Clinical Toxicology

• Toxicology is the science of poisons, dealing with the adverse effects of chemicals on living systems from individual cells to complex ecosystems
• Toxicology studies symptoms, mechanisms, treatments, and detection of poisoning, especially in people
• Paracelsus, known as the Father of toxicology, stated "Sola dosis facit venenum" - meaning the dose makes the poison
• Mathieu Orfila is considered the modern father of toxicology, providing its first formal treatment in 1813
• Branches of toxicology include Environmental Toxicology, Ecotoxicology, Occupational Toxicology, Mechanistic Toxicology, Descriptive Toxicology, Forensic Toxicology, Experimental Toxicology, Regulatory Toxicology, and Clinical Toxicology
• Clinical Toxicology focuses on the effects of substances in patients caused by accidental poisonings or intentional overdoses of medications, drugs of abuse, household products, or various other chemicals
• Hazard is the likelihood that injury will occur in a given situation or setting, while risk is the expected frequency of an undesirable effect arising from exposure to a chemical or physical agent
• Intoxication is the toxicity associated with any chemical substance, while poisoning is a clinical toxicity secondary to accidental exposure
• Overdose is an intentional exposure with the intent of causing self-injury or death
• The HAZMAT diamond is used to communicate the hazards of chemicals, with sections for health hazard, flammability hazard, instability hazard, and special hazards, each assigned a number from 0 to 4 indicating the level of hazard
• Evidence of poisoning includes circumstantial evidence, symptomatic evidence, chemical evidence, post-mortem evidence, and experimental evidence
• Interactions of poison can be additive, synergistic, potentiation, or antagonism, with types of antagonism including functional, chemical, dispositional, and receptor
• Poisoning effects can be local, remote, or combined, with factors affecting poisoning effects including poison-related factors (SoCoR) and patient-related factors (HITA)
• Drugs and their toxic metabolites include various compounds and their corresponding metabolites, detailing the chemical transformations that occur in the body
• The NFPA 704 diamond communicates the hazards of chemicals, divided into health, flammability, instability, and special hazards, each assigned a number from 0 to 4 indicating the severity of the hazard

  
• Hemodialysis works by removing waste, toxins, and excess fluid from the blood when the kidneys can no longer perform this function effectively
• The chemical structure of the drug tamoxifen

  
• The chemical structure of ibogaine

  
• Types of poisoning based on frequency:

  • Acute: marked disturbances of function or death within a short period of time
  • Chronic: progressive deterioration of tissue function due to extended exposure to small doses
  • Cumulative: intensified action when a certain limit is reached, like with metal poisons
• Different outcomes of acute and chronic exposures: for example, benzene can cause CNS narcosis acutely and bone marrow damage leading to leukemia chronically
• Signs and symptoms of poisoning can vary, including odor of breath, skin discoloration, vomitus characteristics, bowel changes, blood changes, urinary changes, visual disturbances, respiratory changes, and other physical changes
• General management of poisoned patients involves initial assessment, evaluation and support of vital functions (ABCs - Airway, Breathing, Circulation), decontamination, diagnosis to identify the poison, and specific tests to detect poisons
• Decontamination methods for different exposures:

  • Inhalation: remove patient from exposure, provide 100% oxygen, assisted ventilation, and bronchodilators if necessary
  • Dermal: remove contaminated materials, wash with soap and cool water
  • Ocular: irrigate eyes with normal saline solution for 15 minutes
  • Oral: decontamination methods include gastric lavage, inducing emesis, and administering precipitants and adsorbents
• Gastric lavage, also known as gastric irrigation or stomach pumping, is used to clean out the stomach contents in cases of poison ingestion or drug overdose, especially when the patient is not alert or has a diminished gag reflex
• The NFPA 704 diamond communicates the hazards of chemicals, divided into health, flammability, instability, and special hazards, each assigned a number from 0 to 4

  
• Whole Bowel Irrigation involves using cathartics like PEG (Golytely®, Colyte®) to induce evacuation of the bowel, indicated for poorly absorbed substances, SR preparations, and body packers of illicit drugs
• Forced Diuresis and Urinary pH Manipulation are applicable for substances primarily eliminated renally with small volume of distribution and little protein binding, examples include osmotic diuretics, sodium bicarbonate, NH4Cl, HCl, and Vitamin C
• Extracorporeal methods for toxin removal include hemodialysis, continuous hemofiltration, hemoperfusion, and the molecular adsorbent recirculating system (MARS), with hemodialysis effective on ethylene glycol, methanol, and paraquat
• Antidotes can be physiological (producing an opposite effect as the poison), chemical (changing the chemical nature of the poison), or mechanical (preventing absorption or removing the poison without changing it)
• Examples of antidotes for specific poisons:

  • Organophosphate: Atropine, Pralidoxime
  • Carbamate insecticide: Atropine
  • Hydrocarbon insecticide: Physostigmine
  • Parathion: Pralidoxime
  • Paraquat: Bentonite, fuller’s earth, Na2SO4
• Chelating agents like Dimercaprol, EDTA, Deferoxamine, Penicillamine, Succimer, and Unithiol form complexes with metals to aid in their elimination from the body
• Hemodialysis is effective on ethylene glycol, methanol, and paraquat, but ineffective on ethanol, theophylline, lithium, and long-acting barbiturates
• The NFPA 704 diamond communicates the hazards of chemicals, divided into sections for health hazard, flammability hazard, instability hazard, and special hazards, each assigned a number from 0 to 4

  
• Ethylene Glycol:

  • Used in anti-freeze and windshield deicing solutions
  • Excreted by the kidney
  • Signs and Symptoms: Severe metabolic acidosis, CNS & cardiopulmonary depression, acute renal failure, seizure
  • Metabolites: Glycolaldehyde, Glycolic acid, glyoxylic acid, oxalic acid causing crystalluria
  • Treatment: Ethanol and fomepizole (Antizol®)
• Methanol:

  • Also known as wood alcohol, carbinol, methyl alcohol
  • Signs & Symptoms: Visual disturbance leading to permanent blindness, metabolic acidosis
  • Metabolite: Formaldehyde, formic acid
  • Treatment: Ethanol and fomepizole (Antizol®)
• Formaldehyde:

  • Also known as formalin, formol
  • Found in embalming fluid
  • Signs and symptoms: Similar to methanol toxicity, local mucosal irritation, systemic CNS depression, coma, metabolic acidosis
  • Treatment: Ammonia and NaHCO3
• Acetone:

  • Also known as 2-propanone
  • Primary ingredient in nail polish remover, airplane glues, varnish, and rubber cement
  • Signs and symptoms: CNS depression leading to coma, respiratory depression
  • Treatment: Neutralization with milk or water
• Hydrocarbons:

  • Mostly derived from petroleum distillation, including gasoline and kerosene
  • Signs and symptoms: Aspiration pneumonia, chemical-induced pneumonitis
  • Treatment: Mineral oil acts as a laxative and prevents aspiration pneumonia, emesis, lavage, adsorption are ineffective and contraindicated
• Cyanide:

  • Found in various fruits and foods
  • Signs and symptoms: CNS and CV disturbances, odor of bitter almonds, cherry red blood
  • Treatment: Amyl nitrite (inhalation), Na nitrite (IV), Na thiosulfate IV, Dicobalt edetate (Kelocyanor®), concentrated hydroxocobalamin
• Carbon Tetrachloride:

  • Standard for hepatotoxicity studies
  • Used in nonflammable cleaning fluids and fire extinguishers
  • Metabolites: Epoxides, Phosgene
  • Treatment: No available antidote, gastric lavage is performed when ingested