Pharmacodynamics

Question 1

What is the difference between pharmacodynamics and pharmacokinetics?

Answer 1

Dynamics= How the drug interacts with the receptors in the body
Kinetics= How the body interacts with the drugs ADME

Question 2

How is drug concentration measured? What is the equation to figure out the concentration of a drug?

Answer 2

Molarity (moles per L)

grams/ litres) / Mr (RFM of drug) = Molarity (conc

Question 3

What is the difference between an agonist and and antagonist?

Answer 3

agonist activates a receptor

antagonist prevents binding of endogenous agonist so prevent receptor activation

Question 4

What is affinity?

Answer 4

How easily a drug will bind to a receptor

Question 5

How can affinity be measured?

Answer 5

Using radioactively labelled ligand and distinguishing between the amount of free and bound ligand

Question 6

What graph describes affinity of a ligand for a receptor? What is the name for the maximum binding capacity (how many receptors present) and the concentration of drug needed to fill 50% of the receptors?

Answer 6

A concentration- binding curve
Bmax is the maximum binding capacity- [drug] needed to bind to every receptor
Kd is dissociation constant, lower Kd means higher affinity

Question 7

If there is 100,000 receptors, how many receptors will be filled at the Kd value? How many will be filled if there is only 10,000 receptors?

Answer 7

50,000 and 5,000 because at Kd conc 50% of the receptors will be filled no matter how many receptors there are

Question 8

If the concentration- binding curve is sigmoidal what has happened?

Answer 8

The drug concentration has been put into logs.

Question 9

What is the ligands efficacy? What governs a ligands efficacy?

Answer 9

The ability of a bound ligand to cause a response
Governed by intrinsic efficacy (ability to cause conformational change to activate receptor) and other cell/ tissue dependant factors

Question 10

How many micro moles (uM) in a milli mole (mM)

Answer 10

1,000

Question 11

Do antagonists have efficacy and affinity?

Answer 11

affinity only as they have no intrinsic efficacy

Question 12

How can the ability of a drug to cause a response me measured?

Answer 12

Measure response (eg amount of secretion) at varying drug concentrations 
Draw concentration- response curve

Question 13

What is the name for the maximum response and the drug concentration needed to give 50% response

Answer 13

Emax is maximum response

EC50 is [drug] needed for 50% response

Question 14

What is EC50 an measure of?

Answer 14

Potency- ability of drug to cause response (affinity+ efficacy)

Question 15

What is the pharmacological difference between dose and concentration of a drug?

Answer 15

Concentration refers to known concentration at site of action
Dose refers to amount of drug given, with conc at site of action unknown

Question 16

What element of drug potency can change for the same drug and receptor?

Answer 16

Affinity and intrinsic efficacy are FIXED

Tissue dependant factors of efficacy can change however

Question 17

How can drug efficacy be determined from a conc- binding and conc- response curve?

Answer 17

If Kd is high (low affinity) but EC50 is low (high potency) then it must have pretty good efficacy.

Question 18

Why may two agonists with the same binding curve and the same intrinsic efficacies have different response curves?

Answer 18

One may have better efficacy, it is simply better at provoking a response

Question 19

What is functional antagonism?

Answer 19

An agonist that blocks an endogenous ligands action by activating a different pathway/ receptor. Eg salbutamol

Question 20

How are salbutamol and salmeterol selective to the B2 receptor in lungs?

Answer 20

Salbutamol- slightly higher affinity (lower Kd) to B2, but mainly by route of administration and selective efficacy
Salmeterol- much higher affinity to B2 than B1, no selective efficacy

Question 21

Why can a full response (Emax) be bought about partial binding- for example at Kd concentration?

Answer 21

Because most cells have many spare receptors- there are more receptors on the cell than needed to evoke a full response

Question 22

Receptors are energy consuming to make so why have spare ones?

Answer 22

Less ligand needs to be produced so saves energy long term

Question 23

What can cause receptor numbers to change? What is clinical consequence of this?

Answer 23

If the receptor is rarely stimulated (low activity), the receptor is expressed more.
Therefor sensitivity to a drug will change the longer you’ve been on a drug/ the more times you’ve been on it

Question 24

What is the difference between full and partial agonists?

Answer 24

Partial agonists have a lower intrinsic efficacy than full agonists because they cause a slow/ partial conformational change

Question 25

Why do partial agonists also have a lower Emax (cant produce full response)?

Answer 25

Because all receptors are filled but lower intrinsic efficacy means response less strong

Question 26

Why are partial agonists useful?

Answer 26

More controlled response
Work in absence of endogenous ligand
Act as antagonists if high levels of full agonists

Question 27

Give an example of a partial agonist and how it can be a more effective pain management and drug detoxing?

Answer 27

Buprenorphine is partial agonist to u opiod receptors
More controlled pain relief than morphine and lower chance of respiratory depression also used on heroine addicts to make withdrawal symptoms less severe

Question 28

How can partial agonists cause a full response (Emax) equivalent to a full agonist?

Answer 28

By having loads of spare receptors, it may take a higher conc of partial agonist for this to be achieved tho

Question 29

What are the types of antagonists?

Answer 29

Reversible and irreversible competitive antagonists and non- competitive antagonists

Question 30

If two drugs have equal responses (Emax) do they have equal efficacy?

Answer 30

Not necessarily, it make take more of one drug to cause a full response
This is because the maxiumum response is often limited

Question 31

What is the name of the concentration of drug needed to inhibit the maximum response by 50%?
What is the name for affinity of a competitive inhibitor?

Answer 31

IC50 is conc antagonist needed for 50% inhibition

Kd is dissociation constant ([drug] needed for 50% binding)

Question 32

Is inhibition of a competitive antagonist surmountable? What will a conc- response curve of a drug look like if competitive antagonist added?

Answer 32

Yes

It will be identical just shifted to the right

Question 33

Give an example of a competitive antagonist

Answer 33

Naloxone- high affinity to u- opioid receptors. Used to reverse respiratory depression due to overdose

Question 34

Is irreversible competitive antagonism surmountable? What is affect on conc- response curve of adding more?

Answer 34

Nope

Same but shifted to left at start (as spare receptors fill) and then Emax decreases as more antagonist added

Question 35

Give an example or a irreversible competitive inhibitor.

Answer 35

Phenoxy benzamine- blocks a1 adrenoreceptors so less vesoconstriction so lower bloop pressure.
Used to treat tumors in adrenal glands because it will not be overcome but the massive quantities of adrenaline being produced

Question 36

What is opposite of allosteric site?

Answer 36

orthosteric site

Question 37

What is effect of non-competitive antagonism on conc- response curve?

Answer 37

Same as irreversible competitive:
Parrellel shift as spare receptors inactivated
Then Emax decreases as more is added becausenot enough receptors able to be activated to create full response no matter how much drug you add

Question 38

Give an example of a non- competitive antagonist

Answer 38

Maraviroc acts on CCR5 which is used by HIV to enter cells. Therefor HIV cannot enter cells and spread (its an antiretroviral drug).