Unit 1 Pharmacology and Cell Pathophysiology Vocabulary
Fundamental Cellular Structures and Energy Production
Cell as the Basic Unit of Life: Foundational to both pathophysiology and pharmacology.
Organelle Structure and Function:
Nucleus: Serves as the control center and contains genetic material (DNA).
Mitochondria: Known as the powerhouse of the cell; primary site for the production of adenosine triphosphate ().
Ribosomes: Responsible for protein synthesis.
Endoplasmic Reticulum (ER): Facilities the transport of proteins and lipids.
Golgi Apparatus: Packages proteins for delivery or secretion.
Lysosomes and Peroxisomes: Functions in waste disposal, detoxification, and enzymatic digestion.
Plasma Membrane: Acts as a semi-permeable barrier and regulator of transport between the intracellular and extracellular environments.
Core Cellular Processes:
Energy production.
Protein synthesis.
Cellular communication.
Reproduction through mechanisms of mitosis and meiosis.
Aerobic Energy Production: Consists of the sequence: Glycolysis Kreb’s Cycle Electron Transport Chain (ETC). This process yields approximately .
Cellular Adaptive Responses and Pathognomonic Identifiers
Homeostasis and Adaptation: Cells undergo changes to maintain stability.
Adaptive (Functional): Compensatory and reversible changes.
Maladaptive (Dysfunctional): Changes that may lead to disease states.
Types of Adaptations:
Atrophy: A decrease in cell size (physiologic or pathologic) occurring via protein degradation and autophagy. Example: Disuse atrophy seen in a casted limb or the aging brain.
Hypertrophy: An increase in cell size due to stimulus or workload.
Physiologic: Weight training (skeletal muscle).
Pathologic: Left Ventricular Hypertrophy (LVH) due to hypertension, which is maladaptive and increases the risk of heart failure.
Hyperplasia: An increase in the number of cells via mitotic activity. Example: Endometrial hyperplasia or Keloid formation.
Metaplasia: Conversion from one adult cell type to another due to chronic irritation. Example: Barrett’s esophagus (squamous cells change to columnar cells). It is reversible but carries a risk of progression to dysplasia.
Dysplasia: Deranged, disordered growth characterized by atypical nuclei and mitotic figures; often considered a precancerous condition. Example: Cervical dysplasia related to HPV.
Neoplasia: Uncontrolled, autonomous, and new cell growth. It is irreversible and a hallmark of cancer.
Benign Neoplasia: New growth that is not harmful (e.g., a nevus/mole).
Malignant Neoplasia: Cancerous growth that is destructive and capable of metastasis.
Diagnostic Terms:
Etiology: The cause or origin of a disease (e.g., sun exposure for skin cancer).
Biopsy: The extraction of tissue for diagnostic examination.
Histology: The microscopic study of tissues.
Pathognomonic Changes: Unique, identifying features specific to a particular disease. Example: The mucosal crater of a peptic ulcer visible on endoscopy.
Mechanisms and Etiologies of Cellular Injury
Sodium/Potassium () Pump Dysfunction: Fails when is low. Leads to the accumulation of intracellular , resulting in water influx and cellular swelling. Muscles and nerves lose polarity, causing lethargy and fatigue.
Calcium () Pump Dysfunction: Maintenance of low intracellular requires . Pump failure causes accumulation, which activates enzymes that damage membranes and DNA. This can lead to pathological calcifications as seen in arteriosclerosis, malignancy, or stenotic valve disease.
Loss of Membrane Integrity: Allows entry of water and toxins; exposes the nucleus and organelles. Leads to energy failure (mitochondrial damage), lysis (lysosomal leakage), and inability to regenerate (nuclear damage).
Intracellular Accumulations: Can be reversible or toxic.
Fat: Examples include alcoholic liver disease.
Cholesterol: Examples include xanthomas.
Environmental Agents: Such as coal dust.
Bilirubin: Causes jaundice.
Genetic Damage: DNA mutations lead to abnormal RNA/proteins, potentially resulting in tumor formation if apoptosis or differentiation is bypassed.
Major Causes of Injury:
Hypoxia: The most common cause; inadequate oxygen supply leads to anaerobic metabolism and lactic acid buildup.
Free Radicals: Toxic by-products of mitochondrial oxidative phosphorylation (respiratory burst). Neutralized by antioxidants (Vitamins A, C, E) and superoxide dismutases. Oxidative stress occurs when radicals exceed neutralizers. Example: Ischemia-reperfusion injury after MI or stroke.
Physical Agents: Trauma, burns, frostbite, and radiation.
Chemical Injury:
Endogenous: Hyperglycemia, hypernatremia.
Exogenous: Carbon Monoxide (CO) poisoning, alcohol (leads to fatty liver changes), and nephrotoxic or hepatotoxic drugs.
Infectious Agents: Bacteria () and viruses (HPV, HIV).
Immunologic Reactions: Allergies and autoimmune disorders like Rheumatoid Arthritis (RA).
Nutritional Imbalances:
Kwashiorkor: Protein starvation leading to ascites.
Marasmus: Calorie and protein starvation leading to cachexia.
Clinical Consequences of Ischemia and Endothelial Dysfunction
Ischemia Tolerance by Tissue Type:
Brain: (least tolerant due to high metabolic demand).
Heart (Myocardium): .
Kidney: .
Skeletal Muscle: .
Skin: Several hours.
Ischemia Outcomes: Ischemic stroke (brain), Myocardial Infarction (heart), Acute tubular necrosis (kidney), Necrosis/perforation (bowel), and Gangrene (limbs).
Endothelial Function: The endothelium lines all blood vessels and regulates vascular tone.
Secretions: Vascular Endothelial Growth Factor (VEGF) for angiogenesis, Nitric Oxide (NO) for vasodilation, and Endothelin for vasoconstriction.
Endothelial Injury: The initial trigger for atherosclerosis.
Causes of Endothelial Injury: Hypertension (shear force), Hyperglycemia (glycation and AGEs), Free radicals (smoking), Angiotensin II (vasoconstriction), and LDL (foam cell/plaque formation).
Programmed Cell Death and Pathological Necrosis
Apoptosis: Programmed, essential cell death for removing unwanted cells and maintaining homeostasis.
Physiologic Examples: Embryogenesis (webbing removal), immune regulation (T-cell elimination), menstrual shedding, and skin/GI turnover.
Dysregulation:
Excessive: Leads to tissue loss (e.g., Spinal muscular atrophy, Hashimoto’s thyroiditis).
Inhibited: Leads to tumor growth (e.g., Prostate cancer, BPH).
Necrosis: Uncontrolled cell death due to severe injury, resulting in cell lysis and inflammation.
Types of Necrosis:
Coagulative: Protein denaturation; architecture is preserved (e.g., MI).
Liquefactive: Enzymatic digestion of tissue (e.g., Brain infarction, abscess).
Caseous: "Cheesy" appearance; combination of coagulative and liquefactive (e.g., Tuberculosis).
Fat Necrosis: Enzymatic destruction of fat (e.g., Acute pancreatitis).
Gangrene: Large area of necrotic tissue.
Dry: Ischemic, tissue shrinks and turns black.
Wet: Bacterial infection, swelling, foul odor.
Gas: Caused by ; produces gas and spreads rapidly.
Basics of Pharmacology: Naming and Classification
Drug Classification:
Pharmacologic Class: Based on the mechanism of action (e.g., ACE inhibitors).
Therapeutic Class: Based on the clinical use or condition treated (e.g., antihypertensives).
Naming Conventions: Classes often share suffixes (e.g., "-pril" for ACEIs).
Nomenclature:
Generic Name: The official, chemical name; one per drug (e.g., lisinopril, ibuprofen).
Brand (Trade) Name: Marketed/trademarked name chosen by the manufacturer; can be multiple (e.g., Advil, Motrin).
Bioequivalence: The FDA requires generic drugs to have the same active ingredient, strength, and route as the brand drug and provide the same clinical benefit.
Medication Categories:
Prescription (Rx): Require provider oversight and authorization.
Nonprescription (OTC): Safe for self-administration for minor ailments.
Controlled Substances: Scheduled based on abuse potential (Schedule I = highest risk, e.g., Heroin; Schedule V = lower risk, e.g., acetaminophen with codeine).
Prescription Components: Must include Patient name, date, drug name, dose, route, frequency, duration/quantity, indication for PRN meds, provider signature, and DEA number if applicable.
Pharmacokinetics: The Life Cycle of a Drug (ADME)
Pharmacokinetics: The movement and modification of a medication inside the body.
Absorption: Movement from the site of administration into the bloodstream. Influenced by route, formulation (Extended Release [XR], Enteric Coated [EC]), blood flow, and pH.
First-Pass Effect: Reduced bioavailability of oral drugs because they are metabolized by the liver before reaching systemic circulation.
Distribution: Movement through the bloodstream to tissues. Influenced by blood flow, protein binding (primarily albumin), and barriers like the Blood-Brain Barrier. High-perfusion organs like the heart, liver, and kidneys receive drugs first.
Metabolism (Biotransformation): Occurs mostly in the liver via CYP450 enzymes.
Phase I (Oxidation): Introduces/exposes functional groups (). Can activate a drug (e.g., Codeine Morphine via CYP2D6).
Phase II (Conjugation): Attaches a water-soluble molecule (glucuronic acid, sulfate, glutathione). This increases water solubility to facilitate excretion. (e.g., Morphine Morphine-6-glucuronide).
Excretion: Removal via kidneys, bile, lungs, or sweat. Also occurs through mammary and seminal glands.
Pharmacodynamics: Mechanisms of Action and Drug Interactions
Pharmacodynamics: Description of how a drug acts on the body (Mechanism of Action [MOA]).
Receptor Interaction:
Agonist: Activates receptors for a full response (e.g., morphine).
Antagonist: Blocks receptors to inhibit a response (e.g., naloxone).
Partial Agonist: Activates with a reduced response (e.g., buprenorphine).
Drug-Drug Interactions:
Additive Effect (): Total effect is the sum of parts (e.g., Acetaminophen + Ibuprofen).
Synergistic Effect (1 + 1 > 2): Combined effect is greater than the sum (e.g., Alcohol + Benzodiazepines; Trimethoprim + Sulfamethoxazole).
Antagonistic Interaction: Drugs neutralize each other (e.g., Albuterol [Beta-agonist] + Propranolol [Beta-blocker]).
Adverse Drug Reactions (ADRs):
Beta-blockers: Can cause bradycardia by antagonizing cardiac beta cells.
ACE Inhibitors: Can cause a dry cough by blocking the conversion of Angiotensin I to II, leading to Bradykinin secretion in the lungs.
Organ Toxicity: Liver (statins, acetaminophen); Kidneys (NSAIDs, aminoglycosides).
Principles of Safe Medication Administration and Nursing Practice
Therapeutic Index (TI): The range between effective and toxic doses.
Wide TI: Safer (e.g., ibuprofen).
Narrow TI: Requires monitoring of peak and trough levels (e.g., warfarin, lithium).
Monitoring Parameters:
Onset: When effect begins.
Peak: Maximum effect.
Duration: How long effect lasts.
Half-life: Determines dosing frequency.
Factors Influencing Response:
Age: Neonates have immature organs; elderly have decreased function.
CYP450 System: Inducers (e.g., rifampin) decrease drug levels; Inhibitors (e.g., grapefruit juice) increase drug levels.
Pharmacogenomics: African American individuals may have lower baseline renin activity, making ACE inhibitors less effective. CYP2D6 poor metabolizers might find codeine ineffective.
Pregnancy Categories: Range from to , where Category is contraindicated due to teratogenicity.
Routes of Administration: Clinical Considerations and Patient Education
Oral (PO)/Enteral: Convenient but has slower onset and first-pass effect. Nursing: Ensure High Fowlers, check swallowing/tube placement. Education: No crushing XR/EC; follow food instructions.
Topical/Transdermal: Localized; avoids first-pass. Nursing: Rotate sites, wear gloves, apply to intact skin. Education: Do not cut patches.
Inhalation: Rapid absorption, targeted to lungs. Nursing: Assess breath sounds, rinse mouth post-use. Education: Use of spacers; rinse to prevent thrush.
Parenteral (IV, IM, SubQ, ID): Rapid onset (especially IV), bypasses GI. Nursing: Sterile technique, site rotation (e.g., for insulin).
Rectal/Vaginal: Useful when PO is contraindicated. Nursing: Sim’s position for rectal; use lubrication. Education: Lie down for after.
Questions & Discussion
Question: A nurse notices a patient is taking both Motrin and ibuprofen. What is the appropriate action?
Answer: Notify the provider; the patient is duplicating therapy (both are ibuprofen).
Question: What is the primary purpose of an adaptive cellular change in response to injury?
Answer: To enable cells to survive and maintain function under persistent stress.
Question: A pathology report indicates deranged cellular growth, varying size/shape, and describes it as precancerous. What is this?
Answer: Dysplasia.
Question: Alcohol abuse leading to fatty changes in the liver is what kind of injury?
Answer: Chemical injury.
Question: After 25 minutes of coronary artery occlusion, what is most likely?
Answer: Irreversible injury to cardiac muscle has begun (tolerance is ).
Question: Why does a diabetic patient develop vascular complications?
Answer: Endothelial injury via glycation and endothelin secretion.