Introduction to Toxicology

• Toxicology is the study of poisons, where "toxi" refers to poisons and "logos" means study.
• A poison is any chemical agent causing serious body injury, disease, or death when applied, introduced, or developed inside the body.
• Toxicology is a branch of pharmacology dealing with the undesirable effects of chemicals on living systems, from individual cells to complex ecosystems.
• It encompasses the adverse effects of chemical, physical, or biological agents on people, animals, and the environment.
• Toxidrome refers to a toxic syndrome, which is a constellation of clinical signs and symptoms suggesting a type of poisoning, e.g., Cholinergic Toxicity = dumbbells.
• "Sola dosis facit venenum" is a quote by Paracelsus meaning "the dose makes the poison".
• Paracelsus is known as the father of toxicology.
• Mathieu Orfila is considered the modern father of toxicology, having written "Toxicologie Générale".
• Toxicologie Generale is a book that briefly describes the symptoms of poison, antidote, detection/identification tests, and dose.
• Orfila classified poisons into irritants, narcotics, narcotic-acrids, and septics or putrefactives.

Branches of Toxicology

• Environmental toxicology deals with the impact of chemicals (as pollutants) on living organisms.
• Ecotoxicology focuses on the toxic effects of agents on populations and communities within ecosystems.
• Occupational toxicology concerns chemicals in the workplace, their diseases, safe usage conditions, and prevention of harmful absorption.
• Monday headache is a classic example caused by Organic Nitrates (NTG) exposure = workers develop tolerance, Organic Nitrates dilates BV (vasodilator) = monday headache & migraine.
• Mechanistic toxicology researches the toxic action mechanisms (toxicodynamics) of poisons Toxicodynamics: Mechanism of Toxicity (MOT).
• Descriptive toxicology involves toxicity testing for safety evaluation and regulatory requirements and Provides information regarding toxic levels.
• Regulatory toxicology gathers/evaluates toxicological data to establish concentration-based "safe" exposure standards and Makes policies.
• Forensic toxicology involves medico-legal aspects of chemical effects on humans/animals, using analytic chemistry & toxicology principles.
• Experimental toxicology investigates toxic effects of chemicals in biological systems, measuring parameters.
• Lethal Dose 50 (LD50) is the dose causing death in 50% of test animals.
• Toxic Dose 50 (TD50) causes toxic effect to humans.
• Threshold Limit Value (TLV) is the safe exposure amount for a time period = more on exposure.
• No Observed Adverse Effect Level (NOAEL) is the amount/highest dose without adverse effects.
• Clinical toxicology focuses on substance effects in patients from accidental poisoning/intentional overdoses Patient care/patient-centered.

Definition of Terms

• Hazard is the likelihood of injury in a situation, reflecting the capacity/probability to cause harm, injury, and death.
• Risk is the expected frequency of an undesirable effect from exposure to a chemical/physical agent.
• Intoxication is toxicity related to any chemical substance.
• Poisoning is a clinical toxicity secondary to accidental exposure.
• Overdose is an intentional exposure causing self-injury/death.

Evidence of Poisoning

• Corpus delicti means there should be evidence before someone is convicted of a crime.
• Circumstantial evidence (moral/indirect evidence) involves deductions from circumstances but it is Not reliable.
• Symptomatic evidence includes symptoms observed, but is not conclusive due to similar symptoms from other diseases.
• Chemical evidence involves analysis of suspected substances or body secretions and Can be obtained while px is still alive.
• Post-mortem evidence is observed through autopsy.
• Experimental evidence is determined through physiologic tests on living animals & may not be conclusive to man since tolerance may not be the same as in man.

Interactions of Poisons

• Additive effect (1+1=2) is the combined effect equals sum of individual effects.
• Synergistic effect (1+1=3) is the combined effect exceeds sum of individual effects.
• Carbon tetrachloride + Ethyl alcohol = CNS depression; Pyrethroids + Piperonyl butoxide (PBO) = good for insects.
• Potentiation (1+0=2) is where exposure to a non-toxic chemical increases the toxicity of another, e.g., Carbon tetrachloride + Isopropyl alcohol = ↑CNS dep fx, ↑Toxicity.
• Antagonism (1+1=0) is co-administration interferes with toxicity of both/one agent, used for antidotes.
• Functional/Physiological Antagonism involves opposite effects on a physiological function, binding to different receptor but opposite fx.
• Anaphylactic shock (↑ histamine) treated with epinephrine, Epinephrine vs Histamine.
• Chemical/Inactivation involves chemical reaction between compounds, reducing toxic compound w/No receptor involved, e.g., Chelators and metals.
• Heparin vs Protamine Sulfate, Warfarin vs Vit. K.
• Dispositional involves changing toxic chemical disposition diminishing concentration/duration.
• E.g. Ipecac, charcoal, pH alteration, metabolism induction or inhibition, still no receptor involved, they just antagonize the ADME process.
• Receptor is also known as Pharmacological antagonism & involves one agonist and one antagonist binding to the same receptor.
• Chemicals compete for the same receptor, decreasing effective binding of toxic compound.
• Naloxone (opioid antagonist) and morphine (opioid agonist) are examples and Naloxone is FDA approved to reverse opioid receptor effects.

Poisoning Effects

• Local effects are impressions made by the poison at the contact site, e.g., corrosives.
• Remote effects occur in areas other than the application site, e.g., Atropine taken orally to produce blurred vision.
• Combination of local and remote effects, e.g., Phosphorus, Cantharidin, Arsenic.

Factors Affecting Poisoning Effects:

• Injected poisons are more toxic compared to those that are swallowed
• Increased dose increases toxicity probability.
• Highly lipid-soluble poisons are absorbed dermally; water-soluble poisons are absorbed faster orally.

Types of Poisoning

• Acute is prompt with marked functional disturbances/death.
• Excessive single dose example = taking 8 tablets of paracetamol then after 15 mins another 8 tablets
• Chronic has gradual/progressive deterioration from small doses over extended time; may/may not result in death.
• Cumulative action increases intensity when reaching a limit.
• Paracetamol (>4g-8 tablets) = toxic dose, Aluminum (too much exposure is toxic).

Duration and Frequency Factors

• Acute: less than 24 hours, generally single dose.
• Subacute: repeated exposure in <1 month.
• Subchronic: repeated exposure for 1-3 months.
• Chronic: repeated exposure for >3 months.
• Acute and chronic exposures lead to outcomes.
• Benzene (CH) produces acute CNS narcosis or chronic bone marrow damage.

Types of Poisoning Based on the Effects

• Irritants cause tissue necrosis on contact (caustic effects) = acid & alkali.
• Neurotics affect the CNS e.g., hallucinogens; causes hallucination, depression, mania, delusion.
• Asphyxiants cause dyspnea (SOB, breathing problem) e.g., methane gas, carbon monoxide.
• Lacrimators stimulate flow of tears (irritates eyes) e.g., organophosphates, onion.
• Sternutators cause excessive sneezing (eg: Red and Black Pepper).
• Globally Harmonized System (GHS) are international symbols.

General Management of Poisoned Patients

• Acute poisoning is intentional, especially in adult px, while childhood death/poisoning is attributed to negligence of the adult accompanying the child
• How do you know How Does the Poisoned Patient Die?
• CNS depression can cause coma from airway obstruction
• Severe hypotension from Shock, possible Lethal Arrhythmia, and even CV toxicity, inflamed heart (because of arrhythmia).
• Date rape drug, Flunitrazepam (Rohypnol®) = arrhythmia: tachycardia.
• Cellular hypoxia (low oxygen).
• Seizure, muscle hyperactivity, possible rigidity.
• Severe organ damage for either acute (immediate) or a long-delayed concept.

Types of Poisoning: Based on the Effects

• Always evaluate and support vital functions

Evaluating Airway

• Obstructed airway
  • Flaccid Tongue: foaming of the mouth. Use position in lateral decubitus.
  • Pulmonary aspiration of gastric contents (hospital). Stomach contents will migrate to the lungs.
  • Respiratory failure (hospital)

Causes of Breathing failure

• Check with an Oximeter
• Carbon Monoxide Poisoning is a good example.
  • Prevent leaving children alone in a car seat, as poisoning may result from the Carabon Dioxide Poisoning
  • Carbon Dioxide is an example of asphyxiants which means is associated with (SOB)
  • Complications with breathing failure include Hypoxia, possible Ventilatory Failure, and Bronchospasm

Evaluating Circulation

• Check their BP, HR and Urinary Output (catheter)

Decontamination

• Look for diagnosis

Test to detect specific poisons

• Use the Beilstein test to detect Chlorine. This test will create a .green flame
• Use the Beilstein Benzoldt to detect Acetone . This test creates an indigotine color.
• Use the Gunning test to detect Bromine This test creates a colored precipitate.
• Use the Water Brown Ring test to detect Nitrite & nitrate. This test creates a brown ring at the interface.
• Use the Lieben's lodoform test to detect detect Methanol. This test creates yellow (iodoform (CHI3)).
• Use the Marsh test to detect Arsenic. This test is soluble in NaOCI
• Rodillon/ Phenol. This test can give light to dark red colors

Test to detect specific poisons

• An overviw of the drugs and the metabolic that may me detected

Clinical Toxology: P2 ~ Steps for Decontamination

Routes Exposure

Removing of toxins by.

• Inhalations. Provide 100% Pure Oxygen, ventilation and bronchodilators
• Dermal: remove contamination with slightly cool water
  • if exposed to acids and bases -wash the wound with cold and or running water with soap
• Occular Exposure: irrigate area with irrigation w 15 minutes -* Do not instill any neutralizing solutions in areas such as the skin and eyes, etc

Common routes of exposure:

• oral exposure
  • Oral and Parental Adminstration

Steps for removing Toxins ~

• Perform a Gastric Lavage:

  • safe and used properly with extreme care
  • perform properly in an ER
  • Also can be called stomach pumping or irrigation
  • Uses Orogastric(mouth0 of nasogastric tubes (to the nose).

• Uses: -* In patients who are not mentally alert -* In patients with decreased gag reflex function -* if ingestion is massive take action and check as early as 1 minutes

  • contraindications -ingestions of hydrocarbons -at risk for Gi perforation -combative or convulsive patient

• Induce Emmesis

  • most convenient with hospital treament
  • perform and use proper Syrup of Ipecac

• contraindications: -*<6 months -seizures - Patients with acid of sharp objectives ingestions

• Precipitations -* Alter poison by chemical reaction

• Adsorbents --Form Physical components

Chemcial antidotes

• Metal Poisons use Dimercaprol of BAL
• Alkoids can use diazapam
• Strychnine can use anticonvulsion meds

10