1. D In this case, the lean body-weight (the 50th percentile of weight for age) is the appropriate weight to use. (Rowland M, Tozer TN. Clinical Pharmacokinetics: Concept and Applications. Lea & Febiger, Philadelphia; pp. 100-110.)

2. C When drug accumulation is expected, which means that the ratio of dosing interval/half-life is less than three, and when there is a need to establish a therapeutic level rapidly, then a loading dose is necessary. Loading dose = Concentration x Volume of distribution. (Kearns GL. Clin Pharmakokinet, 1989; 17[Suppl 1]:29.)

3. C First one has to calculate the creatinine clearance, which is = L x K / serum creatinine, where L is length of the child, K is a constant and it equals .45 for this age. Therefore, the creatinine clearance for this patient = 75 x 0.45 / 1.2. Assuming that the normal creatinine clearance is 100 mL/minute/1.73 M2, the renal index would = 28.1 mL/minute, which is equal to 0.28 for this patient. Plugging all these numbers into the equation provided would result in 4.5 mg/kg/day as the appropriate dose. K = 0.45 for infants; 0.55 for 1-3

years; and for adolescents, 0.7 for boys and 0.55 for girls. (Bennett WM. Clin Pharmakokinet, 1988; 52:326.)

4. E Patients at risk of adrenal hypofunction who are admitted to the PICU (for nontrivial illness) require additional doses of corticosteroid coverage. The physiological dose is 12.5 mg/M2 body surface area (BSA)/day of hydrocortisone. Patients with a febrile illness presumed to be secondary to a nontrivial infection, deserve doubling of the maintenance dose. Patients with a major trauma, major surgery, or generalized sepsis deserve 3-4 times the maintenance dose. When time allows, high-dose corticosteroids must be initiated 1-2 days prior to surgery, and weaned over a period of 5-7 days. Because the risk of undertreatment is higher than overtreatment in patients with a serious illness or trauma, it is reasonable for a clinician to administer 100-200 mg/M2 BSA/day of hydrocortisone to these patients. Gastric acidity partially inactivates oral steroids and, therefore, higher doses are often necessary. (Migeon C. In: Collaly R, et al. Recent Progress in Pediatric Endocrinology, New York, Raven Press, 1981; pp. 465-522.)

5. A Adrenergic receptors comprise four subtypes: a1, a2, P1, and p2. Each of these subtypes and the family keeps growing. a1 Receptors are typical postsynaptic receptors, mediating smooth muscle contraction in both the vascular tree (causing intense vasoconstriction) and the genitourinary system. a2 Receptors include presynaptic and nonsynaptic sites (such as on platelets). a2 Receptors tend to inhibit release of norep-inephrine from sympathetic nerve terminals resulting in relaxation of vascular and GI tract (GIT) smooth muscles. Phenoxybenzamine, or a1 blocking agent, is the most selective a1 blocking agent, and is used for pre-operative management of patients with pheochromocy-toma. Prazosin is a potent but less selective a blocker, and its blockade of a2 receptors (presynaptic receptors) cause uninhibited release of norepinephrine, thus counterbalancing the a1 receptor blockade. Phentolamine is likewise not a selective a1 blocker. Atenolol is a selective p1 blocker. (Bravo E. N Eng J Med, 1984; 311:1298. Hoffman B. N Eng J Med, 1980; 302:1390.)

6. E Cocaine is absorbed from respiratory, GIT, and genitourinary mucosa. It is metabolized in the liver by esterases. It is metabolized by plasma pseudo-cholinesterase and nonenzymatic hydrolysis. The two major cocaine metabolites in urine are benzoylecgo-nine and ecgonine methyl ester. Most urine drug screening tests detect benzoylecgonine. There is a greater potential for toxicity in patients with pseudo-cholinesterase deficiency because cocaine will be less metabolized. Drug abusers ingest an organophosphate in an attempt to prolong the effects of cocaine, which also increases the risk of cocaine toxicity. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 855-856.)

7. D Deferoxamine does interfere with subsequent laboratory determination of iron level, and under these circumstances, the most accurate method of measuring serum iron is using the atomic absorption spectrophotometry method. Interestingly, deferoxam-ine actually potentiates the activity of Yersinia enterocolitis. Children usually require 24 hours or less of deferoxamine therapy. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 532-534.)

8-9. E, E Numerous substitutions of the phenylethylamine structure are possible resulting in different amphetamine-like compounds. These are referred to as amphetamines, although a more precise name, phenylethylamines, exists. The diagnosis of amphetamine overdose depends on a high degree of suspicion along with clinical judgment. Diagnosis by history alone is rarely helpful. There is no reliable blood analysis test and the quantitative urine test is not particularly useful for acute settings. One of the major differentiating features between cocaine and amphetamines is the duration of action, which lasts for about 2 hours in the case of cocaine. The half-life of amphetamines on the other hand ranges from 8 to 30 hours. Amphetamines enhance the release of, and block the reuptake of, catecholamines, resulting in excess stimulation of both a and P receptors. At higher doses, they can cause release of serotonin. The clinical manifestations are that of cardiovascular and CNS excitation. Do not neglect to obtain a rectal temperature in these patients. Hyperthermia, if not recognized and treated aggressively, may be rapidly fatal in association with delirium. These patients are often very agitated and require sedation because agitation against restraints may exacerbate the associated rhabdomyolysis. Benzo-diazepines are the drug of choice because neuroleptic agents lower seizure threshold, alter temperature regulation, and may induce dystonia. Death is often from hyperthermia, dysrhythmias, or intracerebral hemorrhage. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 863-869.)

10-16. B, A, C, C, D, D, E Any child who has ingested more than 20 mg/kg body weight of elemental iron and who has not vomited spontaneously (and is awake) may be given syrup of ipecac and brought to the emergency department. If GI symptoms develop within 6 hours in these children or children who have ingested less than 20 mg/kg body weight of elemental iron and have a level of less than 500 mg/dL of serum iron, they may be discharged home because it is unlikely that children who present within 1 hour of ingestion, and who have not vomited, may benefit from ipecac (if not already given at home), as adult-strength pills are too large to be removed by lavage. Lavage may be performed if chewable forms are ingested or if pill fragments are seen in the vomitus or on the abdominal radiograph.

The properties of iron that promote its toxicity include: (1) first order or concentration dependent absorption that is seen even in the overdose setting, (2) absorbed iron cannot be rapidly excreted. Patients with massive overdose by history or clinical manifestations should be presumed to have taken a significant ingestion prior to determination of serum iron levels. The most valuable time to assess serum iron is 4-6 hours after ingestion. At this time, tablet breakdown is almost complete, but iron has not been completely distributed to tissues.

Because administration of deferoxamine (DFO) interferes with the standard calorimetric method of iron measurement, the laboratory must be informed of this fact. In this case, atomic absorption method is an accurate method and overcomes the false-negative results associated with the former test. DFO is a specific iron-binding agent that binds free inorganic iron to form fer-rioxamine (which is reddish in color) that is excreted in urine. It is given intravenously because GIT absorption is poor. The efficacy of DFO is not explainable entirely on the basis of the amount of iron excreted. Therefore, it is possible that toxicity is prevented by making iron less available for cellular binding where toxicity occurs. Hb, cytochrome, and other protein-bound iron are not chelated. Activated charcoal is ineffective in the setting of iron poisoning, as are any of the lavage solutions that could theoretically bind the iron in the stomach.

(Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 523-530.)

17-23. A/E/A, A, B, D, A, E, C The major metabolic pathway for elimination of salicylates when therapeutic doses are used is conversion to salicyluric acid and salicylphenolic glucuronide. However, this metabolic pathway follows the Michaelis-Menten kinetics, which is a saturable form of kinetics. Therefore, in the setting of overdose, this metabolic pathway becomes completely saturated and an alternative pathway has to be available for metabolism of salicylate. This alternative pathway is option E (salicylate excretion unchanged in urine), and therefore, this route of elimination becomes of paramount importance during salicylate intoxication. Because two of the major pathways become saturated, the half-life increases from 2 to 4 hours at therapeutic doses to as long as 20 hours. Also, protein binding decreases from 90% at therapeutic levels to less than 75% at toxic levels, and Vd increases from 0.2 to 0.3 L/kg. A nomogram is of limited value and was developed to be used only 6 hours or more after a single ingestion of nonenteric coated aspirin when blood pH is known to be 7.4. Repeat testing of serum salicylate levels is mandatory every 2-4 hours after ingestion. In children, the respiratory alka-losis is transient and usually occurs with metabolic aci-dosis.

Respiratory acidosis with salicylate toxicity warrants an evaluation for another toxin or for pulmonary dysfunction, such as pulmonary edema, which is a rare complication of salicylate overdose. Alteration in mental status in the presence of metabolic derangements make pure acetaminophen overdose suspect, and elevation of temperature directly resulting from salicylate toxicity is an indication of severe toxicity, and often is a preterminal condition in the adult population.

Aspirin was the leading cause of child poisoning in the past; however, the incidence of poisoning resulting from aspirin has been declining over the last several years. Because acidemia tends to affect the protein binding of salicylate, hyperventilation to maintain some degree of alkalemia is clinically important in salicylate poisoning. Because salicylates are a weak acid, salicy-lates are ionized and less mobile in an alkaline environment, whereas with acidemia, more salicylate leaves the blood and enters the cerebral spinal fluid.

In the setting of hypokalemia, it is often difficult to achieve alkalinization because under these circumstances, there is a limitation on excretion of hydrogen ion into the tubular lumen, and one has to correct the hypokalemia in order to be able to achieve alkaliniza-tion of the urine.

(Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 501-510.)

24-32. D, A, D, C, E,E, C, D, E Acetaminophen (N-acetyl-P-aminophenol [APAP]) is rapidly absorbed from GIT and peak plasma levels almost always occur within 4 hours of ingestion. The drug is metabolized in the liver by: (1) sulfation; (2) glucuronidation, (3) p-450 oxidase system, producing the intermediate metabolite (NAPQI) thought to be responsible for the toxicity; NAPQI is normally detoxified by conjugation with reduced glutathione and excreted in urine as mercap-turic acid or cysteine conjugates.

A small fraction of acetaminophen is excreted in urine unchanged. This and the product of sulfation and glucuronidation are nontoxic. In the setting of overdose, when more than 70% of glutathione is depleted, NAPQI binds covalently to hepatocytes, inducing hepatic necrosis, which is usually centrilobular with periportal sparing. Children seem to be more resistant to the toxicity of acetaminophen, presumably because of the higher activity of the sulfation pathway. One exceptional group is children on anti-convulsants, such as phenobarbital, which accelerates the p-450 mixed-function oxidase system with production of higher lev els of NAPQI, which is the main metabolite responsible for toxicity. These children are a higher risk and must be treated at a lower level of serum acetaminophen.

Because APAP is so rapidly absorbed through the GIT, gastric emptying is of benefit only in the first 2 hours after ingestion. Because APAP is effectively absorbed to activated charcoal and also because binding of N-acetylcysteine (NAC) to charcoal is probably clinically insignificant, most physicians would use activated charcoal with NAC, with possible repeating of the loading dose of NAC. NAC is taken up by the hepatocytes and acts as a precursor for glutathione and sulfate, replenishing reduced glutathione. When given more than 24 hours after ingestion of APAP, NAC acts as an antioxidant. NAC is administered when APAP is in the toxic range based on the Rumack and Mathew nomogram. NAC is also indicated when (1) initial AST and prothrombin time are elevated, suggesting significant ingestion, (2) when there is a history of prior or present vomiting with ingestion of more than 140 mg/kg body weight, or (3) when there is a history of a large APAP ingestion at an unknown time.

The clinical manifestations of APAP toxicity is divided into four phases: Phase I is characterized by nausea, vomiting, and malaise; phase II is characterized by hepatic dysfunction; phase III is characterized by sequelae of significant hepatic dysfunction with jaundice and coagulopathy; and phase IV occurs if phase III is not reversible.

In younger children with significant toxicity, hypotension, hypothermia, and apnea may be noted. Liver enzymes (alanine aminotranferease and aspartate aminotransferase), bilirubin and prothrombin time and partial thromboplastin time should be measured every 24 hours for 4 days while therapy proceeds. It is important to recognize that APAP measured by the calorimet-ric method is unreliable in the presence of high salicylates, bilirubin levels, or renal failure. In these circumstances, high-pressure liquid chromatography and enzyme immunoassay may be employed.

(Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 487-495.)

33, 34. E, C An acutely poisoned patient with a very high level of theophylline may be awake, alert, and merely tachycardic. If this patient does not exhibit tachycardia, the diagnosis of theophylline overdose is suspect or concurrent ingestion should be excluded.

The cardiac toxicity is owing to massive cate-cholamine (release of epinephrine and norepinephrine) stimulation of the myocardium and is aggravated by hypokalemia, hypercalcemia, and hypophosphatemia. P-Adrenergic stimulation is responsible for the electrolyte abnormalities, acid-base disturbances, and vasodilation. Metabolic acidosis, hypokalemia, and hyperglycemia are recognized features. The hypokalemia is from a transcel-lular shift (into the skeletal muscles).

The cardiovascular toxicity (dysrhythmias and hypotension) is worsened by hypoxia and co-administration of medications with b-adrenergic or anticholinergic activity. Anti-emetics with anticholinergic activity may worsen dysrhythmias, and if a pressor is used to elevate blood pressure, a pure a-adrenergic agent is preferred.

Massive theophylline toxicity can be effectively treated by hemoperfusion, and therefore, strong consideration should be given to initiating transfer of this patient to a facility with these capabilities, while the patient is still stable. At this same time, multiple dose-activated charcoal, intravenous P-blockers, and other supportive measures should be continued. The indications for initiation of hemoperfusion include a theo-phylline level greater than 90 mg/mL at any time; a theophylline level of more than 70 mg/mL 4 hours after ingestion of a sustained release tablet; and a theo-phylline level of more than 40 mg/mL with seizures, hypotension, or dysrhythmias. The author has treated a 2-year-old child with a theophylline level of 120 mg/mL without hemoperfusion.

(Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 567-574.)

35. C Among the opioids in this question, mor-phine-6-P-glucuronide is the most potent. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; p. 776.)

36. B Normeperidine is a metabolic product of meperidine, and it causes CNS excitation and seizures when it accumulates. (Goldfrank LR. Goldfrank's Tox-icologic Emergencies, 6th Edition; pp. 777-778.)

37. A, B, C The dose of sodium nitrite needs adjustment for Hb concentration, whereas sodium thio-sulfate needs adjustment for body weight. The efficacy of both these medications is increased by the coadmin-istration of high concentrations of oxygen. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 1195, 1228,1229.)

38. E All of the above combinations can lead to cyanide production. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 1215-1222.)

39-41. D, C, D An upper GI endoscopy is warranted to evaluate for formations of concretions and bezoars. Hypokalemia is more likely to develop because of the P-adrenergic agonist type effect of theo-phylline. Repeated doses of activated charcoal should be continued throughout the hemoperfusion procedure in order to minimize further absorption of theophylline into the circulatory system. (Goldfrank LR. Gold-frank's Toxicologic Emergencies, 6th Edition; pp. 568-574.)

42. C Intraventricular conduction defects are most commonly associated with propoxyphene overdose. Meperidine has a tendency to cause seizures, morphine causes respiratory insufficiency, and heroine has been associated with pulmonary abnormalities, such as ARDS. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 175, 198, 777.)

43. D Hypotension is multifactored in origin. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 175, 198, 777.)

44,45. A, E Propoxyphene is associated with heart block and intraventricular conduction defect abnormalities. Often, much higher doses of naloxone may be needed to reverse the toxicity resulting from propoxyphene. (Goldfrank LR. Goldfrank's Toxico-logic Emergencies, 6th Edition; p. 198.)

46, 47. B, C Activated charcoal may be helpful in body packers. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 175, 198, 777.)

48. E 3-Methylfentanyl is an extremely potent opioid and may require higher doses of naloxone to reverse its toxicity. (Goldfrank LR. Goldfrank's Toxico-logic Emergencies, 6th Edition; p. 30.)

49-52. B, A, C, C/D/D/A/A/B With methanol intoxication, the onset of toxic symptoms or the development of metabolic acidosis is often delayed for 24 hours, with a range of 1-72 hours from the time of ingestion. Methanol is converted to formaldehyde and then formic acid (FA). The latter is responsible for the toxicity of methanol particularly with late recognition, with subsequent build-up of FA. Two factors that correlate best with poor outcome are: (1) delay of appearance of toxic symptoms for longer than 10 hours, and (2) elevated levels of FA. Clinically, the most characteristic clinical findings are symptoms of blurred vision (the sign of dilated pupils with sluggish response to light) and hyperemia of the optic disc. These features correlate best with metabolic acidosis.

Oxalaturia and elevated levels of glycolic acid are features of ethylene glycol (EG) poisoning. HAGMA and hyperventilation are features of both. The degree of AG or EG poisoning is the largest seen in any metabolic acidosis. However, the onset of high AG metabolic acidosis may be delayed, and therefore, if the clinical suspicion is high, ethanol therapy should be initiated promptly. Because ethanol has a greater affinity for alcohol dehydrogenase than either methanol or EG, when ethanol is administered in sufficient concentration (100-150 mg/dL), it competitively inhibits formation of toxic metabolites, allowing the primary alcohol to be eliminated in urine unchanged. An optimal blood ethanol level, 100-150 mg/dL, should be attained, either orally (using a 15-20% concentration) or intravenously using a 10% concentration. Ethanol should be continued during hemodialysis at a higher dose because ethanol itself is dialyzable.

Alkalinization with NaHCO3 is also helpful because renal clearance of glycolic acid is enhanced and the amount of undissociated FA is decreased at a higher pH, thereby limiting access to the CNS.

Additional therapeutic measures EG ingestion may include 100 mg of thiamine intravenously or 50 mg of pyridoxine intravenously every 6 hours until acidosis is resolved and EG level is zero. Pyridoxine in the presence of magnesium may shunt the metabolism of EG metabolites from glycolic acid to the harmless glycine, and thiamine may reduce production of oxalic acid.

For methanol intoxication, 50-75 mg of folic acid every 4 hours for 24 hours has been suggested. Folic acid may enhance the elimination of FA.

(Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 827-836.)

53, 54. C, C The typical initial dose of naloxone in an adolescent is approximately 2 mg intravenously. If the first dose of naloxone fails to reverse symptoms, then 2-4 mg intravenously should be given up to a total dose of 10-20 mg. In a setting where there is no ventilatory insufficiency, it is not essential to initiate high-dose naloxone. Once the patient responds, two-

thirds of the dose that reversed the respiratory depression needs to be used on an hourly basis until the patient recovers. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 26,27, 100, 422, 770-772, 784,785.)

55-59. D, E, D, C, E Cyclic antidepressants induce their toxic effects by:

a. Inhibition of re-uptake of neurotransmitters such as norepinephrine and Dopamine.

b. Membrane depressant effect by slowing sodium influx into myocardial cells during Phase 0 of depolarization.

c. a-Adrenergic blockade.

d. Inhibition of central sympathetic reflexes.

e. Anticholinergic and antihistamine effects.

Many of the signs noted during toxicity are caused by central and peripheral anticholinergic effects, which include agitation, confusion, hallucinations, coma, seizures (central), tachycardia, hypertension, hyper-thermia, dry skin, and urinary retention (peripheral).

Cyclic antidepressants are divided into first-generation (or tricyclic) antidepressants and second-generation (or cyclic) antidepressants. These drugs have a more specific mechanism of action but their toxicity profile remains the same. Patients with antidepressant overdose often develop wide, complex dysrhythmias, hypotension, and seizures within minutes of ingestion. If a life-threatening event is going to occur, it will occur within the first 6 hours of hospitalization (most often within 2 hours of admission to the emergency department). After initial stabilization, a 12-lead EKG should be obtained and the patient placed on cardiac monitor. The finding of a small S-wave in leads I and AVL and a small R-wave in AVR along with a prolonged QT and sinus tachycardia are highly specific and sensitive for cyclic antidepressants (CAs). However, absence of these EKG changes does not exclude a cyclic antidepressant overdose (CAO). The duration of QRS has been shown to be prognostic of seizures and dysrhyth-mias: QRS greater than 100 msec, 30% risk of seizures; QRS more than 160 ms, 50% risk of dysrhythmias. Blood should be sent for electrolytes, glucose, and if ingestion was intentional, an acetaminophen level. It is not clinically useful or cost-effective to obtain a plasma cyclic antidepressant level because there is no good correlation between levels and symptomatology. However, with levels exceeding 1000 mg/mL, dysrhythmias and seizures are usually seen.

CAs have a membrane depressant effect on the myocardium by slowing sodium influx into the myocardium during phase 0 of depolarization. This leads to intraventricular conduction defects, dysrhythmias, decreased cardiac output, hypotension, and decreased coronary perfusion. The effects of CAs on sodium channels can be attenuated by increasing the blood pH to 7.50-7.55, either by hyperventilation or Na+ HCO3. At this pH, it appears that CA uncoupled from sodium channels, whereas hypotension and acidosis enhance their binding. (Lidocaine may also be effective in treating ventricular dysrhythmias.) Therefore, aggressive treatment of hypotension and metabolic acidosis is essential. If hypotension does not respond to fluid resuscitation, then depending on the underlying etiology, inotropic support or vasopressors may be used. Norepinephrine will increase the vascular tone, whereas dobutamine will increase the contractility without increasing the vascular resistance dramatically. Dopamine should be in this setting because of its arrhythmogenic potential.

Seizures that develop in the setting of CAO are usually brief and respond to lorazepam. For persistent seizures, phenobarbital is recommended. Phenytoin is not recommended because of the potential for dys-rhythmias. Other drugs that must be avoided include: class IA and IC antiarrhythmias (membrane stabilizers); propanolol and verapamil (myocardial depressants); flumazenil (inhibits the chloride channel of a-adrenergic and P-adrenergic receptors similar to CA). Because of the rapid deterioration of mental status in patients with CAO, ipecac should not be used. Multiple dose charcoal does enhance elimination of CA and physostigmine has not been shown to be safe and/or effective in this setting.

(Goldfrank, LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 726-731.)

60. A, B, C, D These are the drugs/toxins that should be in the differential diagnosis of HAGMA:

a. Paraldehyde ingestion can be diagnosed by its distinctive pungent odor. Other findings include: gastritis, mental status changes with possible coma, tubular acidosis, azotemia, oliguria, and proteinuria.

b. Toluene abuse by inhalation takes two forms:

i. Huffers inhale from a toluene-soaked cloth.

ii. Baggers inhale from a plastic bag containing toluene placed over the head.

They may present with HAGMA or renal tubular acidosis. Other symptoms are GI disturbances, musculoskeletal weakness, or neu-ropsychiatric disorders.

c. Isopropyl alcohol ingestion is characterized by hyperosmolality and ketonemia (with ketonuria) but without significant metabolic acidosis.

d. Iboniazide overdose is associated with seizures. Seizing patients should receive 1 g of pyridoxine for every gram of iboniazide ingested at a rate of 1 g every 2-3 minutes. If the seizures stop, the remainder may be given more slowly in D5W. A maximum dose of 5 g may be administered.

(Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 627,628.)

61. D Tachycardia may be a common feature. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 1105-1109.)

62. C Although there are authorities who believe that pralidoxime must be given within 24 hours of exposure to organophosphates, there are also reports that pralidoxime is still effective when administered beyond 24 hours after exposure. (Goldfrank LR. Gold-frank's Toxicologic Emergencies, 6th Edition; pp. 1117,1118.)

63. B Clinical manifestations of organophos-phate poisoning are not seen until a significant portion of the cholinesterase is inhibited, and the end point for atropinization is inhibition or significant reduction in upper airway and tracheal secretions. Tachycardia is not a contraindication to atropine in this setting. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 1117,1118.)

64. 65. D, B During hemoperfusion, compounds are cleared from blood as they come in contact with an adsorbent (surface) material contained in a cartridge, within an extracorporeal circuit. The adsorbent material could be: (1) Charcoal-best for polar compounds, such as salicylates, or (2) Amberlite XAD-4-best for lipid soluble compounds, such as theophylline, phenobarbital, CAs, meprobamate, and digoxin.

Extraction of many of these compounds is almost complete and the clearance often equals the blood flow through the circuit. Many of the pharmacokinetic factors that limit the applicability of diagnosis are not significant during hemoperfusion. Thus, molecular weight, degree of protein, binding in the plasma, and water solubility are not limiting factors during hemop-erfusion because of the high adsorbent area that comes in contact with the blood. The Vd remains important however. Drugs with a large Vd may be completely extracted from the blood as they pass through the adsorbent, but if only a small amount is present in the plasma compartment, only a small total amount may be removed from the body. The most frequent complications are hypotension and thrombocytopenia. Other complications are hypoglycemia, hypocalcemia and hypothermia.

(Rogers MC, et al. Textbook of Pediatric Intensive Care, 2nd Edition; pp. 1302-1304.)

66. E Repeated dose activated charcoal is effective for all of these medications except for iron. Activated charcoal is ineffective in a setting of iron poisoning. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 66-69.)

67. A, A, A Carbamates do not penetrate the CNS, and their effects are usually reversible and transient. Only atropine is usually needed in a setting of overdose. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 2nd Edition; pp. 1304-1307.)

68. D PKa is an important concept in pharmacology particularly in the setting of overdose. For example, with salicylates, which have a PKa of 3.1 at a pH of 3.0, the ratio of ionized to non-ionized is 1:1. However, if the pH is increased to 7.4, the ratio of ionized to non-ionized increases to 2500:1, and this will dramatically help with elimination of the drug through the kidneys. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 503-505.)

69. D Because K+ is exchanged with H+ in the renal tubules, hypokalemia with total body K+ deficit will hinder urinary alkalinization. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 503-510.)

70. E For a compound to be dialyzed efficiently, it must be poorly protein bound (<90%) and highly water soluble, have a small Vd so that the majority of the drug is in the plasma, and have a small molecular-

weight; compounds with a molecular-weight higher than 500 are progressively less dialyzable. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 2nd Edition; pp. 1302-1303.)

71. E See answer to Questions 64 and 65.

72. A, B, B, B Organophosphates bind irreversibly to acetylcholinesterase (the enzyme that normally hydrolyses acetylcholine). As a result, acetylcholine accumulates at the synaptic site with subsequent continuous stimulation of the neuromuscular junction. Clinical manifestations are fasciculations, weakness, and paralysis. Myoclonus is associated with the other three groups of drugs. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 2nd Edition; pp. 1304-1306.)

73. E The pulse oximetry detects the ratio of oxy-Hb to the total Hb and is incapable of measuring the other different types of Hb, such as carboxy-Hb or met-Hb. Therefore, the saturation that is obtained may be erroneous. Under these circumstances, one has to measure the oxygen saturation using the co-oximeter. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 2nd Edition; pp. 122,123, 321, 461.)

74. D Drugs recognized to form gastric concentrations in the setting of overdose include barbiturates, salicylates, ferrous sulfate, and slow-release theo-phylline preparations. In these case circumstances, attempts should be made to eliminate these concentrations from the stomach including use of endoscopy because they contribute to the toxicity of these drugs. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 2nd Edition; pp. 1326-1339.)

75. E Activated charcoal should be administered in almost all cases of poisoning after emesis and lavage are accomplished. Exceptions are in cases of ingestion of (1) Corrosives-whether alkaline or acids, as charcoal does not absorb either one effectively and the dark charcoal may interfere with endoscopic examination; (2) Anticholiner-gics-overdose with ileus is an obvious situation when repeated dose-activated charcoal should not be used; (3) Enteric-coated preparations are not well-adsorbed by activated charcoal. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 2nd Edition; pp. 1326-1339.)

76. C Hypovolemia is the most likely cause of hypotension in a patient with significant intoxication, although other etiologies must be kept in mind and should be appropriately evaluated and treated. (Goldfrank LR. Goldf.rank's Toxicologic Emergencies, 6th Edition; pp. 726-731.)

77. C Alkalosis seems to minimize binding of CAs to sodium channels in the myocardium with resultant suppression of dysrhythmias. (Goldfrank LR. Goldf rank's Toxicologic Emergencies, 6th Edition; pp. 726-731.)

78. E All of the above drugs induce a state of sympathetic stimulation and therefore are likely to be associated with hypertension. (Goldfrank LR. Gold-frank's Toxicologic Emergencies, 6th Edition; pp. 1-100.)

79. A, B, C, D, E Detection of a distinctive odor may be a clue to diagnosis of specific poisoning. This question addresses some clinical examples. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 1-100.)

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