specific drug reactions

Chlorambucil

acts by forming a covalent bond with DNA through alkylation

Aspirin exerts its anti-inflammatory and antiplatelet effects

by undergoing acylation with the serine residue of COX-1

Neostigmine inhibits acetylcholinesterase by

pseudo-irreversible covalent mechanism Carbamylation

Isofluorophate inhibits acetylcholinesterase by

Phosphorylation reaction

Clopidogrel requires metabolic activation to bind to P2Y12 receptor

via a rearrangement reaction

Cephalosporins (such as Cefoxitin) inhibit bacterial transpeptidase

by mimicking the D-Ala-D-Ala sequence and undergoing Acylation

5-Fluorouracil

reacts with thymidylate synthase and methylene-THF to form a stable covalent adduct through alkylation

N7 atom of guanine

DNA atom thats alkylated by chlorambucil

N-ethylmaleimide

forms a covalent bond by alkylating a free thiol group

nucleus

platelets lack which cellular component necessary to synthesize new COX enzymes

highly reactive aziridinium ion intermediate

involved in alkylation reaction

associate carbamylates with

pseudo-irreversible, generates much slowly

Ester group

functional group on aspirin acts as the acyl donor during the irreversible acetylation of cyclooxygenase

Organophosphates like isofluorophate

undergo "aging," that results hydrolysis of an isopropyl phosphoester, rendering the phosphorylation non-reversible

Clopidogrel

thienopyridine antithrombotic agent that undergoes rearrangement following metabolic activation

Cyclooxygenase (COX)

irreversibly inhibited by low-dose aspirin to prevent thromboxane A2 (TXA2) synthesis

Disulfide covalent bond

bond the active metabolite of clopidogrel form with the P2Y12 receptor on platelets

Thymidylate synthase

targeted by 5-FU (via its active metabolite 5-FdUMP) to disrupt DNA synthesis