Basic Principles of Pharmacology

Introduction to Pharmacology and Therapeutic Methods

• Definition of Pharmacology: The study of drugs and their actions or effects on the body. The term is derived from the Greek words $pharmakon$ (drug/medicine) and $logos$ (study).
• Therapeutic Methods: Approaches used to treat illnesses. These are often used in combination rather than in isolation:     * Diet therapy: Use of nutrition and diet to treat conditions.     * Drug therapy: Use of medications specifically (Pharmacotherapy).     * Physiotherapy: Use of physical agents such as water, light, and heat.     * Psychotherapy: Identifying stressors and utilizing methods to reduce them.
• Biologic Therapy: A new class of drugs that has transformed the treatment of patients with disorders where the body attacks its own organs, tissues, and cells.     * Biologic agents: These are large, complex proteins manufactured within a living system.

Drug Nomenclature and Classifications

• Chemical Name: This is the name most meaningful to the chemist. It describes the exact chemical constitution of the drug and the exact placement of its atoms or molecular groupings.
• Generic Name:     * These are important to know because formularies use them.     * These names are not capitalized.
• Official Name: The name as it is listed by the U.S. Food and Drug Administration (FDA).
• Brand or Trademark Name:     * These are registered by the manufacturer.     * These names are capitalized.
• Categorization by Use/Action:     * Body system classification: Categorized by the system they affect (e.g., cardiovascular, gastrointestinal).     * Therapeutic use or clinical indications: Categorized by what they treat (e.g., antacids, antibiotics).     * Physiologic or chemical action: Categorized by how they work at a cellular or molecular level (e.g., anticholinergics, calcium channel blockers).
• Categorization by Availability and Source:     * Prescription: Requires an order by a health professional licensed to prescribe drugs.     * Nonprescription: Over-the-counter (OTC) drugs sold without a prescription.     * Illegal or recreational drugs: Drugs used for nontherapeutic purposes; obtained illegally.     * Biosimilar: A biologic product that is highly similar in structure and function to an existing approved biologic product.

Resources for Drug Information

• Official Sources for American Drug Standards:     * The United States Pharmacopeia (USP)/National Formulary (NF).     * USP Dictionary of USAN and International Drug Names.
• Sources for Prescription and Nonprescription Drugs:     * Package inserts (provided by the manufacturer).     * Nursing journals.     * Electronic databases.
• Common Electronic Databases:     * Cumulative Index of Nursing and Allied Health (CINAHL).     * Lexicomp.     * ePocrates.     * DailyMed.

United States Drug Legislation

• Federal Food, Drug, and Cosmetic Act (1938, 1951, 1962): Provides the legal framework for drug safety and efficacy.
• Controlled Substances Act (1970): Defined five classifications or schedules for controlled substances based on their potential for abuse.     * Schedule I: High potential for abuse; no currently accepted medical use in the U.S. (e.g., heroin, LSD).     * Schedule II: High potential for abuse; currently accepted medical use with severe restrictions.     * Schedule III: Less potential for abuse than Schedule I or II; accepted medical use.     * Schedule IV: Low potential for abuse relative to Schedule III.     * Schedule V: Low potential for abuse relative to Schedule IV.
• DEA Compliance:     * Manufacturers, prescribers, and dispensers must register with the Drug Enforcement Agency (DEA).     * Hospitals must maintain inventory and dispersion control records for all controlled substances.     * Nurses may not have controlled substances in their personal possession.

New Drug Development and Safety Tracking

• FDA Stages of Development:     1. Preclinical research and development: Average time equals $18$ months.     2. Clinical research and development: May require $2$ to $10$ years; the average is $5$ years.     3. New Drug Application (NDA) review: Average time equals $17$ months.     4. Postmarketing surveillance: Ongoing review of the drug's effects after it is on the market.
• Expedited Tracking:     * Fast tracking: Used to expedite development and approval for drugs treating life-threatening illnesses.     * Parallel tracking: Used for patients with life-threatening illnesses who cannot participate in controlled trials when no other alternative exists.
• Safety Warnings:     * Black box warning: Indicates a very serious, life-threatening problem.     * Statistics: There is a $20\%$ probability of a drug acquiring a new black box warning or being withdrawn from the market within $25$ years of release.
• Rare Diseases and Orphan Drugs:     * There are approximately $6000$ rare health conditions affecting about $20$ million Americans.     * Orphan drugs: Medicines developed specifically for rare disorders.     * Orphan Drug Act (1983): Promotes the development of products for the diagnosis or treatment of rare diseases.

Drug Responses and Administration Routes

• Drug Receptors: Specific sites where drugs form chemical bonds to exert an effect.
• Pharmacodynamics: The study of interactions between drugs and their receptors and the series of events that result in a pharmacologic response.     * Agonists: Drugs that interact with a receptor to stimulate a response.     * Antagonist: Drugs that attach to a receptor but do not stimulate a response; they may block other substances from binding.
• Routes of Administration:     * Enteral: Via the gastrointestinal (GI) tract (oral, rectal, or nasogastric routes).     * Parenteral: Bypasses the GI tract; includes subcutaneous ($SC$), intramuscular ($IM$), and intravenous ($IV$) injection.     * Percutaneous: Absorbed through the skin and mucous membranes (inhalation, sublingual, or topical).

Pharmacokinetics: The LADME Process

• L: Liberation: The drug is released from its dosage form and dissolved in body fluid. This process for oral drugs can be influenced by the presence of food and water in the stomach.
• A: Absorption: The drug is transferred from the entry site into the body's circulating fluids.     * Rate depends on route, blood flow, and drug solubility.     * $IV$ medications are absorbed the fastest.     * Topical absorption is influenced by skin thickness and hydration.
• D: Distribution: Drugs are transported throughout the body by fluids to the sites of action.     * Influenced by protein binding and fat solubility.     * Organs with the largest blood supply receive drugs most rapidly.     * Barriers: Some drugs cannot pass the blood-brain barrier or the placental barrier.
• M: Metabolism: The process where the body inactivates drugs.     * Primary organ of metabolism is the liver.     * Secondary sites include the GI tract and lungs.
• E: Excretion: Elimination of drug metabolites and active drug from the body.     * The kidneys are the major organ of excretion.     * Some drugs/metabolites are excreted in feces.

Drug Action Timing and Monitoring

• Half-Life of Drugs: The time required for the concentration of the drug in the body to be reduced by half.
• Timing Definitions:     * Onset of action: When the concentration of a drug at the site of action is sufficient to start a physiologic response.     * Peak action: Time at which the drug reaches the highest concentrations on the target receptor sites.     * Duration of action: How long the drug maintains a pharmacologic effect.
• Drug Blood Levels: Assays used to determine the amount of drug present in the blood. Highly important for drugs with narrow therapeutic ranges, such as anticonvulsants.

Adverse Effects and Interactions

• Types of Effects:     * Desired action: The intended therapeutic outcome.     * Side effects: Predictable, secondary effects.     * Adverse effects: Can be common or serious; often harmful.     * Idiosyncratic reactions: Occur when something unusual or abnormal happens when a drug is first administered.     * Allergic reactions: Occur in patients previously exposed to a drug whose immune systems have developed antibodies.
• Mechanism of Interactions: Occur when the action of one drug is altered by another drug, either increasing or decreasing effectiveness.     * Absorption changes: Mostly occur in the GI tract (e.g., antacids increasing gastric $pH$ and inhibiting dissolution of ketoconazole). Management often involves separating administration times.     * Distribution changes: Usually affect drug binding to inactive sites (proteins). Unbound drugs are the pharmacologically active portion.     * Metabolism changes: Involve inhibiting or inducing enzymes. Inhibition usually leads to increased serum drug levels.     * Excretion changes: Usually occur in kidney tubules by changing $pH$ to enhance or inhibit excretion.
• Named Interaction Effects:     * Additive effect: The combined effect of two drugs is equal to the sum of their individual effects ($1+1=2$).     * Synergistic effect: The combined effect is greater than the sum of the individual effects ($1+1=3$).     * Antagonistic effect: One drug interferes with the action of another, decreasing its effect.     * Displacement: One drug kicks another off a protein binding site, increasing the active amount of the displaced drug.     * Interference: One drug inhibits the metabolism or excretion of another.     * Incompatibility: A chemical or physical reaction that occurs between two drugs, rendering them unsafe or ineffective (often seen in $IV$ tubing).

Questions & Discussion

• Question 1: Which name(s) of a drug should the nurse use when teaching a patient about a new prescription?     * Answer: Generic and trade.
• Question 2: Which source of information is best for the nurse to obtain drug information?     * Answer: Electronic databases.
• Question 3: Which entity is responsible for monitoring drug safety in the United States?     * Answer: U.S. Food and Drug Administration (FDA).
• Question 4: Which drug schedule indicates drugs with the highest risk for abuse?     * Answer: Schedule I.
• Question 5: How many years on average does it take for a drug to be brought to market from the time of its conception?     * Answer: $8$ to $15$ years. (Calculation: Preclinical $1.5$ + Clinical $5$ + NDA $1.5$ = $8$ years; slide mentions average clinical is $5$ but can be up to $10$).
• Question 6: All drugs are processed in the body through pharmacokinetics. What is the correct order that drugs pass through the body?     * Answer: Liberation, absorption, distribution, metabolism, excretion (LADME).
• Question 7: Which route of administration has the fastest rate of distribution?     * Answer: Intravenous.
• Question 8: When the nurse administers a $50\text{ mg}$ dose of a drug with a half-life of $6$ hours, how many milligrams will remain in the body at $24$ hours?     * Answer: $3.13\text{ mg}$. (Calculation: $24 / 6 = 4$ half-lives. $50 \rightarrow 25 \rightarrow 12.5 \rightarrow 6.25 \rightarrow 3.125\text{ mg}$).
• Question 9: A patient starts a new drug used safely for years, has no allergies, and the nurse administers it correctly. Suddenly the patient experiences cardiac arrest. What is this type of reaction called?     * Answer: Idiosyncratic.
• Question 10: A patient reports postoperative pain; the nurse administers $IV$ morphine. $15$ minutes later, the patient is drowsy with slow respirations and low $O_2$ saturation. The nurse administers another drug that decreases the morphine’s action. What is this effect called?     * Answer: Antagonistic.