Chapter 36. Drug Development

Question 1

Guidelines that take into account size, hydrogen-bonding capacity and partition coefficient to determine when a drug is likely to have poor bioavailability.

Answer 1

lipinski’s rules

Question 2

A measure of strength of the interaction of a ligand for a receptor defined by the expression Kd = [R] [L]/[RL] where [R] is the concentration of the free receptor, [L] is the concentration of the free ligand, and [RL] is the concentration of the receptor-ligand complex.

Answer 2

dissociation constant (Kd)

Question 3

The tight junctions between endothelial cells that line blood vessels within the brain and spinal cord.

Answer 3

blood-brain barrier

Question 4

IC50 = Ki (1+ 1 [S]/ KM) An equation that describes the concentration of a drug required to elicit 50% of the maximal biological response (IC50). Note that the IC50 is a function of the inhibition constant of the inhibitor (Ki), the substrate concentration and the KM for the enzyme being inhibited.

Answer 4

CHENG-PRUSOFF equation

Question 5

The fluids and tissues that a drug can occupy after leaving the blood stream.

Answer 5

compartment

Question 6

(pronounced “add-me”) Properties that characterize a drug&#39s ease of absorption, distribution, metabolism, and excretion.

Answer 6

adme

Question 7

A small molecule that binds to a protein, inducing a specific structural change. For instance, a steroid is a ligand for a steroid-hormone receptor.

Answer 7

ligand

Question 8

Accumulations of cholesterol on the arterial walls of patients with high blood levels of cholesterol.

Answer 8

atheroma

Question 9

The modification of drugs to aid in their excretion.

Answer 9

drug metabolism

Question 10

The synthesis of a large number of structurally related compounds with the use of the same chemical reactions but a variable set of reactants.

Answer 10

combinatorial chemistry

Question 11

In drug metabolism, the addition of particular groups to drugs that increase water solubility and provide labels that can be recognized to target excretion.

Answer 11

conjugation

Question 12

The oxidation reactions of xenobiotic compounds, including drugs.

Answer 12

phase I transformation

Question 13

Unwanted effects of drugs.

Answer 13

side effect

Question 14

A measure of the strength of binding of an inhibitor to an enzyme. Ki = [E] [I]/[EI] where [S] is the concentration of free enzyme, [I] is the concentration of free inhibitor, and [EI] is the concentration of the enzyme-inhibitor complex.

Answer 14

inhibition constant (Ki)

Question 15

Compounds, such as drugs, foreign to an organism’s normal biochemistry.

Answer 15

xenobiotic compounds

Question 16

Networks of fine capillaries in the kidney that act as filters.

Answer 16

glomerulus

Question 17

Muscle pain or weakness.

Answer 17

myopathy

Question 18

The quantity defined as the ratio of the peak concentration of a compound given orally to the peak concentration of the same dose injected directly into the bloodstream.

Answer 18

oral bioavailabilty

Question 19

Cycling of compounds from the bloodstream into the intestine and back into the bloodstream, a process that can significantly decrease the rate of excretion of some drugs.

Answer 19

enterohepatic cycling

Question 20

A means of identifying active compounds by screening large libraries of both natural products and purely synthetic compounds prepared in the course of many drug-development programs.

Answer 20

high-throughput screening

Question 21

The metabolism of drugs in the liver resulting from blood flow from the intestine to the liver through the portal vein.

Answer 21

first-pass metabolism

Question 22

Oxidation of the C-3 carbon atom that is ß to a functional group; in the degradation of a fatty acyl CoA molecule, the sequence of oxidation, hydration, and oxidation reactions that converts a methylene group at C-3 into a ß-keto group.

Answer 22

oxidation

Question 23

The conjugation reactions of xenobiotic compounds, including drugs.

Answer 23

phase II transformation

Question 24

The ratio of the dose of a compound that is required to kill one-half of the animals (referred to as the LD50 for “lethal dose”) to a comparable measure of the effective dose, usually the EC50.

Answer 24

therapeutic index

Question 25

A key method in combinatorial chemistry that depends on solid-phase synthetic methods. Reactions are performed on beads. Each of the reactions with the first set of reactants is performed on a separate set of beads. The beads are then pooled, mixed, and split into sets. The second set of reactants is then added. Many different compounds will be produced, but all of the compounds on a single bead will be identical.

Answer 25

split-pool synthesis

Question 26

Designing stable compounds from scratch that have the correct shape and other properties to fit precisely into a binding site of a target molecule, such as an enzyme or receptor.

Answer 26

structure-based drug design

Question 27

A treatment such as sugar pills known to not have intrinsic value.

Answer 27

placebo

Question 28

A relationship between structure and function of molecules.

Answer 28

structure-activity relationship (SAR)

Question 29

The tendency to perceive improvement in a subject who believes that he or she is receiving a potentially beneficial treatment.

Answer 29

placebo effect