Pharmacokinetics

Multiple Short term infusion

Multiple short term infusion A patient is receiving 80 mg of gentamicin as IV infusion over a 30 minute period every 8 hours. Two samples have been obtained: 30 minutes after the end of the short term infusion and 30 minutes before the administration of the next dose. The serum gentamicin concentrations are 4.9 and 1.7, respectively. Assume steady state. Develop a dosing regimen that will produce peak and trough concentrations of about 8 and 1 mg/L, respectively. A. 120 mg Q8H B. 160 mg Q8H C. 140 mg Q12H D. 180 mg Q 12H E. 280 mg Q24H

Drug metabolism and transport Drug metabolism converts a drug to be more ___________, thereby ________________ renal reabsorption. A. hydrophobic, increasing B. lipophilic, increasing C. hydrophilic, decreasing D. lipophilic, decreasing T/F: Metabolism always results in loss of pharmacologic activity

Drug metabolism and transport Which of the following is true about Phase I reactions? A. Involves conjugation B. Makes drug more liphophilic C. Includes hydrolysis, reduction, and oxidation D. Includes glucuronidation, sulfation, and acetylation E. A and D Which of the following is true about Phase II reactions? A. Involves conjugation B. Makes drug more liphophilic C. Includes hydrolysis, reduction, and oxidation D. Includes glucuronidation, sulfation, and acetylation E. A and D

Drug metabolism and transport What is the goal of phase I and II reactions? To convert _______________ to ________________ that are excreted more easily. What enzymes are involved in Phase I? A. UGT B. CYP What enzymes are involved in Phase II?

Drug metabolism and transport For the enzyme CYP2C9, explain what the 2, C, and 9 stand for…. Why does amiodarone increase the AUC and Cmax of Simvastatin, but not Pravastatin? A. Pravastatin is a CYP3A4 substrate, but simvastatin isn’t B. Pravastatin is a CYP2C19 substrate, but simvastatin isn’t C. Simvastatin is a CYP3A4 substrate, but Pravastatin isn’t D. Simvastatin is a CYP2C19 substrate, but pravastatin isn’t

Drug metabolism and transport CYP3A4 is present in which of the following? A. Gut only B. Liver only C. Gut and liver D. Neither gut or liver Grapefruit inhibits CYP3A4 in which of the following?

Drug metabolism and transport Which of the following are uptake transporters? A. Pgp B. OATP C. CYP D. UGT When Simvastatin and Gemfibrozil are given together, Simvastatin has an increase in AUC and Cmax. Which of the following explain this interaction? A. Gemfibrozil is a CYP3A4 inhibitor B. Gemfibrozil is a CYP3A4 inducer C. Gemfibrozil is a OATP inducer D. Gemfibrozil is a OATP inhibitor

Drug metabolism and transport When grapefruit juice is given concomitantly with a CYP3A4 substrate, such as simvastatin, which of the following occur? A. Increased CL B. Decreased CL C. Increased F D. Increased F and Decreased CL When digoxin, a Pgp substrate, is given concomitantly with Quinidine, a potent inhibitor of Pgp, which of the following occur? A. Increased F, Increased CL B. Increased F, Decreased CL C. Decreased F, Increased CL D. Decreased F, Decreased CL

Drug metabolism and transport Which of the following describe the interaction between digoxin, a Pgp substrate, and rifampin, a Pgp inducer? A. Rifampin increases Cmax and AUC in both oral and IV digoxin administration B. Rifampin decreases Cmax and AUC for both oral and IV digoxin administration C. Rifampin ONLY decreases Cmax and AUC for IV digoxin D. Rifampin ONLY decreases Cmax and AUC for oral digoxin

Drug metabolism and transport How do Pgp and CYP3A4 work together? A. They work together, with CYP3A4 pumping the drug out which gives Pgp more time to metabolize the drug B. They work as a cycle, with Pgp pumping the drug out which keeps CYP3A4 from becoming saturated with drug C. Pgp also metabolizes drug, so it decreases the amount of drug that CYP3A4 needs to metabolize D. They don’t—they work separately

Drug metabolism and transport Which CYP enzymes account for the majority of drug metabolizing enzymes? T/F There are functional relevant polymorphisms for 3A4. Which of the following are true? A. CYP3A5, 3A7, 3A4 are found equally in everyone B. CYP3A7 is found mostly in newborns C. CYP3A5 is found in a majority of Caucasian patients D. CYP3A7 is found in a majority of African American patients

Protein binding

Perfusion vs permeability Which of the following drugs would most likely be perfusion rate-limited? A. Hydrophilic, bulky drug B. Lipid soluble, small drug Which of the following drugs would most likely be permeability rate-limited?

Protein binding When equilibrium has been reached, this means that the total concentration may be _____________, and free concentration will be _________________. A. The same, different B. Different, different C. Different, same

Protein binding A drug is 99.9% protein bound, and the therapeutic concentration is 2mg/ml to 5 mg/ml. Calculate fu: A. 0.01, B. 0.1 C. 0.0001 D. 0.001

Protein binding A certain drug is 80% protein bound. Another drug is given that decreases the protein binding to 60%. Which of the following would change? A. Loading dose B. Maintenance dose C. Half life D. AUC, unbound E. None of the above

Protein binding Which of the following do NOT affect the half life of a drug? A. fut B. fup C. CLu D. Vt Which of the following MUST change for you to change the LD? A. CLu C. fut Which of the following MUST change for you to change the MD?*

Protein binding What type of drugs does albumin bind? A. Acidic B. Basic What type of drugs does AAG1 bind? Which type of protein has high capacity, but low affinity? A. Transcortin B. Albumin C. Thyroid binding globulin D. A and C Which type of protein has low capacity, but high affinity?

Protein binding A CKD receiving phenytoin (Css=8mg/L in) has an albumin level of 2g/dl. Determine how to manage the patient. Normal levels are Css= 10-20mg/L, Css,u=1-2mg/L. A. Increase dose, since 8mg/L is below Css B. Decrease dose C. Leave dose the same