toxic

Toxicology

• Toxicon = POISON

• Logos = STUDY

• Branch of Pharmacology that deals with the study of POISON, MECHANISM of toxicity and its TREATMENT

Toxicity

• INTRINSIC ABILITY of an agent to HARM LIVING ORGANISMS

• DEGREE OF A SUBSTANCE to which it can DAMAGE an ORGANISM.

Risk assessment

Estimate of potential effects of poison to human health and environmental significance of various types of chemical exposure.

Hazard

Ability of a chemical agent to cause injury in a given situation or setting

Risk

Expected frequency of the occurrence of an undesirable effect arising from exposure to a chemical or physical agents

Clinical Toxicology

Realm of medical science that is concerned with disease caused by or uniquely associated with toxic substances

Environmental Toxicology

Impacts of chemicals on nonhuman organisms such as fish, birds, terrestrial animals, and plants.

Forensic Toxicology

Medico-legal aspects of harmful effects on humans and animals

Types of Toxicity: Based on Frequency and Duration:

• Acute toxicity

• Repeated exposure

  • Subacute

  • Sub-chronic

  • Chronic

Acute toxicity

Exposure to a chemical for <24HRS

Repeated exposure

• SUBACUTE: exposure to a chemical is for 1 month or less

• SUB-CHRONIC: 1–3 months

• CHRONIC: 3 months/1 year

Types of Toxicity: Based on Legal Viewpoint

• Accidental

• Suicidal

• Homicidal

• Undetermined

Accidental

poison was taken without intention to cause death

Suicidal

poison was taken by victim voluntarily for the purpose of taking his own life.

Homicidal

poison was given willfully and with intent to cause death to the victim.

Undetermined

the history is hazy as to how poison was obtained and why it was administered.

Types of Toxicity: Based on Toxic Effect

• Local effect

• Remote effect

• Systemic effect

Local effect

• Effect at the site of contact

• Acids and Bases: Skin Necrosis

Remote effects

• Effect other than the site of contact

• Paraquat Ingestion: Pulmonary Fibrosis

Systemic effect

• Both local and systemic effect

• Methanol Ingestion: Metabolic Acidosis

Types of Toxicity: Based on Mechanism

• CNS Stimulation

• CNS Depression

• PNS Effects

• SNS Effects

• CVS Effects

• Respiratory System

• Cellular Hypoxia

• Muscle and Bone Effects

• Teratogenic Effects

CNS Stimulation

• Increase Nerve Excitability → Increase Na, Ca, & Glutamate

• These are positive (cationic) substances that cause depolarization (activation of neurons).

• Na⁺ (Sodium) → Triggers muscle contraction and nerve signal transmission.

• Ca²⁺ (Calcium) → Facilitates neurotransmitter release at synapses, helping signal transmission.

• Glutamate → A major excitatory neurotransmitter, promotes neuronal activity and enhances brain signaling.

• ↑ Levels → Convulsion/Seizures

CNS Depression

• Decreased Nerve Excitability occurs due to increased Cl⁻ (Chloride ions) and GABA.

• These are inhibitory neurotransmitters that cause hyperpolarization, making it harder for neurons to fire → leads to relaxation or sedation.

• At high levels, this can progress to respiratory depression, which can be dangerous or fatal.

PNS Effects

• Activation of Muscarinic Receptors leads to cholinergic effects, summarized by the mnemonic DUMBBELSS:

D – Diarrhea

U – Urination

M – Miosis (pupil constriction)

B – Bradycardia (slow heart rate)

B - Bronchoconstriction

E – Emesis (vomiting)

L – Lacrimation (tearing)

S – Salivation

S – Sweating

These are typical parasympathetic (rest-and-digest) responses.

SNS Effects

Associated with "fight or flight" responses:

• M – Mydriasis (pupil dilation)

• A – Agitation

• T – Tachycardia (increased heart rate)

• H – Hypertension (increased blood pressure)

• Seizure

• Sweating

CVS Effects

• Irregular Heartbeat → Arrhythmia

• Vasoconstriction → Increased Blood Pressure/Hypertension

• Vasodilation → Decreased Blood Pressure/Hypotension

Respiratory System

Bronchoconstriction

Cellular Hypoxia

Interference with O2 transport and utilization

Muscle and Bone Effects

Muscle Destruction → Renal Failure (RHABDOMYOLYSIS)

Teratogenic Effects

• Thalidomide

• Warfarin

• Tetracycline

• Lithium

• ACE inhibitors

• Methimazole

• Carbamazepine, Valproic acid

• Diethylstilbestrol (DES)

• Phenytoin

• Ethanol

Thalidomide

• Phocomelia

• No limbs

Warfarin

• Hypoplastic nose

Tetracycline

• Tooth discoloration

• Bone fractures

Lithium

• Ebstein Anomaly

ACE inhibitors

• Renal dysgenesis

Methimazole

• Aplasia cutis

Carbamazepine, Valproic acid

• Neural tube defects

• Spina bifida

Diethylstilbestrol (DES)

• Clear cell adenocarcinoma of the vagina / cervix

• Vaginal/Cervical Cancer

Phenytoin

• Fetal hydantoin syndrome

• Cleft lip palate

• Cognitive impairment

Ethanol

• Fetal alcohol syndrome

• Facial anomalies (Microcephaly)

• Growth retardation

• Neuro-developmental defects

Category A

Adequate and well-controlled studies in pregnant women have not shown an increased risk of fetal abnormalities.

• Safe in animals and humans

Category B

Animal studies have revealed no evidence of harm to the fetus or animal studies have shown an adverse effect; there are no adequate and well-controlled studies in pregnant women, or safe in humans

• Safe in animals, no human studies or

• Not safe in animals, but safe in humans

Category C

Animal studies have shown an adverse effect, and there are no adequate well-controlled studies in pregnant women or

No animal studies have been conducted, and there are no adequate and well-controlled studies in pregnant women.

• Not safe in animals, and no human studies

• Both animals and humans have no adequate and well-controlled studies yet.

Category D

Adequate, well-controlled or observational studies in pregnant women have demonstrated a risk to the fetus; however, the benefits of the therapy may outweigh the potential risks.

• Not safe, benefits outweigh risks

Category X

Adequate, well-controlled, or observational studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. The use of the product is contraindicated in women who are or who may become pregnant.

• Contraindicated in pregnancy = Teratogenic effects

Factors Affecting Poisoning Effects

1. Poison-Related Factors

2. Host Related Factors

Poison-Related Factors

• Concentration & Potency

• Solubility

• Form of poison

• Route of administration

Concentration & Potency

• POTENT DRUGS → Dangerous

• HIGHER CONCENTRATION → Dangerous

Remember: The lower the dose, the more potent it is

Solubility

• LIPOPHILIC/LIPID SOLUBLE DRUGS are more dangerous than polar drugs.

Form of poison

• Gas > Liquid > Solid

Route of administration

• IV > Oral

Host Related Factors

• Age

• Idiosyncrasy

• Tolerance

• Mental State

Age

Very young and very old are at higher risk

• due to immature or declining organ function (e.g., liver, kidneys), making it harder to metabolize and eliminate drugs or toxins

• ↑ concentration = toxicity

Idiosyncrasy

Genetic Problems

Tolerance

Large Dose → To have the same effect

Mental State

Depression And Suicide

Evidence of Poisoning

• Circumstantial

• Post-Mortem

• Experimental

• Chemical

• Symptomatic

Circumstantial

• Deduced from various events or facts.

• Not strong evidence

Post-Mortem

Gathered after an AUTOPSY is performed.

Experimental

Administering the suspected substance to some LIVING ANIMALS and noting the EFFECT OR SYMPTOM

Chemical

Detection of suspected substance via analysis of samples of BODY FLUIDS collected.

Symptomatic

Poisoning SIGNS AND EFFECTS are observed.

Blood Changes: CO and CN

• Cherry red discoloration

Blood Changes: Nicotine

• Dark red

Blood Changes: Aniline and Nitrites

• Chocolate blood

Breath Odor: Ethanol

• Fruity odor

Breath Odor: As, P, Malathion

• Garlic odor

Breath Odor: Cyanide

• Bitter almonds

Breath Odor: Hydrogen Sulfide

• Rotten egg

Breath Odor: Methyl Salicylate

• Oil of wintergreen

Skin Discoloration: Phenol

• Bleaching white

Skin Discoloration: Carbon Monoxide

• Cherry red discoloration

Skin Discoloration: Boric Acid

• Boiled lobster appearance

Vomitus: P and As

• Luminous

Stool Appearance: Fe, Bi, Pb, Charcoal

• Black stool

Stool Appearance: Hemolytic Substances

• Red stool

Urine Discoloration: Rifampicin, Pb, Hg

• Wine/Red/Red brown discoloration

Gum Discoloration: Bi, Pb

• Blue line gum

Gum Discoloration: Hg, As

• Black line gum

Visual Changes: Marijuana

• Blood shot eyes

Visual Changes: Opioids

• Pinpoint pupil

• Coma

• Depression

Visual Changes: Methanol

• Blindness (due to formic acid)

Visual Changes: Anti-cholinergic

• Atropine: Blurred vision

Classification of Toxic Agents

• Based on Target Organ

• Based on Effects

• Based on Origin

Based on Target Organ

• Hepatotoxic

• Nephrotoxicity

• Hematopoietic System

Hepatotoxic

Paracetamol, Anti-TB Medications (RIP), Methanol, Ethanol

Nephrotoxicity

Aminoglycosides

• -mycin, -micin (strepto, tobra, genta)

Hematopoietic System

• Sulfonamides and Methyldopa (HEMOLYTIC ANEMIA; abnormal breakdown of RBC)

• Sulfonamides: Nucleic Acid Synthesis Inhibitor

• Methyldopa: Gestational HTN

• Chloramphenicol (APLASTIC ANEMIA; bone marrow destruction)

Based on Effects

• Irritant

• Neurotoxic

• Carcinogenic

• Asphyxiant

• Lacrimatory

• Rubefacient

• Myotoxic

• Narcotic

Irritant

→ Causes PAIN, INFLAMMATION, NECROSIS

→ Ex: Acids, Bases

Neurotoxic

→ Affects the CNS

→ Ex: Hallucinogens

Carcinogenic

→ Causes INCREASE GROWTH IN CANCER CELLS

→ Ex: Industrial poisons

Asphyxiant

→ Causes DYSPNEA = difficulty of breathing

→ Ex: CO, CN, CO₂

Lacrimatory

→ Causes an INCREASE IN THE FLOW OF TEARS

→ Ex: Organophosphates (pesticides)

• -tabun, -sarin, -soman

Sternutators

→ Causes EXCESSIVE SNEEZING

→ Ex: Veratrum, Capsaicin (from chili)

Asthenics

→ Causes MUSCLE WEAKNESS

→ Ex: NMBs (tubocurarine, pancuronium)

Narcotics

→ Causes MENTAL WEAKNESS AND DEPRESSION

→ “Narkotikus” = sleep

→ Ex: Sedative-Hypnotics, Morphine

True

Irritants:

Coagulative Necrosis (Acid)

• Acids cause coagulation necrosis, which involves the denaturation and precipitation of proteins

Liquefactive Necrosis (Base)

• Bases cause liquefactive necrosis, where tissues are broken down and liquefied.

Based on Origin

• Zootoxin (Source: Animal)

• Phytotoxin (Source: Plant)

• Bacterial Toxin (Source: Bacteria)

• Mycotoxin (Source: Fungi)

Black Widow

• Toxin: LATROTOXIN

• Effects: Increase release of ACh (DUMBBELLS) → Cramping and Rigidity of Muscles