questions 26

Toxicology

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Topic updated on 11/14/17 9:05am

Toxicology Drug Introduction
  • Toxicology medications can be broken down into the following categories 
    • metallic poisoning
    • gas poisoning
    • prescription drugs overdose
    • illegal drugs overdose
    • household substance overdose
 
Treatment Poison(s) Notes
Metallic Poisoning
Deferoxamine
  • Iron
  • Used for aluminum poisoning in renal failure
  • Used in iron overload with repeat transfusions (thalssemia)
  • Iron over load, hemochromatosis
Deferasirox
Prussian blue
  • Cesium
  • Thallium
  • Used in the case of a radioactive incident
Penicillamine
  • Copper (Wilson's disease)
  • Water-soluble form of penicillin
  • Avoid in patients who have penicillin allergy
  • Chelates copper
EDTA
  • Lead
  • Can chelate and deplete calcium ions
Dimercaprol (BAL)
  • Arsenic
  • Lead
  • Mercury
  • Used in conjunction with EDTA for lead poisoning
Succimer
  • Arsenic
  • Lead
  • Mercury
  • Used more commonly in children
Gas Poisoning
100% O2 (consider hyperbaric O2)
  • Carbon monoxide (CO)
  • CO binds with much greater affinity than O2
Amyl and sodium nitrite
  • Cyanide
  • Cyanide found in rodenticides "gopher goitter", released in burning of plastics and wool, and plants such as cassava
  • Cyanide binds Fe3+ of cytochrome oxidase a3 of the electron transport chain (ETC) arresting cellular respiration
  • Nitrites create methemoglobin (Fe3+) intentionally to compete for and bind cyanide so it does not get to the ETC
Sodium thiosulfate
Hydroxycobalamin
Prescription Drug Overdose
N-acetylcysteine 
  • Acetaminophen   
  • Best if given with 8-10 hours
  • Also a mucolytic
Sodium bicarbonate 
  • Salicylates
  • Tricyclic antidepressants (TCA)
  • First sign of OD is hyperventilation and respiratory alkalosis
  • Do not give with physostigmine
  • First check an EKG for QRS prolongation, then treat with sodium bicarbonate in TCA overdose
Potassium iodide
  • Radioactive iodine (I-131)
  • Given to prevent the uptake of I-131
Ammonium chloride (NH4Cl, acidic)
  • Amphetamines (basic)
  • Eliminates amphetamines by acidifying urine which results in a charged amphetamine molecule which is excreted

Atropine

  • Anticholinesterases 
  • Organophosphates
  • Sarin (nerve gas)
  • Removed contaminated clothing if patient was exposed to insectisides
  • Atropine as an anti-cholinergic and combats the excess Ach
  • Pralidoxime if given in a timely manner regenerates acetylcholinesterase reversing the condition (timing is critical)
Pralidoxime
Physostigmine 
  • Antimuscarinic
  • Anticholinergic agents 
  • Atropine overdose
  • Do not give if patient may have TCA OD as it may lead to heart block or asystole
  • Tertiary amine that can cross the blood brain barrier and reverse anticholinergic effects in the CNS
Naloxone/naltrexone
  • Opioids
  • Precipitates withdrawal symptoms in chronic opioid users
  • Use in patients with respiratory depression
  • Opioid withdrawal will NOT kill a patient it is just unpleasant
Flumazenil
  • Benzodiazepines
  • May cause seizures in addicted benzodiazepine users
  • Rarely used with benzodiazepine overdose unless concerned for respiratory depression
  • Otherwise let the patient "sleep off" the benzodiazepines
Glucagon
  • β-blockers 
  • IM glucagon best to reverse beta-blocker overdose
β-blockers (propranolol, esmolol)
  • Theophylline
  • OD symptoms are due to β2 activation: hypotension, tachycardia, hypokalemia, hyperglycemia

Digitalis antibody, lidocaine, Mg2+

  • Digitalis
  • Visual and GI symptoms classically seen in overdose
Methylene blue
  • Methemoglobin
  • Iron in the heme molecule is Fe3+ which cannot bind oxygen until it is reduced to Fe2+ by treatment
Vitamin C
Aminocaproic acid
  • tPA
  • Streptokinase
-
Vitamin K
  • Warfarin
  • Bridge with heparin as warfarin can deplete protein C and S first (anticoagulants) leading to an initial prothrombotic state
Plasma infusion

Protamine

  • Heparin
  • Protamine is a highly positively charged peptide which strongly binds to the negatively charged heparin
Argatroban
  • Direct thrombin inhibitor 
Household Substance Overdose
Ethanol IV infusion
  • Antifreeze (ethylene glycol) 
  • Methanol
  • Think antifreeze when ingested substance is said to be sweet and individual appears "drunk without the typical smell of alcohol"
  • Fomepizole should be followed by dialysis
Fomepizole  
Caustic fluid
  • Perform endoscopy 
  • Irrigation x 15mins for ocular exposure 
  • Do not try to induce vomiting in patient
  • Could perhaps use small amount of diluent
Other
Antivenin
  • Rattlesnake bite
-


Iron Poisoning
  • Most deaths due to iron poisoning (ingestion of iron tablets) occur in children between 12 - 24 months of age
  • Symptoms occur within 30 min to several hours
    • abdominal pain, diarrhea, vomiting
    • cyanosis, drowsiness, hyperventilation resulting from acidosis
  • Death can result in six hours, but an apparent recovery may happen from 6 - 12 hours with death ensuing in the next 12 hours
  • If not treated early, damage to the stomach can lead to pyloric stenosis or gastric scarring
  • Early treatment with deferoxamine can reduce mortality significantly from 45% to 1%
  • Mechanism of action of iron related damage
    • iron overdose results in the peroxidation of membrane lipids leading to cell death
Methanol and Ethylene Glycol Toxicity
  • Each are competitive substrates for alcohol dehydrogenase (ADH) 
  • Methanol
    • metabolized by ADH to formaldehyde followed by aldehyde dehydrogenase to form formic acid which is toxic to the optic nerve
      • early toxicity of formic acid is metabolic acidosis by formic acid itself
      • formic acid also binds to cytochrome oxidase blocking oxidative phosphorylation
      • resulting in lactic acidosis which is the latter and leading cause of the metabolic acidosis
    • signs and symptoms appear within 12 - 24 hours after ingestion
      • CNS depression
        • methanol acts similarly as ethanol as a CNS depressant
      • metabolic acidosis
      • visual changes
        • blindness occurs with as little as 30 mL and death at 100 mL ingestion
  • Ethylene glycol
    • colorless, odorless, sweet-tasting liquid
    • toxicity derives from the hepatic oxidation of ethylene glycol to oxalic acid
      • degraded by same pathway as methanol
        • the glycolic acid produced by aldehyde dehydrogenase is converted in oxalic acid
      • oxalic acid binds calcium and forms calcium oxalate crystals that damage the heart, brain, lungs, kidneys
    • signs and symptoms develop in stages after ingestion
      • first stage: 0.5 - 12 hours
        • stronger inebriant than methanol and ethanol causing mild depression of CNS resulting in seizures and coma
        • patients appear "drunk without smelling like alcohol"
        • within 4 - 12 hours, calcium oxalate crystals deposit in the brain causing CNS toxicity, cerebral edema, meningismus (nuchal rigidity, photophobia, headache without infection or inflammation)
        • hypocalcemia occurs due to binding of calcium by oxalic acid and can cause prolonged QT, arrhythmias, myocardial depression
      • second stage: 12 - 24 hours
        • tachypnea occurs to offset the metabolic acidosis due to the toxic metabolites produced
        • multiorgan failure (CHF, lung injury, myositis) due to widespread crystal deposition
        • NOTE: most deaths occur in the second stage
      • third stage: 24 - 72 hours
        • acute anuric renal failure from crystal deposition but full recovery occurs within weeks to months
  • Treatment
    • IV ethanol (used historically)
      • competitive substrate for ADH and has greater affinity for ADH than methanol and ethylene glycol
    • fomepizole (best initial therapy) 
      • inhibits ADH preventing production of toxic metabolites
      • should be followed by dialysis
Miscellaneous
  • When behavioral changes are recognized in adolescents screen for substance use 


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Qbank (12 Questions)

TAG
(M3.PH.3) A five-year-old girl comes to the emergency department crying, holding her stomach and coughing up pinkish sputum. Her father frantically reports to you that she "swallowed something" at home about two hours ago. After appropriate airway and hemodynamic stabilization, you would next perform esophagogastroduodenoscopy (EGD) if the father tells you that the patient had ingested: Topic Review Topic

1. Iron pills
2. Cyanide
3. Anticholinergics
4. Acetaminophen
5. Drain cleaner

PREFERRED RESPONSE ▶
TAG
(M2.PH.3) A mother brings her 4-year-old daughter to the Emergency Department after finding her in the family's medicine cabinet. The child has been vomiting for the last 2 hours and complaining of abdominal pain. The child is now minimally responsive. Serum bicarbonate is 18 mEq/L. Abdominal radiograph is provided. The emergency room physician correctly starts the child on intravenous fluids and deferoxamine treatment. Poisoning with which of the following is the most likely etiology? Topic Review Topic
FIGURES: A          

1. Acetaminophen
2. Lead
3. Tricyclic antidepressants
4. Iron
5. Aspirin

PREFERRED RESPONSE ▶
TAG
(M2.PH.4) After leaving him alone for approximately 5 minutes, a mother walks into the kitchen to find her 2-year-old child holding an empty bottle of oven cleaner (main ingredient sodium hydroxide). While he is in no apparent distress, she immediately takes him to the emergency department. He is seen within an hour of ingestion. What is the appropriate management of this patient? Topic Review Topic

1. Neutralization of substance
2. Endoscopy
3. Oral fluids
4. Charcoal
5. Ipecac administration

PREFERRED RESPONSE ▶
TAG
(M2.PH.9) A 52-year-old mechanic calls your office and is audibly in panic. He states that a car battery just exploded and sprayed caustic fluid on his face. He reports that his right eye is painfully burning, and he confirms blurred vision out of that same eye. What are the most appropriate immediate instructions to give this patient at this time? Topic Review Topic

1. Present to the local emergency department as quickly as possible
2. Irrigate the eye with tap water for at least 15 minutes
3. Irrigate the eye with an alkaline solution to counteract the acidic car battery fluid
4. Irrigate the eye with an acidic solution to counteract the alkaline car battery fluid
5. Schedule an urgent appointment with a local ophthalmologist

PREFERRED RESPONSE ▶
TAG
(M2.PH.12) A 44-year-old male is rushed to the emergency department after he began complaining of blurry vision in both eyes that developed over the last 45 minutes. He has also experienced excessive sleepiness, having fallen asleep mid-sentence repeatedly over the last several hours. The patient has a past history of alcoholism and reports consuming 1 quart of locally-produced moonshine 12 hours ago. Which of the following sets of signs, symptoms, and findings would be expected upon further evaluation of this patient? Topic Review Topic

1. Photophobia, calcium oxalate crystals on urine microscopy, anion gap metabolic acidosis
2. Abdominal pain, diarrhea, nausea, hematemesis, metabolic acidosis
3. Optic disk hyperemia, anion gap metabolic acidosis, increased osmolar gap
4. Tinnitus, tachypnea, metabolic acidosis, respiratory alkalosis
5. Miosis, diarrhea, increased urination, salivation, elevated troponins, hypomagnesemia

PREFERRED RESPONSE ▶
TAG
(M2.PH.12) A 37-year-old farmer presents to the emergency department with acute onset of complaints of diarrhea, excessive tearing, and increased saliva production. He is concerned that he is dehydrated, as he has also been urinating with increased frequency over the past several hours. Physical exam is significant for a moderately agitated, diaphoretic male who demonstrates pinpoint pupils. You suspect an exposure to a toxic substance might be the cause of his symptoms. Which of the following pharmacologic treatments would be most appropriate for the likely exposure? Topic Review Topic

1. Neostigmine
2. Bethanecol
3. Donepezil
4. Pilocarpine
5. Atropine

PREFERRED RESPONSE ▶
TAG
(M2.PH.14) A 3-year-old girl is brought to the emergency room by her mother. She has been vomiting repeatedly over the last several hours and is complaining of abdominal pain. The patient's mother reports that the emesis has contained streaks of blood. The patient has not had any prior medical issues; and the patient's family history is significant only for anemia in the patient's mother, for which she is being successfully treated with supplementation. An abdominal radiograph is obtained and is shown in Figure A. The cause of this patient's vomiting has been associated with which primary acid-base disturbance(s)? Topic Review Topic
FIGURES: A          

1. Metabolic alkalosis
2. Respiratory alkalosis
3. Respiratory acidosis
4. Metabolic acidosis
5. Mixed respiratory alkalosis and metabolic acidosis

PREFERRED RESPONSE ▶
TAG
(M2.PH.15) A 22-year-old male is found unresponsive by his roommate on the floor of his apartment. He is immediately transported to the emergency department. The patient's medical history is significant for anxiety and major depressive disorder poorly-controlled with amitryptiline. The patient's roommate reports that he noted an empty, open bottle of medicine on the floor of the apartment. Physical exam in the ED is significant for a very lethargic and confused male with dilated pupils and global hyperreflexia. Vital signs are as follows: T 38.7 C, HR 112 bpm, BP 148/92 mmHg, RR 8, O2 sat 94% on room air. The patient's electrocardiogram is shown in Figure A. Basic metabolic panel is significant for a metabolic acidosis. Which of the following antidotes would be the most appropriate treatment for this patient's suspected overdose? Topic Review Topic
FIGURES: A          

1. Dimercaprol
2. Protamine sulfate
3. Flumazenil
4. Sodium bicarbonate
5. Glucagon

PREFERRED RESPONSE ▶
TAG
(M2.PH.23) A 3-year-old male is brought to the local emergency department after his parents became concerned about abrupt onset of unusual behavior over the past several hours. He has developed slurred speech and reported to his parents that he felt dizzy, his "head hurts", and he had a "tummy ache." On physical exam, his vital signs are as follows: T 37.6 C, HR 140, BP 120/85, RR 40, O2 sat 98%. His breathing is notably rapid and shallow. Basic metabolic panel drawn at the time of arrival to the ED shows an elevated anion gap metabolic acidosis. Results from urine microscopy are displayed in Figure A. What is the most appropriate antidote for this child's apparent accidental ingestion? Topic Review Topic
FIGURES: A          

1. Fomepizole
2. Dimercaprol
3. Ethylenediaminetetraacetic acid (EDTA)
4. Ethanol
5. Sodium bicarbonate

PREFERRED RESPONSE ▶
TAG
(M2.PH.46) A 37-year-old female homemaker is rushed to the ED after having been found unresponsive by her 15-year-old son. In the ED she opens her eyes and mumbles incoherently in response to noxious stimuli. She also strikes the ED resident's hand during this examination, but does not follow commands. Her vital signs are: T 98.3 deg F; BP 110/85 mm Hg; RR 15 breaths/min; SpO2 99% on room air. Her medical history is significant for a remote history of depression, anxiety disorder for which she is prescribed alprazolam, and irritable bowel syndrome. Per her son, she takes no other medications. In addition to overdose of her home medication, her toxicology screen is positive for ethanol only. Her EKG is shown in Figure A. Which of the following medications could be considered as an antidote to this patient's overdose? Topic Review Topic
FIGURES: A          

1. Naloxone
2. Diazepam
3. Sodium bicarbonate
4. Flumazenil
5. Fomepizole

PREFERRED RESPONSE ▶
TAG
(M2.PH.4753) A 67-year-old farmer presents to the emergency department with a chief complaint of unusual behavior. His wife states that since this morning he has experienced dryness and flushing of his skin while working outside. As the day went on, the patient found it exceedingly difficult to urinate and had to create significant abdominal pressure for a weak stream of urine to be produced. Currently, the patient seems confused and responds incoherently. The patient has a past medical history of Parkinson's disease, alcohol abuse, irritable bowel syndrome, anxiety, diabetes mellitus, hypertension, constipation and a suicide attempt when he was 23 years old. He is currently taking lisinopril, hydrochlorothiazie, metformin, insulin, benztropine, levodopa/carbidopa, and vitamin C. The only other notable symptoms this patient has experienced are recent severe seasonal allergies. On physical exam you note dry, flushed skin, and a confused gentleman. His temperature is 99.5°F (37.5°C), pulse is 112/min, blood pressure is 130/90 mmHg, respirations are 18/min, and oxygen saturation is 96% on room air. Lab values are ordered. Which of the following is the most likely cause of this patient's presentation? Topic Review Topic

1. Medication
2. Insecticide exposure
3. Alcohol
4. Infection
5. Heat stroke

PREFERRED RESPONSE ▶
TAG
(M2.PH.4754) A 70-year-old man is brought to the emergency department by his wife for incomprehensible speech. Upon first inspection you note the man is drooling and his eyes are tearing excessively. The patient's wife explains that the man was tilling the fields on the family beet farm when she found him collapsed on a pile of freshly picked beets. The patient seemed confused so the wife brought him in promptly, and states it has only been ten minutes since the patient was found down in the fields. Physical exam is deferred due to a confused and combative patient who is speaking clearly yet his sentences do not make any sense. The patients clothes are removed in the ED. Vital signs are currently being obtained. Which of the following is the best initial step in management? Topic Review Topic

1. Sublingual atropine drops
2. Neostigmine
3. Physostigmine
4. 2-pralidoxime
5. Intubation

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