2 - Drug Receptor Interactions

Question 1

What is a drug?

Answer 1

A chemical substance that interacts with a biological system to produce a physiological effect.

Question 2

What are the 4 types of drug targets? Are there any additional ways a drug can work?

Answer 2

(All proteinaceous)

1. Receptors
2. Ion channels
3. Transport systems
4. Enzymes

Non-specific physicochemical properties
Binding to plasma proteins to create a reservoir of inactive drug

Question 3

Where are drug receptors located?

Answer 3

Most are on the cell surface.

Steroid receptors are inside the cell.

Question 4

What is the role of drug receptors?

Answer 4

They are activated by neurotransmitters or hormones.

Question 5

How are drug receptors categorized?

Answer 5

They are defined by their selective agonists and antagonists.

Question 6

How many types of drug receptors are there?

Answer 6

4 types, categorised by structure (transduction system)

Question 7

Examples of drugs that drug receptors?

Answer 7

ACh (agonist), Atropine (antagonist of muscarinic)

Question 8

Use of atropine?

Answer 8

Pre-surgery to dry up secretions

Question 9

How many types of ion channels are there?

Answer 9

2 types, voltage sensitive (VSCC) and receptor linked (nAChR)

nicotinic acetylcholine receptor

Question 10

How are voltage sensitive channels opened?

Answer 10

By a change in membrane potential.

Question 11

What are examples of drugs that target ion channels?

Answer 11

Local anaesthetics (lidocaine) - block voltage sensitive sodium channels

Ca2+ channel blockers, anti-hypertensives (-dipine) - relaxes sympathetic tone of heart to decrease BP

Question 12

What are the roles of transport systems?

Answer 12

They transport substances against their conc. gradient (e.g. glucose, ions, T)

Question 13

What are examples of drugs that target transport systems?

Answer 13

Tricyclic antidepressants (inhibit NorA uptake 1)

Cardiac glycosides - is a cardiac stimulant during heart failure
(inhibits Na+/K+ ATPase, improves contractility through increase in intracellular calcium)

Question 14

How can drugs interact with enzymes and give an example of a drug for each?

Answer 14

Enzyme inhibition (anticholinesterases [glaucoma])

False substrate to false neurotransmitter (methylDOPA to methylNorA [lowers BP])

Prodrugs (chloral hydrate to trichloroethanol [hypnotic drug])

N.B. Enzyme systems can also mediate unwanted effects e.g. paracetamol (methionine as antidote)

Question 15

How can drugs have a non-specific action?

Answer 15

Through their physicochemical properties

e.g. antacids (bases), osmotic purgatives (ability to draw water into gut to soften stool)

Question 16

How do drugs interact with plasma proteins?

Answer 16

Drugs can bind to plasma proteins such as albumin creating a reservoir of inactive drug.

Question 17

What is an agonist?

Answer 17

Something that stimulates or activates a receptor e.g. ACh, nicotine

Question 18

What is an antagonist?

Answer 18

Something that blocks the receptor e.g. atropine (musc), hexamethonium (nico)

Question 19

What two factors determine drug potency?

Answer 19

Affinity - the avidity of which it binds

Efficacy ‘intrinsic activity’ - its action e.g. conformational change of receptor

Question 20

What is avidity?

Answer 20

The sum of the total individual binding interactions or affinities. e.g. low individual affinity but high avidity

Question 21

What is the difference between a full and partial agonist?

Answer 21

Full agonists can generate the maximal agonist response of tissue.

Partial agonists have antagonist activity when administered in the presence of a full agonist e.g. beta blockers.

Question 22

What is ‘selectivity of action’?

Answer 22

The receptor population which the drug interacts with. Will overlap more as drug dosage is increased causing unwanted side effects.

Not the same as specificity as as drugs will overlap to some degree.

Question 23

What is the meaning and importance of the ‘structure activity relationship’?

Answer 23

The activity of a drug is strongly dependent on its structure. ‘Lock and key’ is a good analogy for affinity and efficacy.
Small changes in structure can produce big changes in activity. This can also have a large change in the pharmacokinetics e.g. metabolism and duration of action. It is common to create new antagonists from agonists.

Question 24

What is a ligand?

Answer 24

Any substance that binds to a receptor

Question 25

What is avidity?

Answer 25

The net sum of the individual affinities

Question 26

What is KA

Answer 26

Affinity

The equilibrium constant for the agonist to form a complex with the receptor

Question 27

What is KAR

Answer 27

‘Intrinsic efficacy’
The affinity of the AR complex to the transducer system (e.g. an ion channel opening, linking to an enzyme) and subsequent formation of the ART complex and response.

Question 28

What are the intermolecular forces that attract a drug to its receptor?

Answer 28

Electrostatic, H bonding, Van der Waals, Hydrophobic

Question 29

What is the two axes of the dose response curves?

Answer 29

Y - Tissue response
X - Agonist conc./log agonist conc.

Rectangular hyperbola/Sigmoidal

The difference in maximum height between full and partial agonists represents the difference in efficacy.