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Science
Medicine
Pharmaceutical Sciences
Pharmacology Final Review (Exam 3)
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REVIEW MATHEMATICS REGARDING STEADY STATE
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REVIEW MATHEMATICS REGARDING ELIMINATION CONSTANTS
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What error can result from the analysis of drug concentrations vs. time, when serum samples were not taken frequently enough and/or early enough time points after an IV drug administration. Describe the effects of this error on 2 parameters estimated from the concentration vs. time data.
The could result in mislabeling of the compartment type models which would cause inaccurate dosing regimens and dosing amounts. The elimination rate constant and area under the curve would vary greatly.
List 10 pharmacokinetic parameters that can be calculated from data following a single IV and a single oral dose of the drug.
1. Volume of distribution
2. Area under the curve
3. Elimination constant
4. Absorption constant
5. Elimination half-life
6. Absorption half-life
7. Renal clearance
8. Total body clearance
9. Concentration at time 0
10. Fraction of oral absorption
How does a rate and rate constant differ?
The rate is the amount of drug loss or absorption with units of ug/L, mg/mL, etc. The rate constant is consistent throughout the graph and can be different for elimination or absorption. The rate constant is given in units of time -1.
What is a "flip-flop" model for an orally dosed drug. Diagram the oral dosed concentration vs. time graph and label the pertinent components for a "flip-flop" model.
A flip-flop model occurs when the Ka is less than K, causing a change in IV and oral dosing lines.
With constant rate IV infusion, how can one calculate the time necessary to reach a steady-state drug concentration? Also, how would the concentration-time graph differ if you increased the infusion rate.
The time to reach steady state occurs in 6.65 half lifes (99%), so 6.65 x T1/2 = 99% Css.
The overall concentration to reach steady state would increase, causing a higher plateau, but the time to reach Css would stay the same.
Describe why first pass effect is important in regards to orally dosed drugs.
It is important because orally dosed drugs are typically absorbed through the GI tract (if first-order). Thus, they are filtered through the liver before reaching central circulation. This is important because orally dosed drugs have to be maintained above the minimum effective concentration and below the minimum toxic concentration.
Describe how curve stripping of a pharmacokinetic time vs. concentration graph is accomplished and why it is useful.
It is accomplished by taking the last few points on the oral dosing curve and extrapolating the line back to t=0. Then using the new line (named the terminal line), obtain a y-intercept and k-value. You can then use points from the terminal line and the original curve to obtain a residual line. This is useful to obtain the oral AUC, absorption rate constant and absorption half-life. We then can obtain information for oral administration of a drug.
With IV infusion administration of a drug:
a) how long does it take to get to 90% of steady-state?
b) how long does it take to get to 99% of steady-state?
a) 3.32 half lives
b) 6.65 half lives
Briefly compare/contrast the concepts of physiologic and compartment modeling, to include benefits and downfalls of each.
Benefits of compartment models: Obtain statistical information regarding IV and oral drug administration
Downfall of compartment models: They are considered a "preliminary" model to physiologic modeling and the data can not be 100% certain
Benefit of physiologic models: They give accurate representation at all time points in specific tissues
Downfall of physiologic models: They waste a lot of lab animals because tissue samples need to be obtained at various time points. It is also very difficult mathematically.
Describe the difference between catenary and mammillary compartment models.
Catenary models are a series of compartments, whereas mammillary models have one central compartment with various subgroups. Mammillary models are the most common.
In a two compartment model for IV drug dosage, what do the two individual linear lines stripped from the concentration vs. time graph represent?
They represent elimination and distribution of the drug. They both have variable numbers. A = y-intercept for elimination, B = y-intercept for distribution, a = elimination rate constant (first order), b = distribution rate constant (first order).
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