title: Captopril and lisinopril decrease acetaldehyde effects upon the prothrombin time.
abstract: Captopril, a thiol-containing antihypertensive drug, and lisinopril, an amino-containing antihypertensive drug, will both prolong the prothrombin time (PT) of Level I plasma. Acetaldehyde, a product of ethanol metabolism, also prolongs PT. In a study to examine the interrelationship between hypertension, hemostasis, and alcoholism, an examination of the impact of acetaldehyde on the effects of captopril and lisinopril upon PT was undertaken. It was observed that the pre-mixing of 7.7 x 10(-3) M captopril with 40.6 mM acetaldehyde for 30 min at R.T. prior to the addition to plasma results in a prolongation of PT which is less than that caused by acetaldehyde alone. Successive additions of captopril and acetaldehyde to plasma also yield a PT which is less than that of acetaldehyde alone. These data suggest that captopril may partially inactivate and detoxify the acetaldehyde effect on hemostasis upon interaction to form a thiohemiacetal. Captopril may prolong PT by the reduction of the S-S bridges in the coagulation factors. Lisinopril behaves similarly to captopril, prolonging PT. Successive additions of lisinopril and acetaldehyde, or pre-mixtures thereof, to plasma result in a lesser prolongation of clotting time relative to acetaldehyde alone. Since primary amines similar to that of lisinopril readily form Schiff bases with acetaldehyde, these data suggest that both captopril and lisinopril may act to detoxify the acetaldehyde effect upon plasma, albeit by different mechanisms.
authors.affiliation: Department of Chemistry, Bowling Green State University, Bowling Green, OH 43403, USA. artbrec@bgsu.edu
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Brecher
authors.forename: Rachel
authors.initials: R
authors.lastname: Dubord
mesh_terms: D000079:Acetaldehyde / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D017706:Lisinopril / Q000494:pharmacology*; D011517:Prothrombin Time
chemical_list: D000959:Antihypertensive Agents; D002216:Captopril; D017706:Lisinopril; D000079:Acetaldehyde