Introduction to Pathophysiology + Pharmacology PDF

***Introduction to Pathophysiology + Pharmacology:*** [Process of Disease: ] - Etiology -- the underlying cause or origin of a disease - Pathogenesis -- development of the disease - Diagnosis -- identification of disease - Clinical course -- the natural progression of the disease over t...

***Introduction to Pathophysiology + Pharmacology:*** [Process of Disease: ] - Etiology -- the underlying cause or origin of a disease - Pathogenesis -- development of the disease - Diagnosis -- identification of disease - Clinical course -- the natural progression of the disease over time Pharmacokinetics What the body does to the drug -- how the body absorbs, distributes, metabolizes + excretes a drug ------------------ ---------------------------------------------------------------------------------------------------- Pharmacodynamics What the drug does to the body \*factors such as age, sex/gender, culture, genetics + health status influence how drugs are processed + their effects on the body\* [Dynamic Equilibrium of Drug Concentration: ] - The actual drug concentration in the body is determined by the balance between: - Absorption -- entry of the drug into circulation - Distribution -- transport of drug to tissues - Metabolism -- conversion of drug into active/inactive forms (occurs in liver) - Excretion -- elimination of the drug (occurs in kidneys) - *Critical concentration* -- the amount of the drug needed to cause desired therapeutic effect - *Half-Life* -- the time it takes for the amount of drug in the body to decrease to ½ of its peak level - Knowing the half-life helps in predicting dosing schedules - *Steady-state* concentration is the time during which the concentration of the drug in the body stays consistent -- when the drug concentrations consistently stay within therapeutic limits [Drug Interactions: ] - Drug-Drug -- when 2 drugs enhance or inhibit each other's effects - Drug-Alternative Therapy -- interactions with supplements or herbal remedies - Drug-Food -- food can alter drug absorption or metabolism (grapefruit juice) [OTC Drugs: ] - OTC drugs are convenient, accessible + cost-effective for treating minor conditions - The \#1 thing to consider with OTC drugs is overdose!!! ***Cellular Regulation:*** [Cellular Changes: ] - *Atrophy* -- decrease in cell size - *Hypertrophy* -- increase in cell size - *Hyperplasia* -- increase in the number of cells - *Dysplasia* -- abnormal cell growth of a specific tissues can turn into cancer if not controlled - *Metaplasia* -- replacement of adult cells [Cell Injury: ] - Causes: - Physical -- trauma, temperature extremes - Chemical - toxins, drugs - Biological -- pathogens, viruses, bacteria, infections - Nutritional imbalances -- deficits - Mechanisms: - Free radicals and reactive oxygen species disrupt cellular homeostasis by damaging membranes, proteins + DNA - If there is an imbalance between free radical production + antioxidant defenses, it leads to oxidative stress, contributing to chronic diseases - Hypoxic Cell Injury: - Deprives cells of oxygen + interrupts oxidative metabolism and ATP generation - Leads to cellular swelling (edema) + eventual cell death - Causes could be from ischemia, respiratory disease or inability of the cells to use oxygen [Cell Death:] - Apoptosis -- programmed, regulated cell death - Self-destruction - Eliminates cells that are worn out, have been produced in excess, have developed improperly or have genetic damage - Necrosis -- unregulated cell death resulting from injury - Typically occurs after ischemia, infection or toxin exposure [Homeostasis & Stress Response: ] Homeostasis Maintenance of stable internal conditions ------------- ------------------------------------------------------------------ Allostasis Adaptive response to stress to maintain stability through change - General Adaptation Syndrome Stages - Alarm stage -- sounds the alarm -- "fight or flight" response - Resistance stage -- resists against the stressor - Exhaustion stage -- where disease occurs -- body systems begin to fail - Stress Responses: - Autonomic Nervous System - sympathetic activation increases heart rate, blood pressure + respiratory rate - Endocrine System -- releases cortisol + other hormones to manage stress - Immune System -- chronic stress suppresses immunity - Musculoskeletal System -- causes tension + muscle fatigue - Physiologic Adaptation to Stress - Short term stress enhances survival by mobilizing energy + increasing alertness - Chronic stress can lead to altered physiological + psychological factors ***Immunity, Infection + Inflammation:*** [Inflammation: ] - ***Cardinal Manifestations*** -- - Rubor (redness), tumor (swelling), calor (heat), dolor (pain), loss of function, fatigue - *Acute inflammation* -- relatively short duration + occurs rapidly in response to an injury or infection -- 2 phases - *Vascular* -- involves increased blood flow + changes in the small blood vessels within the microcirculation - Vasodilation increases blood flow to the area which causes redness + warmth - Increased vascular permeability allows plasma proteins + fluids to leak into the tissues causing swelling + pain - *Cellular* -- focuses on the recruitment + activation of leukocytes to the site of injury - *Chronic inflammation* -- longer duration + often has less noticeable symptoms - **Inflammatory Mediators** -- - *Plasma-derived (liver)* - Coagulation factors, complement proteins + kinins - *Cell-derived (WBCS, platelets, endothelial cells)* - *Histamine* -- part of inflammatory response - Produced by basophils + mast cells - Dilates arterioles by stimulating release of nitric oxide - Increases permeability of capillaries to allow WBCs + proteins so that they can enter the tissues - *Prostaglandins* -- induces vasodilation + inhibits platelet aggregation - *Cytokines* -- induce adhesion to endothelial cells promoting migration to injury sites - Has systemic effects such as fever, hypotension, tachycardia + release of neutrophils - Lymphadenopathy (swollen lymph nodes) occur as part of the inflammatory response during illness [Immunity: ] - *Innate Immunity* -- present at birth -- 1^st^ (barriers) + 2^nd^ (inflammation) line of defense - Non-specific, immediate response, short-lived, no memory - Involves physical barriers, phagocytic cells + complement proteins - *Key Mediators:* - Physical + chemical barriers - Cellular mediators -- phagocytes + NK cells - Inflammatory mediators -- cytokines (recruit immune cells to site), histamine + complement proteins - *Adaptive immunity* -- acquired through exposure -- 3^rd^ line of defense - Specific, slower response, long-term, memory - Involves T + B cells with memory for future encounters - *Key Mediators:* - Antigen-presenting cells -- processes. + presents antigens to T cells - Lymphocytes - B cells -- releases antibodies + neutralizes pathogens + marks them for destruction - T cells -- helper (activates B cells, cytotoxic T cells + macrophages through cytokine release) + cytotoxic (kill infected or abnormal cells directly) - Cytokines -- regulates + amplifies the adaptive response - Antibodies -- binds to antigens, neutralizing pathogens + facilitating their destruction - *Primary Immune Response* -- occurs during the 1^st^ exposure to an antigen - T cells activate B cells B cells produce antibodies antibody levels rise (produces IgM first, then IgG) - Can take 2-3 weeks - Produces memory cells for future protection - Ex: vaccination or first exposure to pathogen - *Secondary Immune Response* -- occurs during subsequent exposure to the same antigen - B memory cells respond very quickly antibody levels rise in large quantities (IgG) - Faster + stronger response - Provides long-lasting immunity + better pathogen elimination - Ex: booster dose of vaccine or second exposure to a pathogen - *Antibodies:* - IgA -- found in secretions + on mucous membranes -- prevents antigens from entering the body - IgD -- found on the surface of B cells -- acts as antigen receptor - IgE -- found on mast cells in tissues -- starts an inflammation - IgM -- circulates in body fluids -- forms large complexes by clumping antigens together -- 1^st^ to respond to acute infection - IgG -- circulates in body fluids (most abundant) -- provides long-term immunity by targeting antigens, neutralizing toxins + enhancing phagocytosis - *Hypersensitivity Immune Reactions:* - Type I -- immediate hypersensitivity - Mediated by IgE - Ex: food allergies, hives, anaphylaxis - Type II -- antibody-mediated (cytotoxic) - IgG or IgM attacks antigens on cell surface - Ex: hemolytic anemia, transfusion reaction - Type III -- immune-complex mediated - Mediated by antigen-antibody immune complexes - Triggers inflammation + tissue damage - Ex: lupus, rheumatoid arthritis - Type IV -- cell-mediated (delayed) - Mediated by T cells - Leads to cell lysis - Ex: contact dermatitis, transplant rejection - *Immunodeficiency:* - Inadequate immune response due to impaired function or insufficient production of immune factors - Genetic -- mutation that causes decreased production or poorly functioning components of the immune response - Acquired -- caused by another disease - *Autoimmunity:* - The immune system attacks self-antigens + destroys body's tissues - *Course of Infectious Illness:* - Incubation Period -- time between exposure + symptom onset - Prodromal Phase -- non-specific symptoms - Illness Phase -- specific symptoms of the disease - Convalescence Phase -- recovery + resolution of symptoms [Antibiotics: ] +-----------------------------------+-----------------------------------+ | Bactericidal | Agents that kill bacteria + | | | inhibits cell well synthesis, | | "cidal" = kill | disrupts cell membrane | +===================================+===================================+ | Bacteriostatic | Agents that prevent the growth of | | | bacteria + inhibits DNA | | "static" = stop | synthesis, protein synthesis or | | | blocks metabolism | +-----------------------------------+-----------------------------------+ - *[Broad-spectrum]:* effective against may bacteria species, both Gram-positive + Gram-negative - Targets a broad range of bacteria - Leads to resistance - *[Narrow-spectrum:]* effective against a very limited number of bacterial species - Used as targeted therapy when bacterial pathogen is known - Less likely to lead to resistance - *[Peaks:]* typically measured shortly after administration to check the highest concentration of a drug in the bloodstream - *[Troughs:]* typically checked right before administration of the next dose to check the lowest concentration of a drug in the bloodstream [Complications of Antibiotics: ] - **Pseudomembranous Colitis** -- overgrowth of C. diff due to disruption of normal gut flora - Symptoms - severe diarrhea, abdominal pain, fever - Risks -- broad-spectrum antibiotics - **C. diff Infection** -- antibiotics kill normal gut bacteria, allowing C. diff to flourish - Symptoms -- watery diarrhea, cramping, fever - **Stevens Johnson Syndrome** -- rare, severe hypersensitivity reaction to certain antibiotics - Symptoms -- painful rash, skin blistering, fever, systemic symptoms - Can progress to toxic epidermal necrolysis if severe