Pharmacology and Rational Prescribing – Study Notes

Pharmacology and Rational Prescribing – Study Notes

• Course tone and goals

  • The instructor emphasizes practical pharmacology for a PA (physician assistant) mindset: how to think like a clinician when prescribing.
  • Lectures follow a consistent flow; first few are background-focused.
  • The course is a 1-credit hour class; aim for high performance and GPA support via hints on Canvas and weekly test reviews.
  • Availability and approach: the professor is laid back but maintains high standards; extra study aids and test reviews before exams.
  • Personal background: former pharmacist with public health and health equity focus; involved in local and international work, a Fort Lauderdale project on food insecurity and social determinants of health; also runs a student scholarship and contributes to publications.

• Core definitions: pharmacology, pharmacodynamics, pharmacokinetics

  • Pharmacology = the science of drugs and how they work.
  • Pharmacodynamics (what the drug does to the body): receptor interactions and resulting effects.
  • Pharmacokinetics (what the body does to the drug): ADME = $ext{Absorption}, ext{Distribution}, ext{Metabolism}, ext{Excretion}$.
  • Clinical pharmacology = optimal use of drugs in humans; patient-centered; uses evidence and patient factors to guide drug decisions.
  • The goal: right drug, right dose, right time, right patient.
  • Toxicology = study of harmful effects of substances, including overdoses, environmental toxins, and improper therapeutic use.
  • Poison = any substance causing harm, injury, or death; any drug can be a poison at the wrong dose (e.g., acetaminophen/Tylenol).

• History and regulation milestones

  • FDA-era milestones and safety testing evolution:
  • $1906$: Original Food and Drug Act required labeling but did not require proof of safety or efficacy.
  • $1937$: Elixir Sulfanilamide tragedy – diethylene glycol caused ~107 deaths; highlighted lack of safety testing.
  • $1938$: Federal Food, Drug, and Cosmetic Act – required proof of safety before marketing (efficacy not yet required).
  • $1941$: Sulfadiazine contaminated with phenobarbital caused deaths; spurred Good Manufacturing Practices (GMP).
  • GMP standards: manufacturing must occur in properly equipped facilities with proper practices (not in basements).
  • $1951$: Durham–Humphrey Amendments – defined prescription vs. over-the-counter (OTC).
  • $1952$: Chloramphenicol linked to fatal aplastic anemia; led to adverse event reporting era.
  • $1962$: Thalidomide tragedy – birth defects in thousands of babies; intensified safety and efficacy requirements.
  • Thalidomide tragedy details
  • In 1957 Germany, thalidomide marketed OTC for morning sickness; not approved in the US at the time.
  • In infants, thalidomide caused limb deformities via interference with angiogenesis during early fetal development; risk greatest in the first trimester.
  • Result: strengthened safety and efficacy testing and a formal drug approval process.
  • Drug approval process (four main phases, after preclinical work)
  • Phase 0/Preclinical: drug development and initial studies (mechanism of action, structure).
  • Phase 1: safety and pharmacokinetics; typically 20–80 healthy volunteers; focus on adverse effects and how the drug is absorbed, distributed, metabolized, and excreted.
  • Phase 2: efficacy in patients; determine if the drug works for the intended condition.
  • Phase 3: broader effectiveness and safety; multi-site, diverse patient populations.
  • Phase 4: post-marketing surveillance; ongoing safety monitoring after FDA approval.
  • Investigational New Drug (IND) application: sponsor submits animal data, manufacturing details, chemistry and pharmacology; FDA has 30 days to review.
  • Adverse event reporting and safety systems
  • MedWatch program: FDA's system for adverse drug events; drug manufacturers must report (mandatory); healthcare practitioners report voluntarily.
  • Acknowledges that some signals are caught by clinicians, even if not reported by manufacturers.
  • Special risk management programs
  • Isotretinoin example: iPLEDGE-style programs (in the talk referred to as hypoLEDGE) to ensure appropriate patient selection and monitoring.

• Rational prescribing and evidence-based medicine

  • Goals of rational prescribing (4 core bullets)
  • Maximize benefit: choose the drug with best therapeutic effect and lowest downside.
    • Example: for pain, start with non-opioid options (e.g., acetaminophen) before stronger analgesics when appropriate.
  • Minimize harm: avoid side effects, drug interactions, and unnecessary polypharmacy.
  • Conserve resources: favor cost-effective medications; switch from brand-name to generic where possible.
  • Respect patient autonomy: engage in shared decision-making; provide information on risks, benefits, and alternatives.
  • Brand vs generic considerations
  • Some patients prefer brand due to beliefs about efficacy; most active ingredients are the same, but education is key.
  • Some insurance plans require brand-name only; pricing and formulary considerations apply.
  • First few years after a drug's release may have brand-name monopolies limiting generics (patent/exclusivity effects).
  • Evidence-based medicine (EBM) in practice
  • Venn diagram concept: intersection of clinical judgment, scientific evidence, and patient preferences constitutes EBM.
  • Diagnosis, prognosis, and therapeutic objectives
  • Confirm diagnosis and understand likely progression (e.g., acute bronchitis vs pneumonia) as this shapes drug choice.
  • Define therapeutic objectives: reduce symptoms, cure, or prevent recurrence.
  • Tailor therapy to the patient (age, comorbidities, allergies, socioeconomic status; inpatient vs. outpatient; acute vs. chronic; urgent vs. routine).
  • Start treatment with education and monitoring of efficacy and safety.
  • Individualization and special populations (overview)
  • Age-related considerations: neonates, infants, children, geriatrics; organ maturity and clearance vary.
  • Beers Criteria (Beers List): flags inappropriate medications for elderly; aim to avoid or modify in older adults.
  • Pregnancy and lactation: maternal, fetal, and infant considerations; three-person lens for drug decisions.
  • Patient education impact
  • Poor oral communication is linked to adverse events; education improves efficacy, reduces morbidity/mortality, and lowers drug interactions/toxicity.
  • Use multiple modes of communication; simple language; repeat key points; cover what, why, how, and when.

• Special populations and pharmacology nuances

  • Age and physiology
  • Neonate: birth to 28 days; infants; immature liver/kidney function → slower elimination; drugs linger longer.
  • Children: not just small adults; avoid simply scaling adult doses by weight; limited pediatric testing means reliance on case reports/extrapolation.
  • Geriatrics: 65+; common comorbidities (e.g., CHF, diabetes, HTN, dementia, CKD); Beers Criteria focus.
  • Beers Criteria
  • Flags medications unsafe or inappropriate for elderly; examples include certain anticholinergics like diphenhydramine and amitriptyline; NSAIDs in heart failure are often cautioned.
  • Pregnancy categories (historical) and labeling evolution
  • Old letters: A, B, C, D, X describe fetal risk; A = controlled studies show no risk; B = animal studies no risk; C = animal studies show risk; D = risk to human fetus; X = contraindicated.
  • Today, Pregnancy and Lactation Labeling Rule (PLLR) updates labeling; for this class, categories A–X are used as a learning tool.
  • Pregnancy and lactation considerations
  • Always consider three people: mother, fetus, and infant (if breastfeeding).

• Patient education and communication strategies

  • Joint Commission findings: poor communication contributes to sentinel events and adverse drug events.
  • Education strategies
  • Start with patient’s existing knowledge; ask open-ended questions; use multiple modes (oral, written, demonstrations, QR codes, pamphlets).
  • Use plain language; target reading level around fourth to fifth grade.
  • Cover essential questions: what the medication is for, why it’s important, how to take it, and potential risks.

• Therapeutic outcomes and pharmacovigilance

  • Types of adverse drug reactions (ADRs)
  • Type A (anticipated): dose-dependent, predictable extrapolations of known drug effects (e.g., beta-blocker–induced bradycardia).
  • Type B (bizarre/ idiosyncratic): unpredictable, not dose-related (immune-mediated or genetic variations); can include Stevens–Johnson syndrome.
  • Black box warnings
  • Warnings on drugs indicating serious or life-threatening risks; e.g., antidepressants and suicidality signals; fluoroquinolones and tendon risk; important to review before prescribing.
  • Drug interactions
  • Pharmacokinetic interactions: drugs affecting absorption, metabolism, or clearance (e.g., grapefruit juice inhibiting certain CYP enzymes).
  • Drug–drug vs. drug–food interactions; PK interactions can alter drug levels and efficacy.
  • Genetic polymorphisms and pharmacogenomics
  • Cytochrome P450 enzymes (CYP): mainly $CYP2D6, ext{CYP2C19}, ext{CYP2C9}$; phenotypes include poor metabolizers and ultra-rapid metabolizers, affecting drug exposure and response.
  • Some patients may not respond because of genetic variants influencing metabolism.
  • Prescribing errors and safety
  • Causes include prescribing the wrong drug, incorrect abbreviations, omitted information, and poor dose adjustments for renal/hepatic impairment.
  • Transitions of care (e.g., pre-op to post-op) often lead to changes in med lists and potential errors.
  • As-needed (PRN) orders must specify indication (for what symptom).
  • Importance of clear, legible writing and avoidance of risky abbreviations.

• Prescription writing and drug use terminology

  • Prescription writing basics (outpatient focus)
  • Common fields: patient name, date of birth (two identifiers), medication name and strength, quantity, SIG (directions), date, prescriber signature.
  • Brand vs generic: pharmacies usually dispense generic to lower cost unless brand is required;
    • If brand is required, mark accordingly.
  • Refills: specify number; for many drugs, refills are limited by policy or regulation.
  • NPI number is typically required; a DEA number is only required for controlled substances.
  • Abbreviations and dosing terminology (practice list to know)
  • BID = twice daily; TID = three times daily; QID = four times daily; QHS = at bedtime; Q4H = every 4 hours; PO = by mouth; etc.
  • Do not use certain abbreviations; be familiar with Joint Commission “do not use” list.
  • Do not-use and safety emphasis
  • Miscommunication risk when abbreviations are unclear or misread; ensure clear directions for patients.
  • Controlled substances specifics (Florida-focused overview)
  • Controlled substances are scheduled I–V; schedule I has no accepted medical use; II–V have medical use with varying abuse potential.
  • Common examples: Schedule II (high potential for abuse, but medical use) includes oxycodone, morphine, Adderall; Schedule III–V have decreasing abuse potential.
  • Prescription requirements specifics:
    • Prescriptions may be electronic, verbal/phone, fax, or handwritten; controlled substances require more stringent handling.
    • Florida statutes require certain elements on a prescription (see below) and controlled substances require additional data:
    • DEA number must appear on controlled substance prescriptions; NPI is typically present on the pad or in e-prescribing systems.
    • For controlled substances, some forms must use a standardized counterfoil pad to prevent forgery.
  • Florida prescription requirements (key items to know for exams and practice)
  • Prescriptions must be legibly written or typed.
  • Required fields include:
    • Prescriber name (name of the prescribing practitioner) and their credentials; drug name and strength; quantity; SIG (directions for use); date of prescription; signature.
    • Patient identifiers: patient name and date of birth (two identifiers; date of birth can substitute for phone number).
    • In practice, many systems also require the patient’s date of birth as a primary identifier.
  • Controlled substances additional requirements (Florida)
  • For schedule II–V: alphanumeric quantity is required (e.g., write “30” and the number “30” next to it).
  • Date must be clear and include the year; avoid ambiguous date formats; use mm/dd/yyyy format.
  • PDMP/e-forcing (e-FORCE or PDMP-like checks): require checking patient history prior to dispensing controlled substances to detect potential abuse or duplication.
  • For chronic vs acute pain scheduling (CII):
    • Chronic nonmalignant pain requires explicit nonacute pain language on the prescription; lack of such language can limit to a three-day supply inadvertently.
    • Acute pain limitation: typically up to a three-day supply; can extend to seven days with an acute pain exception.
    • If chronic dosing is intended, the prescription should reflect nonacute pain language; pharmacists/coordinators verify ongoing need.
  • Refills for Schedule II drugs are not allowed; multiple prescriptions on the same day can be used with “do not dispense before” dates if needed, but they cannot be dispensed earlier than the indicated date.
  • Schedule III–V: up to five refills allowed; still subject to PDMP checks and state regulations.
  • e-prescribing and monitoring
  • Most prescriptions are electronic; for controlled substances, PDMP checks are required to monitor patient history and prevent misuse.

• Practical takeaways and study tips

  • Always consider pharmacology in a patient-centered context: safety, efficacy, and real-world use.
  • Remember the four core rational prescribing principles and apply them via case-based thinking.
  • Be prepared to discuss Beers Criteria when treating elderly patients and avoid high-risk meds when possible.
  • In pregnancy, always weigh maternal and fetal/infant risks and benefits; memorize the historical A–X categories as a learning tool, while recognizing PLLR labeling in modern practice.
  • For prescriptions, memorize key Florida requirements and the general structure of a safe prescription, especially for controlled substances.
  • Practice with prescription-writing exercises to reinforce correct formatting, legibility, and order of fields.

• Quick reference formulas and markers (LaTeX)

  • ADME = $ext{Absorption, Distribution, Metabolism, Excretion}$
  • Phase 1, Phase 2, Phase 3, Phase 4 are the main phases in the drug approval process; denote as Phase $1$–Phase $4$.
  • Four main phases count = $4$ steps.
  • Beers Criteria and PLLR labeling are pivotal in planning safer pharmacotherapy in special populations.
  • CYP enzymes mentioned: CYP2D6,
    CYP2C19,
    CYP2C9; genotypes influence metabolic phenotype (poor vs ultra-rapid metabolizers).

• Connections to real-world practice

  • Rational prescribing translates to real patient benefits: appropriate drug choice, dose, timing, and patient engagement.
  • Be mindful of transitions of care to minimize prescribing errors.
  • Use PDMP checks for controlled substances to reduce diversion and misuse.
  • Use patient education strategies to improve adherence and decrease adverse outcomes.

• Ethical, philosophical, and practical implications

  • Balancing patient autonomy with appropriate medical judgment is essential in prescribing.
  • The safety-first approach is reinforced by regulatory history (e.g., thalidomide tragedy) and ongoing pharmacovigilance (MedWatch, Post-marketing surveillance).
  • Equity and access considerations include generic substitutions to improve affordability without compromising efficacy.

• Summary of key terms to memorize

  • Pharmacodynamics, pharmacokinetics, ADME, clinical pharmacology, toxicology, poison, pharmacogenomics, CYP enzymes, Beers Criteria, PDMP, MedWatch, PLLR, DEA number, NPI, SIG, alphanumeric quantity, e-prescribing, control substances scheduling (I–V), nonacute vs acute pain labeling, and the four FDA drug approval phases.

• Note: This set of notes mirrors the lecture flow and highlights every major and minor point shared in the transcript, including examples, practical scenarios, and regulatory frameworks.