Annals of Pharmacotherapy

Ciprofloxacin is a new fluorinated quinolone antibiotic with high activity against a wide spectrum of gram-positive and gram-negative bacteria, including methicillin-resistant Staphylococcus aureus, Enterobacteriaceae, and Pseudomonas aeruginosa. Clinical trials using the oral preparation of ciprofloxacin have demonstrated its effectiveness in a wide variety of infections. In addition, extensive clinical trials with the intravenous preparation are underway.

In vitro and in vivo studies with ciprofloxacin have reported the incidence of resistant organisms to be very low. In addition, the incidence of ciprofloxacin-related side effects throughout its clinical trials has been minimal. Most reports of side effects have been related to the gastrointestinal tract, such as nausea or vomiting. The incidence of adverse experiences in worldwide clinical trials has been reported to be approximately 6.4 percent.

The calcium modulators have been a significant therapeutic advancement for the treatment of angina. Structural analogs of verapamil and nifedipine have been synthesized, as have structurally unique compounds. As the role of calcium in body processes is further elucidated, the efficacy of the calcium modulators is being evaluated for numerous disorders. It is anticipated that the newly synthesized compounds will have specificity toward particular body processes, thus providing efficacy with minimal side effects.

The low incidence of reported heart attacks and cardiovascular-related deaths in Greenland Eskimos and the Japanese has generated interest in the possible protective effect of their diet, which is made up primarily of fish and related marine foods. This paper reviews the current evidence for reducing the risk of cardiovascular disease with fish-oil supplementation, and discusses related clinical data to support the mechanisms proposed. Included is evidence that fish oil can lower certain serum lipid levels, prolong bleeding time, and reduce systolic blood pressure when consumed in moderately large doses. Information on safety and side effects is also presented, such as a possible increase in serum cholesterol levels and annoying side effects that may severely limit widespread use of this food supplement. Presently it remains unanswered whether fish oil should be recommended as a dietary supplement for the prevention and/or treatment of hypercholesterolemia and associated coronary artery disease. Further research is required to demonstrate a clear reduction in cardiovascular mortality before a uniform recommendation can be made.

Pralidoxime chloride is a useful agent in the treatment of organophosphate poisoning. Poisindex, a widely used poisoning treatment resource, recommends dosing pralidoxime chloride as an intermittent iv infusion every 8–12 hours, whereas other authors have used continuous iv infusion with good results. Available animal data suggest that a serum concentration of 4 μg/ml may be a minimal level to protect against the toxic effects of organophosphates. Pharmacokinetic simulations, based on parameters obtained from healthy nonpoisoned subjects, show that pralidoxime levels fall rapidly to <4 μg/ml within 1.5–2 hours after a 1-g iv bolus. Continuous iv infusion (0.5 g/h) maintains pralidoxime levels >4 μg/ml throughout the length of infusion. We conclude that continuous iv infusion of pralidoxime chloride may be the preferred method of administration in patients with acute organophosphate poisoning. Clinical trials will be necessary to document the effectiveness of this regimen.

This comprehensive bibliography is intended to enhance the education of the practitioner, student, and academician in the area of parenteral nutrition. This bibliography is not all-inclusive but serves as an update from the original published in 1983. Of particular note in this work is the addition of topics that reflect a growing interest in medical specialties with regard to patient nutritional status and support.

Antacids and adsorbents are commonly used preparations that are generally considered to be pharmacologically inert and free from adverse effects. They may, however, interact with a diverse range of primary drugs and the sequelae can be disadvantageous to the efficacy of the primary medication. Many such reports in the literature are based on animal experiments, or on single-dose studies in healthy subjects. Some reports are anecdotal and are unconfirmed; others are based solely on in vitro evidence.

Potentially important interactions have been suggested for a relatively small group of drugs: tetracyclines, phenytoin, digoxin, chloroquine, cimetidine, quinidine, nonsteroidal antiinflammatory drugs, and beta-blocking agents. The evidence for these has been critically evaluated, as well as for antacid-anticoagulant and antacid-nitrofurantoin interactions that have been wrongly emphasized in the literature.

The majority of literature reports on interactions with antacids have been overemphasized; only ferrous sulfate-, isoniazid-, and tetracycline-antacid interactions fall into a category I importance (scale I–III of descending importance). This category is for those interactions with good evidence of actual or potential importance in patients or in relevant studies on normal subjects.

A case of a 21-year-old woman who had developed mild hepatotoxicity while receiving choline magnesium trisalicylate therapy is described. She presented with fever and mild hepatic enzyme elevations before salicylate therapy was instituted. Liver function tests (LFT) returned to normal within five days of hospitalization but she continued to develop daily fevers. Blood, urine, and throat cultures were negative. An acute viral illness or reactivation of systemic lupus erythematosus were the suspected diagnoses. Choline magnesium trisalicylate was then administered in an effort to control her fever, and was successful. After three days of salicylate therapy her LFT values began to rise. They continued to rise for five more days before salicylate hepatotoxicity was suspected. Choline magnesium trisalicylate was discontinued after eight days and the patient's LFT quickly returned to normal. The source of fever was never identified, although infection with cytomegalovirus was considered the most likely cause. Salicylate-induced hepatotoxicity is reviewed.

The use of a constant infusion of intravenous morphine sulfate in a patient with severe sickle cell crisis is described. After several days of poor control with intramuscular and intravenous narcotic injections, adequate analgesia was obtained with the infusion of morphine within two hours of initiation of therapy. No adverse effects were noted. With the advantages provided by an intravenous narcotic infusion, this protocol should be considered as a suitable alternative to conventional methods for providing pain control in patients in sickle cell crisis.

A 32-year-old Haitian male with acquired immunodeficiency syndrome presented with complications of Isospora belli enteritis. Therapy with the investigational drug difluoromethylornithine was initiated. Severe thrombocytopenia, nausea, and vomiting developed during intravenous drug therapy and recurred upon rechallenge with low-dose oral difluoromethylornithine. Therapy was discontinued because of these severe adverse effects.

Use of large-volume electronic infusion devices (EID) in an adult general hospital was compared with an established protocol to determine compliance. Data were collected during seven widely spaced inspections of the facility. Forty-six percent of 962 EID were observed to be employed inappropriately. Compliance was nearly identical for both pumps and controllers and for intensive care and non-intensive care areas. Four reasons for employing EID accounted for 48 percent of all inappropriate use. An estimated annual savings of $178 000 to $460 000 might be realized through strict protocol compliance.

It has been reported that intravenous fat emulsions, because of their isotonicity and neutral pH, support microbial growth, but traditional parenteral nutrition solutions, being hypertonic and more acidic, are not as supportive. To date, few studies have documented microbial growth in total nutrient admixtures (TNA) containing dextrose, amino acids, fat, electrolytes, vitamins, and trace elements.

This study was undertaken to analyze the growth of Staphylococcus aureus, Candida albicans and four gram-negative enteric bacilli in three different nutrient admixtures, with and without the inclusion of 5% fat emulsion. The composition of the admixtures was either 5, 10, or 25% dextrose; either 0 or 5% fat; and 3% amino acids, electrolytes, vitamins, and trace elements. All admixtures were innoculated with 100 colony-forming units per milliliter, incubated at room (25°C) or refrigerated (4°C) temperature, with samples withdrawn at 0, 3, 6, 12, 24, and 48 hours and plated in triplicate.

Only C. albicans demonstrated any significant growth regardless of fat content. The pH of the admixtures was similar (acidic), and all solutions were hypertonic and found to inhibit bacterial growth.

Conclusions suggest that TNA, when formulated with normal concentrations of additives, is no more likely to support growth of contaminant organisms than the traditional solutions. This contradicts the notion that the addition of fat to total parenteral nutrition will enhance the ability of these admixtures to support microbial growth.

Studies performed in patients with cystic fibrosis (CF) have suggested altered pharmacokinetic parameters for aminoglycosides. Specifically, increased plasma clearance (CI) of aminoglycosides and increased apparent volume of distribution have been noted. In the present study, tobramycin CI is determined by both serum concentration data and direct renal clearance (Cl_ren). Tobramycin Cl_ren appeared to be directly correlated to the measured creatinine clearance (Cl_cr) (r = 0.93, p <0.01 ). The tobramycin Cl, by both methods of determination, was not elevated in comparison to the Cl_cr or expected values for patients without the disease. These results appear to corroborate a recent study in which the renal and plasma Cl of gentamicin was measured in patients with mild-to-moderate CF and were not noted to be elevated. It is suggested that standard doses of tobramycin be used initially in patients with mild-to-moderate CF with dosage adjustment based on serum concentration data to achieve the desired goals.

We comparatively evaluated the patient preference for each of the three commercially available transdermal nitroglycerin delivery systems using a randomized crossover study design. Preference was determined by ease of application, adhesion, occurrence of local irritation at the site of application, and systemic toxicities. In addition, we recorded the number of nitroglycerin tablets taken and angina attacks reported per treatment course. Each treatment course was one month long, with each patient participating for a total of three months. This allowed all patients to be exposed to each of the three products for one treatment course, thereby serving as their own controls.

Thirty-eight patients completed the three-phase crossover and expressed a preference. Results showed that Transderm-Nitro was significantly preferred over both Nitro-Dur and Nitrodisc (p < 0.005). Most of the preferences were based on cosmetic appearances or adhesive qualities. Additionally, results showed that there was no difference in efficacy among the three products when number of angina attacks reported and number of nitroglycerin tablets taken were compared.

Twenty-five to 50 percent of all antibiotics prescribed for hospitalized patients are for prevention, not treatment, of infection. Procedures to institute rational, cost-effective utilization of these agents should have a significant impact on drug cost and pharmacy inventory. Several authors have described antibiotic cost reduction programs using pharmacy intervention. Unfortunately, measures that are successful in one institution may not be effective or appropriate in another.

A three-year study was undertaken to examine the impact on physician prescribing of an infection control bulletin and formalized recommendations for antibiotic utilization. Patient records also were examined to determine if any change in antibiotic utilization would influence patient morbidity. Over the three examination periods there was a significant reduction in cost of prophylaxis in 7 surgical groups, and a trend toward cost reduction in 21 additional groups. Cost of prophylaxis also increased in other surgical groups. Cost reduction was associated with limited duration of prophylaxis and a shift toward use of first generation cephalosporin products. Patient morbidity did not differ significantly.

In the Republic of Ireland, the state pays the cost of medical care for around 40 percent of the population through the General Medical Services (GMS). Doctors treating GMS patients are entitled to prescribe from an approved list of drugs. In October 1982, many antacids, cough and cold preparations, antihistamines, and mild analgesics were removed from the GMS prescribing list. The visiting rate and the amount of prescribing fell in the GMS during 1982–83. Drug utilization within the GMS was measured using prescription numbers and in the total population using data obtained from pharmaceutical wholesalers expressed as defined daily doses. These results showed substantial changes in GMS prescribing in the utilization of mefenamic acid, carbocysteine, and H₂-receptor antagonists associated with the introduction of the limited list, suggesting a switch to these agents from delisted preparations. The therapeutic and economic implications of this policy are discussed.