Pharmacology
Pediatric Critical Care Review

Hasan   Pappas

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1.         Presumptive, quantitative adjustments of drug regimens in order to compensate for anticipated variations in volume of distribution are usually not practical except with:

 

A.                 Congestive heart failure

B.                 Iatrogenic volume expansion such as septic shock

C.                 Ascites

D.                 Obesity

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2.         A loading dose of a drug is necessary when:

 

A.                 Drug accumulation is not expected but there is a need for rapid acquisition of a therapeutic level

B.                 The dosing interval (T) / half-life is > 3 and there is a need to get a therapeutic level rapidly

C.                 The T / half-life is < 3 but rapid acquisition of a therapeutic level is needed

D.                 None of the above

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3.         A 12-month-old child (weight = 10 kg; length = 75 cm) with a serum creatinine of 1.2 needs amikacin for a gram negative bacterial infection.  The usual dose for amikacin is 15 mg/kg/day and amikacin is 98% excreted in the urine unchanged.  Based on the information provided, the most appropriate dose is:

                        (Clearance =    Length x K       where K = 0.45 for infants

                                                S. creatinine

                         (Dr = Dn   x  (1- [¦ (1 – RI])  where ¦ is 0.98 for amikacin)

                    NOTE:  RI = Renal Index;  Dr = Dose in renal failure;

             Dn = Dose with normal renal function

 

A.                 10 mg/kg/day

B.                 8 mg/kg/day

C.                 4.5 mg/kg/day

D.                 2.5 mg/kg/day

E.                  Can’t be calculated from the data given

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4.         Regarding steroid replacement treatment in children who have been on long-term steroid therapy and admitted to the Pediatric ICU:

 

A.                 Sepsis or major trauma necessitates administration of 3-4 times the maintenance dose

B.                 When in doubt, the clinician could reasonably give 100-200 mg/m2/day of hydrocortisone as a continuous infusion or in divided doses

C.                 High dose hydrocortisone should be started 1-2 days prior to surgery at 4 times the maintenance dose and weaned over 5-7 days

D.                 When converting to oral maintenance, the dose should be double the maintenance dose due to inactivation by gastric acidity

E.                  All of the above

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5.         The most selective a adrenergic blocker is:

 

A.                 Phenoxybenzamine

B.                 Prozocine

C.                 Phentolamine

D.                 Atenolol

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6.         Which of the following is not true regarding cocaine metabolism:

 

A.                 Cocaine is quickly metabolized to benzolecgonine which is excreted in the urine within 24 hours

B.                 Most urine drug screens detect benzolecgonine

C.                 Metabolism of cocaine in the liver is by ester hydrolysis by pseudocholincoterase as well as non-enzymatic hydrolysis

D.                 Cocaine is absorbed from the bladder and vagina

E.                  Cocaine is excreted in the urine unchanged and is detected by most drug screening tests in this form

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7.         Which of the following statements is true regarding deferoxamine:

 

A.                 Efficacy of deferoxamine is related entirely to the actual excretion of the amount of iron ingested in a setting of iron poisoning

B.                 It inhibits virulence of Yersinia enterocolitis

C.                 Lack of color change in urine after administration of deferoxamine is an indication for discontinuing therapy

D.                 Deferoxamine administration interferes with subsequent laboratory determination of iron levels

E.                  Children usually require > 72 hours of deferoxamine therapy

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8.         Regarding diagnosis of amphetamine overdose, choose the most accurate statement:

 

A.                 Diagnosis by history is rarely reliable

B.                 There is no readily available serum analysis

C.                 The qualitative urine test is not valuable in the acute setting

D.                 High degree of suspicion along with clinical judgment may be helpful in diagnosis

E.                  All of the above

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9.         Regarding evaluation of a patient suspected of amphetamine abuse:

 

A.                 Hyperthermia requires immediate attention

B.                 Delirium and agitation are treated with benzodiazepine

C.                 Neuroleptics lower seizure threshold, alter temperature regulation and may cause dystonia in patients with cocaine intoxication that is difficult to differentiate from amphetamine abuse

D.                 Death from amphetamines results from dysrhythmias and intracerebral hemorrhage

E.                  All of the above


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10.       The most valuable time to assess serum iron level after ingestion (when tablet breakdown is complete but iron has not been completely distributed to tissue) is:

 

A.                 2-4 hours

B.                 4-6 hours

C.                 6-8 hours

D.                 8-10 hours

E.                  None of the above

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11.       Properties of iron that help promote toxicity include

 

A.                 First order absorption with poor excretion

B.                 Zero order absorption but rapid excretion

C.                 Zero order absorption, but slow excretion

D.                 None of the above

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12.       In a patient with iron poisoning who is receiving deferoxamine, the most accurate method for measurement of iron is:

 

A.                 Calorimetric method

B.                 Radioimmune assay method

C.                 Atomic absorption spectrophotometric method

D.                 All these methods are equally accurate

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13.       A true statement about use of deferoxamine in iron poisoning is:

 

A.                 Iron that is bound to various proteins is avidly chelated by deferoxamine

B.                 Efficacy of deferoxamine is related entirely to the actual excretion of the amount of iron ingested

C.                 Deferoxamine prevents toxicity by making iron unavailable for cellular binding through formation of furoxamine (FA)

D.                 Cytochrome-bound iron is complexed by deferoxamine

E.                  Deferoxamine is very well absorbed from the gut when given enterally

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14.       In a setting of iron poisoning, gastric lavage is indicated in all of the following circumstances except:

 

A.                 Chewable tablet forms of iron are ingested

B.                 Pill fragments are seen in the emesis

C.                 Pill fragments are seen on the chest or abdominal radiograph

D.                 Any patients with iron poisoning should undergo gastric lavage regardless of type of tablets or time of presentation

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15.       Activated charcoal is ineffective in the setting of iron poisoning.  Which of the following lavage solutions have been shown to dramatically decrease absorption of and the toxicity due to iron:

 

A.                 Phosphate lavage solution

B.                 Bicarbonate lavage solution

C.                 Deferoxamine lavage solution

D.                 None of the above

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16.       Regarding management of a child with iron ingestion/overdose:

 

A.                 Any awake child who has ingested more than 20 mg/kg of elemental iron and who has not vomited spontaneously may be given syrup of ipecac at home and brought to the hospital

B.                 When two children are found sharing a bottle of iron pills, the smaller child would have the greater risk of toxicity

C.                 If  gastrointestinal symptoms do not develop within 6 hours of ingestion, the child may be discharged home safely

D.                 The presence of tachycardia, tachypnea and hypoperfusion necessitates immediate chelation regardless of dose/concentration of  Fe++

E.                  All of the above

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17.       ____    Major metabolic pathway for elimination when therapeutic doses are used

            ____    Becomes of paramount importance during salicylate intoxication

            ____    Follows the Michaelis-Menten Kinetics (saturable kinetics) with overdose of salicylate

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18.       The half-life of salicylates at therapeutic doses is 2-4 hours.  This may be as long as 20 hours in a setting of overdose because:

 

A.                 At high concentration two of the dominant metabolic pathways follow the Michaelis-Menten Kinetics

B.                 Protein binding increases

C.                 Volume of distribution decreases

D.                 pKa changes

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19.       The Done nomogram used in salicylate poisoning does not take into consideration which of the following:

 

A.                 A single acute ingestion of non-enteric coated tablets

B.                 Urinary pH

C.                 Blood pH

D.                 Used only 6 hours or more after ingestion

E.                  Developed in a largely pediatric population

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20.       Regarding evaluation and management of patients with possible poisoning or overdose, which of the following statements is correct:

 

A.                 Respiratory acidosis is a recognized feature of salicylate toxicity

B.                 Alterations in mental status and the presence of metabolic derangements confirms the diagnosis of acetaminophen overdose

C.                 Elevation of temperature directly resulting from salicylate toxicity is seen in mild cases

D.                 In children, the respiratory alkalosis is transient and metabolic acidosis predominates with salicylate overdose

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21.       Regarding salicylate overdose, which of the following statements is least accurate:

 

A.                 Aspirin is the leading cause of childhood poisoning today

B.                 A urine ferric chloride test that turns purple suggests salicylate ingestion

C.                 In an obtunded patient who requires endotracheal intubation, hyperventilation to maintain alkalemia is of paramount importance in salicylate poisoning

D.                 Repeated dose activation charcoal possibly works by preventing desorption of salicylate from charcoal

E.                  Ketonuria is a recognized abnormality in urinalysis

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22.       Which of the following statements regarding management of salicylate poisoning is true:

 

A.                 Following endotracheal intubation, rapid normalization of plasma pH should be attempted

B.                 Renal excretion of salicylate depends to a significant degree on urinary flow, making forced diuresis a remarkably beneficial intervention

C.                 Concomitant alkalinization of blood and urine is not recommended

D.                 Acetazolamide, although less popular, has the same efficiency and safety in maintaining urinary alkalinization as bicarbonate

E.                  The presence of a respiratory acidosis warrants evaluation for another toxin or pulmonary edema

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23.       When it is difficult to achieve an adequate urinary alkalinization in salicylate poisoning, one should suspect all of the following except:

 

A.                 Hypokalemia

B.                 Hypovolemia

C.                 Hyperkalemia

D.                 Excretion of organic acids

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24.       In the setting of acetaminophen overdose, N-acetylcysteine should be withheld in which of the following situations:

 

A.                 When acetaminophen levels will be available, but not until 12 hours after ingestion

B.                 Toxic acetaminophen levels documented, but 26 hours after ingestion

C.                 Toxic acetaminophen levels documented, but patient is already in fulminant hepatic failure

D.                 None of the above

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25.       Which of the following would be an effective therapy for prevention of hepatic injury following severe acetaminophen overdose:

 

A.                 N-acetylcysteine

B.                 Hemoperfusion

C.                 Hemodialysis

D.                 Peritoneal dialysis

E.                  All of the above

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26.       Poor prognostic factors in a patient with acetaminophen overdose and consideration for early referral for possible liver transplantation include:

 

A.                 A rise in PT to 1.8 x control on day 3, Grade III (encephalopathy and an admission serum Cr > 3.3 mg%, all combined

B.                 Admission pH of < 7.3

C.                 An increase in the ratio of Factor VIII to Factor V

D.                 All of the above

E.                  None of the above

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27.       Regarding management of acetaminophen toxicity, which of the following statements is most accurate:

 

A.                 Gastric lavage is useful within the first 24 hours of ingestion

B.                 Activated charcoal is effective within 48 hours of ingestion

C.                 If an acetaminophen level will not be available within 8 hours of ingestion, a dose of N‑acetylcysteine should be given regardless of the amount ingested

D.                 Patients on anti-convulsants should be treated with N-acetylcysteine at a higher level of acetaminophen

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28.       Mechanisms of action of N-acetylcysteine for acetaminophen overdose, when administered within the first 8 hours after ingestion does not include which of the following:

 

A.                 A precursor for glutathione replenishment

B.                 A precursor for sulfate replenishment

C.                 A glutathione substitute to directly conjugate N-acetylbenzoquinoneimine

D.                 Redirection of N-acetylbenzoquinoneimine back to acetaminophen

E.                  An antioxidant

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29.       Mechanisms responsible for the beneficial effects of late administration (> 8 hours) of N-acetylcysteine for acetaminophen overdose include all of the following except:

 

A.                 Possibly a precursor for EDRF

B.                 Decreased neutrophil accumulation

C.                 Improved microcirculatory changes

D.                 Improved tissue O2 delivery or extraction

E.                  Redirection of N-acetylbenzoquinoneimine  back to acetaminophen

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30.       Regarding the overdose with and toxicity from acetaminophen, which of the following statements is least accurate:

 

A.                 Peak plasma levels almost always occur 4 hours after ingestion

B.                 Hepatotoxicity is produced only by products of metabolism through P-450 mixed function oxidase system

C.                 Hepatotoxicity is periportal with centrilobular sparing

D.                 Children appear to be less vulnerable than adults to the toxic effects of acetaminophen

E.                  Patients on anti-convulsants who develop acetaminophen toxicity have higher mortality rate

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31.       Regarding acetaminophen toxicity in overdose settings:

 

A.                 In a younger child with extremely high levels, hypotension, hypothermia, apnea and metabolic acidosis occur

B.                 Liver function tests should be repeated every 24 hours for four days

C.                 Acetaminophen level analyzed by calorimetric method is unreliable in the presence of elevated bilirubin, renal failure or salicylism

D.                 All of the above

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32.       Indications for oral N-acetylcysteine in an acetaminophen overdose include:

 

A.                 Serum acetaminophen in the toxic range on Rumack-Matthew nomogram

B.                 Initial AST and PT that are increased at the time of presentation

C.                 Prior or present vomiting with ingestion of > 140 mg/kg

D.                 History of a large acetaminophen ingestion at an unknown time

E.                  All of the above

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33.       Pharmacologic properties of theophylline that are pertinent to the management of a patient who presents with theophylline overdose does not include which of the following:

 

A.                 Theophylline overdose is associated with release of epinephrine and norepinephrine

B.                 Theophylline toxicity is associated with cAMP production  via b-adrenergic receptor stimulation

C.                 Theophylline toxicity is associated with decreased cAMP degradation via inhibition of phosphodiesterase

D.                 Hypotension is due to peripheral vasodilation secondary to stimulation of B2 receptors

E.                  At very high serum levels, theophylline blocks B2 receptors

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34.       Regarding cardiovascular manifestations of theophylline toxicity, all of the following are true except:

 

A.                 If the patient does not have tachycardia, the diagnosis of theophylline overdose is suspect

B.                 b-adrenergic stimulation is responsible for the electrolyte and acid-base disturbances

C.                 Anti-emetics with anti-cholinergic activity are preferred

D.                 If a pressor is needed to treat blood pressure, a pure a adrenergic agent is preferred

E.                  The cardiovascular toxicity is due to release of epinephrine and norepinephrine

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35.       Which of the following is the most potent opioid:

 

A.                 Morphine sulfate

B.                 Meperidine

C.                 Morphine-6-b-glucuronide

D.                 Codeine

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36.       Seizures developing in a setting of opioid overdose is usually due to hypoxia except when overdose is due to:

 

A.                 Fentanyl

B.                 Meperidine

C.                 Morphine sulfate

D.                 Methadone

E.                  Codeine

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                                    A.        Sodium nitrite

                                                B.         Sodium theosulfate

                                                C.        Both

                                                D.        Neither

 

37.       ____    Dose needs to be adjusted for hemoglobin concentration

            ____    Dose needs to be adjusted for body weight

            ____    Efficacy can be increased by co-administration of 100% O2

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38.       The combustion of which of the following materials may produce cyanide:

 

A.                 Wool and silk

B.                 Synthetic rubber

C.                 Polyurethane

D.                 Nitrocellulose

E.                  All of the above

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39.       A 15-year-old white female who had ingested a bottle full of sustained release theophylline tablets has been admitted to the Pediatric ICU where she has been receiving supportive measures and multidose activated charcoal every hour with intravenous metoclopramide to combat vomiting.  In spite of these aggressive measures, theophylline levels have failed to decline over the last six hours.  The most appropriate next step is:

 

A.                 Upper gastrointestinal tract radiography or endoscopy

B.                 Charcoal hemoperfusion

C.                 Hemodialysis

D.                 Peritoneal dialysis

E.                  None of the above

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40.       In a patient with acute theophylline overdose, which of the following laboratory data is least expected:

 

A.                 Respiratory alkalosis

B.                 Hyperglycemia

C.                 Hyperkalemia

D.                 Leukocytosis

E.                  Metabolic acidosis

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41.       Regarding intensive care management of significant theophylline toxicity, all of the following are true except:

 

A.                 Agitation should be evaluated for hypoglycemia

B.                 A vasopressor with predominantly a-adrenergic activity is preferred to treat hypotension unresponsive to intravenous fluid administration

C.                 Hypotension poorly responsive to fluid and pressors is an indication for hemoperfusion

D.                 Repeated dose activated charcoal should be discontinued during hemoperfusion

E.                  When hemoperfusion and hemodialysis are used in series, the electrolyte abnormalities are easier to correct.

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42.       Which of the following opioid is most likely to cause intraventricular conduction defect, heart block and bigeminy:

 

A.                 Heroin

B.                 Morphine sulfate

C.                 Propoxyphene

D.                 Meperidine

E.                  None of the above

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43.       Hypotension in association with opioid overdose is due to:

 

A.                 Bradycardia

B.                 Histamine release

C.                 Inhibition of the central adrenergic response to bradycardia leading to vasodilation and hypotension

D.                 All of the above

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44.       A 16-year-old was found comatose at home with a heart rate of 45/min and a respiratory rate of 3/min with central cyanosis; pupils were pinpoint.  En route to the hospital, he had two episodes of seizures.  The ECG monitor shows second degree heart block, a heart rate of 43 bpm with evidence of intraventricular conduction defect.  He is given multiple doses of naloxone up to 15 mg which lead to improvement in his mental status but the ECG changes persist.  The most likely explanation is:

 

A.                 Propoxyphene overdose

B.                 Heroin overdose

C.                 Tricyclic overdose

D.                 Phenothiazine overdose

E.                  Meperadine overdose

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45.       When patients develop addiction to opioids, tolerance does not develop to which of the following side effects:

 

A.                 Euphoria

B.                 Sedation

C.                 Miosis

D.                 Constipation

E.                  None of the above

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46.       Regarding gastrointestinal decontamination following opioid overdose, all of the following statements are true except:

 

A.                 The benefits of gastric lavage is greater than expected since opioids delay gastric emptying

B.                 Use of activated charcoal is contraindicated in “body packers”

C.                 Gastric lavage should be followed by activated charcoal

D.                 Elimination of propoxyphene and diphenoxylate is enhanced by multiple dose activated charcoal

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47.       Acute respiratory failure is a recognized complication of opioid overdose.  A true statement regarding this complication is:

 

A.                 Acute respiratory distress syndrome is not seen following overdose with heroin and methadone

B.                 When acute respiratory distress syndrome develops following opioid overdose, it is always present on admission to the hospital

C.                 Pulmonary edema develops following subcutaneous and intravenous abuse as well as following insufflation of opioids

D.                 None of the above

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48.       A 16-year-old is suspected of having opioid overdose.  He shows a definite, but only partial response to naloxone.  He should be evaluated for:

 

A.                 Hypoglycemia

B.                 Hypoxia from ARDS leading to encephalopathy

C.                 Exposure to 3-methylfentanyl

D.                 Post-ictal phase

E.                  All of the above

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49.       With methanol intoxication, which of the following factors has been shown to correlate best with a poor outcome:

 

A.                 Degree of hyperventilation

B.                 Delay of toxic symptoms for > 10 hours

C.                 Degree of headache

D.                 Elevation of blood glycolic acid levels

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50.       With methanol intoxication, the most characteristic finding and the one that correlates best with the degree of metabolic acidosis is:

 

A.                 Dilated pupils with poor response to light and accommodation, and hyperemia of optic disc

B.                 Oxalaturia

C.                 Elevated levels of glycolic acid

D.                 Hyperventilation

E.                  None of the above

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51.       Regarding therapy of ethylene glycol poisoning with ethanol:

 

A.                 When dialysis is initiated, the dose of ethanol should be reduced by 50%

B.                 A concentration of 80-100% should be used for PO route

C.                 Only a 5-10% concentration should be used intravenously to avoid phlebitis

D.                 100-proof whiskey would equal 100% vol/vol ratio

E.                  None of the above


A.        Ethylene Glycol Poisoning

B.         Methanol Poisoning

C.        Both

D.        Neither

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52.       ____    Alkalinization is advantageous

            ____    Charcoal hemoperfusion is indicated

            ____    Peritoneal dialysis indicated

            ____    Pyridoxine 50 mg intravenously every 6 hours converts the metabolism of this substance to a less harmful end product

            ____    Thiamine 100 mg intravenously every 6 hours produces the harmless substance a-OH–b ketoadipic acid

            ____    Folic acid 50 mg intravenously every 6 hours enhances the elimination of toxic byproducts of this toxin

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53.       A true statement regarding use of naloxone for opioid overdose in an adolescent is:

 

A.                 The typical initial dose of naloxone should be 0.1 mg intravenously

B.                 If the first dose fails to reverse symptoms, then no additional doses are necessary

C.                 Blind sublingual naloxone injection may be life saving if the patient is hypotensive and intravenous access can’t be established

D.                 In a setting where there is no ventilatory insufficiency, high dose naloxone is still recommended

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54.       When a patient responds to a naloxone bolus, pharmakokinetic studies indicate that ______ of the initial dose that caused reversal of the respiratory depression, administered each hour is adequate to prevent recurrence of symptoms:

 

A.                 1/3

B.                 1/2

C.                 2/3

D.                 2 times the dose

E.                  None of the above

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55.       A 15-year-old white female who recently had a fight with her boyfriend was found comatose after having ingested a full bottle of amitriptyline.  The least appropriate initial investigation is:

 

A.                 12-lead EKG

B.                 Electrolytes

C.                 Acetaminophen levels

D.                 Tricyclic antidepressant levels

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56.       Seventy minutes after arrival in the emergency department, the patient in Question #55 develops wide complex tachycardia at 160 bpm with a blood pressure of 70/40 mm Hg.  All of the following statements are true except:

 

A.                 This effect is due to slowing of sodium influx into the myocardial cells during phase 0 of depolarization

B.                 This adverse effect can be attended by hyperventilation to a pH of 7.55

C.                 Hypotension should be treated aggressively since lactic acidosis enhances binding of the ingested medication to sodium channels in the myocardium

D.                 Lidocaine may be effective in treating this dysrrhythmia

E.                  Hypertonic saline is as effective as Na HCO3 to treat this dysrrhythmia

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57.       The same patient began to develop generalized tonic clonic seizure activity.  After securing an adequate airway, the following should be done:

 

A.                 Phenytoin should be the drug of choice

B.                 Flumazenil is likely to have some synergic effects in controlling seizure activity

C.                 Benzodiazepines should be avoided

D.                 If the seizure is prolonged, adequate hydration and monitoring of renal function is essential

E.                  All of the above

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58.       True statements regarding the patient referenced in Question #55 include:

 

A.                 This patient should have received ipecac soon after ingestion

B.                 Unlikely amitriptyline, second generation cyclic antidepressant are uniformly less toxic than the first generation

C.                 Multiple  dose activated charcoal enhances elimination

D.                 Physostigmine is a helpful therapeutic modality in this patient if the anti-cholinergic symptoms are severe

E.                  All of the above

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59.       Drugs that should be avoided in the patient in Question #55 include:

 

A.                 Class IA and IC antiarrhythmics

B.                 Phenytoin

C.                 Flumazenil

D.                 Propranolol and Verapramil

E.                  All of the above

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60.       Match the clinical features and medical management to the corresponding drug or toxin in a setting of overdose:

 

                                                A.        Paraldehyde

                                                B.         Toluene

                                                C.        Isoniazid

                                                D.        Isopropyl alcohol

                                                E.         None of the above

 

            ____    Mild metabolic acidosis with ketonuria

            ____    High anion gap metabolic acidosis or non-anion gap renal tubular acidosis

            ____    Seizure responsive to Vitamin B6

            ____    Ketonemia, ketonuria in the absence of metabolic acidosis, but with hyperosmolality

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61.       Regarding organophosphate poisoning, all of the following are true except:

 

A.                 Sweating and fasciculation may precede other symptoms after cutaneous exposure

B.                 Severely poisoned patients are comatose, weak and hypotensive

C.                 The odor of garlic on the breath can be a prominent finding

D.                 Tachycardia and hypertension  are virtually never seen

E.                  An EEG is useful in differentiating severe fasciculations from true seizures

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62.       Pralidoxime (2-PAM) is an acetylcholinesterase reactivator and is the only such drug available in the US for use in patients with organophosphate/pesticide poisoning.  Which one of the following statements is true:

 

A.                 The benefits of pralidoxime is least striking at the nicotinic receptors

B.                 Weakness and muscle fasciculations are contraindications to use of PAM

C.                 Improvement in strength may be observed within 10 minutes of administration

D.                 To be effective, the drug needs to be given within 4 hours of exposure to organophosphates

E.                  Is contraindicated in patients with carbomate poisoning

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63.       Regarding management of organophosphate insecticide poisoning:

 

A.                 Manifestations occur even if only 5% of cholinesterase is inhibited

B.                 Plasma cholinesterase level is lowered by administration of morphine or codeine

C.                 The end point of atropinization is maximum pupillary dilation

D.                 Tachycardia is a contraindication to the use of atropine

E.                  All of the above

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64.       Which of the following factors is least likely to influence the efficacy of hemoperfusion:

 

A.                 Rate of flow

B.                 Affinity of the adsorbent for the drug

C.                 Rate of equilibrium of the drug from peripheral tissue to the blood

D.                 Lipid solubility

E.                  Volume of distribution

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65.       Complications of hemoperfusion include all of the following except:

 

A.                 Hypoglycemia

B.                 Hyperthermia

C.                 Thrombocytopenia

D.                 Hypotension

E.                  Hypocalcemia

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66.       Repeated dose activated charcoal is not recommended for overdose with which of the following drugs:

 

A.                 Phenobarbital

B.                 Carbamazepam

C.                 Digitalis

D.                 Theophylline

E.                  Ferrous sulfate

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A.        Carbamates

                                                B.         Organophosphates

                                                C.        Both

                                                D.        Neither

 

67.       ____    Temporary inactivation of acetylcholinesterase

            ____    Does not penetrate the central nervous system

            ____    Only atropine is indicated as an antidote

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68.       Drug(s) with a low PKa (3-7) which are amenable to alkaline diuresis is/(are):

 

A.                 Phenobarbital

B.                 Isoniazid

C.                 Salicylates

D.                 All of the above

E.                  None of the above

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69.       A 3-year-old with severe salicylate overdose is in the PICU being treated with supportive care and HCO3 infusion.  However, you have not been able to establish an alkaline urine pH.  The most helpful intervention would be:

 

A.                 Administration of large doses of furosemide

B.                 Saline loading

C.                 Increase the dose of HCO3

D.                 Potassium supplementation

E.                  Initiate acetazolamine

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70.       Drugs that are easily dialyzable are characterized by all of the following except:

 

A.                 Have a small volume of distribution (< 2 L/kg)

B.                 Are highly water soluble

C.                 Are poorly protein bound (< 90%)

D.                 Have a small molecular weight

E.                  Have a large volume of distribution

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71.       The clinical usefulness of hemoperfusion is dependent most on which one of the following features of a drug or toxin:

 

A.                 Water solubility

B.                 Protein binding

C.                 Molecular weight

D.                 Lipid solubility

E.                  Volume of distribution

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                                                A.        Fasciculations

                                                B.         Myoclonus

                                                C.        Both

                                                D.        Neither

 

72.       ____    Organophosphate poisoning

            ____    Anti-cholinergic overdose

            ____    Phenothiazine overdose

            ____    Haloperidol overdose

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73.       A 4-month-old who presented with cyanosis and lethargy is noted to have an 88% saturation on pulse oximetry.  PaO2 is 70 torr and the measured O2 saturation (by the co-oxymeter) is 76%.  Possible etiologic agents is/(are):

 

A.                 Benzocaine

B.                 Nitrates

C.                 Nitrites

D.                 Carbon monoxide

E.                  All of the above

Click here for answer 

74.       Which of the following drugs and toxins does not have the tendency to form concretions in the stomach:

 

A.                 Ferrous sulfate

B.                 Salicylates

C.                 Slow release tablets of theophylline

D.                 Acetaminophen

E.                  Barbiturates

  Click here for answer

75.       In treating children with poisoning, use of repeated-dose activated charcoal for a prolonged period of time is contraindicated in cases of ingestion with:

 

A.                 Enteric coated preparation

B.                 Corrosives

C.                 Anti-cholinergics with ileus

D.                 Mineral acids

E.                  All of the above

  Click here for answer

76.       Hypotension in a poisoned child is most closely associated with:

 

A.                 Myocardial depression

B.                 Hypoalbuminemia

C.                 Hypovolemia

D.                 Electrolyte imbalance

E.                  None of the above

  Click here for answer

77.       Dysrhythmias associated with tricyclic anti-depressants are best treated with:

 

A.                 Procainamide

B.                 Quinide

C.                 Na HCO3

D.                 Epinephrine

E.                  None of the above

  Click here for answer


78.       Hypertension is a prominent feature of intoxication with:

 

A.                 Amphetamine

B.                 Dimetab

C.                 PCP

D.                 Cocaine

E.                  All of the above

  Click here for answer

79.       Match the following drugs and toxins to the corresponding odor it is most closely associated with:

 

A.                 Garlic

B.                 Bitter almonds

C.                 Shoe polish

D.                 Pears

E.                  Rotten eggs

 

            ____    Arsenic

            ____    Cyanide

            ____    Nitrobenzone

            ____    Chlorohydrate

            ____    Hydrogen sulfide

  Click here for answer

Answers

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 < 3 and when there is a need to establish a therapeutic level rapidly, then a loading dose is necessary.  Loading Dose = rConcentration ´ Volume of Distribution.  (Kearns GL.  Clin Pharmakokinet, 1989; 17 (Suppl 1); p 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/min/1.73 M2, the renal index (RI) would = 28.1ml/min which is equal to .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.  Guide To Drug Dosage in Renal Failure.  Clin Pharmakokinet, 1988; 52:326)

 

4.             E                              Patients at risk of adrenal hypofunction who are admitted to the pediatric intensive care unit (for non-trivial illness) require additional doses of corticosteroid coverage.  The physiologic dose is 12.5mg/M2 BSA / day of hydrocortisone.  Patients with a febrile illness presumed to be secondary to a non-trivial 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.  Since the risk of under-treatment is higher than over-treatment in patients with a serious illness or trauma, it is reasonable for a clinician to administer 100-200mg/M2 BSA/day of hydrocortisone to these patients.  Gastric acidity partially inactivates oral steroids and, therefore, higher doses are often necessary.  (Migeon C.  Physiology and Pathophysiology of Adrenocortical Function in Infants and Children.  Collaly R, et al.  Recent Progress in Pediatric Endocrinology.  New York, Raven Press, 1981; pp 465-522.

 

 

5.             A                             Adrenergic receptors comprise 4 subtypes:  a1, a2, b1 and b2.  Each of these subtypes and the family keeps growing. a1 receptors are typical post-synaptic 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 norepinephrine from sympathetic nerve terminals resulting in relaxation of vascular and 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 pheochromocytoma.  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 b1 blocker.  (Bravo E.  N Eng J Med, 1984; Vol. 311:1298.  Hoffman B.  N Eng J Med, 1980; Vol 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 pseudocholinesterase and nonenzymatic hydrolysis.  The two major cocaine metabolites in urine are benzoylecgonine and ecgonine methyl ester.  Most urine drug screening tests detect benzoylecgonine.  There is a greater potential for toxicity in patients with pseudocholinesterase deficiency since 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 spectrophotometric method.  Interestingly, deferoxamine 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             Amphetamine (racemic beta-phenylisopropylamine).  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.  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 8-30 hours.  Amphetamines enhance the release of and block the re-uptake of catecholamines resulting in excess stimulation of both a and b 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 since agitation against restraints may exacerbate the associated rhabdomyolysis.  Benzodiazepines are the drug of choice since 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 > 20 mg/kg BW of elemental iron and who has not vomited spontaneously (and is awake) may be given syrup of ipecac and brought to the emergency department.  These children or children who have ingested < 20 mg/kg BW of elemental iron and have a level of < 500 mg/dL of serum iron -- if gastrointestinal symptoms develop within six hours, they may be discharged home since it is unlikely that children who present within one 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 valuabletime to assess serum iron is 4-6 hours after ingestion.  At this time, tablet breakdown is almost complete, yet iron has not been completely distributed to tissues.


Since administration of deferoxamine 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.  Deferoxamine (DFO) is a specific iron binding agent that binds free inorganiciron to form Ferrioxamine (which is reddish in color) that is excreted in urine.  It is given intravenously since 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.  Hemoglobin, cytochrome and other protein-bound iron is not chelated.   Activated charcoal is ineffective in the setting of iron poisoning, nor 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 2-4 hours at therapeutic doses to as long as 20 hours.  Also, protein binding decreases from 90% at therapeutic levels to < 75% at toxic levels, and volume of distribution increases from .2 to .3 liters/kg.  A nomogram is of limited value and was developed to be used only ³ 6 hours after a single ingestion of non-enteric 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 alkalosis is transient and usually occurs with metabolic acidosis.

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 due to 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, salicylates 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 alkalinization 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 four hours of ingestion.  The drug is metabolized in the liver by: 1) sulfation; 2) glucuronidation, 3) P450 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 mercapturic acid or cysteine conjugates.

A small fraction of acetaminophen is excreted in urine unchanged.  This and the product of sulfation and glucuronidation are non-toxic.  In the setting of overdose, when > 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 are children on anti-convulsants, such as phenobarbital which accelerates the p450 mixed-function oxidase system with production of higher levels 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 two 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 > 24 hours after ingestion of APAP, NAC acts as an antioxidant.  NAC is administered when APAP is in the toxic range based on Rumack & Mathew nomogram.  NAC is also indicated when 1) initial AST and PT are elevated, suggesting significant ingestion, 2) when there is a history of prior or present vomiting with ingestion of > 140 mg/kg BW; 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 (AST, ALT), bilirubin and PT and PTT should be measured every 24 hours for four days while therapy proceeds.  It is important to recognize that APAP measured by the calorimetric method is unreliable in the presence of high salicylates or 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 due to massive catecholamine (release of epinephrine and norepinephrine) stimulation of the myocardium and is aggravated by hypokalemia, hypercalcemia and hypophosphatemia.  b-adrenergic stimulation is responsible for the electrolyte  abnormalities, acid-base disturbances, and vasodilation.  Metabolic acidosis, hypokalemia, and hyperglycemia are recognized features.  The hypokalemia is due to a transcellular 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 b-blockers, and other supportive measures should be continued.  The indications for initiation of hemoperfusion include a theophylline level > 90 mg/ml at any time; a theophylline level > 70 mg/ml 4 hours after ingestion of a sustained release tablet; a theophylline level > 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, morphine-6-beta-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 central nervous system excitation and seizures when it accumulates. (Goldfrank, LR.  Goldfrank’s Toxicologic Emergencies, 6th Edition; pp 777-778)

 

37.           A, B, C                   The dose of sodium nitrite needs adjustment for hemoglobin concentration, whereas sodium thiosulfate needs adjustment for body weight.  The efficacy of both these medications is increased by the co-administration 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 gastrointestinal endoscopy is warranted to evaluate for formations of concretions and bezoars.   Hypokalemia is more likely to develop due to the b-adrenergic agonist type effect of theophylline.  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.  Goldfrank’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 due to propoxyphene.  (Goldfrank, LR.  Goldfrank’s Toxicologic 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 Toxicologic 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 > 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 poisoning.  High anion gap metabolic acidosis and hyperventilation are features of both.  The degree of anion gap (AG) or ethylene glycol 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.  Since ethanol has a greater affinity for alcohol dehydrogenase than either methanol or ethylene glycol, 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 IV using a 10% concentration.  Ethanol should be continued during hemodialysis at a higher dose since 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 CNS.

Additional therapeutic measures ethylene glycol ingestion may include:  100 mg of Thiamine IV or 50 mg of Pyridoxine IV every 6 hours until acidosis is resolved and ethylene glycol level is zero (0).  Pyridoxine in the preesnce 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, folic acid 50-75 mg 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, 2/3 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:

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

2)       Membrane depressant effect by slowing sodium influx into myocardial cells during Phase O of depolarization.

3)       a-adrenergic blockade

4)       Inhibition of central sympathetic reflexes

5)       Anticholinergic and antihistamine effects

 

Many of the signs noted during toxicity are due to central and peripheral anticholinergic effects which include: agitation, confusion, hallucinations, coma, seizures (central);   tachycardia, hypertension, hyperthermia, 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 six hours of hospitalization (most often within two 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.  However, absence of these EKG changes does not exclude an overdose with antidepressants (CAO).  The duration of QRS has been shown to be prognostic of seizures and dysrhythmias:  QRS > 100 msec - 30% risk of seizures; QRS > 160 msec - 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 since there is no good correlation between levels and symptomatology.  However, with levels exceeding 1,000 mg/ml, dysrhythmias and seizures are usually seen.

 

Cyclic antidepressants 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 cyclic antidepressants 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 while 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 while 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 dysrhythmias.  Other drugs that must be avoided include:  Class IA and IC antiarrythmias (membrane stabilizers); Propanolol and Verapasmil (myocardial depressants); Flumazenil (inhibits the chloride channel of a-adrenergic and b-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; p 726-731)

60.           A, B, C, D              These are the drugs/toxins that should be in the differential diagosis of high anion gap metabolic acidosis (HAGMA):

1)       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

2)       Toluene abuse by inhalation takes two forms:

a)       Huffers inhale from a toluene-soaked cloth

b)       Baggers inhale from a plastic bag containing toluene placed over the head

                                                        They may present with HAGMA or renal tubular acidosis.  Other symptoms are gastrointestinal disturbances, musculoskeletal weakness or neuropsychiatric disorders

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

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

(Goldfrank, LR.  Goldfrank’s Toxicologic Emergencies, 6th Edition; p 627-628)

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

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

63.           B                             Clinical manifestations of organophosphate poisoning are not seen until a significant portion of the cholinesterase is inhibited, and the endpoint 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, compunds 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, cyclic antidepressants, meprobamate and digoxin.

                                                Extraction of many of these compounds are 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 hemoperfusion because of the high adsorbent area that comes in contact with the blood.  The volume of distribution (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; p 66-69)

 

67.           A, A, A                  Carbamates do not penetrate the central nervous system, 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, 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 2,500:1, 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                             Since 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 volume of distribution (Vd) so that the majority of the drug is in the plasma; and have a small molecular weight – compounds with a molecular weight > 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 64-65.

 

72.           A, B, B, B               Organophosphates bind irreversibly to acetylcholinesterase (the enzyme which 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 oxyhemoglobin to the total hemoglobin and is incapable of measuring the other different types of hemoglobin, such as carboxyhemoglobin or methemoglobin.  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 theophylline preparations.  In these case circumstances, attempts should be made to eliminate these concentrations from the stomach including use of endoscopy, since 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) Anticholinergics – 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.  Goldfrank’s Toxicologic Emergencies, 6th Edition; pp 726-731)

 

77.           C                             Alkalosis seems to minimize binding of cyclic antidepressants to sodium channels in the myocardium with resultant suppression of dysrhythmias. (Goldfrank, LR.  Goldfrank’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.  Goldfrank’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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