4. Pharmacokinetics Flashcards
A dose of 750 mg of acetaminophen is administered to a patient. A blood sample is drawn one hour after the dose is administered. The concentration of acetaminophen is measured as 8 mcg/mL (which is 8 mg/L). Acetaminophen has a volume of distribution of 51 L. Determine the total amount of drug remaining in the body 1 hour after dose administration. Do not enter the units, only the number. Round to the nearest whole number.
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A chemist wishes to increase the rate of gut dissolution of a new tablet formulation. Which of the following would be the most useful option to consider for most medications?
A. Decreasing the surface area of the tablet.
B. Increasing the surface area of the tablet.
C. Adding an emulsifying agent.
D. Instructing the patient to take thirty minutes after the morning dose of a proton pump inhibitor.
E. Instructing the patient to take thirty minutes after the morning dose of an antacid.
B. In order to increase tablet dissolution the chemist could increase the tablet’s surface area and/or decrease the size.
A drug that exhibits first-order kinetics will display the following properties:
A. A linear relationship between dose and serum level
B. A nonlinear relationship between dose and serum level
C. A Michaelis-Menten relationship
D. As the concentration increases the AUC decreases in a corresponding manner
E. Short half-life and increased bioavailability
A. In first-order kinetics, the rate of elimination is directly proportional to the amount of drug remaining in the body.
A medical resident asks the pharmacy student to explain to the medical students why most drugs are weak acids or weak bases. Which of the following points are correct and could be included in the explanation?
A. If the drug dissolves in the gut fluid it will not get absorbed.
B. If the compound is charged it cannot interact with the cell receptors.
C. Weak acids are highly charged compounds in physiological pH.
D. Weak bases are highly charged compounds in physiological pH.
E. Charged compounds dissolve more easily in water than uncharged compounds.
E. In order for absorption to occur the drug has to dissolve in the watery-contents of the stomach. If the drug is a weak acid it will have a negative charge and if it is a weak base more of the drug will be charged because more of the drug will have either lost or gained a proton. Charged compounds dissolve easily in water. A dissolved drug can get absorbed into the blood.
A drug that exhibits Michaelis-Menten kinetics will display the following properties: (Select ALL that apply.)
A. A linear relationship between dose and serum level until the metabolizing enzymes are saturated
B. Improved distribution
C. A nonlinear relationship between dose and serum level
D. Saturable kinetics
E. Poor bioavailability
A, C, D. Michaelis-Menten, or saturable kinetics, begins as first-order, but when the metabolism becomes saturated, the concentration increases rapidly. Drugs with this type of kinetics begin as first-order kinetics, but can change to zero order once a certain dose is reached and metabolizing enzymes are saturated. At this point, toxicity can result.
A new antibiotic for community-acquired pneumonia (CAP) was recently FDA-approved. The drug was presented at the Pharmacy and Therapeutics Committee meeting. The drug monograph included the following information:
Community-acquired pneumonia dosing (IV): 675 mg IV Q8H
Community-acquired pneumonia dosing (PO): 675 mg PO TID
Protein binding: 18%
Metabolism: partially hepatic
Half-life (elimination): 1.6 - 2.1 hours
What is the bioavailability of this new drug?
A. 0%
B. 1%
C. 25%
D. 50%
E. 100%
E.
A newly approved drug has a volume of distribution of 82 L and a clearance of 9.26 L/hr. Calculate the half-life of this drug. Do not enter the units, only the number. Round to the nearest tenth.
6.1
A new antibiotic for community-acquired pneumonia (CAP) was recently FDA-approved. The drug was presented at the Pharmacy and Therapeutics Committee meeting. The drug monograph included the following information: Community-acquired pneumonia dosing (IV): 675 mg IV Q8H Community-acquired pneumonia dosing (PO): 675 mg PO TID Protein binding: 18% Metabolism: partially hepatic Half-life (elimination): 1.6 - 2.1 hours What hospital policy/protocol should this drug be added to?
A. The CAP Policy
B. The Antibiogram Protocol
C. The Therapeutic Interchange Protocol
D. The Pharmacokinetic Policy
E. The High Risk Medication Protocol
C. Drugs like this are easily converted to the oral formulation in the same dose. Most hospitals have a “Therapeutic Interchange” Protocol or “IV to PO” Protocol (approved by the Medical Staff) that allows medications to be converted if certain criteria are met.
A patient has overdosed on phenytoin and is experiencing symptoms of phenytoin toxicity. The prescriber asks how much drug the patient has consumed because he wishes to calculate how long it will take the patient to clear the drug. The pharmacist offers the following correct advice: (Select ALL that apply.)
A. Phenytoin exhibits Michaelis-Menten elimination.
B. Once the metabolizing enzymes are saturated, phenytoin elimination follows zero-order elimination. The elimination will not correlate in a linear fashion with the amount of drug consumed.
C. With significant overdose the patient will display extreme irritability, anxiety and difficulty sleeping and concentrating.
D. With significant overdose the patient will exhibit CNS depressant effects.
E. Phenytoin initially follows first-order elimination.
A, B, D, E. When a drug such as phenytoin is overdosed, the elimination changes from first to zero-order. This is because the enzymes that metabolize phenytoin are full of the drug (or saturated) and cannot metabolize the extra drug. The additional phenytoin will not be subjected to first-pass (it will pass through the saturated liver) and increase the serum concentration dramatically. This is called Michaelis-Menten, or saturable, kinetics. Overdose will produce CNS-depressant effects.
A patient has been using phenytoin 100 mg three times daily for 6 months. A steady state phenytoin level was taken and found to be 9.8 mcg/mL. She recently had a seizure, so the prescriber increased the dose to 100 mg with breakfast and lunch, and 200 mg with dinner. The prescriber calculated that if 300 mg/day provided a level of 9.8 mcg/mL, then 400 mg/day would increase the level to approximately 13 mcg/mL. After the dosage change, the patient started to slur her words, felt fatigued and returned to the medical office office. The level was retaken and found to be 18.7 mcg/mL. At both visits, her serum albumin level was 4.2 g/dL. What is the most likely reason for the phenytoin level?
A. Phenytoin exhibits increased metabolism with higher doses.
B. Phenytoin exhibits Michaelis-Menten kinetics.
C. Phenytoin has reduced protein binding at higher doses.
D. Patient non-compliance.
E. The patient did not take with food.
B. The prescriber did not consider that the drug exhibits Michaelis-Menten kinetics. It is important for pharmacists to be prepared to answer questions about Michaelis-Menten kinetics and patient scenarios.
A patient is being treated with an investigational drug. The investigational drug protocol states that the patient should receive one dose of the drug IV, then no further doses should be given until the level reaches 8.5 mg/L or below. The medication administration record and pertinent information are included below. In an effort to reduce expense, drawing drug levels should be kept to a minimum during the study period.
Investigational Drug Dose #1 administered at 0800 on 1/10/15
Dose infused from 0800 to 1000
Serum level: 1/10/15 @ 4pm = 47.9 mg/L
Serum level: 1/11/15 @ 5pm = 29.7 mg/L
It is currently 5pm on 1/11/15. How many hours will it take for the patient’s serum level to reach exactly 8.5 mg/L so he can receive the next dose of the investigational drug? Round to the nearest whole number.
A. 24 hours
B. 36 hours
C. 65 hours
D. 72 hours
E. 110 hours
65
First calculate the patient-specific ke using the two levels and time between the levels with the formula on page 92: ke = [-ln (29.7 / 47.9)] / 25]. Next, use the same formula and the ke to solve for time to reach 8.5 mg/L (you must rearrange the formula): time between levels (or time to reach 8.5 mg/L exactly) = [-ln (8.5 / 29.7) / ke from the previous calculation] = 65 hours.
An intravenous drug is administered as a 225 mg dose. The resulting AUC is 52 mg x hr/mL. Bioavailability of the oral formulation is 100%. Calculate the clearance of this drug. Do not enter the units, only the number. Round to the nearest hundredth.
4.33 Bioavailability can be presented as a percentage or a decimal. Cl = 225/52 x 1.0 = 4.33 mL/hr.
An oral drug is administered as a 225 mg dose. The resulting AUC is 52 mg x hr/mL. Bioavailability of the oral formulation is 50%. Calculate the clearance of this drug. Do not enter the units, only the number. Round to the nearest two decimal places.
2.16 Bioavailability can be presented as a percentage or a decimal. Cl = 225/52 x 0.5 = 2.16 mL/hr.
AUC values of drug X following IV administration of 50 mg and oral administration of 100 mg were found to be 70 mg x hr/mL and 90 mg x hr/mL respectively. Calculate the absolute bioavailability of drug X. Round to the nearest whole number. Do not enter the percent sign.
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Based on knowledge of functional groups, which drug is amphetamine?
A. Drug A
B. Drug B
C. Drug C
D. Drug D
E. None of these
A. Drug A in Image Group #6 is amphetamine. It contains an amine functional group.
Based on knowledge of functional groups, which drug is an aminoglycoside?
A. Drug A
B. Drug B
C. Drug C
D. Drug D
E. None of these
C. Drug C in Image Group #3 is gentamicin, an aminoglycoside. Based on the name, it would be expected to have amine groups on the structure. The functional group containing nitrogen in structure D is an amide, not an amine.
Based on knowledge of functional groups, which drug is aspirin?
A. Drug A
B. Drug B
C. Drug C
D. Drug D
E. None of these
B. Drug B in Image Group #2 is acetylsalicylic acid (aspirin). It is the only drug in this grouping that contains an acidic functional group.
Based on knowledge of functional groups, which drug is sulfamethoxazole?
A. Drug A
B. Drug B
C. Drug C
D. Drug D
E. None of these
C. Drug C in Image Group #1 is sulfamethoxazole. It is the only drug in this grouping that contains a sulfonamide functional group.
Phenothiazines contain a thioether functional group. Which drug is a phenothiazine?
A. Drug A
B. Drug B
C. Drug C
D. Drug D
E. None of these
A.
Which drug contains a carboxyl (carboxylic acid) functional group?
A. Drug A
B. Drug B
C. Drug C
D. Drug D
E. None of these
B. Drug B in Image Group #7 is ibuprofen. It contains a carboxyl functional group.
Which drug contains a ketone functional group?
A. Drug A
B. Drug B
C. Drug C
D. Drug D
E. None of these
D. Drug D in Image Group #5 is fenofibrate. It contains a ketone functional group.
