2535 patho week 2

Lilley (2020) Chapter 2- Pharmacological Principles

Overview

• Drug: Any chemical affecting physiological processes of a living organism.

• Pharmacology: Science of drugs, encompassing:

  • Absorption

  • Biochemical effects

  • Biotransformation (metabolism)

  • Distribution

  • Drug history/origin

  • Receptor mechanisms

  • Excretion

  • Mechanisms of action

  • Physical & chemical properties

  • Therapeutic effects (beneficial)

  • Toxic effects (harmful)

• Subspecialties: Include pharmaceutics, pharmacokinetics, pharmacodynamics, pharmacogenetics, pharmacoeconomics, pharmacotherapeutics, pharmacognosy, toxicology.

• Importance for Nurses: Understand drug effects and appreciate therapeutic benefits and potential toxicity.

• Drug Names:

  • Chemical name: Describes chemical composition.

  • Generic name: Simpler, used in official drug listings.

  • Trade name: Registered trademark, commercial use restricted to patent owner.

• Patent Life: 20 years in Canada; 10 years for development and 10 for sales profit.

• Therapeutic Equivalence: Programs select preferred agents despite differing active ingredients, proven same therapeutic effects are necessary.

• Drug Classification: Based on structure (e.g., β-adrenergic blockers) or therapeutic use (e.g., antibiotics, antihypertensives).

• Phases of Pharmacology:

  • Pharmaceutics: Study of dosage forms' influence on body effects.

  • Pharmacokinetics: Study of body's effect on the drug.

  • Pharmacodynamics: Study of drug's effects on the body.

• Pharmacokinetics: Study of what the body does to the drug; involves absorption, distribution, metabolism, and excretion.

• Pharmacodynamics: Involves drug-receptor relationships.

• Pharmaceutical Phase: Initial phase of drug activity.

• Pharmacokinetic Phase: Involves processes affecting the drug.

• Pharmacodynamic Phase: Focuses on drug effects on the body.

• Pharmacotherapeutics: Clinical use of drugs to prevent and treat diseases; defines drug actions and cellular processes.

• Pharmacological Classes: Drugs are categorized based on physiological functions (e.g., β-adrenergic blockers) and diseases treated (e.g., anticonvulsants, anti-infectives).

• Health Canada: Regulates drug approval and clinical use; mandates expiration dates.

• Off-Label Prescribing: Use of drugs for non-approved indications; requires clinical judgement.

• Toxicology: Study of toxic effects; often overlaps with pharmacotherapy.

• Pharmacognosy: Study of natural drug sources (plants and animals).

• Pharmacoeconomics: Focuses on the economic aspects of drug therapy.

• Pharmacology is a dynamic science incorporating chemistry, physiology, and biology.

Pharmaceutics

• Drug dosage forms have varying pharmaceutical properties.

• Provides rate of dissolution (solid forms & absorption).

• Oral drugs can be:

  • Solid (tablet, capsule, powder)

  • Liquid (solution, suspension).

• Liquid drugs (e.g., elixirs, syrups) are absorbed faster than solid forms.

• Enteric-coated tablets are not absorbed until they reach the intestines due to their coating, resulting in slower absorption.

• Particle size affects dissolution speed, affecting onset of action (e.g., micronized vs. nonmicronized fenofibrate).

• Injectable drugs are usually straightforward in design; some are formulated to reduce toxicity (e.g., liposomal amphotericin B).

• Combination dosage forms contain multiple drugs (e.g., Caduet).

• Designed for accurate and convenient drug delivery with minimal adverse effects.

• Time-release technology allows continuous drug release in the GI tract:

  • Results in prolonged absorption and duration of action.

• Extended-release forms (e.g., SR, CR, XL) must not be crushed to avoid toxicity.

• Crushing tablets or opening capsules may facilitate patient adherence.

• Thin-film drug delivery dissolves in the mouth for rapid absorption.

• Topically applied drugs may work directly on skin or must pass through a barrier to circulation.

• Parenteral forms (injections) require safe characteristics:** pH must match blood**.

• Intravenous injections assume 100% absorption immediately into the bloodstream.

Pharmacokinetics

• Pharmacokinetics: Study of what happens to a drug from administration to elimination.

• Key characteristics of pharmacokinetics:

  • Onset of action: Time required for a drug to elicit a therapeutic response.

  • Peak effect: Time required to reach maximal therapeutic response.

  • Duration of action: Length of time that concentration is sufficient to elicit a therapeutic response.

• Focus areas consist of:

  • Absorption: Movement of drug into circulation.

  • Distribution: Transport of drug throughout the body.

  • Metabolism: Biochemical alteration of the drug.

  • Excretion: Elimination of drugs from the body.

Absorption

• Absorption: Movement of a drug from its site of administration into the bloodstream for distribution to tissues.

• Bioavailability: Extent of drug absorption.

• A drug absorbed from the intestine must first pass through the liver before reaching systemic circulation.

• A drug with a high proportion converted into inactive metabolites in the liver has reduced bioavailability.

• Such drugs are said to have a high first-pass effect (e.g., oral nitrates).

• First-pass effect reduces bioavailability to less than 100%.

• Intravenous drugs are 100% bioavailable since they directly enter systemic circulation.

• Oral drugs have reduced bioavailability (less than 100%) due to a fraction of the drug reaching systemic circulation.

• Bioequivalence: Two medications with the same bioavailability and concentration of active ingredient (e.g., trade-name vs generic drugs).

• Various factors affect drug absorption rate.

• Drug administration routes affect rate and extent of absorption:

  • Enteral (gastrointestinal tract)

  • Parenteral

  • Topical

Route

Enteral Route

• Drug absorption happens through mucosa of the stomach or intestines into systemic circulation.

• Rate of absorption can be influenced by many factors.

• Drugs absorbed from the intestinal lumen travel to the liver via the portal vein for metabolism.

• Enteric coating protects the stomach, allowing absorption in the intestines.

• Taking enteric-coated medication with large meals may cause it to dissolve prematurely, reducing absorption.

• Drugs with a high first-pass effect may have diminished active ingredients in the circulation.

• Nitroglycerin has minimal effect when taken orally due to rapid liver metabolism, but effective when taken sublingually.

• Parenteral doses are smaller than enteral doses for drugs with high first-pass effect, achieving the same effect.

• Acidity and contents of the stomach (time, age, medications) can alter drug absorption.

• Gastrointestinal transit can be slowed by certain drugs, affecting absorption.

• Conditions like short bowel syndrome and gastric dumping can further alter absorption rates.

• Sublingual and buccal routes enable rapid absorption due to rich blood supply, bypassing the liver.

Parenteral Route

• Fastest absorption route; includes injection methods (IV, IM, SC).

• Intravenous delivers directly into the bloodstream, distributed through blood.

• Intramuscular and subcutaneous injections are absorbed more slowly.

• Parenteral administration bypasses first-pass metabolism of the liver.

• Suitable for drugs that cannot be taken orally, yet still require cellular absorption for efficacy.

• Subcutaneous Injections: Administered into fatty subcutaneous tissue.

• Intradermal Injections: Given under epidermal layers into the dermal layer.

• Intramuscular Injections: Administered into muscle tissue; absorbed faster due to higher blood supply compared to subcutaneous injections.

• Methods to Enhance Absorption: Apply heat or massage the injection site to increase blood flow.

• Factors Reducing Absorption: Cold, hypotension, or poor peripheral blood flow can compromise circulation.

• Depot Drugs: Formulated for slow absorption over days to months (e.g., methylprednisolone acetate, medroxyprogesterone acetate).

• Topical Route: Involves application to skin, eyes, ears, nose, lungs, rectum, or vagina; delivers uniform drug amount over longer period; slower onset compared to other routes.

• First-Pass Effect: Avoided by most topical routes except rectal, which has mixed absorption.

• Common Topical Forms: Include ointments, gels, creams (e.g., sunscreens, antibiotics).

• Transdermal Route: Delivers drugs via adhesive patches (e.g., fentanyl, nitroglycerin, nicotine); designed for constant drug delivery over time.

• Inhalation Route: Drugs delivered as micrometre-sized particles to lungs; rapid absorption in alveoli.

• Examples of Inhaled Drugs: Zanamivir for influenza, salbutamol for asthma, fluticasone for inflammation.

Distribution

• Distribution: Transport of a drug by the bloodstream to its site of action.

• Rapid Distribution Areas: Heart, liver, kidneys, brain.

• Slower Distribution Areas: Muscle, skin, fat.

• Elimination: Drugs are metabolized and excreted primarily by the liver and kidneys.

• Binding: Only unbound drug molecules can freely distribute to extravascular tissue; albumin is the most common blood protein carrying protein-bound drug molecules.

• Free Drug: The unbound portion is pharmacologically active.

• Bound Drug: Considered pharmacologically inactive.

• Drug Toxicity Risk: Low albumin levels (e.g., from extensive burns, malnourishment) increase the fraction of free drug and risk toxicity.

• Drug-Drug Interaction: Occurs when two highly protein-bound medications compete for albumin binding sites, leading to an increase or decrease in the action of one of the drugs.

• Volume of Distribution: Theoretical volume within compartments (e.g., blood, total body water, body fat) where drugs may be distributed.

• Hydrophilic Drugs: High water soluble; small volume of distribution and high blood concentrations.

• Lipophilic Drugs: Fat-soluble; large volume of distribution and low blood concentrations.

• Distribution Challenges: Areas with poor blood supply (e.g., bone) or barriers (e.g., blood-brain barrier) hinder drug distribution.

Metabolism

• Metabolism: Also known as biotransformation, is the step after absorption and distribution.

• Involves biochemical alteration of a drug into:

  • Inactive metabolite

  • More soluble compound

  • More potent metabolite (conversion from inactive prodrug to active form)

  • Less active metabolite

• Liver: Main organ responsible for metabolism; other tissues include skeletal muscles, kidneys, lungs, plasma, and intestinal mucosa.

• Hepatic metabolism involves cytochrome P450 enzymes (or P450 enzymes), controlling reactions for drug metabolism, mainly targeting lipid-soluble drugs (lipophilic).

• Water-soluble drugs (polar) can be metabolized through simpler reactions (e.g., hydrolysis).

• Drug molecules are substrates for specific enzymes, identified by standardized designations.

• Variability in biotransformation occurs between patients, influenced by age, liver health, genetics, diseases, and concurrent medications.

• Nurses should monitor for factors affecting transformation, as accumulation of active metabolites may lead to toxicity.

• Enzyme inhibitors can decrease or delay metabolism, leading to drug accumulation and toxicity.

• Enzyme inducers stimulate metabolism, causing decreased pharmacological effects, often from repeated administration.

Excretion

• Excretion: Elimination of drugs from the body (parent compounds or metabolites).

• Primary organ: Kidney, responsible for drug elimination.

• Other organs involved: Liver and bowel.

• Metabolism: Most drugs are metabolized in the liver before reaching the kidneys.

• Drugs undergo biotransformation to a less active form; only a small fraction excreted as original compound.

• Metabolized drugs become polar and water-soluble, facilitating kidney elimination.

• Kidney excretion involves:

  • Glomerular filtration.

  • Active tubular reabsorption.

  • Active tubular secretion.

• Free (unbound) water-soluble drugs undergo passive glomerular filtration.

• Urine elimination processes: filtration, reabsorption, and secretion.

• Chronic kidney disease affects renal drug elimination; may require dosage adjustments based on creatinine clearance or glomerular filtration rate.

• Biliary excretion: Drugs eliminated in feces after liver uptake and bile release.

• Enterohepatic recirculation: Fat-soluble drugs can be reabsorbed into bloodstream, persisted longer in body.

• Less common routes: Lungs, sweat, salivary, and mammary glands.

Half-Life

• Half-Life: Time required for serum drug levels to reduce by 50% during the elimination phase.

• Elimination Rate: Measures how quickly the drug is cleared from the body.

• Example: Peak level of 100 mg/L; measured level at 8 hours is 50 mg/L, indicating a half-life of 8 hours.

• After about five half-lives, approximately 97% of the drug is eliminated, making remaining levels negligible for effects.

• Steady State: Achieved when drug elimination equals drug absorption, usually after four to five half-lives.

• Prolonged half-life means longer time to reach steady-state levels.

• Consistent drug levels at steady state correlate with maximum therapeutic benefits.

Onset, Peak and Duration

• Pharmacokinetic Terms: Absorption, Distribution, Metabolism, Excretion

• Drug Actions: Interaction between drug and cell (e.g., action on a receptor)

• Drug Effects Terms: Onset, Peak, Duration, Trough

  • Onset of Action: Time required for therapeutic response

  • Peak Effect: Time required to reach maximal therapeutic response

  • Duration of Action: Length of time concentration remains sufficient for response

• Blood Concentration Levels:

  • Peak Level: Highest blood level; too high can cause toxicity

  • Trough Level: Lowest blood level; too low may not produce therapeutic response

• Toxicity: Can be mild (e.g., excessive sedation) or severe (e.g., organ damage)

• Therapeutic Drug Monitoring: Measures peak and trough values to verify drug exposure, maximize effects, and minimize toxicity; typically done by clinical pharmacists.

Pharmacodynamics

• Pharmacodynamics: Relationship between drug concentrations and pharmacological response.

• Drug-induced changes: Affect normal physiological functions.

• Therapeutic effect: Positive change in a faulty physiological system; goal of drug therapy.

• Understanding pharmacodynamics helps assess a drug's therapeutic effect.

Mechanism of Action

• Drugs can produce therapeutic effects in several ways.

• Effects depend on the target cells or tissue.

• Can modify the rate or strength of cell function.

• Cannot cause functions outside of natural physiology.

• Actions occur through receptors, enzymes, and nonselective interactions.

• Some drugs may have an unknown or unclear mechanism of action, yet still exhibit observable effects.

Enzyme Interactions

• Enzymes: Substances that catalyze nearly every biochemical reaction in a cell.

• Drugs: Produce effects by interacting with enzyme systems.

• Selective Interaction: Process where drugs can either inhibit (more common) or enhance (less common) enzyme action.

• Drug-Enzyme Interaction: Occurs when a drug chemically binds to an enzyme, altering its interaction with normal target molecules in the body.

Nonselective Interactions

• Nonspecific mechanisms of action: Drugs that do not interact with receptors or enzymes.

• Main targets: Cell membranes and various cellular processes (e.g., metabolic activities).

• Actions: Can physically interfere with or chemically alter cellular structures/processes.

• Examples: Some cancer drugs and antibiotics.

• Mechanism: Incorporate into normal metabolic processes, causing defects in final products or states.

• Potential defects: Improperly formed cell wall leading to cell death through lysis, or lack of necessary energy substrates causing cell starvation and death.

Pharmacotherapeutics

• Establish an end point or expected outcome of drug therapy before initiation.

• Desired therapeutic outcome is patient-specific.

• Collaboration with the patient and, if appropriate, other health care team members.

• Outcomes must be clearly defined, measurable, or observable through patient monitoring.

• Outcome goals should be realistic and prioritized to address essential needs.

• Examples of outcomes include:

  • Curing a disease

  • Reducing pre-existing symptoms

  • Slowing a disease process

  • Preventing unwanted conditions

  • Improving quality of life.

• Patient therapy assessment integrates medical knowledge and patient history.

• Considerations include:

  • Current drugs (prescription, OTC, natural, illicit)

  • Pregnancy and breastfeeding status

  • Concurrent illnesses affecting medication initiation.

• A contraindication occurs when a condition makes medication use dangerous.

• Assessments ensure an optimal therapeutic plan.

• Treatment plans can involve types of therapies such as:

  • Acute therapy

  • Maintenance therapy

  • Supplemental (replacement) therapy

  • Palliative therapy

  • Supportive therapy

  • Prophylactic therapy

  • Empirical therapy.

Types of Therapy

Acute Therapy

• Acute therapy: Involves intensive drug therapy for patients who are acutely ill or critically ill.

• Purpose: Needed to sustain life or treat disease.

• Examples:

  • Administration of vasopressors to maintain blood pressure and cardiac output after open heart surgery.

  • Use of volume expanders for patients in shock.

  • Intensive chemotherapy for patients with newly diagnosed cancer.

Maintenance Therapy

• Maintenance Therapy: Prevents progression of diseases.

• Purpose: Does not eradicate existing problems; instead, it helps manage chronic illnesses.

• Examples:

  • Hypertension: Maintains blood pressure within target limits to prevent end-organ damage.

  • Oral Contraceptives: Used for birth control.

Supplemental Therapy

• Supplemental (or replacement) therapy: Supplies needed substances for normal function.

• Needed when substance cannot be made by the body or is produced in insufficient quantity.

• Examples:

  • Administration of insulin to patients with diabetes.

  • Administration of iron to patients with iron-deficiency anemia.

Palliative Therapy

• Goal of Palliative Therapy: Make the patient as comfortable as possible.

• Focuses on providing relief from symptoms, pain, and stress of a serious illness.

• Aims to improve quality of life for both the patient and the family.

• Typically used in the end stages of an illness when curative therapy has failed.

• Can be provided alongside curative treatment.

• Examples: Use of high-dose opioid analgesics to relieve pain in the final stages of cancer.

Supportive Therapy

• Supportive therapy maintains the integrity of body functions during recovery from illness or trauma.

• Examples include:

  • Provision of fluids and electrolytes to prevent dehydration in patients with influenza who are vomiting and have diarrhea.

  • Administration of fluids, volume expanders, or blood products to patients who have lost blood during surgery.

Prophylactic Therapy and Empirical Therapy

• Prophylactic Therapy: Drug therapy for prevention of illnesses or undesirable outcomes during planned events.

  • Example: Disease-specific vaccines for individuals traveling to endemic areas.

• Empirical Therapy: Based on clinical probabilities; involves drug administration based on an uncertain but high likelihood of a pathological condition.

  • Example: Use of antibiotics for organisms commonly associated with specific infections before culture results are available.

Monitoring

• Effectiveness evaluation: Assess the clinical response of the patient post-therapy implementation.

• Familiarity required: Understand both the drug’s therapeutic action (beneficial effects) and adverse effects (predictable adverse drug reactions).

• Monitoring examples:

  • Observe for therapeutic effects: e.g., reduced blood pressure with antihypertensives.

  • Monitor for toxic effects: e.g., leukopenia after chemotherapy.

  • Perform pain assessments after pain medication administration.

• Adverse effects: Identify that there may be many less common and less identifiable adverse drug effects.

• Consult resources: Use references, pharmacists, or poison control for uncertainty regarding adverse effects.

• Potential toxicity: All drugs can have cumulative effects and be potentially toxic.

• Recognizing toxic effects: Integral component of monitoring, as drug accumulation can occur if absorbed faster than elimination or if administered before previous metabolism/clearance.

• Knowledge of metabolism: Understanding the organs involved in metabolizing and eliminating drugs helps anticipate and treat potential problems.

Therapeutic Index

• Therapeutic Index: Ratio of a drug’s toxic level to its therapeutic benefits.

• Safety of drug therapy is determined by this index.

• Low Therapeutic Index indicates a small difference between therapeutically active dose and toxic dose.

  • Greater likelihood of adverse reactions; requires closer monitoring.

  • Examples: Warfarin, Digoxin.

• High Therapeutic Index suggests rare association with overdose events.

  • Example: Amoxicillin.

Drug Concentration

• Drug concentrations are essential for evaluating clinical response to drug therapy.

• Certain drug levels are linked to therapeutic responses, while others are linked to toxic effects.

• Toxic drug levels arise when normal metabolism and excretion mechanisms are compromised.

• Common causes include reduced liver and kidney functions or immature liver/kidneys (e.g., in neonates).

• Dosage adjustments are necessary for patients with compromised metabolism and excretion.

Patient’s Condition

• Consider patient-specific factors:

  • Weight: Obesity, weakness, or wasting of the body

  • Critical illness presence

  • Concurrent diseases or other medical conditions

• Drug response variation based on:

  • Physiological demands: Diseases, infections, cardiovascular function, gastrointestinal function

  • Psychological demands: Stress, depression, anxiety

• Therapeutic response may be altered by these factors.

Tolerance and Dependence

• Tolerance: Decreasing response to repeated drug doses.

• Dependence: Physiological or psychological need for a drug.

  • Physical dependence: Need to avoid withdrawal symptoms (e.g., tachycardia in opioid dependence).

  • Psychological dependence (Addiction): Obsessive desire for drug effects.

    • Often involves recreational use of benzodiazepines, narcotics, and amphetamines; can result from chronic pain.

Interactions

• Drug interactions occur with other drugs, foods, or lab test agents.

• Knowledge of drug interactions is vital for monitoring drug therapy.

• Older adults are more sensitive and often on multiple medications, increasing interaction likelihood.

• OTC medications and natural products can interact with prescribed drugs.

• Food can also significantly impact drug effectiveness.

• Alteration of drug action can increase or decrease effects (beneficial or harmful).

• Significant interactions require therapy adjustments and are discussed in the text.

• Pharmacokinetics phases affected: absorption, distribution, metabolism, excretion.

• Drug interactions often involve competition for metabolizing enzymes (e.g., cytochrome P450).

• Additive effects occur when two similar-action drugs enhance each other (1 + 1 = 2).

• Synergistic effects: one drug enhances the action of another (1 + 1 > 2). Example: hydrochlorothiazide with lisinopril.

• Antagonistic effects: combined drug effects are less than their sum (1 + 1 < 2). Example: ciprofloxacin with antacids.

• Incompatibility refers to chemical deterioration when mixing drugs (e.g., furosemide and heparin sodium).

Adverse Drug Events

• Adverse Drug Events (ADEs): Any undesirable occurrence involving medications.

• Patient outcomes of ADEs can range from no effects or mild discomfort to life-threatening complications, permanent disability, disfigurement, or death.

• ADEs can be preventable (related to medication errors) or nonpreventable.

• Common causes of ADEs include errors by caregivers (both professional and nonprofessional) and malfunctioning equipment (e.g., intravenous infusion pumps).

• Internal ADEs may occur when a patient fails to follow prescriptions or engages in harmful behaviors (e.g., alcohol consumption).

• Potential ADEs: Imminent issues detected before occurrence (near misses).

• A unique type is an adverse drug withdrawal event, resulting from abruptly stopping therapy (e.g., hypertension from discontinuing blood pressure medication).

• Medication errors (MEs): Situations compromising the Ten Rights of medication use (e.g., right patient, right drug, etc.) and are more common than ADRs.

• Adverse Drug Reactions (ADRs): Unexpected and undesirable reactions at therapeutic doses; outcomes may range from mild to severe.

• Severe ADRs can lead to hospitalization, organ damage, congenital anomalies, or need for specific interventions to prevent permanent impairment or tissue damage

• ADRs specific to drug groups discussed in corresponding chapters.

• Four General Categories:

  • Pharmacological Reaction:

    • Extension of drug’s normal effects in the body.

    • Example: lowering blood pressure to unconsciousness.

    • Predictable, well-known; results in minor/no changes in management.

    • Frequency and intensity result from dose; typically resolve with dose change or discontinuation.

  • Allergic Reaction (Hypersensitivity):

    • Involves the immune system.

    • Immunoglobulins recognize the drug as foreign.

    • Immune response may lead to binding of immunoglobulin proteins.

    • Release of chemical mediators: histamine, cytokines, leading to reactions.

    • Range from mild (skin erythema/rash) to severe (bronchial constriction, tachycardia).

• Contraindication: Use of any drug is contraindicated if the patient has a known allergy to that specific drug product.

• Allergy Information: Reported by patients or observed by healthcare providers; must be documented thoroughly.

  • Example: "Penicillin; skin rash, pruritus" or "Penicillin; urticaria and anaphylactic shock requiring emergency intervention."

• Extreme Cases: In severe conditions (e.g., cancer, snakebite), administering a drug may be reasonable despite reported allergies. Premedication may be required (e.g., acetaminophen, diphenhydramine, prednisone).

• Idiosyncratic Reaction: An unexpected reaction not due to known drug properties or allergies, often a genetically determined response.

  • Study: Known as pharmacogenetics.

  • Typically caused by enzyme deficiencies or excesses.

  • Example: G6PD deficiency.

• Adverse Drug Reactions (ADRs): Can result from drug interactions, where multiple drugs produce an unintended effect.

  • Interactions can be beneficial or harmful; most clinically significant interactions are harmful.

Other Drug Effects

• Other Drug-Related Effects: Important to consider during therapy include teratogenic, mutagenic, and carcinogenic effects.

• Teratogenic Effects: Results in structural defects in the fetus; caused by teratogens.

  • Prenatal Development: Sensitive; disruption can lead to teratogenic effects.

  • Vulnerability: Fetus most vulnerable from third week to third month of development.

  • Congenital Anomalies: Different types can arise from drugs administered during pregnancy.

  • Health Canada: Safety classification for drugs used in pregnancy described in Chapter 4.

• Mutagenic Effects: Permanent changes in the genetic composition of organisms; can alter chromosome structure or DNA code.

  • Mutagens: Agents causing mutations; include radiation, viruses, and chemicals (e.g., benzene).

  • Active primarily during cell reproduction (mitosis).

• Carcinogenic Effects: Cancer-causing effects of drugs, chemicals, radiation, and viruses; agents causing these are called carcinogens.

PHARMACOGNOSY

• Plants: Important resource for medicinal preparations.

• Pharmacognosy: Process of identifying medicinal plants, their ingredients, pharmacological effects, and therapeutic efficacy.

• Many drugs used today are synthetically derived, but most were initially isolated from nature.

• Major groups of wild plants in Canada have edible members used by indigenous people.

• Common medicinal sources: Algae (e.g., seaweed), fungi (e.g., mushrooms), roots.

• Main sources for drugs: Plants, Animals, Minerals, and Laboratory synthesis.

• Alkaloids: Weak acids/bases from plants; examples include atropine, caffeine, nicotine.

• Animals: Source of hormone drugs (e.g., conjugated estrogens from pregnant mares, known as Premarin).

• Insulin sources: Pigs (porcine) and humans, with human insulin being more common due to recombinant DNA techniques.

• Other common mineral sources: Salicylic acid, aluminum hydroxide, sodium chloride.

PHARMACOECONOMICS

• Pharmacoeconomics: Study of economic factors influencing the cost of drug therapy.

• Example: Cost-benefit analysis of competing antibiotics for hospital formulary inclusion.

• Studies examine treatment outcomes data (e.g., recovery rates) in relation to the total costs of treatment.

TOXICOLOGY

• Toxicology: Study of poisons and unwanted responses to drugs and chemicals.

• Focuses on adverse effects of chemicals on living organisms.

• Clinical toxicology: Care of patients who have been poisoned.

• Causes of poisoning: Drug overdose, ingestion of household cleaning agents, snakebites.

• Poison control centres: Healthcare institutions with trained personnel to manage poisoning cases.

• Staff includes pharmacists, nurses, and physicians for triaging calls.

• Effective treatment priorities:

  • Preserve vital functions: Maintain airway, breathing, and circulation.

  • Prevent absorption of toxic agent or speed its elimination from the body.

• Common poisons and their specific antidotes are documented.

SUMMARY

• Understanding pharmacological principles is essential in drug therapy for safe nursing practice.

• Key areas include pharmacokinetics, pharmacodynamics, pharmacotherapeutics, and toxicology.

• Medications can treat disease but require up-to-date knowledge and clinical skills.

• Engage in critical thinking and decision making to prevent harmful treatments.

• Apply pharmacological principles to ensure safe and effective drug therapy.

• Always act on behalf of the patient and respect their rights.

• Summary of nursing considerations for various drug administration routes is found in Table 2.3.

Loeffler and Hart (2020) Chapter 3

Approach to Patient Care

Symptomatic Disease

• Patient Assessment Process:

  • Takes minutes to weeks depending on disease complexity.

  • Most diagnoses made from detailed history and physical examination.

• History Gathering:

  • Patient describes circumstances of problem emergence, including:

    • Severity: (sharp, dull, aching)

    • Quality: Timing (morning/evening, before/after meals, worsening during activity).

• Physical Examination:

  • Visual Inspection of:

    • Skin, Nails, Oral Mucous Membranes.

  • Use of Specialized Instruments:

    • Otoscope: inspect ear canal.

    • Ophthalmoscope: inspect retina.

    • Vaginal Speculum: inspect vagina and cervix.

  • Listening: Using Stethoscope for heart and breath sounds.

  • Percussion: Tapping to detect fluid in cavities.

  • Palpation: Applying pressure to find growths.

• Supplementary Procedures:

  • Used for additional information:

    • Radiologic tests: e.g., gastrointestinal endoscopy, bone assessments, artery patency tests.

    • Laboratory tests: measure metabolic products, assess organ function.

• Symptomatic Approach:

  • Suitable for acute diseases:

    • e.g., sinusitis, UTIs, bone fractures, myocardial infarction, ear infections.

  • Highlights chronic diseases:

    • Atherosclerosis, diabetes, hypertension, cancer, autoimmune diseases.

    • Poor outcomes if not treated early, leading to management vs. cure discussion.

    • Emphasis on early detection before symptoms emerge.

Asymptomatic Disease

• Early Diagnosis: Improves management and delays complications.

• Requires regular examinations (e.g., dental appointments, well-baby checks, physical exams).

• Screening: Identifies disease before symptoms appear to either cure or delay progression.

  • Example: Cancer screening for early detection.

• Involves gathering patient history, physical examinations, and targeted laboratory/radiologic tests.

• Explores risk factors for disease (e.g., smoking, family history).

  • Important for diseases like breast/ovarian cancer.

• Screening techniques include:

  • Dental exams for caries.

  • Breast palpation for lumps.

  • Skin inspections for cancers.

  • Pap test for cervical cancer.

  • Mammography for breast cancer.

• Screening decisions depend on:

  • Likelihood of disease.

  • Availability of treatment.

  • Cost of tests.

• Radiographic techniques can detect lung cancer but are expensive and involve radiation risk.

• Hypertension screening is simple and effective; requires a blood pressure cuff and lifestyle changes.

• Screening is reactive, treating early stages but does not prevent disease.

• Preventive measures are ideal for maintaining health and avoiding disease development.

Potential Disease

• Preventive Medicine: Discipline focused on disease prevention.

• Preventable Infectious Diseases: Smallpox, bubonic plague, typhoid fever, typhus, measles, diphtheria, whooping cough (reduced by immunization and sanitation).

• Example Diseases: Dental caries and periodontal disease (decreased by fluoride in drinking water).

• Lifestyle Links:

  • Alcohol: Traumatic accidents, liver disease.

  • Smoking: Various cancers, especially lung cancer.

  • Unprotected Sex: Risk for STDs (gonorrhea, syphilis, cervical cancer, HIV) and unintended pregnancies.

  • Sedentary Lifestyle & High-Fat Diet: Linked to chronic diseases (diabetes, obesity, atherosclerosis, cancers).

• Public Health Efforts: Promote healthful lifestyles, smoking cessation, nutrition counseling, exercise programs.

• Service Accessibility: Effective only if available to the public; many avoid preventive care until symptomatic.

• Vulnerable Populations: High incidence of preventable diseases in inner cities, poor, rural areas, and Native American populations.

• Systemic Approach: Ensuring screening tests and medications are accessible to those in need, necessitating commitment from public health departments to support underserved communities.

Diagnostic Tests and Procedures

• Test: Analysis performed on a specimen removed from a patient.

• Procedure: Involves manipulation beyond standard physical examination.

• Specimens: Obtained for tests through procedures.

• Pathologist: Most tests performed or supervised by a pathologist.

• Physicians: Procedures performed by various physicians, including radiologists and primary care providers.

Clinical Procedures

• Primary healthcare practitioners can perform common or simple tests and procedures themselves.

• Examples include:

  • Urinalysis

  • Vaginal smears for fungi detection

  • Throat cultures

• Primary care physicians may obtain samples for laboratory analysis:

  • Skin biopsies

  • Pap smear

  • Blood draws for serologic tests

• Manipulative procedures (e.g., sigmoidoscopy for distal colon examination) require specialists and specialized equipment (e.g., slit lamp examination of the eye).

Radiologic Procedures

• Radiology: Discipline using techniques like X-rays, CT scans, ultrasound, and nuclear medicine to diagnose disease.

• Purpose: Extends physical examination into areas not visualizable without surgery.

• X-rays: Depend on absorption properties of tissues; creates roentgenogram (X-ray image).

• Bone absorbs X-rays, appearing white; air-filled cavities appear dark.

• Fluoroscope: Allows live viewing of movements (e.g., barium passage) with X-rays.

• Limitations: X-rays mainly evaluate dense (bone) and light (lung) tissues.

• Contrast agents: Radiopaque chemicals that appear white on images; highlight hollow structures (e.g., bowel, blood vessels).

• Barium enema: Example of contrast use to show structural abnormalities.

• CT (Computed Tomography): Sophisticated X-ray technique creating cross-sectional images using computer analysis of absorption patterns.

• MRI (Magnetic Resonance Imaging): Uses radio-frequency signals and magnetic fields; does not use X-rays.

• Produces T1 (strong for lipids) and T2 (strong for water) images; no radiation exposure but requires stillness in a noisy space.

• MRI: Used for orthopedic and neurologic imaging; provides detailed anatomic information.

• MRI's confinement and noise can be intolerable; time and expense hinder routine use.

• Ultrasound: Utilizes high-frequency sound waves; greatest contrast in soft tissues and liquids.

• Ideal for cystic structures: gallbladder, urinary bladder, and pregnant uterus; preferred for gallstone detection.

• Safe during pregnancy, no radiation risk; detects twins, ectopic pregnancies, and fetal anomalies.

• Nuclear medicine: Involves injecting radioactive materials; evaluates localization within tissues.

• Scans for radioactivity recorded as nuclear isotope scans; assesses organ functional activity.

• PET: Uses positron-emitting radionuclides (C, N, O); converts matter to energy.

• Nuclear medicine shows functional status but is costly and exposes patients to radiation.

• Use in medicine is therefore limited.

Anatomic Pathology Tests and Procedures

• Surgical Pathology: Involves the diagnosis of lesions in tissue samples from patients.

• Diagnosis: Based on gross (naked-eye) and microscopic examination by a pathologist.

• Biopsy: Procedure to obtain small specimens of tissue.

  • Partial (Incisional) Biopsy: Includes part of the lesion, primarily for diagnosis.

  • Needle Biopsy: Involves needle insertion into solid organs to aspirate tissue, used for liver, kidney, and prostate diseases.

  • Excisional Biopsy: Entire small lesion is removed for diagnosis and treatment.

• Resection: Removal of large specimens in surgery, typically for treatment.

• Preparation: Biopsy and resection specimens require days for microscopic slide preparation and examination.

• Frozen Section: Rapid diagnosis option, prepared in minutes for immediate evaluation by the pathologist.

• Cytology Specimens: Consist of cells scraped from surfaces; primarily used to detect cancer cells.

  • Cytotechnologist examines stained smears; pathologist interprets abnormalities.

  • Body fluids (e.g., urine, sputum, cerebrospinal fluid) can be submitted for cytologic examination, mostly from uterine cervix (e.g., Pap smears).

• Fine-Needle Aspiration (FNA): Uses small needle for cytologic material collection; faster and less expensive than open biopsy, but may not always be adequate for diagnosis.

• Autopsy: Postmortem examination of organs to determine the cause of death and evaluate disease extent.

  • Important for identifying new diseases and informing treatment plans.

• Forensic Pathology: Investigates accidental and criminal deaths, often in collaboration with law enforcement.

  • Forensic pathologists typically work in metropolitan areas and support public health through evidence from investigations.

Clinical Pathology Tests and Procedures

• Clinical Pathology: Branch of pathology for laboratory tests on tissues and fluids.

• Laboratory Sections: Includes chemistry, hematology, blood bank (transfusion medicine), immunopathology, microbiology, cytogenetics.

• Biochemical Tests: Most common, used to evaluate organ function or detect abnormalities in blood.

  • Common test substances: Sodium, Potassium, Chloride, Calcium, Carbon Dioxide.

• Homeostasis: Serum electrolytes must remain in narrow ranges; abnormal values may indicate issues with lungs, heart, kidneys, or endocrine system.

• Glucose Monitoring: Routine screening for diabetes (both fasting and non-fasting).

• Liver Function Tests: ALT, AST indicate liver injury; Alkaline Phosphatase, Bilirubin, GGT = bile export issues.

• Kidney Assessment: BUN and creatinine measure kidney's ability to excrete waste.

• Lipid Testing: Cholesterol and triglycerides assessed for atherosclerosis risk.

• Urinalysis: Tests for microbes, red/white blood cells, glucose, and protein; identifies UTIs, kidney function, liver disorders.

• Chemistry Panel and Urinalysis: Most common tests in the lab.

• Additional studies for metabolic, immunologic, or toxicologic issues may be performed.

• Complete Blood Count (CBC): Common hematologic test measuring hemoglobin, RBCs, WBCs, and evaluating blood morphology.

• Red Blood Cells (RBCs): Transport oxygen; CBC parameters provide insights into oxygen transport health.

• White Cell Count: Indicates immune status; neutrophil increase suggests bacterial infection, and lymphocyte increase suggests viral infection.

• Platelets: Involved in clotting; indicates bone marrow response if immature cells are found.

• Special tests for anemia and coagulation disorders are available.

• Transfusion Medicine: Involves procurement, testing, processing, storage, and administration of blood components.

• Evaluation of adverse reactions to transfusion therapy.

• Immunopathology: Detects antigens and antibodies in blood and tissue; studies lymphocytes.

• Utilizes immunologic techniques to detect diseases such as immunodeficiencies, allergic diseases, and certain cancers.

• Microbiology Laboratory: Focuses on detecting pathogenic microorganisms in patient samples.

• Determines susceptibility to therapeutic agents.

• Bacterial Culture: Most common test; easy growth and sensitivity testing to antibiotics.

• Shift toward molecular tests for rapid and sensitive results.

• Example: Identification of Mycobacterium tuberculosis in days, even from suboptimal specimens.

• Molecular Techniques: Useful when cultures fail, for slow-growing organisms, or special media.

• Antimicrobial Sensitivity Testing: Can also be done with molecular methods.

• Cytogenetics: Examines chromosomal and genetic makeup for diagnosing disorders like trisomies, translocations, and deletions.

Molecular Diagnosis and Proteomics

• Molecular methods: Essential adjunctive diagnostic tools.

• Anatomic pathologists: Traditionally use pattern recognition for tumors.

• Microbiologists: Rely on cultures to identify pathogens.

• Molecular diagnosis: Identifies the molecular signature of neoplasms and microorganisms.

• Each organism or tumor has a unique genetic signature.

• Involves sequencing DNA/RNA with a known nucleic acid probe.

• PCR (Polymerase Chain Reaction): Amplifies gene sequences for detection.

• Fluorescent probes added to detect the presence of specific primers.

• Differentiates tumors that appear identical under a microscope based on their DNA profiles.

• Pharmacogenomics: Predicts drug responses based on a patient’s genetic makeup for proper dosing.

• Detects specific gene sequences or genetic defects for targeted care.

• Pathologists utilize molecular methods for diagnosing inherited disorders, cardiovascular diseases, and immunoglobulin abnormalities.

• DNA profiling: Standard in criminal investigations and law enforcement.

Public Health Laboratories

• Public Health Laboratories: Established by governments to control communicable diseases.

• Microbiologic Tests: Perform tests like blood tests for syphilis and rabies, and viral cultures and PCR to identify epidemics.

• Water Testing: Important aspect of community health.

• State Health Laboratories: Serve as a reference laboratory and link with the National Communicable Disease Laboratory in Atlanta, Georgia.

• Reporting: Highly contagious diseases must be reported to state authorities.