Annals of Pharmacotherapy

Octreotide is an investigational synthetic peptide exhibiting actions similar to those of endogenous somatostatin. It has a longer half-life than the native hormone and can be administered by subcutaneous injection. Octreotide inhibits the secretion of growth hormone and numerous regulatory peptides of the gastroenteropancreatic system. Trials evaluating the clinical utility of octreotide indicate efficacy in the management of symptoms associated with acromegaly and hypersecretory neuroendocrine tumors, and in the control of nontumoral secretory diarrheas. Octreotide therapy is well tolerated. This agent should prove useful in the symptomatic control of a number of rare hypersecretory disorders.

Weight gain associated with antidepressant therapy is a common problem that often results in noncompliance. Some authors suggest that monoamine oxidase inhibitors (MAOI) are less likely to produce weight gain than tricyclic antidepressants. This paper addresses the relative potential for weight gain with the MAOI. Assessing the potential for antidepressant-induced weight gain necessitates separating the weight changes associated with alterations in mood disorders from those due to drug-induced alterations in appetite control. The mechanisms of appetite control are reviewed briefly followed by proposed mechanisms by which the MAOI may alter this control. A literature review suggests that phenelzine is the MAOI most likely to induce weight gain; reports of isocarboxazid-induced weight gain are less common. There are no cases of tranylcypromine-induced weight gain in the literature that are clearly associated with the drug. The MAOI probably have different effects on the mechanisms of appetite control.

Zindotrine, a new bronchodilator, may be an alternative to theophylline in treating reversible airflow obstruction. Efficacy and cardiovascular effects of a single 300 mg oral dose of zindotrine were compared with placebo in a two-period, double-blind, crossover trial. Twelve subjects with airflow obstruction reversible after isoproterenol and theophylline completed the trial. Improvement in pulmonary function (forced vital capacity [FVC], forced expiratory volume in one second, and forced expiratory flow rate from 25 to 75 percent of FVC) was greater after zindotrine than with placebo. Pulmonary function tests increased 15 percent or more over baseline in 30 minutes after active drug, lasting up to 6 hours. Mild decreases in heart rate and mean blood pressure occurred after both treatments, with changes equal in both treatment groups. Six subjects had mild subjective side effects after zindotrine (headache, dizziness, vertigo, flushing, and heartburn) compared with one report of lightheadedness after placebo. A single dose of zindotrine 300 mg provides effective bronchodilator action with a relatively prolonged response and tolerable side effects.

Twenty severely brain-injured patients with Glasgow Coma Scale scores of 4–9 were prospectively randomized to receive one of two standard amino acid formulas, starting with the first day of hospital admission up to day 14 postinjury. Formula 2 (patient group 2) had 54 percent more leucine, 53 percent more isoleucine, 74 percent more valine, 28 percent less phenylalanine, 31 percent less methionine, 111 percent more proline, 38 percent less alanine, and 38 percent less glycine than formula 1 (patient group 1). Groups 1 and 2 received statistically equal overall mean parenteral nutrition calories and protein (2173 ± 147 vs. 2059 ± 143 kcal, and 77 ± 12 vs. 83.1 ± 6 g, respectively). There was a significant difference in overall mean urinary urea nitrogen excretion (group 1 = 24.6 ± 1.3 vs. group 2= 18.3 ± 1.1, p = 0.02) and nitrogen balance (group 1 = −8.0 ± 2.1 vs. group 2 = + 1.8 ± 1.2, p = 0.01). Mean overall isoleucine values were significantly higher in group 2 (overall mean 77 μmol/L vs. 62 μmol/L, p = 0.04). Phenylalanine levels were significantly higher in group 1 (107 μmol/L) versus group 2 (82 μmol/L) patients (p = 0.01). Arginine levels were significantly higher in group 1 (78 μmol/L) versus group 2 (49 μmol/L) patients (p = 0.0002). This observation suggests that some standard intravenous amino acid formulas may be more apt to promote positive nitrogen balance than others.

Our objective was to prospectively study febrile and chill reactions associated with two amphotericin B (AB) infusion rates, slow (2-hour) versus rapid (45 minute). Seventeen consenting bone marrow transplant recipients in whom AB was to be initiated for documented or suspected fungal infections were recruited. After standardized premedication, patients received eight daily AB infusions (0.5 mg/kg/d, concentration 0.25 mg/ml). Rate was assigned using a randomized, crossover pair design. Axillary temperature, chills, and meperidine dose required to resolve chills were monitored for each infusion. For the first pair of infusions, fever (defined as a rise of 1 °C) occurred frequently, in 12 of 17 (70.5 percent) and 13 of 17 patients (76.4 percent), with a mean rise of 1.7 °C (range 1.1–3.7) and 1.7 °C (1.1–3.5) degrees for the 45-minute and 2-hour infusions, respectively (p > 0.10). Chills were observed in 15 of 17 (88.2 percent) and 14 of 17 (82.3 percent) recipients of the 45-minute and 2-hour infusions, respectively. The time of onset (p > 0.10) and the duration of chills (p = 0.08) were similar for both infusion rates. Meperidine requirements for rapid and slow infusions were similar as well (p = 0.12). These data suggest that for patients free of preexisting renal and cardiac disease, rapid AB infusions are well tolerated and produce adverse reactions (fever and chills) similar in nature and severity to slower infusions.

Two elderly patients diagnosed with Pseudomonas aeruginosa urinary tract infections were treated with oral norfloxacin in the recommended dose of 400 mg q12h. Initially, antimicrobial susceptibility data indicated the organisms were sensitive to norfloxacin. Six to eight days into therapy urine cultures became positive for P. aeruginosa once again; this time, however, susceptibility reports indicated the organisms were now resistant to norfloxacin. Since cross-resistance among norfloxacin, other quinolones, and cephalosporins can occur, we recommend repeated urine cultures during and after norfloxacin therapy in elderly patients with complicated P. aeruginosa urinary tract infections.

Sudden death has been reported in psychiatric patients before and after the advent of antipsychotic medications. A case of sudden death following chlorpromazine administration in a schizophrenic patient is presented. After receiving a mean daily dose of 780 mg for five days, the patient died suddenly. Laboratory work on day 2 of hospitalization indicated a calculated creatinine clearance of 14 ml/min. The autopsy was noncontributory except for a blood chlorpromazine concentration of 1534 ng/ml. The potential cause of death in this patient and the proposed mechanisms of sudden death in psychiatric patients are discussed. The effect of renal and hepatic disease on chlorpromazine plasma concentrations is presented. This case is the first report of sudden death in a psychiatric patient with a documented elevated antipsychotic plasma concentration. It is also the first report of an elevated chlorpromazine blood concentration in a patient with renal insufficiency.

A case of a patient who had an acutely toxic reaction to cocaine ingestion and later developed acute renal failure secondary to rhabdomyolysis is described. Evidence of rhabdomyolysis was noted by the combination of myalgia, urine discoloration, and elevated serum concentrations of muscle enzymes. Although the mechanism of the rhabdomyolysis is unknown, the clinical presentation resembled that of a norepinephrine-induced vasoconstrictive effect that alters the metabolic demands of the muscle in such a way that the muscle is damaged.

Propranolol hydrochloride is a beta-adrenergic blocking drug used in a variety of clinical conditions. Overdoses can result in severe hypotensive states usually associated with bradycardia or asystole or with profound myocardial depression. We report on an 18-year-old man who ingested a massive dose of propranolol HCl in a suicide attempt. The patient was brought to the hospital in an unresponsive state within 30 minutes of ingestion. He was initially stabilized but subsequently died nine hours after the drug was ingested. Invasive monitoring during this period revealed the shock to be secondary to marked depression of his systemic vascular resistance. Cardiac rhythm and left ventricular output were maintained throughout the attempted resuscitation. This hemodynamic picture suggests that decreased systemic vascular resistance may be another mechanism of shock in significant propranolol HCl overdoses.

Skin rash, fever, and eosinophilia developed in a previously healthy 35-year-old woman three weeks after starting carbamazepine. Fulminant respiratory and renal failure ensued. Autopsy showed pneumonitis, nephritis, serositis, pancreatitis, hepatitis, and carditis, characterized by an infiltrate of eosinophils and lymphocytes. The severity, duration, and extensive organ involvement of the reaction make this case unique.

A 36-year-old woman was admitted for initiation of hemodialysis for chronic renal failure. Two days after catheter placement the patient developed a fever that persisted and resulted in subsequent removal of the catheter. Although blood cultures were negative, cultures of the catheter tip were positive for Staphylococcus epidermidis. An initial vancomycin dose was well tolerated, but the patient later experienced numbness and tingling of her lower back accompanied by pain ten minutes after initiation of the second dose. Symptoms abated when the vancomycin infusion was discontinued, and the drug was subsequently well tolerated when reinstituted at a slower infusion rate. Similar symptoms were observed five minutes into a vancomycin infusion a week later that also resolved after decreasing the infusion rate. Patients on hemodialysis receiving vancomycin should be carefully monitored during drug administration for the development of paresthesia and spasmodic lower back pain.

Two hundred older women with urinary incontinence were studied to observe the influence of their prescription and nonprescription drug use on symptoms of incontinence. Ninety percent of women reported using medication, with an average use of four drugs. Medications statistically associated with urinary incontinence symptomatology were prostaglandin inhibitors, diuretics, and estrogen therapy. Further studies are needed to clarify the relationship between medication usage and the presence and severity of urinary incontinence.

A universally accepted description of appropriate therapy for treatment of congestive heart failure (CHF) has yet to be agreed upon, especially in the elderly. Numerous studies have provided data that question use of a digitalis glycoside as the agent of choice in treatment of chronic CHF. Several clinicians have suggested that diuretics, particularly thiazide diuretics, be used as initial agents in the treatment of this condition. Evidence now demonstrates that drug therapy with enalapril or the combination of hydralazine and isosorbide dinitrate reduces the mortality related to chronic CHF. Additional studies are required to clarify respective roles of diuretics, digitalis glycosides, and vasodilators in the management of chronic CHF.

Recent studies of higher education in America have raised concern over the lack of integrity and coherence, the absence of vigorous intellectual exchange, and the dominance of careerism in the undergraduate curriculum. Observations and recommendations emanating from studies of pharmaceutical education acknowledge the importance of problem-solving abilities but emphasize the inculcation of knowledge relevant to professional functions and the development of skill in contemporary practice. The current emphasis placed on training students for pharmacy practice found in the pharmacy curriculum causes the objective of achieving intellectual growth to be overshadowed. Balance must be restored. The pharmaceutical sciences, taught for their value as academic disciplines and for their integrity with other branches of science, could serve as the stimulus for intellectual growth of students. An academic baccalaureate program with a major in pharmaceutical sciences as the required base for professional education is proposed as a remedy.

This article presents a stepwise approach for conducting a meta-analysis of epidemiological studies based on proposed guidelines. This systematic method is recommended for practitioners evaluating epidemiological studies in the literature to arrive at an overall quantitative estimate of the impact of a treatment. Bendectin is used as an illustrative example. Meta-analysts should establish a priori the purpose of the analysis and a complete protocol. This protocol should be adhered to, and all steps performed should be recorded in detail. To aid in developing such a protocol, we present methods the researcher can use to perform each of 22 steps in six major areas. The illustrative meta-analysis confirmed previous traditional narrative literature reviews that Bendectin is not related to teratogenic outcomes in humans. The overall summary odds ratio was 1.01 (χ² = 0.05, p = 0.815) with a 95 percent confidence interval of 0.66–1.55. When the studies were separated according to study type, the summary odds ratio for cohort studies was 0.95 with a 95 percent confidence interval of 0.62–1.45. For case-control studies, the summary odds ratio was 1.27 with a 95 percent confidence interval of 0.83–1.94. The corresponding chi-square values were not statistically significant at the p = 0.05 level.