Agonists and Antagonists Flashcards
(27 cards)
Types of receptors
- Ligand-gated ion channels - fast neurotransmitters, e.g. nicotinic
- G-protein coupled receptors - slow neurotransmitters, e.g. Ach, NA
- Kinase-linked receptors - e.g. insulin
- Nuclear receptors - e.g. sterioid hormones
Receptor sub-types
- Cholinergic - muscarinic, nicotinic
- Adrenergic - beta2 (lungs), beta1 (heart), alpha1 (blood vessels)
General principles of drug action
- Agonists
- Antagonists
- Partial agonists
- Inverse agonists
- Allosteric modulations
Agonists
Agonists mimic endogenous ligands. They bind to a receptor and cause a secondary effect.
Antagonists
Antagonists bind to a receptor and prevent the action of an agonist. Most are competitive and reversible.
Affinity
Binding of drug to receptor
Efficacy
Response to binding (intrinsic activity)
Effect formula
Effect = maximal effect x [D] / (K + [D])
Potency
Measure of the drug dosage needed to produce a particular therapeutic effect.
Determined by the strength of binding of a drug to a receptor or the receptor affinity for the drug
Efficacy
Measure of the effectiveness of a drug in producing a maximum response.
Full agonists have high efficacy, antagonists have no efficacy
ED50
The dose that produces a 50% effect
Dose-Response Measurement
Measure the effect of an agonist on a response (BP, contraction/relaxation of a piece of smooth muscle)
Plot the response (%max) against the log of the dose (mol/L) to give a sigmoid dose-response curve
Note - Histamine has a steeper curve and shifted more to the left than Acetylcholine
Types of drug antagonism
- Competitive (or surmountable) antagonism
- Non-competitive (or irreversible) antagonism
- Physiological antagonism
Competitive antagonism
- Agonists and antagonists compete for the same receptor sites
- Maximal effect unchanged (antagonism is surmountable)
- Parallel shift to the right
- A high enough dose of agonist can overcome the antagonist
Non-competitive antagonism
- Irreversible antagonists can act on the receptor itself, binding irreversible
- Cause a change in the receptor so that the agonist can no longer bind
- A maximum effect is no longer produced (except in the case of spare receptors)
Spare receptors
- Are important in non-competitive antagonism as a receptor reserve can allow a maximum response to be reached
Physiological antagonism
- Occurs when 2 agonists act on different receptors to produce opposite effects
- The drugs have different mechanisms of action
- E.g. bronchoconstriction due to histamine can be treated with adrenaline which acts as a vasodilator
Partial agonists
Full agonists bind to receptors and very efficiently give a response. Partial agonists are less ‘efficacious’
- never achieve maximum effect
- also act as an antagonist
Dose response curve does not reach the maximal response obtained for a full agonist.
Inverse agonists
Some receptors are constitutively active, even in the absence of any agonist. An inverse agonist restores the receptor to its inactive state.
The presence of an inverse agonists will increase the proportion of inactive receptors. Mechanism of action is thought to involve the destabilisation of G-protein receptor coupling
Potentiation of agonists
Usually occurs due to the decreased inactivation of an agonist
- Acetylcholine in the presence of anticholinesterase
- Noradrenaline in the presence of an uptake blocker (e.g. cocaine)
Allosteric modulators
- Bind to a separate site on the receptor from agonists called an allosteric site
- Occupation of this site can either increase or decrease the response to an endogenous agonists, depending on whether it is positive or negative modulation
Quantitative and quantal response
Quantitative response: is measured in gradual steps, e.g. fall in blood pressure
Quantal response: is all or none, e.g. responders or non-responders
ED50 and LD50
ED50: Percent requiring the dose to achieve the specified effect
LD50: Percent requiring the dose for a lethal effect
Therapeutic and toxic ratio
Therapeutic ratio = LD50/ED50
Toxic ratio = TD50/ED50
