Pharmacodynamics

Question 1

What unit do we use to consider drug concentration?

Answer 1

Molarity

Question 2

What is a ligand ?

Answer 2

A molecule or ion that binds specifically to a receptor

Question 3

If a drug is an antagonist, what effect does it have on the receptor?

Answer 3

Block the binding of its endogenous ligand

Question 4

If a drug is an agonist, what effect does it have on the receptor?

Answer 4

Activate the receptor to bind its ligand, alters receptor conformation (switches On)

Question 5

Receptor activation is governed by intrinsic efficacy. What does this mean?

Answer 5

the relative ability of a drug-receptor complex to produce a maximum functional response.

Question 6

What is the ligands efficacy?

Answer 6

The ability of a ligand to cause a measurable response

Question 7

What two factors is efficacy governed by?

Answer 7

Intrinsic efficacy

Plus cell/tissue dependent factors

Question 8

Do antagonists have affinity, efficacy and/or intrinsic efficacy?

Answer 8

Recess affinity for the receptor only. Block the effects of agonists (no intrinsic efficacy)

Question 9

How do we measure drug-receptor interactions by binding?

Answer 9

Often by binding of a radioactively labelled ligand to cells or membranes prepared from cells

Low ligand concentration = low binding

Question 10

What is Bmax?

Answer 10

Maximum binding capacity (receptors saturated). Independent of ligand concentration. Gives information on receptor number

Question 11

What is Kd?

Answer 11

The drug dissociation constant, drug concentration that’s required to occupy 50% of available receptors gives an idea of affinity.

Lower Kd = higher affinity

Question 12

What is the effect of drugs with high affinity?

Answer 12

High affinity allows binding at low concentrations, reflects the amount of drug regard needs to be given

Question 13

If you plot log[drug] vs proportion of bound receptors, what is the shape of the curve?

Answer 13

Sigmoidal

Question 14

What is the EC50 of a drug?

Answer 14

The effective concentration which gives 50% of the maximal response

Question 15

What is the difference between drugs dose and concentration?

Answer 15

The concentration is known for a drug at the site of action
The dose is when the concentration at the site of action is unknown - give a toeing a specific dose in mg for example, but don’t know concentration at site

Question 16

What is Ec50 a measure of?

Answer 16

Potency (how well a drug works)

Question 17

What three things are required for a ligand to have potency?

Answer 17

1. Affinity - ligand binding to receptor
2. Intrinsic efficacy - receptor activation
3. Cell/tissue specific components

2+3 = efficacy

Question 18

What are spare receptors?

Answer 18

Receptors that don’t contribute to response (where less than 100% occupancy = 100% response)
Often seen when receptors are catalytically active (e.g. Tyrosine kinase of GPCR)

Question 19

Why do spare receptors exist?

Answer 19

Because of amplification in the signal transduction pathway (response limited by a post-receptor event)

Question 20

What is the benefit of having spare receptors?

Answer 20

Spare receptors increase sensitivity- allow response at low concentrations of agonist

Question 21

Receptor number can be altered by what?

Answer 21

Activity (increase with low activity, decrease with high activity)
Also physiological, pathological and drug-induced changes

Question 22

What is a full agonist?

Answer 22

Where EC50 is less than/equal to Kd (spare receptors)

Often endogenous ligand

Question 23

What is a partial agonist?

Answer 23

Where EC50 is approx = Kd. So no spare receptors, all receptors occupied, insufficient intrinsic efficacy for maximal response (cannot change into right shape)
Lower efficacy that full agonists

Question 24

What is the relevance of partial agonist? (3)

Answer 24

Allow a more controlled response
Work in the absence or low levels of (endogenous) ligand
Can act as antagonist if levels of full agonist

Question 25

What are opioids?

Answer 25

Used for pain relief and also recreationally (e.g. Heroin)

Action primarily as an agonist to μ-opioid receptor (GPCR)

Question 26

Changing the number of receptors can change a partial agonist into a full agonist, how?

Answer 26

Partial agonist still has low intrinsic efficacy at each receptor BUT sufficient number of receptors to generate a full response

Question 27

The maximal possible response is limited, meaning that equal responses …….

Answer 27

Do not mean equal strength (efficacy)

Question 28

What are the three types on antagonist?

Answer 28

Reversible competitive
Irreversible competitive
Non-competitive

Question 29

What does reversible competitive antagonism depend on?

Answer 29

Relied on dynamic equilibrium between ligands and receptors (greater [antagonist] = greater inhibition)

Question 30

What effect do reversible competitive antagonists have in the agonist-response curve?

Answer 30

Cause parallel shift to the right of the agonist concentration-response curve (further right with increased agonist concentration)

Question 31

What is Naloxone?

Answer 31

is a high affinity, competitive antagonist at μ-opioid receptors. (Competes (successfully) with heroin and other opioids for receptors)

Question 32

What is irreversible competitive antagonism?

Answer 32

When the antagonist dissociates from receptor slowly or not at all. With increased [antagonist] or increased time, more receptors blocked

(Can’t be overcome by increasing agonist conc)

Question 33

What is the effect of irreversible competitive antagonists on the agonist concentration-response curve?

Answer 33

cause a parallel shift to the right and at higher concentrations suppress the maximal response (as spare receptors filled by antagonist)

Question 34

What is non-competitive antagonism?

Answer 34

Binds at an allosteric site (no competition for binding site)

Similar effects to irreversible competitive antagonism