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# Study Questions-Drug Disposition

1. What factors will affect diffusion of a nonionized drug and a drug which can be ionized across a
membrane?

Nonionized
• Fick’s law is main factor – moves from high concentration to low concentration. The larger the
concentration gradient the more movement occurs.
• Lipid-water partition coefficient.

Ionized
• Fick’s law
• pH of the solution as well as pKa of the drug.
• Lipid water partition coefficient.
• Carriers present

## Pharmakokinetics – input related to exposure (ADME)

Pharmacodynamics – exposure related to response (how the drug creates its effect)

3. Write out the Henderson-Hasselbalch equations for a weak acid and a weak base.

4. What is ion trapping? How does ion trapping differ for a weak acid and a weak base?

Ion trapping (pH partitioning)—Drugs accumulate on the side of membrane where pH favors ionization
(i.e., base to acid side) because its movement back to the other side is prevented due to the polarity
created. Bases accumulate in areas of decreased pH while acids accumulate in areas of increased pH.

5. How would ion trapping affect the absorption of a weak base from the stomach as compared to the
small intestine?

The pH of the stomach is ~1.5, meaning the basic drug would be predominantly ionized and unable to be
absorbed (trapped in the stomach).
The pH of the small intestine is ~7.5 meaning the basic drug would at least be partially (if not extensively
– depending on pKa) unionized and able to be absorbed from this site (partition out of – trapped
elsewhere).
6. How is it possible to have a volume of distribution for a specific drug that is much greater than the
total volume of the body?

The greater the extent to which the drug favors partitioning into the tissue, the greater the apparent total
volume of distribution is due to the decreased plasma concentration. This is used to describe the extent of
drug located in areas other than the plasma.

7. Drug X is present in plasma at a steady state concentration of 32 mg/ml. The T1/2 for drug X is 10
hours. How long would it take for the steady state concentration of drug X to decrease to 2
mg/ml (assuming a one compartment model)?

8. Write the equation for determining the rate of elimination of a drug which does exhibit
capacity-limited kinetics. How could this equation be simplified when considering a drug such as
phenytoin?
Phenytoin has a saturable pathway, meaning that the
concentration is high enough to create a saturated
elimination pathway resulting in the equation:
Rate of elimination = Vmax
This is also the equation for aspirin, and ethanol.

9. Which route of administration would be best for dosing a rather irritating chemical? Which routes
of administration would be suitable for avoiding the first pass effect?

IV routes are best for irritating chemicals because the drug is immediately removed from the site of
administration and significantly diluted by blood.

Routes that avoid the first-pass effect include IV, IM, SC, rectal (around 50%), sublingual, and
transdermal. Inhalation technically avoids first-pass effect for the most part but has mechanisms that have
a similar effect on bioavailability.

10. List two plasma proteins that are usually involved in binding drugs. What general types of drugs
bind to each protein and how could the level of each protein present in plasma be changed as a
result of disease?

Albumin
• Generally binds acidic drugs
• Liver disease often results in hypoalbuminemia

α1-acid glycoprotein
• Generally binds basic drugs
• Cancer, arthritis, and Crohn’s disease all cause increased synthesis of α1-acid glycoprotein and
lead to more extensive basic drug binding
11. Describe the major features of brain capillaries that contribute to the blood brain barrier.

## Astrocyte end-foot process

TIGHT JUNCTIONS
Pericyte
P glycoprotein – also found in the choroid plexus (produces CSF – located in the ventricles of the brain)

## 12. Under what circumstances could the GFR increase or decrease?

GFR increases with increased renal blood flow, diabetes insipidus diabetes mellitus.
GFR decreases with decrease in renal blood flow, in renal failure.
Alterations in oncotic pressure may cause an increase or decrease in GFR.
Efferent or afferent constriction or dilation can cause changes in GFR.
Changes in hormone levels may also cause changes in GFR.

13. Describe how altering urine pH would change the reabsorption of weak acids or weak bases.

Increasing acidity (decreasing pH) of the urine would favor the reabsorption of acidic drugs while
decreasing the reabsorption of basic drugs.
Increasing alkalinity would have the opposite affect.
This is all due to level of ionization.

## 14. How is GFR determined?

GFR is determined by measuring the clearance of creatinine or inulin because they are freely filtered but
not reabsorbed or secreted.

15. Describe the pathway the bile that is formed in the liver takes prior to release into the small
intestine.

Canaliculi  Hepatic Duct  Cystic Duct  (starts traveling away from small intestine into…) Gall
bladder  Storage in gall bladder  back down Cystic Duct  Common Bile Duct  Small intestine
*The Sphincter of Oddi is located at the end of the common bile duct and controls the release of bile into
the duodenum.

16. How would the presence or absence of glucuronidase in the intestine alter enterohepatic cycling?

Glucuronidase converts conjugates into the less water-soluble unconjugates so they may then be
reabsorbed. This increase in reabsorption increases the half-life of the compound.

Using antibiotics decreases the bacteria population in the intestines and therefore the amount of
glucuronidase. This means that enterohepatic cycling during abx treatment often allows less absorption
(and a shorter half-life) of materials otherwise normally reabsorbed.