Annals of Pharmacotherapy

Milrinone is a bipyridine derivative with positive inotropic and vasodilating properties. The intravenous form of the drug has been approved by the Food and Drug Administration (FDA) for short-term management of congestive heart failure (CHF). The FDA has requested additional mortality data prior to approval of the oral form. Milrinone produces positive inotropic and vasodilating effects through unknown mechanisms, and causes a dose-dependent increase in cardiac index and a decrease in systemic vascular resistance and pulmonary capillary wedge pressure. It is extensively absorbed following oral administration with an elimination half-life of approximately 1.5–2 hours and a corresponding duration of action of 3–6 hours. Its major route of elimination is renal (83 percent). The intravenous dose is 50 μg/kg given over ten minutes, followed by a maintenance infusion of 0.375–0.75 μg/kg/min titrated to the desired hemodynamic response. The average effective oral dosage is 7.5–10 mg four to six times daily. Milrinone is most effective in the short-term management of CHF where the majority (60–80 percent) of patients have symptomatic and hemodynamic improvement as well as increases in exercise duration. However, many patients do not derive long-term benefit from milrinone therapy. Available evidence suggests that milrinone does not arrest the natural progression of CHF, and some investigators feel it may actually worsen CHF and shorten patients' length of survival. Milrinone has been generally well tolerated with a low risk of major organ toxicity. The most common adverse reactions with intravenous milrinone include ventricular arrhythmias (12 percent) and supraventricular arrhythmias (4 percent). Oral milrinone may cause gastrointestinal disturbances (11 percent), cardiac arrhythmias (7 percent), headache (7 percent), dizziness (6 percent), palpitations (6 percent), fatigue (3 percent), tachycardia (2 percent), and increased hepatic enzymes (2 percent). Although not proven, the major concern with milrinone is its potential to be proarrhythmic, leading to a higher incidence of sudden death in patients treated over the long term. Experience with milrinone indicates that its usefulness may be limited to the short-term treatment of CHF. Until mortality evaluations are complete, the role of milrinone in the long-term management of CHF will remain undefined.

Since its inception, the field of parenteral nutrition has continued to evolve requiring the expertise of several health care disciplines. This feature has made nutrition support unique among clinical subspecialties. As a member of this team, the pharmacist plays a critical role in the provision of sterile admixtures, compatible nutritional formulations, and cost-effective, therapeutically equivalent strategies. The pharmacist has become more involved in the clinical care of the patient, with particular emphasis on the development of drug-induced metabolic disorders. The multitude of drugs prescribed to hospitalized patients increases the potential for serious metabolic disturbances. This is especially true in the critical care setting where sudden changes in metabolism (e.g., acid-base homeostasis, fluid and electrolyte balance) may result in profoundly negative effects. The critical care setting also represents the most sensitive period of hospitalization where even subtle changes in metabolic homeostasis may assume major clinical significance. Early recognition of offending agents and the institution of appropriate intervention may avert serious iatrogenic diseases. The nutrition support team is in a unique position to address many such disorders through selective manipulation of the various components in the parenteral nutrient admixture. The ability of the pharmacist to recognize the development of drug-induced metabolic disorders lends further support for clinical pharmacy in nutrition support services.

Test dose methods have been used to predict the maintenance dosage of lithium carbonate tablets in bipolar patients. These methods require a lithium analytical method that is accurate to the second decimal place. Successful use of these test methods has employed the atomic absorption spectrophotometric method, yet many hospitals use a flame spectrophotometric method. We evaluated a two-point method to predict lithium maintenance dosages of slow-release lithium carbonate tablets in 20 bipolar patients using both assay methodologies. No clinically significant differences were found between the two sets of predictions, suggesting that either assay methodology has requisite sensitivity and accuracy for use in test dose predictions of lithium maintenance dosages.

The formation rate constant and elimination rate constant for 3-hydroxyquinidine were determined in eight patients with ventricular tachycardia. These two parameters (mean ± SD) were found to be 0.784 ± 0.202 and 0.042 ± 0.058 h⁻¹, respectively. Coefficients of determination for the computer-generated line of best fit for serum concentration-time data were 0.986 ± 0.008. Patients received two infusions of quinidine gluconate 5 mg/kg over 30 minutes separated by a 20–30 minute electrophysiologic testing period. Unbound and total 3-hydroxyquinidine concentrations were also determined. Among the eight patients, 3-hydroxyquinidine was 61.9 percent bound. Studies in healthy volunteers had shown 50 percent binding. Linear regression of unbound and total 3-hydroxyquinidine was described by the equation Y = 0.3814X–1.448, r = 0.813. Although half-lives of 3.5–12.4 hours had been reported in healthy volunteers, prolonged half-lives were observed in all but two of our arrhythmia patients.

A 12-year-old girl with sickle cell hemoglobinopathy presented with a Salmonella osteomyelitis of her right humerus requiring six weeks of parenteral antibiotic therapy. Home therapy was evaluated. Due to the frequency of the medication administration (every six hours) and the apprehension of the family members, a Pharmacia-Deltec CADD-VT Infusion Pump was chosen for drug administration. Based on the stability of ampicillin, 1.3 g q6h was administered to provide a minimum of 1 g for the last dose of a 24-hour cycle. Ampicillin 6 g contained in 100 mL of sterile water for injection provided a 60 mg/mL solution with an osmolarity of 347 mOsmol. The pump was programmed to deliver 22 mL of solution over one hour, every six hours. A keep-vein-open rate of 0.2 mL/h maintained line patency. A 100 mL cassette of solution prepared daily was replaced on the pump by a home therapy nurse each morning. At the end of six weeks of therapy, the osteomyelitis was eradicated. We found the use of an ambulatory infusion pump an effective, convenient, and cost-saving method of treatment for our patient.

Rifampin can be associated with severe adverse effects such as hepatitis, acute renal failure, hemolytic anemia, and thrombocytopenia. Thrombocytopenia has traditionally been associated with intermittent therapy. This article reports the occurrence of rifampin-associated thrombocytopenia in an indigent patient after a four-month lapse in therapy for pulmonary tuberculosis. The patient's platelet count dropped rapidly to a level of 1000/mm³ after receiving a single 600 mg dose of rifampin. After returning to a normal level of > 100 000/mm³, the patient's platelets again dropped to 1200/mm³ with readministration of rifampin. The long-term therapy necessary to eradicate the Mycobacterium tuberculosis organism makes economic considerations important. This patient and other indigent patients who may be poor compliers because they are unable to buy the necessary medication may be at a higher risk for adverse reactions.

The aim of this study was to establish the performance of pharmacokinetic methods employing little data on serum drug concentrations obtained in routine therapeutic drug monitoring of imipramine. Forty-three and 123 serum levels were obtained in 8 adult depressive patients (aged 57–80 y) and 34 enuretic children (aged 5–13 y), respectively. Forecasting of the serum concentrations was performed based on mean population pharmacokinetic parameters (method A), with knowledge of one steady-state serum concentration (method B), and from two or more steady-state serum concentrations (method C). The accuracy and precision of each method were evaluated from the mean prediction error (ME) and from the root mean squared prediction error (RMSE), respectively. The values of ME and RMSE of methods B and C proved to be significantly lower than those found using method A. Method C was the most precise and accurate in both populations. Method A underestimates the serum concentrations observed in adults (ME >0) but overestimates them in children (ME <0), although to a lesser extent. The study shows that it is possible to obtain a good estimation of individual dosage needs from one or more serum concentrations obtained at steady state. Clinical application of these methods (B and C) yields an increase in the efficiency and safety of the treatment, particularly in special populations such as geriatric and pediatric patients.

Branched-chain amino acid-enriched formulas have been evaluated in a number of clinical trials. The efficacy of these solutions in the management of stressed patients is controversial. This review discusses the proposed benefits of the branched-chain amino acid-fortified solutions and summarizes prospective clinical trials regarding their use in stressed patients. A cost comparison is also included.

The critically ill, stressed patient has been characterized as having altered cellular metabolism. Altered protein metabolism is manifested as negative nitrogen balance, reduced whole-body protein synthesis, and increased proteolysis. An increased oxidation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine has also been observed. Exogenous administration of BCAA as part of a total parenteral nutrition (TPN) regimen has been proposed to compensate for the altered protein metabolism in the stressed patient by sparing endogenous sources of BCAA, thereby reducing skeletal muscle catabolism and increasing protein synthesis. Numerous clinical studies have been performed investigating this theory. The results are controversial. Differences in study outcomes appear to be related to study design, especially patient selection. Our review of those studies which were randomized, prospective, and controlled indicates that an improvement in nitrogen retention and visceral protein status can be achieved in stress-stratified patients who receive a TPN regimen containing a BCAA-enriched formula. The significance of these outcomes on morbidity, length of hospital stay, and mortality has not been evaluated.

This study assessed the impact of physician exposure to clinical pharmacy services on the appropriateness of physician prescribing and on medication costs. Two study sites were used: FPC (primary resident training office without clinical pharmacist) and PMC (satellite office with clinical pharmacist). The same physicians provided care at both study sites. Exposed patient encounters were selected from encounters during each resident's rotation at the PMC satellite. Unexposed patient encounters were selected from encounters at the FPC immediately prior to each resident's exposure to clinical pharmacy services. A blind review panel evaluated case abstracts of the patient encounters for appropriateness of drug choice, daily dosage, dosing interval, duration of treatment, clarity of instructions, and monitoring data; potential severity of the patient problem; and difficulty of the clinical decision. After adjusting for covariables (potential severity, difficulty, patient age, sex, Medicaid status, therapeutic category, and type of medical problem), physician-patient encounters in which family practice residents were exposed to clinical pharmacy services were rated significantly more appropriate for choice of drug prescribed, daily dosage chosen, dosing interval selected, clarity of prescription instructions, and monitoring data. Costs of acute medications, as measured by average wholesale price per day, per dose, and per treatment course, were also significantly lower for clinical pharmacy-exposed physician-patient encounters.

The Three Mile Island (TMI) nuclear emergency in the U.S. in March 1979 marked the first occasion when use of potassium iodide (KI) was considered for thyroid blocking of the population in the vicinity of a potentially serious release of fission products from a nuclear power reactor. In face of a demand that could not be satisfied by commercial supplies of low-dose KI drug products from the U.S. pharmaceutical industry, the Food and Drug Administration directed the manufacture and stockpiling of sufficient quantities of saturated solution of potassium iodide (SSKI) to provide protection for one million people in the event of a large-scale release of radioiodines. Although the drug was not used, the experience of producing, stockpiling, and making ready for use a large quantity of the drug resulted in significant public policy, regulatory, and logistical issues. A number of these issues have been resolved through scientific debate and consensus, development of official guidance regarding the proper role of KI in nuclear emergencies, and the approval of New Drug Applications for KI products specifically intended for thyroid blocking in nuclear emergencies. Other issues regarding broad-scale implementation of the guidelines remain today. This paper traces the history of the development and implementation of the use of KI from pre-TMI to the present.