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PHARMCOKINETICS ALLIE PUNKE CRITICAL CARE ABSORPTION ABSORPTION • Passive diffusion OR Carrier-mediated absorption is affected in critically ill patients? • What is the preferred route to feed a critically ill patient? Why? • What class of drugs may further decrease gut blood flow (and therefore absorption)? • If given medication for stress ulcer prophylaxis, how can this affect absorption? ABSORPTION • AB was admitted to the ICU. She is being started on enteral nutrition. What (if any) modifications should be made avoid an interaction with phenytoin? • A. Nothing. It does not interact with phenytoin. • B. Stop the feedings for about 30 minutes when giving phenytoin to prevent a high concentration • C. Stop the feedings for about 2 hours when giving phenytoin • D. The phenytoin dose should be increased to counteract any absorption problems. ABSORPTION • When a patient is receiving enteral nutrition, there are a few medications that interact with the feedings. • Phenytoin • Effect: Dec. serum levels • What to do: Hold tube feedings ~2 hours around dose • Warfarin • Effect: Decreased INR • What to do: Hold tube feedings or increase dose (more so if expecting to be on feedings for long term) • +/- Fluroquinolones • Effect: Maybe decreased levels…maybe not clinically significant. Also, can depend on site of infection (UTI vs bacteremia) CRITICAL CARE VOLUME OF DISTRIBUTION VOLUME OF DISTRIBUTION • What are some factors that can change Vd in ICU patients? • Giving large volume of fluids • pH changes • Protein binding • Albumin is…. Increased Or decreased in patients? • AAG is….Increased Or decreased in patients? VOLUME OF DISTRIBUTION • MB is admitted to the ICU. Her pH is 7.18. Which of the following types of drugs would have an increased volume of distribution? • • • • A. Acidic drugs B. Basic drugs C. Neither D. Both VOLUME OF DISTRIBUTION • AB is admitted to the ICU and needs to be started on an aminoglycoside. Based on other critically ill patients, AB will also likely require: • A. Higher loading dose • B. Lower loading dose • C. Loading dose will not change Follow up: Why did we give AB a higher LD? • A. Increased excretion of the drug • B. Increased volume of distribution • C. Both • D. Neither VOLUME OF DISTRIBUTION • Remember… • Volume of distribution is used to calculate LD • Clearance is used to calculate MD • Be able to take these principles and apply to a patient’s dosing regimen CRITICAL CARE METABOLISM METABOLISM • Be able to recognize which drugs are low E vs high E (as well as the equations). • Be able to recognize which drugs are bound to albumin vs AAG METABOLISM • AB is a patient in the ICU. Her albumin level recently fell to 1.9 from 4. Do any of her drugs need to be adjusted? • • • • A. Phenytoin dose needs to be lowered. B. Phenytoin and morphine doses need to be lowered. C. Ceftriaxone dose needs to be lowered. D. Morphine dose needs to be lowered. METABOLISM METABOLISM • AB is started on propofol for sedation. Her albumin level is still low around 2.4. Should the propofol dose be adjusted? • • • • A. Yes, the Css and Css,u are both affected. B. No, neither the Css or Css,u are affected. C. Yes, because the Css is affected. D. Yes, because the Css,u is affected. CRITICAL CARE EXCRETION EXCRETION • Renal function…. • Decreased GFR • Difficult to determine • Acute kidney injury possibly may receive CRRT • Fluctuating status of renal excretion QUESTIONS? [email protected]