Essentials of Pathophysiology & Pharmacology Mediation Errors and Safety in Drug Administration

What is pathophysiology?

The study of structural and functional alterations in cells, tissues, and organs leading to disease. It encompasses both causes and risk factors

Etiology

The precise cause or origin of a disease state (e.g., biological, chemical, genetic)

Idiopathic disease

Diseases with unknown causes

Multifactorial disease

Diseases with multiple contributing variables

The Disease Progression

The full progression of signs and symptoms from onset until resolution, transition to a chronic state, or death

Acute diseases

Short duration, resolve within 2 weeks

Subacute diseases

Last 2 weeks to 6 months

Chronic diseases

Last over 6 months, often lifetime

Pathogenesis

Step-by-step structural/cellular development of a disease from exposure through progression

Incubation & Early Infection

(day 1-10) highly contagious period

Pulmonary Phase

Virus spreads to lower respiratory tract and infects type II alveolar cells via ACE2 (covid) Impaired gas exchange → ↓ oxygenation

Hyper-inflammatory Phase (severe disease)

Excessive immune response leading to a severe cytokine storm

Clinical manifestations

signs and symptoms of a disease; direct result of pathophysiology

Signs

observable and measurable (e.g., fever, cough)

Symptoms

subjective and recognized only by the patient (e.g., dyspnea, pain, fatigue)

Asymptomatic state

Infection present without overt clinical signs or symptoms (e.g., COVID-19)

Syndromes

a collection or recognizable pattern of medical signs, symptoms, and laboratory findings that consistently occur together

Symptoms of UTI

Dysuria, fever, confusion, fatigue, urinary frequency

Symptoms of respiratory tract infection

Tachypnea, wheezing, low oxygen saturation, fever, fatigue, cough, pain

Symptoms of systemic inflammatory (rheumatoid arthritis)

Fever, malaise, pain, swelling, and elevated inflammatory biomarkers

Disease complications

unexpected, negative outcomes resulting from disease progression, medical procedures, or treatments

Disease-related complications

Result from progression of the underlying disease.

• Myocardial infarction → Heart failure
• Type 2 diabetes → Renal failure

Iatrogenic complications

Caused unintentionally by medical care or treatment.

• Hospital-acquired infections (HAIs)
• Medication adverse effects
• Post-procedure complications
• Iatrogenic delirium

Mortality

The number of deaths within a specific population

Morbidity

The overall impact of disease on patient health and quality of life

DALYs

Disability-Adjusted Life Years measures total burden by combining years lost to premature death and disability.

DALY = Years of Life Lost (YLL) + Years with Disability (YLD)

Diagnosis

the identification and labeling of a disease based on signs and symptoms, health history, physical examination, laboratory tests, and diagnostic studies

Diagnostic testing

Used to confirm, rule out, or evaluate disease processes and progression

Prognosis

• Predicted course and outcome of a disease

• Depends on disease type, severity, and patient factors

Disease management

Strategies to treat disease, reduce symptoms, and prevent complications

Primordial

Addressing broad social, economic, and environmental conditions to minimize health hazards

Primary prevention

Action taken to prevent disease occurrence (e.g., vaccination, hand hygiene, health education)

Secondary prevention

Early detection of disease by screening ((e.g., rapid antigen screening, routine mammograms)

Tertiary prevention

Minimizing the impact of existing conditions and preventing complications (e.g., pulmonary or cardiac rehabilitation, chronic illness management)

Antivirals target the…

virus

Anti-inflammatory therapies target…

the immune response

Monoclonal antibodies

Provide temporary passive immunity by blocking pathogens

Vaccines

Stimulate the body's own immune response for longer-term protection

Nutritional therapy

Supports health and may reduce risk factors

• Example: Vitamin D deficiency associated with increased COVID-19 severity risk

Non-pharmacologic therapies

Physical/occupational therapy, oxygen, complementary therapies

Surgical therapy

Treats specific disease conditions

Endemic

Persistent, baseline level of a disease within a specific geographic area or population (malaria, seasonal flu, chicken pox)

Epidemic

Sudden, unexpected increase in disease cases above normal baseline levels (ebola, measles, SARS, opioid overdoses)

Pandemic

Epidemic spread across multiple countries, continents, or worldwide (e.g., Covid-19 pandemic declared by WHO on March 11, 2020, first pandemic declaration since H1N1 influenza in 2009)

Incidence

Rate of new cases diagnosed over a specific timeframe (e.g. Heart disease responsible for 1 in every 5 deaths )

Prevalence

Total existing cases (new + old) in a population at a specific point in time (e.g., over 607 million confirmed COVID-19 infections worldwide (Nov 2018- Sep 2022)

Pharmacology

The study of chemicals and active biological agents that interact with living organisms to produce functional changes

• Includes the origin of the drug and chemical composition

• Covers pharmacokinetics and pharmacodynamics

Pharmacokinetics

How does the body process the drug? ADME: Absorption, Distribution, Metabolism, Excretion

Pharmacodynamics

How does the drug affect the body? Receptor binding, enzyme inhibition, post-receptor effects

Pharmacogenetics

Study of how individual genetic variations influence personal response to specific medications

• Variability in drug responses: Different individuals and ethnicities

• Identify factors impacting therapeutic effects: Higher risk for adverse reactions and side effect

Chemical name

Describes exact chemical and molecular structure (e.g., 1-(isopropyl amino)-3-(1-naphthyloxy) propan-2-ol (chemical name for propranolol)

Generic name

Official non-proprietary name assigned by USAN (e.g., acetaminophen, ibuprofen, alprazolam,  metformin, diphenhydramine)

Brand/trade name

Proprietary name chosen by the pharmaceutical manufacturer (e.g., Tylenol, Motrin, Advil, Xanax, Glucophage, Benadryl)

Black box warnings

Highest level of FDA safety alert, indicating risks of severe, life-threatening adverse reactions

Teratogenic risks

Ability of a drug or chemical agent to cause irreversible structural defects in a developing fetus

Absorption

How drugs enter the body and bloodstream

Distribution

How drugs travel throughout the body

Metabolism

How the body transforms drugs

Excretion

How drugs leave the body

Disintegration

Breakdown of oral drug form into small particles

Dissolution

Combining small drug particles with liquid to form a solution

Active transport

Requires energy and carrier substance (enzyme)

Pinocytosis

Cell carries drug across membrane by engulfing drug particles

Drug solubility

Ability to dissolve

Concentration

High concentration gradients speed absorption

Circulation

Blood flow at the administration site

Mucosal integrity

State of the absorptive surface

Local pH

Affects ionization and transport

First-pass effect

A critical hepatic process for orally administered drugs:

"Orally administered drugs pass from the gastrointestinal tract through the portal vein to the liver."

Bioavailability

The percentage (%) of active drug reaching systemic circulation intact

Oral route bioavailability

< 100% Typically

Reduced significantly by incomplete gastrointestinal absorption and first-pass hepatic degradation

Oral / Enteral Tube (PO/NG/G-Tube)

Direct GI delivery. Subject to first-pass hepatic metabolism.

• Clinical Care: Flush tubes before, between, and after each medication. Never crush enteric-coated (EC) or extended-release (ER/XR) formulations.

Sublingual/buccal

Rapid absorption via oral mucosa directly into systemic circulation.

• Clinical Care: Bypasses first-pass metabolism without an invasive injection. (e.g., Nitroglycerin, SL Fentanyl)

Transdermal/topical

Applied to skin or mucous membranes for local or systemic effect. Bypasses first-pass metabolism.

• Clinical Care: Always remove old patches before applying new ones; clean skin and rotate application sites to prevent skin breakdown or inadvertent overdose

Intradermal (ID)

injection into dermis; slow local absorption. (e.g., TB skin test/Mantoux, allergy testing)

Subcutaneous (SubQ)

Injection into adipose tissue; slow, sustained systemic absorption. (e.g., Insulin, Heparin, Enoxaparin)

Intramuscular (IM)

Injection into deep muscle tissue; rapid systemic absorption due to high vascularity. (e.g., Vaccines, long-acting antipsychotics)

Intravenous (IV)

Direct vascular infusion; 100% immediate bioavailability with zero absorption delay. (e.g., Emergency resuscitation, continuous infusions)

Perfusion dependency

Well-perfused organs (heart, liver, kidneys, brain) receive rapid distribution.Poorly perfused tissues (fat, bone, skin) receive drug slowly

Plasma protein bound drugs

medications that attach to proteins in the blood, primarily albumin

Free (unbound) drugs

the active form of a medication in the bloodstream. They are not bound to plasma proteins and can move freely to: Cross cell membranes, Bind to receptors, Exert therapeutic or toxic effects, Undergo metabolism and elimination

Bound Fraction

Drug bound to plasma protein (primarily Albumin) is pharmacologically inactive

Free Fraction

Unbound active drug capable of crossing cell membranes to exert effects

Hypoalbuminemia Risk

Low plasma albumin levels create higher unbound free fractions, raising toxicity risk.

Blood flow

Abscesses, exudates, glands, & tumors decrease distribution

Blood Tissue Affinity

Some drugs accumulate in fat, bone, liver, muscle, & eye tissue (e.g., amiodarone – can cause lung toxicities)

Primary site of metabolism

Liver

• Liver enzymes convert or transform drugs to inactive metabolites or water-soluble substances for excretion

Half-life

Time it takes for ½ drug concentration to be eliminated

• Metabolism affects ½ life

• Liver dysfunction prolongs ½ life

Short Half-Life (e.g., 1–2 hours)

The body eliminates the drug rapidly. To maintain a therapeutic concentration, the medication must be given frequently throughout the day or via continuous IV infusion. Heparin requires continuous IV infusion or frequent dosing

Long Half-Life (e.g., 24+ hours)

The drug remains in systemic circulation for an extended period, requiring less frequent administration.Example: Levothyroxine (half-life approx 7 days) is dosed only once daily

Main route of excretion

the kidneys

Other routes include: 

• Liver, bile, feces, lungs, saliva, sweat, & breast milk

• Kidneys filter free unbound drugs, water-soluble drugs and unchanged drugs

• Protein-bound drugs can not be excreted via kidneys

Creatinine Clearance

a lab test that shows how well the kidneys are working, specifically how well they are clearing creatinine from the blood and sending it out in the urine ( same as glomerular filtration rate )

Pharmacodynamics is

the study of the way drugs affect the body

Stimulation

The drug increases the activity of a specific organ or system.

• Example: Adrenaline stimulates the heart and increases heart rate and blood pressure

Depression

The drug reduces or slows down normal activity of a body system.

• Example: Benzodiazepines (e.g., diazepam) depress the central nervous system, leading to sedation or reduced anxiety

Irritation

The drug causes mild inflammation or stimulation at the site of action.

• Example: Laxatives (e.g., bisacodyl) irritate the intestinal lining to stimulate bowel movement

Replacement

The drug replaces missing or deficient substances in the body.

• Example: Insulin is used in people with diabetes to replace insufficient natural insulin. Thyroxine for hypothyroidism

Cytotoxic action

The drug kills specific cells, often cancer or rapidly dividing cells.

• Example: Chemotherapy drugs like cyclophosphamide destroy cancer cells

Antimicrobial action

The drug kills or inhibits the growth of microorganisms like bacteria, viruses, or fungi.

• Example: Antibiotics like penicillin kill bacteria

Modification of immune status

The drug either boosts or suppresses the immune system.

• Example: Vaccines boost immunity. Corticosteroids or immunosuppressants (like cyclosporine) reduce immune activity, useful after organ transplants.