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An antagonist can produce a biological response by binding to a receptor.
False
A competitive antagonist binds to the same site as the agonist.
True
Increased concentration of a competitive antagonist results in a shift to the left in the log concentration response curve.
False
An antagonist has an intrinsic activity value of 1.
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Non-competitive antagonists affect the maximal response of a concentration-response curve.
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Reversible binding of a competitive antagonist can be overcome by increasing the concentration of the agonist.
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The degree of rightward shift in the concentration-response curve is unrelated to antagonist concentration.
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An inverse agonist has an intrinsic activity value less than zero.
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An inverse agonist induces the same signaling outcome as agonists.
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Agonists have a higher affinity for the R* state in the two-state model.
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Antagonists have a greater affinity for R compared to R*.
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Desensitization occurs when the effect of a drug diminishes from repeated use.
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The median effective dose (ED50) is the dose that produces a therapeutic effect in 25% of the population.
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A biased agonist can selectively trigger multiple signaling pathways.
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Refractoriness can result from receptor changes or exhaustion of mediators.
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A frequency distribution curve can be used to measure all-or-nothing drug responses.
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An allosteric antagonist binds to the same site as an agonist.
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Increased concentration of a competitive antagonist results in an increase in EC50 values.
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The maximum response is not affected by a non-competitive antagonist concentration.
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An inverse agonist increases the binding affinity at the receptor site.
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Physiologic antagonism refers to two drugs having opposing actions.
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Beta blockers are examples of non-competitive antagonists.
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EC50 values for a non-competitive antagonist decrease with increasing antagonist concentration.
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Binding strength can be categorized as reversible or irreversible antagonism.
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An antagonist binds to a receptor and alters the biological response.
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The effects of a competitive antagonist can be fully reversed by increasing the dosage of an agonist.
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The intrinsic activity of a full agonist is defined as zero.
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Non-competitive antagonists can reduce the maximal effect of an agonist.
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The degree of rightward shift in a concentration-response curve is unrelated to antagonist concentration.
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The EC50 value increases with higher concentrations of a competitive antagonist.
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An inverse agonist produces the opposite effect of an agonist without binding to the receptor.
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A population study for 'all-or-none' responses can measure the effects of antagonists on a population-wide basis.
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An allosteric antagonist binds to the same site as an agonist.
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The EC50 value increases with higher concentrations of a non-competitive antagonist.
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A competitive antagonist can shift the log concentration dose-response curve to the right without affecting the maximum response.
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Irreversible antagonists can be functionally equivalent to reversible antagonists at high concentrations.
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Physiological antagonism involves two drugs that enhance each other's effects.
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EC50 values decrease with the increasing concentration of a competitive antagonist.
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Inverse agonists and agonists induce the same signaling outcomes at a receptor.
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Chemical antagonists bind to endogenous ligands to inhibit their effects.
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Inverse agonists bind preferentially to the R state in the two-state model.
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Antagonists in the two-state model favor the R* state over the R state.
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Desensitization occurs when a drug's effect diminishes with repeated use.
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The median effective dose (ED50) represents the dose required to elicit a therapeutic effect in 100% of the population.
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A biased agonist can selectively trigger only one specific signaling pathway.
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Tolerance develops more quickly than desensitization.
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Refractoriness in drug response can occur due to loss of receptors.
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A frequency distribution curve represents responses that are measured on a continuous scale.
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A non-competitive antagonist's effect on the log dose response curve is that the EC50 decreases with increasing concentration.
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Irreversible antagonists and reversible antagonists behave identically at high concentrations.
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Functional antagonism decreases the effect of a second messenger while keeping the agonist binding affinity unchanged.
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Allosteric antagonists bind to the same site as agonists, resulting in increased receptor activation.
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The EC50 of a competitive antagonist shifts to the left with increased concentration.
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Physiologic antagonism occurs when two drugs enhance each other’s effects.
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Beta blockers are examples of non-competitive antagonists.
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An inverse agonist has an intrinsic activity value that is greater than zero.
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An antagonist has an intrinsic activity value that is always greater than 0.
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A non-competitive antagonist can change the EC50 value but not the maximal response.
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A competitive antagonist binds irreversibly to the receptor site of an agonist.
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Increasing concentrations of a non-competitive antagonist will always decrease the EC50 values.
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An agonist and an inverse agonist can induce the same response at a receptor site.
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The degree of the rightward shift in a concentration-response curve due to a competitive antagonist is inversely proportional to the antagonist concentration.
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Physiologic antagonism refers to two drugs having similar actions that produce a combined effect.
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A biased agonist can activate multiple signaling pathways selectively without influencing other pathways.
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An inverse agonist induces the opposite signalling outcome to that of agonists.
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Inverse agonists have a higher affinity for the R* state than for the R state in the two-state model.
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Antagonists have a definitive preference for either the R state or the R* state in their binding affinity.
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Desensitization and tolerance occur at the same rate in drug responses.
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A biased agonist selectively triggers multiple signalling cascades in a receptor.
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The median effective dose ED50 indicates the drug dose needed to achieve therapeutic effect in 50% of individuals.
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A frequency distribution curve is only applicable to continuous drug response measurements.
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Long-term antagonist treatment can lead to structural changes or loss of receptors.
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Study Notes
Antagonists
- Antagonists bind to a receptor but do not produce a biological response
-
Intrinsic activity or efficacy, is the ability of a ligand to produce a response
- Full agonists have an intrinsic activity of 1 (α=1)
- Partial agonists have an intrinsic activity of less than 1 but more than 0 (1> α >0)
- Antagonists have an intrinsic activity of 0 (α=0)
- Inverse agonists have an intrinsic activity of less than 0 (α < 0)
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Competitive antagonists bind to the same site as the agonist, and the two compete with each other
- Orthosteric refers to a molecule that interacts with the same binding site as the endogenous ligand
- In reversible competitive antagonism, the effect can be overcome by an excess of agonist
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Non-competitive antagonists bind to a different site from the agonist
- Allosteric antagonists or inhibitors bind to a site distinct from the active site of the receptor
- Non-competitive antagonism can appear the same as irreversible competitive antagonism
- Spare receptors refer to the presence of more receptors than necessary to elicit a maximal response
- Functional antagonism occurs when two drugs have opposing effects on the same pathway without interacting with the same receptor
- Desensitization or tachyphylaxis is when the effect of a drug diminishes when it is given repeatedly or continuously
- Tolerance is when desensitization develops more slowly
- Refractoriness can be due to changes or losses in receptors, exhaustion of mediators, increased metabolic degradation, or physiological adaptation
- Biased agonists selectively trigger one of the signaling cascades of a receptor
- Quantal dose-response curves can be constructed for drugs that elicit ‘all-or-none’ responses, e.g., sleep, death, infection, pregnancy, or the presence or absence of epileptic seizures
- The median effective dose 50% (ED50) is the dose required to produce a therapeutic effect in 50% of the population
The Two-State Model
- The two-state model proposes that receptors exist in two conformations, an inactive state (R) and an active state (R*)
- Agonists have higher affinity for R*
- Inverse agonists have higher affinity for R
- Antagonists have equal affinity for R and R*
Types of Antagonists
- Physiologic antagonism occurs when two drugs have opposing effects on the same pathway but act on different receptors
- Pharmacokinetic antagonism occurs when one antagonists inhibits the metabolism or absorption of another drug
- Chemical antagonism occurs when antagonists bind directly to the agonist and prevent it from acting on the receptor
-
Competitive antagonists are typically reversible or irreversible
- Reversible competitive antagonists bind reversibly to the receptor and can be displaced by excess agonist
- Irreversible competitive antagonists bind irreversibly to the receptor
- Non-competitive antagonism is typically allosteric, meaning that the antagonist binds to a site other than the active site of the receptor
Antagonists
- Antagonists bind to receptors but either have no effect or prevent the effects of an agonist.
- Antagonists can be classified by how and where they bind, their binding strength, and their binding site.
- Competitive antagonists bind to the same site as the agonist and compete with the agonist for binding.
- Non-competitive antagonists bind to a different site from the agonist.
Competitive Antagonists
- Competitive antagonists can be reversible or irreversible.
- Reversible competitive antagonists can be overcome by increasing the concentration of the agonist.
- Irreversible competitive antagonists bind permanently to the receptor.
Non-Competitive Antagonists
- Non-competitive antagonists are also called allosteric antagonists or inhibitors.
- They bind to a different site from the agonist and prevent the agonist from binding.
Effects of Antagonists on Dose-Response Curves
- Competitive antagonists shift the dose-response curve to the right, increasing the EC50.
- Non-competitive antagonists decrease the maximal response (Emax) and may also increase the EC50.
- In the presence of spare receptors, non-competitive antagonists may only decrease Emax when the receptor reserve is used up.
Inverse Agonists
- Inverse agonists induce an opposite signaling outcome to agonists.
- Inverse agonists have a higher affinity for the inactive form of the receptor (R).
Desensitization/Tachyphylaxis
- Desensitization or tachyphylaxis occurs when the effect of a drug diminishes when it is given repeatedly or continuously.
- Tolerance is similar to desensitization but develops more slowly.
Biased Agonists
- Biased agonists selectively trigger one of the signaling cascades activated by a receptor.
Quantal Dose-Response Curves
- Quantal responses are all-or-nothing responses, such as sleep, death, or infection.
- Quantal dose-response curves can be used to measure the potency and safety of drugs.
Median Effective Dose (ED50)
- The ED50 is the dose required to produce a therapeutic effect in 50% of the population.
- The ED50 helps identify the drug dose required to elicit therapeutic benefit.
Antagonists
- Antagonists bind to a receptor but do not cause a response, instead preventing the effects of an agonist.
- Intrinsic activity (α) describes the ability to produce a response; full agonists α=1, partial agonists 1> α >0, antagonists α =0, inverse agonists α < 0.
Competitive Antagonists
- Bind to the same site as the agonist, competing for the binding site.
- Orthosteric binding.
- If binding is reversible, the effect is surmountable by excess agonist.
- Increasing antagonist concentration results in parallel right-ward shifts of the concentration-response curve.
- EC50 increases with increasing antagonist concentration.
- Maximal response stays the same.
Non-Competitive Antagonists
- Bind to a different site from the agonist, known as an allosteric antagonist or inhibitor.
- Effects appear similar to irreversible competitive antagonists.
- EC50 decreases with increasing antagonist concentration.
- Emax reduces with noncompetitive antagonist concentration.
- Maximal response falls with increasing antagonist concentration, except if spare receptors are present.
Antagonism that does not affect agonist binding
- Affinity for the receptor is unchanged, EC50 remains unaffected.
- Size of the response decreases due to reduced second messenger activity.
Functional Antagonism
- Occurs when two drugs have opposing effects on the same cellular pathway.
- Example: muscarinic receptor (m2, m4) and β-adrenergic receptor (β 1, β 2, β 3) both act on the same enzyme, adenylyl cyclase.
Antagonist Classifications
- Physiologic, pharmacokinetic, chemical.
- Competitive and non-competitive.
Antagonists - Overview
- Classified by how and where they bind.
- Binding strength is either reversible or irreversible.
- Binding site is either competitive or non-competitive.
Antagonists - Examples
-
Competitive:
- Reversible: beta blockers, antihistamines.
- Irreversible: clopidogrel, phenoxybenzamine.
-
Non-competitive:
- Allosteric site: channel blockers – diltiazem, verapamil.
-
Chemical:
- Binding endogenous ligand: etanercept, TNF-α and TNF-β.
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Pharmacokinetic:
- Increasing metabolism: St John’s wort, oestrogen.
-
Physiological:
- Actions oppose each other: salbutamol in asthma.
Inverse Agonists
- Induce an opposite signaling outcome compared to agonists.
- Results with antagonists are predictable.
The Two-State Model
- Receptors exist in two states: R (inactive) and R* (active).
- Agonists have a higher affinity for R*.
- Inverse agonists have a higher affinity for R.
- Antagonists have an equal affinity for R and R*.
Loss of Drug Response or Desensitisation
- Desensitization / tachyphylaxis: The effect of a drug diminishes when it is given repeatedly or continuously.
- Tolerance: Similar, but develops more slowly.
- Refractoriness can be due to:
- Change or loss of receptors (most agonists).
- Exhaustion of mediators (amphetamine).
- Increased metabolic degradation (alcohol).
- Physiological adaption (diuretics-> RAS).
Biased Agonists
- Receptors can switch on more than one signalling pathway.
- Biased agonists selectively trigger one of these signalling cascades.
Quantal Dose-Response Curves
- Used for measuring effects that are 'all-or-nothing', e.g., sleep, death, infection, pregnancy.
- The response (y) axis is the percentage of people who respond to a particular dosage.
Median Effective Dose (ED50)
- The dose required to produce a therapeutic effect in 50% of the population.
- Helps identify the drug dose required to elicit therapeutic benefit.
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Description
This quiz dives into the role of antagonists in pharmacology, covering their interaction with receptors and intrinsic activity. You will learn about different types of antagonists, including competitive and non-competitive, as well as concepts like full and partial agonists. Test your understanding of these key concepts!
