bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of Tranquilizer Use among Australian Vietnam War Veterans
Authors: Alderman Christopher P , Gilbert Andrew L , Condon John T
Published: June 2003

OBJECTIVE:

To examine characteristics of tranquilizer use in a cohort of Australian Vietnam War veterans.

DESIGN:

Prospective analysis of medication use and assessment of social and clinical variables, including tranquilizer dependence.

PATIENTS:

Fifty-one Australian Vietnam War veterans were recruited from the department of psychiatry of an Australian teaching hospital. All subjects were men, with a mean ± SD age of 52.2 ± 3.3 years.

MAIN OUTCOME MEASURES:

A structured interview was used to obtain details of medical and psychiatric history, medication use, substance use, forensic history, and health service utilization data. Anxiety was assessed using the Hamilton Anxiety Rating Scale (Ham-A). A validated tranquilizer dependence rating scale was administered for each patient.

RESULTS:

Commonly used tranquilizers included diazepam (n = 19 patients) and zopiclone (26). Most patients (44) reported the use of one or more drugs for the purpose of nighttime sedation, while exclusive daytime use of tranquilizers for anxiolytic effect was uncommon. The median time spent in the hospital during the preceding year was 21.0 ± 56.8 days. Symptoms of anxiety were prevalent, with a mean Ham-A score of 35.5 ± 7.8. Screening criteria suggestive of tranquilizer dependence were met in 34 subjects. Health service utilization was correlated with tranquilizer intake and overall medication use. Tranquilizer dependence was independently associated with cigarette smoking (p = 0.039; odds ratio = 5.13, 95% CI 1.08 to 24.33).

CONCLUSIONS:

This study provides insight into the nature of tranquilizer use in an Australian population of Vietnam War veterans. The extensive use of these drugs suggests that further research and possibly intervention in this area is needed.
Leukotriene Receptor Antagonists in the Treatment of Allergic Rhinitis
Authors: Maynard Michelle L , Ernst Michael E
Published: June 2003

OBJECTIVE:

To review the literature examining the clinical use of leukotriene receptor antagonists in the treatment of allergic rhinitis.

DATA SOURCES:

Biomedical literature accessed through MEDLINE (1990–November 2000) and Current Contents (week 35 of 1999 to week 48 of 2000). Key terms included leukotriene antagonists, montelukast, zafirlukast, and rhinitis (allergic).

DATA SYNTHESIS:

Preliminary evidence on the clinical use of either montelukast or zafirlukast as monotherapy is equivocal, with one study noting benefit and another noting lack of benefit in symptom amelioration. A third study suggests that these agents may have a role in further modifying allergic rhinitis symptoms when used in combination with standard treatments.

CONCLUSIONS:

Future large-scale studies should assess the efficacy of these agents in the treatment of allergic rhinitis, in particular, to identify subsets of patients likely to derive the most benefit. Available data suggest it is reasonable and safe to add these agents to standard therapy if symptomatology remains unresolved.
Desensitization Protocols for Vancomycin Hypersensitivity
Authors: Wazny Lori D , Daghigh Behnam
Published: June 2003

OBJECTIVE:

To discuss the pathophysiology of vancomycin-induced immediate hypersensitivity reactions, review the process of vancomycin desensitization, and provide specific directions for ordering and preparing rapid and slow desensitization protocols.

DATA SOURCES:

A MEDLINE search (1966–February 2001) of English-language literature pertaining to vancomycin desensitization and hypersensitivity reactions was performed. Tertiary sources were also used.

DATA EXTRACTION:

Published clinical studies and case reports.

DATA SYNTHESIS:

The pathophysiology of vancomycin-induced hypersensitivity reactions is discussed along with the procedure of vancomycin desensitization. Desensitization should be considered in Red Man syndrome (RMS) that does not respond to the usual treatment measures, and in vancomycin-induced anaphylaxis. Rapid desensitization is preferred as it is effective in the majority of patients and enables therapeutic dosing of vancomycin within 24 hours. In patients who fail rapid desensitization, a slow desensitization protocol may be tried.

CONCLUSIONS:

Vancomycin-induced immediate hypersensitivity reactions include RMS and anaphylaxis. Vancomycin desensitization should be considered for severe RMS reactions not responding to usual measures and in anaphylactic reactions to vancomycin, when substitution of another antibiotic is not feasible.
The Debate regarding Continuous Use of Oral Contraceptives
Authors: Clarke Amanda K , Miller Sarah J
Published: June 2003

OBJECTIVE:

To determine whether oral contraceptives (OCs) can be used safely in a continuous manner to prevent monthly withdrawal bleeding.

DATA SOURCES:

Search of MEDLINE (1966–2000), International Pharmaceutical Abstracts (1970–2000), and the Internet.

DATA SYNTHESIS:

Several prospective studies have assessed the efficacy of continuous cycle OCs in preventing monthly withdrawal bleeding. Monophasic OCs are useful for this purpose. In studies using traditional OC regimens as a control, patients receiving continuously administered OCs experienced more breakthrough bleeding and spotting. Continuous use of OCs decreased headache and other menstruation-associated symptoms. No long-term trials have assessed the impact of continuous use of OCs on risk of cancer, thromboembolic disease, or fertility, concerns raised by opponents of the method.

CONCLUSIONS:

From the data available, continuous use of OCs is an effective method for delaying withdrawal bleeding. Long-term safety data are not available.
Photopatch Testing in Seven Cases of Photosensitive Drug Eruptions
Authors: Lee Ai-Young , Joo Hyun-Joong , Chey Won-Young , Kim Young-Gull
Published: June 2003

OBJECTIVE:

The most important goal in the management of photosensitive drug eruptions, as in other types of drug eruptions, is identification of the causative drugs to prevent reexposure to them.

CASE SUMMARIES:

Seven patients whose lesions were mainly distributed on sun-exposed areas underwent laboratory tests, phototests, and photopatch tests with suspected drugs. Phototests were done with ultraviolet A (UVA), UVB, and visible light. Drugs used in the photopatch tests were usually prepared as 10% concentrations in petroleum base, which did not produce reactions in 10 control subjects, followed by irradiation of suberythema doses of UVA. Systemic provocation by oral administration of small doses of causative drugs with irradiation of suberythema doses of UVA was performed to confirm the results of skin tests in four patients. Two patients were not rechallenged with the causative drugs. None of the patients had systemic lupus erythematosus, porphyria, or pellagra. All showed positive reactions to photopatch testing. Systemic provocation confirmed the results of photopatch tests in four patients. The two patients who were not rechallenged had no recurrence of lesions. One patient ingested only one drug at the time of eruptions, and provocation or avoidance was not attempted. A photoallergic mechanism was considered in five cases.

CONCLUSIONS:

Although there is no information about the appropriate concentrations or vehicles for suspected drugs, photopatch testing could be reliable for identification of causes of photosensitive drug eruptions. Besides piroxicam (a well-known photosensitizer) and carbamazepine, isoniazid and triflusal were identified as the causes of the reactions.
Fatal Fetal Outcome with the Combined Use of Valsartan and Atenolol
Authors: Briggs Gerald G , Nageotte Michael P
Published: June 2003

OBJECTIVE:

To report a case of anhydramnios, pulmonary hypoplasia, very small placenta, and fetal death in a pregnancy complicated by chronic hypertension and diabetes mellitus that had been treated through the first 24 weeks of gestation with valsartan and atenolol.

CASE SUMMARY:

A 40-year-old Hispanic woman with well-controlled chronic hypertension and diet-controlled type 2 diabetes mellitus was treated with valsartan and atenolol until pregnancy was diagnosed at 24 weeks' gestation. An ultrasound examination revealed normal fetal growth and anatomy but anhydramnios (amniotic fluid index 0). Valsartan was discontinued, and amniotic fluid volume normalized within two weeks. Intrauterine fetal death was documented at 33 weeks' gestation. Labor was induced, with the delivery of a stillborn female fetus with small, hypoplastic lungs (weight 41% of expected) and an extremely small, 148-g placenta (weight 48% of the 10th percentile for gestational age).

DISCUSSION:

The use of valsartan, a selective angiotensin II receptor antagonist (ARA), in human pregnancy has not been reported, but this class of agents would be expected to cause fetal toxicity similar to that observed with angiotensin-converting enzyme inhibitors. This toxicity includes reduced perfusion of the fetal kidneys, resulting in anuria, oligohydramnios, and subsequent pulmonary hypoplasia. The small hypoplastic lungs and very small placenta were probably a consequence of valsartan and atenolol combination therapy.

CONCLUSIONS:

Resolution of anhydramnios after discontinuing valsartan is evidence for ARA-induced fetal toxicity. The pulmonary hypoplasia observed in the stillborn infant was a direct result of the severe oligohydramnios. The cause of fetal death nine weeks later is uncertain, but because the woman's chronic hypertension and diabetes were well controlled, we believe the primary cause was chronic placental insufficiency resulting from the previous combination of valsartan and atenolol.
Fluvoxamine Augmentation Increases Serum Mirtazapine Concentrations Three- to Fourfold
Authors: Anttila Sami AK , Rasanen Ilpo , Leinonen Esa VJ
Published: June 2003

OBJECTIVE:

To report two cases of interaction between fluvoxamine and mirtazapine.

CASE SUMMARY:

A 17-year-old boy was treated with mirtazapine 30 mg/d. The addition of fluvoxamine 100 mg/d to the regimen caused a threefold increase in the mirtazapine concentration. This interaction was associated with increased anxiety. A second patient, a 43-year-old woman, was treated with mirtazapine 15 mg/d. There was a fourfold increase in her mirtazapine concentration and simultaneous mood improvements after augmentation with fluvoxamine 50 mg/d.

DISCUSSION:

This is the first report of any interaction between fluvoxamine and mirtazapine. Mirtazapine is mainly metabolized by cytochrome P450 isoenzymes CYP1A2, CYP2D6, and CYP3A4. Fluvoxamine and cimetidine inhibit the same isoenzymes, but fluvoxamine is probably the only agent that causes a clinically significant interaction.

CONCLUSIONS:

Adding fluvoxamine to treatment with mirtazapine may cause a significant increase in mirtazapine concentration. This interaction may necessitate adjustment of the mirtazapine dosage.
Symptomatic Hyperbilirubinemia with Indinavir/Ritonavir—Containing Regimen
Authors: Rayner Craig R , Esch Lori D , Wynn Heather E , Eales Richard
Published: June 2003

OBJECTIVE:

To report a case of symptomatic hyperbilirubinemia resulting from the addition of ritonavir to an indinavir-containing antiretroviral regimen.

CASE SUMMARY:

A 27-year-old white woman developed symptomatic hyperbilirubinemia and anemia while receiving an indinavir/ritonavir—containing antiretroviral (ARV) regimen that required disruption of therapy. Extensive laboratory examinations were performed including determination of indinavir and ritonavir concentrations. The findings were attributed to two independent processes, an unconjugated hyperbilirubinemia due to indinavir and anemia due to zidovudine.

DISCUSSION:

Indinavir-induced hyperbilirubinemia is generally regarded as an adverse event with no clinical relevance that does not cause significant liver toxicity and does not necessitate discontinuing indinavir. It manifests primarily as an increase in unconjugated bilirubin and is reported to be dose related. We believe that the severe hyperbilirubinemia in this patient was a result of high indinavir concentrations that occurred due to metabolic inhibition caused by ritonavir. The anemia in this case was consistent with erythrocyte maturation arrest due to zidovudine rather than hemolysis.

CONCLUSIONS:

Combination ARV therapy is the current standard of care for treating patients infected with HIV. It is important for providers to consider that, despite much improved pharmacokinetic profiles associated with pharmacokinetically enhanced protease inhibitor regimens, there may be undesirable effects that may differ in frequency or severity than when drugs are used individually.
Hypertension as a Complication of Topical Testosterone Therapy
Authors: Tangredi Joseph F , Buxton Iain LO
Published: June 2003

OBJECTIVE:

To report a patient developing hypertension following the use of testosterone gel.

CASE SUMMARY:

A 65-year-old white man who was placed on topical testosterone therapy to increase libido developed hypertension and increased hematocrit simultaneously. After discontinuation of the testosterone, the hematocrit returned to mid-normal reference range and blood pressure returned to normal; he had been normotensive prior to topical testosterone use.

DISCUSSION:

The popularity of hormone replacement for women for the maintenance of appearance and lifestyle and the prevention of complications such as osteoporosis has been established over several decades, and the complications and risks and benefits of this therapy have been well described. More recently, and particularly with the availability of topical preparations of testosterone, hormone replacement for men is becoming popular with both older male patients and their physicians. We describe a case of hypertension as a complication of the application of topical testosterone and link this adverse effect to the known anabolic effects of testosterone.

CONCLUSIONS:

Clinicians should be cautious in prescribing topical preparations of testosterone for the proper administration by the patient and alert to the development of hypertension in this population at increased risk for cardiovascular events due to their age.
An Unusual Presentation of Sertraline and Trazodone Overdose
Authors: Adson David E , Erickson-Birkedahl Sherrie , Kotlyar Michael
Published: June 2003

OBJECTIVE:

To report an unusual and life-threatening presentation of an overdose of sertraline and trazodone.

CASE SUMMARY:

A patient with a history of depression ingested sertraline 6000 mg and trazodone 1300 mg in a suicide attempt. Twenty-four hours after antidepressant administration, the patient presented with symptoms of selective serotonin-reuptake inhibitor (SSRI) overdose and serotonin syndrome, and later developed an enlarged tongue consistent with angioedema. A compromised airway resulted and endotracheal intubation was necessary. After intubation, the symptoms subsided and the patient recovered.

DISCUSSION:

Although SSRIs and trazodone are generally considered to be relatively safe in single-agent overdose, serious delayed reactions can occur, especially if several agents are involved. In this case the patient initially presented with symptoms typical of an SSRI overdose that did not appear to be exceptionally dangerous. Over time, symptoms consistent with angioedema appeared that necessitated intubation. Although previous reports of angioedema have been reported with SSRIs, this is the first report, to our knowledge, of a presentation this severe.

CONCLUSIONS:

This case demonstrates that overdose with the newer antidepressants can result in unusual and delayed presentations and must be treated with caution.
Exaggerated Levothyroxine Malabsorption Due to Calcium Carbonate Supplementation in Gastrointestinal Disorders
Authors: Csako Gyorgy , McGriff Nayahmka J , Rotman-Pikielny Pnina , Sarlis Nicholas J , Pucino Frank
Published: June 2003

OBJECTIVE:

To describe a patient with primary hypothyroidism in whom ingestion of levothyroxine with calcium carbonate led to markedly elevated serum thyrotropin concentrations.

CASE SUMMARY:

A 61-year-old white woman with primary hypothyroidism, systemic lupus erythematosus, celiac disease, and history of Whipple resection for pancreatic cancer was euthyroid with levothyroxine 175–188 μg/d. After taking a high dose of calcium carbonate (1250 mg three × daily) with levothyroxine, she developed biochemical evidence of hypothyroidism (thyrotropin up to 41.4 mU/L) while remaining clinically euthyroid. Delaying calcium carbonate administration by four hours returned her serum thyrotropin to a borderline high concentration (5.7 mU/L) within a month. Serum concentrations of unbound and total thyroxine and triiodothyronine tended to decrease, but remained borderline low to normal while the patient concomitantly received levothyroxine and calcium carbonate.

DISCUSSION:

Concomitant administration of levothyroxine and calcium carbonate often results in levothyroxine malabsorption. While in most patients the clinical consequences of this interaction, even with prolonged exposure, are relatively small, overt hypothyrodism may develop in patients with preexisting malabsorption disorders. However, as the current case illustrates, the clinical manifestations of the initial levothyroxine deficit may not always be apparent and, of all usual laboratory thyroid function tests, only thyrotropin measurement will reliably uncover the exaggerated levothyroxine malabsorption.

CONCLUSIONS:

Decreased absorption of levothyroxine when given with calcium carbonate may be particularly pronounced in patients with preexisting malabsorption disorders. Once recognized, a change in drug administration schedule usually minimizes or eliminates this interaction.
FDA Labeling System for Drugs in Pregnancy
Authors: Boothby Lisa A , Doering Paul L
Published: June 2003

OBJECTIVE:

To review the current Food and Drug Administration (FDA) pregnancy labeling system, examine the new FDA-proposed pregnancy labeling system for form and content, and provide comments on its suitability for implementation.

DATA SOURCES:

Data were obtained from the FDA's Web site ( www.fda.gov ), PubMed, Federal Register, LexisNexis, Physician's Desk Reference (PDR), Drugdex, and Current Contents.

STUDY SELECTION:

Research and articles involving drugs and pregnancy, drugs and lactation, and the subcommittee meeting of the FDA were included.

DATA EXTRACTION:

Prospective, case-control studies from pregnancy registries.

DATA SYNTHESIS:

Currently, only 40% of drugs in the PDR have pregnancy categories listed. The medical profession has resorted to other means to assess pregnancy risk, such as retrospective chart review, case reports, and consultation with experts such as regional drug information centers.

CONCLUSIONS:

The proposed pregnancy labeling system strives for more clinical usefulness by reliance on human data derived from pregnancy registries. The clinical usefulness of the new labeling remains to be seen.
Stability of Cisplatin, Doxorubicin, and Mitomycin Combined with Ioversol for Chemoembolization
Authors: Mayer Michael I , Weickum Ricke J , Solimando Dominic A , Fileta Bader B , Abdel-Rahim Maged M , Fant Gregory V
Published: June 2003

OBJECTIVE:

To evaluate the chemical stability of a mixture of cisplatin 10 mg/mL, doxorubicin 5 mg/mL, and mitomycin 1 mg/mL in sodium chloride 0.9% (NS), and sodium chloride 0.9% and ioversol 68% (NSI).

METHODS:

The agents were reconstituted with NS and NSI in two groups. One syringe was made and stored protected from light at 4, 25, and 37 °C. Triplicate HPLC determinations were performed on each syringe at each time period. Drug concentration at T0, 4, 12, 24, 72, and 120 hours were recorded.

RESULTS:

Cisplatin in NS remained stable for five days at all three temperatures and lost 12.7% at 37 °C in 120 hours in NSI. Doxorubicin in NS remained stable throughout the five days at 4 and 25 °C, but lost 13.1% at 37 °C in 24 hours. Doxorubicin in NSI remained stable for five days at 4 °C and lost 16.3% at 25 °C by day 5, and 18.8% at 37 °C in 24 hours. Mitomycin in NS lost 15.8% at 4 °C within 24 hours, and 24.7% at 25 °C and 36% at 37 °C within four hours. Mitomycin in NSI was stable for 72 hours at 4 °C, 24 hours at 25 °C, and less than four hours at 37 °C.

CONCLUSIONS:

These agents in NS are stable for 12 hours at 4 °C. In NSI, they are stable for 72 hours at 4 °C.
Treatment of Insomnia in Hospitalized Patients
Authors: Lenhart Susan E , Buysse Daniel J
Published: June 2003

OBJECTIVE:

To provide recommendations for the short-term management of insomnia in hospitalized patients and review patient assessment, nonpharmacologic treatment modalities, and selection of hypnotic medications.

DATA SOURCES:

Review articles and primary literature representative of current knowledge regarding the treatment of insomnia were identified by MEDLINE search (1966–January 2001). Search terms included insomnia (sleep initiation and maintenance disorders), benzodiazepines, zaleplon, zolpidem, and trazodone.

DATA SYNTHESIS:

Literature regarding the management of insomnia in hospitalized patients is limited; therefore, data pertinent to the treatment of ambulatory patients must be extrapolated to the inpatient setting. When evaluating insomnia in hospitalized patients, it seems reasonable to obtain a thorough history and physical examination to identify potential underlying etiologies. Treatment of these underlying etiologies should be considered. When the use of a sedative—hypnotic agent is necessary, medication and dose selection should be based on the pharmacokinetic and adverse effect profiles of each agent. Patient-specific characteristics should also be considered to provide effective treatment while minimizing adverse effects.

CONCLUSIONS:

Nonpharmacologic approaches to the treatment of insomnia should be considered for hospitalized patients. When sedative—hypnotic medications must be administered, the pharmacokinetic profile of intermediate-acting benzodiazepines (e.g., lorazepam, temazepam) makes them good first-line agents. Zaleplon and zolpidem are also attractive hypnotic agents; however, they are typically reserved for second-line therapy due to cost. Trazodone may be an alternative for patients unable to take benzodiazepines.
Phenytoin and Fluorouracil Interaction
Authors: Gilbar Peter J , Brodribb T Robert
Published: June 2003

OBJECTIVE:

To report a probable drug interaction between phenytoin and fluorouracil.

CASE REPORT:

A 66-year-old white man started adjuvant chemotherapy for colon cancer with weekly bolus injections of fluorouracil and leucovorin calcium. He had been taking phenytoin 300 mg/d for epilepsy for more than four years. Eleven weeks later, the patient was reported to be unsteady on his feet and had fallen several times. The serum phenytoin concentration at that time was 36 μg/mL. The phenytoin dosage was decreased and the symptoms resolved. Phenytoin concentrations were monitored and the dosages were adjusted accordingly throughout the remaining 15 weeks of treatment with fluorouracil. After completion of chemotherapy, the phenytoin dose was gradually increased to the original dose with no signs of toxicity.

DISCUSSION:

Phenytoin is principally metabolized by CYP2C9. Inhibition of that isoenzyme by fluorouracil, and possible interference with its synthesis, appears to be the most likely cause of this interaction. The reduction in saturating substrate concentration of phenytoin was reduced as a result of this interaction, thus causing decreased clearance and increased serum concentrations. No previous interaction between phenytoin and fluorouracil has been reported. Both phenytoin and warfarin are metabolized by CYP269 and therefore exhibit the same spectrum of interactions when that isoenzyme is inhibited. Interactions have been reported with concurrent administration of warfarin and fluorouracil.

CONCLUSIONS:

The nature and extent of this phenytoin—fluorouracil interaction should be elucidated by in vitro investigations and a prospective study. Until then, clinicians should be aware of this potentially serious drug interaction and monitor patients closely for phenytoin toxicity.
Severe Pancytopenia Associated with Low-Dose Methotrexate Therapy for Rheumatoid Arthritis
Authors: Calvo-Romero José María
Published: June 2003

OBJECTIVE:

To report the occurrence of severe pancytopenia associated with low-dose methotrexate (MTX) therapy for rheumatoid arthritis.

CASE SUMMARY:

Two patients developed severe pancytopenia after 10 days (cumulative dose 15 mg) and 23 months (cumulative dose 1030 mg), respectively, of low-dose MTX therapy for rheumatoid arthritis. Both patients had renal impairment. One died and the other recovered completely.

DISCUSSION:

Pancytopenia is a rare adverse effect of low-dose oral MTX therapy. The exact mechanism for development of pancytopenia is unknown, although it is likely that several factors play a role. The most important risk factor for MTX toxicity is impaired renal function. This adverse effect may occur at any time during MTX therapy.

CONCLUSIONS:

Severe pancytopenia associated with low-dose MTX therapy for rheumatoid arthritis is a potentially serious complication that may occur at any time during therapy. This adverse effect is more likely to occur in patients with renal impairment.
Nateglinide Therapy for Type 2 Diabetes Mellitus
Authors: Levien Terri L , Baker Danial E , Campbell R Keith , White John R
Published: June 2003

OBJECTIVE:

To review the pharmacology, pharmacokinetics, dosing guidelines, adverse effects, drug interactions, and clinical efficacy of nateglinide.

DATA SOURCES:

Primary and review articles regarding nateglinide were identified by MEDLINE search (from 1966 to January 2001); abstracts were identified through the Institute for Scientific Information Web of Science (from 1995 to January 2001) and the American Diabetes Association; additional information was obtained from the nateglinide product information.

STUDY SELECTION/DATA EXTRACTION:

All articles and meeting abstracts identified from the data sources were evaluated and all information deemed relevant was included in this review. Much of the information was from abstracts or the product labeling, since few clinical studies have been published in the medical literature.

DATA SYNTHESIS:

Nateglinide is a novel nonsulfonylurea oral antidiabetic agent that stimulates insulin secretion from the pancreas. It has a rapid onset and short duration of action, allowing administration before a meal to reduce postprandial hyperglycemia. Improvement in glycemic control with nateglinide monotherapy has been demonstrated in patients not previously treated with antidiabetic medications. Greater improvement in glycemic control was observed when nateglinide was administered in combination with metformin.

CONCLUSIONS:

Nateglinide is similar to repaglinide, but has a quicker onset of action, quicker reversal, and does not usually require dosage titration. Based on the pharmacodynamics of nateglinide and repaglinide, nateglinide produces a more rapid postprandial increase in insulin secretion, and its duration of response is shorter than that of repaglinide. The risk of postabsorptive hypoglycemia should be lower than with either sulfonylureas or repaglinide.
Nonprescription Drug—Related Problems and Pharmacy Interventions
Authors: Westerlund LO Tommy , Marklund Bertil RG , Handl Wolfgang HA , Thunberg Margareta E , Allebeck Peter
Published: June 2003

OBJECTIVE:

To document the number and types of drug-related problems (DRPs) identified in customers purchasing nonprescription products in Swedish pharmacies; describe the distribution of DRPs by customer's gender, age, underlying ailment, and class of drug; determine whether problems are identified to the same extent in pharmacies with staffed nonprescription self-service departments as in pharmacies with over-the-counter sales; and document the number and types of pharmacy interventions to prevent or resolve DRPs, including reasons for drug switches and referrals to physicians.

METHODS:

A computerized instrument for documentation of DRPs and pharmacy interventions was developed. The study was conducted in 45 volunteer pharmacies in Sweden during 10 weeks in late 1999.

RESULTS:

A total of 1425 problems and 2040 interventions were recorded by 308 pharmacy practitioners. Relatively fewer DRPs were documented in pharmacies with self-service departments. The most common DRPs were uncertainty about the indication for the drug (33.5%) and therapy failure (19.5%). Dyspepsia was the most frequently specified symptom (11.4%). Consumers of dermatologic products had significantly higher rates of problems than expected in relation to sales volume. The most common ways of responding to a problem were with consumer drug counseling (61.1%), switching of drugs (43.9%), and referral to a physician (27.5%).

CONCLUSIONS:

The study has demonstrated a need for more professional attention and intervention by pharmacy staff to prevent and rectify DRPs in nonprescription consumers. It seems especially important to make sure that consumers receive the appropriate drugs for their current ailments.
Risk of Extrapyramidal Syndromes with Haloperidol, Risperidone, or Olanzapine
Authors: Schillevoort Igor , de Boer Anthonius , Herings Ron MC , Roos Raymund AC , Jansen Paul AF , Leufkens Hubert GM
Published: June 2003

OBJECTIVE:

To compare the risk of extrapyramidal syndrome (EPS) between risperidone, olanzapine, and haloperidol, taking into account patients' past antipsychotic drug use and past EPS.

METHODS:

Data were obtained from the PHARMO-database, containing filled prescriptions of 450 000 community-dwelling people in the Netherlands from 1986 through 1999. We defined cohorts of first-time users of haloperidol, risperidone, or olanzapine aged 15 to 54 years. In the first 90 days of treatment, we assessed the occurrence of EPS, defined as first use of any antiparkinsonian agent. We estimated relative risks of EPS for risperidone and olanzapine versus haloperidol using a Cox proportional hazards model. Patients were subdivided according to prior use of antipsychotic and antiparkinsonian drugs.

RESULTS:

We identified 424 patients starting treatment with haloperidol, 243 with risperidone, and 181 with olanzapine. Prior use of antipsychotic plus antiparkinsonian medication was significantly more frequent among users of risperidone and olanzapine than in those using haloperidol (36.2%, 40.3%, and 4.5%, respectively; p < 0.001). Within most subgroups of comparable treatment history, patients using risperidone and olanzapine showed reduced risks of EPS compared with haloperidol, although some of these findings did not reach statistical significance (RR 0.03–0.22). However, this was not observed for patients using risperidone who had experienced EPS in the past (RR 1.30; 95% CI 0.24 to 7.18).

CONCLUSIONS:

In general, we observed reduced risks of EPS for risperidone and olanzapine compared with haloperidol within subgroups of patients with a similar treatment history. However, the added value of risperidone in patients who have experienced EPS in the past needs further study.
Possible Interaction of Zopiclone and Nefazodone
Authors: Alderman Christopher P , Gebauer Markus G , Gilbert Andrew L , Condon John T
Published: June 2003

OBJECTIVE:

To describe a case in which concurrent treatment with nefazodone was associated with an elevation in the plasma concentration of zopiclone, possibly resulting in enhanced hypnosedative efficacy.

CASE REPORT:

An 86-year-old white woman was treated with nefazodone for depression. Zopiclone was also introduced for the management of insomnia, but she subsequently experienced morning drowsiness. The concentration of zopiclone in plasma was subsequently measured eight hours after administration on two occasions, during nefazodone therapy and after its withdrawal. After discontinuation of nefazodone, the plasma concentration of the S-enantiomer of zopiclone decreased from 107 to 16.9 ng/mL, while the R-enantiomer plasma concentration decreased from 20.6 to 1.45 ng/mL.

DISCUSSION:

Nefazodone is a relatively potent inhibitor of CYP3A4, a hepatic isoenzyme thought to play a major role in the metabolic elimination of zopiclone. The substantial decrease in the plasma zopiclone concentrations observed after withdrawal of nefazodone likely reflects a drug interaction. Despite the normally short elimination half-life of zopiclone, the residual sedation initially observed in this case suggests that the interaction may have clinical significance.

CONCLUSIONS:

The features observed in this case suggest the possibility of a drug—drug interaction between nefazodone and zopiclone. Further prospective investigation is required to elucidate the nature and magnitude of this effect.
Use of Enteral Nutrition for Stress Ulcer Prophylaxis
Authors: MacLaren Robert , Jarvis Catherine L , Fish Douglas N
Published: June 2003

OBJECTIVE:

To review the controversies involving the use of enteral nutrition support for stress ulcer prophylaxis and formulate recommendations.

DATA SOURCES:

A MEDLINE search (1966–December 2000) was conducted using the MeSH of nutrition, ulcer, critical care, and acid to identify relevant articles. References of selected articles were reviewed, and relevant abstracts from critical care or gastrointestinal journals identified.

DATA EXTRACTION:

Animal and human data from prospective studies, retrospective studies, and case series were evaluated for the effects of enteral nutrition on gastric pH, intramucosal pH, gastrointestinal blood flow, development of macroscopic mucosal erosions, and hemorrhage.

DATA SYNTHESIS:

Intragastric administration of enteral nutrition has variable effects on gastric pH, enhances regional distribution of gastrointestinal blood flow, and may lower intramucosal pH. All substrates (carbohydrate, lipid, amino acid), when administered into the stomach, reduce the occurrence of mucosal erosions but do not entirely prevent their development. Few studies of stress ulcer prophylaxis regimens have reported use of enteral nutrition. Limited retrospective data suggest enteral nutrition support may be effective for preventing gastrointestinal hemorrhage, but the results of prospective studies are confounded by poor study design.

CONCLUSIONS:

Definitive recommendations regarding the role of enteral nutrition for stress ulcer prophylaxis are not possible due to the lack of prospective, randomized studies. Therefore, the use of enteral nutrition as the only therapeutic agent for stress ulcer prophylaxis should be discouraged until definitive data are available. Initiation and discontinuation of pharmacologic stress ulcer prophylaxis should be independent of enteral nutrition.
Pharmacokinetics of para-Aminosalicylic Acid Granules under Four Dosing Conditions
Authors: Peloquin Charles A , Zhu Min , Adam Rodney D , Singleton Michael D , Nix David E
Published: June 2003

OBJECTIVE:

To determine the pharmacokinetics and relative bioavailability of para-aminosalicylic acid (PAS) granules.

DESIGN:

Phase I pharmacokinetics study.

SETTING:

University of Arizona School of Pharmacy.

PARTICIPANTS:

Sixteen healthy male and female volunteers aged 36 ± 8 years.

INTERVENTIONS:

Subjects received single doses of PAS granules (6 g) combined with cycloserine 500 mg, clofazimine 200 mg, ethionamide 500 mg, and pyridoxine 100 mg. Drugs were given on an empty stomach after an overnight fast (reference) with high-fat food, with orange juice, and with antacids.

MEASUREMENTS AND RESULTS:

Four subjects did not complete all four treatments due to adverse events or personal reasons. Plasma and urine samples were collected for 48 hours and measured by a validated HPLC assay. Pharmacokinetic data analysis was performed with WinNonlin using noncompartmental methods and a one-compartmental model. Bioequivalence testing was performed using the mean ratios of the maximum concentrations (Cmax) and AUC0-∞ of PAS, with 90% confidence intervals. Compared with the fasted condition, food increased Cmax 1.5–fold and AUC0-∞ 1.7-fold, and it doubled the time to maximum concentration (tmax). The least-squares mean ratios (treatment/reference) for Cmax were 0.90 (58% to 139% CI), 1.16 (75% to 179% CI), and 0.82 (52% to 127% CI) with orange juice, food, or antacid treatment, respectively. Corresponding ratios for AUC0-∞ were 1.05 (71% to 155% CI), 1.52 (103% to 224% CI), and 0.84 (57% to 125% CI), respectively.

CONCLUSIONS:

Food significantly enhanced the absorption of PAS, while orange juice and antacids had minor effects.
Galantamine: A New Alzheimer Drug with a Past Life
Authors: Pearson Vincent E
Published: June 2003

OBJECTIVE:

To review the historic, pharmacologic, pharmacokinetic, therapeutic, and toxicologic features of galantamine, a new acetylcholinesterase inhibitor, and to assess its role in the treatment of Alzheimer disease symptoms.

DATA SOURCES:

A search of articles was conducted using MEDLINE, TOXLINE, and the literature database PsychInfo, from 1966 to June 1999. The manufacturers, Janssen and SoPharm (Bulgaria), were contacted to obtain relevant preclinical data. Published textbooks of meeting symposia were also reviewed.

STUDY SELECTION:

Studies with animals and humans addressing preclinical pharmacology, human studies on pharmacokinetics, open clinical trials, and controlled studies were evaluated.

DATA EXTRACTION:

Relevant data were extracted from published studies and meeting abstracts only.

DATA SYNTHESIS:

Galantamine has an extensive record of activity as a reversal agent for neuromuscular blockade. Galantamine is also effective in the treatment of mild to moderate Alzheimer disease symptoms. Its efficacy versus similar Alzheimer treatment agents has yet to be determined. Adverse effects are gastrointestinal in nature and usually appear during the first weeks of therapy.

CONCLUSIONS:

Galantamine is a useful agent for the treatment of Alzheimer disease and for the reversal of neuromuscular blockade. It acts as both an acetylcholinesterase inhibitor and a nicotinic receptor agonist.
A Comparison of Clinical Outcome Studies among Cholesterol-Lowering Agents
Authors: Lousberg Tammy R , Denham Anne M , Rasmussen Jon R
Published: June 2003

OBJECTIVE:

To review and compare clinical trials of cholesterol-lowering agents that evaluated clinical end points as the primary outcome measure; specifically, to determine whether all agents that decrease cholesterol impact clinical outcomes similarly.

DATA SOURCES:

Primary articles were identified through a MEDLINE search (1966–February 2001) and through secondary sources.

STUDY SELECTION AND DATA EXTRACTION:

All of the articles identified from the data sources were evaluated. Articles that included clinical end points as the primary outcome measure were included in this review.

DATA SYNTHESIS:

Clinical trials were assessed according to study population (primary vs. secondary prevention of coronary artery disease), baseline and follow-up lipid profiles, and clinical outcome data. Both cardiac and noncardiac morbidity and mortality were evaluated. The differences in study populations, study methods, and changes in lipid values were compared and contrasted between trials to evaluate their effect on outcomes.

CONCLUSIONS:

Niacin and bile acid sequestrants should be considered as add-on therapy when therapeutic goals cannot be attained with a hydroxymethyl glutaryl—coenzyme A reductase inhibitor (statin). Estrogen therapy cannot be recommended solely for cardioprotection. Fibrates are most effective in patients with high baseline triglycerides, low baseline high-density lipoprotein cholesterol, and low to average low-density lipoprotein cholesterol (LDL). Statins are considered first line for the treatment of elevated LDL in both the primary and secondary prevention of coronary heart disease. They are well tolerated, have the strongest data to support their use, and have been shown to decrease total mortality.
Bupropion versus Selective Serotonin-Reuptake Inhibitors for Treatment of Depression
Authors: Nieuwstraten Carmine E , Dolovich Lisa R
Published: June 2003

OBJECTIVE:

To compare the benefits and risks of bupropion and selective serotonin-reuptake inhibitors (SSRIs) in adults with depression.

DATA SOURCES:

MEDLINE (1966–September 1999), Embase (1980–August 1999), PsycINFO (1887–August 1999), International Pharmaceutical Abstracts (1970–August 1999), and CIANHL databases were searched. References from the selected citations, review articles, and the manufacturer were also screened.

STUDY SELECTION:

Included studies were randomized, double-blind, controlled trials evaluating bupropion versus SSRIs for depression in adults. Studies were assessed independently in duplicate. Discrepancies were resolved by consensus.

DATA ANALYSIS:

Data are reported as absolute weighted mean differences or relative risks and 95% confidence intervals comparing bupropion relative to SSRIs. Data not combined are presented qualitatively.

DATA SYNTHESIS:

Six full-length studies were included of 257 citations identified. SSRI comparators were fluoxetine, sertraline, and paroxetine. No differences in Hamilton Rating Scale for Depression (HAM-D) and Clinical Global Impressions Scale for Improvement of Illness (CGI-I) were found, but data were not able to be quantitatively combined. The absolute weighted mean differences were 0.10 (95% CI −0.2 to 0.4) for the CGI for Severity of Illness and 0.37 (95% CI −0.85 to 1.6) for the Hamilton Rating Scale for Anxiety measurements. Relative risks of bupropion compared with SSRIs were 0.6 (95% CI 0.41 to 0.89), 0.31 (95% CI 0.16 to 0.57), and 0.27 (95% CI 0.15 to 0.48) for nausea, diarrhea, and somnolence, respectively. Sexual arousal disorder, orgasmic dysfunction, and sexual desire disorder occurred less with bupropion than with SSRIs, with relative risks of 0.46 (95% CI 0.26 to 0.83), 0.22 (95% CI 0.12 to 0.40), and 0.65 (95% CI 0.51 to 0.84), respectively.

CONCLUSIONS:

Bupropion and SSRIs have similar effectiveness; however, bupropion was associated with less nausea, diarrhea, somnolence, and sexual dysfunction.
Use of Metformin in Polycystic Ovary Syndrome
Authors: Koch Yvonne De Sloover , Ernst Michael E
Published: June 2003

OBJECTIVE:

To review the use of the insulin-sensitizing agent metformin in women with polycystic ovary syndrome (PCOS).

DATA SOURCES:

Biomedical literature was accessed through MEDLINE (1996–March 2001) and the Iowa Drug Information Service. Key terms included metformin and polycystic ovary syndrome.

DATA SYNTHESIS:

A number of small clinical studies have examined the use of metformin in the treatment of PCOS. Women treated with metformin demonstrated normalization of endocrine function with minimal adverse effects.

CONCLUSIONS:

Metformin can be beneficial in normalizing menstrual irregularities and stimulating ovulation in previously anovulatory women. Metformin therapy is well tolerated by the majority of patients and should be considered for use in women with PCOS.
Stability of Piperacillin and Ticarcillin in AutoDose Infusion System Bags
Authors: Zhang Yanping , Trissel Lawrence A
Published: June 2003

OBJECTIVE:

To evaluate the physical and chemical stability of piperacillin sodium 3 and 4 g/100 mL and ticarcillin disodium 3 g/100 mL each admixed in NaCl 0.9% injection packaged in AutoDose Infusion System bags.

DESIGN:

Triplicate test samples of the penicillin antibiotics in NaCl 0.9% injection were packaged in ethylene vinyl acetate (EVA) plastic containers, AutoDose bags, designed for use in the AutoDose Infusion System. Samples were stored protected from light and evaluated at appropriate intervals for up to seven days at 23 °C and up to 30 days at 4 °C. Physical stability was assessed using turbidimetric and particulate measurement as well as visual inspection. Chemical stability was assessed by HPLC.

RESULTS:

All of the penicillin admixtures initially were clear when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low initially and exhibited little change in the ticarcillin disodium samples throughout the study. The piperacillin sodium samples exhibited small increases in measured haze throughout the study, but no accompanying increase in particulates ≥1.04 μm was found. All samples were essentially colorless throughout the study. HPLC analysis found some decomposition in the samples. Piperacillin sodium exhibited a 9–10% loss after five days at 23 °C. In the samples stored at 4 °C, piperacillin sodium exhibited acceptable stability through 21 days of storage, but losses exceeded 10% after 30 days. Ticarcillin disodium exhibited a 7% loss after three days, but 14% after five days at 23 °C. Less than 7% loss occurred after 21 days, but 12% loss after 30 days at 4 °C.

CONCLUSIONS:

Piperacillin sodium and ticarcillin disodium exhibited physical and chemical stability consistent with previous studies on these drugs. The AutoDose Infusion System bags were not found to adversely affect the physical and chemical stability of these penicillin antibiotics.
Olanzapine-Induced Diabetic Ketoacidosis
Authors: Ragucci Kelly R , Wells Brian J
Published: June 2003

OBJECTIVE:

To report the case of a patient taking olanzapine who developed diabetic ketoacidosis (DKA).

CASE SUMMARY:

A 46-year-old African American woman with no previous history of diabetes mellitus was admitted to the hospital and subsequently diagnosed with DKA and acute pancreatitis. The patient had been taking olanzapine, valproic acid, carbamazepine, hydrochlorothiazide/triamterene, and conjugated estrogens prior to admission. Olanzapine was the last medication added to the regimen. In addition to clinicians treating the DKA with appropriate interventions, olanzapine (due to possible association with hyperglycemia and DKA) as well as valproic acid (due to possible association with pancreatitis) were discontinued from the medication regimen. The patient was discharged home and her most recent glycosylated hemoglobin and fasting glucose concentrations have been within the normal range.

DISCUSSION:

Atypical antipsychotics, such as olanzapine, have been associated with hyperglycemia and possibly DKA. We believe that this occurred in our patient who had no previous history of diabetes mellitus. Possible mechanisms of action and potential confounding variables are discussed.

CONCLUSIONS:

Clinicians should monitor blood glucose concentrations periodically in patients taking olanzapine, especially in those patients with risk factors for diabetes mellitus.