Pharmokinetics 1 Flashcards Preview

ESA 2- Membranes and Receptors > Pharmokinetics 1 > Flashcards

Flashcards in Pharmokinetics 1 Deck (96):
1

How do all drugs exert their effects?

By binding to a target

2

What are the majority of drug targets?

Proteins, with some exceptions

3

Give an example of an exception to drug targets being proteins

Some antimicrobial and antitumour drugs bind DNA

4

What do must drugs bind with?

Receptors

5

Is drug binding to receptors reversible?

Usually

6

What is binding of drugs to receptors governed by?

Association and dissociation rates

7

Give 7 targets for drugs

Enzymes 
GPCRs
Ion channels 
Nuclear hormone receptors 
Integrins
Other receptors

8

What % of drug targets are enzymes?

47%

9

What % of drug targets are GPCRs?

30%

10

What % of drug targets are ion channels?

7%

11

What % of drug targets are transporters?

4%

12

What % of drug targets are nuclear hormone receptors?

4%

13

What % of drug targets are other receptors?

4%

14

What % of drug targets are integrins?

1%

15

What is critical in determining drug action?

The concentration of drug molecules around receptors

16

What do drugs of equivalent molar concentrations have?

The same concentration of drug molecules

17

Do drugs of equivalent concentrations by weight have the same concentration of drug molecules?

They may not

18

How much does 1 mole contain?

6x10^23

19

What does 1 molar solution contain?

1 mole in 1 litre

20

How do you calculate grams per litre?

Molecular weight x molarity

21

What do agonists do?

Bind to receptors and cause a response

22

What do agonists have?

Both affinity and efficacy

23

What do antagonists do?

Bind to receptors, but do not cause a response

24

What do antagonists have?

Affinity only

25

What is affinity?

The likelihood of a ligand binding to its target

26

What is efficacy?

The likelihood of activation

27

How is binding information often obtained?

By the binding of a radioligand

28

What is a radioligand?

A radioactive version of the ligand

29

What is Bmax?

The maximum binding capacity

30

What does Bmax give?

Information about the number of receptors

31

What is Kd?

The dissociation constant

32

What is Kd a measure of?

Affinity

33

How is Kd worked out?

It is the concentration needed for 50% occupancy

34

What does a lower Kd value relate to?

A higher affinity

35

On what scale is [drug] usually shown

Logarithmic

36

Where in concentration response curves used?

In measured in a response in cells/tissues

37

When are dose response curve used?

When measuring a response in a whole animal

38

What is Emax?

The maximum response

39

What is EC 50 ?

The effective concentration giving 50% of the maximal response

40

What is EC 50 a measure of?

Potency

41

What is potency?

A combination of both affinity and efficacy

42

What governs potency?

The number of receptors

43

In what terms is efficacy measured?

Relative- no absolute scale

44

What may agonists with different Emax value have?

Different efficancy

45

Do agonists with the same Emax values have identical efficacy?

Not always

46

Why may two drugs with the same Emax values not have the same efficacy?

They may differ in affinity, meaning that the relationship between occupancy and response will be different- one may be more able to convert binding into function

47

What is the treatment goal is asthma?

To activate ß2-adrenoceptors to relax the airways

48

What is the problem with activating ß-adrenoceptors to treat asthma?

There are ß-adrenoceptors elsewhere in the body

49

Give an example of where ß-adrenoreceptors are found elsewhere in the body?

ß1 in the heart increase the force and rate of contraction

50

What is salbutamol?

A ß2-adrenoagonist

51

What is the Kd of salbutamol?

20µM for ß1
1µM for ß2

52

What is the result of the lower Kd for ß2?

It has a higher affinity

53

Why can salbutamol be used in treatment of asthma?

Because of the higher affinity for ß2-receptors, as well as ß2 selective efficacy and route of administration- this limits ß1 activation and side effects

54

What is the route of administration of salbutamol in the treatment of asthma?

Oral spray

55

What is salmeterol?

A longer acting ß2-adrenagonist than salbutamol

56

How does salmeterol differ from salbutamol?

It has no selective efficacy

57

How does salmeterol prevent ß1 activation and side effects?

Purely through differences in affinity

58

What is the Kd of salmeterol?

1900nm for ß1
0.55nm for ß2

59

What will less than 100% receptor occupancy give in some cases?

100% response

60

What is true when 100% receptor occupancy gives 100% response?

EC50 is less than Kd

61

Describe the relationship between receptor occupancy and response?

Non-linear

62

What is the relationship between receptor occupancy and response influenced by?

Both the transduction system/amplification produced by second messengers, and the properties of the tissue

63

What is meant by spare receptors?

Some tissues have more receptors than required to produce a maximal response

64

What is the advantage of spare receptors?

It increases sensitivity, allowing for responses at low concentrations of agonist

65

What does number of receptors have an effect on?

Potency

66

What is a partial agonist?

A drug that cannot produce a maximal effect, even with full receptor occupancy

67

How can a partial agonist be identified?

By comparing the ability of different agonist to evoke responses in a tissue

68

What is the EC50 of a partial agonist equal to?

Its Kd

69

What is the potency of a drug dependent on?

Both its affinity and efficacy

70

Are partial agonists more or less potent than full agonists?

Can be either

71

Is a partial agonist always so?

No

72

What does wether an agonist is partial or not depend on?

The tissue and the biological response

73

What are opioids used for?

Pain relief  Recreationally

74

What can opioid cause?

Respiratory depression, leading to death

75

How do opioids act?

Primarily through the µ-opioid receptor (GPRC)

76

How do morphine and buprenorphine differ?

Morphine is a full agonist of the receptor 
Buprenorphine is a partial agonist, with a higher affinity but lower efficacy

77

Why is buprenorphines high affinity and low efficacy advantageous?

If it provides adequate pain control it is preferable, as there is less respiratory depression

78

What are the types of antagonist?

Reversible competitive 
Irreversible competitive
Non-competitive

79

What is the most common form of antagonist?

Reversible competitive

80

Where is reversible competitive antagonism important?

In therapeutics

81

What does reversible competitive antagonism rely on?

A dynamic equilibrium between ligands and receptors

82

What is IC50?

The concentration of antagonist giving 50% occupancy

83

How can reversible competitive antagonists be overcome?

By high concentrations of agonists

84

Give a therapeutic example of a reversible competitive antagonist?

Naloxone

85

What is naloxone?

A high affinity, competitive antagonist of µ-opioid receptors

86

What is naloxone used to do?

Reverse opioid mediated respiratory depression

87

Why can naloxone be used to reverse opioid mediated respiratory depression?

Its high affinity means it will compete effectively with other opioids for receptors

88

When does irreversible competitive antagonism occur?

When the antagonist dissociates slowly, or not at all

89

What do irreversible competitive antagonisms cause to the concentration-reponse curve?

A permanent shift to the right

90

What do irreversible competitive antagonists do at high concentrations?

Suppress the maximal response

91

Why do irreversible competitive antagonists suppress the maximal response at higher concentrations?

As spare receptors are filled by the antagonist, not leaving enough receptors free to illicit a maximal response

92

Give a therapeutic example of irreversible competitive antagonism?

Phenoxybenzamine

93

What is Phenoxybenzamine?

A non-selective irreversible α1-adrenoreceptor blocker

94

Where is Phenoxybenzamine used?

In hypertension episodes in pheochromocytoma

95

What is pheochromocytoma?

A tumour of the adrenal gland, which causes excessive NA/Adrenaline secretion leading to vasoconstriction

96

What is non-competitive antagonism?

The allosteric binding of an antagonist to a receptor (not the ligand binding site)