week 1

PHARMACOLOGY NOTES

Intro to Patho-Pharm

  • Course: NURS 309 PATHO-PHARM I
  • Instructor: S. Tullos, EdD, MNSC, RN

Cellular Biology

Overview

  • Cellular structures and functions discussed in Chapter One of Huether & McCance.

Cellular Organelles

  • Microfilaments: Cytoskeletal structures providing shape and support.
  • Cilia: Hair-like structures aiding in movement of substances across cell surfaces.
  • Cytoplasm: Gel-like substance filling the cell, containing organelles.
  • Vaults: Nucleoprotein complexes associated with cellular transport.
  • Cell Junctions:
    • Desmosome: Adhering junction providing mechanical strength.
    • Gap junction: Communicating junction allowing for intercellular signaling.
  • Ribosome: Site of protein synthesis; can be free in the cytoplasm or bound to the rough endoplasmic reticulum (RER).
  • Nucleus: Cellular control center housing genetic material.
  • Plasma Membrane: Protects cell integrity and regulates substance passage.
  • Endoplasmic Reticulum:
    • Rough ER: Studded with ribosomes; synthesizes proteins.
    • Smooth ER: Synthesizes lipids and detoxifies.
  • Golgi Apparatus: Modifies, sorts, and packages proteins for secretion or use within the cell.
  • Mitochondrion: Powerhouse of the cell; produces ATP via oxidative phosphorylation.
  • Lysosome: Contains digestive enzymes for waste processing.
  • Peroxisome: Contains enzymes for oxidation reactions.

Cellular Functions

  • Movement: Muscle cells exhibit contraction.
  • Conductivity: Nerve cells transmit signals.
  • Metabolic Absorption: All cells take in nutrients and compounds.
  • Secretion: Glandular cells release substances like hormones or enzymes.
  • Excretion: All cells eliminate waste products.
  • Respiration: Occurs in mitochondria for energy production.
  • Reproduction: Cells undergo division to form new cells.
  • Communication: Cells maintain homeostasis through signaling.

Cellular Communication and Homeostasis

Types of Signaling

  • Contact-Dependent Signaling: Involves direct communication between adjacent cells via membrane-bound receptors.
  • Remote Signaling: Signaling molecules (hormones, neurotransmitters) travel through the bloodstream to target cells.

Signaling Categories

  1. Paracrine: Signal affects neighboring cells only.
  2. Autocrine: Cell signals itself (e.g., cancer cells).
  3. Endocrine: Hormonal signaling through the bloodstream.
  4. Neurotransmitter Signaling: Nerve cells release neurotransmitters to stimulate target cells across a synapse.

Cellular Metabolism

  • Anabolism: Building processes using energy; for example, synthesizing proteins from amino acids.
  • Catabolism: Breakdown processes releasing energy; for example, the hydrolysis of carbohydrates into glucose.
  • ATP: Adenosine triphosphate serves as the main energy currency of the cell.
  • Oxidative Phosphorylation: ATP is generated in the mitochondria.

Altered Cellular and Tissue Biology

Cellular Adaptation Mechanisms

  • Atrophy: Decrease in cell size due to decreased workload or stimulus.
  • Hypertrophy: Increase in cell size due to increased workload.
  • Hyperplasia: Increase in cell number due to stimulatory signals.
  • Metaplasia: Replacement of one cell type with another, often due to irritation or chronic injury.
  • Dysplasia: Abnormal cell growth; can be reversible and indicates a precancerous condition.

Cellular Injury: Reversible vs Irreversible

Causes of Cellular Injury

  • Hypoxia: Insufficient oxygen due to factors such as respiratory issues, anemia, or poisoning (interfering with oxidative enzymes).
  • Ischemia: Insufficient blood flow leading to oxygen and nutrient starvation.
  • Anoxia: Complete lack of oxygen results in cell death.

Cellular Responses to Injury

  1. Decrease in ATP production, affecting sodium-potassium pumps.
  2. Cellular swelling indicating dysfunction and potential necrosis.

Table 4.1: Types of Progressive Cell Injury and Responses

  • Adaptation: Responses including atrophy, hypertrophy, hyperplasia, metaplasia.
  • Active Cell Injury: Immediate response involving loss of ATP and cellular swelling.
  • Reversible Injury: Recovery may occur with restoration of blood flow and oxygenation.
  • Irreversible Injury: Severe injury leading to cell death (necrosis or apoptosis).

Free Radicals and Reactive Oxygen Species

  • Mechanisms of Damage:
    • Lipid peroxidation affecting cell membranes.
    • Alteration of proteins leading to loss of function.
    • Damage to DNA causing mutations.
  • Chemical Agents: Common toxins include carbon tetrachloride, lead, carbon monoxide, ethanol, and various drugs.

Liver Injury Mechanisms

Factors Leading to Hepatotoxicity

  • Gene Regulation: Epigenetic changes and transcription factors affect liver's response to injury.
  • Xenobiotics: Foreign compounds affecting liver metabolism and detoxification processes.
  • Environmental Factors: Toxins, drugs, and even dietary substances can contribute to liver stress.
  • Inflammation: Chronic conditions leading to damage and necrosis of liver cells.

Chemical Exposure Impacts

  • Acetaminophen: Toxic metabolite formation can lead to hepatocyte injury and necrosis in high doses.
  • Carbon Tetrachloride: Causes lipid peroxidation and membrane damage.

Examples of Cellular Injury Types

Intentional and Unintentional Injuries

Types:

  • Suffocation, Blunt Force, Sharp Force injuries, Gunshot Wounds, Chemical Burns, Falls, Poisoning, etc.

Accumulations / Infiltrations in Cells

Types of Accumulatory Change

  • Pigments:
    • Melanin: Protects against UV damage.
    • Hemoproteins: Including excess iron (hemosiderin), leading to conditions like hemochromatosis.
    • Lipofuscin: Age-related pigment accumulation indicating cell wear and tear.
  • Urate Accumulation: Leads to gout due to excess uric acid.

Necrosis Types

  1. Coagulative: Tissue firmness; usually in response to ischemia.
  2. Liquefactive: Transformation into liquid due to hydrolytic enzyme action, typically in brain tissues.
  3. Caseous: Cheese-like appearance often associated with tuberculosis.
  4. Fat Necrosis: Related to fatty tissue damage, due to enzymes like lipase.
  5. Gangrenous: Death of tissue from severe hypoxia, which may present as either dry or wet form based on tissue reaction.
  6. Gas Gangrene: Infective process, notably with Clostridium bacteria.

Apoptosis and Self-Digestion Mechanisms

  • Apoptosis: Natural process of programmed cell death.
  • Autophagy: Cellular self-digestion recycling cellular components due to stress or damage.

Aging Processes

  • Cellular Aging: Atrophy, decreased function, and cell death over time.
  • Tissue Aging: Results in systemic issues, including stiffness and sarcopenia (decline in muscle mass).
  • Frailty: Assessment of balance, strength, and overall health in older adults.

Death and Postmortem Changes

Physiological Changes After Death

  • Algor Mortis: Body cooling.
  • Livor Mortis: Pooling of blood in lower areas historically; areas appear purple.
  • Rigor Mortis: Stiffening of muscles post-death
  • Postmortem Autolysis: Decay processes postmortem leading to discoloration and bloating.

Clinical Judgment in Nursing

NCSBN Clinical Judgment Measurement Model Layers

  1. Recognizing Cues: Identifying patient signals.
  2. Analyzing Cues: Interpreting data.
  3. Prioritizing Hypotheses: Ranking patient issues.
  4. Generating Solutions: Formulating actions.
  5. Evaluating Outcomes: Assessing effectiveness of interventions.

Drug Development Process

Phases of Drug Testing

  1. Preclinical: Laboratory testing in vitro and in vivo (about 10-15 years).
  2. Phase I: Small group trials for safety.
  3. Phase II: Testing for efficacy.
  4. Phase III: Large-scale clinical trials for therapeutic use.
  5. Post-marketing Surveillance: Ongoing monitoring after drug approval.

Costs and Timeline

  • Typical costs: approximately $2.6 billion to develop.
  • Total time: can exceed a decade.

Ethical Considerations in Drug Development

  • Autonomy: Respecting patients' rights and choices.
  • Beneficence: Acting in the patient’s best interest.
  • Justice: Fair distribution of research benefits and burdens.

Informed Consent

  • Patients must understand the purpose, risks, and benefits of treatment.
  • Consent should be voluntary and clearly communicated at an appropriate reading level.

Drug Standards and Classifications

  1. Chemical Name: Describes the chemical composition.
  2. Generic Name: Nonproprietary name (e.g., ibuprofen).
  3. Brand Name: Proprietary name (e.g., Advil).
  4. Over-the-Counter (OTC): Medications that can be purchased without prescriptions, with safety instructions provided.

Pharmacokinetics and Pharmacodynamics

Pharmacokinetics

  1. Absorption: Movement of drugs into circulation influenced by numerous factors including route of administration and patient conditions.
  2. Distribution: Movement from circulation to sites of action; affected by protein binding and barriers such as the blood-brain barrier.
  3. Metabolism: Mainly occurs in the liver; can alter drug efficacy and toxicity.
  4. Excretion: Elimination from the body, crucial for drug safety; monitored by renal function tests.

Pharmacodynamics

  • Involves the action of drugs on target receptors and tissues. Key concepts include:
    • Dose-Response Curves: Measuring the physiological response linked to drug concentration.
    • Therapeutic Index: Ratio between effective and toxic doses, crucial for maintaining safety margins in drug administration.
    • Side Effects and Adverse Reactions: Understanding potential risks and patient management strategies.

Drug Interactions

Types of Interactions

  1. Pharmacokinetic Interactions: Affecting absorption, metabolism, and excretion of drugs.
  2. Pharmacodynamic Interactions:
    • Additive: Combined effects of drugs.
    • Synergistic: Enhanced effects of combined drugs.
    • Antagonistic: One drug diminishes the effect of the other.

Conclusion

  • This detailed overview provides comprehensive insights into key concepts in clinical pharmacology, cellular biology, and drug development, crucial for nursing practice and patient care management.

References:

  • Huether & McCance (2026, 8th Ed.)
  • McCuistion (2026, 12th Ed.)