Drug-Receptor interactions

Question 1

Define a drug

Answer 1

A chemical substance of known structure. not including food, that when administered produces a biological effect

Question 2

Why do drugs show side effects and toxicity

Answer 2

1. Drugs are insufficiently selective
   2.Drugs may be very selective but target site may underlie many processes across the whole body leading to off target/side effects and toxicity
   3.Use of the drug across a long time period can cause permanent changes in structure and function
   4.Not knowing enough about the disease and how it works
   5.Patient variability
   6.drugs interacting with each other

Question 3

State how drugs can be administered (10 ways)

Answer 3

I PUT A QUESTION ON PADLET FOR CONIBEAR CHECK IF ANSWER
CHECK IF JOHAN ANSWERED QUESTION ON G PROTEINS

Question 4

Why is it important to use the generic name of a drug and not the brand

Answer 4

The generic name gives information about the site of action. brand names tell nothing e.g. statins like simvastatin and fluvastatin (lower levels of LDLs in blood) end in the word statin telling you they are statins, beta blockers (inhibit beta adrenoreceptors) also end in “lol” normally

Question 5

Why are drugs taken (5)

Answer 5

1. To produce a cure - antibiotics
2. To suppress symptoms - anti allergy
   3.To prevent a disease or symptom - Aspirin
   4.Diagnose a disease - neostigmine
3. recreational

Question 6

Define an agonist

Answer 6

A drug that evokes a response when combined with a receptor.

Question 7

Define an antagonist

Answer 7

A drug that prevents the action of another drug, transmitter or naturally occurring hormone

Question 8

Explain the difference between agonist and antagonist

Answer 8

An agonist binds to a receptor to active the receptor while antagonist bind to receptor and do not activate it instead they occupy the site to prevent it from being activated

Agonists have efficacy antagonists do not

Question 9

What is the law of mass action equation and what does it define

Answer 9

It defines the relationship between the quantity/ concentration of free drug and the number of drug receptor target.

rate of reaction is proportional to the concentration of the reactants

Question 10

Equation for the concentration of drug receptor complexes
And the equation for rate of dissociation and rate of association

Answer 10

[D] + [R] (reversible reaction arrow) [DR]

Rate of association = k+1[D][R]
(the +1 is subscript)

rate of dissociation = k-1[DR]
(the -1 is subscript)

Question 11

What is the relationship between the rate of association and dissociation at equilibrium

Answer 11

equal

Question 12

Explain the term Kd(subscript) what its used for and what it means

Answer 12

The binding of a drug to a receptor is governed by affinity. higher affinity = stringer binding. Kd(subscript) quantifies affinity

Kd(subscript) = [D][R]/[DR]
units of Kd(subscript) are molar

the value is Kd(subscript) is the concentration of drug that drug that occupies 50% of the receptors

lower the Kd(subscript) = higher affinity

Question 13

Describe the measure used to quantify drug binding

Answer 13

Drug binding is quantified by determining the Kd(subscript) value.
Kd(subscript) is the concentration of drug that occupies 50% of the binding sites
it is the measure of affinity and a constant

Question 14

What are the conditions needed for the receptor occupancy equation to be valid.

Answer 14

1. Equilibrium
   2.1drug molecule binds to one receptor molecule
2. Drug concentration at recpetor same as that applied to system
3. A negligible amount of drug added is bound
4. the binding of one drug molecule does not effect the binding of another

Question 15

What is does the shape of the curve look like when drug concentration (x) and fractional occupancy (y)

Answer 15

a smooth curve with an asymptote which represents total number of receptors.
A large increase in fractional occupancy with a small increase in drug concentration at the beginning.

conclusions
1. receptor occupation increases with drug concentration
2.binding is saturable

Question 16

What is a semi-log plot and why is it normally used instead of a linear plot

Answer 16

It means using log([DRUG]) instead of [DRUG]

changes the rectangular hyperbola shape into a sigmoidal shape.
allows us to see the threshold of binding easier
gives a better definition of the maximum

Question 17

What are the units of Kd(subscript)

Answer 17

Molar

Question 18

What’s the relationship between the affinity of a drug and the position of the binding curve on the axis (concentration fractional occupancy graph)

Answer 18

The higher the affinity the lower the Kd(subscript) value and the binding curve is more to the left of the graph
leftmost curve has the highest Kd(subscript)

Question 19

What does an agonists ability to produce a pharmacological effect depend on

Answer 19

1. the binding of the drug to the receptor (affinity).
   2.activation of receptors and production of response(efficacy).

Question 20

define efficacy

Answer 20

The rate at which an agonist activates the DR complex

[DR]⇌[DR*]
rate of forward reaction = alpha
rate of back ward reaction = beta

Question 21

Describe full and partial agonist

Answer 21

A full agonist is where the bound agonist resides is the active DR complex for most of the time and is capable of evoking a maximum response. high efficacy

partial agonist is where the agonist resides in the inactive DR complex most of the time and cannot evoke a mix response. low efficacy
A partial agonist must bind to all the receptors to produce its max response, the max response is less than the full response that the tissue is capable of.
Still have therapeutic value

Question 22

What is the name of the shape of the curve in a concentration response graph when its a linear plot

Answer 22

Rectangular hyperbola

Question 23

What is the name of the shape of the curve in a concentration response graph when its a Semi-log plot

Answer 23

sigmoidal
this uses log of concentration instead if concentration
it condenses the rate of concentrations

Question 24

What is EC50

Answer 24

the concentration of drug that produces 50% of the max response - this quantifies the potency of an agonist

Question 25

When functional response and binding curves are plotted on the same graph what determines the separation between the curves and what does it show

Answer 25

efficacy - greater efficacy = greater distance between them
it shows that there is not a 1 to 1 relationship between response and occupancy. this gives rise to spare receptors

Question 26

What does the proportion of receptors in the receptor reserve depend on

Answer 26

Efficacy and number of receptors

Question 27

What is potency

Answer 27

How much of a drug is needed to produce a particular response.
higher potency = less drug concentration
lower potency = greater drug concentration

Question 28

What are the components of a biological response

Answer 28

Affinity, efficacy, receptor number

Question 29

Name a therapeutic use of partial agonists and how.

Answer 29

Salbutamol (asthma thing)
During an asthma attack there is a contraction in the bronchi smooth muscle, this muscle relaxes by activation of b2 adrenergic receptors
adrenaline can activated these receptors as well as b1 and b2 receptors on the heart this causes and increase of heart rate and force of contraction. therefore adrenaline would relax the bronchi smooth muscles but would put the patient at serious risk of heart attack. Salbutamol is a selective b2 adrenoreceptor agonist, but a partial agonist. the magnitude of efficacy of a partial agonist is dependant on receptor number. bronchi muscles have a large number of b2 receptors where as the heart has very few. causing a significant response in the bronchi muscles but not the heart.

Question 30

What are the different types of antagonism and how do they work

Answer 30

Competitive - binds to the antagonist recognition site preventing the agonist from binding
Non-competitive - does not bind to the agonist site but prevents the agonist from binding in another way
Uncompetitive - when the antagonist binds to the activated receptor
physiological - when a neurotransmitter/ hormone is countered by the action of another neurotransmitter/hormone

Antagonism may be reversible or irreversible

Question 31

How can reversible competitive antagonism be overcome

Answer 31

It can be overcome by increasing the concentration of agonist

Question 32

What is Kb and what does it represent and units

Answer 32

The equilibrium constant for the antagonist
units are molar
the lower the concentration of kb the better the reversible competitive antagonist is.

Question 33

What is the Gaddum-schild equation

Answer 33

[D1]/[D1]’ = 1+ [B]/[kb]

B = antagonist