33. Drug Receptor Interaction

Question 1

Why is it important to study receptors?

Answer 1

1. Pharmaceutical industry and drug development- need to understand them to develop drugs
2. Important for physiology of endogenous transmitters- transmitters and hormones act primary upon receptor targets.
3. Chemical toxicity- many toxic mechanism are receptor mediated
4. Viral toxicity- viruses and other microorganism can target receptors.

Question 2

Describe type 1 Ligand-gated ion channels? (3pts)

Answer 2

1. Channel found on the cell membrane
2. When a molecule binds on the receptor the channel will open and negatively or positively charged ions will come in to cause depolarisation or hyperpolarisation.
3. Quick process

Question 3

Describe g-protein couples receptors? (3pts)

Answer 3

1. Drug activates G-protein couple receptor
2. This induces a cascade of secondary messengers e.g the g protein that can inhibit or synthesise an enzyme on the cell membrane which can lead to phosphorylation or opening of other ion channels.
   3 . This will induce a pharmacological response e.g increased heart rate or contraction of muscles.

Question 4

Describe Agonists? (3pts)

Answer 4

1. Drugs that occupy receptors and activate them
2. Can show action by looking at low dose response curve
3. As concentration increases of agonist the pharmacological response increases.

Question 5

Describe antagonists? (2pts)

Answer 5

1. Drugs that occupy receptors but do not activate them. Antagonists block receptor activation by agonists.
2. At one point if you increase concentration of antagonist the pharmacological response is 0 however if you add an antagonist to an agonist an agonist will reduce the activity of the agonist.

Question 6

Describe partial agonists?

Answer 6

Drugs which produce a biological effect but never the maximum of which the tissue is capable. Partial agonists posses antagonist properties.

Question 7

Describe inverse agonists?

Answer 7

An agonist that produces an opposing biological response to that observed by a full agonist.

Question 8

How is a agonist receptor complex formed? (5pts)

Answer 8

1. Add agonist to a receptor
2. Agonist will interact with receptors to form an agonist receptor complex
3. A drug will bind to this receptor. Occupation is governed by affinity
4. Once the drug binds to the receptor it becomes activated
5. This induces a pharmalogical response e.g the release of neurotransmitters.

Question 9

What is efficacy?

Answer 9

The ability of a drug to induce a pharmacological response

Question 10

What is affinity?

Answer 10

The measure of how tightly or loosely the drug binds to the receptor.

Question 11

What do full agonists have?

Answer 11

Full agonists have a high efficacy which means they have the maximum ability to induce a pharmacological response.

Question 12

Describe the binding of agonists to receptors?

Answer 12

1. The receptor binds to the cell membrane of the agonist.
2. The drug will interact and bind to the receptor. This interaction can be a tight interaction or a weak one.
3. How tightly the agonist binds to the receptor depends on the different bonds which occur between the agonist and the receptor. Hydrogen bonds, ionic bonds and vdw forces have weak bonds whilst covalent bonds are strong.

Question 13

Describe receptor binding in autoradiogrpaphs?

Answer 13

1. yellow colour/red colour= receptor is more abundant

2. Blue colour= receptor is less abundant

Question 14

How does heroin produce pleasure?

Answer 14

Heroin binds to highly abundant receptors in the reward region of the brain therefore produces pleasure.

Question 15

Why is the thalamus important?

Answer 15

Thalamus is important because it modulates pain. Morphine is an opioid which acts on the opioid receptor and suppresses pain.

Question 16

Describe the law of mass action?

Answer 16

The interaction between an antagonist receptor complexes are reversible due to the weak bonds between them. The reversibility of binding of an agonist receptor is governed by the law of mass action. The law of mass action states that reversibility of binding is dependant on the concentration of the reactants involved. If more agonists are added more receptors will be occupied by the agonist and therefore the agonist receptor complex will start increasing because more receptors will bind. Eventually maximum amounts of receptors will be bound to the antagonists and it will saturate so no more agonist-receptors complexes will form.

Question 17

What happens when no drug is added?

Answer 17

There is 0 binding of that receptor

Question 18

What happens when you increase drug concentration?

Answer 18

More receptors will be occupied by the drug. It will come to a point where a maximum amount of receptors are bound by the drug and the plot has reached its saturation plot. increasing the concentration of the drug will make no difference.

Question 19

What is the B max?

Answer 19

The maximum amount of receptors bound by the agonists

Question 20

What is the KD?

Answer 20

The kd is the measurement of concentration of the drug that is needed to bind to half the maximum amount of receptors. Each drug has its own kd value. Kd is the ability of a drug molecule to bind to a receptor site. It is inversely correlated with affinity- the higher the kd value the lower the affinity and the less loosely it is bound to the receptor. The lower the kd value the higher the affinity and the more tightly the receptor is bound to the drug.

Question 21

Describe the dose-response curve of adrenaline?

Answer 21

1. Add 0 adrenaline= 0 pharmacological response

2. As you increase concentration of adrenaline heart rate increases till it reaches its maximum efficacy.

Question 22

Describe treshold concentraion?

Answer 22

The minimum concentration of a drug to induce a pharmacological response

Question 23

What is the maximum pharmacological response?

Answer 23

The efficacy of a drug

Question 24

What is EC50?

Answer 24

Effective concentration giving 50% biological response. The potency of the drug. The higher the EC50 the lower the potency of the drug. The lower the EC50 the higher the potency of the drug.

Question 25

What is potency?

Answer 25

Refers to the concentration of the drug required for the effect. The less concentration required the more potent the drug.

Question 26

The lower the EC50?

Answer 26

The higher the potency of the drug

Question 27

Describe the drugs which treat pain?

Answer 27

Fenatyl and morphine is used to treat severe pain because they are highly potent and have a higher efficacy which means it has a maximum response allowing it to suppress pain effectively. Asprin is used to treat mild pain such as headaches as it has a high EC50 which means that a lot of asprin is needed to reach 50% of the maximum pharmacological response and is less potent.

Question 28

Why is heroin addictive?

Answer 28

Heroine is addictive because it binds to the opioid receptor which induces a sense of reward. Heroine addicts therefore crave heroin because it produces pleasure. If people stop taking heroin they suffer withdrawal symptoms such as intense stomach pain, joint aches and tremors.

Question 29

What is Buprenorphine?

Answer 29

A partial agonist which is used for the management if ophiod addiction. It is a opipod drug which binds to the opiod receptor with higher affinity than heroine which means it displaces heroin from the binding site. It will then induce a pharmacological response of pleasure however the rewarding effect is much less than the one produced by heorine. The partail efficacy of Bupernorphine reduces withdrawal symptoms. Eventually the desire for heroine is reduced till it diminishes and you are on Buprenoprhine for a long period of time.

Question 30

Describe competitive antagonists?

Answer 30

Drugs which will compete for the same active site as the agonists. The competitive antagonist will eventually displace the agonist from its binding site thus blocking the receptor.

Question 31

Describe non-competitive functional antagonits?

Answer 31

Antagonists which bind on the receptor but in a different binding site to the agonist binding site. This blocks the receptor functionally.

Question 32

Describe non-competitive allosteric antagonists?

Answer 32

Drugs which act on a different binding site as the agonist binding site. This interaction causes the 3rd shape of the agonist binding site to change which means an agonist cannot bind to its binding site. As a result the receptor becomes inactive.

Question 33

Describe the process of competitive antagonism? (5pts)

Answer 33

1. Competitive antagonist will compete with the agonist for the same binding site
2. Eventually the antagonist will displace the agonist from its binding site
3. The antagonist then binds to the receptor instead
   4,. Receptor inactivates
4. There is a lack of pharmacological response

• Increasing agonists will cause the antagonists and agonists to compete with each other on the same active site. Eventually the agonist will outcompete the antagonist for the binding of the binding site.
• A concentration of an agonist must increase to overcome the antagonistic binding on the receptor.

Question 34

Describe a dose-response curve?

Answer 34

• Adding a competitive antagonist will cause the dose-response curve to be shifted to the right. Increasing the competitive antagonist will eventually outcompete the antagonist.
• A much higher concentration of the agonist is needed to induce a maximum pharmacological response when the competitive antagonist is present compared to when the agonist is alone. The maximum efficacy remains the same.

Question 35

Why do heroin addicts overdose?

Answer 35

Heroine addicts overdose due to respiratory depression. Opiods like heorine act on opiod receptors inducing a reward and respiratory depression which can be fatal.

Question 36

What is naloxone?

Answer 36

Nalaxone is a competitive antagonist which acts on the same binding site as heroine. It has a high affinity for the opiod receptor and will therefore displace the heroine from binding to the opiod receptor and will bind to it instead. This reverses the pharmacological response of heroine and will therefor reverse the opiod induced respiratoy depression. Heroine addicts carry a epipen with them which contain naloxone so if they do overdose they can inject themselves with it thus reversing respiratory depression and saving their life.