Ondansetron in the treatment of intractable nausea associated with theophylline toxicity.

OBJECTIVE: To report the efficacy of ondansetron in the treatment of a patient poisoned with theophylline. PATIENT: A 36-year-old man who ingested 6 g of sustained-release theophylline. INTERVENTION: Ondansetron 8 mg intravenously after clinical failure of other antiemetics. RESULTS: Subjective relief of nausea within minutes, enabling the patient to tolerate multiple doses of activated charcoal and whole bowel irrigation. CONCLUSIONS: Ondansetron may offer an alternative to present antiemetic therapy in the poisoned patient.

Current trends in the pharmacotherapy for gastroesophageal reflux disease.

Medical therapy for gastroesophageal reflux disease should entail a multistep approach. After life-style changes, many patients will require histamine2 receptor antagonists in conventional doses with repeated therapeutic courses, if not continuous maintenance. Prokinetic agents are potentially useful in those patients with impaired motor function of the esophageal or gastric smooth muscle. Combination therapy with histamine2 receptor antagonists and prokinetic agents or sucralfate provides modest healing benefit, if any, over that by histamine2 receptor antagonists alone. For patients with more severe refractory disease, omeprazole has provided unequaled healing rates and accelerated symptomatic relief. High-dose (twofold or more standard dose) histamine2 receptor antagonist therapy may also heal high-grade esophagitis, but the reported experience is small. After healing is achieved, an attempt should generally be made to "step down" therapy to standard-dose histamine2 receptor antagonist as maintenance. Finding the least amount of drug to control symptoms and maintain the integrity of the esophageal mucosa would minimize cost and potential long-term risk.

Current trends in the pharmacotherapy for peptic ulcer disease.

A variety of options are available for the medical treatment of peptic ulcer disease, including antacids, histamine2 receptor antagonists, omeprazole, prostaglandin analogues, and sucralfate and bismuth formulations. Seventy percent to 90% of peptic duodenal and gastric ulcers will heal after 4 to 8 weeks of therapy. Combination regimens using these agents have not been demonstrated to be superior to single-agent therapy. Aggressive acid suppression with "high-dose" histamine2 receptor antagonists or omeprazole accelerates healing of ordinary ulcers and promotes healing of previously refractory ulcers. Although ulcer recurrence is diminished by continuous "maintenance" therapy with the aforementioned agents, recurrence seems to be dramatically suppressed after eradication of Helicobacter pylori from the gastroduodenal mucosa.

Attitudes among Department of Veterans Affairs pharmacists toward postgraduate education and training.

The results of a survey of the attitudes of Department of Veterans Affairs (VA) pharmacists toward postgraduate education and training are reported. In January 1990 an anonymous questionnaire was mailed to 800 randomly selected VA pharmacists. The mailing occurred one month after the announcement of new policies for recruiting and retaining VA pharmacists that allow salaries to be determined on the basis of education, job responsibilities, publishing, and other professional activities and accomplishments. Recipients were asked to provide educational and demographic data, information on their work settings and job responsibilities, and their perceptions of the benefits of and barriers to additional education and training. Of the 800 questionnaires mailed, 310 (38.8%) usable responses were received. The majority (77%) of the pharmacists held B.S. degrees only. One-day to one-week training programs had been attended by 74.5% of the respondents; at least 61.6% desired to attend such programs, and many indicated the desire to attend longer training programs. Some 48.3% of the B.S.-level pharmacists had expressed an interest in earning another pharmacy-related degree. More than 40% of the respondents saw time, money, and the location of programs as barriers. Perceived benefits included personal development, enhanced job satisfaction, and improved patient care; only 1.9% perceived no benefit. Seventy-seven percent believed that salary should reflect the level of professional training. VA pharmacists desire additional education and training and believe that such programs may enhance patient care and reduce staff turnover.

Concurrent review of the duration of antimicrobial prophylaxis in surgery.

The administration of prophylactic antibiotics in surgery is appropriate for many patients. Data have shown extending the duration of prophylaxis beyond 48 hours does not lower the rate of postoperative-infection. The purpose of this project was to concurrently assess the duration of prophylactic antibiotic use. A total of 95 patients were monitored over 3 weeks. Eighty patients (84.2%) received antimicrobial therapy. In 23 of these patients (28.75%) the duration of antibiotic administration was longer than 2 days without clinical or microbiological evidence of infection. In 5 other patients only postoperative antibiotics were prescribed. The cost difference between the actual duration of antibiotic administration and 2 days of the same regimen was +1,364.58. Extrapolating for one year, it can be estimated that antibiotic costs could be reduced about +23,600. Pharmacists can focus on the duration of antibiotic prophylaxis as a cost containment measure.

The effect of sucralfate on the steady-state serum concentrations of phenytoin.

The effect of sucralfate on steady-state phenytoin concentrations was evaluated in 6 normal volunteers. The subjects took phenytoin at bedtime until steady-state was confirmed (8 to 9 days) and then took in addition sucralfate 1g four times daily for a further 7 days. Serum phenytoin concentrations were measured on days 1, 3, and 7 of sucralfate administration. Measured phenytoin concentrations were 10.9 +/- 3.0 mcg/ml and 11.0 +/- 3.1 mcg/ml before sucralfate and 10.8 +/- 3.1 mcg/ml, 11.4 +/- 3.2 mcg/ml, and 11.1 +/- 2.5 mcg/ml during sucralfate administration (p greater than 0.05; ANOVA). These results suggest there is not a significant drug interaction between sucralfate and phenytoin.

Lipid and lipoprotein changes during the seven days off oral contraception in women using two triphasic preparations.

This study was designed to determine whether mean values for lipids and lipoproteins changed during the 21 days on oral contraceptive (OC) preparations and during the seven days off the pills. The design allowed for comparison of the effects of Triphasil and Ortho 777 and for examining the consistency over two pill cycles. The mean values for total cholesterol, HDL-cholesterol, LDL-cholesterol and HDL3-subfraction were consistently lower on Day 20 when compared to Day 2 (p less than 0.05) for the two cycles and higher on Day 2 of Cycle II when compared to Day 20 of Cycle I. This fall-rise-fall pattern was consistent for cholesterol in 17 out of 28 of the women studied and these women were heavier (p less than 0.05), had a greater mean Quetelet Index (p less than 0.05) and had been using OCs for a shorter mean period of time (p less than 0.05). Consistently higher apolipoprotein A1 mean values were found on Day 20 of both cycles for Triphasil users compared to Ortho 777 users (p less than 0.02). This paper discusses the importance of these findings in relation to study design when measuring for differences between OC preparations and changes over time.

PIP: This study was designed to determine whether mean values for lipids and lipoproteins changed during the 21 days on oral contraceptives (OCs) and during the 7 days off the pill. The design allowed for comparison of the effects of Triphasil and Ortho 777 and for examining the consistency over 2 pill cycles. The mean values for total cholesterol, HDL-cholesterol, LDL-cholesterol, and HDL3-subfraction were consistently lower on day 20 when compared to day 2 (P0.05) for the 2 cycles and higher on day 2 of cycle 2 when compared to day 20 of cycle 1. This fall-rise-fall pattern was consistent for cholesterol in 17 of 28 women studied and these women were heavier (P0.05), had a greater mean Quetelet Index (P0.05), and had been using OCs for a shorter mean period of time (P0.05). Consistently higher apolipoprotein Al mean values were found on day 20 of both cycles for Triphasil users compared to Ortho 777 users (P0.02). This paper discusses the importance of these findings in relation to study design when measuring for differences between OCs and changes over time.

Time course of gentamicin serum concentration rebound following hemodialysis.

The rebound in gentamicin serum concentration following hemodialysis was studied in six patients with chronic renal failure. The patients were not infected at the time of the study and received a single dose of gentamicin 2 mg/kg before hemodialysis. Serum samples were obtained immediately after dialysis and at 0.5, 1, 2, and 3 hours following hemodialysis. The average increases in gentamicin serum concentrations were 3.6 percent at 0.5 hour, 12.6 percent at 1 hour, and 6.6 percent at 2 hours. An average decline of 4.2 percent occurred at three hours. Only the increase seen at one hour was significantly different from the gentamicin serum concentration immediately following hemodialysis. This rebound was of small magnitude, though, and may not be clinically significant.

Digoxin-diltiazem interaction: a pharmacokinetic evaluation.

The pharmacokinetics of digoxin were studied before and after a 2 week course of diltiazem, 30 mg four times daily, in 7 healthy volunteers. Each subject received an IV dose of digoxin before starting diltiazem and again on day 15 of the study. Diltiazem was continued until all sera and urine were collected. During the control and diltiazem phases, respectively, the terminal elimination rate constants were 0.0231 +/- 0.007 h-1 and 0.0254 +/- 0.007 h-1, the volumes of distribution were 10.5 +/- 3.95 l/kg and 10.2 +/- 3.26 l/kg, and the total body clearances were 3.72 +/- 0.78 ml X min-1 X kg-1 and 4.09 +/- 0.94 ml X min-1 X kg-1. None of these pharmacokinetic parameters of digoxin were significantly different before or during diltiazem administration. Overall, there does not appear to be an interaction between digoxin and diltiazem.

Theophylline serum concentrations in ambulatory patients with chronic obstructive pulmonary disease.

A two-part study was designed to investigate the application of theophylline serum concentration data at a Veterans Administration Medical Center. The investigation was unique in its use of ambulatory patients instead of hospitalized patients as study subjects for assessing the use of laboratory tests. As has been found in other studies that examined different drugs and involved hospitalized subjects, this investigation discovered significant problems in the ordering, application, and documentation of these data when judged against established criteria. There was no significant difference in the appropriate use of these drugs between physicians specializing in pulmonary versus general medicine. Of clinical importance also are the findings that confirm a positive correlation between the proper use of these tests and improvement in patient outcome, and the demonstrated relationships between clinical symptoms and subtherapeutic and toxic serum concentrations of theophylline.