EB

Pharmacology: Therapeutic Index, ADRs, and Patient Safety

Therapeutic Index, Toxicology Concepts, and Nursing Implications

  • Case example and context

    • Digoxin is discussed as a drug used for heart-related conditions; focus on toxic effects and the importance of checking drug levels when symptoms suggest toxicity.
    • Mention of a case study in slides related to this material.

  • Key pharmacology definitions

    • Maximal efficacy: the greatest effect a drug can produce.
    • Relative potency: the amount of drug needed to produce a given effect; a more potent drug requires a smaller dose to achieve the same effect.
    • Narrow therapeutic index (TI): small difference between the dose or concentration that produces the desired effect and the dose or concentration that produces toxicity.
    • MEC = Minimum Effective Concentration: the plasma concentration at which therapeutic effects begin.
    • MTC = Minimum Toxic Concentration: the lowest plasma concentration at which toxic or unacceptable effects begin to occur.

  • Narrow therapeutic index (TI) implications

    • Statement: A narrow TI means a small difference between MEC and MTC.
    • Expressed concept: MEC ext{ and } MTC ext{ are close or } |MTC - MEC| ext{ is small}
    • Practical consequence: small dosing errors can lead to toxicity or subtherapeutic effects.
    • Example context: medications used for seizure control (seizure medications) and drugs like digoxin are given as examples where TI considerations are critical.
    • Supporting details: MTC is defined as the lowest plasma drug concentration at which toxic or unacceptable effects begin to occur.

  • Supporting therapies in acute illness

    • Dehydration and management: dehydration reduces physiological function and requires supportive care.
    • Supportive therapy: supports body function during acute illness or recovery (e.g., fluids, electrolytes).
    • The fastest way to correct dehydration and electrolyte disturbances: Intravenous fluids (IV).

  • Therapeutic strategies and care approaches

    • Prophylactic therapy: preventive treatment; example—preoperative antibiotics (surgeons may pre-treat with antibiotics).
    • Palliative therapy: care aimed at improving quality of life, particularly in end-of-life situations; not a cure but comfort-focused.
    • Context of palliative care: emphasis on quality of life in end-stage disease; focus on comfort and sometimes relevant to nursing practice, not only for terminal patients but also broader care planning.
    • In recent years (approximately over the last eight, ten, fifteen plus years): growing emphasis on palliative care in hospital settings to improve patient comfort.

  • Adverse drug reactions (ADRs): side effects vs reactions

    • Distinction:
    • Side effect: an expected, often predictable effect of a drug, which may appear at therapeutic doses; common due to individual variability.
    • ADR (adverse drug reaction): an unwanted, noxious response to a drug at doses normally used for prevention, diagnosis, or therapy, or for modification of physiologic function.
    • Note on terminologies used in the transcript: ADRs are occasionally labeled as ABR in the spoken content; conceptually refer to adverse drug reactions.

  • Types of adverse drug reactions (ADRs)

    • Intrinsic ADRs (the most common):
    • Direct extension of the known pharmacodynamic actions of the drug.
    • Predictable and dose-dependent.
    • Examples include toxic reactions and tachyphylaxis.
    • Tachyphylaxis: a diminishing response to successive doses of a drug, often due to receptor saturation or other pharmacodynamic changes; common with drugs acting on the nervous system.
    • Related concepts: tolerance (decreased response to a drug with regular use) and dependence (physical or psychological dependence).
    • Idiosyncratic ADRs (uncommon and unpredictable):
    • Not explained by the drug’s known pharmacodynamics; about 30% of ADRs fall into this category.
    • Independent of dose and may be genetically linked.
    • Example emphasis: allergic reactions.
    • Anaphylaxis as a specific severe ADR:
    • Life-threatening, acute reaction requiring immediate treatment.
    • Typical treatment: epinephrine (adrenaline).
    • Allergic reactions: unpredictable, may be immune-mediated; signs relate to stimulation of the immune system.
    • Carcinogenic effects: some drugs have carcinogenic potential; described as unpredictable and not easily explained by pharmacodynamics.
    • Enzyme-specific and unaltered responses: not terms used to describe ADRs in this content.

  • Practical examples and terminology clarity

    • Anaphylaxis management emphasized: epinephrine is the standard immediate intervention.
    • Tachyphylaxis noted as a diminishing response, particularly with CNS-active drugs; receptor saturation helps explain why increasing doses yield less response.
    • Genetic factors: idiosyncratic reactions may be genetically linked; individual genetic differences can underlie unpredictable ADRs.
    • The concept that some adverse effects or reactions may be dose-independent or unpredictable is highlighted under idiosyncratic ADRs.

  • Patient safety and nursing practice principles

    • Core emphasis: patient safety is the number one priority.
    • Five rights of medication administration (mentioned as a safety framework):
    • Right patient
    • Right drug
    • Right dose
    • Right route
    • Right time
    • Three checks during medication administration:
    • Check when pulling the medication from the shelf.
    • Check during preparation/drawing up the medication.
    • Check before administration to the patient.
    • Two identifiers for patient verification:
    • Examples include patient name and a second identifier (e.g., date of birth or medical record number).
    • ABNE process: a framework referenced for medication administration (master the ABNE process).
    • Pharmacokinetics fundamentals (absorption, distribution, metabolism, excretion) are crucial for predicting how drugs work.
    • Pharmacodynamics: understanding drug action and receptor theories helps explain why drugs have particular effects.
    • Monitoring and therapeutic drug monitoring: assess therapeutic effects and signs of toxicity; drug levels can be critical in guiding care.
    • Advocacy and readiness to intervene: be prepared to call and question or escalate if patient safety is at risk; patient advocacy is essential.
    • Handling patient refusals:
    • Document refusals.
    • Engage with the patient to explain the purpose of the drug and its benefits.
    • Use patient-friendly strategies, such as showing packaging to help reassure patients, particularly when generics look different.
    • Special considerations for elderly patients and generic substitution:
    • Generics may look different from brand-name products; visual differences can concern patients; show packaging to aid acceptance.

  • Final takeaways for practice

    • Always prioritize patient safety and adhere to safety protocols (five rights, three checks, two identifiers).
    • Maintain strong knowledge of pharmacokinetics and pharmacodynamics to predict drug behavior and potential adverse effects.
    • Be vigilant for both predictable ADRs (intrinsic) and unpredictable ADRs (idiosyncratic), and know the appropriate immediate interventions (e.g., epinephrine for anaphylaxis).
    • Use therapeutic drug monitoring when indicated to prevent toxicity, especially for drugs with narrow TI (e.g., digoxin).
    • Communicate effectively with patients and families, particularly around end-of-life care, palliative options, and ensuring comfort and dignity.

  • Quick glossary recap

    • MEC: Minimum Effective Concentration
    • MTC: Minimum Toxic Concentration
    • TI: Therapeutic Index (conceptual difference between MEC and MTC; narrow TI implies small gap)
    • Tachyphylaxis: diminishing response to a drug over time
    • ADR/ADR terminology: adverse drug reaction; intrinsic vs idiosyncratic
    • Anaphylaxis: life-threatening hypersensitivity reaction treated with epinephrine
    • Palliative care: care focused on quality of life rather than cure

  • Observations on expression from the transcript

    • Several terms appear in shorthand or with minor transcription inconsistencies (e.g., "ABR" for ADR, "Tactaphylaxis" for tachyphylaxis, "Jotson" as an unclear reference).
    • The content emphasizes practical nursing actions and safety culture (three checks, five rights), pharmacology fundamentals, and patient-centered care.

  • Questions for review

    • Define MEC and MTC and explain how they relate to a narrow TI.
    • What are the five rights of medication administration?
    • How do intrinsic and idiosyncratic ADRs differ in terms of predictability and dose dependence?
    • What is tachyphylaxis, and why is it especially relevant for drugs acting on the nervous system?
    • When is epinephrine indicated, and what is its purpose in treatment?
    • How should nurses handle patient refusals or concerns about medication appearance (e.g., generics vs. brand-name packaging)?