Week 4 - Pharmacokinetics - Nichols

Question 1

Membrane flux is directly proportional to:

See equation!

Answer 1

-Concentration gradient
-diffusion constant
-membrane water coefficient
-membrane surface area
permeability constant

Question 2

Membrane flux is inversely proportional to:

See equation!

Answer 2

• Membrane thickness

- size of molecules passing through

Question 3

Using renal ion trapping, you could administer sodium bicarbonate in order to:

Answer 3

Eliminate a weak acid in the urine.

this is because increasing urine pH promotes elimination of weak acids

Question 4

Weak bases get trapped in what kind of environments?

Answer 4

Acid environments.

Question 5

What attribute of ABC and SLC carriers could explain their role in drug-drug interaction?

Answer 5

Both are selective and inhibited by closely related compounds

Question 6

What is Lipinski’s Rule of 5 ????

Answer 6

To have good bioavailability drugs must:

• Have less than 5 hydrogen bond donors (OH or NH)
• Have less than 10 hydrogen bond acceptors (total O or N)

So basically a small, moderately lipophilic molecule

Question 7

What is the apparent volume of distribution?? ( Vd )

Answer 7

Volume in which the drug appears to be distributed.

Total grams in body / total concentration in a measured compartment (g/L)

Answer will be in liters

Question 8

Considering a drug that distributes mostly to the whole body water of the patient. How will the Vd differ between a fit patient and one with a lot of body fat?

Answer 8

The proportion of fat compared to water content is higher in a patient with a lot of body fat. This means that concentration of drug per liter is going to be greater in fattier patient. This will cause the apparent volume of distribution (Vd) to be smaller in the fattier patient.

Question 9

Considering a drug that distributes lipophilically. How will the Vd differ between a fit patient and one with a lot of body fat?

Answer 9

Because there is a higher proportion of fat per amount of weight in a fattier patient, more of the drug will perfuse into the fat. This will leave a lot more drug in the serum of the lean patient, and the concentration will be greater. So the fit patient will have a smaller Vd in this case.

Question 10

What exactly is the Cytochrome P450 system (CYP) ????

Answer 10

Numerous enzymes in class, localized to smooth ER.
-Responsible for phase 1 metabolism of many drugs
(anything to add?)

Question 11

Inhibitors of Biotransformation (drug metabolism) :

Answer 11

Microsomal Drug oxidation

• competitive inhibition
• inhibition of P450 (cietidine, keotconazole, grapefruit)

Nonmicrosomal Drug oxidation

• disulfuram (inhbitis aldehyde dehydrogenase)
• iproniazid (inhibits monoamine oxidase)

Question 12

Stimulators of Biotransformation (drug metabolism):

Answer 12

Induce expresssion of P450:

• phenobaritol
• carcinogenic hydrocarbons
• alcohol
• rifampin

Enhanced clearance of drug ( seems like tolerance)

Question 13

Don’t memorize maybe, but be familiar with a few things in regards to Phase 1 and Phase 2 reactions:

Answer 13

Phase 1:
Add or expose functional group
Oxidation most common rxn
Metabolites generally more polar and can be active or inactive

Phase 2:
Synthetic reactions
Glucuronidation most common reaction  (acetylation or methylation also happen)
Metabolites generally more polar
Inactivation results