Introduction to Pharmacology – Part 2

UNDERSTANDING ESSENTIAL DRUG INFORMATION

• Core goal: Equip clinicians with the minimum, yet complete, set of facts needed to prescribe, dispense, administer, and monitor medications safely and effectively.
• Major domains of information to master:
  • Mechanism of action / expected pharmacologic action.
  • Therapeutic uses (indications).
  • Side-effect profile versus adverse drug reactions (ADRs).
  • Contraindications, precautions, and black-box warnings.
  • Drug–drug and food–drug interactions.
  • Monitoring parameters (labs, vital signs, therapeutic drug levels).
  • Patient-specific variables: age, pregnancy status, genetics, comorbidities.
• Clinical significance: Understanding these domains allows for individualized therapy, risk minimization, and rapid identification of complications.

EXPECTED PHARMACOLOGIC ACTION VS. THERAPEUTIC USE

• Expected pharmacologic action (EPA):
  • Describes how a drug works at the molecular, cellular, or system level (mechanism of action).
  • Example: β-blockers competitively inhibit β₁-adrenergic receptors, reducing heart rate and contractility.
• Therapeutic use (TU):
  • Describes why we give the drug—the clinical condition(s) treated or prevented.
  • Example: The above β-blocker’s TU includes hypertension, angina, post-MI mortality reduction, and some arrhythmias.
• Key distinction: A single EPA can translate into multiple TUs, and different drugs with different EPAs can share the same TU.
• Clinical application: When selecting therapy, providers weigh whether the EPA logically addresses the pathophysiology underlying the patient’s condition.

SIDE EFFECT VS. ADVERSE DRUG REACTION (ADR)

• Side effect:
  • An expected, typically dose-dependent, secondary effect related to the pharmacologic action of a medication.
  • Usually predictable and often tolerated or mitigated (e.g., nausea or headache with many agents).
• Adverse Drug Reaction:
  • Any unintended, harmful response occurring at normal doses.
  • May be unpredictable, severe, or idiosyncratic (e.g., hepatotoxicity, severe bleeding, irreversible cardiomyopathy).
• Comparative examples from slide:
  • Side effects: nausea, headache.
  • ADRs: heart damage (cardiotoxicity), major bleeding (hemorrhage).
• Nursing implication: Always document and differentiate; an ADR often warrants discontinuation, whereas a side effect may be managed.

COMMON ADVERSE DRUG EFFECT CATEGORIES

• Central Nervous System (CNS) effects: dizziness, sedation, seizures, psychosis.
• Gastrointestinal (GI): nausea, vomiting, diarrhea, constipation, GI bleed.
• Hematologic: thrombocytopenia, agranulocytosis, aplastic anemia.
• Toxicity (organ-specific): nephrotoxicity, hepatotoxicity, ototoxicity, cardiotoxicity.
• Hypersensitivity (immunologic): rash, urticaria, Stevens-Johnson syndrome, serum sickness.
• Electrolyte imbalances: hypo/hyper-kalemia, hypo/hyper-natremia, hypo-magnesemia.
• Altered glucose metabolism: drug-induced hypo- or hyper-glycemia.
• Teratogenicity: congenital malformations or fetal demise when exposure occurs during pregnancy.
• Significance: Categorization helps anticipate required monitoring (e.g., CBC for hematologic toxicity, CMP for electrolytes).

ANAPHYLACTIC SHOCK

• Definition: Acute, life-threatening, systemic hypersensitivity reaction mediated by IgE and massive histamine release.
• Hallmark features: airway edema, bronchospasm, hypotension, tachycardia, urticaria/angioedema, potential cardiovascular collapse.
• Onset: Seconds to minutes post-exposure to allergen.
• Immediate management:
  1. Intramuscular epinephrine (first-line).
  2. Airway support and high-flow O₂.
  3. IV fluids for hypotension.
  4. Adjuncts: antihistamines, corticosteroids, β₂-agonists.
• Prevention: Detailed allergy histories; emergency action plans; patient education on epinephrine autoinjector use.

TOLERANCE VS. CUMULATIVE EFFECT VS. TOXICITY

• Tolerance:
  • A reduced response over time to the same drug dose due to pharmacodynamic (receptor down-regulation) or pharmacokinetic (enzyme induction) mechanisms.
  • Clinical outcome: escalating doses are required to achieve prior effect (e.g., opioids, benzodiazepines).
• Cumulative effect:
  • Drug concentration builds because elimination ≠ administration rate, often in renal or hepatic impairment.
  • Presents as exaggerated pharmacologic activity despite standard doses.
• Toxicity:
  • Quantifiable drug concentration or clinical state that produces harmful effects; may result from overdose, interaction, organ failure, or narrow therapeutic window.
• Inter-relationships: Cumulative effect can precipitate toxicity; developing tolerance may tempt clinicians to increase dose, risking toxicity if elimination pathways saturate.

PRECAUTIONS VS. CONTRAINDICATIONS

• Precaution ("use with caution"): Condition in which drug may be used but requires extra monitoring, dose adjustment, or patient counseling.
  • Example: NSAIDs with mild renal impairment.
• Contraindication: Situation where drug administration should not occur because risk >> benefit.
  • Absolute: e.g., isotretinoin in pregnancy (severe teratogenicity).
  • Relative: e.g., β-blockers in controlled asthma—may be used if compelling indication and careful monitoring.
• Clinical action: Verify orders against patient history; if a contraindication exists, clarify or substitute.

DRUG–DRUG INTERACTIONS (DDIs)

• Mechanisms:
  1. Pharmacodynamic (additive, synergistic, antagonistic at receptor or physiologic level).
  2. Pharmacokinetic: altered absorption, distribution, metabolism (enzyme induction/inhibition of CYP450), or excretion.
• Possible Results (as per slide table):
  • Decrease action of one or more drugs (therapeutic failure).
  • Increase action (enhanced effect/toxicity).
  • Cause new or intensified ADRs.
• Clinical tools: Interaction checkers, medication reconciliation, therapeutic drug monitoring.

FOOD–DRUG INTERACTIONS

• Three broad outcomes:
  1. Increase pharmacologic activity.
  2. Decrease pharmacologic activity.
  3. Produce toxic/adverse responses.

Examples That INCREASE Drug Activity

• Insulin or oral hypoglycemics + alcohol → heightened hypoglycemia.
• Statins, calcium channel blockers, erectile-dysfunction drugs + grapefruit juice → CYP3A4 inhibition → elevated serum levels → myopathy, hypotension, priapism respectively.

Examples That DECREASE Drug Activity

• Warfarin + vitamin K-rich foods (leafy greens) → antagonism → subtherapeutic INR.
• Digoxin + high-fiber diets/herbal bulking agents → reduced absorption → loss of efficacy.
• Tetracyclines / ciprofloxacin + dairy (milk, yogurt, cheese) → chelation with Ca^{2+} → ↓ absorption.

Examples That PRODUCE TOXIC / ADVERSE RESPONSES

• Acetaminophen + alcohol → synergistic hepatotoxicity (↑ N-acetyl-p-benzoquinone imine formation).
• MAO inhibitors + tyramine-rich foods (aged cheeses, cured meats, beer) → hypertensive crisis (excess norepinephrine).

DRUG THERAPY ACROSS THE LIFESPAN

• Neonates/Infants: immature hepatic enzymes, renal function; require weight-based doses and heightened toxicity vigilance.
• Children: rapid metabolic rates; some drugs need higher mg/kg than adults.
• Pregnancy: teratogenic risk; altered plasma volume and protein binding.
• Lactation: potential drug excretion into breast milk; consider infant exposure.
• Older Adults: ↓ renal/hepatic clearance, polypharmacy, altered receptor sensitivity; start low, go slow.
• Ethical note: Age-appropriate consent/assent and caregiver education mandatory.

CLIENT INSTRUCTIONS FOR MEDICATION TEACHING

• Initiate teaching as soon as possible after admission to promote early comprehension and adherence.
• Essential content to cover:
  • Purpose of each medication.
  • Generic and brand names.
  • Correct administration method, route, and schedule.
  • Potential adverse effects and necessary precautions (what to report, when to seek help).
• Educational strategies:
  • Gauge cognitive level; adapt language complexity.
  • Use interpreters for language barriers.
  • Employ varied teaching tools: written handouts, pictograms, videos, med calendars, pill organizers.
• Evaluation of learning:
  • Ask specific, open-ended questions ("What will you do if you miss a dose?").
  • Identify misunderstandings promptly.
  • Request return demonstrations or teach-back (e.g., insulin injection technique).

NEXT STEPS / COURSE LOGISTICS

• Complete the Introduction to Pharmacology module test: 25 questions.
• Due date: 7-13-25 by 1159 p.m. (23:59).
• Recommended: review these notes, textbook chapters, and practice calculations before attempting the test.