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MedST IB: Mechanisms of Drug Action (MoDA) > 1.0 Drug Receptor Interactions > Flashcards

1.0 Drug Receptor Interactions Flashcards

1
Q

What forces are involved in binding ligand to receptor? (stronger to weakest)

A

1) Covalent<br></br>2) Ionic<br></br>3) H-bond<br></br>4) Van der Waals<br></br>5) Hydrophobic

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2
Q

What is an agonist?

A

Binds to a receptor and generates a response

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3
Q

What is an antagonist?

A

A drug which opposes the action of an agonist drug<br></br><br></br><b>Competitive</b> = same binding site. No efficacy<br></br><br></br><b>Non-competitive</b><br></br>- Different mechanisms<br></br>1) Binds to allosteric site → ↓ agonist binding<br></br>2) Irreversible binding to same site<br></br>3) A drug that activates another pathway → opposing the effect of agonist (functional non-competitive agonist)

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4
Q

Define affinity

A

<b>Amount of receptor that is bound by a given concentration of drug</b><br></br><br></br>How tight the drug-receptor complex it

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5
Q

Define dissociation

A

How readily the drug unbinds

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6
Q

Define affinity constant

A

Inverse of the concentration of drug needed to occupy half the receptors

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7
Q

What are the equations for affinity constant?

A

1) K+1/K+2<br></br>2) 1/Kd

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8
Q

Define efficacy

A

<b>Relationship between the amount of receptor occupied by drug and the size of the response</b><br></br><br></br>The maximum response measured when all receptors are occupied with drug

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9
Q

Define EC₅₀

A

Concentration of drug that leads to 50% of maximal response

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10
Q

Define potency

A

<b>Potency refers to the concentration of a drug causing a particular magnitude of response (e.g. EC₅₀)</b><br></br><br></br>Combination of affinity and efficacy

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11
Q

Define selectivity

A

<b>A drug is selective for a particular receptor if it has a high affinity for one particular receptor type and low affinity (if any) for others</b>

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12
Q

Define IC₅₀

A

<b>Antagonist concentration needed to reduce agonist response by 50%</b><br></br>This is not constant (↑ [agonist] → ↑ IC₅₀)

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13
Q

Name an agonist and antagonist for muscarinic and nicotinic receptors:

A

<b>Muscarinic</b><br></br>Agonist = Muscarine<br></br>Antagonist = Atropine<br></br><br></br><b>Nicotinic</b><br></br>Agonist = Nicotine<br></br>Antagonist = d-tubocurarine

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14
Q

What is Ka?

A

Affinity constant<br></br>↑K₁ → ↑ affinity of drug to receptor<br></br>Units = M⁻¹

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15
Q

What is Kd?

A

Dissociation constant (K₁=1/Kd)<br></br>Units = M<br></br><br></br><b>Kd = concentration of drug that gives half the maximum occupancy</b>

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16
Q

What is K₂?

A

Affinity constant for antagonist

17
Q

What is pA₂?

A

Log(K₂)<br></br><br></br>The concentration of antagonist needed to shift EC₅₀ across 2 fold = 10^pA₂

18
Q

What is the formula for fraction of receptors bound?

A

“<div><img></img></div>”

19
Q

What makes up total binding of a drug?

A

<b>1) Specific binding</b><br></br>- Binding to receptor<br></br>- Saturable<br></br><br></br><b>2) Non-specific binding</b><br></br>- Binding to sites away from receptor<br></br>- Linear and non-saturable

20
Q

What is the spare receptor (receptor reserve) concept?

A

Only a fraction of the receptors are needed to produce a maximum response<br></br><br></br>In these situations Kd&raquo_space; EC₅₀

21
Q

What is the significance of receptor reserve?

A

1) Allows lower concentrations of drug/molecule to cause effect (this is useful as agonists can therefore be low affinity, meaning that their effect has rapid onset and offset)<br></br><br></br>2) Maximum response can still be achieved despite some loss of receptors through desensitisation/ antagonism

22
Q

Give some reasons why EC₅₀ and Kd are not the same:

A

1) Receptor reserve<br></br>2) Response may occur before drug-receptor binding interaction reaches equilibrium<br></br>3) Response may occur due to >1 pathway<br></br>4) Concentration of drug bathing tissues may be different to concentration of drug reaching receptors

23
Q

How long does nACh channel open for when agonist binds?

A

1ms (allowing 10,000 Na⁺ to enter)

24
Q

What are the subunits of nACh?

A

α x 2<br></br>β <br></br>γ <br></br>δ<br></br><br></br>Each subunit has M1-M4 stretches. M2 from each unit lines the pore

25
Q

What is receptor desensitization?

A

Prolonged exposure to an agonist → receptors are prevented from producing their normal effect (transduction mechanism is uncoupled)<br></br><br></br>Desensitisation may include a change in drug affinity or a change in number of receptors (or both)

26
Q

What are the mechanisms of desensitization in β₂ adrenoreceptor?

A

<b>1) Uncoupling</b><br></br>Seconds → minutes<br></br>a) Heterologous desensitization (PKA)<br></br>b) Homologous desensitization (βARK)<br></br><br></br><b>2) Sequestration</b><br></br>Minutes<br></br>Receptors taken up by endocytosis<br></br><br></br><b>3) Downregulation</b><br></br>Minutes → hours<br></br>PKA alter mRNA stability → ↓ receptors

27
Q

How many membrane spanning segments do voltage gated ion channels have?

A

4 groups of 6 membrane spanning segments<br></br>(Na⁺ + Ca²⁺ channels = one polypeptide, K⁺ channel = 4 polypeptides)

28
Q

What are the three Na⁺ channel conformations?

A

1) Open<br></br>2) Closed<br></br>3) Inactive/refractory

29
Q

What fibres are preferentially targetted by LAs?

A

Aδ +C

30
Q

What is use-dependence?

A

Rate of channel block is dependent on the rate at which the nerve is stimulated

31
Q

What is voltage dependence?

A

Rate of channel block is faster if more channels open (Pre-pulse depolarisation causes faster nerve block than pre-pulse hyperpolarisation)

32
Q

What is the pKa of lidocaine?

A

8-9

33
Q

How does benzocaine enter the cell?

A

Non charged, therefore enters the cell using hydrophobic pathway

34
Q

How does lidocaine enter the cell?

A

1) Binds to and stabilises the inactive conformation of the channel<br></br>2) Crosses membrane in uncharged form<br></br>3) Blocks channel in charged form<br></br>4) Shows use dependence + voltage dependence

35
Q

Give three types of Ca²⁺ channel:

A

1) L-type<br></br>2) T-type<br></br>3) N-Type

36
Q

What are the three different responses to depolarisation (modes) that L-type calcium channels show?

A

Mode 1 - channel opening is in bursts followed by long closed intervals<br></br>Mode 2 - Very long openins<br></br>Mode 0 - Channel doesn’t open

MedST IB: Mechanisms of Drug Action (MoDA) (10 decks)

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