Drug-receptor interactions

Question 1

Define drug

Answer 1

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

Question 2

What are drug target sites?

Answer 2

Receptors
Ion channels
Transport systems
Enzymes

All proteins! RITE

Question 3

What are agonists and antagonists?

Answer 3

Antagonists - block receptors (don’t produce a response when bound to receptor: they just get in the way of agonists)
Agonists - ligands that stimulates the receptors to generate a response
Receptors are defined by agonists and antagonists

Question 4

How many types of receptors are there?

Answer 4

4

Question 5

What are the two different types of acetylcholine receptors?

Answer 5

Nicotinic receptors

Muscarinic receptors

Question 6

Give an example of an agonist and antagonist

Answer 6

Agonist - ACh

Antagonist - Atropine (used an anaesthetic premedication to dry up secretions)

Question 7

What are the two types of the ion channels?

Answer 7

1) Voltage-sensitive e.g VSCC Voltage sensitive calcium channel
2) Receptor-linked e.g nAChR Nicotinic ACh Receptor

Question 8

Give an example of a calcium channel blocker?

Answer 8

Nifedipine (-dipine; means calcium channel blocker)

Question 9

What is meant when we talk about transport systems?

Answer 9

Transport systems against concentration gradients (glucose, ions, NTs). E.g Na+/K+ATPase

Question 10

What type of drug can target ion channels?

Answer 10

Local anaesthetics - Sodium/Calcium channel blockers –> fewer action potentials = pain reduced

Question 11

What type of drug targets transport systems?

Answer 11

TCAs (Tricyclic anti-depressants) - targets NA uptake 1. Act as inhibitors of NA uptake 1 reducing NA reuptake into the neurone
Cardiac glycosides

Question 12

What are the three methods which drugs can interact with enzymes to produce a response in the body?

Answer 12

i) enzyme inhibitors
ii) false substrates
iii) prodrugs

Question 13

Give an example of an enzyme inhibitor drug?

Answer 13

Anticholinesterases (neostigmine)

Question 14

Give an example of a false substrate drug?

Answer 14

methyldopa (antihypertensive)

Question 15

Give an example of a prodrug?

Answer 15

chloral hydrate (insomnia)

Question 16

What are PPB drugs?

Answer 16

Plasma protein binding drugs. They create a reservoir of of drugs within the blood - does not create a physiological response. Warfrin

Question 17

What does the potency (power) of a drug depend on?

Answer 17

Affinity - the avidity of the drug to its binding site. High avidity = good affinity. How willing the drug binds to the receptor
Efficacy - the ability of the drug to cause a conformation change in the receptor. The ABILITY of the drug to GENERATE A RESPONSE.

Question 18

What can describe a drug with a high affinity and avidity?

Answer 18

Powerful agonist

Question 19

Define full agonist?

Answer 19

A drug that can produce the maximum response of a tissue

Question 20

Define partial agonist?

Answer 20

A drug can produce a response but not the maximum response of the tissure

Question 21

What happens when you have a full an partial agonist together?

Answer 21

The partial agonist has some antagonist activity against the full agonist because it occupies some of the receptors so the full agonist cant occupy this space to generate a maximum response.

Question 22

Define seletivity

Answer 22

Drugs that have a preferential action towards a specific receptor. This becomes a problem when you try to increase the dose and the drug starts stimulating other receptors.

Question 23

How do cardiac glycosides work?

Answer 23

Drug that targets Na+/K+ transport pump system. They are cardiac stimulant drugs - digoxin slows Na+/K+ pump down resulting in a knock on effect that increases the intracellular calcium concentration. Increases the force of contraction

Question 24

What is the difference between receptors and transport system?

Answer 24

The transport system does not mediate a response, all they do is allow a NT to bind to a protein and move it somewhere else.

Question 25

How does methyldopa work?

Answer 25

It works as an antihypertensive. The enzymes think that it is producing NA but in reality Methyl NA is produced. Methyl NA is a worse vasoconstrictor than NA = Reduced TPR = Reduced BP. The Methyl NA is a false transmitter

Question 26

Give an example of an unwanted effect of drug interaction with enzymes.

Answer 26

Paracetamol overdose

Question 27

What drugs produce responses due to their physiochemical properties?

Answer 27

General anaesthetics
Antacids
Osmotic Purgatives

These are all non-specific drug action

Question 28

Draw the dose-response curve of a full and partial agonist

Answer 28

See diagram: Agonist concentration against tissue response

Question 29

Draw the log dose-response curve of a full, partial and full with low affinity agonist

Answer 29

See diagram

Question 30

In terms of potency how can an antagonist be described as?

Answer 30

It has affinity but NO efficacy

Question 31

What are the two main types of antagonists and examples?

Answer 31

Competitive: Atropine and Propanolol
Irreversible: Hexamethonium

Question 32

What are the two main mechanisms of irreversible antagonism?

Answer 32

They can bind more tightly with covalent forces so they can’t be shifted or they may bind to a different site from the agonist (not competing - could be inside the channel of an ion channel)
Surmountable vs Insurmountable antagonism

Question 33

Describe what is meant by receptor reserve?

Answer 33

‘Spare receptors’ - Some tissues don’t require all the receptors to be occupied to generate a maximal response. This increases the sensitivity of the tissue to the agonist and increases the speed of the response

Question 34

Draw the effect of the antagonist graph

Answer 34

See diagram

Question 35

What is propanolol used for?

Answer 35

Competitive Beta Blocker

Question 36

What is atropine used for?

Answer 36

Used as anaesthetic premedication to dry up secretions

Also used to treat organophosphate poisoning - see lecture on Cholinomimetics