Which of the following statements is true regarding Drug-receptor bonds?

The mechanism of action of aspirin involves the irreversible inhibition of the cyclo-oxygenase (COX) enzyme. Aspirin transfers its acetyl group to a serine residue in the active site of the COX enzyme. This acetylation reaction forms a stable covalent bond, which permanently inactivates the enzyme molecule. This is a classic and frequently cited example of a drug forming a covalent bond with its target receptor (in this case, an enzyme), leading to a long-lasting pharmacological effect.

A. Covalent bonds are the strongest type of drug-receptor bond and are typically considered irreversible or very slowly reversible, not "mostly reversible."

B. Weaker, reversible interactions such as electrostatic, hydrogen, and van der Waals bonds are far more common in drug-receptor binding than strong covalent bonds.

C. Covalent bonds, which involve the sharing of electrons between atoms, are significantly stronger than electrostatic bonds, which are based on the attraction between opposite charges.

D. Hydrophobic interactions are important for the binding of lipid-soluble (lipophilic) drugs to nonpolar regions of receptors, not for highly water-soluble (hydrophilic) drugs.

1. Brunton

L. L.

Hilal-Dandan

R.

& Knollmann

B. C. (Eds.). (2018). Goodman & Gilman's The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill.

Chapter 3

"Pharmacodynamics: Molecular Mechanisms of Drug Action

" Section: "Receptors

" Sub-section: "Drug-Receptor Bonds

" describes covalent bonds as strong and typically irreversible.

Chapter 38

"Anti-Inflammatory

Antipyretic

and Analgesic Agents

" Section: "Aspirin and Other Salicylates

" details the mechanism of aspirin

stating it "irreversibly acetylates cyclooxygenase" via a covalent bond.

2. Katzung

B. G. (Ed.). (2018). Basic & Clinical Pharmacology (14th ed.). McGraw-Hill.

Chapter 2

"Drug Receptors & Pharmacodynamics

" Section: "The Nature of Receptors

" discusses the types of drug-receptor bonds

noting that covalent bonds are strong and often result in irreversible action.

Chapter 36

"Nonsteroidal Anti-Inflammatory Drugs

" Section: "Aspirin

" explicitly states

"Aspirin is a nonselective COX inhibitor; it irreversibly inhibits COX-1 and COX-2 by covalent acetylation of a serine residue in the active site of the enzyme."

3. University of California

San Francisco (UCSF) School of Pharmacy. (n.d.). Pharmacodynamics I: Drug-Receptor Interactions [Courseware]. In this material

the hierarchy of bond strengths is established (Covalent > Electrostatic > Hydrogen > Hydrophobic > Van der Waals)

and the rarity and irreversible nature of covalent bonds in pharmacology are highlighted.