Medchem : Receptors, Drug Action and SAR. Final

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Questions and Answers

How does long-term exposure to a drug that acts as an agonist typically affect postsynaptic receptors?

It can lead to receptor internalization or recycling, depending on neurotransmitter levels. (correct)
It consistently increases the number of receptors available on the postsynaptic membrane.
It has no significant impact on the number or sensitivity of postsynaptic receptors.
It directly increases neurotransmitter synthesis within the presynaptic neuron.

What primary role do autoreceptors play in regulating synaptic activity?

Inhibiting neurotransmitter release and modulating cyclic AMP, calcium, and potassium levels. (correct)
Directly activating postsynaptic receptors to propagate the signal.
Increasing the synthesis of neurotransmitters within the presynaptic neuron.
Enhancing the release of neurotransmitters into the synaptic cleft.

How do allosteric modulators influence the action of agonists at a receptor?

By competing with agonists for occupancy at the primary binding site.
By directly altering gene expression to change the number of receptors produced.
By binding to a separate site on the receptor, which affects the receptor's interaction with the agonist. (correct)
By independently causing full activation or complete inhibition of the receptor.

What distinguishes drug specificity from drug selectivity?

Specificity implies direct binding and activity changes at one receptor, while selectivity indicates a drug binds one receptor more strongly or with higher activity compared to others. (A) Signup and view all the answers

Which scenario exemplifies a drug exhibiting specificity for one receptor yet demonstrating non-selectivity?

A drug binding to the CXCR6 receptor and causing activity there but also causing activity at CCR7 because CXCR6 dimerizes with CCR7. (C) Signup and view all the answers

How is Structure-Activity Relationship (SAR) best defined in the context of drug discovery?

The analysis to understand the quantitative relationship between variations in a drug's chemical structure and its biological activity. (C) Signup and view all the answers

What crucial role does the pharmacophore play in SAR studies?

Identifying and arranging the atoms and groups responsible for a biological molecule's specific biological activity. (A) Signup and view all the answers

In SAR studies, what does the medicinal chemistry technique of 'truncation' aim to achieve?

To identify the minimum structural features required for drug activity. (D) Signup and view all the answers

A researcher is studying a new drug that shows high efficacy at a specific receptor but also binds to several other receptors with lower affinity. Which of the following terms best describes this drug's behavior?

Selective (D) Signup and view all the answers

A medicinal chemist is trying to optimize a lead compound. They remove a large, flexible substituent from the molecule, resulting in a significant loss of activity. What might be the most likely explanation for this observation?

The substituent was crucial for binding to the receptor. (A) Signup and view all the answers

A drug binds to a receptor, but the resulting complex doesn't trigger the expected cellular response. In SAR terms, which aspect of the drug's relationship to the receptor is most likely deficient?

Efficacy (B) Signup and view all the answers

A non-competitive antagonist impacts an agonist's activity in what way?

A decrease in Emax and no change in EC50. (C) Signup and view all the answers

Why is antagonism caused by a non-competitive antagonist considered insurmountable?

Insurmountable, because the agonist cannot achieve Emax, no matter the concentration (D) Signup and view all the answers

What statement differentiates full agonists, partial agonists, and antagonists?

Full agonists elicit a maximal response (Emax = Bmax), partial agonists elicit a less than maximal response (Emax < Bmax), and antagonists block the ability of an agonist to activate the receptor (no response) (B) Signup and view all the answers

How would you best describe an inverse agonist?

A drug that binds to the inactive receptor state and negatively activates the effector, resulting in a negative Emax. (D) Signup and view all the answers

What are the intrinsic activity (alpha) values for a full agonist, partial agonist, antagonist, and inverse agonist?

1, between 0 and 1, 0, between 0 and -1 (D) Signup and view all the answers

How does the presence of a partial agonist affect the Emax of a full agonist when both bind to the same receptor?

The partial agonist will lower the overall response because it occupies receptor sites without fully activating them, thus decreasing the Emax of the full agonist. (D) Signup and view all the answers

Which of the following best defines pharmacokinetics (PK)?

What the body does to the drug as it moves through the body, including absorption, distribution, metabolism, and excretion (ADME). (D) Signup and view all the answers

How can the absorption process influence a drug's pharmacodynamic effects?

By affecting how much of the drug enters the bloodstream, thus impacting free drug concentration. (C) Signup and view all the answers

A patient's liver function can significantly impact drug concentrations and effects by influencing which PK process?

Metabolism (B) Signup and view all the answers

How does pharmacogenomics contribute to variability in drug response?

By studying how genes affect a person's response to a drug, impacting pharmacokinetics, pharmacodynamics, and toxicology. (A) Signup and view all the answers

Drug-receptor interactions can initiate intracellular signaling cascades by:

Binding to receptors on cells, initiating communication and signaling from outside the cell to inside the cell. (A) Signup and view all the answers

Prolonged exposure to a drug can lead to compensatory mechanisms and tolerance, where the body:

Adapts to normalize the signal by changing synthesis, storage, release, receptor binding, and metabolism. (C) Signup and view all the answers

How does neurotransmitter binding affect receptor number?

Leads to endocytosis and receptor degradation. (B) Signup and view all the answers

Two drugs produce the same maximal effect but have different EC50 values. Drug X has an EC50 of 5 nM, while Drug Y has an EC50 of 500 nM. Which drug is more potent?

Drug X, because it requires a lower concentration to achieve 50% of the maximal effect. (A) Signup and view all the answers

Which of the following options best describes the relationship between Kon, Koff, and drug residence time?

Drug residence time is inversely proportional to Koff and is calculated as 1/Koff. (D) Signup and view all the answers

What is the formula for calculating drug residence time?

Residence Time = 1 / Koff (D) Signup and view all the answers

If the Koff rate decreases while the Kd (dissociation constant) remains constant, what must happen to the Kon rate?

The Kon rate must decrease. (D) Signup and view all the answers

Which of the following is an advantage of a drug with fast receptor kinetics (rapid Kon and Koff)?

Quick onset and offset of action, useful for acute conditions. (D) Signup and view all the answers

In which therapeutic area would a drug with slow receptor kinetics (slow Kon and Koff) be most advantageous?

Long-term anxiety control. (A) Signup and view all the answers

Which of the following is a key assumption of the Law of Mass Action in drug-receptor interactions?

One drug molecule binds to one receptor molecule reversibly. (A) Signup and view all the answers

How do spare receptors affect the relationship between receptor occupancy and drug response?

They allow a maximal response (Emax) to be achieved without occupying all available receptors. (C) Signup and view all the answers

In the presence of spare receptors, how does the EC50 relate to the Kd?

EC50 is lower than Kd (D) Signup and view all the answers

In the presence of a competitive antagonist, what change will occur to the agonist dose-response curve?

No change in Emax and a shift of the curve to the right, indicating an increase in EC50. (C) Signup and view all the answers

Is the antagonism caused by a competitive antagonist surmountable or insurmountable?

Surmountable, because the agonist can still achieve Emax at higher concentrations (A) Signup and view all the answers

Choose the statement that best describes insurmountable antagonism:

The maximal response to the agonist is reduced, regardless of the concentration of the agonist. (D) Signup and view all the answers

If a drug has a high Kon and a low Koff, what does this indicate about its receptor binding?

Fast association and slow dissociation, leading to long receptor occupancy. (D) Signup and view all the answers

How is drug potency affected by the presence of spare receptors??

Potency is increased, requiring lower concentrations of the drug for the same effect. (C) Signup and view all the answers

What is the primary function of the pharmacophore in drug design?

To identify the chemical functional groups on a molecule that interact with the target, causing positive interactions. (B) Signup and view all the answers

How does 'truncation' in SAR (Structure-Activity Relationship) studies aid in identifying the pharmacophore?

By systematically removing and replacing chemical groups with a hydrogen to determine the minimum structural features necessary for activity. (B) Signup and view all the answers

Which statement accurately defines the Therapeutic Index (TI)?

The ratio of the TD50 (toxic dose in 50% of the population) to the ED50 (effective dose in 50% of the population). (D) Signup and view all the answers

What does a high Therapeutic Index (TI) suggest about a drug's safety profile?

The drug is relatively safe, as there is a large separation between the dose required for therapeutic effect and the dose that causes toxicity. (A) Signup and view all the answers

Which of the following accurately describes the Certain Safety Factor (CSF)?

The ratio of the toxic dose in 1% of the population to the effective dose in 99% of the population. (C) Signup and view all the answers

Which formula is correctly used to calculate the Certain Safety Factor (CSF)?

CSF = Toxic Dose (1%) / Effective Dose (99%) (B) Signup and view all the answers

Under which circumstance is the Certain Safety Factor (CSF) a more pertinent measurement than the Therapeutic Index (TI) for safety assessment?

When the drug response does not follow the law of mass action. (A) Signup and view all the answers

What does it signify when a drug is described as having a narrow therapeutic window?

There is a small difference between the effective dose and the toxic dose, increasing the risk of adverse effects. (C) Signup and view all the answers

How does a narrow therapeutic window influence the dosage and monitoring of a patient taking the drug?

Dosing must be carefully controlled, and the patient should be closely monitored for signs of toxicity. (A) Signup and view all the answers

What is indicated by a drug that has a wide therapeutic window?

The drug is relatively safe, allowing for a broader range of doses without significant risk of toxicity, simplifying dosing and monitoring (A) Signup and view all the answers

Which of the following statements provides the MOST accurate definition of Emax?

The maximal response that a drug can produce, regardless of the concentration. (A) Signup and view all the answers

Which statement best describes EC50?

The drug concentration that produces 50% of the maximal effect. (A) Signup and view all the answers

How do you define drug potency in pharmacology?

The amount of drug required to produce a particular effect. (C) Signup and view all the answers

What is the significance of drug efficacy in pharmacology?

The maximal effect a drug can produce. (A) Signup and view all the answers

Which of the following best describes drug affinity?

A measure of how tightly a drug binds to its receptor. (C) Signup and view all the answers

Flashcards

Drug Specificity

A drug directly causes activity changes at one specific receptor.

Drug Selectivity

A drug binds one receptor more strongly than others, causing activity changes.

Example of Specific but Non-Selective Drug

Drug binds to CXCR6 receptor and causes activity there but also causes activity at CCR7 because CXCR6 dimerizes with CCR7.