Drugs And Receptors (8) Flashcards
What’s the most common drug target?
- Proteins
- GPCRs
How do drugs exert their effects?
- By binding to a target.
What is the equation for molarity?
- Molarity= g/L / MWt
How many atoms are thee in a mole?
- 6x10^23
Drug action on a receptor is dictated how?
- Affinity and intrinsic efficacy
How is binding governed?
- Association and dissociation
- Affinity
The activation of a drug and receptor is governed how?
- Intrinsic efficacy
How do antagonists work in respect to affinity and intrinsic efficacy?
- Have affinity only
- No intrinsic efficacy
- Blocks effects of agonists
How can drug-receptor interactions by binding be measured?
- Via binding of radioactively labelled ligand to cells/membranes prepared from cells.
- Low ligand conc = low binding
- High ligand conc = high binding
What is Kd?
- Dissociation constant
- Measure of affinity
- Concentration of ligand required to occupy 50% of the available receptors
- Lower Kd = higher affinity
What is B max?
- Max binding capacity - gives information about receptor number
What are examples of responses from drugs?
- Change in signalling pathway
- Change in cell/tissue behaviour (e.g. Conc)
What is meant by EC50, what is it a measure of and what is it dependent on?
- Effective concentration giving 50% of maximal response
- Measure of potency
- Affinity+efficacy=potency
What is meant by concentration?
- Known concentration of drug at site of action e.g. Cells and tissues
What is meant by dose?
- Concentration at site of action unknown (don’t know how body will react)
What are the characteristics of drugs that need to be taken into account in a clinical setting?
- Affinity
- Efficacy
- Selectivity (off target effects?)
- Drug metabolism/pharmacokinetics (how body deals with it)
- Physicochemical properties (solubility/pH/stability/crystallinity)
Why may selectivity be a problem?
- If isn’t selective then will have effects on other receptors
- e.g adrenaline on B adrenoceptors, useful for asthma but may also increase heart rate.
What is selectivity based on?
- Affinity
In some cases <100% occupancy leads to 100% response why is this?
- Spare receptors
Why may spare receptors exist?
- Amplification in signal transduction pathway response limited by post-receptor event.
What do spare receptors allow for in terms of sensitivity?
- Increases
- Allows responses at low concentrations of agonist
A change in receptor number can lead to what?
- Change in agonist potency (max response)
- E.g. 10,000 is full response. If only have 5000 receptors means can’t get full response
How does tolerance to drugs arise?
- Receptor number decreases when there’s a high activity
- Too high=no receptors available.
When is buprenorphrine used and why?
- Adequate pain relief but no respiratory problems
- Higher affinity but lower efficacy than morphine
What role can a partial agonist act as?
- Act as an antagonist to a full agonist
- Has a higher affinity but doesn’t turn on receptor as well
What are partial agonists dependent on?
- Compound and systemic
- Increase receptor number can change a partial agonist into a full agonist, still has a low intrinsic efficacy but there are sufficient receptors to contribute to a full response
What are the types antagonists?
- Reversible/irreversible competitive antagonism
- Non-competitive antagonism (allosteric/post-receptor)
Describe what reversible competitive antagonism is.
- Competitive inhibition
- Relies on dynamic eqm between ligands and receptors
- As antagonist concentration concentration increase response decreases
What is irreversible competitive antagonism?
- When agonists slowly dissociate or not at all
- With more time or antagonist concentration more receptors are blocked by antagonist. Non-surmountable
- At higher conc suppresses max response
What effect does irreversible competitive antagonist have on an agonist - conc response curve?
- Parallel shift to the right as spare receptors filled by antagonist
What is non-competitive antagonism?
- No competition for binding site but affects orthosteric affinity and or efficacy
- Non competitive inhibition
