Lec 1.pdf

Toxicology Lecture 1-Introduction Poison Vectors by Vecteezy Maha Wally, Ph.D. Department of Pharmacology Faculty of Pharmacy-The British University in Egypt AY 2024/2025 – S1  Lecture content o Terminology o Areas of To...

Toxicology Lecture 1-Introduction Poison Vectors by Vecteezy Maha Wally, Ph.D. Department of Pharmacology Faculty of Pharmacy-The British University in Egypt AY 2024/2025 – S1  Lecture content o Terminology o Areas of Toxicology o Classification of toxic agents o Classification of toxic effects o Classification of toxic exposure o Interaction of toxic agents o Adverse drug reactions Assessment Vectors by Vecteezy  Terminology “All substances are poisons; there is none which is not a poison. It is the dose that differentiates between a poison and a medicine.” Paracelsus Toxicology “Father of Toxicology” Study of the harmful effects of chemicals on living organisms. Toxicologist Studies the nature of toxic effects. Assesses the probability of their occurrence. Xenobiotic Any substance foreign to the normal physiology of the body. Can have beneficial or toxic effects on the body. Examples: Pharmaceuticals , chemicals.. etc Poison Vectors by Vecteezy  Terminology Toxic agents Any substance that can produce an adverse biological response. Classified according to their nature: chemical, physical, or biological. Toxin o Produced by biological systems. (Plants, animals or bacteria) ex. venoms Snake Vectors by Vecteezy Toxicant o Produced as a by-product of human activities. (Man-made) ex. Industrial wastes Factory Waste Vectors by Vecteezy  Areas of Toxicology Mechanistic toxicology Identifies the mechanisms by which a chemical causes toxic effect. ex. Cellular, biochemical & molecular mechanisms Drugs Vectors by Vecteezy Descriptive toxicology Concerned with toxicity testing to evaluate risks of exposure to chemicals. “Toxicity Tests”: Performed on experimental animals to establish how much of a chemical would cause illness or death. Law Vectors by Vecteezy Clinical toxicology Concerned with diseases caused by toxic substances. Doctor Vectors by Vecteezy 4 gram) ex. Drugs with low therapeutic index (digoxin) 2. Drugs of abuse o Recreational drugs used for used for non- therapeutic reasons. ex. Alcohol, morphine, amphetamines … Addiction Vectors by Vecteezy  Classification of toxic agents Toxic agents can be classified according to their: Source 3. Industrial agents o Substances used in workplace. ex. Heavy metals, solvents … Chemical Vectors by Vecteezy 4. Environmental agents o Substances causing air, water or soil pollution. ex. Pesticides, car exhausts, smoke … Car smoke Vectors by Vecteezy  Classification of toxic agents Toxic agents can be classified according to their: Source 5. House-hold agents o Substances used at home. ex. Cleaning agents, cosmetics … Cosmetics and cleaning Vectors by Vecteezy 6. Natural agents o Substances from plants or animal origins. ex. Mushrooms, snake bites, spider stings … Mushroom and spider Vectors by Vecteezy  Classification of toxic agents Toxic agents can be classified according to their: Source 7. Radiation o Exposure to radiation in medical setting. ex. Frequent exposure to diagnostic x-rays o Exposure by accident to radioactive materials released from a nuclear reactor. Industrial Vectors by Vecteezy ex. Chernobyl disaster in 1986  Classification of toxic effects Immediate Delayed toxic effect toxic effect Occurs after a single Versus Vectors by Vecteezy administration of time from exposure to toxic agent. toxic agent. Example Example Most toxic substances Carcinogenic substances → Have long latency periods → Can take up to 20 years for tumors to appear Poison Vectors by Vecteezy  Classification of toxic effects Reversible Irreversible toxic effect toxic effect Versus Vectors by Vecteezy The ability of a tissue to regenerate determines whether the toxic effect is reversible or irreversible. Examples Liver → high regeneration ability → damage mostly reversible CNS → low regeneration ability → damage mostly irreversible Carcinogenic & teratogenic → irreversible Vectors by Vecteezy Poison Vectors by Vecteezy  Classification of toxic effects Local Systemic toxic effect toxic effect Occurs at the site of Versus Vectors by Vecteezy Requires absorption/ contact between the distribution from biological system exposure site to the & the toxicant. target sites. Example Example Corrosive effect of Potassium cyanide chemicals affects almost all body cells’ ability to use oxygen. Poison Vectors by Vecteezy Classification of toxic exposure According to route of exposure According to duration & frequency of exposure According to circumstance of exposure According to incidence of exposure Poison Vectors by Vecteezy  Classification of toxic exposure According to route of exposure: The major routes through which a toxic agent enters the body: o GIT →ingestion o Lungs → inhalation o Skin → topical o Parenteral → injection Toxic agents produce the greatest effect & the most rapid response when given directly into the bloodstream (IV route). Drugs Vectors by Vecteezy Poison Vectors by Vecteezy  Classification of toxic exposure According to route of exposure: Some substances may be more toxic by one route & not by others: o Ingested chemicals: →Absorption → distribution to liver → may be detoxified. o Inhaled chemicals: → Immediately enter the blood circulation without detoxification. ∴The route of administration affects the toxicity of agents. Ex. A neurotoxic agent that is detoxed in the liver would be less toxic when given orally than when inhaled as it will pass through the liver before it reaches the CNS. Poison Vectors by Vecteezy  Classification of toxic exposure According to duration & frequency of exposure: Acute exposure Exposure to a chemical for < 24 hrs. Time Vectors by Vecteezy → Could be single administration of a very toxic substance or repeated administration of a slightly toxic substance within 24 hrs. o Death usually occurs in cases of acute exposure. Poison Vectors by Vecteezy Subchronic exposure Repeated exposure to a chemical for 1-3 months. Chronic exposure Repeated exposure to a chemical for > 3 months. o Chronic bronchitis → cigarette smokers o Liver cirrhosis → alcoholics Poison Vectors by Vecteezy  Classification of toxic exposure According to circumstance of exposure: Accidental Unintended & occurs by accident. Common in children & elderly (amnestic patients). Amnesia Vectors by Vecteezy o Incorrect intake of drugs o Ingestion of pesticides o Combination of cleaning agents which react together Suicidal Intentional & deliberate to cause self-harm. Examples: o Cyanide (poison pill) was commonly used by undercover agents to escape interrogation if captured by the enemy. o Overdose with CNS depressants such as barbiturates. Criminal/homicidal Intentional to cause harm to another person. Poison Vectors by Vecteezy  Classification of toxic exposure According to incidence of exposure: At home Ex. Exposure to toxic doses of carbon monoxide due to incorrect usage of heaters. Cartoon Vectors by Vecteezy Occupational Occurs at workplace such as industrial & agricultural premises due to exposure to hazardous chemicals or wastes. Ex. Inhalation of toxic gases, exposure to irritants … Poison Vectors by Vecteezy  Interaction of toxic agents Usually, we are exposed to more than one chemical at the same time. Some of these can affect the toxic effects of others (Increase/ decrease/ no change) Examples o Chronically diseased patients receive a mixture of drugs. o Drinking water may contain small amounts of pesticides, solvents & other chemicals. o Air may contain traces of smoke, car exhausts, inhaled chemicals. + Drugs Vectors by Vecteezy  Interaction of toxic agents When 2 toxic agents are combined they could have one of the following effects Additive effect (ex: 2 + 3 = 5) o When the combined effect of two chemicals is equal to the sum of the effects of each agent alone. Synergistic effect (ex: 2 + 2 = 20) o When the combined effects of two chemicals are much greater than the sum of the effects of each agent alone. + Drugs Vectors by Vecteezy  Interaction of toxic agents When 2 toxic agents are combined they could have one of the following effects Potentiation (ex: 0 + 2 = 10) o When one substance does not have a toxic effect on a certain organ but when added to another chemical makes that chemical much more toxic. Antagonism (ex: 4 + 6 = 8) o When two chemicals administered together interfere with each other’s actions or one interferes with the action of the other. + Drugs Vectors by Vecteezy  Interaction of toxic agents There are 4 types of antagonism Functional antagonism o When two chemicals counterbalance each other by producing opposite effects on the same physiologic function. o Example: - Barbiturate intoxication causes severe fall in blood pressure → Can be antagonized by IV administration of norepinephrine (vasopressor). Chemical antagonism o A chemical reaction between two compounds produces a less toxic product. o Examples: - Metal toxicity is antagonized by metal chelators - Animal toxins are antagonized by antitoxins Drugs Vectors by Vecteezy  Interaction of toxic agents There are 4 types of antagonism Dispositional antagonism o When the absorption, metabolism, distribution, or excretion of a chemical is altered so that its concentration or duration of its presence at the target organ are diminished. Receptor antagonism o When two chemicals compete to the binding on the same receptor. o Receptor antagonists are termed blockers. Drugs Vectors by Vecteezy  Adverse Drug Reactions (ADRs) Adverse drug reactions Harmful/unintended reactions to medicines that occur at doses normally used for treatment. Adverse drug reactions Vs. Toxicity Toxicity usually occurs at high doses above therapeutic use. Most common causes: o Incorrect diagnosis o Prescription of incorrect drug or incorrect dosage or inappropriate duration o Patient-specific conditions Ex. genetic or allergic conditions o Self-medication o Not following the instructions for taking the medication o Drug interactions or food interactions o Use of counterfeit medicines Ex. Does not contain the active ingredients or contains fatal ingredients  Adverse Drug Reactions (ADRs) ADRs can be classified into 6 types: Type A “Augmented” Type B “Bizarre” Type C “Continuous” Type D “Delayed” Type E “End of use” Sick Vectors by Vecteezy Type F “Failure of efficacy”  Adverse Drug Reactions (ADRs) ADRs can be classified into 6 types: Type A “Augmented” o Results from predictable pharmacological effects of the drug. “ dose-dependent effect” o Includes side effects/augmented effect of drugs. Examples: - Heparin → bleeding - Tricyclic antidepressants → anticholinergic side effects - Insulin → Hypoglycemia Type B “Bizarre” o Results from unexpected/unpredicted reaction to the drug. “ dose-independent effect” o Can be triggered by any dose. Examples: - Allergic reactions - Anaphylactic shock - Idiosyncratic reactions ex. drug-induced lupus Sick Vectors by Vecteezy  Adverse Drug Reactions (ADRs) ADRs can be classified into 6 types: Type C “Continuous” o Results from chronic usage of the drug. “Dose & time related” Examples: - Corticosteroids chronic treatment → Osteoporosis - NSAIDs chronic treatment → Nephrotoxicity Type D “Delayed” o Appears long after drug exposure. “Latency period” Examples: - Carcinogenic & teratogenic effect of some drugs Sick Vectors by Vecteezy  Adverse Drug Reactions (ADRs) ADRs can be classified into 6 types: Type E “End of use” o Appears after sudden stopping of the drug. “withdrawal symptoms” Examples: - Benzodiazepines → rebound insomnia - Corticosteroids → Acute adrenal insufficiency due to atrophy of adrenal gland and lack of endogenous ACTH production Type F “Failure of efficacy” o Appears due to undesirable reduction in drug effect. Examples: - Drug interactions affecting metabolism - Decreased effect of antibiotics due to resistance Sick Vectors by Vecteezy  Practice Questions 1. Spider venom is considered a toxicant. (True/False) 2. An additive effect is when the sum of effect of two chemicals is greater than the sum of effect of each one alone. (True/False) 3. Metal chelators act through functional antagonism. (True/False) 4. Adverse drug reactions are defined as …….. 5. The area of toxicology concerned with the health effects of chemicals in the workplace is called ……… 6. List 4 sources of toxic agents. 7. Compare between type A & B of adverse drug reactions giving examples. Book Vectors by Vecteezy  Thank you Poison Vectors by Vecteezy