Principles of Pharmacology

Question 1

List 6 drugs which produce their effects due to their physicochemical properties.

Answer 1

Antacids
– sodium bicarbonate

Bulk laxatives
– methylcellulose

Osmotic laxatives
– magnesium sulfate

Osmotic diuretics
– mannitol

General anaesthetics
– halothane

Alcohol

Question 2

Define potency

Answer 2

Concentration of a drug required to produce a defined effect. High potency drugs produce there effect at low concentration

Question 3

Define efficacy

Answer 3

capacity of a drug to produce a response in its target cell after binding to a receptor

Question 4

Define Affinity

Answer 4

The binding strength of the drug receptor interaction.

Potent drugs have high affinity

Question 5

Wha type of ligand posses affinity but not efficacy?

Answer 5

Antagonists

Question 6

What type of ligand posses both affinity and efficacy

Answer 6

Agonists

Question 7

Define Chemical and Biological specificity

Answer 7

Chemical specificity is how complimentary a ligand is to its receptor

Biological specificity is how complimentary the receptor is the to the ligand

Question 8

Whats the difference between an exogenous and an endogenous agonist

Answer 8

endogenous found within the body e.g. ACh

exogenous agonists are drugs/chemicals

Question 9

Describe the relationship between a drug ad its response

Answer 9

produce a hyperbole
produces a sigmoidal curve is drug concentration is logged

graded level of increase of the response changes as concentration varies

saturating the maximal response cannot be exceeded

exhibits threshold the minimum concentration required for a response to be recorded.

Question 10

Where does this curve shift if we increase potency

Answer 10

to the left ie to lower drug concentrations

Question 11

how do you calculate KD and what is it

Answer 11

KD is the dissociation constant used as a measure of affinity of a drug.

KD= [A] x [R] / [AR]

Question 12

what is Ec50

Answer 12

concentration of a drug that produces exactly half the maximal response

Question 13

what is Emax

Answer 13

concentration of a drug that produces the maximal response

Question 14

what is p

how do we calculate it?

Answer 14

p is a measure of the occupancy of receptors

p= [A]/ KD + [A]

Question 15

What is the patch clamp technique?

Answer 15

looks at the activity of a single receptor through extraction using a micropipette
an electrode is use to measure the current produced across the membrane showing response of ion channelled o agonist

found that opening of ion channels was binary and that for partial agonists the frequency of open channels changes not magnitude.

Question 16

what is the effect of neutral agonist?

why is there is the response curve never at zero?

Answer 16

neutral agonists would result in no response ie flat line at 0

however there is always some spontaneous channel opening meaning response curve is never at zero when it starts there is always a background level.

Question 17

what are high efficacy agonists?

Answer 17

channel opens when agonist binds as there is a high efficacy
means receptors can cause a a maximal response –> high potency

Question 18

how can some agonists cause a maximal response without stimulating all receptors?
what are these known as?

Answer 18

these are known as super agonists and have a very high potency meaning they only have to bind to a few receptors to cause a maximal response

Question 19

what are low efficacy agonists?

where is the dose response curve?

Answer 19

agonist binding doesn’t always open channels may have a lower efficacy
therefore there is a lower maximal response so the curve is underneath that of a full agonist

Question 20

what are inverse agonists?

Answer 20

have a negative efficacy reverse effects of agonist

cause endogenous agonised levels to decrease (basal level decreases) by reducing spontaneous channel opening

Question 21

Whats an allosteric agonist

Answer 21

bind to separate allosteric binding site on receptor and increase the receptors affinity for another agonist making it more likely to bind.

Question 22

What is the GABA a receptor?

what effect does benzodiazepine have on this receptor?

Answer 22

a ligand gated chloride ion channel
allosteric binding of benzodiazepine results in a conformational change in the receptor making it more complimentary to GABA. therefore GABa is more likely to bind and cause channel opening and hyperpolarisation

Question 23

what are and what is the effect of competitive antagonists on a dose response curve?

Answer 23

competitive antagonists bind reversibly to the same site as an agonist

causes a parallel shift of the does response curve to higher concentrations (right) decreasing the likelihood of a receptor-agonist complex forming
maximal response can be achieved but a higher conc of agonist is required

Question 24

What receptor does atropine bind to?

what is its effect?

Answer 24

muscarinic ACh receptors

has a competitive antagonist effect

Question 25

what is naloxone ?

what is its effect?

Answer 25

used in heroine overdoses

has a competitive antagonistic effect reducing the binding of heroine to receptors.

Question 26

what is an irreversible antagonist

Answer 26

bind irreversibly at the same site as the agonist
decreases the no of receptors available and therefore decreases the maximal response to agonists
curve shifts to higher concentrations (right) with lower maximal response

Question 27

What happens to receptors that are poisoned or have a high efficacy agonist bound to them?

Answer 27

they are internalised and broken done by lysosomes in the cell
new receptors are made and synthesised therefore the need for the drug doesn’t disappear

Question 28

What is the spare receptor effect

Answer 28

irreversible antagonists may be countered by the spare receptor effect as due to their high efficacy less receptors have to be occupied to have the full effect
this means the maximal response may still be achieved if sufficient agonist is added or the antagonist is removed.

Question 29

What are allosteric antagonists

Answer 29

bind reversibly at allosteric site on receptor . This results in a conformational change in the receptor making it less complimentary to the agonist it normally binds.

Question 30

To which receptor does phenoxybenzamine bind?

What is its effect?

Answer 30

• Alpha adrenoceptors.

- Irreversible antagonistic effect.

Question 31

what are channel blockers?

Answer 31

bind inside ligand gated ion channels preventing the passage of ions/molecules through the channels.

Question 32

Give an example of a group of drugs that are channel blockers

Answer 32

Local anaesthetics block voltage gated sodium channels in sensory neurones in the PNS

Question 33

What are physiological antagonists?

Answer 33

produce the opposite effect to that of an agonist on a tissue using a mechanism that does not involve the use of the same type of receptor

Question 34

give an example of physical antagonistm

Answer 34

glucagon has a opposite effect to that of insulin and uses different specific receptors therefore it is a physiological antagonist of insulin

Question 35

What is desensitisation?

Answer 35

prolonged repeated exposure to an agonist reduces the response to that drug
e.g. heroine your body becomes used to it and you have to take more and more to get a high

Question 36

what are dirty drugs?

Answer 36

Drugs that bind to multiple receptors

Question 37

given an example of a dirty drug and its role.

Answer 37

• Quetiapine.

- An antipsychotic.

Question 38

What are the five receptor superfamilies?

Answer 38

1 - Integral ion channels.

2 - Integral tyrosine kinases.

3 - Steroid receptors (nuclear receptors).

4 - GPCRs.

5 - Cytokine receptors. (use JAK-SAT signalling pathway)

Question 39

Give an example of a integral tyrosine kinase receptor

Answer 39

Insulin receptor

Question 40

Give an example of a nuclear receptor

Answer 40

Oestrogen

Androgen receptors

Question 41

give 2examples of cytokine receptors

Answer 41

growth hormone receptors

prolactin receptors