Elevated plasma free drug concentrations of propranolol and diazepam during cardiac catheterization

Patients who undergo cardiac catheterization are frequently taking propranolol and are often premedicated with diazepam. Because the intensity of a drug's action is determined by free, or non-protein-bound, levels in plasma, changes in the degree of protein binding may profoundly alter the pharmacologic effect. We examined the effects of heparin on the free levels of propranolol and diazepam in six patients who underwent cardiac catheterization. After heparinization, the free fraction of diazepam increased more than fourfold, from 1.8 +/- 0.1% to 7.9 +/- 1.2% (p < 0.002) and the free levels increased from 2.0 +/- 0.5 to 8.4 +/- 2.2 ng/ml (p < 0.025); the free fraction of propranolol increased from 7.4 +/- 0.9% to 12.5 +/- 1.4% (p < 0.001). The increase in free drug concentration was associated with elevated free fatty acid levels, which rose from 181 +/- 7 micrograms/ml to 596 +/- 119 micrograms/ml (p < 0.02). Increases in the free levels of propranolol and diazepam produced by heparinization during cardiac catheterization may result in increased pharmacolaogic effect, such as excessive sedation or respiratory depression.