Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Care - Pharmacology 2024 > Lecture 2: drug-receptor interactions > Flashcards

Lecture 2: drug-receptor interactions Flashcards

1
Q

Examples of drugs that don’t require a target receptor to evoke biological responses

A

osmotic diuretics (e.g., mannitol),
antidotes for heavy metal poisoning, and most laxatives (e.g., lactulose, polyethylene glycol),
antacids neutralizing the hydrochloric acid in stomach)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Where did the concept of receptor evolve from

A

pioneering work of Lanley and Ehrich

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

how do most drugs work?

A

in a structurally specific way (their therapeutic and toxic effects stem from their interactions with specific cellular target molecules collectively known as receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What determines the concentration of drug required to form a significant number of drug-receptor complexes?

A

affinity for binding a drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

high affinity =

A

less drug dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what limits the maximal effect a drug may produce?

A

the total number of receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what provides the specificity of the overall drug-receptor interaction

A

the ensemble of the interactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

receptor is associated with

A

enzyme(?)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

van der Waals

A

hydrophobic (dislikes water)
weak bond

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

how is affinity measured/reported?

A

by the Kd value

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

affinity contributes to overall..

A

potency
efficacy
duration of drug action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Non-covalent bonds

A

Ionic Bonds
Dipole Interactions
Hydrogen Bonds: a specialized type of Dipole-Dipole bond
van der Waals Interactions
Hydrophobic Bonding
Chelation and Complexation
Charge Transfer Interactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

ionic bond

A

complete transfer of valence electron to attain stability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Dipole interaction

A

partial charge bonded with opposite partial charge

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Hydrogen bond

A

H–F,O,N

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

van der Waals

A

all Carbons
hydrophobic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

hydrophobic interaction

A

arise as a consequence of the interaction of their hydrophobic (i.e., “water-disliking”) amino acids with the polar solvent, water.

the tendency of nonpolar molecules to minimize their contact with water.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

chelation and complexation

A

Chelation is the complexation process by which a metal ion is bound to more than one atom in a single ligand.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is a charge transfer interaction

A

an electron donor acceptor complex can be defined as an association of two or more molecules, or of different parts of a large molecule, in which a fraction of electronic charge is transferred between the molecular entities.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

which bonds are permenant

A

covalent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

most drugs are…

A

proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is Kd?

A

a concentration and it quantifies the ‘affinity’ for a particular drug for its receptor.

If the Kdis low, the binding affinity is high, and vice versa.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

It is the ____ of the drug that produces a fractional occupancy of 50%…

A

concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

According to the Clark’s occupancy theory, the maximal response to the drug …

A

is equal to the maximal tissue response, leading to the expectation that all agonists would produce the same maximal response.

For some drugs, e.g., the partial agonists, maximum response can never be achieved even at extremely high doses. (Limitation 1 of the theory)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

examples of Therapeutic index (TI)

A

penicillin (high window) and warfarin (low window)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

list of protein receptors

A

enzymes
ionotropic/ion channels
metabotropic
kinase linked and related receptors
nuclear receptors
cytoskeletal or structural proteins
transporters/carrier proteins

27
Q

example of enzyme receptors

A

dihydrofolate reductast: receptor for antineoplastic drug methotrexate

28
Q

example of iontropic receptors/ion channels

A

ligand gated channels and voltage gated channels

29
Q

example of metabotropic receptors

A

G-protein coupled receptors binding to endogenously produce hormones
neurotransmitters

30
Q

what are kinase linked and related receptors

A

receptors for various growth factors and for some anticancer drugs

31
Q

examples of nuclear receptors

A

receptors for thyroid hormone
some fat-soluble vitamins and steroids

32
Q

examples of cytoskeletal or structural proteins

A

tubulin, the receptor for colchicine, and anti-inflammatory agent

33
Q

examples of transporters or carrier proteins

A

NA+, K+, ATPase, the receptor for cardiac glycosides

34
Q

examples of non-protein receptors

A

nucleic acids (DNA/RNA)
membranes
fluid compartments

35
Q

____ receptors can be coupled to respective executioner or effector components that orchestrate diverse cellular effects which may occur over a wider time scale

A

GPCR

36
Q

how fast are effects produced by the following receptors channels:
- ion channels:
- steroid and thyroid hormones:
- GPCRs:

A
  • ion channels: (milliseconds)
  • steroid and thyroid hormones: (several minutes)
  • GPCRs: (seconds to minutes)
37
Q

laws of occupancy theory:

A

The drug (D) and receptor (R) bind reversibly to form a drug-receptor complex (DR) in 1:1 stoichiometry. The DR complex generates a response (E): D + R ↔️ DR → E.

The magnitude or intensity of the response is directly proportional to the amount or concentration of the DR complex ([DR]) formed: (E ∝ [DR]).

The maximum possible response (Emax) is elicited when all the receptors (RT) become occupied by the drug, forming the DR complex: (when [DR] = [RT], E = Emax).

38
Q

equation for fractional occupancy

A
39
Q

Limitations of occupancy theory

A

1.) According to the Clark’s occupancy theory, the maximal response to the drug is equal to the maximal tissue response, leading to the expectation that all agonists would produce the same maximal response. For some drugs, e.g., the partial agonists, maximum response can never be achieved even at extremely high doses. (Limitation 1 of the theory)

2.) Second, the occupancy theory assumes that the relationship between occupancy and response is linear and direct. Therefore, a 50% receptor occupancy will result in a half-maximal response and thus KD equals to EC50 (i.e. the concentration of drug producing 50% of Emax).

This is rarely seen in biological systems. Nickerson (1956) first showed that agonists such as histamine could produce a maximal tissue response at extremely low receptor occupancies (far less than maximal). (Limitation 2 of the theory)

40
Q

According to the Clark’s occupancy theory, the maximal response to the drug is equal to

A

the maximal tissue response

41
Q

what are spare receptors?

A

receptors that remain unbound when an agonist is producing its maximal biologic response

receptor reserve’ –> and drugs need to occupy only a minor proportion (≤10%) of the total receptor population to evoke a maximum response.

42
Q

Are Kd and EC50 always equal?

A

NO

43
Q

what is the overall transduction process that links drug occupancy of receptors and pharmacologic response?

A

coupling

44
Q

what is coupling determined by?

A

downstream biochemical events that transduce receptor occupancy into cellular responses

45
Q

define efficacy

A

the ability of a ligand to initiate receptor activation

46
Q

what kind of ligand has both affinity and efficacy?

A

agonist

47
Q

types of agonists

A

1.) Full agonists: mimic the physiologic agonist, e.g., isoproterenol (β-adrenergic agonist).
2.) Partial agonists: activate receptors but are unable to elicit the maximal response of the receptor system; e.g., Dobutamine (a partial agonist at β-adrenergic receptor).
3.) Inverse agonists: Inverse agonists cause constitutively active targets to become inactive; e.g., antihistamines are considered as inverse agonists of H1 receptor.

48
Q

types of antagonists

A

1.) Competitive or reversible inhibition - bound to active site (noncovalent) - Examples: ACEI, rennin inhibitors, angiotensin receptor inhibitors.

2.) Non-competitive or irreversible inhibition - bound to active site (covalent) - Examples: inhibitors of acetylcholine esterase such as physostigmine, neostigmine etc., cyclooxygenase (COX) inhibition by aspirin, phenoxybenzamine antagonism of α-adrenergic receptor.

3.) Allosteric inhibition - different binding site which morphs the active site (noncovalent mostly) - Examples: nonnucleotide reverse transcriptase inhibitors, antihistamines binding to histamine H1 receptor.

49
Q

what kind of ligand has affinity but lacks efficacy?

A

antagonists

50
Q

advantages and disadvantages of noncompetitive (irreversible) antagonism

A

Advantages: duration of action is independent on the drug half life. e.g. Aspirin and proton pump inhibitors (esomeprazole, omeprazole)

Disadvantage: reversal of drug effect in case of toxicity is complicated.

51
Q

less commonly know antagonists that act as antagonists of particular receptors without direct interaction with these receptors

A

Physiological antagonists: two drugs acting on different cognate receptors have opposing pharmacological actions; e.g., histamine acts on receptors of the parietal cells of the gastric mucosa to stimulate acid secretion, while omeprazole blocks this effect by inhibiting the proton pump; the two drugs can be said to act as physiological antagonists.

Pharmacokinetic antagonists: decreases another drug’s concentration at the site of action—-> reduce bioavailability, and thus the concentration of an agonist at its site of action through induction of drug metabolizing enzymes in the liver (e.g., Phenobarbital reducing the anticoagulant effect of warfarin this way), impaired absorption from GI tract or enhancement of renal excretion.

52
Q

___ produce a lower response at full receptor occupancy than do ___

A

partial agonist; full agonist

53
Q

when there is [ ] of a full agonist and partial agonist together, what is the relationship?

A

inverse

54
Q

potency refers to …

A

the concentration (EC50) or dose (ED50) of a drug required to produce 50% of that drug’s maximal effect.

55
Q

the potency of the drug depends on …

A

affinity Kd
coupled response

56
Q

what is the therapeutic window?

A

the range between the minimum toxic dose and the minimum therapeutic dose
- of greater practical value in choosing the dose for the pt

57
Q

define idiosyncratic drug response

A

unusual and infrequent response mostly due to genetic factors

58
Q

define pharmacodynamics and describe its role in therapeutics

A

The drugs effect on the body

pharmcotherapeutics , our drug choice is dictated by what we need our drug to do, its pharmcodynamics if you will. Example, tissue plasminogen activator TPA is a powerful medicine that can break down blood clots. It is useful for a situation like ischemic stroke where a blood clot is the problem. However we wouldn’t use it for a cold since we have no reason to assume it will alleviate cold symptoms or otherwise combat rhinovirus

59
Q

what is TD50

A

TD50 is the dose required to produce a toxic effect in 50% of the population

60
Q

LD50 is

A

the amount of a material, given all at once, which causes the death of 50% (one half) of a group of test animals

61
Q

What is ED50

A

The ED50 (median effective dose) is the dose of a medication that produces a specific effect in 50% of the population that takes that dose.

62
Q

Define Therapeutic Index

A

defined as the ratio of the TD50 to ED50 from some therapeutically relevant effect

63
Q

narrow therapeutic index is observed with_____

A

highly potent drug

64
Q

example for when therapeutic drug monitoring (TDM) is recommended

A

use with lithium (bipolar disorder) due to its narrow therapeutic range and phenytoin

Care - Pharmacology 2024 (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions