engleski

A dynamical model for the separation of secondary resistance from tolerance to nitroglycerin infusion

A dynamic model for the estimation of a residual hypotensive efficacy of nitroglycerin (NG) infusion was constructed to distinguish secondary resistance from tolerance to NG, as lost vs weakened efficiency. The model was tested by individual comparison in 82 of 92 patients with acute myocardial infarction or unstable angina. Ten patients were excluded from the study protocol due to complications that required therapy modification. NG infusion (20 micrograms/ml) efficiency was initially confirmed by a 10% decrease in the mean brachial artery (cuff) blood pressure. The infusion (63 hours mean duration) was discontinued every 12 hours for 30 minutes and pressure changes were analyzed. If NG hypotensive efficacy was maintained (as proved by at least 10% pressure increase), infusion was carried on using the initial dose. Lack of 10% pressure increase after 30-minute infusion discontinuity (tolerance) indicated the need for an increase in the NG dose until 10% pressure decrease (not below 105/60) was obtained. Lack of 10% pressure decrease, with a 5-fold increase in NG dose (up to 320 micrograms/ml), was considered to be a sign of secondary resistance. There were no proceeding complications and tolerance was found in 72 patients. Beside tolerance, secondary resistance was simultaneously present in 16 patients, while the NG efficacy was restored by dose increase in the remaining 78% of tolerant patients. "Paradoxical" pressure decrease was noted in 12 tolerant patients after the infusion interruption, while "paradoxical" pressure increase was observed in 3 resistant patients during the infusion acceleration.

nitroglycerin; drug tolerance; drug resistence; methodology

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