MCMP 824: Lecture 1

Question 1

Log D will never be ______ log P

Answer 1

above

Question 2

Challenges associated with drug design and administration (5)

Answer 2

1) a drug must have the correct molecular structure
2) a drug must have chemical properties that favor absorption into the circulatory system
3) drug chemistry or dosage must account for metabolism
4) drug chemistry or dosage must account for non-specific protein binding

Question 3

a drug must have the correct molecular structure which is critical for?

Answer 3

activation of the receptor AND ONLY the receptor

Question 4

the drug will bind to its receptor and

Answer 4

alter it’s activity with selectivity

Question 5

drug chemistry or dosage must account for metabolism why?

Answer 5

body has enzymes that attack these “drugs” which often happen in the liver. We have to account for those properties to create an effective drug

Question 6

drug chemistry or dosage must account for non-specific protein binding why?

Answer 6

a lot of proteins exist within your systemic circulation and and the serum protein can act like a sink that can affect the effective concentration of your drug

Question 7

often drugs inhibit the activity of _______ and often bind ______ with substrates.

Answer 7

• enzymes

- competitively

Question 8

what is a drug? (4)

Answer 8

• molecular entity
• organic functional groups
• characteristic 3D pattern
• elicits a biological response

Question 9

Ideal structural properties of drugs (4)

Answer 9

1) log P between -0.4 and 5.6
2) molecular weight between 160 and 480 Da
3) total number of atoms between 20 and 70
4) some combination of functional groups

Question 10

what are 4 of these combiational functional groups?

Answer 10

1) aliphatic or aromatic rings
2) carboxamide group
3) aliphatic amine (tertiary)
4) alcoholic hydroxy group, carboxy ester, or keto group

Question 11

why do we care about the ideal properties of a drug?

Answer 11

these properties ensure movement through lipid membrane and the ability to present functional groups in an arrangement able to bind drug receptors

Question 12

in general, functional groups contribute ?

Answer 12

polarity

Question 13

aerol groups and aliphatic hydrocarbon groups contribute

Answer 13

lipophilicity

Question 14

the actions of drugs result from their

Answer 14

chemical structures

Question 15

a drug can be thought of as a 3D collection of

Answer 15

specific groups - generally polar

Question 16

functional groups are attached to a _____ ____ that is generally

Answer 16

• carbon skeleton

- non-polar

Question 17

the following parameters play a role in linking molecular structure to a specific pharmacological activity (6)

Answer 17

1) molecular size
2) molecular shape
3) functional group distribution
4) stereochemistry
5) electronic effects
6) chemical reactivity

Question 18

drugs with ____ __ ____ typically elicit similar pharmacological activites

Answer 18

similar chemical structures

Question 19

how can we identify critical aspects or motifs AKA critical functional groups that we need to keep a drugs activity

Answer 19

use the simplest structures to identify minimal motifs (functional groups) involved in receptor binding

Question 20

small structural differences can lead to major differences in (2)

Answer 20

potency and pharmacological activity

Question 21

two drugs with the same molecular formula and core carbon framework but with a different ____ ____ of _____ _____, are likely to have different biological activites

Answer 21

• 3D arrangement of functional groups

Question 22

what is the example of 3D arrangements and subtle differences that we talked about?

Answer 22

cocaine + atropine

Question 23

pharmacodynamics is the study of

Answer 23

how a drug modifies an organism

Question 24

pharmacokinetics is the study of how

Answer 24

the organism modifies a drug

Question 25

_______ ( ) - drugs that are poorly solvated by water or are water hating and typically non-polar

Answer 25

hydrophobic (lipophilic)

Question 26

_____ ( ) - molecules that are readily solvated by water or are water loving, typically polar

Answer 26

hydrophilic (lipophobic)

Question 27

what are some examples of hydrophilic molecules

Answer 27

• OH
• COO-
• NH3+

Question 28

these are molecules that contain both hydrophobic and hydrophilic groups (also known as ______)

Answer 28

• surface active agents

- detergents

Question 29

how does the structure of a drug affect its transport in the body is an example of

Answer 29

pharmacokinetics

Question 30

the ______ and ____ ____ of a drug to the site of action are critical parameters for therapy

Answer 30

• absorption

- effective distribution

Question 31

orally administered drug: GI tract and other biologic ____ act like lipid barriers

Answer 31

membranes

Question 32

most drugs are absorbed through membranes by

Answer 32

passive diffusion

Question 33

the absorption rate of a drug is related to the drug’s _____

Answer 33

lipophilicity

Question 34

in general, more ____ ____ are absorbed more efficiently

Answer 34

Hydrophobic (lipophilic)

Question 35

the _______ form of an acidic or basic drug is preferentially absorbed

Answer 35

unionized

Question 36

things that have _____ are really disfavored and cannot be absorbed through the lipid bilayer

Answer 36

charged

Question 37

major route of drug administration: ________ drug must be absorbed to enter ______

Answer 37

• extravascular

- circulation

Question 38

binding of drug molecule to the surface of the skin or mucosa / “on the surface”

Answer 38

adsorption

Question 39

movement of a drug into deep layers of the skin without reaching the bloodstream

Answer 39

penetration

Question 40

permeation of a drug through capillary walls into the circulatory system

Answer 40

absorption

Question 41

drug must be in ___ ___ to be absorbed

Answer 41

aqueous solution

Question 42

most drugs reach their target through ____ ____ through the lipid bilayer where the drug is dissolved in ___ ___ and then has to dissolve in the _____ inside that bilayer.

the extent to which that happens is dependent on ____ and also on _____ state because ____ things are extremely ___ and not very ___ at all within that bilayer

Answer 42

• passive diffusion
• aqueous solution
• lipophilic
• lipophilicity
• ionization
• charged
• polar
• soluble

Question 43

transport through a semipermeable membrane =

Answer 43

passive diffusion

Question 44

drug dissolves in the ____ part of the membrane, then redissolves in the ___ ___ on the opposite side

Answer 44

• lipid

- aqueous medium

Question 45

extent to which the drug dissolves in the membrane depends on the drug ____ and on the ____ at the absorption site: drug must be _____ to be absorbed

Answer 45

• pKa
• pH
• unionized

Question 46

as drug on the other side of the membrane is swept away by the ____ ___, more drug is absorbed from the ____ so that in the end ALL of the drug is absorbed

Answer 46

• circulatory system

- outside

Question 47

partition coefficient is the measure of

Answer 47

“how well” a drug can move through the lipid bilayer

Question 48

a drug’s lipophilicity is determined quantitatively by calculating its

Answer 48

partition coefficient, Log P

Question 49

the higher the P value, the more

Answer 49

lipophilic (hydrophobic) a drug

Question 50

organic layer is on?

aqueous layer is on?

Answer 50

• top

- bottom

Question 51

if log P = 0, which phase contains more of the drug?

Answer 51

they contain equal amounts of drug

Question 52

more negative (like -2) Log P will be

Answer 52

hydrophilic (lipophobic)

Question 53

more positive (2) a Log P will be or more in organic layer

Answer 53

hydrophobic (lipophilic)

Question 54

log p ranges from ______ to _____ for typical drugs

Answer 54

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