Nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications today. Although their exact mechanism of action is unclear, inhibition of prostaglandin synthesis contributes significantly to their analgesic, anti-inflammatory, antipyretic, and antiplatelet effects. In recent years, additional mechanisms of action have been proposed for NSAIDs, and these may explain the variability commonly noted in patient response and tolerability to individual NSAIDs. NSAID therapy is not without risk, and serious adverse effects involving the gastrointestinal tract, kidneys, blood, and liver have been reported.

Administration guidelines for parenteral drug therapy. Part II: Adult patients.

This two-part review covers the specifics of intravenous dosing of medications as they pertain to pediatric and adult patients. Part I provides the complete introduction and references used for both parts (Journal of Pharmacy Technology 1989; 5:101-27).

Adverse effects of hypolipidaemic drugs.

Cholestyramine, colestipol, clofibrate, gemfibrozil, nicotinic acid (niacin), probucol, neomycin, and dextrothyroxine are the most commonly used drugs in the treatment of hyperlipoproteinaemic disorders. While adverse reaction data are available for all of them, definitive data regarding the frequency and severity of potential adverse effects from well-controlled trials using large numbers of patients (greater than 1000) are available only for cholestyramine, clofibrate, nicotinic acid and dextrothyroxine. In adult patients treated with cholestyramine, gastrointestinal complaints, especially constipation, abdominal pain and unpalatability are most frequently observed. Continued administration along with dietary manipulation (e.g. addition of dietary fibre) and/or stool softeners results in diminished complaints during long term therapy. Large doses of cholestyramine (greater than 32 g/day) may be associated with malabsorption of fat-soluble vitamins. Most significantly, osteomalacia and, on rare occasions, haemorrhagic diathesis are reported with cholestyramine impairment of vitamin D and vitamin K absorption, respectively. Paediatric patients have been reported to experience hyperchloraemic metabolic acidosis or gastrointestinal obstruction. Concurrent administration of acidic drugs may result in their reduced bioavailability. Serious adverse reactions to clofibrate will probably limit its role in the future. Of particular concern are ventricular arrhythmias, induction of cholelithiasis and cholecystitis, and the potential for promoting gastrointestinal malignancy which far outweigh the reported benefits in preventing new or recurrent myocardial infarction, cardiovascular death and overall death. Patients with renal disease are particularly prone to myositis, secondary to alterations in protein binding and impaired renal excretion of clofibrate. Drug interactions with coumarin anticoagulants and sulphonylurea compounds may produce bleeding episodes and hypoglycaemia, respectively. Nicotinic acid produces frequent adverse effects, but they are usually not serious, tend to decrease with time, and can be managed easily. Dermal and gastrointestinal reactions are most common. Truncal and facial flushing are reported in 90 to 100% of treated patients in large clinical trials. Significant elevations of liver enzymes, serum glucose, and serum uric acid are occasionally seen with nicotinic acid therapy. Liver enzyme elevations are more common in patients given large dosage increases over short periods of time, and in patients treated with sustained release formulations.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of three algorithms used to evaluate adverse drug reactions.

The consistency of three algorithms in evaluating adverse drug reactions (ADRs) was studied. As part of a hospital's ADR protocol, doctor of pharmacy students were required to collect and summarize all ADR data. Algorithms by Kramer, Naranjo, and Jones were used to evaluate all ADRs between January and May 1984. Kramer's algorithm was used for every reported ADR; Naranjo's and Jones' algorithms were used to check consistency in scoring among ADRs already scored with the Kramer algorithm. The two numerical scales (Kramer and Naranjo) were compared using linear regression. The results of all three algorithms were translated into categories of suspicion (A = definite or probable; B = probable; C = possible; and D = unlikely, doubtful, or remote) and evaluated for consistency with a weighted kappa (kw) statistical test. A total of 28 ADRs were evaluated, and the correlation (r = 0.87) between the total numerical scores of the Kramer and Naranjo algorithms was significant. Comparison of the Kramer and Naranjo algorithms showed 67% agreement with a kw value of 0.43 (-1 = perfect disagreement and +1 = perfect agreement). Similarly, there was 67% agreement (kw = 0.48) between Kramer's algorithm and Jones' algorithm. Agreement between Naranjo's and Jones's algorithms was 64%, but the kw value was only 0.28. The simpler and less time-consuming Naranjo algorithm compared favorably with the Kramer algorithm in scoring ADRs; more data are needed to support the use of the Jones algorithm.

Program coordinated by a drug information service to improve adverse drug reaction reporting in a hospital.

A program coordinated by a drug information service to improve adverse drug reaction (ADR) reporting in a hospital is described. At a 520-bed teaching hospital, the drug information service was asked to design a new adverse drug reaction reporting system that would encourage clinicians to report ADRs. A new system was implemented on a general medical unit: A physician, pharmacist, or nurse telephoned the drug information service when an adverse drug reaction was suspected, and drug information personnel followed up on the report, completing all subsequent investigation and documentation. A standard algorithm was used to evaluate causality of the reported reactions. Pertinent data were entered on a form and retained in the drug information service. The primary physician's approval was obtained before a reaction could be reported on an FDA drug-experience form. Drug information service personnel reviewed the ADR data monthly to detect any trends that clinicians should be aware of and to prepare a report for the pharmacy and therapeutics committee. Nurses, physicians, and pharmacy personnel were oriented to the new system before its implementation and were subsequently informed about reported ADRs and use of the system through newsletters and meetings. In the initial three-month period, 23 ADRs involving 19 drugs were reported from the medical unit; in a six-month period before development of the new system, no ADRs had been reported. This ADR reporting system developed and implemented by the drug information service was effective in improving reporting of adverse drug reactions.

Induction of hemolytic anemia by nonsteroidal antiinflammatory drugs.

The incidence of immune hemolytic anemia (IHA) is increasing. The proliferation of pharmaceuticals is a contributing factor to this increase. IHA is an uncommon, though significant, adverse effect of a wide variety of drugs. Several recent case reports have implicated the nonsteroidal antiinflammatory drugs (NSAIDs). Because of the extensive use of this class of drugs, a review of case reports, clinical studies, and in vitro research was conducted on NSAID-induced IHA. Mefenamic acid, ibuprofen, sulindac, naproxen, tolmetin, feprazone, and aspirin are reported to cause IHA, with mefenamic acid most frequently implicated. Mefenamic acid appears to cause hemolytic anemia by an autoimmune mechanism similar to methyldopa and aspirin by an immune complex mechanism. However, there is insufficient information concerning ibuprofen, sulindac, naproxen, tolmetin, and feprazone to assign specific mechanisms of immune hemolysis. In individuals with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, aspirin at usual therapeutic doses is not a predisposing factor to hemolysis unless other risk factors are present. Although individuals with G-6-PD deficiency are at increased risk of developing hemolytic anemia when exposed to oxidizing stresses, the use of NSAIDs does not appear to increase this risk significantly. Because NSAID-induced IHA occurs infrequently and the sensitivity of currently used tests to detect drug-dependent antibodies is limited, routine serologic testing in patients receiving NSAIDs is not justified. If hemolytic anemia occurs in a NSAID-treated patient and the history is consistent with a drug-induced etiology, the NSAID should be discontinued. With discontinuation of the offending agent, the prognosis is good. There is a rapid hematologic recovery, with a slow resolution of abnormal serologic findings.

Drug information quality assurance program used to appraise students' performance.

A quality assurance program developed for a drug information service was used to objectively measure the performance of doctor of pharmacy degree students on rotation in the service. Two five-point rating scales based on objective criteria were developed so that judgmental and nonjudgmental drug information responses could be evaluated separately. Preceptors used the scales to evaluate 30 randomly selected responses from each of 22 Pharm.D. students (15 responses from midrotation and 15 from the end of the rotation). Written responses were also evaluated on a five-point scale by the requesters. In all of the evaluations, a score of 5 was excellent and a score of 1 was unacceptable. The preceptors assigned a score of 5 to 52.3% of the 660 responses evaluated, 4 to 29.1%, 3 to 12.9%, 2 to 4.5%, and 1 to 1.2%. No significant difference was found based on the academic quarter during which the rotation took place. The difference in scores between judgmental and nonjudgmental responses was not significant. End-of-rotation scores tended to be higher than midrotation scores, although the difference was not significant. Testing for interrater reliability revealed moderate agreement between raters. Requesters gave mean scores higher than 4 for accuracy, completeness, objectivity, and usefulness of the written responses. Timeliness scores were significantly lower but still acceptable. A drug information quality assurance program provided a structured, objective means of evaluating student performance.

Sexually transmitted diseases: an update.

Although the 1993 CDC treatment guidelines for STDs contained relatively few changes from the 1989 guidelines, some recently marketed medications now appear in the list of recommended and alternative treatment regimens. Pharmacists must consider differences in dosage formulations (intramuscular versus oral), cost, and length of treatment when choosing the antibiotic or antiviral to be listed in a hospital or managed care formulary. Additionally, pharmacists should recognize that some STD therapies are now given once daily instead of in a 7-day course. When an antibiotic or antiviral prescription order is presented, pharmacists should determine why the patient is receiving this therapy. Verifying the disease process will help the pharmacist counsel the patient on the therapy. In some instances, therapy may be appropriately administered in the emergency room or the pharmacy, to ensure that the patient complies with the medication regimen. Verifying compliance will be especially important for patients who are expected to ingest only one dose, rather than a seven-day course of therapy. By initiating such programs, pharmacists can help prevent drug-resistance problems and ensure compliance.

Selective use of online literature searching by a drug information service.

The use of online searching in a drug information center on a regular but selective basis is described. Of 90-100 information requests received monthly in a university-affiliated drug information center located within the health sciences library, five to eight computer searches are performed. All other questions are answered using a manual search. The computer searches are conducted by a medical librarian who works closely with the pharmacist. For each search, the library charges the drug information center for at least 12 minutes of connect time; charges cover the library's direct costs only. The drug information center is staffed by a director and assistant director; in addition, Pharm.D. students and clinical pharmacy residents work there. Factors influencing the decision to do an online rather than a manual search include budgetary constraints, how quickly an answer is needed, the success of a preliminary manual search, and the complexity of the request. Considerations for conducting online searches through a library rather than by the staff of the drug information center include requisite search skills, costs, and accessibility to computer search services. The selective use of online searches through a health sciences library is a viable means of accessing online information in a drug information center that cannot support its own online literature-retrieval system.

Drug information centers: ASHP's role and effect of clinical pharmacy.

The role of the American Society of Hospital Pharmacists in fostering the drug information movement is described, and the effects of clinical pharmacy practice on drug information centers are outlined. ASHP has been an early and consistent supporter of the pharmacists' role in providing drug information. In 1968 the Society adopted a statement that outlined the role and expected competencies of drug information specialists. Accreditation standards for specialized residencies in drug information practice were adopted in 1982. On a broad scale, drug information pharmacists foster rational drug therapy through input on pharmacy and therapeutics committees. In general, when decentralized drug distribution and clinical pharmacy services are implemented in a hospital, the number of questions asked of a drug information center decreases, but the type of question changes. Drug information pharmacists working with clinical pharmacists provide a communication system for providing other health-care practitioners with information necessary for optimal drug therapy in particular patients. To increase the efficiency of drug information centers, drug information pharmacists must incorporate computer technology into their practice sites.

Evaluation of patient medication counseling sources.

Seven sources of information on patient medication counseling were evaluated. Each source was reviewed for inclusion of five types of information on 20 drugs selected randomly from the top 200 prescription drugs. The ASHP's Medication Teaching Manual was the most complete source in terms of including the largest number of sample drugs. Apelgren and Rowles's Handbook for Counseling Patients on Their Medications, Griffith's Drug Information for patients, Maudlin and Young's Drug Consultation Guide, and Smith's Medication Guide for Patient Counseling were nearly as complete in this regard. In terms of including information in each of the five categories for the sample drugs, the U.S. Pharmacopeia Dispensing Information and the Medication Teaching Manual ranked highest. Cost, size, format, and indexing of the sources are compared, and special features and limitations of the source are presented. All the publications are at least adequate patient counseling sources, although some are more complete and thorough than others.

Prospective cost analysis of moxalactam versus clindamycin plus gentamicin for endomyometritis after cesarean section.

The direct and indirect costs associated with either moxalactam or clindamycin plus gentamicin as treatment for endomyometritis after emergent cesarean section were compared in an open, randomized prospective trial of 114 patients. A total of 58 patients were assigned to receive moxalactam, 2 g intravenously (i.v.) every 8 h for 5 doses, followed by 2 g every 12 h and prophylactic vitamin K (10 mg) intramuscularly, and 56 patients were assigned to receive clindamycin (600 mg) i.v. every 6 h plus gentamicin (1.5 mg/kg) i.v. every 8 h. Prothrombin times were measured in moxalactam-treated patients, and patients treated with clindamycin plus gentamicin had urinalyses and blood urea nitrogen and serum creatinine determinations performed before and after treatment. Also, gentamicin levels in serum were determined as clinically indicated. A satisfactory treatment response was defined as the resolution of signs and symptoms of endomyometritis within 3 days of the start of antibiotic therapy. Satisfactory responses were demonstrated in 78% of the moxalactam-treated patients and 84% of patients treated with clindamycin plus gentamicin. Mean hospital costs for laboratory tests ($30.30 versus $4.53) and mean patient charges for laboratory tests ($76.39 versus $27.81) and medications ($539.45 versus $421.82) were significantly higher in patients treated with clindamycin plus gentamicin (P less than 0.05), while mean medication costs to the hospital were greater in the moxalactam group ($255.47 versus $195.68; P less than 0.05). However, total patient charges and total hospital drug-associated costs were not significantly different for the two group. In this tudy, moxalactam was similar in efficacy and, despite its higher acquistion cost, was comparable in total hospital costs and patient charges to clindamycin plus gentacmicin in treating endomyometritis.

Update and review of chemonucleolysis.

To update the status of chymopapain in the treatment of herniated intervertebral discs, a review of the current literature and data from an unpublished Texas study are presented. Studies in animals and humans have consistently demonstrated that chymopapain can dissolve the nucleus pulposus. Twenty-eight uncontrolled and unblinded clinical trials involving 2845 patients showed a positive response rate of 75%. Side effects occurred in 2.4% of chymopapain-treated patients. Anaphylaxis, the most serious adverse reaction associated with chemonucleolysis, was noted in less than 1% of patients. No deaths were reported. The first double-blind, placebo-controlled study of chymopapain in the United States demonstrated no significant efficacy, but both the design and execution of the study have been criticized. Two recent double-blind, placebo-controlled studies showed success rates of 73% and 80% for chymopapain, significantly higher than for placebo treatment. Postinjection back pain and muscle spasm were the most common side effects related to chymopapain administration in one of the trials. In the uncontrolled Texas study the success rate in 408 patients treated by chymopapain was 93%. Chemonucleolysis has achieved a success rate comparable with that of surgery in the treatment of symptomatic herniated discs. Appropriate use of chymopapain can result in substantial savings in time and hospital costs.

Drug utilization review of sedative/hypnotic agents in Texas Medicaid patients. Texas Medicaid Vendor Drug Program Drug Utilization Review Board.

OBJECTIVE: To assess use of sedative/hypnotic agents in Texas Medicaid patients and evaluate practitioner receptiveness to intervention letters concerning sedative/hypnotic prescribing generated by the Texas Medicaid Drug Utilization Review (DUR) Board. DESIGN: Retrospective DUR. SETTING: Texas Medicaid retrospective DUR program. PATIENTS OR OTHER PARTICIPANTS: 244 Texas Medicaid patients and 291 Texas physicians. INTERVENTION: Patient profiles for Texas Medicaid patients were reviewed retrospectively to quantify sedative/hypnotic prescribing practices. Intervention letters were prepared and sent to physicians directly involved in the care of patients receiving excessive sedative/hypnotic therapy. Physician responses were categorized based on information presented in the intervention letter and circumstances surrounding the identified patient. Prescribing practices were assessed approximately 1 year after the intervention to determine the impact of intervention letters on prescribing. MAIN OUTCOME MEASURE: Physician response to intervention letter. RESULTS: Responses were received from 208 of 291 physicians (71.5%). Approximately 40% of physicians agreed in principle with the suggestions offered by the Texas Medicaid DUR Board to minimize chronic sedative/hypnotic use. Almost one-half of these physicians had discontinued sedative/hypnotic therapy for the identified patients 1 year after the intervention. Approximately 9% justified continued sedative/hypnotic use based on patient diagnosis or refractory response to treatment, and 55 physicians (26.4%) were unwilling to alter therapy because of patient-specific factors. CONCLUSION: Through the use of retrospective DUR, Texas Medicaid patients receiving excessive amounts of sedative/hypnotic agents were identified and improvements in sedative/hypnotic therapy were initiated. DUR can be useful not only in identifying problem areas, but also in encouraging physicians to modify prescribing practices through educational means.

Improving access to computer-based library and drug information services in patient-care areas.

A project to increase access to drug and biomedical information through electronic linkage of drug information and library services to three patient-care areas is described. In February 1987, microcomputer work stations were installed in the Bexar County Hospital District's hospital emergency department, medical residents' office, and ambulatory-care clinic, as well as in The University of Texas Health Science Center's library reference area and drug information service office. Drug information was available on compact disk through the Micromedex Computerized Clinical Information System (CCIS) database, which includes DRUGDEX, POISINDEX, EMERGINDEX, and IDENTIDEX. Each work station was also connected to the library's computer via modem, allowing access to the Library Information System, books, journals, audiovisual materials, miniMEDLINE, and an electronic mail system. During the six-month project, the system was used 5487 times by 702 people. The system was successful in providing drug and other information in clinical settings and in introducing clinical staff members to new information technology. To increase access to the system after the project ended, the CD-ROM version was discontinued, and the distributed tape version of CCIS for VAX computers was added to the library's online information system, making drug information more available throughout the campus and teaching hospitals. In 1988-89 an average of 200 people accessed the tape version of CCIS each month. Although it is difficult to replace the convenience of an onsite library, at least some drug and biomedical information needs in the clinical setting can be met through computer networking.

P & T committee review of misoprostol: prevention of NSAID side effects is key--roundtable discussion.

Misoprostol, a prostaglandin of the E series, was recently introduced for the prevention of NSAID-induced gastric ulcers. Misoprostol was classified as "1A" (denoting a new chemical entity that is a significant therapeutic advance) for purposes of review priority by the Food and Drug Administration in 1988. A dosage of 200 micrograms qid is recommended for prophylaxis, for the duration of NSAID therapy. Misoprostol is generally well-tolerated, with some patients reporting diarrhea. Misoprostol should not be given to pregnant women because of its uterotonic effects. (Please see full prescribing information for a discussion of the safety profile of misoprostol.) Because of the magnitude of the problem of NSAID-induced gastric ulceration and the expense of treatments and hospitalizations, the use of misoprostol in preventing these ulcers should be clinically beneficial, and may contribute to significant cost savings in the hospital and other managed-care settings.