Name of Department : NURSING (ENGLISH)

Course Code and Name : PHARMACOLOGY

Course Week : Week 5
Course Day and Time : Frıday 09:00-10:50
Course Credit/ACTS
Information : 2/3
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 |

Drug Metabolism, Drug Addiction and Treatment

Define biotransformation and its role in pharmacokinetics.
Explain the phases and pathways of drug metabolism.
Discuss factors influencing biotransformation.
Understand the clinical relevance of biotransformation in nursing practice.
Understand the biological basis of drug addiction.
Identify common treatments and nursing interventions for drug dependence.
 | DAILY FLOW |

09.00-09.50/ 1st Hour

10.00-10.50/ 2nd 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).
Process of toxicant exposure leading to a biological
response through three stages:

Toxicokinetics

Toxicodynamics

Response
 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, response
of an individual organism (example, drug therapy).

2. Quantal Dose-Response Curve: All-or-nothing responses in a population (mortality).

Key Concepts in Dose-Response Curves:

Threshold Dose: The minimum dose required to elicit a toxic effect.

LD50 (Lethal Dose 50): The dose required to kill 50% of a population.

Therapeutic Index (TI): Ratio of toxic dose (TD50) to therapeutic dose (ED50) to assess drug safety
Dose-Response Relationship
Types of Toxic Effects
 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).

3. Local and Systemic Toxicity:
 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 ( through enzymes like
cytochrome P450).
• Phase II Reactions: Conjugation (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 (mitochondria), or DNA.

2. Enzyme Inhibition:

• Inhibition of critical enzymes in biochemical pathways ( cyanide blocking cellular

respiration).

3. Oxidative Stress:

• Excessive generation of reactive oxygen species (ROS) leading to cellular damage

(paracetamol-induced liver toxicity).

4. Immune Responses:

• Allergic reactions or hypersensitivity (e.g., penicillin-induced anaphylaxis).

Principles of Treatment and Prevention
Principles of Treatment and Prevention
Principles of Treatment and Prevention
 Principles of Treatment and Prevention
1. Prevention of Absorption:

 Activated Charcoal:
Activated charcoal binds to toxins in the gastrointestinal tract, helping to
prevent their absorption into the bloodstream. It is commonly used in cases
of poisoning and overdose.
Dosage: Typically, 50g for adults and 25g for children.
Note: Charcoal should be administered soon after ingestion of the toxin for it
to be effective. It is generally not effective for certain substances like alcohol,
metals (iron, lead), and acids.
 Emesis: Induction of vomiting (only in specific cases, not
recommended for corrosive substances or if there’s a risk of
aspiration).
 Principles of Treatment and Prevention
2. Enhancing Elimination:

 Hemodialysis:
Hemodialysis is a medical procedure used to filter toxins directly from
the blood, primarily in cases of severe poisoning or when the toxin is
known to be dialyzable (example methanol, ethylene glycol, lithium).

 Forced Diuresis:
Forced diuresis involves increasing urine output to enhance the
excretion of certain toxins. This can be achieved by administering
diuretics, such as:
 Furosemide: A loop diuretic that increases urine output.
 Mannitol: An osmotic diuretic that promotes diuresis, particularly
useful in cases where rapid fluid movement is required.
 Principles of Treatment and Prevention
3. Antidotes:
Drug Overdose/Poison Antidote

Paracetamol N-acetylcysteine

Opioids Naloxone

Organophosphate, Carbamates Atropine, Pralidoxime

Belladonna (Atropine) Poisoning Physostigmine

Mushroom Poisoning Atropine

Benzodiazepine Flumazenil

Arsenic Poisoning Dimercaprol

Iron Desferrioxamine

Warfarin Vitamin K

Heparin Protamine Sulfate

Copper, Gold, Lead, Mercury, Zinc Penicillamine

Beta Blocker Adrenaline

 Principles of Treatment and Prevention

4. Supportive Care:

 Primary Focus: Ensure proper airway, breathing, and circulation (often

referred to as the "ABCDE) to stabilize the patient while the body processes
and eliminates the toxin.

 Temperature Management: Unconscious patients may develop hypothermia.

To prevent this, they should be wrapped in blankets to conserve body heat.

 Convulsion Control: For prolonged or recurrent convulsions, intravenous

diazepam can be administered to control seizures.
 Principles of Treatment and Prevention

5. Prevention of Repeated Poisoning

 Follow-Up and Counseling: In cases of suicidal poisoning, psychiatric follow-up

and counseling are essential to address underlying issues and prevent future
incidents.

 Safety Measures for Accidental Poisoning:

• Proper Labeling and Storage: Ensure toxic substances are clearly labeled,
locked away, and kept out of reach of children.

• Safe Drug Storage: Keep medications and other potentially toxic items in
secure locations to minimize the risk of accidental ingestion, especially by
children.
Principles of Treatment and Prevention
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.
• Dimercaptosuccinic acid (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 6

Sympathomimetic and Sympatholytic Drugs

“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