Annals of Pharmacotherapy

The abuse of cocaine in this country has reached epidemic proportions and has generated great concern for the effects of the drug on the fetus when used during pregnancy. Although educational campaigns cite adverse fetal effects as a deterrent to using the drug, there are limited data on which to base a true risk assessment. This paper reviews the published studies of pregnancy outcome in cocaine-abusing mothers, with special focus on structural malformations and other neonatal risks.

This article reviews the pharmacokinetics, clinical use, and adverse effects of trimethoprim/sulfamethoxazole (TMP/SMX) in renally impaired patients. Renal dysfunction changes the pharmacokinetics of both component drugs. TMP and SMX disposition are not significantly altered until creatinine clearance is <30 mL/min, when SMX metabolites and TMP accumulate and may lead to toxicity. Renal dysfunction, however, does not preclude the use of TMP/SMX to treat susceptible infections, even when creatinine clearance is < 15 mL/min. Adverse effects may occur more frequently in renally impaired patients but are not clearly related to increased serum concentrations of either drug. Guidelines for appropriate dosing and monitoring of TMP/SMX therapy in these patients are presented.

A single dose of cefonicid given 3.5–5.0 hours or 0.5–1.0 hour preoperatively was compared with cefoxitin given as five doses beginning 0.5–1.0 hour preoperatively for prophylaxis of infection in 202 patients undergoing vaginal or abdominal hysterectomy. The administration of cefonicid 3.5–5.0 hours preoperatively was intended to simulate situations where surgery may be delayed or prolonged. The trial was double-blind, and patients were randomized to one of the three regimens. Operative site infections were noted in 6.2 percent of patients (7/113) who received cefonicid 3.5–5.0 hours preoperatively, in 7.0 percent of patients (3/43) who received cefonicid 0.5–1.0 hour preoperatively, and in 4.3 percent of patients (2/46) who received cefoxitin (p > 0.05). Enterococci were isolated most frequently from operative-site infections. When administered 3.5–5.0 hours preoperatively, cefonicid was as effective as more traditional regimens.

Butorphanol/diazepam was compared with thiopental for induction of anesthesia, and the thiopental-sparing effects of butorphanol/diazepam determined. One hundred women, American Society of Anesthesiology physical status class I, undergoing ambulatory, elective termination of pregnancy were randomized to receive either butorphanol 2 mg plus diazepam 10 mg, or thiopental, until loss of the lid reflex occurred. The butorphanol/diazepam group received supplemental thiopental as necessary to attain adequate induction of anesthesia. The combination of butorphanol and diazepam significantly reduced the thiopental dose required to produce loss of the lid reflex, from 4.2 ± 0.8 to 0.8 ± 0.6 mg/kg (p < 0.005), with 22 percent of the patients not requiring supplemental thiopental. The intraoperative course and anesthetic requirements were similar between the two groups. Lower recovery room rating scale values upon arrival at the recovery room were attributed to significantly higher weight-normalized doses of butorphanol (p = 0.004) and diazepam (p = 0.005). The duration of the recovery room stay was 68.8 ± 24.9 min for the control group, and 80.8 ± 29.0 min for the butorphanol/diazepam-treated patients (p = 0.026). There were no clinically significant differences in anesthesia or postanesthesia recovery. The combination of butorphanol and diazepam has a significant thiopental-sparing effect, and is a useful induction technique for short, ambulatory surgical procedures.

The effect of food on the bioavailability of a nifedipine sustained-release preparation was studied. Each of seven male volunteers received a single oral 20 mg dose with 100 mL of water under two conditions, fasting and after a meal, with a crossover after a seven-day wash-out period. Blood samples were drawn at time zero (just prior to dose), and 1, 2, 3, 4, 6, 8, 10, and 12 hours after dosing. Nifedipine assays were performed by gas chromatography. The area under the serum concentration-time curve (AUC) from 0 to 12 hours and maximum serum concentration (C_max) were significantly increased by food. Blood pressure was significantly decreased by food. The mean AUC for fasting and meal conditions were 315.0 and 411.4 ng•h/mL, and the mean C_max were 42.6 and 86.6 μg/mL, respectively. The results indicate that food may increase the bioavailability of nifedipine sustained-release preparation.

A 77-year-old woman with suspected coronary artery disease underwent an oral dipyridamole/thallium-201 myocardial imaging study. Approximately 75 minutes after ingestion of dipyridamole 300 mg suspension, the patient developed chest pain, hypotension, nausea, and diaphoresis. An electrocardiogram revealed ST-T wave changes suggestive of inferior ischemia. Appropriate therapeutic measures, including aminophylline and nitroglycerin, were instituted. Delayed thallium images revealed reversible ischemia in the anteroseptal and posterobasal regions with a fixed defect in the inferobasal region. Cardiac enzyme studies were also indicative of acute myocardial injury. The patient subsequently underwent coronary arteriography and four-vessel coronary artery bypass grafting and was discharged without further complication. This report raises concerns about the potential danger of dipyridamole in patients with severe coronary artery stenosis and collateral circulation. Prophylactic aminophylline should be considered in these patients.

The potential interaction between certain antibiotics and digoxin has been discussed in the literature; however, few cases of actual erythromycin-induced digoxin toxicity have been reported. We present a case in which an 86-year-old woman who was taking digoxin 0.25 mg/d developed probable digoxin toxicity after the administration of erythromycin for the treatment of otitis media and streptococcal pharyngitis. Her digoxin concentration increased from a trough of 1.9 to 5.1 nmol/L six days after the erythromycin was started. Digoxin was discontinued and restarted approximately six weeks later when the patient's atrial fibrillation and congestive heart failure recurred. Her digoxin dose at this time was 0.125 mg/d and resulted in steady-state concentrations of 1.2, 1.4, and 1.2 nmol/L over the next year. Erythromycin inhibition of Eubacterium lentum, which converts digoxin into digoxin-reduction products in the gut, is the proposed mechanism of this interaction.

A 74-year-old woman experienced an apparent psychotic reaction several hours after administration of iv midazolam as a premedicant for gastroscopy. The reaction included confusion, hallucinations, and hostility and required administration of haloperidol to calm her. The woman subsequently underwent colonoscopy with meperidine as a premedication and experienced no behavioral changes. Although other causes cannot be completely ruled out, the evidence points strongly to midazolam as the precipitating agent for the psychotic reaction.

A patient was admitted complaining of fever and headache. He was suspected of meningitis due to nuchal rigidity, and a lumbar puncture was performed. The patient was diagnosed as having cryptococcal meningitis, as Cryptococcus neoformans was found in an India ink preparation of the cerebrospinal fluid. Both amphotericin B and low-dose flucytosine (50 mg/kg/d) were concomitantly administered to the patient and his clinical symptoms improved. However, the combination therapy induced granulocytopenia and thrombocytopenia, which resolved after discontinuance of the drugs. Amphotericin B alone failed to cause granulocytopenia or thrombocytopenia. These results suggest that the mechanisms of granulocytopenia and thrombocytopenia may be toxic reactions to flucytosine in the azotemic state caused by amphotericin B. Our report emphasizes the need for clinicians to monitor for granulocytopenia and thrombocytopenia in patients receiving treatment with both amphotericin B and flucytosine, even when flucytosine is administered in a low dose.

Cimetidine, the first marketed histamine₂-receptor antagonist, has been shown to decrease the clearance of warfarin consistently through inhibition of cytochrome P-450 metabolism. The clinical significance of this drug–drug interaction has been questioned due to: (1) the lowering of the warfarin therapeutic range, (2) the lowering of the total daily therapeutic cimetidine dosage, (3) the advent of once-daily cimetidine dosing, and (4) the demonstration that the clearance of the less active warfarin R-enantiomer is decreased to a greater extent than the more active S-enantiomer. Ranitidine has been implicated in both increasing and decreasing warfarin's hypoprothrombinemic effect (noted in the warfarin package insert), despite the majority of investigations demonstrating no warfarin clearance changes. Careful examination of the implicating data indicates that the majority of the warfarin pharmacodynamic and pharmacokinetic variance that occurs with combined ranitidine-warfarin therapy cannot be attributed to a drug–drug interaction. No data are available to implicate the newer histamine₂-antagonists, famotidine and nizatidine, in causing a decrease in warfarin metabolism.

The purpose of this article is to provide an overview of the emerging discipline of pharmacoeconomics. Specific methodologies and terms are defined. Pharmacoeconomic research is described, related to, and contrasted with clinical drug trials. Additionally, we present a brief overview of the general steps taken designing a pharmacoeconomic study. Finally, several issues centering around pharmacoeconomic analysis are presented for discussion and debate. The need for high-quality pharmacoeconomic research is stressed along with the need for appropriate education of individuals trained in the health sciences.

Prescription drug profiles of 116 human immunodeficiency virus (HIV)-infected patients taking zidovudine in 1988 were surveyed. Patients received the drug an average of 236 days. About one-third (32 percent) required reduced dosage presumably because of hematologic toxicity and this was associated with length of time on the drug. Zidovudine dosage reduction was not associated with concurrent therapy with either acetaminophen or acyclovir. Concomitant drug therapy was common, especially with systemic antifungals (47 percent), antivirals (33 percent), nonsteroidal antiinflammatory drugs (23 percent), and antidepressants (20 percent), as well as topical fungicides (35 percent) and antiinflammatory agents (28 percent). Over three-fourths of patients on zidovudine were on chemoprophylaxis for Pneumocystis carinii pneumonia, most often with pentamidine inhalation therapy. This study showed that the HIV-infected patient population is being treated concomitantly with many pharmacologic agents prescribed by various medical specialties.

There are always high expectations for a new year—and certainly we will have even higher expectations for a new century. To continue leadership in the 21st century, the American pharmaceutical industry must make a stronger commitment to new product research and development and the profession of pharmacy must commit to development of services needed for new, high-technology products and devices that will often be parenterally administered, bulky, nontraditional, patient-tailored, infrequently administered, and device-oriented. It is suggested that pharmacy must initiate efforts to include drug administration as a pharmaceutical service. Other actions are suggested to modify the curricula preparing pharmacists and to recruit a wider variety of students. A number of other professional initiatives are recommended and discussed to position pharmacy for enhanced clinical services. The issue of subperformance by pharmacists is discussed by pointing out that there is a significant difference in what often is, what should be, and what could be pharmacy service.