bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxicity of Polysaccharide–Iron Complex Exposures Reported to Poison Control Centers
Authors: Klein-Schwartz Wendy
Published: June 2003

OBJECTIVE:

To evaluate the toxicity of polysaccharide–iron complex (PIC) exposures reported to poison centers in the US.

DESIGN:

A retrospective analysis of potentially toxic exposures to PIC without concomitant substances reported to the American Association of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System from 1990 to 1998 was performed.

RESULTS:

Of 810 potentially toxic exposures to PIC, 55.9% occurred in females, 43.8% in males; in 0.3%, gender was unknown. The majority of exposures (74.4%) involved children under six years of age. The reasons for exposure were: 86.7% unintentional, 11.6% intentional, and 1.6% adverse reaction. The most frequently reported clinical effects attributed to PIC were vomiting (n = 23), diarrhea (10), nausea (11), abdominal pain (10), and lethargy/drowsiness (7). While the majority of exposures were managed outside a healthcare facility, management site varied depending on age (management in non-healthcare facility in 71.8% of exposures in children under six years of age vs. 44.9% in adolescents and adults). The majority of outcomes (95.6%) were no effect, minor effect, unrelated effect, not followed since nontoxic, or not followed since only minimal toxicity possible. Of two cases coded as moderate effect, it could not be determined whether the symptoms were related to PIC in one, and in the second case inspection of the poison center record revealed that the actual outcome was minor effect. There were no major effects or deaths.

CONCLUSIONS:

There were no serious adverse events following PIC exposure reported to the AAPCC. Although more data are needed, these findings suggest reduced toxicity for PIC relative to other forms of iron.
Hyperglycemia Associated with Protease Inhibitors in an Urban HIV-Infected Minority Patient Population
Authors: Dever Lisa L , Oruwari Patrick A , Figueroa Wanda E , O'Donovan Carmel A , Eng Robert HK
Published: June 2003

BACKGROUND:

Hyperglycemia and new-onset diabetes mellitus have been reported to occur in HIV-infected patients treated with protease inhibitors.

OBJECTIVE:

To determine the effect of protease inhibitor therapy on serum glucose in a predominantly minority patient population.

DESIGN:

Retrospective record review.

SETTING:

Clinical HIV program of an urban Veterans Affairs medical center.

PATIENTS:

All HIV-infected patients receiving a protease inhibitor over a one-year period from September 1996 through August 1997.

RESULTS:

One hundred seventeen patients not previously known to be diabetic received protease inhibitors; seven (6%) developed symptomatic diabetes mellitus. Eight other patients had one or more serum glucose values >150 mg/dL. Mean random glucose values for patients who did not develop diabetes were higher during therapy than prior to initiation of protease inhibitors.

CONCLUSIONS:

Urban minority HIV-infected patients receiving combination antiretroviral therapy including a protease inhibitor may be at increased risk for the development of hyperglycemia and diabetes mellitus. Risk factors for diabetes mellitus should be identified and blood glucose monitored in all patients receiving protease inhibitors.
A Chronobiologic Approach to the Pharmacotherapy of Hypertension and Angina
Authors: Munger Mark A , Kenney Julie K
Published: June 2003

OBJECTIVE:

To review the chronobiology of hypertension and coronary artery disease and the application of chronotherapeutics to their treatment and prevention.

DATA SOURCES:

Clinical trials and review articles (English-language) on the topic of chronotherapy and cardiovascular disease were identified via a MEDLINE search from 1990 to March 2000, using the search terms chronotherapy, circadian rhythm, cardiovascular disease, hypertension, and angina.

DATA EXTRACTION:

Search and evaluation focused on published clinical trials and review articles of circadian variation associated with pharmacotherapy for cardiovascular disease.

DATA SYNTHESIS:

The existence of circadian rhythm in cardiovascular disease is well established. Heart rate and blood pressure peak during the morning hours and reach a nadir at bedtime. The incidence of myocardial infarction, stroke, sudden cardiac death, and myocardial ischemia also increases during the early-morning hours. Based on these relationships, researchers have begun to apply the science of chronotherapeutics, or timing of drug effect with biologic need, to improve cardiovascular outcomes. This includes administering traditional agents at specific × throughout the day and developing new agents — Chronotherapeutic formulations with special release mechanisms — Targeted at inducing the greatest effect during the morning surges. Chronotherapeutic agents are specifically designed to provide peak plasma concentrations during the early-morning hours, when effect appears most needed; lowest concentrations occur at night, when heart rate and blood pressure are lowest and, consequently, cardiovascular events are least likely to occur.

CONCLUSIONS:

Whether chronotherapy of cardiovascular disease offers an advantage in long-term outcomes over traditional therapy must be studied in clinical trials.
Anaphylactic Reactions to Proton-Pump Inhibitors
Authors: Natsch Stephanie , Vinks Mattheus HAM , Voogt Adrianne K , Mees Eric B , Meyboom Ronald HB
Published: June 2003

OBJECTIVE:

To report two cases of anaphylactic reactions to proton-pump inhibitors (PPIs).

CASE SUMMARIES:

A 54-year-old woman who had taken omeprazole in the past was treated with omeprazole 40 mg and developed periorbital edema, edema of the skin, pruritus, nausea, and vomiting about 45 minutes after taking one capsule. Five months later, she was treated with lansoprazole 30-mg capsules. Again, within 45 minutes she developed an even more serious reaction, with pruritus and urticaria on her whole body, increased sweating, facial edema, and loss of consciousness. A 61-year-old man took one tablet of pantoprazole 40 mg one year after first being treated with the drug. Within hours after ingestion, he developed malaise, generalized pruritus and urticaria, a swollen tongue and eyes, and diffuse sweating; his blood pressure decreased to 75/50 mm Hg.

DISCUSSION:

Because of the acute onset of symptoms and close temporal association with exposure to the drug, as well as previous exposure to it, the reactions can be classified as anaphylactic shock to PPIs. These benzimidazole derivatives are chemically related; observations in a few patients, such as the first case above, suggest that cross-sensitivity may occur. The Uppsala Monitoring Centre (UMC) has received a total of 42 reports of anaphylactic reactions or anaphylactic shock in association with PPIs. These reports account for 0.2% of the total of reported suspected adverse drug reactions to PPIs, compared with 0.8% anaphylactic reactions in the UMC database as a whole.

CONCLUSIONS:

These findings suggest that the chemically related PPIs can, as a group, cause anaphylactic reactions; however, the rate is comparatively low. Since anaphylaxis is a potentially serious reaction, more precise information is needed regarding its frequency, and healthcare professionals need to be aware of this possibility when prescribing these agents.
Voriconazole: A New Triazole Antifungal
Authors: Sabo Janelle A , Abdel-Rahman Susan M
Published: June 2003

OBJECTIVE:

To review the currently available information on the pharmacology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage guidelines of voriconazole. Comparative data for voriconazole and other azole antifungal agents are described where available.

DATA SOURCES:

A MEDLINE search restricted to English-language articles (1966 to September 1999) was conducted, and an extensive review of journals and meeting abstracts was performed. MeSH headings included itraconazole, fluconazole, voriconazole, UK-109,496, and amphotericin B.

DATA EXTRACTION:

The data on pharmacokinetics, adverse effects, and drug interactions were obtained from open-label and controlled studies and case reports. Controlled studies and case reports were evaluated to demonstrate the efficacy of voriconazole in treatment of various fungal infections.

DATA SYNTHESIS:

Voriconazole is a derivative of fluconazole that demonstrates enhanced in vitro activity against existent and emerging fungal pathogens. Limited data have revealed a favorable pharmacokinetic and safety profile for the agent. Moreover, select clinical trials and case studies of voriconazole suggest good in vivo efficacy against several fungal pathogens including Candida, Aspergillus, and Scedosporium.

CONCLUSIONS:

Voriconazole has shown promise in the treatment of superficial and systemic mycoses. While several unresolved issues remain, voriconazole may be a viable therapeutic alternative for fluconazole-resistant mucocutaneous candidiasis and in cases of mild to moderate systemic mycoses requiring chronic treatment or that are refractory to currently available agents.
Warfarin and Celecoxib Interaction
Authors: Mersfelder Tracey L , Stewart Lisa R
Published: June 2003

OBJECTIVE:

To report a case of increased international normalized ratio (INR) in a patient receiving warfarin and celecoxib.

CASE SUMMARY:

A 73-year-old white woman with hypothyroidism and heart failure was admitted to the hospital with increased orthopnea, dyspnea on exertion, and hemoptysis. On laboratory evaluation, she was noted to have an increased INR. The only reported change in her medications was the addition of celecoxib approximately five weeks before admission. Her INR had previously been stable. After discontinuation of warfarin and celecoxib, fresh frozen plasma and vitamin K were administered to normalize INR. The patient was not rechallenged.

DISCUSSION:

Warfarin is an oral anticoagulant with numerous reports of drug interactions. It is possible that other drug therapies or disease states may have contributed to the elevation in INR; however, the observed increase in INR occurred five weeks after beginning celecoxib therapy. The Food and Drug Administration has issued a notice about the possibility of interactions between these two medications.

CONCLUSIONS:

Celecoxib may potentiate the anticoagulant effects of warfarin. Patients receiving warfarin should be carefully monitored when adding, changing, or removing celecoxib from their medication regimen.
A Multicenter Drug Use Surveillance of Intravenous Immunoglobulin Utilization in US Academic Health Centers
Authors: Chen Connie , Danekas Lynne H , Ratko Thomas A , Vlasses Peter H , Matuszewski Karl A
Published: June 2003

BACKGROUND:

The role of intravenous immunoglobulin (IVIG) in treating a variety of diseases is controversial and under active investigation for at least two reasons: first, a severe shortage of IVIG products exists in the US; second, numerous off-label (not specified in the Food and Drug Administration [FDA]–approved label) uses for IVIG have been, and continue to be, described in the literature. However, most off-label uses are not supported by evidence from properly designed clinical trials.

OBJECTIVE:

To assess inpatient use of IVIG in a sample of US academic health centers and to compare it with published evidence-based model guidelines for IVIG use.

METHODS:

Data on the use of IVIG and subsequent clinical outcomes in 251 patients were collected prospectively from 12 institutions. Recommendations from consensus guidelines were used to categorize patients who received IVIG into one of four groups: labeled uses; off-label, recommended; off-label, recommended as alternative; and off-label, not recommended. Outcomes were scored according to guideline criteria.

RESULTS:

One hundred seven patients (43%) received IVIG for indications contained in the FDA-approved product label, 130 patients (52%) received IVIG for off-label indications, and 14 (5%) received undefined treatment. Among all patients administered IVIG, 31 (12%) were treated for off-label recommended reasons; 64 (26%) received off-label recommended as alternative therapy; and 35 (14%) received off-label not recommended therapy, as defined by model guidelines. Outcomes were not significantly different between the groups.

CONCLUSIONS:

Our findings suggest that IVIG continues to be used to treat a wide variety of conditions not specified in the product label. Furthermore, a substantial proportion of the reported off-label uses are not recommended according to evidence-based guidelines.
Hypertensive Crisis and Myocardial Infarction following Massive Clonidine Overdose
Authors: Frye Carla B , Vance Michael A
Published: June 2003

OBJECTIVE:

To describe a patient who experienced a hypertensive crisis and myocardial infarction following a massive dose of parenteral clonidine.

CASE SUMMARY:

A 62-year-old white woman with stage 3 breast cancer metastatic to the spine and a history of hypertension received a combined injection of hydromorphone 48.3 mg and clonidine 12.24 mg subcutaneously in an attempt to refill an implanted epidural infusion pump. She promptly developed mental deterioration, blurred vision, worsening respiration, tachycardia, and hypertension. She was immediately treated with naloxone, but subsequently experienced hypertensive urgency, a short-duration tonic–clonic seizure, and an anteroseptal myocardial infarction. Cardiac catheterization showed no arteriolar narrowing or blockage, but an anterior infarct was confirmed.

DISCUSSION:

Clonidine is a commonly used α-adrenergic agonist. At usual oral doses of 0.2–2 mg/d, it acts centrally to produce hypotensive effects; at doses >7 mg/d, it acts peripherally to stimulate α1- and α2-adrenergic receptors, leading to vasoconstriction and increased blood pressure. These effects are not easy to control by standard medical therapies and can cause significant morbidity.

CONCLUSIONS:

Clonidine, although a safe medication with usual dosages, must be used with caution when given in injectable form. An overdose of this α-adrenoreceptor agonist can produce significant vasospasm and hypertensive emergency. Drugs used to treat overdose, such as naloxone, can potentiate clonidine's adverse effects, leading to further morbidity.
Clozapine-Induced Hypersalivation
Authors: Davydov Liya , Botts Sheila R
Published: June 2003

OBJECTIVE:

To review underlying pathophysiology and possible treatments for clozapine-induced hypersalivation.

DATA SOURCES:

Primary literature was accessed through MEDLINE (1966–May 1999). Key search terms included clozapine, hypersalivation, sialorrhea, and treatment.

DATA SYNTHESIS:

Hypersalivation occurs in up to 54% of patients receiving clozapine. An evaluation of studies and case reports focusing on management of clozapine-induced hypersalivation was conducted.

CONCLUSIONS:

It is unclear whether clozapine increases salivation through its muscarinic M4 receptor activation and/or blockade of α2-adrenoceptors, or by causing a distortion in swallowing reflex. Treatment options include chewing gum, reducing the dosage of clozapine, or prescribing pharmacologic agents such as anticholinergics or α2-adrenoceptor agonists.
Pharmacists' Knowledge and Attitudes toward Herbal Medicine
Authors: Chang Ziba Gorji , Kennedy Daniel T , Holdford David A , Small Ralph E
Published: June 2003

OBJECTIVE:

The use and sales of herbal medications have increased dramatically over the past several years. Pharmacists are in an ideal position to educate patients about herbal medicines. This study was intended to determine the knowledge and attitudes of pharmacists regarding herbal medications.

METHODS:

A survey was distributed to pharmacists at several state and regional meetings in Virginia and North Carolina between August and October 1998. The survey evaluated demographic data, attitudinal scales, and a 15-item herbal medicine knowledge test. Pharmacists immediately returned the surveys to the distributor on completion.

RESULTS:

Of the 217 surveys distributed, 164 met the inclusion criteria for further evaluation. Of the pharmacists surveyed, 68.0 % practiced in a community pharmacy, 45.1% had previous continuing education on herbal medications, and 73.6% sold herbal medications in their practice settings. The average score on the herbal knowledge test was 6.3 (maximum score of 15). Pharmacists with previous continuing education scored significantly higher than those without prior continuing education (p < 0.001). Of the 15 questions, the five that pharmacists were most likely to answer correctly assessed the uses of herbal medications. Additionally, pharmacists with prior continuing education or with access to herbal medication information at their practice site were more likely to agree that providing information about herbal medication is a pharmacist's professional responsibility (p = 0.02 and p = 0.01, respectively).

CONCLUSIONS:

The findings from this study demonstrate that pharmacists were more likely to answer correctly about the uses of herbal medications than about drug interactions, adverse drug effects, and precautions of herbal medications. Additionally, pharmacists with previous continuing education on herbal medications were more knowledgeable about these products. With the increasing use of herbal medications, there is a greater need for pharmacy training programs in this area.
Miglitol: Assessment of its Role in the Treatment of Patients with Diabetes Mellitus
Authors: Campbell Lance K , Baker Danial E , Campbell R Keith
Published: June 2003

OBJECTIVE:

To evaluate miglitol, a new oral α-glucosidase inhibitor, and discuss its pharmacology, therapeutics, pharmacokinetics, dosing guidelines, adverse effects, drug interactions, and clinical efficacy.

DATA SOURCES:

A MEDLINE English-language only database search using the keywords miglitol, glyset, and Bay m 1099 (1985 to December 1999), was completed to identify relevant articles including reviews, recent studies, and abstracts; American Diabetes Association 1999 Annual Meeting abstracts; Pharmacia & Upjohn data on file and product information.

STUDY SELECTION:

The clinical trials that were selected to be reviewed in detail were randomized, double-blind studies with at least 100 patients in the intention-to-treat group.

DATA EXTRACTION:

All articles and abstracts were reviewed along with the product labeling from Pharmacia & Upjohn.

DATA SYNTHESIS:

Miglitol is an α-glucosidase inhibitor that exerts its effect through the delayed absorption of complex carbohydrates in the small intestine, resulting in a decrease in postprandial glucose concentrations that are directly correlated with the dietary carbohydrate content. Both small, short-term trials and large, clinical trials show a decrease in postprandial glucose concentrations and a modest decrease in glycosylated hemoglobin of approximately 0.5–1.0% as a result of miglitol's action. The adverse effects of miglitol are mild and transitory and include flatulence, diarrhea, and abdominal pain. The incidence of gastrointestinal problems may be reduced with a small initial dose, which is slowly titrated as tolerated.

CONCLUSIONS:

Miglitol is an effective and safe treatment option in patients with type 2 diabetes mellitus who are inadequately controlled with diet or oral sulfonylurea therapy. Miglitol is a good choice of therapy in Hispanic, African-American, and elderly patients, or any patients in whom hypoglycemia, weight gain, or lactic acidosis are risks. No published studies comparing miglitol with acarbose have been published, but there appears to be no major clinical or financial advantages to using one agent over the other.
Helicobacter Pylori Eradication in Clinical Practice: Retreatment Rates and Costs of Competing Regimens
Authors: Fairman Kathleen A , Motheral Brenda R
Published: June 2003

OBJECTIVE:

To measure outcomes for eradication regimens for Helicobacter pylori infection in routine clinical practice.

DESIGN:

Retrospective analysis of an integrated medical and pharmacy claims database identified patients treated from June 1, 1995 through May 31, 1996, and followed the patients' claims until December 31, 1996.

SETTING:

The database represented multiple health plans throughout the US.

PATIENTS:

Patients were ≥16 years old, continuously enrolled from April 1, 1995, to December 31, 1996, and met clinical (diagnostic or procedural) criteria.

INTERVENTION:

Patient cohorts were treated with bismuth-based triple (n = 98), proton-pump inhibitor (PPI)–based triple (n = 180), or PPI-based dual (n = 337) regimens.

OUTCOME MEASURES:

Retreatment; monthly postregimen medical expense, controlling for preregimen expense; and drug cost per successfully treated patient. Cox regression (retreatment analysis) and ANCOVA (postregimen expense analysis) adjusted for age, gender, diagnostic/procedural criteria met by patient, and specialty physician use.

RESULTS:

Retreatment rates were higher (p < 0.05) for PPI-based dual than bismuth-based or PPI-based triple-therapy cohorts. Retreatment rates for bismuth- and PPI-based triple-therapy cohorts were not significantly different. Total and follow-up (excluding the first 2 wk of treatment) expenses were higher for retreated than nonretreated patients (p < 0.01). Total expenses were higher for the PPI-dual cohort (p < 0.05) than for triple cohorts. Drug costs per successfully treated patient were $30 for bismuth-based, $172 for PPI-based triple, and $208 for PPI-based dual-therapy regimens.

CONCLUSIONS:

PPI-based dual-therapy regimens are not cost-effective in H. pyloritreatment. Further study should compare more costly (PPI-based) versus less costly (bismuth-based) triple-therapy regimens.
Long-Term Treatment with Warfarin in Chinese Population
Authors: Chenhsu Rou-Yee , Chiang Shu-Chiung , Chou Mei-Huei , Lin Ming-Fang
Published: June 2003

OBJECTIVE:

To estimate the incidence of and risks for bleeding and thromboembolic events after warfarin anticoagulation. We also explored the dosage and international normalized ratio (INR) among Chinese patients during long-term warfarin therapy.

METHODS:

The population in this retrospective study consisted of inpatients of the only medical center for northern Taipei City, whose initial course of warfarin therapy continued for more than four weeks. Enrollment began in June 1995 and ended in February 1996. Follow-up was completed in March 1998. Relevant data were collected by chart review. The rate of events was calculated using the Kaplan—Meier method, and risk factors were identified by the Cox proportional hazard model.

RESULTS:

During the study period, 226 patients were identified. The total follow-up time was 248.7 patient-years. Sixty-one patients (27.0%) received anticoagulation for mechanical prosthetic valve, but their duration of therapy accounted for 48.6% of the total patient-years of follow-up. The starting dosage (mean ± SD) was 3.4 ± 1.4 mg/d (range 1.3–10); the maintenance dosage was 3.1 ± 1.2 mg/d (range 1.2–7.7). There were 1060 dosing adjustments and 3398 INR measurements collected for these patients. The independent determinants of maintenance dosage were age, body weight, and indication of mechanical prosthetic valve. The INR was 1.9 ± 0.5 (range 1.0–3.7). The cumulative probabilities for hemorrhage at 12, 24, and 34 months were 24.5%, 32.3%, and 38.4%, respectively. The corresponding figures for thromboembolism were 8.5%, 10.7%, and 10.7%, respectively. Three hemorrhages were fatal. After adjusting for other patient characteristics, increasing age was the only independent risk factor identified for bleeding.

CONCLUSIONS:

Antithrombotic efficacy seemed to be maintained, although the mean INR was 1.9. Even so, the substantial incidence of bleeding, especially fatal bleeding, remains a concern. Low-intensity anticoagulation might be needed for Chinese patients during long-term warfarin therapy.
Angiotensin II Receptor Blockers in Patients with ACE Inhibitor–Induced Angioedema
Authors: Warner Kelly K , Visconti James A , Tschampel Marva M
Published: June 2003

OBJECTIVE:

To determine the safety of using angiotensin II receptor blockers in patients who have experienced angioedema following treatment with angiotensin-converting enzyme (ACE) inhibitors.

DATA SOURCES:

Clinical literature identified through MEDLINE (January 1966–August 1999). Key search terms included angioneurotic edema, angiotensin-converting enzyme inhibitors, receptors–angiotensin, and losartan.

DATA SYNTHESIS:

ACE inhibitor–induced angioedema occurs with an incidence of 0.1–0.5%. Alternative therapy is necessary for patients who experience this potentially life-threatening adverse effect. Since angiotensin II receptor blockers do not increase concentrations of bradykinin, the proposed mechanism of ACE inhibitor–induced angioedema, they were presumed to be safe alternatives. Recent case reports, however, document angioedema following therapy with angiotensin II receptor blockers; 32% of the reported patients experienced a prior episode of angioedema attributed to ACE inhibitor therapy.

CONCLUSIONS:

Until the exact cause of both ACE inhibitor– and angiotensin II receptor blocker–induced angioedema is determined, angiotensin II receptor blockers should be used with extreme caution in patients with a prior history of angioedema.
Combined Aspirin/ACE Inhibitor Treatment for CHF
Authors: Olson Kari L
Published: June 2003

OBJECTIVE:

To review the literature evaluating the interaction between angiotensin-converting enzyme (ACE) inhibitors and aspirin in patients with congesitve heart failure (CHF).

DATA SOURCES:

A literature search through MEDLINE (1966–March 2001) and EMBASE (1966–March 2001) identified randomized, double-blind, controlled trials evaluating the use of ACE inhibitors and aspirin in patients with CHF.

DATA SYNTHESIS:

No prospective study has evaluated the effects of aspirin and ACE inhibitors on clinical outcomes of patients with CHF. All have been short-term studies evaluating the effects on hemodynamic parameters only.

CONCLUSIONS:

While the potential for an interaction between ACE inhibitors and aspirin exists, the results from ongoing prospective trials will help determine the efficacy of using both agents in patients with CHF.
Bupropion-Induced Serum Sickness–Like Reaction
Authors: McCollom Robert A , Elbe Dean HT , Ritchie Alec H
Published: June 2003

OBJECTIVE:

To report three cases of serum sickness–like reaction (SSLR) associated with bupropion ingestion.

CASE SUMMARY:

A 27-year-old woman, a 46-year-old man, and a 43-year-old woman presented to our emergency department within a three-week period with symptoms consistent with SSLR. Symptoms consisted of pruritic skin rash, tongue swelling, and arthralgias. All three patients had initiated bupropion therapy within two to three weeks prior to arrival.

DISCUSSION:

This is the second published case describing SSLRs associated with bupropion. Reports of urticaria and rash with bupropion use are numerous and the incidence has been estimated at between 1% and 4%. Arthralgia and arthropathy with bupropion use are reported much less commonly. The onset of symptoms of SSLRs typically begins six to 21 days after administration of the causative agent. SSLRs are usually self-limiting, lasting four to 14 days.

CONCLUSIONS:

SSLRs following bupropion ingestion appear to be rare. However, the fact that this cluster of patients presented to our emergency department within a three-week period suggests that this reaction may be underreported.
Acute Profound Thrombocytopenia following Abciximab Therapy
Authors: Bishara Amira I , Hagmeyer Kathleen O
Published: June 2003

OBJECTIVE:

To report a case of acute, profound thrombocytopenia (APT), defined as an abrupt drop in platelet count to <20 000/mm3 that occurred within 24 hours of administration of an abciximab bolus, to summarize other abciximab-associated APT cases reported in the literature, to review the postulated mechanisms behind this reaction, and to emphasize the importance of periodically monitoring platelet counts after initiating abciximab therapy.

DATA SOURCES:

MEDLINE and Index Medicus searches restricted to English-language literature from 1993 through June 1999 were conducted. MeSH headings included abciximab, ReoPro, thrombocytopenia, and glycoprotein IIb-IIIa (GP IIb-IIIa) inhibitors. References of the articles obtained were also reviewed.

DATA EXTRACTION:

Search and evaluation were focused on published case reports and reviews of abciximab-induced APT, as well as the incidence of thrombocytopenia from the drug compared with that from other GP IIb-IIIa inhibitors.

DATA SYNTHESIS:

Platelet aggregation has been identified as the structural basis for coronary thrombosis. This may lead to ischemic complications during acute coronary syndromes or following coronary intervention procedures. The use of GP IIb-IIIa inhibitors such as abciximab as antiplatelet agents has been effective in reducing these ischemic complications. We summarize 15 published cases of abciximab-associated APT gathered from data on 2482 patients treated with the drug. Prior to suspecting abciximab, other potential causes of thrombocytopenia should be evaluated. It is important to monitor the platelet count at baseline, two hours after initiating abciximab, and 24 hours after initiation of therapy or prior to discharge, whichever comes first, to identify patients at risk for developing APT. If APT occurs and is left untreated, it can produce excessive hemorrhage and ischemia, potentially leading to death. Platelet transfusions have been more effective than immunoglobulin in the management of APT.

CONCLUSIONS:

Abciximab-induced APT has a low incidence of occurrence. If it does develop and is not recognized or treated promptly, it can lead to serious hemorrhagic complications. Consequently, monitoring the platelet count two hours after initiation of the infusion is essential. If APT develops, abciximab should be discontinued and a platelet transfusion should be considered.
Use of Gabapentin in the Treatment of Neuropathic Pain
Authors: Laird Michael A , Gidal Barry E
Published: June 2003

OBJECTIVE:

To evaluate the role of gabapentin for the treatment of neuropathic pain.

DATA SOURCES:

Clinical literature was identified through MEDLINE (from 1990 to October 1999). Key search terms were gabapentin and pain.

DATA SYNTHESIS:

Neuropathic pain can be a problematic, chronic syndrome that is frequently refractory to current drug treatments. Gabapentin is a newer generation antiepileptic drug that is commonly used in treatment of neuropathic pain. An evaluation of clinical trials using gabapentin to treat neuropathic pain was performed.

CONCLUSIONS:

Gabapentin appears to be effective in treating various neuropathic pain disorders. Gabapentin may have advantages over current therapies, such as a favorable safety profile and lack of drug interactions; however, cost issues and limited experience may limit the use of gabapentin as a first-line option.
Alatrofloxacin-Induced Seizures during Slow Intravenous Infusion
Authors: Melvani Sharmila , Speed Bryan R
Published: June 2003

OBJECTIVE:

To report a case of seizures associated with slow infusion (1–2 h) of alatrofloxacin, the prodrug of trovafloxacin.

CASE SUMMARY:

A 37-year-old Asian man was admitted to the hospital for a distal pancreatectomy and drainage of a pseudocyst. Postoperative complications developed, which included peritonitis and pneumonia, requiring intensive care admission. Cultures from peritoneal drainage fluid and sputum isolated Klebsiella pneumoniae and Pseudomonas aeruginosa, respectively. He was treated with multiple courses of antibiotics, including intravenous gentamicin, metronidazole, vancomycin, meropenem, and ceftazidime. After three weeks, the patient still had sepsis and began therapy with alatrofloxacin in addition to ceftazidime and vancomycin. Alatrofloxacin infusion was administered according to product information instructions. Fifteen minutes after the first dose was started, the patient developed generalized clonus. On rechallenge, infusing at half the initial rate, the seizure recurred; consequently, the infusion was discontinued and replaced with intravenous ciprofloxacin and metronidazole. The patient remained seizure free thereafter.

DISCUSSION:

Fluoroquinolones have been implicated in central nervous system adverse effects, including seizures, which have been reported with other fluoroquinolones but not with alatrofloxacin or trovafloxacin. In these reports, the patients often had preexisting risk factors such as increased age and electrolyte imbalances. The only apparent predisposition in this patient was mild hyponatremia.

CONCLUSIONS:

Alatrofloxacin may cause seizures even during slow infusion. This case highlights the need for caution when commencing parenteral fluoroquinolone therapy, particularly with a new agent.
New Competition in the Realm of Renin—Angiotensin Axis Inhibition; the Angiotensin II Receptor Antagonists in Congestive Heart Failure
Authors: Martineau Pierre , Goulet Jude
Published: June 2003

OBJECTIVE:

To critically review the studies comparing angiotensin II (AgII) receptor antagonists with placebo or angiotensin-converting enzyme (ACE) inhibitors in patients with congestive heart failure (CHF).

DATA SOURCES:

A MEDLINE search (1988 to January 2000) was used to identify pertinent literature. Additional references were also retrieved from selected articles.

STUDY SELECTION:

As most published CHF studies were performed with candesartan and losartan, these agents are the main focus of this article. However, all identified comparative clinical studies were reviewed and included, regardless of the agent used.

DATA SYNTHESIS:

AgII receptor antagonists inhibit the effects of AgII at its sub-type 1 receptor, independently of AgIIs synthesis pathway. They present a hemodynamic profile similar to that of ACE inhibitors, without reflex neurohormonal activation. They have been shown to be at least as effective as ACE inhibitors in improving symptoms, exercise capacity, and New York Heart Association functional class in CHF patients. Although the ELITE (Evaluation of Losartan in the Elderly) trial suggested that losartan improved survival compared with captopril, this study was not designed to look at mortality. ELITE-II, an adequately powered study, showed no difference in mortality rates between patients taking captopril and those taking losartan. The combination of AgII receptor antagonists and ACE inhibitors provides additional benefit on blood pressure lowering and prevention of ventricular remodeling. AgII receptor antagonists are well tolerated, with an incidence of adverse effects similar to or lower than that of ACE inhibitors. Their lack of effect on bradykinin degradation might explain their lower incidence of cough.

CONCLUSIONS:

The data cumulated thus far in patients with CHF highlight that ACE inhibitors must remain the treatment of choice and that AgII receptor antagonists may be considered as an acceptable alternative for patients who are intolerant to ACE inhibitors.
Documentation of Clinical Interventions by Pharmacy Faculty, Residents, and Students
Authors: Taylor Charles T , Church Chelsea O , Byrd Debbie C
Published: June 2003

OBJECTIVE:

To describe the influence of pharmacy faculty, residents, and students at a community hospital by documenting the number and types of interventions attributable to their involvement in patient-care activities.

METHODS:

Between September 1, 1997, and May 31, 1999, data were collected using a computerized documentation system to characterize the intervention type, significance, and value of services rendered by an education group composed of pharmacy faculty (n = 2), residents (n = 4), and students (n = 22).

RESULTS:

The number, nature, and outcome category for all interventions were documented using an existing computerized documentation system. The education group accounted for 13% (n = 2873) of total clinical activities documented (n = 21 817). The most common activities reported were discharge counseling/education (31%), consultation by physicians and therapeutic recommendations (15%), and route conversion (6%). Interventions documented by the education group were classified as medium or high significance 50% of the time. Sixteen percent ($172 655) of the estimated cost avoidance documented by the pharmacy department was attributed to the education group.

CONCLUSIONS:

This study demonstrates that educational activities by pharmacy faculty, residents, and students have a positive influence on patient care in a community hospital.
Sucrose Analgesia for Minor Procedures in Newborn Infants
Authors: Masters-Harte Lory D , Abdel-Rahman Susan M
Published: June 2003

OBJECTIVE:

T o evaluate the role of intraoral sucrose and other sweet-tasting solutions for the management of pain associated with minor procedures in newborns.

DATA SOURCES:

A search of MEDLINE articles from 1966 to August 1999 and an extensive review of journals was conducted. MeSH headings included analgesia, sucrose, and neonate.

DATA SYNTHESIS:

Newborn infants regularly undergo minor invasive procedures for which analgesics are not routinely used. Intraoral sucrose and other sweet-tasting solutions appear to diminish surrogate biomarkers of pain response as evidenced by a reduction in crying time, smaller increases in heart rate, and lower pain scale ratings.

CONCLUSIONS:

These studies appear to suggest that sucrose solution 0.5 g provides effective analgesia with no reported adverse effects.
Olanzapine-Induced Glucose Dysregulation
Authors: Bettinger Tawny L , Mendelson Stacy C , Dorson Peter G , Crismon M Lynn
Published: June 2003

OBJECTIVE:

To report a patient who developed severe exacerbation of type 2 diabetes mellitus after the initiation of olanzapine therapy.

CASE SUMMARY:

A 54-year-old African-American woman developed severe glucose dysregulation 12 days after the initiation of olanzapine. Prior to starting olanzapine therapy, the patient's diabetes was controlled by diet modification with a glycosylated hemoglobin of 6.5%. During olanzapine therapy, blood glucose concentrations could not be regulated despite use of antidiabetic agents, insulin, and dietary interventions. The patient also gained a total of 13 kg. Two weeks after discontinuation of all antipsychotic medications (olanzapine, quetiapine), the patient's blood glucose concentrations became better regulated and remained better controlled until discharge.

DISCUSSION:

All atypical antipsychotics are associated with weight gain. Obesity is a well-documented risk factor for developing type 2 diabetes mellitus. Currently there are only six published reports that implicate olanzapine as being associated with glucose dysregulation. The exact cause of glucose dysregulation with olanzapine is unclear, but weight gain does not seem to be the sole etiology. It has been hypothesized that serotonin (5-HT1A) antagonism may decrease the responsiveness of the pancreatic β-cells. This would then result in inappropriately low insulin secretion and, therefore, hyperglycemia. Based on the Naranjo probability scale, the likelihood that olanzapine caused the glucose dysregulation in our patient was possible.

CONCLUSIONS:

Although olanzapine has shown greater clinical efficacy and is associated with fewer extrapyramidal side effects than typical antipsychotics, it may produce exacerbation or new emergence of diabetes mellitus. Further examination of the incidence and etiology of glucose dysregulation after the initiation of olanzapine therapy is necessary.
Entacapone
Authors: Chong Barbara S , Mersfelder Tracey L
Published: June 2003

OBJECTIVE:

To introduce entacapone, a new catechol- O-methyltransferase inhibitor, and discuss its pharmacology, pharmacodynamics, pharmacokinetics, clinical efficacy, drug interactions, adverse events, dosage guidelines, and therapeutic and formulary considerations.

DATA SOURCE:

A MEDLINE database search (1966–December 1999) was performed to identify relevant English-language articles including recent studies, abstracts, and reviews. Search terms included entacapone, OR-611, catechol- O-methyltransferase inhibitor, and Parkinson's disease.

STUDY SELECTION:

Relevant published human studies were chosen to summarize the pharmacokinetics, clinical efficacy, adverse effects, and drug interactions.

DATA EXTRACTION:

All available human clinical trials were reviewed.

DATA SYNTHESIS:

Entacapone is the second medication of a new class of drugs, the catechol- O-methyltransferase inhibitors, indicated for clinical use as an adjunct to levodopa/carbidopa to treat patients with idiopathic Parkinson's disease who experience the signs and symptoms of end-of-dose wearing-off. Entacapone in combination with levodopa/dopa decarboxylase inhibitor has been shown to increase the AUC of levodopa, which leads to less fluctuation of levodopa plasma concentrations. Clinically, the duration of motor response to levodopa was prolonged as reflected by an increase in the mean on time. The addition of entacapone resulted in a decrease in the mean daily dosage of levodopa. The recommended dosage of entacapone is 200 mg administered orally with each dose of levodopa/carbidopa, up to a maximum of eight doses per day. Common adverse effects include dyskinesia, nausea, diarrhea, and urine discoloration.

CONCLUSIONS:

Entacapone should be considered as add-on treatment to levodopa/carbidopa in Parkinson's disease patients with end-of-dose wearing-off effect.
Fatal Systemic Reaction after Multiple Doses of Intravesical Bacillus Calmette-Guérin for Polyposis
Authors: Peyrière Hélène , Klouche Kada , Béraud Jean-Jacques , Blayac Jean-Pierre , Hillaire-Buys Dominique
Published: June 2003

OBJECTIVE:

To report a case of fatal systemic reaction after intravesical administrations of bacillus Calmette-Guérin (BCG) for polyposis.

CASE SUMMARY:

A 72-year-old white man was treated by monthly injections of intravesical BCG immunotherapy for polyposis of the urinary bladder. He received a total of eight injections; four hours after the seventh injection, he presented with pyrexia associated with chills, sweating, headache, and vomiting, which quickly resolved. Four hours after the eighth injection, the patient presented with the same symptoms plus a left-hemisphere deficiency. Results of a cerebral scan performed at this time were normal. The clinical status of the patient quickly worsened, with the appearance of disseminated intravascular coagulation, acute anuric renal insufficiency, rhabdomyolysis, hemolysis, and cytolytic and cholestatic hepatitis. The patient required hemodialysis and symptomatic treatment. Lactic acidosis with hemolytic—uremic syndrome appeared, and he died as the result of a multivisceral (respiratory, renal, hepatic) deficiency.

DISCUSSION:

The patient presented with symptoms compatible with a severe systemic reaction to BCG therapy, a rare but possible adverse effect.

CONCLUSIONS:

BCG instillation is a valuable tool in the therapy of bladder carcinoma, but increasing reports of severe adverse reactions should continue to remind practicing urologists to be alert to the possibility of common and uncommon reactions after its use.
Acquired Factor VIII Inhibitor in a Patient with Chronic Myelogenous Leukemia Receiving Interferon-Alfa Therapy
Authors: English Kerri E , Brien William F , Howson-Jan Kang , Kovacs Michael J
Published: June 2003

OBJECTIVE:

To report a case of an acquired factor VIII inhibitor associated with the use of interferon-alfa.

CASE SUMMARY:

A 58-year-old white man with newly diagnosed chronic myelogenous leukemia (CML) was initially treated with hydroxyurea. Interferon-alfa therapy was started six weeks later in order to enhance the response, with gradual reduction and eventual discontinuation of hydroxyurea. Interferon-alfa was continued for one year. Following bone marrow aspiration at one year, the patient developed significant bleeding and bruising at the site of extraction. His hemoglobin decreased from 11.3 to 9.3 g/dL and his activated partial thromboplastin time was elevated at 72 seconds. The factor VIII concentration was 0.02 units/mL; factor VIII inhibitor concentration was 58 Bethesda units. A diagnosis of an acquired factor VIII inhibitor was made, and the patient was treated with activated factor VII concentrates and prednisone. Interferon-alfa was discontinued, and the inhibitor subsequently disappeared over the next six weeks. The patient did not have any further bleeding problems.

DISCUSSION:

Acquired factor VIII inhibitors other than in patients with hemophilia are rare. To date, there are no reported cases of factor VIII inhibitors associated with CML. Moreover, the temporal association with interferon-alfa administration suggests a causal relationship. There are only two previous case reports suggesting interferon-alfa as a cause of factor VIII inhibitors.

CONCLUSIONS:

Induction of factor VIII inhibitors is a serious potential complication of therapy with interferon-alfa. We suggest that a diagnosis of an acquired factor VIII inhibitor be considered in patients who experience unexplained bleeding with interferon-alfa therapy.
Ambulatory Care Pharmacy Services: Has the Agenda Changed?
Authors: Carter Barry L , Helling Dennis K
Published: June 2003

OBJECTIVE:

To provide an extensive review of ambulatory care clinical pharmacy services and evaluate the services and research data in the field.

DATA SOURCES:

MEDLINE was searched from January 1992 through July 1999. Search terms included pharmacy, clinical pharmacy, and pharmaceutical care, cross-referenced with ambulatory care, primary care, family medicine, and managed care.

STUDY SELECTION:

Relevant peer-reviewed studies and reports since our previous article in 1992 were selected and described. Literature prior to 1992 was briefly reviewed.

DATA SYNTHESIS:

The relevant literature was reviewed and some examples from the authors' institutions are provided. Much research has continued to be published documenting the value of clinical pharmacy services in ambulatory care, including in community pharmacy, anticoagulation services, family medicine, primary care clinics, Veterans Affairs Medical Centers, and managed care. However, these innovative services are underrepresented in the community at large. The vast majority of the public does not have access to these types of services.

CONCLUSIONS:

There will be continued and dramatic expansion of ambulatory care pharmacy services in the new decade beginning in the year 2000. It will be critical that standards of practice be very high. We believe there is a critical need for visible demonstration projects and large multicenter research projects that demonstrate the value of these services.