Pharmacodynamics (session 6) Flashcards

1
Q

How do drugs exert an effect?

A

By binding to a target

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2
Q

True or false: the concentration of drug molecules around receptors is critical in determining drug action

A

TRUE

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3
Q

True or false: most drugs bind irreversibly to receptors

A

FALSE - reversibly

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4
Q

What does a ligand need in order to bind to a receptor?

A

Affinity for the receptor

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5
Q

What is the ability to generate a response called?

A

Efficacy

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6
Q

What is intrinsic efficacy?

A

The ability to switch a receptor on

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7
Q

What is the difference between agonists and antagonists?

A

Agonists have intrinsic efficacy and efficacy

Antagonists have affinity only (no efficacy or intrinsic efficacy)

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8
Q

How do we measure drug-receptor interactions by binding?

A

By binding of a radioactively labelled ligand (radioligand) to cells or membranes prepared from cells (many cells/many receptors)

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9
Q

What is Bmax?

A

Maximum binding capacity (info about receptor number)

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10
Q

What is Kd?

A

Dissociation constant-index of affinity, tells you about the strength of the interaction. Concentration of ligand required to occupy 50% of the available receptors

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11
Q

What does a low value of Kd mean?

A

High affinity

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12
Q

What is EC50?

A

Effective concentration giving 50% of the maximal response - measure of agonist potency

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13
Q

What does EC50 depend on?

A

Affinity and intrinsic efficacy and cell/tissue-dependent factors such as the number of receptors

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14
Q

What effect do beta2-adrenoceptors have on asthma?

A

Relaxation of airways

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15
Q

Why is it hard to design a drug that only targets beta2-adrenoceptors?

A

The binding site for beta1 and beta2 are very similar

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16
Q

What is sensitivity?

A

Concentration of ligand that causes a response

17
Q

Why have spare receptors?

A

Increase sensitivity to a ligand-allows responses at low concentrations of agonist

18
Q

Why do morphine doses have to be increased, even if the pain is the same?

A

System becomes less sensitive

19
Q

Give an example of a full agonist

A

ACh

20
Q

What is the relevance of partial agonists? (3)

A
  1. Can allow a more controlled response
  2. Work in the absence or low levels of ligand
  3. Can act as an antagonist if there are high levels of full agonist
21
Q

What is an example of a partial agonist and what is its clinical implication?

A

Opioids - for pain relief but cause respiratory depression (can lead to death as it inhibits respiration)

22
Q

What is buprenorphine used for clinically?

A

To enable gradual withdrawal of morphine and prevent use of heroin

23
Q

What does reversible competitive antagonism rely on?

A

Dynamic equilibrium between ligands and receptors - increasing concentration of antagonist leads to antagonist out competing agonist and response is inhibited

24
Q

What is IC50?

A

Concentration of antagonist giving 50% inhibition

25
Q

Naloxone is a high affinity, competitive antagonist at mu-opioid receptors. Why might such a compound be useful clinically?

A

Reversal of opioid-mediated respiratory depression-high affinity so it will compete effectively with other opioids (eg heroin) for receptors

26
Q

When does irreversible competitive antagonism occur?

A

When the antagonist dissociates slowly or not at all

27
Q

What is the difference between reversible and irreversible competitive antagonism?

A

Reversible is surmountable (adding more agonist nullifies the effect of the antagonist) whereas irreversible is non-surmountable

28
Q

What is the site where endogenous ligands bind to a GPCR called?

A

Orthosteric site

29
Q

Give an example of an allosteric compound used clinically

A

Maraviroc - binds to allosteric site on chemokine receptor 5 (CCR5) on lymphocytes and changes conformation so HIV cannot bind and cannot enter cells. Used to treat AIDS