Pharmacokinetics and Pharmacodynamics
The relationships between drugs and the body can be described by pharmacokinetics and pharmacodynamics.Pharmacokinetics describes what the body does to the drug through absorption, distribution, metabolism, and excretion, whereas pharmacodynamics describes what the drug does to the body.Photo Credit: Getty Images/Ingram PublishingWhen selecting drugs and determining dosages for patients, it is essential to consider individual patient factors that might impact the patient’s pharmacokinetic and pharmacodynamic processes. These patient factors include genetics, gender, ethnicity, age, behavior (i.e., diet, nutrition, smoking, alcohol, illicit drug abuse), and/or pathophysiological changes due to disease.For this Discussion, you reflect on a case from your past clinical experiences and consider how a patient’s pharmacokinetic and pharmacodynamic processes may alter his or her response to a drug.To PrepareReview the Resources for this module and consider the principles of pharmacokinetics and pharmacodynamics.Reflect on your experiences, observations, and/or clinical practices from the last 5 years and think about how pharmacokinetic and pharmacodynamic factors altered his or her anticipated response to a drug.Consider factors that might have influenced the patient’s pharmacokinetic and pharmacodynamic processes, such as genetics (including pharmacogenetics), gender, ethnicity, age, behavior, and/or possible pathophysiological changes due to disease.Think about a personalized plan of care based on these influencing factors and patient history in your case study.BELOW IS THE QUESTION——————-Post a description of the patient case from your experiences, observations, and/or clinical practice from the last 5 years. Then, describe factors that might have influenced the pharmacokinetic and pharmacodynamic processes of the patient you identified. Finally, explain details of the personalized plan of care that you would develop based on influencing factors and patient history in your case. Be specific and provide examples.BELOW IS THE REQUIRED READING—————Learning ResourcesRequired Readings (click to expand/reduce)Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants (2nd ed.) St. Louis, MO: Elsevier.Chapter 1, “Prescriptive Authority” (pp. 1-3)Chapter 2, “Rational Drug Selection and Prescription Writing” (pp. 4-7)Chapter 3, “Promoting Positive Outcomes of Drug Therapy” (pp. 8-12)Chapter 4, “Pharmacokinetics, Pharmacodynamics, and Drug Interactions” (pp. 13-33)Chapter 5, “Adverse Drug Reactions and Medication Errors” (pp. 34-42)Chapter 6, “Individual Variation in Drug Response” (pp. 43-45)American Geriatrics Society 2019 Beers Criteria Update Expert Panel. (2019). American Geriatrics Society 2019 updated AGS Beers criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society, 67(4), 674-694. doi:10.1111/jgs.15767American Geriatrics Society 2019 updated AGS Beers criteria for potentially inappropriate medication use in older adults by American Geriatrics Society, in Journal of the American Geriatrics Society, Vol. 67/Issue 4. Copyright 2019 by Blackwell Publishing. Reprinted by permission of Blackwell Publishing via the Copyright Clearance Center.This article is an update to the Beers Criteria, which includes lists of potentially inappropriate medications to be avoided in older adults as well as newly added criteria that lists select drugs that should be avoided or have their dose adjusted based on the individual’s kidney function and select drug-drug interactions documented to be associated with harms in older adults.Drug Enforcement Administration. (2021). CFR – Code of Federal Regulations Title 21. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=1300This website outlines the code of federal regulations for prescription drugs.Drug Enforcement Administration. (n.d.-a). Mid-level practitioners authorization by state. Retrieved May 13, 2019 from http://www.deadiversion.usdoj.gov/drugreg/practioners/index.htmlThis website outlines the schedules for controlled substances, including prescriptive authority for each schedule.Drug Enforcement Administration. (2006). Practitioner’s manual. Retrieved from http://www.legalsideofpain.com/uploads/pract_manual090506.pdfThis manual is a resource for practitioners who prescribe, dispense, and administer controlled substances. It provides information on general requirements, security issues, recordkeeping, prescription requirements, and addiction treatment programs.Drug Enforcement Administration. (n.d.-b). Registration. Retrieved February 1, 2019, from https://www.deadiversion.usdoj.gov/drugreg/index.htmlThis website details key aspects of drug registration.Fowler, M. D. M., & American Nurses Association. (2015). Guide to the code of ethics for nurses with interpretive statements: Development, interpretation, and application (2nd ed.). American Nurses Association.This resource introduces the code of ethics for nurses and highlights critical aspects for ethical guideline development, interpretation, and application in practice.Institute for Safe Medication Practices. (2017). List of error-prone abbreviations, symbols, and dose designations. Retrieved from https://www.ismp.org/recommendations/error-prone-abbreviations-listThis website provides a list of prescription-writing abbreviations that might lead to misinterpretation, as well as suggestions for preventing resulting errors.Ladd, E., & Hoyt, A. (2016). Shedding light on nurse practitioner prescribing. The Journal for Nurse Practitioners, 12(3), 166-173. doi:10.1016/j.nurpra.2015.09.17This article provides NPs with information regarding state-based laws for NP prescribing. CORE SKILL: applying ADME to a SPECIFIC patient, and explaining why the same dose behaves differently in different bodies. The assignment wants a personalized plan, not a textbook recital.
PHARMACOKINETICS — what the BODY does to the DRUG:
— ABSORPTION: route, bioavailability, FIRST-PASS METABOLISM (oral drugs traverse the liver before reaching systemic circulation — which is why IV, sublingual, and transdermal routes bypass it and require different doses). GI factors: pH, motility, food, gastric surgery, emesis.
— DISTRIBUTION: volume of distribution; PROTEIN BINDING (albumin) — and here is the clinically loaded point: in hypoalbuminemia (malnutrition, liver disease, nephrotic syndrome, cancer cachexia), the FREE (active) fraction of highly protein-bound drugs rises, so a “normal” total drug level can conceal toxicity. Phenytoin and warfarin are the classic examples. Also: the blood-brain barrier, lipophilicity, and body composition (obesity and aging increase fat mass, prolonging the effect of lipophilic drugs like diazepam).
— METABOLISM: CYP450 enzymes, phase I (oxidation) and phase II (conjugation). INDUCERS (carbamazepine, rifampin, phenytoin, St. John’s wort — an OTC/herbal that patients don’t report unless asked) lower levels of co-administered drugs; INHIBITORS (fluoxetine, paroxetine, ketoconazole, and grapefruit juice, which inhibits intestinal CYP3A4) raise them. PROdrugs require metabolism to become active — CODEINE must be converted by CYP2D6 to morphine, so ULTRARAPID 2D6 metabolizers can achieve toxic morphine levels (this is why codeine is contraindicated in children post-tonsillectomy and in breastfeeding mothers — there were infant deaths) while POOR metabolizers get no analgesia at all. That single example demonstrates pharmacogenomics, prodrug metabolism, and polymorphism at once, and it is worth building a paper around.
— EXCRETION: renal (estimate with eGFR/creatinine clearance — and note that serum creatinine ALONE is a poor guide in the elderly and in low-muscle-mass patients, because low muscle mass produces a deceptively normal creatinine despite reduced renal function), hepatic/biliary.
PHARMACODYNAMICS — what the DRUG does to the BODY: receptor binding, agonist/antagonist/partial agonist, therapeutic index, dose-response, potency vs. efficacy, tolerance, and receptor up/down-regulation.
PATIENT FACTORS TO ADDRESS EXPLICITLY (the rubric requires them): AGE (neonates — immature enzymes and reduced protein binding; elderly — reduced renal and hepatic clearance, altered body composition, polypharmacy); GENDER; GENETICS (CYP2D6/2C19 polymorphisms, HLA-B*1502); PATHOPHYSIOLOGY (renal impairment, hepatic impairment, heart failure reducing perfusion, cancer cachexia); BEHAVIOR (adherence, alcohol, tobacco — which INDUCES CYP1A2 — diet, herbal supplements).
FOR THE CASE (e.g., the patient with metastatic cancer): trace the specific mechanism — hepatic metastases impair metabolism; renal metastases impair excretion; cachexia lowers albumin and raises free drug fraction; nausea/vomiting impairs oral absorption. Then state the CONCRETE PLAN CHANGE: dose reduction, alternate route, extended interval, therapeutic drug monitoring, avoidance of high-protein-bound or hepatically cleared agents.
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