Search

Since the classical work of Crum-Brown and Frazier nearly one hundred years ago, which demonstrated that relatively simple alterations in chemical structure could modify substantially the pharmacological properties of alkaloids, interest in Structure-Activity Relationships (SAR) has been ever increasing. Never before has the chemically oriented biologist had such a formidable list of compounds to consider. In association with any given pharmacological action, there are many compounds which obviously have similar structures, but there are also many where chemical similarities are not so apparent. On the basis of what have appeared to be “similar” chemical compounds, many of the SAR advances have occurred in autonomic pharmacology. The approach that has been used with cholinesterase inhibitors has certainly yielded many active compounds, with the net result of advancement in both therapeutic application and our understanding of drug-enzyme interaction. If workers concerned had not used the principles of SAR in their design of drugs, progress which resulted would probably have been considerably less.

Antibiotic administration during surgery may be associated with hazards not normally encountered in unanesthetized subjects. We submit this contention on the bases of recent evidences in the literature and our laboratory investigations stimulated by clinical experiences. The potential dangers are not those usually associated with prolonged or repeated administration of these drugs, such as allergic responses, blood dyscrasias, nephro- and ototoxic phenomena, but rather acute states of respiratory or circulatory depression. A drug may be therapeutic under usual circumstances of administration and toxic when altered conditions prevail. The patient during surgery is indeed different from an unanesthetized subject. A number of factors could conceivably affect his response to a drug. Anesthesia poses the possibility of drug interaction with a variety of agents used for that purpose. Changes in concentrations of circulating hormones in response to surgical stress and anesthesia may modify the effect of exogenous agents. Hemodynamic changes such as