PHA 4120
First Exam
Fall 1996
NOTE: This page should be viewed with a
graphic based browser such as Netscape 2 or later version.
1. Chose whether the following statements for a low extraction drug are True or False
2. Listed below are 4
drugs and their physicochemical properties. Choose the
drug(s) that most appropriately complete(s) each of the
following statements:
| Property | Drug A | Drug B | Drug C | Drug D |
| Molecular weight |
85,000 | 273 | 315 | 378 |
| pKa | - | base | neutral | acid |
| pKa=2 | pKa=11 | |||
| Polarity of unionized form | Protein | non-polar | non-polar | extremely polar |
| fu | 0 | 0.01 | 1.0 | 0 |
| fuT | 0 | 0.01 | 0.1 | 0 |
| E(liver) | no metabolism | 0.01 | 0.95 | no metabolism |
3. Chose whether the following statements
are True or False (5 pts)
| Drugs which are very lipophillic tend to distribute well into body tissues. | |
| Drugs with a high Kp value have a large volume of distribution (assume drug is able to cross membranes). | |
| The volume of distribution depends on the ability of the drug to pass membranes and the degree of plasma and tissue binding. | |
| The extraction ratio for a high extraction drug is relatively independent of the plasma protein binding. | |
| The extraction ratio for a low extraction drug is independent of the tissue protein binding. |
4. Complete the following
statements (4 points)
| A | The maximum value which hepatic clearance can approach that of the | |
| B | The smallest possible volume of distribution of a drug is that of | |
| C | The larger the elimination rate constant of a drug the __the half-life. | |
| D | A neutral, lipophyllic drug is likely to be
absorbed faster in the ___ than in the ____ (Fill in which section of the GI tract) |
|
| E | The higher the hepatic extraction ratio of a drug, the ___ the oral bioavailability |
5. Increasing the following parameters will result in a decrease in the rate of active transport of a drug (4 points)
| decrease in transporter molecules | |
| reduction in ATP | |
| increase in the partition coefficient of the drug between lipid and water | |
| more efficient removal of the drug from the drug stream close to the site of absorption |
6. Explain the term volume
of distribution in your own words (no equations). Do not use
more than 30 words.
7. What might be the rationale for a drug
company to develop an insulin aerosol?
8. You are a research pharmacist involved
with animal studies for new drugs. You are provided the
following data from a recent in vitro study of two Drugs A
and B (i.e. conducted in a test tube) which shows the
half-life for the metabolism of two different drugs by one
enzyme.
Drug A |
Drug B |
||
| Initial Concentration(mg/L) | half-life(hr.) | Concentration (mg/L) | half-life (hr.) |
| 50 | 2.5 | 50 | 3 |
| 100 | 5 | 100 | 3 |
| 200 | 10 | 200 | 3 |
a) Which drug is exhibiting zero order metabolism and why?
-Keep your answer short.
b) What is the rate constant (Km) of the metabolic reaction for drug A? To receive complete credit the units of Km must be correct.
c) What is the rate constant (Km) of the metabolic reaction
for Drug B? To receive complete credit the units of Km must
be correct.
9. A drug is given as an I.V. bolus
injection. The rate of change of the plasma concentration
follows zero order kinetics. Give the differential equation
describing the above situation.
Solve the differential equation to obtain an expression
for C in terms of t.
10. Patient JA is a asthmatic patient receiving theophylline. After having received an i.v. bolus dose of theophylline JA's theophylline plasma concentrations are determined to be 11.5 and 4.5 mg/ml 1 and 6 hours after administration of the dose. Calculate the elimination rate constant and the half-life of theophylline in this patient.
Click
here to type answer. Use lower case and commas where
necessary. Chose the drug(s) that most complete(s)
this statement.