LD

Phato-Pharm Week 2 Lecture

First Line of Defense

  • Definition: Physical barriers from mouth to anus (gastrointestinal tract), respiratory tract, and genitourinary tract acting as the initial barrier against pathogens.
  • Secretions and chemical defenses: mucus, saliva, tears; respiration-related secretions; lysosomes; defensins; collectins.
  • Exceptions: Some individuals are born with impaired first-line defenses (e.g., severe combined immunodeficiency, SID) — examples discussed include the “boy in the bubble.”
  • Concept to remember: First line is a barrier; second line is triggered when pathogens invade or injury occurs.

Second Line of Defense

  • Triggered by infection or trauma (inflammation) regardless of the injury type (e.g., sprained ankle, laceration, brain injury).
  • Purpose: Contain and eliminate the offending agent and begin restoration of homeostasis.
  • Early signs that inflammation is underway (clinical manifestations):
    • Local: redness (erythema), heat, swelling (edema), pain, loss of function.
    • Systemic: fever (systemic warmth from pyrogens).
  • Key processes involved: vascular changes (vasodilation, increased capillary permeability), plasma protein cascades, cellular infiltration, thrombosis (clotting), and nerve activation (pain).
  • Acute inflammatory response overview (from textbook slide):
    • Triggers: tissue injury or infection.
    • Early actors: mast cells, plasma proteins, macrophage activation.
    • Outcomes: vascular and cellular responses leading to the five classic signs and systemic effects when extensive.

Inflammation: Key Concepts and Mediators

  • Mast cells: central to initiating inflammation; release histamine upon activation.
    • Histamine receptors: H1 (pro-inflammatory) and H2 (anti-inflammatory, helps turn off inflammation).
    • Other mediators from mast cells: prostaglandins (pain and protection of the stomach lining), leukotrienes.
  • Prostaglandins: contribute to pain and inflammation; protective role in gastric mucosa; NSAIDs inhibit prostaglandin synthesis (trade-off: reduced pain but potential GI risk).
  • Bradykinin: another plasma protein mediator contributing to pain and vasodilation.
  • Pattern Recognition Receptors (PRRs): cellular receptors that detect danger signals.
    • Types of signals detected:
    • Pathogen-associated molecular patterns (PAMPs): indicate infection (e.g., bacteria).
    • Damage-associated molecular patterns (DAMPs): indicate tissue damage.
    • Receptor families mentioned: pattern recognition receptors, NOD-like receptors, toll-like receptors (and others referenced in class notes).
  • Cells involved in inflammation:
    • Macrophages (including specialized forms such as alveolar macrophages in the lung, microglia in the brain).
    • Natural killer (NK) cells: recognize and eliminate virus-infected or malignant cells; act in the circulatory system.
  • Cytokines and chemokines: signaling proteins that regulate inflammation.
    • Pro-inflammatory cytokines: IL-1, IL-6, TNF-α (and others like IL-6, IL-1, TNF). Promote fever and acute-phase reactions.
    • Anti-inflammatory cytokines: IL-10, others; help terminate inflammation.
    • Chemokines: promote phagocytosis and wound healing by recruiting immune cells.
  • Leukotrienes and prostaglandins as inflammatory mediators; leukotriene modifiers may be used in asthma/COPD to modulate respiratory inflammation.
  • Complement system: a group of plasma proteins that augment inflammation and assist in pathogen clearance.
  • Exudates and wound fluids (as part of inflammation):
    • Serous exudate: clear, watery; few cells.
    • Serosanguineous: thin, pink-tinged fluid (water + blood).
    • Sanguineous/hemorrhagic: bloody drainage.
    • Fibrous exudate: thick, fibrous material.
  • Acute-phase reactants often monitored in labs, e.g., C-reactive protein (CRP); elevated CRP indicates inflammation.
  • Systemic inflammatory response: fever, tachycardia, leukocytosis (WBC >
    10{,}000/$ ext{µL} commonly cited as upper normal range), pain, and other signs depending on the pathogen and tissue involved.
  • The inflammatory response is essential for survival, but it must be tightly regulated; prolonged or excessive inflammation can be life-threatening.

Wound Healing and Exudate in Inflammation

  • Wound healing concepts:
    • Primary intention: clean, well-approximated edges; minimal tissue loss.
    • Secondary intention: significant tissue loss; healing via granulation tissue, epithelialization, and remodeling.
  • Phases of wound healing:
    • Inflammation (initial)
    • Proliferation: granulation tissue formation and epithelialization
    • Remodeling (maturation): collagen realignment and scar formation
  • Scar types and collagen issues:
    • Normal scar vs hypertrophic scar vs keloid.
    • Contractures can occur with severe burns (third/fourth degree) limiting movement.
  • Factors affecting wound healing:
    • Ischemia (reduced blood flow) can lead to tissue death.
    • Excessive bleeding, comorbidities (e.g., diabetes) slow healing due to poor perfusion and neuropathy.
    • Ischemia can cause hypoxia and necrosis in wounds.
  • Complications in healing:
    • Dehiscence: wound edges separate, sometimes due to poor suture technique or poor skin health (ischemia, necrosis).
    • Infection and pus formation indicate healing problems.
  • Anti-inflammatory medications and wound healing:
    • NSAIDs and other anti-inflammatories reduce inflammation and pain but can impact healing if overused; they also can cause GI irritation via prostaglandin inhibition.

Anti-Inflammatories: Mechanisms and Counseling

  • Trade-offs of anti-inflammatory drugs:
    • Prostaglandin inhibition reduces pain and inflammation but can compromise gastric mucosal protection.
    • Analgesic and antipyretic effects; some have anticoagulant properties via platelet inhibition.
  • Aspirin (acetylsalicylic acid):
    • Roles: anti-inflammatory, analgesic, antipyretic, and anticoagulant.
    • Important safety note: Avoid giving aspirin to children due to risk of Reye syndrome after viral infections.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs):
    • Common examples: ibuprofen, naproxen.
    • Mechanism: inhibit cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis.
    • Uses: relief of inflammation and pain; particularly useful for musculoskeletal conditions (e.g., osteoarthritis, rheumatoid arthritis, gout).
    • Dosing considerations: NSAIDs may be prescribed at higher doses than OTC formulations; use as needed during flares rather than daily for chronic conditions unless advised.
  • COX-2 inhibitors (selective NSAIDs):
    • Example: celecoxib.
    • Intended to reduce GI side effects, but still require caution.
  • Special dosing and administration notes:
    • Some NSAIDs are enteric-coated or extended/sustained-release to minimize gastric irritation; do not crush these forms.
    • Some drugs interact with alcohol; avoid alcohol while taking certain NSAIDs and antibiotics, and be mindful of interactions with other meds.
  • Pharmacist/clinician counseling themes:
    • Assess patient medications for interactions and organ function (renal and hepatic) prior to NSAID use.
    • Check for history of peptic ulcer disease, bleeding disorders, and peripheral edema.
    • Explain that annual vaccination and travel-related immunizations may require adjustment of medications or timing.
    • For DMARDs and anti-rheumatic drugs, note immunosuppressive potential and infection risk.
  • Disease-modifying antirheumatic drugs (DMARDs):
    • Immunosuppressive and disease-modifying; include various antimalarials and other agents.
  • Gout-specific medications:
    • Colchicine as an anti-inflammatory option for gout.

Immunizations, Immunity, and Vaccines

  • Active acquired immunity: obtained through exposure to antigens or vaccinations; generates long-lasting immune memory.
  • Passive acquired immunity: transferred antibodies (e.g., maternal antibodies to infant); temporary.
  • Immunoglobulin (Ig) classes (overview from notes):
    • IgG: most abundant antibody in serum; provides long-term immunity.
    • IgE: triggers allergic responses.
    • IgM: large, early antibody; initial response to infection.
    • IgA: found in secretions (mucosal surfaces: saliva, tears, etc.).
    • IgD: less well characterized; participates in B-cell receptor activity.
  • Herd immunity: higher vaccination rates in a population reduce transmission risk and protect those who are not vaccinated.
    • Conceptual example: if many are vaccinated and protected, the pathogen struggles to spread, lowering risk to others.
  • Vaccination schedules and travel considerations:
    • CDC immunization schedules exist for children (birth to 18) and adults.
    • Typical infant vaccines (examples discussed): Hepatitis B, Rotavirus, DTaP, Haemophilus influenzae type b (Hib), Pneumococcal conjugate vaccine, Inactivated Poliovirus, influenza; catch-up schedules exist for those behind.
    • Travel vaccines and measles/mumps/rubella (MMR), yellow fever, rabies, hepatitis A, hepatitis B, etc., may be required or recommended depending on destination; CDC travel pages provide country-specific requirements.
    • Annual influenza vaccination recommended for all individuals aged 6 months and older.
    • Pneumococcal vaccines recommended for older adults (e.g., 65+).
    • Flu vaccine production considerations: vaccine strain drift vs shift; major shifts (e.g., H1N1) can require reformulation for subsequent seasons.
  • Vaccine safety and administration:
    • Most vaccines have mild, expected reactions (low-grade fever, soreness at injection site).
    • Contraindications exist; keep an up-to-date vaccination record and assess safety and timing for each patient.
  • Immunization terminology and testing:
    • Direct measurement of antibody classes and responses can guide immunization decisions and anticipated protection.

Infection: Transmission, Stages, and Pathogens

  • Transmission pathways: direct vs indirect contact; portals of entry/exit; environmental reservoirs.
  • Communicability vs infectivity vs pathogenicity:
    • Communicability: how easily a pathogen spreads between people.
    • Infectivity: ability to invade and multiply within a host (probability of infection after exposure).
    • Pathogenicity: ability to cause disease once infection occurs.
  • Stages of infection:
    • Incubation period: time from exposure to first signs/symptoms; varies by pathogen.
    • Example: chickenpox incubation ~14-21 days; exposure at an airport may lead to symptoms 2-3 weeks after exposure.
    • Illness phase: symptomatic period with targeted symptoms.
  • Examples of pathogens:
    • Bacteria: can produce toxins; Staphylococcus aureus cited as an example.
    • Viruses: common cold is the most common viral infection in adults; influenza season considerations.
    • Fungi: fungal infections such as candidiasis discussed; travel- and environment-related exposures.
  • Antiviral, antibacterial, and antifungal considerations:
    • Antibiotics target bacteria; not effective against viruses (misuse can lead to resistance).

Antibiotics: Mechanisms, Dosing, and Resistance

  • Key distinctions:
    • Bacteriostatic: inhibits bacterial growth (needs host immune system to clear infection).
    • Bactericidal: kills bacteria outright.
  • Minimum Effective Concentration (MEC): the lowest concentration of an antibiotic needed to stop growth or kill bacteria; used to guide dosing.
  • Dosing examples and variability:
    • Amoxicillin for strep throat: typical dosing in children may be 40-45\,\text{mg/kg/day}; for otitis media, 85-90\,\text{mg/kg/day} (varies by infection and patient factors).
  • Cultures and sensitivities:
    • Start broad-spectrum therapy initially, then tailor to the pathogen once culture and sensitivity results return.
    • Combination therapy vs synergistic effects: sometimes combining antibiotics yields a greater effect than either alone (e.g., amoxicillin + clavulanate forming Augmentin).
    • Resistant pathogens and healthcare-associated infections (HAIs).
  • Adverse effects and safety considerations:
    • Allergies/hypersensitivity (rash, itching; risk of anaphylaxis).
    • Superinfection and organ toxicity risks.
    • Narrow-spectrum, broad-spectrum, and extended-spectrum classifications.
  • Common antibiotic classes and examples mentioned:
    • Penicillins: amoxicillin (broad-spectrum); penicillinase-resistant variants; extended-spectrum penicillins.
    • Cephalosporins: five generations; multiple oral forms.
    • Macrolides: erythromycin; azithromycin (Z-Pak).
    • Oxazolidinones and related agents (e.g., linezolid) discussed generally.
    • Lipoglycopeptides and lipopeptides: vancomycin, daptomycin (for MRSA and resistant organisms).
    • Tetracyclines: doxycycline.
    • Fluoroquinolones: ciprofloxacin (used for various infections, including considerations for anthrax exposure historically).
    • Antimalarials and other agents mentioned in broader context (e.g., chloroquine); not primary targets for bacterial infections.
  • Important clinical notes:
    • Avoid combining certain antibiotics unless synergistic benefit is expected.
    • Consider drug-specific cautions (e.g., fluoroquinolones in certain populations; avoid in pregnancy depending on agent).
    • Always consider patient-specific factors (allergies, kidney/liver function, drug interactions).

Practical Considerations for Practice

  • Medication reconciliation:
    • Always obtain a current medications list from patients to assess interactions and contraindications (renal or hepatic impairment affecting excretion/metabolism).
  • Infection control implications:
    • Recognize stages of infection for appropriate isolation and public health considerations.
  • Documentation importance:
    • For wound care, document drainage type (serous, serosanguineous, sanguineous, purulent) and dressing changes frequency.
  • Patient education themes:
    • Clarify when to take NSAIDs (flare-ups vs daily use), hydration, stomach protection with prostaglandin considerations, and the need to avoid NSAIDs in certain ulcer conditions.
    • Explain vaccine benefits, safety, possible mild reactions, and travel vaccine requirements.
    • Emphasize the need to complete prescribed antibiotic courses (unless directed otherwise) and report adverse effects.