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Pharmacokinetics/ Pharmacodynamics Joseph M. Swanson, Pharm.D., FCCP, FCCM University of Tennessee College of Pharmacy Memphis, Tennessee Christopher A. Droege, Pharm.D., FCCP, FCCM, FASHP UC Health…

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Pharmacokinetics/Pharmacodynamics Pharmacokinetics/ Pharmacodynamics Joseph M. Swanson, Pharm.D., FCCP, FCCM University of Tennessee College of Pharmacy Memphis, Tennessee Christopher A. Droege, Phar…

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Learning Objectives 3 min

Pharmacokinetics/Pharmacodynamics Learning Objectives 1. Describe the changes in critically ill patients that alter drug absorption. 2. Explain how critical illness affects drug distribution. 3. D…

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Pharmacokinetics/Pharmacodynamics subcutaneously every 12 hours, and fosphenytoin 150 mg intravenously every 8 hours. 2. Which most accurately assesses the risk factors for the decreased absorption…

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Exam Content Outline 1 min

Pharmacokinetics/Pharmacodynamics BPS Critical Care Pharmacy Examination Content Outline This chapter covers the following sections of the Critical Care Pharmacy Examination Content Outline: 1. Doma…

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Pharmacokinetics/Pharmacodynamics I.  INTRODUCTION Pharmacokinetics (PK) refers to the movement of a drug throughout the body, particularly absorption, distribution, metabolism, and excretion (ADME)…

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Pharmacokinetics/Pharmacodynamics C. Subcutaneous/Intramuscular/Sublingual – Subcutaneous and intramuscular drug administration avoids first-pass metabolism by the liver and can increase the bioavai…

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Pharmacokinetics/Pharmacodynamics III.  ABSORPTION A. Bioavailability (F) refers to the percentage of an administered dose of drug that reaches the systemic circulation. All non-intravenous medicati…

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Pharmacokinetics/Pharmacodynamics activity of the low-molecular-weight heparin certoparin in critically ill patients, of whom 40.3% were receiving vasopressors. Less than 50% of patients receiving st…

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Pharmacokinetics/Pharmacodynamics 1. Drug-enteral-nutrition interactions: Some drugs potentially interact with enteral nutrition. The degree of interaction and clinical significance varies. a. Cipr…

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Pharmacokinetics/Pharmacodynamics Patient Case 2. I.L. is a 32-year-old man receiving stress ulcer prophylaxis with esomeprazole 40 mg intravenously every day. Which drug will most likely have an in…

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Data Tables 3 min

Pharmacokinetics/Pharmacodynamics D. Protein Binding – Many drugs are bound to serum protein carriers such as albumin, AAG, lipoproteins, and cortisol-binding protein. Albumin and AAG are particular…

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Pharmacokinetics/Pharmacodynamics F. Extracorporeal Membrane Oxygenation – Use of extracorporeal membrane oxygenation (ECMO) in critically ill patients has increased over the years. Depending on the…

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Pharmacokinetics/Pharmacodynamics Patient Cases 3. R.H. is 20-year-old man who presents to the emergency department with nausea and vomiting. His vital signs are significant for heart rate 130 beats…

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Pharmacokinetics/Pharmacodynamics C. Hepatic Metabolism – Hepatic clearance refers to the volume of blood that is completely cleared of drug by the liver per unit of time. The ability of the liver t…

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Pharmacokinetics/Pharmacodynamics Figure 1 shows how a change in each variable of CLH affects the Css and Cssu. For high extraction ratio drugs, altered hepatic blood flow affects both the Css and th…

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Pharmacokinetics/Pharmacodynamics E. Low Extraction Ratio Drugs – Drugs with a low hepatic extraction ratio undergo a lower degree of hepatic enzyme metabolism; therefore, clearance is limited by he…

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Pharmacokinetics/Pharmacodynamics F. Effect of Changes in Intrinsic Clearance 1. Drug interactions – A major mechanism for altered intrinsic clearance is not caused by changes in critical illness,…

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Pharmacokinetics/Pharmacodynamics c. Phase II enzymatic activity may also be enhanced in patients with TBI, as evidenced by increased lorazepam clearance. Similar data for lorazepam were noted in th…

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Pharmacokinetics/Pharmacodynamics VI.  EXCRETION A. Renal Excretion 1. For most drugs, the kidneys are the primary site for excretion of the parent drug, metabolites, or both. Urinary excretion of…

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Pharmacokinetics/Pharmacodynamics c. Impaired renal clearance i. Decreased renal excretion of drugs during AKI is the most widely applicable change occurring in critically ill patients. Depending o…

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Pharmacokinetics/Pharmacodynamics v. The recommendations include using the estimated GFR (eGFR) or CrCl to assess renal function for drug dosing. The update provides several equations that can be us…

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Pharmacokinetics/Pharmacodynamics where dose is the desired dose for CKRT, dose n is the normal dose of a drug, CLnonrenal is the nonrenal clearance of a drug, Qeff is the effluent rate, SC…

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Pharmacokinetics/Pharmacodynamics suggesting cutoffs of about 40% for carbapenems, 50% for penicillins, and 50%–75% for cephalosporins (Clin Infect Dis 2008;26:1-10). Modeling usually suggests improv…

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Pharmacokinetics/Pharmacodynamics 6. Nonantibiotic drugs: PD studies of other drugs in critically ill patients are sparse. a. The PD parameter for continuous infusions of many anticoagulants is the…

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Data Tables 2 min

Pharmacokinetics/Pharmacodynamics Table 2. TDM Ranges for Select Drugs Used in Critically Ill Patients Drug Timing of Blood Sample Therapeutic Rangea Unbound Therapeutic Range Amikacin Peak (extended…

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Pharmacokinetics/Pharmacodynamics Determination of the calculated peak concentration: Cmax = C1 (eke(t)) where Cmax is the calculated peak concentration and t is the time between the C1 and the end of…

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Pharmacokinetics/Pharmacodynamics B. Drug Nomograms/Protocols – A nomogram is a diagram representing the relationship between three or more variables using scales arranged such that one variable can…

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Pharmacokinetics/Pharmacodynamics REFERENCES Aarab R, van Es J, de Pont AC, Vroom MB, Middeldorp S. Monitoring of unfractionated heparin in critically ill patients. Neth J Med. 2013;71(9):466-471. h…

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Pharmacokinetics/Pharmacodynamics needing replacement—evidence and implications? A systematic review. Surgery. 2006;139(3):419-432. https:// doi.org/10.1016/j.surg.2005.07.035 Brown CS, Liu J, Riker…

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Pharmacokinetics/Pharmacodynamics β-lactam infusion in severe sepsis. Am J Respir Crit Care Med. 2015;192(11):1298-1305. https://doi.org/10.1164/ rccm.201505-0857oc Fernandez C, Buyse M, German-Fatta…

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Pharmacokinetics/Pharmacodynamics Jochberger S, Mayr V, Luckner G, et al. Antifactor Xa activity in critically ill patients receiving antithrombotic prophylaxis with standard dosages of certoparin:…

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Pharmacokinetics/Pharmacodynamics on phenytoin metabolism in neurotrauma patients. J Clin Pharmacol. 1997;37(2):129-139. https://doi. org/10.1002/j.1552-4604.1997.tb04771.x Mehta NM, Halwick DR, Dods…

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Pharmacokinetics/Pharmacodynamics Staphylococcus aureus infections: a revised consensus guideline and review by the American Society of Health- System Pharmacists, the Infectious Diseases Society of…

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Pharmacokinetics/Pharmacodynamics identifying at-risk patients. Crit Care. 2013;17(1):R35. https://doi.org/10.1186/cc12544 van den Broek MP, Groenendaal F, Egberts AC, Rademaker CM. Effects of hypot…

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Answers & Explanations 4 min

Pharmacokinetics/Pharmacodynamics ANSWERS AND EXPLANATIONS TO PATIENT CASES 1. Answer: B Increasing the concentration of an antibiotic at an infection site is most important (Answer B is correct).…

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Pharmacokinetics/Pharmacodynamics changes, this ratio changes. The unbound steady-state concentration does not change, but the total concentra- tion decreases, which causes the change in the ratio.…

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Self-Assessment 4 min

Pharmacokinetics/Pharmacodynamics ANSWERS AND EXPLANATIONS TO SELF-ASSESSMENT QUESTIONS 1. Answer: B Decreased anti-Xa activity occurs in critically ill patients receiving several different low-mole…

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Pharmacokinetics/Pharmacodynamics that the Vd has changed, which would likely result in lower or unchanged concentrations (Answer B is incor- rect). Vancomycin tissue penetration may be better if in…

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