M&R Session 8 Flashcards Preview

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Flashcards in M&R Session 8 Deck (82):
0

Which drugs do not bind to proteins?

Anti microbial
Anti tumour

1

What equation is used to calculate molarity?

Grams per litre/molecular weight

2

Why must drug concentrations be considered in molarity?

Using equal weights of substances w/ different molecular weights leads to different concentrations of molecules

3

What is the critical determinant of drug action?

The molarity of drug molecules around receptors

4

What law does drug binding obey?

Mass action

5

What forms the dynamic equilibrium between ligand, receptors and the complex they form upon binding?

Association and dissociation

6

What is related to the binding of drug molecules to receptors?

[reactants]
[products]
Le Chatelier's principle

7

What two characteristics do agonists have?

Affinity
Intrinsic efficacy

8

What governs receptor activation to give intracellular effects?

Intrinsic efficacy

9

What is intrinsic efficacy?

The ability to turn a receptor on by forming an activated receptor

10

What is efficacy?

Ability to cause coupling leading to cellular action
Ability to generate a biological response

11

What determines efficacy?

Cell/tissue-dependent factors

12

Why can an antagonist not cause a response?

It only has affinity so cannot convert the receptor to an active form - no conformational change

13

How do antagonists prevent receptors being turned on?

Prevent agonist binding

14

What two methods are used to measure drug-receptor interactions?

Binding w/radioligand
Relation b/w [drug] and response

15

Describe the process of radioligand binding.

Bind radioligand to cells/prepared membranes --> separate bound and free radioligand --> low [ligand] = low binding,

16

What is B(max)?

The concentration at which all receptors are full

17

What is Kd?

The dissociation constant = 50% occupancy
Measure of affinity

18

Is Kd affected by receptor number?

Nope

19

What does a low Kd indicate?

High affinity

20

What is K(A)?

Index of affinity determined by functional assay

21

What is the definition of a logarithm?

The exponent by which a fixed (base) value has to be raised to give a particular number

22

How is [drug] usually expressed?

On a logarithmic scale giving a sigmoidal curve

23

Can Kd be used for agonists and antagonists?

Yes, it can be used for any type of ligand

24

What does receptor response require?

Efficacy

25

What type of ligand must be used to measure drug-receptor interactions by relation b/w [drug] and response?

An agonist

26

What is E(max)?

Effect maximum; a tissue can only secrete/contract so much

27

What is EC50?

Effective concentration giving 50% of the maximal response

28

Define concentration in relation to drug action.

Known [drug] at site of action e.g. in cells and tissues

29

Define dose.

Concentration at an unknown site of action e.g. dose to a patient (mg or mg/kg)

30

What is potency?

How good a drug is at generating a biological response

31

What does potency depend on?

Affinity
Intrinsic efficacy
Efficacy

32

What is the key determinant of efficacy?

The number of receptors present

33

What factors must be considered in drug action?

Affinity
Efficacy
Selectivity
Pharmacokinetics
Physiochemical properties

34

What is the therapeutic target used in asthma treatment?

Beta 2-adrenoreceptors

35

Why do agonists for asthma treatment need to have specificity rather than just their usual high selectivity?

So they do not act on beta 1-adrenoreceptors in the heart

36

What is functional antagonism?

Where the antagonist of the action not the receptor

37

How is Salbutamol utility increased?

Beta 2-selective efficacy
Route of administration

38

Describe the action of Salbutamol.

Binds slightly preferentially to beta 2 and is particularly good at turning beta 2 on

39

Describe the action of Salmeterol.

Long acting
Selectivity based on affinity as it has no selective efficacy

40

What problems are associated with Salbutamol and Salmeterol respectively?

Salbutamol: can act on beta 1-adrenoreceptors in heart --> increases HR --> angina (common in elderly w/asthma)
Salmeterol: insoluble so cannot be given IV when nebuliser no longer an option

41

When are spare receptors often seen?

When receptors are catalytically active

42

Give two examples of receptor types you would expect to see spare receptors with.

Tyrosine kinase
GPCRs

43

Why do spare receptors exist?

B/c of amplification and response limited by post-receptor event

44

In asthma what percentage of M3 muscarinic receptors are activated to give maximal contraction?

10%

45

Describe the relationship b/w drug concentration and its Kd if there are no spare receptors.

For full receptor response requires >> Kd of drug

46

What effect do spare receptors have on sensititvity?

Increase

47

Describe the response when there are spare receptors present.

Occurs at lower [agonist]
Occurs at Kd
Decreased [drug] for full response

48

What does changing receptor number do?

Changes agonist potency
Can affect the maximal response

49

Describe the relationship b/w [drug], its effects and receptor number.

Same [drug] has different effects depending on receptor number

50

What happens if receptor number is low?

There is 100% occupancy but insufficient receptors for a full response

51

What can cause up-regulation of receptors w/low activity and down-regulation w/high activity?

Physiological, pathological or drug-induced changes

52

What is tachyphylaxis?

Desensitised receptors

53

How can partial agonists not elicit maximal response with full receptor occupancy?

Insufficient efficacy creates a different activated receptor so it is turned on but not fully

54

What tends to happen with the binding curve and function curve for a partial agonist?

Overlap so EC50 ~ Kd

55

What type of receptors do opioids primarily bind to?

Mu-opioid

56

Why is buprenorphine sometimes used clinically instead of morphine?

It has a higher affinity but lower efficacy so can give sufficient pain control with a lower risk of breathing depression

57

What type of agonist is heroin?

Full

58

Which mixed agonist/antagonist is used to aid heroin withdrawal?

Buprenorphine

59

What can cause a partial agonist to act as a full agonist?

Increased receptor number (low efficacy but enough receptors --> full response)

60

What indicates intrinsic activity?

Maximal response

61

Can full agonists w/identical intrinsic activities have different efficacies?

Yes

62

What can be said about the response of two full agonists with equal intrinsic activity?

They have the same maximum response

63

In which direction does the response curve of a drug move with increasing potency?

Left

64

What does reversible competitive antagonism rely on?

A dynamic equilibrium b/w ligands and receptors

65

What is K50?

The concentration of antagonist which gives 50% inhibition
Index of antagonist potency determined by [agonist]

66

What is the difference between Kd and KB?

Kd = antagonist affinity derived from radioligand
KB = antagonist affinity derived pharmacologically

67

How do reversible competitive antagonists affect agonist concentration-response curves?

Cause parallel shift to right

68

Which drug can be used clinically to reverse opioid-mediated respiratory depression?

Naloxone

69

When does irreversible competitive antagonism occur?

When the antagonist dissociates slowly or not at all

70

How does irreversible competitive antagonism affect the agonist concentration-response curve?

Parallel shift to right and suppresses maximal response

71

How does irreversible competitive antagonism suppress maximal response?

Spare receptors are filled by antagonist therefore there are insufficient receptors for a full response

72

How does phenoxybenzamine work?

Non-selective alpha 1 adrenoreceptor blocker that binds covalently so no matter how much adrenaline/NA present vasoconstriction is not caused

73

What mechanism of action does Clopidogrel use to prevent thrombosis?

Irreversible P2Y12 antagonist which prevents cytochrome P450 metabolism

74

What is non-competitive antagonism?

Endogenous ligand binds to orthosteric site on extracellular part of GPCR

75

What are allosteric sites?

Binding sites for agonists and molecules that enhance or reduce ability of endogenous ligand to turn receptor on

76

What type of antagonism does non-competitive antagonism resemble when comparing [agonist]-response curve?

Irreversible competitive antagonism

77

Describe an NMDA (excitatory glutamate) receptor.

Inotropic receptor
Ligand gated ion channel
Distinct glutamate and ketamine binding sites

78

What effects can binding at an NDMA produce?

Analgesia
Decreased central excitation

79

Describe the allosteric sites of GPCRs.

High specificity
High receptor subtype selectivity

80

Are GPCRs competitive?

No

81

What do GPCRs often require to function?

Orthosteric ligand