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Chapter 59: Clinical Pharmacology and the Kidney

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A 65-year-old African–American man with a longstanding history of uncontrolled diabetes mellitus and chronic kidney disease is admitted with volume overload, dyspnea, and hypertension (160/95). His BUN and serum creatinine are 45 mg/dL and 3.8 mg/dL, respectively, and his corresponding eGFR is 18 mL/min/1.73 m2. Urine dipstick is positive for protein (+++) and serum albumin is 2.5 g/dL.

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Which ONE of the following statements is CORRECT regarding the oral bioavailability of drugs in this patient?

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A. Diabetes may lead to slowed gastric emptying, but generally this does not affect oral bioavailability.

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B. Hypoalbuminemia leads to reduced protein binding and thus decreased oral bioavailability.

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C. Volume overload leads to edema of the GI tract, which may result in a significant increase in oral bioavailability.

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D. Concurrent administration of antacids facilitates absorption and oral bioavailability.

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E. First pass metabolism in the GI tract has no clinically significant effects on oral bioavailability.

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The answer is A. Delayed gastric emptying related to gastroparesis may be present in diabetic patients. GI motility may be decreased and can affect the time required to reach the maximal plasma concentration. However, this typically does not affect the maximal plasma concentrations (Cmax) achieved and the overall extent of absorption, so bioavailability is not affected.

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A 65-year-old African–American man with a longstanding history of uncontrolled diabetes mellitus and chronic kidney disease is admitted with volume overload, dyspnea, and hypertension (160/95). His BUN and serum creatinine are 45 mg/dL and 3.8 mg/dL, respectively, and his corresponding eGFR is 18 mL/min/1.73 m2. Urine dipstick is positive for protein (+++) and serum albumin is 2.5 g/dL. Which ONE of the following statements is CORRECT regarding possible alterations in volume of distribution (VD) in the patient?

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A. Hypoalbuminemia leads to decreased VD of protein bound drugs.

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B. Uremia may lead to decreased tissue binding and decreased VD of digoxin.

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C. Increased total body water may lead to volume overload and decreased VD of hydrophilic drugs such as aminoglycosides.

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D. VD of drugs with large baseline VD (ie, >2 L/kg) are most commonly affected by acute changes in volume status.

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E. VD does not change until renal replacement therapy is initiated.

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The answer is B. The VD of digoxin is decreased by up to 50% in patients with stage 5 CKD. The ...

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