Applied Pharmacology ALH 130 B — Comprehensive Notes

Pharmacology: Comprehensive Study Notes

• Pharmacology is an expansive and challenging topic. It is the study of medicine and improves health if applied properly, but results in devastating consequences if applied improperly.

Interrelated Subject Areas

• Anatomy and physiology
• Microbiology
• Chemistry
• Pathophysiology

Challenges of Pharmacology

• Pharmacology is challenging due to differences in:
  • Drug names
  • Drug interactions
  • Adverse effects
  • Mechanisms of action
  • Patient/organism responses

Healthcare Practitioners Who Prescribe Drugs

• Physicians
• Physician assistants
• Dentists
• Advanced registered nurse practitioners (APRNs)
• Mottos/phrases seen: "I have pills for that." (contextual reminder of broad prescribing scope)

Nurses as Healthcare Providers

• Nurses are healthcare providers who:
  • Administer drugs
  • Provide drug education
  • Advise patients regarding healthcare needs
  • Manage drugs
  • Enforce drug laws
  • Report effectiveness of drugs
• Other professionals who may administer drugs: [contextually implied, not listed as explicit roles in all slides]

Pharmacology and Therapeutics

• Pharmacology: the study of how drugs improve the health of the human body
• Therapeutics: the branch of medicine concerned with the treatment of disease and suffering
• Pharmacotherapeutics: the use of medicine to treat disease

Medications/Drugs: Classifications

• Medicines are classified as traditional drugs, biologics, and natural alternatives
• therapeutic vs non-therapeutic agents (examples follow)

Drugs as Chemical Agents

• Drugs produce biological responses within the body
• Some are medically therapeutic
• Food and air are necessary for life
• Household products, cosmetics, chemicals can also affect body function but are not medically therapeutic
• Examples of non-therapeutic agents: v Antiperspirants, v Sunscreens, v Toothpaste, v Shampoos

Table 1-1: Characteristics of Traditional Therapeutic Drugs, Biologics, and Natural Alternative Therapies

• Traditional Drug Therapies: $ext{synthetically produced in a laboratory}$; $ext{routinely prescribed or administered by healthcare providers}$
• Biologics: $ext{naturally produced by the body itself, in animal cells, or in microorganisms}$; include hormones, monoclonal antibodies, vaccines; $ext{routinely prescribed or administered by healthcare providers}$
• Natural Alternative Therapies: $ext{naturally produced}$; include herbs, extracts, vitamins, minerals, or dietary supplements; recommended depending on the healthcare provider

Medication Availability

• Medications are available by prescription or over the counter (OTC)
• See your pharmacist
• Note: The slide shows some garbled text (likely decorative/placeholder elements) but the intended meaning: Rx vs OTC availability

Prescription Drugs Require a Physician’s Order

• Healthcare practitioner examines patient
• Healthcare practitioner determines a specific diagnosis
• Healthcare practitioner orders proper drug

OTC Drugs Do Not Require Physician’s Order

• Advantages of OTC drugs:
  • Proper drug ordered (clarified by the label and pharmacist)
  • Amount and frequency controlled by labeling
  • Instructions on use and adverse effects
  • No appointment with healthcare provider required
  • Easily obtained
  • Less expensive
• Disadvantages of OTC drugs:
  • May react with foods, herbal products, and prescription or other OTC drugs
  • Drug may impair ability to function
  • May choose wrong drug
  • Self-treatment can be ineffective
  • Potential for injury if disease progresses without proper treatment
• Differences in prescription medications in other countries can vary (contextual discussion prompt)

Pharmaceutics

• Pharmaceutics is the science of pharmacy. It involves:
  • Preparation of drugs
  • Dispensing of drugs to patients after examination by a licensed provider
• Not the same as pharmacology

Pharmacist

• Pharmacists catalog signs, symptoms, adverse effects, and drug interactions
• Advise patients about taking drugs and undesirable symptoms or interactions

Knowledge Check (Conceptual)

• Pharmacotherapy involves the science of therapeutics and pharmaceutics. What does this mean? (Consider the integration of drug action with therapeutic outcomes and the formulation/distribution aspects.)

Drug Regulation: Why Regulations Exist

• Drug regulations protect the public from drug misuse
• Early lack of standards led to dangerous products (e.g., rattlesnake oil for rheumatism)
• First standards were formularies

Figure 1-1: Historical Timeline of Regulatory Acts, Standards, and Organizations

• 1820: U.S. Pharmacopoeia (USP) published as first comprehensive drug standards
• 1852: American Pharmaceutical Association (APhA) founded; National Formulary (NF) established
• USP continued cataloguing drug-related substances and products
• 1862: Beginning of the Federal Bureau of Chemistry under Lincoln; later became FDA
• 1902: Biologics Control Act to regulate serums and blood products
• 1906: Pure Food and Drug Act for labeling
• 1912: Sherley Amendment to prohibit false therapeutic claims
• 1938: Food, Drug, and Cosmetic Act; NDA concept introduced; drugs must be tested before marketing
• 1944: Public Health Service Act; covers biologics and communicable diseases
• 1975: USP-NF becomes a single standardized publication
• 1986: Childhood Vaccine Act; FDA authority to recall biologics and penalties for misuse
• 1988: FDA established as a federal agency
• 1992: Prescription Drug User Fee Act (PD UFA); requires user fees; FDA staffing increased; reorganization
• 1994: Dietary Supplement Health and Education Act (DSHEA); requires labeling; FDA authority to remove risky supplements
• 1997: FDA Drug Modernization Act; reauthorized PD UFA; major reform in drug review process since 1938
• 2002: Bioterrorism Act; guidelines for toxins; safety and health measures
• 2007: FDA Amendments Act; enhanced post-market reviews and the Critical Path Initiative
• 2011: Health Care Reform law provisions; generic biologics approval; increased rebates and benefits
• 2012: Renewal of the Prescription Drug User Fee Act

Time and Stages of Drug Approval

• There are $4$ stages of approval for therapeutic and biologic drugs:
  • Preclinical investigation
  • Clinical investigation
  • Submission of a new drug application (NDA) with a review
  • Postmarketing studies

Preclinical Investigation

• Basic science research
• Tests on cells or animals
• Drug dose range examined
• Adverse effects observed
• Results are always inconclusive

Clinical Investigation

• Involves clinical pharmacology
• Evaluation of drugs for human benefit
• Clinical phase trials I, II, and III

Submission of NDA with Review

• Third stage of drug approval
• Clinical phase III trials and animal testing may continue
• New drug approved or rejected
• Approved → process goes to final stage; Rejected → process stops until concerns addressed

Postmarketing Studies

• Takes place after NDA review is completed
• New drug placed on the market
• Check for new harmful effects in larger groups of humans
• Drugs removed if serious problems occur

Time to Approve: Balancing Speed and Safety

• Government agencies face tension between speeding up approvals and ensuring safety
• Reasons to speed up: consumer groups, drug manufacturers
• Reasons to delay: outdated guidelines, poor communications, agency understaffing

Policy and Regulation Details

• Prescription Drug User Fee Act of 1992: $5$-year trial basis; manufacturers pay substantial fees; FDA hires more staff; FDA reorganized
• FDA Modernization Act of 1997: Reauthorized PD UFA; allowed information on unapproved uses
• Other FDA challenges: new drugs developed faster; risks may be harder to assess quickly

Bioterrorism Preparedness

• Healthcare providers must be prepared for biological/chemical attacks and pandemics
• Goals of bioterrorists: widespread panic and casualties
• U.S. agencies involved:
  • Centers for Disease Control and Prevention (CDC)
  • Department of Defense (DoD)
  • Department of Homeland Security (DHS)
• Prioritized citizen preparedness

Most Worrisome Threats (Bioterrorism Context)

• Acutely infectious agents: Anthrax, Smallpox, Plague
• Haemorrhagic viruses
• Incapacitating chemicals: Nerve gas, Cyanide, Chlorinated agents
• Nuclear and radiation emergencies

Drugs as Powerful Weapons Against Bioterrorism

• Treat infectious agents
• Treat chemical poisoning
• Treat nuclear/radiation poisoning

Treatment Chapters (in Textbook Structure)

• Chapter 9: Treatment of chemical nerve warfare agents
• Chapter 27: Antibiotics for infectious diseases
• Chapter 33: Treatment of radiation exposure

Drug Classes, Schedules, and Categories

Drug Organization and Classifications

• Drugs may be organized by therapeutic and pharmacologic classifications
• Therapeutic classifications: what the drug does clinically (e.g., anticoagulant, antihyperlipidemic, antihypertensive, antidysrhythmic, antianginal)
• Pharmacologic classifications: how the drug produces its effect in the body

Therapeutic Focus and Mechanism of Action

• Therapeutic usefulness examples:
  • Anticoagulant (influences blood clotting)
  • Antihyperlipidemic (lowers cholesterol)
  • Antihypertensive (lowers blood pressure)
  • Antidysrhythmic (treats abnormal heartbeat)
  • Antianginal (t Treats chest pain/angina)
• Mechanism of action examples:
  • Diuretic lowers plasma volume
  • Calcium channel blocker blocks Ca2+ entry into cells
  • ACE inhibitor blocks angiotensin-related activity
  • Adrenergic blocker inhibits sympathetic nervous system actions
  • Vasodilator dilates peripheral blood vessels

Drug Names: Chemical, Generic, Trade, and Combination Names

• Drugs have multiple names:
  • Chemical name
  • Generic name
  • Trade (brand) name
  • Combination names
• POST A GIF of funny pronunciation (note: decorative element on slide; not relevant to content)
• Example: Acetaminophen
  • Chemical name: N-(4-hydroxyphenyl)acetamide
  • Generic name: Acetaminophen
  • Trade name: Tylenol

Chemical Name

• Assigned by IUPAC
• A drug has only one chemical name
• Often complex and hard to pronounce
• Examples: N-(4-hydroxyphenyl)acetamide
• Acetaminophen example: Tylenol

Generic Names

• Assigned by U.S. Adopted Name Council
• Less complicated; routinely used by providers
• Memorization often required for pharmacology students
• Example: Acetaminophen

Trade (Brand) Names

• Assigned by the marketing company
• Marketability focus; easy to remember
• Also called proprietary, product, or brand name
• Proprietary rights: 17 years after filing with FDA
• Example: Acetaminophen → Tylenol

Combination Names

• More than one active generic ingredient
• Harder to remember
• Examples: DayQuil (Acetaminophen, Dextromethorphan, Phenylephrine); Lortab (Acetaminophen and Hydrocodone); Tylenol 3 (Acetaminophen and Codeine)

Examples: Generic Drugs and Trade Names

• aspirin → Brand examples: Acuprin, Anacin, Bayer, Bufferin, Ecotrin, etc.
• diphenhydramine → Brand examples: Benadryl, Sominex, Unisom, etc.
• ibuprofen → Brand examples: Advil, Motrin, etc.

Knowledge Check: Names of Drugs

• What are the differences between a chemical, a generic, and a trade name?
• Which name is most often used to describe the active ingredients within a drug product? (Answer: Generic name)

Trade vs Generic: Key Differences

• Differences include price, formulations, and bioavailability
• Generics are usually less expensive
• Bioavailability is the physiologic ability of a drug to reach target cells and produce a therapeutic effect
• Negative formulary: list of trade-name drugs that pharmacists may not dispense as generics

Drug Schedules

• Drugs with potential for misuse are categorized into schedules: I–V
• Highest to lowest potential for abuse
• Controlled substances are restricted by the Controlled Substances Act (1970) and revisions
• Strict monitoring guidelines

Drug Schedule Examples

• Schedule I: Very high abuse potential; high risk of dependence; examples include heroin, LSD, peyote, methaqualone, MDMA
• Schedule II: High abuse potential; high dependence; examples include morphine, methadone, oxycodone, fentanyl, amphetamine, methamphetamine, methylphenidate, many others
• Schedule III: Moderate to low; includes certain codeine products, buprenorphine, ketamine, anabolic steroids
• Schedule IV: Low potential for abuse; includes benzodiazepines, certain sedatives
• Schedule V: Very low potential for abuse; includes certain cough preparations with limited codeine

Pregnancy Categories

• All prescription drugs are classified by safety in pregnancy categories: A, B, C, D, X
• Teratogen: any substance harmful to a developing fetus or embryo
• Category A safest; X most harmful

Pregnancy Safety Categories: Examples

• Category A: Lowest risk (ferrous fumarate, levothyroxine, potassium salts, prenatal vitamins, thyroid-related products)
• Category B: Animal studies show no risk or humans show no risk
• Category C: Animal studies show risk; controlled human studies not performed
• Category D: May cause harm to fetus but benefits may outweigh risks in life-threatening situations
• Category X: Highest risk; not to be used in pregnancy

Drug Administration Principles: Safety and Administration

• Administration basics (general nursing principles):
  • Confirm drug ordered
  • Identify drug name (generic and trade) and drug classification
  • Confirm intended use and expected therapeutic effects
  • Check contraindications and special considerations
  • Review side effects and reason for use in this patient
  • Confirm pharmacy supply and administration method/dosage range
  • Adhere to nursing process considerations
• Goal: limit number and severity of adverse drug events

Adverse Events and Reactions

• Adverse event (AE): any undesirable experience associated with a medical product in a patient
• Adverse drug effect/event: AE resulting from drug administration
• Side effect: nontherapeutic reaction to a drug

Allergic Reactions and Anaphylaxis

• Allergic reaction: hyper-response to an allergen; vary in severity; can be serious
• Must be carefully monitored and prevented when possible; should be documented
• Anaphylaxis: severe, life-threatening shock; symptoms include severe shortness of breath, sudden drop in blood pressure, tachycardia

Drug Administration Rights and Checks

• Rights: Right patient, Right medication, Right dose, Right route of administration, Right time of delivery, Right documentation
• Checks: (1) with MAR when removing from storage, (2) with MAR during preparation/pouring, (3) before administering to the patient
• Rights form the basis of proper drug delivery

Compliance and Noncompliance

• Compliance: taking medication as prescribed and per instructions
• Responsible adults have the right to refuse medications
• Successful pharmacotherapy depends on patient compliance
• Reasons for noncompliance include: high cost, lack of insurance coverage, forgetting doses, side effects, fear of dependence

Abbreviations in Drug Administration

• Abbreviations used to guide directions and times (policy-dependent): STAT, prn, routine, standing orders, etc.
• Common abbreviations and meanings include:
  • ac: before meals; PO: by mouth; ad lib: as desired; AM: morning; bid: twice daily; qid: four times daily; q2h: every 2 hours; q4h: every 4 hours; gtt: drop; cap: capsule; IM: intramuscular; IV: intravenous; Rx: prescription; tab: tablet; etc.
• Agency policies require review of orders within specified time frames (usually every $7-10$ days)

Systems of Measurement

• three systems: Metric, Apothecary, Household
• Examples and conversions provided (e.g., 1 mL equals 15–16 minims or 15–16 drops; 1 teaspoon ~ 5 mL; 1 oz ~ 30 mL; 1 cubic centimeter (cc) equals 1 mL; 1 grain ~ 60–65 mg; 1 g = 1000 mg; 1 kg = 2.2 lb)
• Presentations use the metric system mainly for dosing

Drug Administration: Practical Steps

• Review medication order; check for allergies
• Hand hygiene and gloves if indicated
• Aseptic technique when preparing/administering medications
• Identify patient by name and check identification band; verify against MAR
• Check for allergies; verify allergy band if worn
• Ensure proper equipment and supplies at bedside (water, cups, etc.)
• Inform patient about the drug, purpose, and route
• Position patient for proper administration route
• Use unit-dose packaging at bedside when possible
• Do not leave medications at bedside unless explicitly instructed
• Document administration and patient responses on MAR

Enteral Drugs

• Given orally or via nasogastric (NG) or gastrostomy (G) tubes
• Oral administration is the most common, convenient, and least costly
• Absorption occurs via oral mucosa, stomach, or small intestine

Tablets and Capsules

• Most common drug form; easy to use
• Some are scored for easy splitting
• Enteric-coated tablets: designed to dissolve in the small intestine; do not crush
• Orally disintegrating tablets (ODTs) and oral soluble films: quick dissolving and absorption in mouth/cheek
• Sustained-release (SR, XR, LA): designed to dissolve slowly; increases duration

Oral Medication Disadvantages

• Requires patient conscious and able to swallow
• Some drugs are inactivated by digestive enzymes
• First-pass metabolism: absorbed in small intestine, travels to liver, may be inactivated
• GI motility can vary significantly
• Patients may dislike swallowing large pills

Sublingual and Buccal Administration

• Sublingual: under the tongue; medication not destroyed by digestive enzymes; no first-pass metabolism
• Buccal: in the cheek;

Nasogastric and Gastrostomy Tube Medication Administration

• Usually in liquid form
• Solid drugs should not be rushed through tubes (risk of clogging)
• Sustained-release drugs should not be crushed or given via NG/G-tubes
• Same physiologic process as oral route

Topical Drugs

• Locations: skin and membranous linings of eye, ear, respiratory tract, urinary tract, vagina, rectum
• Applications: dermatologic preparations; instillations/irrigations; inhalation

Parenteral Administration (Non-oral/Non-topical Routes)

• Via needle into skin layers, subcutaneous tissue, muscles, or veins
• Intradermal (ID)
• Subcutaneous (SC)
• Intramuscular (IM)
• Intravenous (IV)

Administration Angles (Examples)

• Intradermal: needle bevel up at $10^ ext{o}–15^ ext{o}$
• Subcutaneous: skin pinched; needle at $45^ ext{o}$ or $90^ ext{o}$ depending on tissue
• Intramuscular: skin taut; needle at $90^ ext{o}$

Injection Sites and Visual Aids

• Intravenous injections, Intramuscular injections, Subcutaneous injections mentioned with typical sites and illustrations
• Examples: deltoid (shoulder), vastus lateralis (thigh), abdomen, upper outer arms, etc.

Pharmacokinetics (ADME)

• Focuses on what the body does to drugs; four processes: Absorption, Distribution, Metabolism, Excretion

Absorption

• First step in drug transport; movement of a substance across membranes from administration site to target cells
• Many drugs cross multiple membranes to reach targets

Distribution

• How drugs are transported throughout the body after absorption or direct administration into bloodstream
• Involves binding to proteins or tissues; concept of bioavailability
• Barriers include blood-brain barrier, blood-placental barrier, blood-testis barrier

Metabolism

• Process by which drugs are made less or more active; total set of chemical reactions in the body
• Occurs in nearly all cells/organs; liver is the primary site
• Includes biotransformation; chemical conversion to active/inactive forms
• Prodrugs require metabolism to become active
• First-pass effect: drugs absorbed from the gut travel to the liver via the portal circulation for metabolism, potentially reducing active drug levels systemically
• Products of metabolism may have greater, lesser, or different activity than parent compound

Excretion

• Removal of drugs from the body; last step of pharmacokinetics
• Modes: urination, exhalation, defecation, sweating
• Enterohepatic recirculation (biliary recycling) can prolong drug action; drugs excreted via bile may require renal elimination

Pharmacokinetics Knowledge Check

• What does pharmacokinetics mean? Describe the four major parts: Absorption, Distribution, Metabolism, Excretion

Medication Elimination and Half-Life

• Rate of elimination and half-life influence drug responsiveness and dosing
• Rate of elimination: amount of drug removed per unit time from the body by physiologic processes
• Half-life (t1/2): time for drug plasma concentration to decrease by one-half

Importance of Elimination Rates and Half-Life

• Essential for determining proper dosing intervals and amounts

Pharmacodynamics

• Focuses on what the drugs do to the body; mechanisms of drug action
• Influences include absorption rate, dosing frequency, disease state (liver/kidney), food-drug interactions, concentration, genetics, drug-drug interactions, half-life, excretion rate, metabolic rate (lower in children and older adults)

Receptors and Drug Action

• Receptors are cellular structures to which drugs bind to produce a response
• Classic theory explains how drugs modify body processes via receptors
• Receptor: structural component of a cell to which a drug binds in a dose-related manner
• Receptor locations: plasma membrane, cytoplasm, or nucleus

Agonists vs Antagonists

• Agonist: binds to receptor and produces a cellular response; facilitates cellular action; therapeutic action occurs when present in bloodstream
• Antagonist: binds to receptor and blocks or diminishes the pharmacologic response; blockers
• Visual sequence on slide demonstrates agonist and antagonist interactions at receptor sites

Potency and Efficacy

• Potency: drug strength at a given concentration/dose
• Efficacy: maximum therapeutic effect achievable by the drug as concentration increases
• Illustrative comparisons show Drug A vs Drug B in potency and efficacy

Pharmacodynamics Knowledge Check

• Define pharmacodynamics; explain the role of receptors, agonists, and antagonists; differentiate potency from efficacy

Medication Errors

• Medication errors are preventable events that can significantly impact treatment outcomes

Medication Error Framework (NCCMERP)

• National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP)
• Medication error index: classifies errors into nine categories by harm potential

Contributors to Medication Errors

• Both healthcare providers and patients contribute

Healthcare Providers: Potential Error Causes

• Omitting one of the rights of drug administration
• Failing to perform agency system checks
• Failing to account for patient variables (age, body size, cognitive function, renal/hepatic function)
• Administering drugs when unsure of correct drug/dose/route
• Verbal orders, phone orders, incomplete orders, illegible orders leading to misinterpretation

Patients: Potential Error Causes

• Taking drugs prescribed by multiple providers without informing all providers
• Filling prescriptions at multiple pharmacies
• Not filling prescriptions
• Taking incorrect doses or times; improper storage or use of leftovers
• Not asking questions when unclear

Managing Medication Errors

• Errors should be documented; notify prescribing provider first, then nurse/charge manager
• Monitor patient for adverse effects
• All errors should be reported and investigated
• Risk Management and The Joint Commission: sentinel events (unexpected, serious/fatal injuries)

Reducing Medication Errors

• Positive patient identification
• Ask about allergies, current health concerns, OTC/herbal supplements
• Consider cognitive/functional impairments and organ function
• Avoid ambiguous abbreviations
• Never administer a medication without understanding its uses and side effects
• Clarify illegible orders with the prescriber
• Do not leave medications at bedside; ensure patient-specific administration
• Practice the rights of medication administration
• Document administration per institutional policy
• Check drug calculations and dosing; be alert for long-acting forms with indicators (LA, XL, XR)
• Be cautious of drugs with look- or sound-alike names

Patient Education and What to Teach

• Names, uses, dosages, timing and method of administration for all medications including OTCs and herbal supplements
• Adverse effects to report immediately
• Read labels before taking medications; use the provided medication device for liquids
• Maintain a list of all medications (Rx, OTC, herbal, dietary supplements)
• Use one pharmacy for all prescriptions if possible
• Encourage patients to ask questions

Closing Reflection

• The material emphasizes safe practice, regulatory context, pharmacokinetic/pharmacodynamic principles, classification and naming of drugs, and the crucial role of education and error prevention in pharmacotherapy.