Session 8 Flashcards

(16 cards)

1
Q

Describe the terms affinity intrinsic efficacy and efficacy

A

Affinity - the likelihood of a ligand binding to its target
Intrinsic Efficacy - the ability of a ligand to activate a receptor once it is bound
Efficacy - the ability of a ligand to cause a response (intrinsic efficacy plus cell/tissue dependent events).
An antagonist has affinity but no efficacy

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2
Q

How are drug-receptor interactions measured?

A

By binding of a radioligand

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3
Q

What is the name and symbol given to:
The concentration of ligand that a receptor has 50% occupancy
The maximal binding capacity of a receptor
And what is the use of each?

A

Kd, dissociation constant. A measure of affinity.

Bmax, maximum binding capacity. A measure of receptor number.

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4
Q

What is the name and symbol given to:
The effective concentration of ligand giving 50% of the maximal response
The maximal response of a receptor
And what is the use of each?

A

EC50, a measure of potency. It is governed by affinity and efficacy.
Emax, maximal response

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5
Q

What is IC50?

A

Inhibitory concentration giving half the maximum inhibition

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6
Q

What is the difference between concentration and dose?

A

Concentration - known concentration of the drug at the site of action
Dose - when the concentration at the site of action is unknown

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7
Q

Discuss affinity and efficacy of two common drugs used to treat asthma

A

Salbutamol - B2 agonist. Only 20 fold higher affinity for B2 but utility enhanced by B2 selective efficacy (limits B1 side effects) and route of administration (oral spray).
Salmeterol - longer acting B2 agonist and has a high B2 selective affinity but no selective efficacy (selectivity based on affinity) and is insoluble.

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8
Q

For any ligand-receptor complex what factors can influence potency?

A

Cell/tissue dependent factors including receptor number (affinity and intrinsic efficacy are fixed)

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9
Q

What are partial agonists and what are their properties?

A

Agonists that can’t produce a maximal response even with full receptor occupancy. EC50=Kd. They can be more or less potent than full agonists.
They have a lower intrinsic ACTIVITY (related to maximal amplitude of response) and hence lower efficacy.

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10
Q

Why can partial agonists be advantageous?

A

They can allow a more controlled response, they work in the absence of endogenous ligand and can act as an antagonist if high levels of the full agonist is present.

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11
Q

Explain the concept of spare receptors

A

In some cases, less than 100% receptor occupancy will give maximal response (EC50

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12
Q

Explain a clinical use of a partial agonist

A

Buprenorphine has a higher affinity but a lower efficacy than morphine - it is a partial agonist of the m-opioid receptor. This can reduce change of respiratory depression whilst still providing pain relief.
Buprenorphine can be used as a gradual a withdrawal from heroin addiction and prevent the use of other opioids by blocking their action.

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13
Q

Give a therapeutic example of a reversible competitive antagonist

A

Naloxone - high affinity competitive antagonist at m-opioid receptors used to reverse opioid mediated depression

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14
Q

Give a therapeutic example of an irreversible competitive antagonist

A

Phenoxybenzamine - non selective irreversible A1 adrenoreceptor antagonist used in hypertension episodes in pheochromocytoma (a tumour of the adrenal gland which causes excessive Catecholamine synthesis leading to vasoconstriction.

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15
Q

What are the different types of antagonist?

A

Reversible competitive antagonism
Irreversible competitive antagonism
Non competitive antagonism (allosteric binding)

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16
Q

Why are allosteric sites useful therapeutic targets?

A

They provide diversity amongst receptor subtypes.