MPharm PHA115: Drug-Receptor Concepts

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Questions and Answers

What is the formula for calculating the Therapeutic Index of a drug?

median effective dose (ED50) / median toxic dose (TD50)

median toxic dose (TD50) / median effective dose (ED50) (correct)

median toxic dose (TD50) + median effective dose (ED50)

median effective dose (ED50) - median toxic dose (TD50)

Which statement best describes the significance of the Therapeutic Index?

It indicates the efficacy of a drug in treating diseases.

It measures the concentration of a drug in the bloodstream.

It provides a measure of the benefit to risk ratio of the drug. (correct)

It evaluates the speed of drug absorption in the body.

How can drugs mediate similar effects through different receptors?

By utilizing different types of receptors in various tissues. (correct)

By activating the immune system.

By binding to identical receptors in the same tissue.

By increasing the heart rate only.

Which of the following is an example of a drug with a narrow Therapeutic Index?

Warfarin Signup and view all the answers

What role do identical receptors in different tissues play in drug action?

They can mediate identical effects across various tissue types. Signup and view all the answers

What happens during receptor uncoupling?

Receptors are removed from their effector systems. Signup and view all the answers

What is an example of a drug that may cause exhaustion or depletion of mediators?

Amphetamines Signup and view all the answers

How is relative selectivity defined in drug action?

The degree to which a drug acts on a site compared to all possible sites. Signup and view all the answers

What is the therapeutic index concept concerned with?

The ratio of therapeutic effects to fatal side effects. Signup and view all the answers

Physiological adaptation as a tolerance mechanism is characterized by:

Compensatory adjustments that diminish drug effects. Signup and view all the answers

What distinguishes absolute selectivity from relative selectivity?

Absolute selectivity results in no side effects, while relative allows for them. Signup and view all the answers

What might be a reason for undesirable side effects of a drug?

Binding to non-target receptors. Signup and view all the answers

Enhanced metabolism of a drug often results from:

Induction of metabolizing enzymes. Signup and view all the answers

What is competitive antagonism?

An interaction where the agonist and antagonist compete for the same receptor binding site. Signup and view all the answers

What is the outcome of reversible competitive antagonism on the agonist log D-R curve?

A parallel shift to the right with no reduction in maximal response. Signup and view all the answers

In irreversible competitive antagonism, which of the following occurs?

A fraction of receptors is permanently unavailable for agonist binding. Signup and view all the answers

What characterizes non-competitive antagonism?

The antagonism cannot be overcome by increasing the concentration of the agonist. Signup and view all the answers

Which of the following describes chemical antagonism?

Direct interaction between the antagonist and agonist rendering the latter inactive. Signup and view all the answers

What is the defining feature of pharmacokinetic antagonism?

It reduces the effective concentration of the agonist at the site of action. Signup and view all the answers

Which of the following best describes physiological antagonism?

Two drugs eliciting opposite effects on different receptors. Signup and view all the answers

What is the primary effect of synergism or potentiation?

The combined effect exceeds the algebraic sum of their individual effects. Signup and view all the answers

What type of drug-responsive variation is termed tolerance?

A decreased responsiveness with repeated exposure to a drug. Signup and view all the answers

Which mechanism is not associated with acquired tolerance?

Increased efficacy of the drug after long-term use. Signup and view all the answers

What aspect does inter-patient variation in drug responsiveness refer to?

Differences in response when the same dose is administered to various individuals. Signup and view all the answers

What describes pharmacodynamic mechanisms of drug tolerance?

Down-regulation or modification of receptors influencing drug effectiveness. Signup and view all the answers

Which of the following is an example of intra-patient variation in drug responsiveness?

A single patient showing different responses to a drug over time. Signup and view all the answers

What could lead to lack of efficacy in drug response variation?

Variations in metabolic processes or binding affinities. Signup and view all the answers

Study Notes

MPharm Programme - Drug-Receptor Concepts

This is a module for the MPharm programme (PHA115) at the University of Sunderland.
The module covers drug-receptor concepts 3 and 4.
Dr G Boachie-Ansah is the lecturer, and contact details are provided.

Drug-Drug Interactions

The slides focus on drug-drug interactions, including antagonism, summation/additivity, and synergism/potentiation.

Drug Antagonism

Drug antagonism occurs when the effect of one drug is diminished or eliminated by another.
Types of drug antagonism include competitive, non-competitive, chemical, pharmacokinetic, and physiological/functional antagonism.

Competitive Antagonism

Agonist and antagonist drugs compete for the same receptor binding site.
Antagonist binding reduces agonist binding, thus reducing agonist effects.
Two subtypes:
- Reversible/surmountable: The agonist effect can be restored by increasing the agonist concentration.
- Irreversible/insurmountable: The antagonist effect cannot be overcome by increasing the agonist concentration.
Reversible competitive antagonism results in a parallel shift to the right on the agonist log D-R curve, with no reduction in the maximal response.

Irreversible Competitive Antagonism

The antagonist drug irreversibly binds to the receptor (due to high affinity or covalent bonding).
A fraction of receptors permanently unavailable for agonist binding.
The antagonism cannot be overcome by increasing the agonist concentration.
This leads to two effects on the agonist log D-R curve:
- Reduction in the slope of the curve.
- Reduction in the maximal response.

Non-competitive Antagonism

The antagonist drug does not compete with the agonist for the same receptor binding site.
The antagonist may bind to a different site on the receptor or interfere with response coupling.
The antagonism cannot be overcome by increasing the agonist concentration.
Leads to reduced slope and maximal response on the agonist log D-R curve.

Chemical Antagonism

Results from direct interaction between antagonist and agonist drugs.
The antagonist binds to/combines with the active drug (agonist) in solution.
The active drug is rendered inactive or unavailable to interact with its receptors.
Examples include protamine vs heparin and dimercaprol vs heavy metals (Hg, Cu, Pb).

Pharmacokinetic Antagonism

The antagonist drug reduces the effective concentration of the agonist at its site of action.
Possible mechanisms include:
- Reduced absorption from the gastrointestinal tract (GIT).
- Increased metabolic degradation.
- Increased renal excretion.
Examples include ferrous salts vs tetracycline antibiotics, phenobarbital vs warfarin, and NaHCO3 vs aspirin.

Physiological/Functional Antagonism

The interaction of two opposing agonist effects in a single biological system cancels out each other's effect.
The two drugs elicit opposing responses by acting on different receptors.
Examples include acetylcholine vs noradrenaline (affecting heart rate) and glucocorticoids vs insulin (affecting blood sugar levels).

Summation/Additivity

Summation occurs when the combined effect of two drugs eliciting the same overt response is equal to the algebraic sum of their individual effects.
Additivity happens when the effects of two drugs acting through the same mechanism add up to the predicted expected response based on simple addition.

Synergism/Potentiation

Synergism or potentiation occurs when the combined effect of two drugs is greater than the algebraic sum of their individual effects.
The synergist may increase the concentration of the other drug at its receptor sites, or increase the responsiveness of the receptor-effector protein.
Examples include tyramine & MAO inhibitors, and benzodiazepines & GABA (GABAA receptor).

Variation in Drug Responsiveness

This section focuses on patient variability in drug response.
- Scope includes inter-patient and intra-patient variations.
- Possible consequences include lack of efficacy and unexpected side effects.
- Possible mechanisms include pharmacokinetic and pharmacodynamic factors.
- Qualitative and quantitative variations in drug responses are listed.
- Tolerance, innate vs acquired, and tolerance vs tachyphylaxis are discussed.

Acquired Tolerance

A progressive, acquired decrease in responsiveness to a drug following exposure.
- This can be due to a number of mechanisms
  - Pharmacodynamic, including receptor down-regulation and uncoupling.
  - Metabolic tolerance related to induction of enzymes in drug metabolism.
  - Exhaustion/depletion of mediators.
  - Physiological adaptation.

Clinical Selectivity

This section discusses the concept of clinical selectivity of drugs, specifically focusing on:
- Absolute vs Relative Selectivity
- Therapeutic vs undesirable/side effects.
- Concept of Therapeutic Index (TD50/ED50).
- The margin of safety, the benefit to risk ratios and examples of drugs are noted.

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Description

This quiz covers key concepts from the MPharm programme module on drug-receptor interactions, specifically focusing on drug-drug interactions and various types of drug antagonism. Explore competitive, non-competitive, and other forms of antagonism as outlined in the course material.