Deadly Single Dose Agents

Article Author:
Michael Euwema
Article Editor:
Terrell Swanson
Updated:
9/8/2018 5:46:52 PM
PubMed Link:
Deadly Single Dose Agents

Introduction

Although the basics of evaluating and treating most unknown ingestants are well known, many overdoses require very specific treatment if the patient is to have any chance of survival. Countless studies have been published supporting Dr. Gideon Koren's 1993 landmark article “Medications Which can Kill a Toddler with One Tablet or Teaspoonful” in the Journal of Toxicology. While each has its own merits, most focus solely on pediatric overdoses and relatively few of them provide an exhaustive list or act as a “quick-reference” when dealing with real-time ingestions. 

Despite widespread public education, childproof containers, and other safety measures, accidental overdoses continue to occur.  In the United States, poison control centers receive over 2.2 million calls each year, 47% of which concern children less than six years of age.  Most pediatric accidental ingestions involve cosmetics and personal care products, followed by cleaning products, and then analgesics and prescription medications.  Adult overdoses usually are due to intentional ingestion of analgesics and sedative hypnotics. 

Following are the list of toxic drugs (in decreasing severity/difficulty of treatment) included in this summary: 

  1. Alpha-2 Adrenergic Agonists - Clonidine, Naphazoline, Oxymetazoline, Tetrahydrozoline
  2. Sulfonylureas - Chlorpropamide, Glyburide, Glipizide, Glimepiride
  3. Calcium Channel Blockers - Nifedipine, Verapamil, Diltiazem, Amlodipine, Nicardipine
  4. Beta Blockers - Metoprolol, Labetalol
  5. Tricyclic Antidepressants - Imipramine, Desipramine, Amitriptyline, Nortriptyline
  6. Opioids - Codeine, Hydrocodone, Methadone, Morphine, Heroin
  7. Anti-diarrheals - Lomotil (Diphenoxylate + Atropine), Loperamide
  8. Salicylates/Methyl salicylates - Bengay, Wintergreen Oil, Peptobismol, Tiger Balm
  9. Antipsychotics - Loxapine, Thioridazine, Chlorpromazine
  10. Antimalarials - Chloroquine, Hydroxychloroquine, Quinine
  11. Antiarrhythmics - Quinidine, Disopyramide, Procainamide, Flecainide
  12. Terpenoid (Camphor) - Analgesic, Anti-itch, and Cooling Gels, Vicks, Tiger Balm
  13. Non-alkaloidToxic Lignan - Podophyllin, Condylox
  14. Plant Toxin / Secondary metabolite - Colchicine
  15. Oral Acetylcholinesterase Inhibitors - Rivastigmine, Donepezil, Tacrine, Galantamine
  16. Methylxanthine - Theophylline: 1,3-dimethylxanthine
  17. Partial Opioid Agonist / Synthetics - Buprenorphine / Fentanyl
  18. Toxic Alcohols - Methanol, Ethylene Glycol
  19. Caustics / Household Products - Acidic or Alkaline household products, hydrofluoric acid, selenious acid, ammonia fluoride, Methacrylic acid (cosmetic glue), Naphthalene (moth balls)

Function

Toxicokinetics

1. Alpha-2 Adrenergic Agonists: Alpha-2 receptors mediate the transmission of neurotransmitters (acetylcholine & norepinephrine) across the synapse effectively antagonizing them

2. Sulfonylureas: Stimulates the pancreas to increase insulin production

3. Calcium Channel Blockers: Decrease cardiac inotropy and increase vasodilation; can also block insulin secretion in the setting of overdose which can directly affect the heart and thereby worsening shock

4. Beta Blockers: Direct action on the heart causing bradycardia (less severe in children); blockage of gluconeogenesis leading to hypoglycemia; central nervous system (CNS) depression (crosses blood-brain barrier due to high lipid solubility)

5. Tricyclic Antidepressants: Block fast sodium channels, leading to intraventricular conduction delay; wide QRS and right axis deviation on EKG

6. Opioids: Direct suppression of CNS respiratory center leading to hypoxic respiratory failure

7. Anti-diarrheals: Biphasic toxicity - first anticholinergic effects (Lomotil) and then a longer lasting opioid effect (Lomotil and Imodium)

8. Salicylates/Methyl salicylates: Direct stimulation of CNS respiratory center (respiratory alkalosis) then metabolic acidosis 

9. Antipsychotics: Block post-synaptic dopamine receptors and the reticular activating system (also some serotonin antagonism)

10. Antimalarials: Sodium channel blockade; QRS widening

11. Antiarrhythmics: Sodium channel blockade; QRS widening

12. Terpenoid (Camphor): Topical rubefacient induces local hyperemia and warmth

13. Non-alkaloid Toxic Lignans: Interrupt cell mitosis by binding to tubulin and disrupting the microtubular network, thereby disturbing cellular protein assembly and leading to sepsis and multisystem organ failure

14. Plant Toxins/Secondary metabolites: Same as the lignan. Interrupt cell mitosis by binding to tubulin and disrupting the microtubular network, thereby disturbing cellular protein assembly and leading to sepsis and multisystem organ failure

15. Oral Acetylcholinesterase Inhibitors: Act on nicotinic and muscarinic receptors; cholinergic toxidrome

16. Methylxanthines: Inhibit phosphodiesterase enzymes which increase cAMP and cGMP to cause bronchodilation

17. Partial Opioid Agonist/Synthetics: Direct suppression of CNS respiratory center (one lick can be enough to be toxic in a child)

18. Toxic Alcohols: Metabolized into toxic chemicals like aldehyde, organic acids, acetone

19. Caustics/Household Products: Direct mucosal and pulmonary damage (toxicity related to pH < 3 and > 13), methemoglobinemia (methacrylic acid), cyanide (metabolite of acrylonitrile)

Symptoms/Physical Findings/Labs/EKG

1. Alpha-2 Adrenergic Agonists: Opioid toxidrome, altered mental status

2. Sulfonylureas: Anorexia, weakness, prolonged hypoglycemia up to 18-24 hours, lethargy, seizure, coma, headache, confusion, irritability

3. Calcium Channel Blockers: Hyperglycemia, cardiovascular collapse, bradycardia, hypotension (verapamil and nifedipine worst)

4. Beta Blockers: Bradycardia and hypotension (generally not as severe in children), hypoglycemia, seizures, reflex tachycardia, 2nd- and 3rd-degree heart block, Torsades de pointes

5. Tricyclic Antidepressants: Seizures, anticholinergic toxidrome, hypotension, metabolic acidosis, cardiac conduction abnormalities (QRS prolongation and prominent R in aVR, hypotension, CNS depression, tachycardia then torsades de pointes)

6. Opioids: Hypoxic respiratory failure, miosis, CNS depression

7. Anti-diarrheals: Initially anticholinergic toxidrome then opioid toxidrome; cardiac dysrhythmias, ataxia, irritability, hypokalemia, myopathy, neuropathy, AMS, ocular toxicity, ototoxicity

8. Salicylates/Methyl salicylates: Nausea and vomiting, diaphoresis, hyperthermia, tinnitus, CNS depression, hyperventilation, primary metabolic acidosis, pulmonary edema, cerebral edema, coma

9. Antipsychotics: Seizures, anticholinergic toxidrome, prolonged QTc, wide QRS, tachycardia, hypotension

10. Antimalarials: Delirium, coma, dysrhythmias, seizures, prolonged QT, widened QRS, hypotension, hypoglycemia, visual disturbances (blurry, diplopia, altered color perception)

11. Antiarrhythmics: Nausea and vomiting, hypotension, QRS widening, heart block, hyperthermia, hypoglycemia, bradycardia, tachyarrhythmias, ventricular tachycardia/fibrillation, torsades de pointes

12. Terpenoid (Camphor): Respiratory suppression, status epilepticus, typical odor, GI distress, sense of warmth, CNS hyperactivity then depression

13. Non-alkaloid Toxic Lignan: GI symptoms, CNS changes (confusion, coma, delirium, hallucinations), pancytopenia

14. Plant Toxin / Secondary metabolite: Same as lignan. GI symptoms, CNS changes (confusion, coma, delirium, hallucinations), pancytopenia

15. Oral Acetylcholinesterase Inhibitors: Increased level and duration of neurotransmitters

16. Methylxanthine: Vomiting, anxiety, agitation, seizures, ventricular dysrhythmias, hypotension, tachycardia

17. Partial Opioid Agonist/Synthetics: Opioid Toxidrome, agitation

18. Toxic Alcohols: Confusion, vomiting, seizures, hypopnea, cyanosis, hypothermia, syncope

19. Caustics/Household Products: Drooling, perioral burns, respiratory distress, dysphagia, metabolic effects (methemoglobinemia, hemolysis, cyanide toxicity)

Issues of Concern

Treatment / Management (current recommended antidotes listed first)

1. Alpha-2 Adrenergic Agonists: Naloxone (antidote); supportive care, airway protection, respiratory support, atropine, IV fluids, vasopressors

2. Sulfonylureas: Octreotide (antidote); serial glucose monitoring, glucagon, GI decontamination, IV dextrose bolus (can overstimulate the pancreas and cause rebound hypoglycemia), 24-hour observation

3. Calcium Channel Blockers: High Dose Insulin/euglycemic therapy (antidote); other antidotes (weaker evidence) such as lipid emulsion, IV calcium, methylene blue (amlodipine), ECMO for cardiovascular collapse, atropine, cardiac pacing, pressors

4. Beta Blockers: Glucagon (antidote); monitoring, vasopressors, cardiac pacing, whole bowel irrigation, calcium 

5. Tricyclic Antidepressants: Sodium Bicarb/Lipid Emulsion (antidotes); aggressive ABCs, urine alkalinization, activated charcoal, benzodiazepines (may rapidly deteriorate)

6. Opioids: Naloxone (antidote); supportive care, airway protection, respiratory support, 24 hours observation for longer acting opioids

7. Anti-diarrheals: Naloxone (antidote); fluids, airway support, supportive care

8. Salicylates/Methylsalicylates: Sodium bicarbonate (antidote); urine alkalinization, supportive care, activated charcoal, dialysis. May require long observation (may not peak until 24 hours)

9. Antipsychotics: Sodium bicarbonate (antidote); supportive care, benzodiazepines, cardiac monitoring, GI decontamination

10. Antimalarials: Sodium bicarbonate (antidote); ECMO, supportive care, benzodiazepines, cardiac monitoring, glucose, (severe – epinephrine, intubation, gastric lavage)

11. Antiarrhythmics: Sodium bicarbonate (antidote); supportive care, cardiac monitoring, intravenous fluid bolus

12. Terpenoid (Camphor): Supportive Care; benzodiazepines, airway monitoring, remove chemical if possible

13. Non-alkaloid Toxic Lignan: Supportive care; remove topicals, GI decontamination 

14. Plant Toxin/Secondary metabolite: Supportive Care; remove topicals, GI decontamination

16. Methylxanthine: Supportive care; IV Fluids, benzodiazepines, antiemetics, activated charcoal, inotropes

17. Partial Opioid Agonist/Synthetics: Narcan (antidote); supportive care, airway protection, respiratory support

18. Toxic Alcohols: Ethanol, fomepizole (antidote); supportive care, specific treatment depends on type of alcohol

19. Caustics/Household Products: (multiple specific treatments) supportive care, airway protection, dilution, cyanide kit, methylene blue

Clinical Significance

Although there is little primary research into poisonings, there are numerous case reports and summary articles on the topic.  Novel therapies are being devised and tested all the time; for example, methylene blue in amlodipine overdose and “old” therapies such as ECMO are being used more often and with greater success.  In treating patients be sure to liberally utilize the regional poison control center to ensure the use of the latest therapies and best management available. Toxicologists are always standing by to assist. Also, numerous web resources, such as UpToDate and eMedicine, and textbooks, such as Goldfrank, provide very specific and current treatment protocols. Observation and supportive care are sufficient for most toxic ingestions, but some, like these highly dangerous substances, require specific treatment and a knowledgeable clinician.