Ch 13 FREQUENCY OF DOSING

Question 1

enzymes responsible for phase 1
oxidation of drugs

Answer 1

cytochrome P450 (CYP450)

Question 2

CYP3A isoforms

Answer 2

In adults CYP3A4 is the most abundant, and there is low expression, and hence function, of CYP3A4 at birth

Question 3

Short t ½

Answer 3

-drug will need to be taken more often to stay in therapeutic range

Question 4

dosing and narrow therapeutic window

Answer 4

Drugs with a narrow therapeutic window, very toxic drugs should also be taken in small doses very frequently or infused intravenously.

Question 5

Volume of Distribution

Answer 5

often reported as litres per kilogram (L/kg)

Drugs tend to go to all of the three distinct compartments of body water
-intracellular water (28L)
-extracellular water
-The water between the cells is called
interstitial volume (10 L)
- the serum (4L)

Question 6

Drugs with Low to Moderate Volume of Distribution

Answer 6

If the drug all stayed in the plasma, it would have a volume of distribution of 4 L

More common are drugs that stay in the extracellular water only. Drugs that have low lipid solubility, such as the antibiotics amoxicillin and gentamicin, tend to stay outside of the cells. If the drug never goes into the cells, the volume of distribution is equal to the plasma plus
interstitial fluid together, or 14 L in a 70 kg person

Question 7

Drugs with High to Extremely High Volume of Distribution

Answer 7

-will penetrate the tissues
-high lipid solubility or high tissue binding
so that they will distribute to intracellular, plasma, and interstitial volume
-easily cross the placenta because of their lipid solubility and may accumulate in the fetus. In many ways, the fetus can be thought of as another compartment

very high Vd indicates is that it would take that volume of plasma to recover all of the drug that has been administered, not that the person has suddenly increased in volume. For example, if a drug has a Vd of 168 L (such as diazepam), there is so little drug in the plasma that it would take 168 L to recover all of the drug

Question 8

Loading Dose

Answer 8

The amount of drug required to immediately reach the therapeutic range

D = Vd x C0

Question 9

pregnancy blood volume

Answer 9

-increases 40 to 45%
-progressive hypervolemia
-the increase in plasma is greater than the increase in erythrocytes, which leads to a modest decrease in hematocrit and in hemoglobin concentration