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PHRM 501 > Exam 2- Drug Target Interactions > Flashcards

Exam 2- Drug Target Interactions Flashcards

1
Q

Agonist

A

activator

  • May be direct or indirect
  • Any activity usually begins with a conformational change of receptor
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2
Q

Anatgonist

A

inhibitor

  • Usually competes for binding with other/ endogenous ligands (prevents receptor activation)
  • If its tight/covalent, then its non-competable with agonists
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3
Q

Competitive

A

binds to the same site

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4
Q

Allosteric

A

binds to a different site

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5
Q

Histamine H2 receptor

A
  • present significantly only in the GI tract ( stomach and small intestine)
  • Its endogenous ligand is histamine
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6
Q

Histamine does what

A

stimulates gastric acid production

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7
Q

Pepcid - Famotidine is what

A

H2 receptor antagonist
- Its a competitive antagonist for histamine
- It blocks histamine from binding, hence less acid is produced
Used to treat GERD

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8
Q

The more interactions of a drug with its receptor

A

the greater the affinity

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9
Q

The greater the affinity of the receptor for a drug

A

the more of that drug will be bound at a given drug concentration

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10
Q

Affinity is expressed as

A

Kd

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11
Q

Kd =

A

[D][R] / {DR]

  • expressed in molar units, uM, nM, pM
  • concentration of drug at which half of the receptor is bound
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12
Q

D

A

concentration of free drug

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13
Q

R

A

concentration of free receptor

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14
Q

DR

A

Concentration fo bound drug-receptors

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15
Q

A small Kd indicates

A

high affinity

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16
Q

Adding drug shifts the equilibrium

A

to the left which forms more drug-bound receptors

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17
Q

More drug bound receptors equals

A

greater biological effect

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18
Q

As we increase drug concentration

A

we increase the amount of receptor binding

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19
Q

At drug conc. = Kd

A

theres an equal amount of bound/ free receptors

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20
Q

It takes a lower conc. of a drug with a small Kd

A

to reach the same level of receptor binding

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21
Q

The weaker a drug- receptor is

A

the more it wants to dissociate into its free drug

- The Kd will be high

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22
Q

The stronger a drug-receptor interaction is

A

the more it wants to remain in its undissociated for

- The Kd will be low

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23
Q

If it takes a long time to form [DR], then

A

[D] may diffuse or be transported away from target organ by blood flow

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24
Q

Pharmakon

A

poison/ drug

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25
Q

Pharmacology

A

study of substances that interact with living systems through chemical processes, especially binding to regulatory molecules and activating or inhibiting normal body processes

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26
Q

Toxicology

A

branch of pharmacology dealing with the undesirable effects of chemicals on living systems, from cells to humans, to environments and ecosystems

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27
Q

Drug

A

any substance that changes biological function through chemical (covalent/ non-covalent) interactions
- Have a beneficial effect in an addition to any deleterious effects

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28
Q

Receptor

A

The biological target of the agonist or antagonist. Its function changes when bound to an endogenous ( anything that originates internally) ligand or drug

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29
Q

Osmotic agents

A

move water

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30
Q

Antacids

A

neutralize acid

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31
Q

Posion

A

almost exclusively toxic effects (although anything can cause harm in a dose-dependent manner, including manner)

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32
Q

Toxins

A

Biological poisons (made by a biological system

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33
Q

Properties of drugs

A
  1. Physical properties
  2. Molecular size
  3. Reactivity and bond formation
  4. Shape
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34
Q

Physical properties of drugs

A

Solid, liquid or gas at RT- determines best route of administration

  • Solubility
  • Ionization state
  • Hydrophobicity
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35
Q

Size

A

MW can vary greatly

  • most often 200-500 Da
  • Has to fit well in receptor, with level of specificity, be absorbed and move throughout the boy
  • very large drugs often require direct compartment administration
  • Size and MW are usually but not always proportional
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36
Q

Reactivity and bond formation

A

Drugs interact with receptors via chemical bonds

37
Q

Strongest to weakeast bonds

A
  1. Covalent- rare, strong and virtually irreversible
  2. Ionic
  3. Hydrogen bonds
  4. Hydrophobic bonds
38
Q

Shape

A

determines receptor binding

  • Lock and key model
  • Effected by chirality/ stereoisomerism
39
Q

Racemic mixture

A

a solution in which there is an equal amount of two enantiomers

40
Q

Racemic drugs

A

A single enantiomer is more susceptible to metabolizing enzymes
- one enantiomers duration of action, or elimination half-life may vary dramatically from the other

41
Q

Which of the following is a TRUE statement?
A.Enantiomeric drugs are usually equipotent or equi‐effective
B.All drugs are poisons at high enough doses
C.Antagonists inhibit receptor function
D.Most clinically efficacious drugs are<100MW

A

C. Antagonists inhibit receptor function

42
Q

Which is an example of a pharmacokinetic effect?

  1. An increase in BP upon drug dosing
  2. An amount of drug released into urine
  3. An immune reaction to a drug
  4. The decomposition of a drug during storage
A
  1. An amount of drug released into urine
43
Q

Receptor

A

What a drug binds to

  • The component of a cell or organism that interacts with a drug and starts the events leading to drug effect
  • Mediators of Mechanism of Action
44
Q

If the drug binds to site on receptor other than original ligand/agonist binding site, it is called

A

Allosteric interactor

45
Q

Allosteric antagonist cannot

A

be overcome with increased agonist

46
Q

Orthosteric site

A

site at which the agonist binds to

47
Q

Competitive agonist

A

blocks activity of natural agonist. It competes with the agonist to bind to that site

48
Q

Allosteric site

A

Site other than the normal binding site of the agonist

-Not competitive

49
Q

Drug generally binds to receptors ->

A

some effect

50
Q

Drug +Receptor ->

A

D+R complex -> effect

Simple

51
Q

D+R ->

A

D+R complex -> effector molecule -> effect

More complex

52
Q

D+R ->

A

D+R complex -> activation of coupling mechanism -> effector molecule -> effect
Most complex

53
Q

Receptors can be

A

in the active form (Ra) or inactive for (Ri)

54
Q

Basal tone/ constitutes activity

A

a pool of receptors will exist in each form (Ra and Ri)

55
Q

What do agonist do to equilibrium

A

it shifts the equilibrium

Ra->Ri and vice versa but more is going to the active form Ra

56
Q

An Full agonist will

A

shift all receptors into active form

57
Q

A partial agonist will

A

shift only some receptors into active form

  • Even if you add more drug, you cant get anymore Ra activation
  • produces a lower effect at full receptor occupancy than full agonists
58
Q

Partial agonists have

A 
low intrinsic(natural) activity which is independent of receptor activity
- can competitively inhibit full agonist activity
59
Q

An antagonist will

A

block the activity of the natural agonist

60
Q

A inverse agonist will

A

block the original activity of the receptor.
In the graph the curve goes down
- shuts down 100% of activity

61
Q

Treatment of a receptor with an allosteric inhibitor
A. Overall response would be diminished, compared to agonist alone
B. More agonist would be required to reach the same response
C. Response would be enhance, as compared to agonist alone

A

A. Overall response would be diminished, compared to agonist alone

62
Q

Inverse antagonist

A

no such thing

63
Q

A receptor is stimulated with a full competitive agonist. A non-competitive (allosteric) agonist is added. What happens to the response

A
  • Response is increased

- Adding a non-competitive agonist to an agonist, it will increase the response

64
Q

A receptor is stimulated with a partial agonist. An antagonist is added. What happens to the response?

A

Response is diminished

  • Adding an antagonist will inhibit the activity of the agonist
65
Q

A drug was administered that lowered Peripheral Vascular Resistance (PVR) below basal tone

A

Inverse agonist

66
Q

If a drug was administered that maintained PVR at basal tone, even in the presence of endogenous ligand. You would predict the drug to be an

A

Neutral antagonist

67
Q

Orphan receptors

A

Receptors that have no known agonists, activities or related drugs

68
Q

Regulatory proteins

A
  • mediate action of endogenous chemical signals

- Ex: GABA-R

69
Q

Enzymes are proteins that

A

Mediate chemical reactions/ structural conversions (EX: DHFR)

70
Q

Transporters proteins

A

Move things often across membranes

Ex: Na+/ K+

71
Q

Structural proteins

A

provides tissue or cellular structure ( Ex: actin, microtubules/tubulin

72
Q

Important aspects of drug

A
  • Receptors as the link between drugs and their effects
  • Receptors regulate/ mediate chemical signaling and provide good drug targets
  • determine therapeutic and toxic drug effects
73
Q

Emax

A

the maximal effect for a given agonist or partial agonist

74
Q

EC50

A

the concentration of agonist ( or partial agonist) needed to give 50% Emax (maximal effect)

75
Q

Antagonism

A

The antagonist does not activate the receptor, but it block its activation by the endogenous agonist by

  • competing for binding with agonist
  • irreversibly binding
  • binding at the allosteric site (allosteric antagonist)
76
Q

For a noncompetitive antagonist, increasing agonist will

A

recover some E but NEVER reach Emax

77
Q

For a competitive antagonist, increasing agonist

A

will recover E and will eventually reach Emax

78
Q

EC50 increases as

A

the affinity of the antagonist increases

- agonist becomes weaker as EC50 increases

79
Q

How does Emax change when the affinity of the antagonist increases

A

It stays the same

80
Q

Low Kd means

A

high affinity

81
Q

IC50 or Ki

A

Drug inhibitory activity

82
Q

If Kd&raquo_space; IC50 this suggests that

A

there are lots of spare receptors

- You do not need to stimulate all of the receptors to get the full effect

83
Q

Irreversible antagonist

A
  • can be caused by covalent or exceptionally tight binding (picomolar)
  • receptor is unavailable for agonist binding
  • Good bc it can better control naturally fluctuating agonist, such as hormones and catecholamines
  • Bad bc if overdosed, it cannot pharmacologically agonize. They also tend to be less specific
  • kills the receptor
  • In the diagram this would be represented by a straight line
84
Q

IC50

A

concentration of antagonist that blocks 50% of activity

85
Q

Potency

A

requires lowest amount of drug to have full effect

  • lowest conc of drug to reach highest Emax
  • smaller E50 -> more potent
86
Q

Efficacy

A

Drug with the highest maximal response is more efficacious

87
Q

The orthosteric site is

A

where the ligand bind, aka the active site

88
Q

With fixed agonist, increasing antagonist will

A

diminish E

PHRM 501 (21 decks)

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