Pharmacology

Question 1

What is a receptor?

Answer 1

A macromolecule in the membrane or inside the cell that chemically binds a ligand (drug).

Question 2

What are different receptors activated by?

Answer 2

Different (sometimes the same) signalling molecule

Question 3

How many different receptors exist?

Answer 3

4

Question 4

What are the four different types of receptors?

Answer 4

Ionotropic receptor channel
Receptor enzyme
Integrin receptor
G-Protein coupled receptor

Question 5

What is an ionotropic receptor?

Answer 5

A receptor that is also an ion channel

Question 6

What is a receptor enzyme?

Answer 6

Receptor that functions as an enzyme

Question 7

What is an integrin receptor?

Answer 7

Receptor that directly affects an enzymes activity

Question 8

What does a G-protein coupled receptor look like?

Answer 8

7 transmembrane spanning segments

Question 9

What type of response can a receptor evoke?

Answer 9

Membrane permeability
Metabolism
Secretory activity
Rate of proliferation or differentiation
contractile activity
The process is called signal transduction

Question 10

What type of chemical messenger binds to an intracellular receptor?

Answer 10

A lipid soluble receptor, steroid hormones

Question 11

Where are the receptors found that can influence the transcription of DNA?

Answer 11

Within the nucleus

Question 12

What response can steroids have on transcription?

Answer 12

They are a transcription factor and can alter the rate of transcription

Question 13

What are the tyrosine kinase receptor enzymes involved in?

Answer 13

Proliferation and differentiation

Question 14

Define affinity

Answer 14

The extent which a drug binds to receptors at any given drug concentration or the firmness with which the drug binds to the receptor.

It is the strength of chemical attraction between the drug and the receptor

Question 15

Define efficacy

Answer 15

The maximum response that can be achieved with a drug.

It determines how good the drug is at activating the receptor

Question 16

When will you get the maximum response from a drug?

Answer 16

When all the relevant receptors are bound to the drug

Question 17

Why is the concentration / response graph curved?

Answer 17

Because it is more likely for a ligand to hit a free receptor at the start of a reaction then the end

Question 18

What is the EC50?

Answer 18

It is the concentration of a drug at half of its maximal response

Question 19

What graph is used to determine the EC50?

Answer 19

The log of drug concentration against the increasing response

Question 20

What does the EC50 indicate?

Answer 20

The affinity of the drug for the receptor, a smaller EC50 indicates a smaller amount of drug is needed to evoke the same response, therefore the drug has a higher affinity

Question 21

How does efficacy affect the EC50?

Answer 21

It doesn’t

Question 22

What is an agonist?

Answer 22

It mimics the normal effect of the receptor

Question 23

What is an antagonist?

Answer 23

It blocks the normal effect of the receptor

Question 24

How many different receptors can a strand of drug bind to?

Answer 24

As many as the drug has conformational shapes to the receptor

Question 25

What are the sources of calcium ions?

Answer 25

Internal stores via inisitol triphosphate From outside the cell via ligand or voltage gated channels Via inhibition of calcium transport out the cell

Question 26

What are the effects of calcium in the cell?

Answer 26

Can regulate the activity of the target protein e.g of Protein Kinase C Can bind to calmodulin which directly activates a target protein Works via some other calcium binding protein e.g troponin

Question 27

What is a secondary messenger?

Answer 27

Second messengers are small molecules and ions that relay signals received by cell-surface receptors to effector proteins.

Question 28

What are the possible effects of a secondary messenger?

Answer 28

Make channels open wider Regulate protein synthesis Regulate the release of calcium Regulate the synthesis of RNA in the nucleus Might act on microtubules making things secrete things out of the cell

Question 29

What is intracellular calcium?

Answer 29

Intracellular calcium ([Ca2+]i) is a secondary messenger which regulates numerous cellular processes and, therefore, its concentration is tightly regulated.

Question 30

Intracellular calcium storage

Answer 30

Organelles which repetitively release and then reaccumulate Ca2+ ions in response to specific cellular events eg - mitochondria and the endoplasmic reticulum.

Question 31

What does the size of the response depend on?

Answer 31

Drug affinity - does it bind to a receptor? Drug efficacy - does it activate the receptor?

Question 32

What happens to a subunit of a G protein when the G protein coupled receptor is activated?

Answer 32

It regulates an enzyme that produces a secondary messenger, e.g Regulates adenyl cyclase, which in turn produces the second messenger cAMP (cyclic AMP) This in turn regulates the activity of another enzyme, PKA (protein kinase A) which then goes off to phosphorylate proteins

Question 33

What happens when phospholipase C is regulated?

Answer 33

Two secondary messengers are regulated, these (diacylglycerol and Inisitol triphosphate) - These are responsible for activation of Protein Kinase C and the release of calcium ions from internal stores

Question 34

Give examples of receptors with intrinsic enzyme activity

Answer 34

Tyrosine kinases Receptor guanylyl cyclases - retina

Question 35

What type of enzyme can receptors interact with directly?

Answer 35

JAK kinases

Question 36

What are JAK kinases involved in?

Answer 36

Protein synthesis

Question 37

What is the result of activation of Adenylyl cyclase by a G protein?

Answer 37

Makes cAMP (secpndary messenger) which activates a protein kinase

Question 38

What can one signalling molecule act on?

Answer 38

Several receptor subtypes

Question 39

What is an example of one signalling molecule that can act on several receptor subtypes?

Answer 39

Adrenaline – the endogenous agonist activates all adrenoceptors (α1, α2, β1, β2) like a “master key”

Question 40

What are selective agonists?

Answer 40

Drugs that activate only some of those receptors

Question 41

What is an example of a selective agonist?

Answer 41

Salbutamol - a β2 agonist | Used in treatment of asthma

Question 42

What is a selective antagonist?

Answer 42

Drugs that block only some of those receptors

Question 43

What is an example of a selective antagonist?

Answer 43

Propranolol - a β1 and β2 antagonist | Used in treatment of arrythmias

Question 44

An antagonist at a pharmacological receptor is likely to have what combination of affinity and efficacy?

Answer 44

High affinity and no efficacy Pharmacological antagonists are characterised by having high affinity (so bind readily to the receptor) but low or no efficacy (so have no effect, and stop the ligand binding to prevent its effect too).

Question 45

An agonist at a pharmacological receptor is likely to have what combination of affinity and efficacy?

Answer 45

High affinity and high efficacy

Question 46

Why do agonists have high efficacy?

Answer 46

They are able to cause a conformational change in the receptorwhereas regular drugs don’t necessarily cause any changes

Question 47

Describe some of the sources of drugs

Answer 47

Natural products from nature Synthetic drugs from the pharmaceutical industry Biotechnology using living systems to make therapeutic agents. Gene therapy

Question 48

How do drugs act?

Answer 48

Interfering with a binding site - a receptor

Question 49

Give examples of binding sites

Answer 49

Cell surface and intracellular receptors Ion channels Carriers Enzymes Nucleic acids

Question 50

What is transmembrane signalling?

Answer 50

Recognition and binding of an extracellular signal by an integral membrane receptor protein and the generation of intracellular signals by one or more effector proteins.