Lecture Notes: Inflammation, Infection, and Pharmacology Review
Major Concerns
- Colonization: act of establishing presence
- Agents of Disease: Inflammation and Infection
Characteristics of Organisms
- Infection: presence and multiplication in host
- Infectivity: ability to invade and multiply
- Mutualism: organism and host derive benefits from each other
Terms
- Opportunist pathogens: prey on host with weak immune system
- Virulence: severe disease producing ability
- Toxigenicity: ability to produce soluble toxins
Bacteria and Virus
- Bacteria: killed by antibiotics; examples include E. coli, anthrax
- Virus: antivirals; HIV, Hepatitis, rhinovirus
Panculture
- Broad culture sampling from blood, sputum, urine, wound, stool, etc. covers infection sources
- Growth in 24 hours prompts consideration of antibiotics; final at 48 hours helps determine meds
Environment
- Germs like hot, humid, moist areas
- Airborne: TB, anthrax (droplet spread for others e.g., COVID)
- Contaminated food
- Seasonal patterns: flu
- Dense populations: colleges, campuses, schools
- Contaminated water
- Blood-borne: HIV
Diagnosis
- Culture
- Serology: study of plasma/serum
- Monoclonal Antibodies: lab-made proteins that mimic antibodies and target specific diseases; effective with COVID
Systemic Manifestations
- Anorexia
- Arthralgia
- Myalgia
- Fever
- Headache
- Tachypnea
- Tachycardia
Leukocytosis Manifestations
- Systemic treatment vs localized treatment
- Cytokine release can cause shock, organ failure, death
- White blood cells should be 4{,}000-10{,}000 per mm³
- Infection is present if white blood cells are elevated
- Triggers: Stress, leukemia/lymphoma, burns and trauma, meds (heparin, steroids)
- Smoking
Acute Phase
- Begins within hours of inflammation
- Localized inflammation may progress to lymphatic involvement; lymph nodes may enlarge and be painful
- Acute phase proteins released from liver: Fibrinogen, CRP, and serum amyloid A (SAA)
- Stimulated by cytokines
- Body ramps up acute phase before illness is subjectively felt
Pyrexia
- Fever
- Antipyretics used to reduce fever
- Prostaglandins: mediator chemicals released during trouble; promote fever, pain, inflammation
- Prostaglandins produced via COX pathways; early signals include inflammation, pain, fever
- Ibuprofen blocks prostaglandins (reduces fever/inflammation) but may affect other protective processes
- Hypothalamus acts as the body's thermostat
- Fever ↑ metabolism: higher heart rate, blood pressure, digestion changes; may necessitate more fluids and medication adjustments
- Prodromal phase: nonspecific complaints
Cells of Inflammation
Chronic Inflammation
- (Conceptual level; ongoing inflammation can lead to tissue damage and remodeling)
Wound Healing
- Phases: Inflammatory Phase, Proliferative Phase, Remodeling Phase
- Chill, vasoconstriction to limit spread; flushing; defervescence (heat redirected to surface)
- Acute Response: endothelial cells regulate vessel diameter; platelets accumulate
- WBCs: neutrophils are primary responders; CBC with differential (diff) used to assess shift
- Monocytes/macrophages produce prostaglandins, leukotrienes, platelet-activating factor, and cytokines
- Vascular changes: initial vasoconstriction to contain; subsequent vasodilation to recruit more cells;↑ blood pressure locally; mediators drive inflammation
- Prolonged irritation or foreign body presence sustains inflammatory mediators
- Phases of healing: Inflammatory Phase → Proliferative Phase (cell production) → Remodeling Phase (scar formation)
- Remodeling can result in abnormal scar formation (keloids)
Factors Affecting Healing
- Nutrition
- Age
- Immunocompromised status
- Blood flow
- Infection presence
Chain of Transmission (Infection Control)
- Destroy the reservoir
- Block the portal exit
- Block the transmission
- Block portal entry
- Reduce victim susceptibility
H1 Antagonists
- Therapeutic uses: mild allergy; severe allergy (adjunct); motion sickness; insomnia; common cold (anticholinergic effects reduce rhinorrhea)
- Adverse Effects: sedation (less with newer generations); non-sedative CNS effects (dizziness, fatigue, coordination problems, confusion); GI effects (nausea, vomiting, loss of appetite, constipation)
- Overuse risk: excessive diphenhydramine associated with increased dementia risk
- Drug interactions
Anticholinergic Considerations and Second Generation Antihistamines
- Anticholinergic effects: sympathetic nervous system actions; avoid with certain fruit juices; CNS depressant effects; caution in pregnancy/lactation
- Acute toxicity: wide safety margin; generally accessible; CNS and anticholinergic reactions possible; children may exhibit CNS excitement; severe cases can cause coma or cardiac issues
- Management: supportive care; activated charcoal; cathartics; seizures treated with IV benzodiazepines; hyperthermia managed with cooling
- Second-generation antihistamines: less sedation; cross the blood-brain barrier poorly
- Cetirizine (Zyrtec), Fexofenadine (Allegra), Loratadine (Claritin) among typical examples
- Often taken orally; improved safety/efficacy profile
- Some products advise avoiding certain foods or timings for absorption
- Paradoxical reactions can occur in some patients
Glucocorticoid Drugs
- Metabolic effects: elevated blood glucose due to cortisol; monitor for hyperglycemia
- Potassium: risk of hypokalemia
Cyclooxygenase Inhibitors (and Corticosteroids)
- Anti-inflammatory effects; include corticosteroids
- Salt and water retention: edema risk
- Musculoskeletal effects: reduced muscle mass; decreased bone matrix; thinning of skin
- Interferes with tissue healing
- Redistribution of fat: moon face, buffalo hump
- Possible retinopathy/retinol effects
Nonendocrine Disorders
- Cardiovascular effects: low dose may increase capillary permeability and alter vasoconstriction; potential blood pressure changes
- Possible decreases in RBC and WBC counts
Stress Effects
- During stress, adrenal glands secrete glucocorticoids and epinephrine to maintain BP
- Prolonged stress can lead to adrenal gland atrophy and glucocorticoid insufficiency
- In severe stress, risk of circulatory failure and death
- Patients can become steroid-dependent and may struggle to raise BP after stress without steroids
Pharmacology (Anti-Inflammatory/Immunomodulatory Use)
- Primary uses: anti-inflammatory, analgesic, antipyretic
- Indications: rheumatoid arthritis, lupus, inflammatory bowel disease
- Overuse can suppress immune response
- Consider potential drug interactions
Uses
- Anti-inflammatory, analgesic, antipyretic roles; broad therapeutic applications
Adverse Effects
- Gastric ulceration
- Bleeding
- Renal impairment