Chapter 12

Upon completion of the chapter and exercises, the student pharmacist will be able to

1. Define dose rate and dose interval and how they influence the average concentration at steady state (Css,avg) and peak-to-trough ratio (P:T).

2. List the factors influencing the bioavailability of an orally administered drug.

3. List the determinants of volume of distribution and determine how changes in volume of distribution may change dosing needs.

4. List the determinants of renal clearance and determine how drugs and disease may alter renal clearance and thus alter Css,avg and/or P:T of a given drug cleared by the kidney.

5. List the determinants of hepatic clearance and determine how drugs and disease may alter hepatic clearance and thus alter Css,avg and/or P:T of a given drug cleared by the liver.

6. Given appropriate concentration–time data, calculate k, t1/2, Cmax, Cmin, and AUC for that drug in that patient.

7. Explain the reasons for drug monitoring and how that will impact the patient's outcome.

8. Discuss the attributes of extended-interval dosing and traditional dosing for aminoglycosides.

You are the student pharmacist rounding with the team this month and patient X is not doing as well as the neurology team would like. The neurology resident and medical student come to you to discuss what they might do about pain control and seeing if they can "wake the patient up by reducing his medications." There are really two issues. They have started to reduce the morphine dose in an effort to see if the patient will begin to respond to the team, but so far he has not. Alternatively, they are slightly hesitant to reduce the dose because even though the dose of morphine seems to be high enough to keep him from responding to pain, he appears to the team to be agitated. The team is coming to you to see what other drugs on the patient profile may be confounding patient improvement.

As the student pharmacist responsible for working with the team this month, you are expected to participate in solving the problem. First, you must decide what the problem is.

1. What other drugs is the patient being given that may interact?

2. You find there are no pharmacologic or pharmacokinetic drug interactions. What problems are specifically related to the morphine?

3. What do you know about the absorption of morphine across the blood–brain barrier (BBB)? What happens to the Tmax or AUC?

4. Does trauma cause any change in protein binding or transport, α1-acid glycoprotein, albumin, or P-glycoprotein?

5. What happens to the metabolism of morphine in the brain? What happens to the T1/2? Are the active metabolites responsible?

6. Once you have determined the answers to the above questions, what would be your response to the medical student and resident?

Hypothesize several scenarios for the morphine problem above; include not only ...

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