Lecture 2 (Intro to MedChem) Flashcards Preview

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Flashcards in Lecture 2 (Intro to MedChem) Deck (76):
1

Free bases or acids are often ____

liquid (oils)

2

Are they better or worse than a salt?

WORSE
-less water soluble than ionized form
-difficult to measure (because they are hygroscopic)
-difficult to make into a dosage form
-less stable

3

Why do we want to make a salt out of the free acids/bases?

because they are easier/better to work with (see previous card) and are more stable

4

Drug absorption across biological membranes is better in the ______ state

unionized

5

T or F: good drugs have only either lipid or water solubility

FALSE
-most efficient drugs have some degree of water and lipid solubility

6

explain solubility

for a chemical to dissolve in a particular solvent the compound must be able to form attractive forces with the molecules of the solvent

7

it is possible to estimate the solubility properties of drug by examining its _____

structure

8

Can we alter the solubility of a drug?

explain the 3 ways

YES
-use acid or base to make the drug into a salt
OR
-add substituents that are very water soluble:
-adding groups that are H bond donors and acceptors
-adding groups that can ionize
OR
-changing dose form

9

Are dispersion forces strong or weak?

weak

10

Dispersion forces are called ??

london forces
(wrongly called van der waals attraction)

11

Where do dispersion forces occur?

between induced and instantaneous formed dipoles

12

As molecule gets larger, dispersion forces get _____

larger
(disperson forces increase as the total area for interaction between molecules increases)

13

Why do larger molecules become liquids? (ex. butane, hexanes, and octane are liquids but methane, ethane, and propane are gases)

increasing size = increasing dispersion forces

(also increasing weight is a factor)

14

What is stronger: dispersion forces or dipole-dipole bonds?

dipole-dipole bonding

15

Where does a dipole-dipole bond occur?

happens between permanent dipoles

note** these are not formal charges (that would be an ionic rxn)

16

H-bonding is a special kind of ??

dipole-dipole bonding

17

H-bonding is _____ than ordinary dipole-dipole bonding

stronger

18

When does H-bonding happen?

-happens between atoms with highly electronegative atoms attached to H

19

H-bonding plays a big role in making things more ??

hydrophilic (water soluble)

20

Molecules with many H-bond donors and acceptors are more ____ soluble

water

21

What is the H-bond donor?

electronegative atom with an attached hydrogen

22

What is the H-bond acceptor?

electronegative atom with a FREE (not tied up in resonance) lone pair of electrons

23

Are S, Cl, and F, weak or strong H-bond acceptors?

weak

24

SH is NOT an H-bond ____

donator

25

Amide N is NOT an H-bond _____

acceptor (lone pair on amide N cannot accept H-bonding due to resonance)

26

Why are intermolecular H-bonds between drug molecules in solution very uncommon?

Because H2O molecules will out compete the other drug molecules

in order to form a H-bond between drug molecules, it would first have to break the H-bonds formed with water (and this would require energy)

27

Explain how intramolecular H-bonds form in water (Note** very different than intermolecular H-bonds which we just previously deduced were very uncommon in water)

Bc the H-bonding pair are always super close in proximity it is easier to form H-bonds

28

What is intramolecular H-bonds forming in water known as?

effect of local concentration

(bc it is similar to having high concentrations of each other)

29

How does having too many H-bonds affect absorption?

those H-bonds have to be broken in order to cross the lipid membrane

**this represents the idea of having a practical limit H-bonds

30

Breaking H-bonds with water (in order to cross membranes) is _____

unfavorable

31

You don't want to have too many H-bond donors and acceptors or the drug will not _____

absorb

32

What is an ionic bond?

electrostatic interaction between cations and anions

33

Are ionic bonds strong?

yeah man

34

What is an ion-dipole bond?

electrostatic interaction between a nation/anion and a dipole

35

When are ion-dipole bonds important?

between drugs and water

36

Can covalent bonds happen between drugs and solvent?

NO WAY JOSE

37

Where can covalent bonds be present?

can be part of drug receptor interactions (but this is rare)

38

Why is a covalent interaction between a drug and receptor BAD?

-because if the receptor is covalently attached to the drug - the receptor is not the receptor anymore

-it is now a foreign protein that the body attacks

39

What is the solubility o fa drug a function of?

It is a function of the lipophilic and hydrophilic groups within its STRUCTURE

40

How can we determine the relative solubility of a drug?

-can be determined with the PARTITION COEFFICIENT

41

What is the partition coefficient?

P = [drug in hydrophobic/lipophilic solvent (ex. octanol)]/ [drug in hydrophilic solvent (water)]

42

logP = ?

pi (not actual pi) - different kind of pi

43

What are the 2 very common functional groups that often increase water solubility?
Explain yourself

N and O

-they polarize the molecule and act as H-bond acceptors and donors (with an attached hydrogen)

44

Ionizable groups increase ____ solubility

water

45

Give 3 examples of groups that increase lipid solubility

alkyl chains
alkyl rings
aromatic groups

46

Hydrophilic groups have a _____ pi value

negative

47

Lipophilic groups have a _____ pi value

positive

48

LogPcalc value greater than +0.5 = ?

lipophilic

49

LogPcalc values less than +0.5 = ?

hydrophilic

50

understand slide 21

ok man

51

one of the most important factors effecting the ____ of drugs is the LogP

potency

52

Explain the 3 types of ways to cross biological membranes

-passive diffusion through aqueous channels

-passive diffusion through lipid (most important mechanism of absorption across membranes)

-facilitated transport (energy required)

53

What is 1 other important thing to consider when thinking about the ways that molecules can move through biological membranes?

blood flow

**once a drug crosses the membrane and if the blood takes it away then it will make an equilibrium so as to drag more drug across the membrane

54

Why do drugs need to be hydrophilic?

Dissolution:
-needs to have sufficient solubility so they dissolve out of solid dosage forms

Distribution:
-needs to have some solubility in biological fluids to transport to site of action

55

Why won't drugs that are too hydrophilic be absorbed across biological membranes?

-because they form too many H-bonds that need to be broken (which causes energy) in order for absorption to occur

56

When _____ there is sufficient lipophilicity to cross membranes

unionized

57

When ____ there is sufficient water solubility for dissolution and distribution

ionized

58

About 85 % of drugs have functional groups that are ___ to some extent

ionized

59

What is ionization controlled by?

pKa and external pH

60

pH of blood

7.4

61

pH of sweat/saliva

6

62

pH of fasting stomach

1

63

pH of fed stomach

3-7

64

pH of fasting duodenum

5

65

pH of fed duodenum

6

66

pH of colon

7-8

67

Why don't we absorb too many drugs in the stomach?

due to mucous layer

68

Where does a lot of absorption occur?

small intestine (specifically duodenum)

69

When you put an acidic drug into a decreasing pH (acidic environment) it will increase the ____ form

unionized

70

The unionized form of the drug is better at ???

crossing biological membranes

*remember the unionized form is more lipophilic (i.e. can cross those lipid membranes better than the ionized form which is more water soluble)

71

When you put a basic drug into an increasing pH (basic environment) it will increase the ____ form

unionized

72

addition of base or hydroxide ion will ___ pH

increase

73

addition of acid or hydrogen ion will ___ pH

decrease

74

unionized form of the drug ____ better

absorbs

75

Describe interfacial tension

-when you put a lipophilic compound into water - you get few but stronger water-water H bonds at the non-polar/water interface

76

Water molecules at the interface are more orientation ally restricted which results in a ____ of entropy (change in S)

decrease