Faculty Bibliography

The toxins that adversely affect the blood are diverse. In addition to the metals, animal venoms, oxidizing agents, and asphyxiants discussed, there are hydrocarbons such as benzene and phenol that suppress hematopoiesis. Ingestions of excessive amounts of oral anticoagulants and warfarin-containing rodenticides may result in bleeding abnormalities due to inhibition of vitamin K dependent clotting factors. The list of possibilities is virtually endless. Although it is commonly thought that certain plant ingestions such as castor beans (Ricinus communis), rosary pea beans (Abrus precatorius), and the false morel (Gyromitra esculenta) could result in hemolysis, no evidence of this can be found in the literature. The variety of ubiquitous nature of many of these toxins should cause clinicians to maintain a high 'index of suspicion' and include toxins in the differential diagnosis of selected hematologic diseases

Naloxone hydrochloride is extremely valuable for diagnosing and managing the opioid overdose. Due to naloxone's short half life and a long duration of action of most opioids, repeated naloxone dosing often is required to prevent the recurrence of respiratory depression. An alternative to repeated bolus administration is a continuous IV infusion. We conducted a two-phase study to determine the pharmacokinetics of naloxone and to develop a continuous dosing nomogram. In the first phase seven patients were given an IV bolus dose alone and serial plasma naloxone levels were determined. Naloxone elimination was found to be biexponential with the mean beta half life equal to 0.023 +/- 0.002 reciprocal minutes in two patients and 0.015 +/- 0.02 reciprocal minutes in five patients. In the second phase ten volunteers were given either a 2-mg or a 4-mg bolus dose followed by a 1.5-mg/hr or a 3-mg/hr continuous infusion. The mean volume of distribution of the central compartment was found to be 0.806 +/- 0.408 L/kg. The mean beta rate constant of elimination was found to be 0.036 +/- 0.027 reciprocal minutes. A computer simulation of the pharmacokinetic parameters determined in our study found that a continuous infusion of two-thirds of the bolus dose that resulted in reversal each hour will maintain the plasma naloxone levels equal to or greater than the naloxone levels that would have existed 30 minutes following the bolus dose.