but personnel and equipment to obtain urgent intravenous access should be readily available. 13: A -Bacillus anthracis Anthrax is a zoonotic disease caused by Bacillus anthracis, which is a gram-positive, encapsulated, spore-forming rod that occurs in many areas of the world. B anthracis spores can remain viable in the soil for decades (Item C13A), representing a major reservoir of infection for herbivorous livestock through ingestion. Human infection occurs through contact with infected animals or contaminated animal products, including carcasses, hides, hair, wool, meat, bone meal, and other contaminated foodstuffs. Depending on the route of infection, anthrax disease may manifest in three different forms: cutaneous, inhalational, and gastrointestinal. Approximately 95% of all human anthrax cases are cutaneous anthrax. The incubation period of cutaneous anthrax is 1 to 12 days. The initial skin lesion is a pruritic papule that resembles an insect or spider bite, as described for the boy in the vignette. The papule progresses to the development of a central vesicular or bullous lesion that becomes necrotic and hemorrhagic and forms a central black painless eschar, which is the classic lesion of anthrax (Item C13B). There is marked surrounding edema, swelling, induration, and erythema of the involved area but no associated tenderness. Regional lymphadenopathy, fever, malaise, and headache also may be present. In most cases, the eschar falls off in 1 to 2 weeks, and total resolution occurs in 6 weeks. Infections caused by methicillin-resistant Staphylococcus aureus (MRSA), the bite of Loxosceles laeta, Francisella tularensis, and Yersinia pestis are associated with pain, rapid progression, and in most cases, systemic symptoms. Skin and soft-tissue infections due to MRSA have been described as resembling a "spider bite" that is very tender, with progressive worsening of the erythema, warmth, and tenderness (Item C13C). It is not associated with the development of a bullous, necrotic lesion with eschar. The bite of Loxosceles laeta (the brown recluse spider) may resemble the cutaneous lesion of anthrax, but it is very painful (Item C13D). Also, symptoms develop shortly after the bite and progress rapidly within 24 hours. Francisella tularensis is the agent that causes tularemia. Signs and symptoms develop within 3 to 5 days of exposure and include the abrupt onset of fever, chills, headache, malaise, and fatigue as well as the development of a progressively enlarging, tender, localized lymphadenopathy and a red, painful papule (Item C13E) in a region draining into the involved lymph nodes. The signs and symptoms of Yersinia pestis (plague) develop abruptly and
include fever; chills; weakness; headache; and extremely tender, rapidly enlarging swelling of the lymph nodes of the groin, axilla, or neck. 16: C- serum acetaminophen concentration Treatment of a patient who has ingested an unknown substance or substances, such as the one described in the vignette, should focus initially on stabilization of vital functions; treatment of the patient's symptoms; and identification of agents that are potentially fatal, have delayed clinical toxicity, or for which antidotal therapy is indicated. The evaluation should include a screening history to identify circumstances surrounding the event, potential environmental exposures, available medications or toxins, and previous medical or psychiatric history. The physical examination should focus on vital sign abnormalities, pupillary size and reactivity, skin findings, and mental status. These components are likely to yield the most useful clues to toxins that have identifiable symptom complexes (Item C16A). Laboratory testing should assess the patient's acid/base status, oxygenation and ventilation, glucose concentration, and anion gap. Qualitative urine drug testing may be obtained but has significant limitations, including the small number of drugs tested (typically drugs of abuse) and screening thresholds that may produce false-negative results. Therefore, the results of urine toxicologic screening rarely affect treatment plans. Quantitative drug concentrations should be measured based on the information gleaned from the initial history, physical examination, and screening laboratory testing, although acetaminophen and salicylate concentrations should be measured for every patient who has an unknown, mixed, or intentional ingestion. Acetaminophen is of particular concern because it causes few initial symptoms, is a common agent in adolescent and adult intentional ingestions, and may require antidotal therapy to prevent potential fatal liver damage. Abdominal radiographs may be considered to examine the patient for radio-opaque substances (Item C16B). A complete blood count is not likely to provide information leading to the identification of a toxin. Measurement of serum ammonia may be indicated if acetaminophen is identified as the ingested agent because toxicity can lead to hepatic damage. Carboxyhemoglobin should be measured in the patient whose history is suggestive of carbon monoxide exposure. Increased serum osmolality may provide indirect evidence of alcohol ingestion, although a quantitative serum test for alcohols is more useful in this setting. 32: A- diphenhydramine overdose The patient described in the vignette is exhibiting symptoms of anticholinergic toxicity. The classic mnemonic "hot as a hare, dry as a bone, blind as a bat, red as a beet, and mad as a hatter" aptly describes a number of the commonly seen signs and symptoms, including hyperpyrexia, dry skin, dilated pupils, flushing, and delirium. In addition, affected patients typically exhibit tachycardia and hypertension. The clinical syndrome caused by anticholinergic toxicity is due to competitive inhibition of acetylcholine binding to the postganglionic parasympathetic muscarinic receptors by the offending agent. Many commonly used medications have anticholinergic properties, including antihistamines, tricyclic antidepressants, antispasmodics, and mydriatics. For this patient, diphenhydramine is the most likely culprit. Treatment of anticholinergic poisoning is primarily supportive, with stabilization of vital functions (the ABCs) of greatest importance, followed by appropriate decontamination (eg, activated charcoal for ingestions, skin cleansing and removal of transdermal delivery devices for dermal absorption). Agitation and seizures may be treated with benzodiazepines. Physostigmine, a cholinergic agent that competitively inhibits acetylcholinesterase, may be more effective for the treatment of severe agitation than benzodiazepines, but significant toxicity risks make its use controversial. Hypoglycemia can cause altered mental status but typically produces bradycardia, hypotension, and coma, rather than agitation. Intracranial hemorrhage can be seen in patients who have varicella-related thrombocytopenia, although affected patients frequently present with hemorrhagic skin lesions (Item C32). In addition, patients who have intracranial hemorrhage typically present with focal neurologic findings and bradycardia with hypertension, if intracranial pressure is increased. The classic presentation of Reye syndrome includes sudden onset of protracted vomiting without fever in association with lethargy that progresses to delirium, seizures, stupor, and coma. Reye syndrome typically occurs 5 to 7 days after the onset of a viral illness, following apparent improvement in the child's initial symptoms. It results from mitochondrial dysfunction leading to liver failure and cerebral edema. Ninety percent of cases have been reported to follow an upper respiratory tract infection; varicella has been associated with 5% of cases. Central nervous system complications of varicella are uncommon and may include cerebellitis, transverse myelitis, peripheral neuritis, and optic neuritis. Cerebellitis is the most common presentation of encephalitis and typically presents on the third to eighth day of illness with ataxia. Meningoencephalitis presents with fever, meningeal signs, seizures, and altered mental status. 192: B- bedside glucose determination The approach to any pediatric patient who presents with acute alteration in mental status should include assessment of airway patency, adequacy of oxygenation, ventilation, and perfusion as well as a bedside glucose determination. Hypoglycemia may result from a variety of causes, including inborn errors of metabolism, poisonings, sepsis, shock, liver failure, and starvation. Signs and symptoms of hypoglycemia are related to counterregulatory epinephrine release and cerebral glucopenia. These include diaphoresis, tachycardia, tremulousness, pallor, irritability, somnolence, and coma. Unrecognized hypoglycemia can cause mortality as well as significant morbidity from seizure activity and if chronic, impaired brain development. Because hypoglycemia is treated easily with intravenous dextrose, oral glucose, or in some settings, glucagon, rapid diagnosis is critical. A number of poisonings are well known causes of hypoglycemia in children and include oral hypoglycemic agents, insulin, beta-blockers, salicylates, and ethanol. Ethanol intoxication with hypoglycemia is a likely cause of the symptoms described for the patient in the vignette because of the parents' report of unsupervised activity in an environment where ethanol was accessible. Other clues to ethanol ingestion in children who have hypoglycemia include an anion gap acidosis, an osmolar gap, and an elevated lactate value. The hypoglycemia caused by ethanol is related to gluconeogenesis
inhibition and is not responsive to glucagon. Although acetylcholinesterase and blood alcohol determinations, measurement of serum osmolality, and a urine toxicology screen may be indicated in the evaluation of a patient who has acute alteration of mental status, the bedside glucose determination is the most appropriate initial test because it permits rapid identification of hypoglycemia and prompt treatment. 208: A- atropine The patient described in the vignette is exhibiting the classic symptoms of cholinergic poisoning. These symptoms can be remembered using the mnemonic "SLUDGE" (salivation, lacrimation, urination, diarrhea, gastric emesis) and are due to irreversible inhibition of acetylcholinesterase and excess acetylcholine at the neuromuscular junction. The resulting overstimulation of cholinergic receptors causes the muscarinic symptoms noted previously. Nicotinic symptoms, which include muscle twitching, weakness, and paralysis, also may result. Organophosphate exposure can occur though ingestion as well as dermal absorption and inhalation. These compounds are found commonly in the home environment as components of lawn and garden care products, scabicides, and interior insecticides. The treatment of cholinergic poisoning involves patient stabilization, decontamination, and administration of antidotes. Significantly symptomatic patients may require intubation for airway protection and pulmonary toilet as well as assisted ventilation with 100% oxygen for respiratory muscle weakness and hypoxia. Systemic decontamination with activated charcoal as well as dermal decontamination should be performed. Dermal decontamination may be facilitated by cleansing the skin with a dilute bleach solution. Contaminated clothes should be discarded because laundering may not remove the toxin. The mainstay of stabilization and treatment for cholinergic poisonings is the administration of atropine. Atropine competes with acetylcholine at the cholinergic receptors and decreases the muscarinic cholinergic effects. The doses of atropine used in this setting are higher than those used for symptomatic bradycardia from other causes. An initial atropine dose of 0.05 mg/kg should be administered and doubled every 3 to 5 minutes until the pulmonary muscarinic symptoms (bronchorrhea, bronchospasm) are controlled. Nicotinic neuromuscular symptoms are treated by adding pralidoxime, a cholinesterase reactivating agent, to atropine therapy. N-acetylcysteine is used to treat acetaminophen poisoning, which causes few, if any, acute symptoms. Naloxone is an opiate antagonist used to treat symptomatic opiate overdoses, which are characterized by miosis, bradycardia, and respiratory depression without bronchorrhea. Octreotide is a somatostatin analog that inhibits insulin release and is indicated in the treatment of sulfonylurea overdoses, which cause profound hypoglycemia unresponsive to dextrose administration. Physostigmine is a cholinergic agent that may be used in significantly symptomatic anticholinergic poisonings. Because the patient's symptoms are not consistent with overdoses of any of these drugs, treatment with these agents is not indicated.