No abstract

We cared for a 4-year-old patient who had undergone orthotopic liver transplantation and was placed on a ventilator for respiratory distress associated with Pneumocystis carinii pneumonia. The neuromuscular blocking agent pancuronium bromide 1 .O-1.2 mg every hour as needed was used to facilitate artificial ventilation for 40 days. On discontinuation of pancuronium, the patient experienced severe, generalized neuromuscular dysfunction. Because no improvement was seen for 2 weeks, the acetylcholinesterase inhibitors edrophonium and pyridostigmine were instituted. Shortly thereafter the patient's condition began to improve. Gradual improvement occurred over 3-4 months and the patient has since returned to baseline neurologic function. We suggest that long-term pancuronium use was the cause of the patient's prolonged paralysis. The improvement experienced after the initiation of antidotal therapy strongly supports our proposal. (Pharmacotherapy 1989;9(3):154-157)Pancuronium, a nondepolarizing, neuromuscular blocking agent, was introduced in the United States in 1972.' It is 5 times more potent than D-tubOcUrarine, and has few cardiovascular, histamine-releasing, and hormonal actions.2 It combines with cholinergic receptors at the postsynaptic membrane of the neuromuscular iunction and prevents transmission ranges from 0.06-0.10 mg/kg.3 Paralysis is maintained by administering an additional 2-4 mg every 1-2 hours as needed.3 We cared for a child who experienced prolonged muscle paralysis after longterm pancuronium therapy. Case Reportof neuroelectrical impulses by acetylcholine.' It also acts to a lesser extent by presynaptic inhibition of the release of acetylcholine molecules from the nerve terminal into the synaptic cleft.' Pancuronium acts only on striated muscle; it causes no change in smooth muscle f~n c t i o n .~ Neuromuscular blockade produced by the drug may be reversed by acetylcholinesterase inhibitors such as edrophonium, pyridostigmine, and neostigmine.4Pancuronium is used to eliminate the spontaneous resistance efforts of patients during surgery or mechanical ventilation by providing skeletal muscle relaxati~n.~ The intravenous single initial dose From the DeDartments of Pharmacv Practice (Drs. Shaefer and A 4-year-old, 12.4-kg girl underwent orthotopic liver transplantation in October 1986 for biliary atresia. In March 1988 she was admitted for treatment of Pneumocystis carinii pneumonia. Four days after admission she required intubation. Pancuronium, initially 1.0 mg every hour as needed and later increased to 1.2 mg every hour as needed, was given to facilitate ventilation therapy. The frequency of dosing was determined by the nurse caring for the patient based on pulse oximetry and arterial blood gas values. The patient was 100% paralyzed the majority of the time because when her level of paralysis was allowed to decrease, her oxygen saturations dropped below acceptable levels. Pancuro-Miwa) and Surbery (Drs. Wood and Shaw). Universitv of Nebras-nium was administered dailv for 40 davs (total 438 _ _

Hypertrichosis is a well-recognized adverse effect of therapy with either cyclosporine or minoxidil. We present a case of extreme hypertrichosis in an eight-year-old male liver transplant recipient who received concurrent cyclosporine and minoxidil therapy. A review of drug-induced hypertrichosis is presented.

When the 4 NSAIDs are compared in epidemiologic studies, there is no quantitative basis for identifying 1 as more or less toxic than the others, underlining the hazard of deriving quantitative conclusions from spontaneous reports. Spontaneous reports are an unreliable measure of risk; rather, they may provide evidence of the relative awareness of specific toxic effects among physicians.

Possible ketoconazole-induced hypoglycemia TO THE EDITOR: Several cases of ketoconazole-induced testicular' and adrenal' hypofunction have been reported. These reactions may be due to inhibited hydroxylation of II-deoxycortisol, which results in diminished production of cortisol and a blunted cortisol response to corticotropin (ACTH).3 This impaired cortisol response may predispose some patients to hypoglycemia. We report a possible case of ketoconazole-induced hypoglycemia.A 22-year-old man with a two-day history of fever, sinusitis, and possible seizureswas admitted to the intensivecare unit after lumbar puncture and clinical signs indicated pneumococcal meningitis.Vital signs were BP 120/80 mm Hg, T 37.5°C, P 100 bpm, and R 4O/min. Temperature and respirations returned to normal over the course of hospitalization.Pertinent laboratory test results were: blood glucose 233 mg/dL (normal 60-110),serum potassium 2.9 mEq/L (3.5-4.7), serum phosphate 1.5 mg/dL (2.5-4.5), and albumin 3.9 gm/dL (3.4-5.2). A drug screen revealed serum salicylate concentrations of 7.8 mg/dL (therapeutic 2-29).Drug therapy included penicillin G K 3 million units iv q4h, phenytoin I g iv followed by 300 rng po qd, propoxyphene napsylate 100mg q4h prn pain, and oxazepam 10 mg q6h prn agitation. Tho doses of oxazepam were given on the day of admission. Ketoconazole 200 mg po hs was ordered for a fungal infection in the groin area; clotrimazole 1.0070 and fluocinonide 0.05% cream were applied to the affected area tid. A bolus of potassium chloride 20mEq was given iv, followed by an infusion of dextrose 5% in sodium chloride 0.45% with KCI 40mEq at 125ml/h. The infusion wasstopped on day 3, as the serum potassium was 4.4 mEq/L. Dextrostix determinations were performed qid in order to monitor the hyperglycemiaseen on admission.On day 2 the penicillin dose was changed to 2 million U q2h. Three doses of both propoxyphene and oxazepam weregiven. Further doses of oxazepam were not administered. Serum phenytoin on this day was 12.3I"g/ml (normal 10-20). Dextrostix determinations were within normal limits.On day 3 propoxyphene was givenat 8 pm. The patient refused dinner due to lack of appetite. Dextrostix measurements were normal.

Propafenone hydrochloride was approved for marketing by the United States (U.S.) Food and Drug Administration (FDA) in November 1989. During U.S. clinical trials of propafenone, one case of agranulocytosis was seen. Seven additional cases have been reported outside the U.S. One German report of profound but reversible granulocytopenia appeared in 1982. In January 1991, the FDA reviewed adverse events reported with propafenone. Four reports of agranulocytosis were identified and are described. The reporting rate of approximately one case of agranulocytosis per 10,000 propafenone prescriptions per year likely underestimates the true incidence of this adverse event.

This double-blind, crossover trial compared the sensory and product preparation characteristics of two cholestyramine powder preparations. The study involved 100 healthy volunteers, aged 22-65 (mean 42 years). Questran, a currently marketed product containing sucrose as a sweetener, was compared with Questran Light, a new formulation substituting aspartame for 90 percent of the sucrose. Comparisons were conducted with the two products mixed in water and orange juice. The subjects expressed a significant overall preference for the new formulation mixed in either water (77 percent) or orange juice (80 percent) (p less than 0.01 in both comparisons). Subjects expressed an overwhelming preference for the old product (99 percent) with respect to ease of preparation, although the ratings of the new product were generally neutral rather than negative. The new product is somewhat more difficult to prepare compared with the old cholestyramine preparation, but offers significantly increased patient acceptance based on sensory evaluations.

All hospitals should have a formal adverse drug reaction (ADR) reporting program in place in order to meet their professional obligation as members of the health care community and to help ensure quality of care within their institution. Although ADR reporting is the responsibility of all health professionals, in actuality it belongs to the hospital pharmacy department. Implementation of an ADR reporting program is similar to that of other quality assurance programs in that it needs to be tailored to the needs and resources of the individual hospital. However, the following steps are integral to any ADR reporting program: defining ADRs ; developing mechanisms for the identification and investigation of ADRs ; designing means for maintaining the program: and designating personnel to carry out the program. This article will discuss each of these steps and make suggestions to assist readers in implementing an ADR reporting program in their hospitals.