Bruce H. Ackerman

Disturbances of Taste and Smell Induced by Drugs

We reviewed the current literature (1980–1990, 1991–1996) concerning drugs associated with anosmia, hyposmia, dysgeusia, parageusia, and ageusia, and the impact of these adverse effects. Case reports of patients with sudden and delayed onset of one of these disorders with evidence for implication of a drug were included. Disturbances of taste and smell among the elderly and chronically ill, including those with thermal injury, decreases interest in eating and secondarily impairs healing of wounds. Mechanisms involved with these sensory disturbances include deposition of silver sulfate in nerves after use of topical agents containing silver, altered influx of calcium and other ions, chelation or depletion of tissue‐bound zinc, disturbed bradykinin catabolism and second messenger synthesis, catabolism, and altered prostaglandin systems. Other mechanisms, particularly prolonged chemosensory disorders after early drug discontinuation, remain unknown.

Isopropanol Ingestion: A Report Of Six Episodes With Isopropanol and Acetone Serum Concentration Time Data

The disposition of isopropanol and its major metabolite acetone were observed in six isopropanol ingestion episodes among five patients. Serum admission isopropanol and peak acetone concentrations ranged from 16.5 to 220 mg/dL and 141 to 585 mg/dL respectively. Ingestions ranged from 120 to 300 mL of 70% isopropanol with concomitant ethanol ingestion in two episodes. The isopropanol and acetone apparent half-lives ranged from 2.9 to 16.2 hours (h) and 7.6 to 26.2 h respectively. Two episodes of isopropanol ingestion were observed within a 9 month period in patient one. Isopropanol terminal elimination rate constants were 0.043 and 0.085 per hour (per h) with no marked difference in acetone terminal elimination rate constants (0.025 and 0.033 per h). Discrepancy between the two isopropanol elimination rate constants reflected concomitant ethanol abuse with the first ingestion. Reductions in isopropanol and acetone half-lives were also noted among patients requiring ventilatory support.

Vancomycin serum protein binding determination by ultrafiltration.

Sixty-two serum concentrations were obtained from 12 infected patients enrolled in a vancomycin pharmacokinetic study. Both unbound and total serum vancomycin concentrations were measured using ultrafiltration and a commercial fluorescent polarization immunoassay. Ultrafiltrates were obtained by centrifugation at 1000 × g for ten minutes at room temperature and their assay indicated a range in protein binding from 7.9 to 71 percent. The mean protein binding (mean ±SD) was 41.95 ± 14.15 percent. No measurable adsorption of vancomycin onto the ultrafiltration membrane was noted. Orthogonal regression of unbound versus total vancomycin concentrations was described by the equation y=0.597x-0.362 with a correlation coefficient of 0.948.

Pharmacokinetic Characterization of the Postdistribution Phase of Prohormone Atrial Natriuretic Peptides Amino Acids 1–98, 31–67, and Atrial Natriuretic Factor During and After Rapid Right Ventricular Pacing in Dogs

Release rate constants and disappearance rate constants were determined for three atrial natriuretic peptides consisting of amino acids 1–98 (i.e., proANF 1–98), the midportion of the ANF prohormone consisting of amino acids 31–67 (i.e., proANF 31–67) and amino acids 99–126 (i.e., ANF) after right ventricular pacing at 100, 125, 150, and 180 bpm in six male mongrel dogs. Right atrial and femoral vein blood was obtained at baseline, and at 5, 12, 19, 26, 56, 86, 116, 146, and 206 minutes after right ventricular pacing. Resulting plasma concentration‐time data derived parameters were compared. The disappearance rate constants for atrial and femoral venous proANF 1–98 were 0.0144 ± 0.0087 (X ± SD) and 0.0175 ± 0.0075 min−1, respectively (t = 0.6158) and release rate constants were 0.1569 ± 0.1504 and 0.0670 ± 0.0393 min−1, respectively (t = 1.8269; P > .05). The proANF 31–67 disappearance rate constants were 0.0139 ± 0.0082 and 0.0148 ± 0.0132 min−1, respectively (t = 0.1192) and release rate constants were 0.0957 ± 0.0414 and 0.1984 ± 0.1762 min−1, respectively (t = 1.4812). The ANF elimination phase disappearance rate constants were 0.0663 ± 0.0273 and 0.1116 ± 0.0539 min−1 (t = 2.0923, P > .05), respectively, and the release rate constants were 0.1335 ± 0.0532 and 0.1638 ± 0.0520 min−1 (t = 0.7878, P > .05), respectively. These data indicate that proANF 1–98 and proANF 31–67 circulating β post‐distribution half‐lives are approximately 45 minutes whereas β half‐life of ANF is 10 minutes. Persisting concentrations of proANF 1–98 and proANF 31–67 in plasma may better explain the proported sustained pharmacologic effects that have been attributed to ANF, which has a mean a distribution phase half‐life of 3.5 minutes and a β half‐life of 10 minutes.

A case report of intravenous malathion injection with determination of serum half-life.

We report a case of intravenous malathion poisoning. Serum pseudocholinesterase (PChE) levels were undetectable for 24 hours post injection and increased to 9 IU/mL (normal 7-19) at 7 days. A concomitant decrease of serum malathion was seen with the increasing PChE. The half-life was calculated to be 2.89 hours.

Free drug monitoring by liquid chromatography and implications for therapeutic drug monitoring

Abstract Free (non-protein bound) drug monitoring is very complex but new advances in separation of protein bound from free drug by ultrafiltration can facilitate free concentration therapeutic drug monitoring. Free drug can be separated from protein-bound drug by means of ultrafiltration in which the free drug passes through the membrane filter while the protein bound drug is retained. The ultrafiltrate is then subjected to chromatographic analysis (HPLC). Limitations include a sufficient sample for these highly protein bound drugs and detector sensitivity at the low free drug concentrations. Free drug fractions that have been successfully analyzed by HPLC include disopyramide, phenytoin, carbamazepine, and propranolol. HPLC offers important advantages over immunoassays, since chromatographic methods can also measure the amount of metabolite present. The detection of metabolites can be important, e.g. N-desisopropyl disopyramide which displaces disopyramide from its binding sites on alpha-one acid glycop...

Burn center management of operating room fire injuries.

Approximately 100 operating room (OR) fires occur per year in the United States, with 15% resulting in serious injuries. Intraoperative cautery was frequently associated with OR fires before 1994; however, use of supplemental oxygen (O2), ethanol-based products, and disposable drapes have been more frequently associated with OR fires. Fires resulting from cosmetic and other small procedures involving use of nasal canula O2 and electrocautery have been described in six published reports. We report five thermal injury cases admitted to our burn treatment center because of fires during surgical procedures over a 5-year period. Two patients undergoing supraorbital excision experienced 2.5 and 3% TBSA involvement burns; in a third patient surgical excision of a nasal polyp resulted in a 1% TBSA burn; in a fourth patient an excisional biopsy of a lymph node resulted in a 2.75% TBSA burn; and the last patient was burned during placement of a pacemaker, with resulting TBSA of 10.5%. Two of the five patients required intubation for inhalational injury. Two patients required tangential excision and grafting of their thermal injuries. All patients had received local or parenteral anesthesia with supplemental O2/nitrous oxide (N2O) for surgical procedure. There are a number of ignition sources in the OR, including electrocautery, lasers, and faulty OR equipment. The risk of OR fires increases with surgical procedures involving the face and neck, including tracheostomy and tracheobronchial surgery. The common use of O2/N2O mixtures or enriched O2 for minimally complex surgical procedures and disposable drapes adds to the risk of an OR fire: the O2/N2O provides a fuel source, and the disposable drapes trap thedelivered gas. Electrocautery near an O2/N2O source resulted in the five thermal injuries and warrants careful reconsideration of technique for surgical procedures.

Interpretation of urine quantitative 11-nor-delta-9 tetrahydrocannabinol-9-carboxylic acid to determine abstinence from marijuana smoking

Verification of abstinence from cannabinoid use after initial identification requires documentation of falling quantitative levels of urinary 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) over an extended time period. We present a case in which normalization of quantitative urinary THC-COOH results to urinary creatinine is required to correctly interpret a series of quantitative levels and confirm abstinence from marijuana smoking.

Phenytoin and plasmapheresis: importance of sampling times and impact of obesity.

The effect of plasmapheresis (PP) on total and free phenytoin clearance is reported. An obese patient with the diagnosis of thrombotic thrombocytopenic purpura (TTP) was treated with PP. Twelve episodes of PP, having exchange volumes of 1.5-2.25 times the plasma volume with a mean +/- SD 7.7 +/- 0.8 L of plasma removed, were studied. A significant (p < 0.05) difference was observed with a mean change in plasma phenytoin concentrations from pre- to end-PP of 7.32 +/- 2.5 mg/L compared to 1.98 +/- 0.7 mg/L observed pre-PP to 1 h post-PP. These values corresponded to 48.4 +/- 11.6 and 15.0 +/- 6.7% decreases in phenytoin concentrations at the two aforementioned time periods. To prevent misinterpretation of plasma phenytoin concentrations, samples should not be obtained for at least 2 h after PP.

Low-volume whole bowel irrigation and salicylate absorption: a comparison with ipecac-charcoal.

Study Objective. To evaluate two methods of gastrointestinal decontamination, low‐volume whole bowel irrigation (WBI) and activated charcoal, for their ability to prevent absorption of salicylate.