33. Drug Receptor Interaction Flashcards
Why is it important to study receptors?
- Pharmaceutical industry and drug development- need to understand them to develop drugs
- Important for physiology of endogenous transmitters- transmitters and hormones act primary upon receptor targets.
- Chemical toxicity- many toxic mechanism are receptor mediated
- Viral toxicity- viruses and other microorganism can target receptors.
Describe type 1 Ligand-gated ion channels? (3pts)
- Channel found on the cell membrane
- 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.
- Quick process
Describe g-protein couples receptors? (3pts)
- Drug activates G-protein couple receptor
- 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.
Describe Agonists? (3pts)
- Drugs that occupy receptors and activate them
- Can show action by looking at low dose response curve
- As concentration increases of agonist the pharmacological response increases.
Describe antagonists? (2pts)
- Drugs that occupy receptors but do not activate them. Antagonists block receptor activation by agonists.
- 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.
Describe partial agonists?
Drugs which produce a biological effect but never the maximum of which the tissue is capable. Partial agonists posses antagonist properties.
Describe inverse agonists?
An agonist that produces an opposing biological response to that observed by a full agonist.
How is a agonist receptor complex formed? (5pts)
- Add agonist to a receptor
- Agonist will interact with receptors to form an agonist receptor complex
- A drug will bind to this receptor. Occupation is governed by affinity
- Once the drug binds to the receptor it becomes activated
- This induces a pharmalogical response e.g the release of neurotransmitters.
What is efficacy?
The ability of a drug to induce a pharmacological response
What is affinity?
The measure of how tightly or loosely the drug binds to the receptor.
What do full agonists have?
Full agonists have a high efficacy which means they have the maximum ability to induce a pharmacological response.
Describe the binding of agonists to receptors?
- The receptor binds to the cell membrane of the agonist.
- The drug will interact and bind to the receptor. This interaction can be a tight interaction or a weak one.
- 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.
Describe receptor binding in autoradiogrpaphs?
- yellow colour/red colour= receptor is more abundant
2. Blue colour= receptor is less abundant
How does heroin produce pleasure?
Heroin binds to highly abundant receptors in the reward region of the brain therefore produces pleasure.
Why is the thalamus important?
Thalamus is important because it modulates pain. Morphine is an opioid which acts on the opioid receptor and suppresses pain.
Describe the law of mass action?
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.
What happens when no drug is added?
There is 0 binding of that receptor
What happens when you increase drug concentration?
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.
What is the B max?
The maximum amount of receptors bound by the agonists
What is the KD?
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.
Describe the dose-response curve of adrenaline?
- Add 0 adrenaline= 0 pharmacological response
2. As you increase concentration of adrenaline heart rate increases till it reaches its maximum efficacy.
Describe treshold concentraion?
The minimum concentration of a drug to induce a pharmacological response
What is the maximum pharmacological response?
The efficacy of a drug
What is EC50?
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.