Core Pharmacology

Question 1

What are Small molecule drugs?

Answer 1

These are synthetic small molecules

They can be made in the lab and purified

Question 2

What are the most druggable proteins?

Answer 2

G protein coupled rectors
Kinases
Ion channels

Question 3

Why do we develop small molecule drugs?

Answer 3

These are selective and specific for ion channels, transporters and enzymes

Question 4

What happens when receptors are targeted by drugs?

Answer 4

They induce a change in the functioning of cells

These changes are sensitive to change

Question 5

Examples of neuroreceptors?

Answer 5

Alpha adrenoreceptors
Histamine receptors
These are all involved in neurotransmission

Question 6

What do neuroreceptors do and what type of receptor are they?

Answer 6

They detect very small molecules like histamine or noradreanline
They are all amines in the catecholamine category of receptors.

Question 7

What is the problem with neuroreceptors such as the alpha adrenoreceptors and the histamine receptors?

Answer 7

They are quite similar

Although expressed in different areas and they have different roles they can all respond to the same neurotransmitter

So designing drugs specific to a SUBTYPE is very hard

Question 8

What is the negative impact of too high a concentration of a drug?

Answer 8

Increasing it too much will see the drug bind to other types of proteins

Question 9

What is the difference between an agonist which causes a direct and indirect response

Answer 9

An agonist is said to give a DIRECT response when it only actives a specific protein and doesn’t activate any other proteins after that. (So only one protein receptor is affected)

An agonist which causes an INDIRECT response - this just means that the agonist may affect a receptor AND further proteins to cause a change of function in a cell. (So the agonist affects multiple proteins)

Question 10

What does an inverse agonist do?

Answer 10

It binds to a receptor to STABILISE it and STOP it from signalling further. The receptor keeps its shape.

Question 11

Some receptors show constitutive activity. What does this mean and where can you typically find these receptors?

Answer 11

These receptors work continuously and can be switched ON without the help of an agonist

These receptor proteins are often FREE FLOATING in the plasma membrane and cytosol.

They occasionally move into a conformation which causes signalling and allow a signal to open an ION channel for example

Question 12

What two main affects can a drug have on a ion channel?

Answer 12

• it can cause the ion channel to become blocked - stopping the flow of ions

Or it can act as a modulator and ALTER the behaviour of ion channels - this affects the gating mechanism and can make the channel stay open for LONGER or SHORTER amounts of time

Question 13

Whats the difference between inhibitors and false substrates?

Answer 13

Inhibitors bind to a receptor / protein to INHIBIT or alter its activity

False substrates are something which an enzyme will hydrolyse by mistake without realising its not the correct substrate

Question 14

What is a prodrug??

Answer 14

This a drug which is metabolised by an enzyme to become an active drug

You can see this example in the liver, when certain drugs enter and are metabolised, allowing a stronger drug to be formed.

Question 15

What are transporters?

Answer 15

These carry drugs across a membrane

Question 16

What are two drugs which target microtubules?

Answer 16

Colchicine - this affects the stability of some microtubules in cells. This drug particularly helps to treat gout - which is cause by the build up of uric acid between joints causing inflammation

Paclitaxel - this is used to treat cancer. This stops microtubules from stabilising and thus stops them being pulled apart.

Question 17

Features of a ligand gated ion channel? And how can we tell them apart from other channels?

Answer 17

These channels have multiple transmembrane domains which anchor themselves into the membrane. Its a sequence of amino acid which can create their pore

Question 18

Features of a G-protein coupled receptor?

Answer 18

These have 7 transmembrane domains which anchor proteins to the membrane

Alone, these protein receptors cannot cause signalling! They need other proteins to stimulate them for signalling to occur!

Question 19

How do G proteins work?

Answer 19

They rely on a binding protein (remember there are alpha and beta sub units) which binds to GTP. For a signal to occur they rely on the GTP binding protein to leave and for a signal to be induced.

Question 20

Kinase linked receptor features?

Answer 20

These only have a single transmembrane protein domain

They rely on kinase enzymes

These receptors have a ligand binding site which usually stick out

Growth factors tend to bind to these

Question 21

Nuclear receptors? How many transmembrane domains?

Answer 21

These lack a transmembrane domain?

So they are not found anchored in the plasma membrane of a cell

They have a DNA binding domain in which they can fulfil their actions

SO THESE BIND TO DNA

Question 22

There are 4 different types of ligand gated ion channel. Describe the cis loop type:

Answer 22

Cis loop type:

• e.g. nicotinic receptor
• this has 4 transmembrane protein domains
• its receptor is made up of 5 proteins with the same structure
• it has a pentameric assembly

Question 23

There are 4 different types of ligand gated ion channel. Describe the ionotropic glutamate receptor family:

Answer 23

• these have 3 TRANSMEMBRANE domains and are made up of 4 proteins
• this have a tetrameric assembly

Question 24

There are 4 different types of ligand gated ion channel. Describe the p2x receptor family:

Answer 24

Their ligand is ATP

They have 2 transmembrane domains and their receptors are made of three proteins

Question 25

There are 4 different types of ligand gated ion channel . Describe the Calcium release type

Answer 25

These need a ligand to bind to them to become gated
These are found on the endoplasmic reticulum remember
They need 4 proteins to come together to function