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PATHO > Lecture 3: membrane permeability and partitioning of drugs > Flashcards

Lecture 3: membrane permeability and partitioning of drugs Flashcards

1
Q

Hydrophilic groups

A

-lipophobic
-love water
-usually polar and capable of H bond formation

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2
Q

Hydrophilic functional groups

A

-alcohol
-carboxylic acid
-amine
-ketone
-amide
-ester

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3
Q

Hydrophobic groups

A

-lipophilic
-hate water
-usually non-polar hydrocarbons

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4
Q

Hydrophobic functional groups

A

-methyl
-chloro
-phenyl
-hexyl
-cyclohexyl

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5
Q

Hotseat: Which molecule is more hydrophobic?

A

The one with a CH3 group instead of OH group

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6
Q

Hotseat: Which molecule is more hydrophobic?

A

the one with the hexyl group instead of alcohol group

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7
Q

Lipinski’s rule of five

A

-describe druglikeness (orally active drugs)
-based on observation that orally active drugs are usually small and lipophilic

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8
Q

Lipinski’s rule

A

-no more than 5 H-bond donors (-OH, -NH)
-no more than 10 H-bond acceptors (O, N)
-mass less than 500
-LogP < 5

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9
Q

LogP

A

-Log value of partition coefficient (P)
-measure lipophilicity
-most drugs have values from -1 to 4

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10
Q

LogP < 0

A

drug favors water

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11
Q

LogP = 0

A

equal

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12
Q

LogP > 0

A

drug favors 1-octanol

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13
Q

larger LogP

A

-more lipophilic
-more hydrophobic

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14
Q

typical LogP values

A

-1 to 4

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15
Q

The logP value of drug A is 2. what is the ratio of the concentration
of the drug in the organic phase to that in the aqueous phase?

A

100:1

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16
Q

Activity versus LogP

A

-parabola curve opening downwards

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17
Q

optimal logP (logP0)

A

-logP value relating to maximum drug activity

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18
Q

Lipophilicity

A

-improves permeation
-too much can hinder crossing

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19
Q

Drug Partitioning Through Multiple Compartments
Separated by Membrane Barriers

A

LogP= 0 diffuses the quickest and more evenly
LogP= 3 diffused similarly to -3 but sticks around the membrane bc of attraction

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20
Q

Calculated LogP (CLogP)

A

-sum of pi values of the molecule’s fragments

21
Q

Fragments

A

-additive
-structural

22
Q

LogP of benzene is 2.13. What is ClogP of the following compound?

A

ClogP = sum of pi values of:
-I
-OH
-CH3
-ONH2
=1.65

23
Q

Is this example molecule (1.65) more or less hydrophobic than benzene (2.13)?

A

less hydrophobic

24
Q

Acidic and basic drugs in the aqueous phase

A

-may exist in ionic and neutral forms

25
Q

Organic phase

A

-drug only in neutral form
-[HA]

26
Q

Partitioning of acidic and basic drugs

A

-dependent on pH
-increase in ionization leads to accumulation of drug in aqueous phase

27
Q

Increase in ionization

A

= accumulation of drug in aqueous phase

28
Q

Partition coefficient (P)

A

= [HA]org / [HA] aq

29
Q

Distribution coefficient (D)

A

= [HA] org / [HA]aq+[A-]aq
-more informative than P

30
Q

Organic

A

HA

31
Q

Aqueous

A

HA <-> A- + H+

32
Q

Drug HA is an acidic drug with
logP = 2 and pKa = 4

At pH=1:

A

D ~ P
-[A-]aq negligible compared to [HA]aq

33
Q

Drug HA is an acidic drug with
logP = 2 and pKa = 4

At pH=7:

A

D &laquo_space;P
-[A-]aq much greater than [HA]aq

34
Q

Distribution of an ACIDIC drug: at higher pH

A

-logD &laquo_space;logP
-drug may NOT cross lipid membrane well

35
Q

Distribution of an ACIDIC drug: when pH&raquo_space; pKa

A

LogD = LogP - (pH - pKa)

36
Q

Distribution of a BASIC drug: at LOWER pH

A

logD &laquo_space;logP
-may NOT cross lipid membrane well

37
Q

Distribution of a BASIC drug: when pH &laquo_space;pKa

A

LogD = LogP- (pKa - pH)

38
Q

Drug B is a basic drug with
logP = 2 and pKa = 7

at pH= 10

A

D ~ P
[BH+]aq negligible to [B]aq

39
Q

Drug B is a basic drug with
logP = 2 and pKa = 7

at pH = 4

A

D &laquo_space;P
[BH+]aq is much greater to [B]aq

40
Q

[HA]

A

[B] in basic drugs

41
Q

[A-]

A

[BH+] in basic drugs

42
Q

Graph of Distribution of an acidic drug

A

decreasing log function as pH increases

43
Q

Graph of Distribution of a basic drug

A

increasing log function as pH increases

44
Q

The logP value of drug A is -1. what is the ratio of the concentration of the drug in the organic phase to that in the aqueous phase?

A

1:10

45
Q

Which of the following is a hydrophobic functional group?

A

-CH2CH3

46
Q

The structure of naproxen is shown below. The pKa of the drug is 4.15, and the LogP is 3.18. Which of the following statements about LogD is INCORRECT?

A

LogD is much greater than 3.18 at pH 10.0.

47
Q

LogP of benzene is 2.13. What is ClogP of p-methylphenol? The structure of the compound and the table of pi values are given for your information.

pi values: 0.56 and -0.67

A

2.02

48
Q

Select the most lipophilic (hydrophobic) compound from the following. The table of π values is given for your information.

A

groups with positive pi values

PATHO (31 decks)

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