2nd Week Pharmacology: Introduction to Toxicology PDF

 PHYSICAL THERAPY AND REHABILITATION Name of Department : (ENGLISH) Course Code and Name : PHARMACOLOGY Course Week : Week 2 Course Day and Time : Thursday 09:00-11:50 Course Credit/ACTS Information : 3/6...

 PHYSICAL THERAPY AND REHABILITATION Name of Department : (ENGLISH) Course Code and Name : PHARMACOLOGY Course Week : Week 2 Course Day and Time : Thursday 09:00-11:50 Course Credit/ACTS Information : 3/6 Examination Type and Gradings : Midterm and Final exam Instructor’s Name & Surname : Assist.Prof. GLORIA NNADWA ALHASSAN E-mail & Phone: : [email protected] Instructor’s Room : B-Block Third floor Office Hours : 12:00 GBS Link : https://gbs.gelisim.edu.tr/en/lesson-details-17-319-12132 ALMS Link : https://lms.gelisim.edu.tr/almsp/u/Home/Index AVESIS Link : https://avesis.gelisim.edu.tr/ | 14 WEEKS’S COURSE CONTENTS |  | WEEKLY LEARNING OUTCOMES | By the end of this week, students will be able to: 1. Define toxicology and its scope. 2. Understand the dose-response relationship.Discuss the factors affecting toxicity. 3. Explore different types of toxic agents and their mechanisms. 4. Explain key principles of treatment and prevention of poisoning. | ABOUT THE PREVIOUS COURSE | Introduction to Pharmacology.  | DAILY FLOW | 09.00-09.50/ 1st Hour 10.00-10.50/ 2nd Hour 11.00-11:50/3rd Hour  | Introduction to Toxicology | Definition of toxicology is "the science of poisons.“ The study of the adverse effects of chemicals or physical agents on living organisms Adverse effects may occur in many forms, ranging from immediate death to subtle changes not realized until months or years later. They may occur at various levels within the body, such as an organ, a type of cell, or a specific biochemical  | Scope of Toxicology| 1. Environmental Toxicology: Impact of pollutants (air, water, soil) on human and animal health. 2. Forensic Toxicology: Detection of poisons, drugs, and other harmful agents in legal cases. 3. Pharmacological Toxicology: Adverse effects of drugs and chemicals on biological systems.  | History of Toxicology | Historical figures like Paracelsus: "The dose makes the poison" ( even water can be toxic at high enough doses). Toxicology is largely concerned with the interaction of toxicants and biological systems. While toxicodynamic investigates the effect of the toxicant on the organism. Toxicokinetic looks at how the organism affects the toxicant (absorption, biotransformation, distribution, and elimination).  Dose-Response Relationship The relationship between the dose of a substance and the response it produces. Types of Dose-Response Curves: 1. Graded Dose-Response Curve: Response increases continuously with increasing dose (e.g., drug therapy). 2. Quantal Dose-Response Curve: All-or-nothing responses in a population (e.g., mortality). 3. Threshold Dose: The minimum dose required to elicit a toxic effect. 4. LD50 (Lethal Dose 50): The dose required to kill 50% of a population. 5. Therapeutic Index (TI): Ratio of toxic dose (TD50) to therapeutic dose (ED50) to assess drug safety Dose-Response Relationship  Types of Toxic Effects 1. Acute and Chronic Toxicity 2. Reversible and Irreversible Toxicity 3. Local and Systemic Toxicity  Types of Toxic Effects 1. Acute and Chronic Toxicity: Acute Toxicity: Effects that occur shortly after exposure to a toxic agent ( poisoning from a high dose). Chronic Toxicity: Long-term effects from repeated or continuous exposure ( lead poisoning).  Types of Toxic Effects 2. Reversible and Irreversible Toxicity: Reversible: Toxic effects that can be undone ( liver damage from alcohol that heals over time). Irreversible: Permanent damage (nerve damage from certain heavy metals).  Types of Toxic Effects 3. Local and Systemic Toxicity: Local: Toxic effects occur at the site of contact (e.g., skin irritation from a chemical). Systemic: Toxic effects occur throughout the body after absorption (e.g., organ damage from ingestion).  Factors Affecting Toxicity 1. Factors Related to the Toxicant a. Chemical Structure: Determines how a substance interacts with biological systems. b. Solubility: Water-Soluble: Easier to excrete but may damage kidneys (e.g., certain heavy metals). Fat-Soluble: Accumulate in tissues and are released slowly, leading to chronic toxicity (e.g., DDT). c. Stability: Unstable compounds may form reactive metabolites (e.g., acetaminophen toxicity due to reactive metabolites). d. Route of Exposure: Oral, dermal, inhalation routes have different absorption and toxicity profiles.  Factors Affecting Toxicity 2. Host Factors Influencing Toxicity a. Age: Infants and the elderly are more sensitive to toxins due to immature or compromised detoxification systems. b. Sex: Hormonal differences can affect metabolism and response to toxins (males and females metabolize alcohol differently).  Factors Affecting Toxicity 2. Host Factors Influencing Toxicity c. Genetics: Genetic polymorphisms in drug-metabolizing enzymes ( CYP450) can influence susceptibility to toxicity. d. Health Status: Pre-existing conditions like liver or kidney disease can increase vulnerability to toxins. e. Nutritional Status: Poor nutrition may impair the body’s ability to detoxify harmful substances (e.g., vitamin deficiencies).  Factors Affecting Toxicity 3. Environmental and Behavioral Factors a. Exposure Duration and Frequency: Short-term high-dose exposures may lead to acute toxicity, while long-term low-dose exposures can cause chronic toxicity. b. Co-exposure to Multiple Chemicals: Synergistic Effect: Combined exposure to certain substances results in greater toxicity (alcohol and acetaminophen). Antagonistic Effect: One chemical reduces the toxic effect of another. c. Lifestyle Factors: Smoking, alcohol use, and poor diet may enhance the toxicity of certain chemicals.  Factors Affecting Toxicity 4. Absorption, Distribution, Metabolism, and Excretion (ADME) a. Absorption: How the toxicant enters the body (e.g., through skin, lungs, gastrointestinal tract). b. Distribution: How the toxicant moves throughout the body, often bound to proteins ( toxins can accumulate in fat tissues).  Factors Affecting Toxicity 4. Absorption, Distribution, Metabolism, and Excretion (ADME) c. Metabolism (Biotransformation): Phase I Reactions: Oxidation, reduction, hydrolysis (e.g through enzymes like cytochrome P450). Phase II Reactions: Conjugation (e.g., with glucuronic acid) to make toxicants water- soluble for excretion. d. Excretion: Removal of toxins via urine, feces, breath, sweat, etc.  Types of Toxic Agents 1. Chemical Toxicants: Pesticides: Organophosphates, DDT (effects on the nervous system, endocrine disruption). Heavy Metals: Lead, mercury, arsenic (neurotoxicity, carcinogenicity). Drugs: Overdose of medications like acetaminophen, NSAIDs, and opioids. 2. Biological Toxins: Bacterial Toxins: Botulinum toxin, tetanus toxin. Plant Toxins: Ricin, alkaloids. Animal Toxins: Snake venom, spider venom. 3. Physical Agents: Radiation: Ionizing radiation leading to DNA damage and cancer. Thermal Burns: Chemical burns from acids or bases.  Mechanisms of Toxicity 1. Cellular Damage: Direct damage to cell membranes, organelles (e.g., mitochondria), or DNA. 2. Enzyme Inhibition: Inhibition of critical enzymes in biochemical pathways (e.g., cyanide blocking cellular respiration). 3. Oxidative Stress: Excessive generation of reactive oxygen species (ROS) leading to cellular damage (e.g., paracetamol-induced liver toxicity). 4. Immune Responses: Allergic reactions or hypersensitivity (e.g., penicillin-induced anaphylaxis).  Principles of Treatment and Prevention 1. Prevention of Absorption: Activated Charcoal: Binds toxins in the gastrointestinal tract to prevent absorption. Emesis: Induction of vomiting (only in specific cases, not recommended for corrosive substances). 2. Enhancing Elimination: Hemodialysis: Filters toxins from the blood in cases of severe poisoning. Forced Diuresis: Increasing urine output to enhance excretion.  Principles of Treatment and Prevention 3. Antidotes: Specific agents that neutralize toxins (e.g., N-acetylcysteine for acetaminophen poisoning, atropine for organophosphate poisoning). 4. Supportive Care: Ensuring proper airway, breathing, and circulation while the body processes and removes the toxin. Principles of Treatment and Prevention  Case Studies Case study 1: A patient takes an overdose of acetaminophen (paracetamol), resulting in severe liver damage. What is the Symptom, Treatment and outcome ? Case study 2: A 5-year-old child is diagnosed with lead poisoning. The source of lead exposure is thought to be old lead-based paint in the family’s home. What is the Sources, symptoms, and long-term effects ?  Case Studies Symptoms: Early signs: Nausea, vomiting, sweating, and general malaise. After 24-48 hours: Signs of liver damage become apparent, including elevated liver enzymes (AST, ALT), jaundice, and in severe cases, hepatic failure. Treatment: 1.Activated Charcoal (within 1 hour of ingestion): Reduces absorption of the drug in the gastrointestinal tract. 2.N-acetylcysteine (NAC): Acts as a glutathione precursor and helps restore depleted glutathione levels. NAC neutralizes NAPQI, reducing liver damage. It is most effective when administered within 8-10 hours of overdose. 3.Supportive Care: Monitoring liver function, hydration, and managing symptoms. Outcome: Early administration of N-acetylcysteine can prevent severe liver damage and improve patient survival. If untreated, acetaminophen overdose can lead to fulminant hepatic failure and death, potentially requiring a liver transplant.  Case Studies 2 Symptoms: Acute Symptoms: Abdominal pain, constipation, vomiting, and fatigue. Neurological Symptoms: Irritability, attention deficits, learning difficulties, and in severe cases, seizures. Chronic Exposure: Long-term developmental delay, lower IQ, and behavioral disorders. Treatment: 1.Chelation Therapy: Dimercaprol or EDTA (calcium disodium edetate) are chelating agents that bind to lead and enhance its excretion through urine. Succimer (DMSA) is often used in children with elevated blood lead levels. 2. Removing the Source of Lead: Addressing the environmental source, such as the removal of lead-based paint or contaminated soil. 3.Supportive Care: Nutritional support with calcium and iron to reduce lead absorption. Outcome: Chelation therapy effectively reduces lead levels in the blood, but some neurological damage from chronic exposure may be irreversible. Prevention of future exposure is crucial to avoid further harm.  | WHAT TO TAKE HOME? | 1. Define toxicology and its scope. 2. Understand the dose-response relationship. 3. Discuss the factors affecting toxicity. 4. Explore different types of toxic agents and their mechanisms. 5. Explain key principles of treatment and prevention of poisoning.  | QUESTIONS AND SUGGESTIONS | Case study 1: A patient takes an overdose of acetaminophen (paracetamol), resulting in severe liver damage. What is the Symptom, Treatment and outcome ? Case study 2: A 5-year-old child is diagnosed with lead poisoning. The source of lead exposure is thought to be old lead-based paint in the family’s home. What is the Sources, symptoms, and long-term effects ? Review factors influencing toxicity and key treatment principles.  | RECOMMENDED DAILY STUDIES | Goodman & Gilman's the Pharmacological Basis of Therapeutics  | REFERENCES | 1.Goodman & Gilman's the Pharmacological Basis of Therapeutics 2. Medical Pharmacology and Therapeutics 5th Edition by Derek G. Waller BSc DM MBBS FRCP (Author), Anthony Sampson MA PhD FHEA FBPhS 3. Dale's Pharmacology Condensed E-Book Book by C. P. Page and Simon Pitchford 4. Undergraduate Pharmacology 2nd Edition by K. Mukhopadhyay (Author) 5.Shayne CG. Introduction: drug Discovery in the 21stCentury. Drug Discovery Handbook, Wiley Press, 2005; 1-10. | ABOUT THE NEXT WEEK | Week 3 Pharmacokinetics and pharmacodynamics “Victory is for those who can say "Victory is mine". Success is for those who can begin saying "I will succeed" and say "I have succeeded" in the end.” ― Mustafa Kemal Atatürk