Drug Receptor Interaction Flashcards
Why is it important to study receptors?
- Pharmaceutical industry and drug development - Some Target G-protein coupled receptors
- Physiology of endogenous transmitters- Transmitters and hormones act primarily upon receptor targets
- Chemical toxicity -Many toxic mechanisms are receptor mediated
- Viral Toxicity -Viruses and other microorganisms can target receptors
How do drugs bind to receptors?
• Ligand-gated ion channels (ionotropic receptors) - Causes hyperpolarisation or depolarisation
• G-protein coupled receptors (metabotropic receptors) - Causes activation of G-protein which induces the activation of a second messenger response
-Binding is reversible because of the types of Binding; hydrogen, ionic, vdW,covalent (strong)
What is the Law of Mass Action?
• Low [Agonist] and lots of Receptors free = few Agonist-Receptor interactions. More AR interaction if more agonist, but it starts to saturate at one point (saturation curve).
• Increase [A] = more Agonist-Receptor interactions. The reaction is driven to the right of the equilibrium
• Continue increasing [A] – few Receptors free, reaction reaches maximal
• Equilibrium constant (KA)- When 50% of receptors are free and bound to agonist.
• Smaller KA means agonist has a greater AFFINITY for receptor (it binds more) than a drug with a higher KA value
Because of finite number of receptors, after a certain concentration, it will saturate.
• Bmax – maximum number of receptors bound to your ligand.
• KD value – concentration of the drug needed to obtain half Bmax (measurement of affinity) how much of drug needed to bind half of receptors.
• KD value inversely proportional to its affinity. The higher the KD value, the lower the affinity (less strongly binds to receptors)
Draw and describe the reaction between agonist and receptor
Agonist – drug that binds to a receptor and causes a biological response (responses such as contraction of muscle, release of neurotransmitter etc.).
• Agonist binds on receptor and forms an agonist-receptor complex
• Found in equilibrium, complex can dissociate, to form an agonist and receptor again.
• Most agonists bind reversibly to their receptors.
• Interactions take place upon binding (formation of H-bonds, Ionic etc.)
-Antagonist – Drug that binds on receptor but don’t cause any biological effect. Can block the effect of an agonist
-Partial agonist – induces pharmacological effect but not at maximum level of an agonist.
-Inverse agonist - Produce an opposing response by an agonist (agonist contracts muscle, inverse agonist relaxes muscle)
What is drug affinity and efficacy?
Affinity – Ability of a drug/ligand to bind to a receptor site. How strong/ weak binds to receptor.
Efficacy – Ability of a drug to induce a biological response (release of neurotransmitter, muscle contraction etc.)
What is drug potency?
The amount of drug required to produce a given percentage of its maximal effect.
A drug can have high potency but poor efficacy, meaning that response is seen at very low doses and remains small even at high doses.
Compare full and partial agonists
- People may become dependent on drugs, and may suffer from withdrawal symptoms.
- E.g.) Buprenorphine for opioid addiction.
- A partial agonist, binds on receptor like heroin, but doesn’t give a maximum response as heroin will do.
- Reduces withdrawal symptoms, and are present at receptors. Have high affinity but less efficacy. This drug recues heroin-induced highs.
Full-full efficacy whereas partial less.
Compare competitive and non-competitive antagonism
Competitive Antagonism – Drug which competes for the same active site of the receptor as the agonist
It will block the pharmacological effect of the agonist. Displaces the agonist from the active site.
Curve shifted to the right.
Linear part is parallel
Non-competitive antagonism - Drug which acts and binds on a different site on agonist, still gets a response, but never reaches maximum response.
E.g.) Ketamine blocks glutamine receptors by acting at a different site in the receptor structure to glutamate.
Explain applications of antagonism in pharmacotherapy
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Irreversible antagonism
Antagonist binds to receptor and stays there, reducing number of receptors which can be occupied by drugs.
E.g.) Aspirin, acetyl group forms covalent bond in enzyme and blocks substrate entering the enzyme and inhibits.
What determines drug efficacy
a) Threshold concentration
Threshold dose enough to cause biological response
b) EC50 = effective concentration giving 50% biological response
Used to compare drug potency (determined by affinity and efficacy).
Lower the EC50, the higher the efficacy (inversely proportional) and so more effective. If EC50 is higher, the less the efficacy and so less effective
c) Maximal concentration
Determine maximum concentration for maximum effect
• Shape of graph is sigmoidal
• It increases and eventually saturates (because of finite number of receptors)
• Antagonist has no effect, as it binds but has no response, so it will be parallel to x axis. Has 0 efficacy
• Antagonist can have high affinity but 0 efficacy
