PHARMACOLOGY

Question 1

What is EC50?

Answer 1

Concentration of drug needed to achieve 50% of the maximum effect of a drug

Question 2

Write the equation for the law of mass action and explain what it is

Answer 2

A law that states the rate of the chemical action is directly proportional to the product or the concentration of the reactants

Question 3

Give an example of one drug that can bind to multiple targets

Answer 3

Steroid hormones bind to nuclear receptors however recent findings have found that they can also bind to GCPRs

Question 4

What are the two different features of Quetiapine?

Answer 4

At low doses it is a sedative and at high doses it is an antipsychotic. This means two different doings of the same drug is equivalent to two different drugs

Question 5

Give 3 types of endocrine drug receptors

Answer 5

• Enzymes
• Ion channels
• Transporters

Question 6

What are physiological receptors

Answer 6

Receptors for hormones or neurotransmitters like acetylcholine

Question 7

Give 4 ways drugs can regulate cell function

Answer 7

• Altered membrane potential
• Altered enzyme activity
• Altered gene expression
• Most drugs affect via physiological receptors where they act like hormones

Question 8

What is an inverse agonist?

Answer 8

A ligand that binds to the same receptor binding site as an agonist but has the opposite effect as an agonist. It also surpasses spontaneous receptor signalling when it is present

Question 9

Explain what super agonists and spare receptors are

Answer 9

Super agonists are agonists that have such a high efficacy that they don’t need to bind to all the available receptors in order to produce a maximal response. The left over receptors are ‘spare receptors.’ The Emax is above 100%

Question 10

What are partial agonists?

Answer 10

Even when they have bound to all of the receptors available, they still can’t produce the maximal response

Question 11

What are competitive antagonists?

Answer 11

Bind at the site where the endogenous agonist would normally bind e.g propanolol and beta-adrenergic receptors, atropine and muscarinic receptors. They compete for the binding site

Question 12

What are irreversible antagonists

Answer 12

They bind to a receptor very strongly e.g covalent bond and they stay there. They may reduce the number of receptors by poisoning some and this reduces the maximum response

Question 13

What happens to a membrane receptor once it has been inactivated by an irreversible antagonist?

Answer 13

The receptor is inactivated and they are internalised where they go inside the cell into vesicles. Small vesicles form early endosomes which fuse with other vesicles to become more acidic and have more degrading enzymes. Receptor is broken down by enzymes and ingredients are recycled.

Question 14

What are allosteric antagonists?

Answer 14

They bind to the receptor away from the binding site and reduce its affinity for the agonist - rare in pharmacology, more common with enzymes

Question 15

What are physiological antagonists?

Answer 15

They prevent the action of agonists but not by binding to the receptor. They use other mechanisms for example they interfere with some pre receptor metabolism. Endocrine disruptors inhibit conjugation reactions

Question 16

What are channel blockers?

Answer 16

Bind inside the channel and block the passage of ions

Question 17

Why are nicotinic acetylcholine receptors pentamers?

Answer 17

Have 5 subunits and once acetylcholine has bound, they have a change in conformation which allows the pore to open up and acetylcholine can pass through

Question 18

What are integral tyrosine kinases/ receptor tyrosine kinases (RTKs)?

Answer 18

A subclass of tyrosine kinases that are involved in mediating cell-to-cell communication and controlling a wide range of complex biological functions, including cell growth, motility, differentiation, and metabolism e.g insulin receptors. They are activated by ligands that bind to them

Question 19

How do nuclear receptors respond when binding to steroids?

Answer 19

• Steroid hormones bind to nuclear receptors inside the cell in the nucleus or cytoplasm
• Without a steroid present it is unfolded
• With a steroid present it is folded
• There is a DNA binding domain which mediates the binding of nuclear receptors to sites within the genome

Question 20

What are the 3 regions on a nuclear receptor?

Answer 20

• DNA binding domain
• Ligand binding domain
• Response element

Question 21

What does heterotrimeric mean in relation to GPCRs?

Answer 21

It refers to the 3 subunits of the G protein - alpha, beta and gamma.

Question 22

What is a common target of G proteins?

Answer 22

Adenylyl cyclase enzyme. When this enzyme is activated, it catalyses the second messenger cAMP from molecules of ATP. In humans, cAMP is involved in responses to sensory input, hormones, and nerve transmission, among others.

Question 23

What are the 3 types of G subunits and what do they do?

Answer 23

Gi - inhibitory effect on adenylyl cyclase
Gs - Stimulating effect on adenylyl cyclase
Gq - has a separate intracellular signalling mechanism which activates phospholipase C

Question 24

What is the different between cytokine receptors and tyrosine kinase receptors

Answer 24

In cytokine receptors, the enzymes are not covalently bound. They have non-covalently bound enzymes in the cytoplasmic regions