L06 - Receptors and the effects of drugs Flashcards
What are agonists?
Substances that produce an effect by binding to the receptor
What are antagonists?
A substance which interferes with or inhibits the the effects/ physiological action of another (block effects by binding to receptor)
What is the patch-clamp technique?
A laboratory technique in electrophysiology used to study ionic currents in individual isolated living cells, tissue sections, or patches of cell membrane
Give some examples of competitive antagonists
- Atropine at muscarinic receptors
- Propranolol at beta-adrenoceptors
- Sildenafil at phospho-diesterase 5 (PDE5) competing with cGMP
What is the action of competitive antagonists?
- Bind reversibly at the same site as the (natural) agonist
- Produce parallel shift to the right of agonist dose/ response curves
What is the action of irreversible antagonists?
- Bind irreversibly at the same site as the agonist
- Forms a covalent bond or binds incredibly tight
- Decreases the maximal response to agonists
- May produce an initial shift to the right of the dose/ response curve with no decrease in max
- Evidence for spare receptors
Give some example of irreversible antagonists
- Phenoxybenzamine at alpha-adrenoceptors
2. Second/ third generation proteasome inhibitors (based on bortezomib)
What are the different types of antagonism?
- Competitive antagonists
- Irreversible antagonists
- Allosteric antagonists
- Channel blockers
- Physiological antagonists
What is the action of allosteric antagonists?
- Bind (reversibly) at a distinct site from the agonist and decrease agonist affinity
- Reduce likelihood of agonist binding
What is the action of channel blockers?
- Bind inside the channel (‘plug’) and prevent the passage of ions
- Binding of channel blockers tends to be enhanced by receptor action (use dependence)
What is the action of ‘physiological antagonists’?
- Antagonise the physiological effect of some agonists, but via different mechanism
Give some examples of allosteric antagonists
- Gallamine at the muscarinic receptors
2. Beta-carbolines at the GABAA reecptor
Give some examples of channel blockers
- Phencyclidine at the NMDA receptor
Give some examples of physiological antagonists
- Endocrine disruptors - some of the inhibit conjugation reactions
- Epinephrine and other such substances that are physiological antagonists to histamine
- Several substances that have anti-histaminergic action despite not being ligands for the histamine receptor
What is desensitisation?
Prolonged or repeated exposure to an agonist reduces the response to that drug
