bluuebunny/crossref_metadata_2025 huggingface dataset:
Ondansetron in the Treatment of Intractable Nausea Associated with Theophylline Toxicity
Authors: Sage Therese A. , Jones William N. , Clark Richard F.
Published: January 2017

OBJECTIVE:

To report the efficacy of ondansetron in the treatment of a patient poisoned with theophylline.

PATIENT:

A 36-year-old man who ingested 6 g of sustained-release theophylline.

INTERVENTION:

Ondansetron 8 mg intravenously after clinical failure of other antiemetics.

RESULTS:

Subjective relief of nausea within minutes, enabling the patient to tolerate multiple doses of activated charcoal and whole bowel irrigation.

CONCLUSIONS:

Ondansetron may offer an alternative to present antiemetic therapy in the poisoned patient.
Effect of Seven Fluoroquinolones on the Determination of Serum Creatinine by the Picric Acid and Enzymatic Methods
Authors: Massoomi Firouzan , Mathews Herbert G. , Destache Christopher J.
Published: January 2017

OBJECTIVE:

To investigate in vitro the interaction of seven fluoroquinolone antibiotics with the determination of serum creatinine by the picric acid and enzymatic methods.

DESIGN:

This blind, in vitro study assayed duplicate serum samples for creatinine by the picric acid and enzymatic methods with averaged spiked concentrations of 2.71, 13.56, 27.12, and 108.47 μmol/L of ciprofloxacin, fleroxacin, lomefloxacin, ofloxacin, 1-ofloxacin, sparfloxacin, and temafloxacin. Cefoxitin (in concentrations of 233.9, 1169.6, 1754.4, and 2339.2 μmol/L) was used as a positive control for the picric acid assay.

SETTING:

University-affiliated hospital, Department of Pharmaceutical Services and Clinical Chemistry section of the Department of Pathology.

MAIN OUTCOME MEASURE:

The serum creatinine samples spiked with the seven substituted fluoroquinolones and cefoxitin were assayed by both the picric acid and enzymatic assays. Statistical analysis compared the spiked samples with blank serum by Student's t-test and concentration ranges were compared by analysis of variance. A statistically significant interference with serum creatinine was p<0.05.

RESULTS:

None of the substituted fluoroquinolones interfered significantly with the determination of serum creatinine by either method. Cefoxitin significantly interfered with the determination of serum creatinine by the picric acid method.

CONCLUSIONS:

Fluoroquinolones do not interfere with the determination of serum creatinine by either the picric acid or enzymatic method.
Natural Products and the Athlete: Facts and Folklore
Authors: Barron Richard L. , Vanscoy Gordon J.
Published: January 2017

OBJECTIVE:

To contrast scientific facts with suggested manufacturers' claims regarding food supplements (natural products) marketed for enhanced athletic prowess.

DATA SOURCES:

A MEDLINE search was performed to obtain documentation supporting the claims of natural-product manufacturers. In addition, several references pertaining to pharmacognosy, natural products, herbs, pharmacy practice, and sports medicine were reviewed. Claims were obtained from promotional advertisements in bodybuilding magazines, product labels, and fact sheets for sales representatives in nutrition and health-food stores.

DATA EXTRACTION:

We reviewed all of the clinical trials, published between 1966 and 1992, relative to the manufacturers' claims regarding these products.

DATA SYNTHESIS:

Pertinent human and/or animal studies supporting each natural product were compared with the manufacturers' claims.

CONCLUSIONS:

We found that there was no published scientific evidence to support the promotional claims for a large proportion of the products (8/19,42 percent). Only 4 of 19 products (21 percent) were associated with any documented human clinical trials supporting their promotional claims. Six of 19 agents (32 percent) had some scientific documentation to support their promotional claims; however, these products were judged to be marketed in a misleading manner.
Unmasking the Significant Enzyme-Inducing Effects of Phenytoin on Serum Carbamazepine Concentrations during Phenytoin Withdrawal
Authors: Chapron Dennis J. , LaPierre Barbara A. , Abou-Elkair Mervet
Published: January 2017

OBJECTIVE:

We report on two patients who appeared to exhibit profound induction of carbamazepine metabolism during cotherapy with phenytoin. Gradual withdrawal of phenytoin confirmed this impression.

DESIGN:

Two case studies.

RESULTS:

Two patients receiving carbamazepine and phenytoin as combination anticonvulsant therapy were admitted for comprehensive rehabilitation. A 23-year-old man had therapeutic serum phenytoin concentrations, but his serum carbamazepine concentrations were so low that they were nonquantifiable. Doubling the daily carbamazepine dosage did not yield quantifiable serum concentrations. When the daily phenytoin dosage was tapered from 500 to 200 mg, the carbamazepine concentration rose to 10.0 μg/mL. No further changes in serum carbamazepine concentrations were observed when the phenytoin was discontinued. A 49-year-old man was receiving large daily dosage of phenytoin (600 mg) and carbamazepine (2300 mg). In the process of tapering and discontinuing phenytoin, the patient became lethargic and confused. These signs and symptoms suggested carbamazepine toxicity. The patient was eventually stabilized on a carbamazepine dosage of 1200 mg/d, which produced a serum concentration of 8.4 μg/mL. When this patient had been receiving concurrent phenytoin therapy, approximately twice as much carbamazepine (2300 mg) was required to maintain a similar serum concentration.

CONCLUSIONS:

Phenytoin is a potent inducer of carbamazepine metabolism. Whenever phenytoin dosages are tapered and discontinued in patients receiving these medications concomitantly, frequent serum carbamazepine monitoring is recommended during the ensuing deinduction phase.
Clonidine Patch Ingestion in an Adult
Authors: Raber Jack H. , Shinar Chris , Finkelstein Stuart
Published: January 2017

OBJECTIVE:

To report a case of deliberate ingestion of a clonidine hydrochloride patch in an adult.

CASE SUMMARY:

A patient at a psychiatric hospital with a diagnosis of major depression and polysubstance abuse was administered a clonidine patch for opiate detoxification. The patient subsequently chewed and swallowed the patch (total clonidine content: 5 mg); he was subsequently transferred to a nearby general medical hospital for management of obtundation and profound sinus bradycardia.

DISCUSSION:

The use of clonidine in withdrawal states is discussed. The primary adverse effects attributable to clonidine overdose, hypotension, and profound sinus bradycardia, may be managed symptomatically. Accidental ingestion of clonidine patches by infants and children has previously been reported in the literature. This is the first reported case of deliberate ingestion of a clonidine patch in an adult.

CONCLUSIONS:

Before initiating topical clonidine therapy for chemical withdrawal states, patients should be evaluated carefully for suicide potential and a history of previous suicide attempts. If a patient expresses suicidal ideation or has attempted suicide in the past, he is probably not a candidate for topical clonidine therapy in either the inpatient or outpatient setting.
Nicotine Transdermal Systems
Authors: Gora Mary Lea
Published: January 2017

OBJECTIVE:

To review the role of transdermal nicotine as an aid to smoking cessation.

DATA SOURCES:

A MEDLINE search was performed that included clinical studies published in English involving transdermal nicotine; references used in those articles were screened for additional published information.

STUDY SELECTION:

Published clinical trials were reviewed with particular emphasis on controlled trials that evaluated safety and efficacy.

DATA SYNTHESIS:

Transdermal nicotine therapy has been shown to be a safe and effective pharmacologic aid in a smoking cessation program when used in conjunction with a psychologic or behavior support system. Habitrol, Nicoderm, Nicotrol, and PROSTEP differ in some characteristics (i.e., delivery systems, total nicotine content and amount absorbed, rate of delivery, recommended duration of application); however, the clinical implication of these differences has not been determined.

CONCLUSIONS:

Transdermal nicotine is effective for patients who are motivated to quit smoking and receive concomitant behavior support.
Intrathecal Baclofen for Severe Spasticity Secondary to Spinal Cord Injury
Authors: Lewis Kelly S. , Mueller Wade M.
Published: January 2017

OBJECTIVE:

To evaluate the use of intrathecal baclofen for the treatment of muscle spasticity in patients with spinal cord injury.

DATA SOURCES:

A MEDLINE search was used to identify relevant and pertinent literature. Information was obtained from open-label clinical trials, abstracts, conference proceedings, and review articles. Index terms in the search included baclofen, spasticity, intrathecal drug infusion, spinal cord disease, and neurosurgery.

DATA EXTRACTION:

Studies were selected for review if they evaluated intrathecal baclofen in patients with spinal cord injury. Emphasis was placed on human studies published in the English language. Trials were reviewed by dosage regimen, therapeutic response, adverse effects, and complications.

DATA SYNTHESIS:

Thus far, intrathecal baclofen administration shows promise in the treatment of spasticity resulting from spinal cord trauma. Few complications and adverse effects have been reported.

CONCLUSIONS:

Muscle spasms and spasticity constitute a significant problem in spinal cord injuries, interfering with rehabilitation and leading to inconveniences and complications in these patients. Oral baclofen is the drug of choice for spasticity due to spinal cord trauma. It often is ineffective, however, because of the large dosages required to cross the blood-brain barrier and the subsequent appearance of central nervous system adverse effects. These adverse effects are not tolerated by many patients. Intrathecally administered baclofen has been approved by the Food and Drug Administration (FDA) for the treatment of spasticity in patients with spinal cord injury who are refractory to or cannot tolerate oral baclofen. It is intended for use only in implantable pumps approved by the FDA for the administration of baclofen into the intrathecal space. Intrathecal administration achieves high concentrations in the spinal cord with small dosages, thus reducing the incidence of central nervous system adverse effects. To date, approximately 350 patients with spinal cord injury have been treated with intrathecal baclofen. Reductions in spasticity have been demonstrated in both open-label and placebo-controlled trials. Patients also often make substantial gains in activities of daily living. Few adverse effects and complications have been reported. However, tolerance to the clinical effects of intrathecal baclofen has been reported. Further studies are needed to determine specific patient populations that may benefit most from intrathecal baclofen administration. Individual dosage ranges and follow-up care also need to be defined more completely. In addition, the question of whether tolerance detracts from long-term clinical benefits with intrathecal baclofen needs to be addressed.
A Practical Alternative to Conventional Aminoglycoside Dosing Methods
Authors: Goldman Morton P. , Fuller Matthew A.
Published: January 2017

OBJECTIVE:

One-compartment pharmacokinetic equations are adequate to perform clinical dosing adjustments for aminoglycoside monitoring. This article describes the Fuller-Goldman (FG) method, an alternative method of aminoglycoside dosage adjustment after serum concentrations have been obtained. The FG method uses pharmacokinetic principles, but does not use standard pharmacokinetic equations (SPE) for aminoglycoside dosage adjustment. A comparison of the FG method to SPE is also presented.

DATA SOURCES:

Information was obtained from pharmacokinetic textbooks and references using basic pharmacokinetic concepts. Forty sets of peak and trough serum drug concentrations were randomly chosen, retrospectively, from routine pharmacokinetic service data. All of the patients were men with a variety of infectious diseases and cared for on general surgical and medical floors, intensive care units, and a spinal cord injury unit.

STUDY SELECTION:

No studies have previously been published using this dosing method.

DATA EXTRACTION:

Peak and trough data were extracted from routine pharmacokinetic monitoring forms kept by the coordinator of the Pharmacokinetic Monitoring Service at the Department of Veterans Affairs Medical Center.

DATA SYNTHESIS:

The FG method is characterized by assumptions and limitations similar to those of standard pharmacokinetic dosing methods. Forty sets of data were evaluated using both the FG method and SPE. These data were analyzed using mean percent differences of projected dosages and projected half-lives (t1/2s) as measures of the average magnitude of the discrepancy between the two methods. Ninety-five percent confidence intervals for mean percent differences also are provided.

CONCLUSIONS:

The FG method overestimated by 10.18 percent the dosage recommendations of the SPE method. This method also underestimated t1/2 by 2.96 percent, compared with SPE. The FG method is a viable alternative aminoglycoside dosing technique that requires one to use learned pharmacokinetic concepts.
Sotalol: A Breakthrough Antiarrhythmic?
Authors: Nappi Jean M. , McCollam Patrick L.
Published: January 2017

OBJECTIVE:

To review the pharmacology, pharmacokinetic, dosing, adverse effects, and therapeutic uses of sotalol.

DATA IDENTIFICATION:

Articles were identified with an English-language literature computer search via Knowledge Finder, using the term sotalol, and with an extensive search of bibliographies of identified articles.

STUDY SELECTION:

Relevant or representative animal studies, human trials, and case reports were selected for evaluation.

DATA EXTRACTION:

The literature was assessed for quality, methodology, and outcome information.

DATA SYNTHESIS:

Sotalol is a racemic compound with Class II (beta-blocking properties) and Class III (prolonged action potential) antiarrhythmic activity. It has been suggested that the plasma concentration associated with QTc prolongation (a measure of the Class III action) is much greater than that associated with beta-blockade. Therefore, sotalol is categorized as a Class III antiarrhythmic agent. The l-isomer is responsible for the beta-blocking activity, whereas both isomers have Class III properties. After oral dosing in fasting patients with normal renal function, sotalol is >90 percent absorbed, achieves peak serum concentrations in 2–4 h, is excreted unchanged 80–90 percent in the urine, has a volume of distribution of 1–2L/kg, and has an elimination half-life of about 12 h. Sotalol is effective in patients with life-threatening ventricular arrhythmias that have been refractory to other conventional antiarrhythmic drugs. In general, sotalol appears to be well tolerated, with many of its adverse effects caused by beta-blocking activity. As with other antiarrhythmic agents, the possibility of proarrhythmia (frequently torsade de pointes) exists.

CONCLUSIONS:

Racemic sotalol is an effective Class III antiarrhythmic agent approved by the Food and Drug Administration for the treatment of documented life-threatening ventricular arrhythmias. Investigations continue with racemic sotalol in the management of supraventricular arrhythmias. Trials with the d-isomer are also ongoing.
Bacillary Angiomatosis in a Patient with AIDS
Authors: Teague A. Christine , Parks Sharon K.
Published: January 2017

OBJECTIVE:

To report the clinical presentation and response to antimicrobial therapy of presumed bacillary angiomatosis in an AIDS patient.

DESIGN:

Single case report.

SETTING:

A 1058-bed, university teaching hospital.

PATIENT:

28-year-old HIV-positive man (T4 lymphocyte count <3/mm3), who was diagnosed with AIDS in 1984.

RESULTS:

The skin lesions responded promptly to treatment with doxycycline and erythromycin.

CONCLUSIONS:

Bacillary angiomatosis is an infection that occurs with endstage AIDS. Skin lesions have recognizable characteristics and respond promptly to appropriate antibiotic therapy.
Drug Disposition in Neonates with Patent Ductus Arteriosus
Authors: Gal Peter , Gilman Jamie T.
Published: January 2017

OBJECTIVE:

To review the literature on the physiologic changes created by neonatal patent ductus arteriosus (PDA) and the potential impact on drug disposition in these infants.

DATA SOURCES:

An Index Medicus and bibliographic search of the English-language literature pertaining to neonatal PDA and drug usage in newborns.

DATA SYNTHESIS:

PDA in premature infants is associated with a variety of physiologic changes that could alter drug disposition. Perfusion of drug-elimination organs (i.e., liver and kidney) may be diminished, resulting in decreased drug elimination. Further, the general fluid overload state associated with PDA may result in larger volumes of distribution (Vd), and dilutional effects for many drugs. Drug absorption, Vd, tissue penetration, and clearance may be affected by the physiologic changes incurred by a PDA. Although the pharmacokinetics of several categories of therapeutic agents may be affected by a PDA, disposition changes with the aminoglycosides and indomethacin have been the best documented. The most reliable pharmacokinetic change appears to be related to drug Vd. The interpretation of many of these studies is confounded by a potential drug interaction with the concurrent administration of indomethacin for PDA closure.

CONCLUSIONS:

Close therapeutic drug monitoring is indicated in newborns with PDAs as abrupt changes in drug disposition can occur with PDA closure. PDA-induced changes in specific pharmacokinetic parameters of agents such as the aminoglycosides, indomethacin, and perhaps vancomycin may prove to be a valuable diagnostic adjunct for the identification of babies with undiagnosed PDA. More research into this pharmacophysiologic aspect of pharmacokinetics is warranted.
Assessing Physician Choice of Nonsteroidal Antiinflammatory Drugs in a Health Maintenance Organization
Authors: Kaplan Barbara , Farris Karen B. , Kirking Duane M.
Published: January 2017

OBJECTIVE:

To develop a categorization scheme for grouping various nonsteroidal antiinflammatory drugs (NSAIDs) by relative safety; to develop a method to quantify the appropriateness of the initial and subsequent choices of NSAID therapy; to assess whether NSAID prescribing was consistent with the developed criteria; to examine the cost of inappropriate, acute NSAID use as defined by the established criteria.

DESIGN:

Retrospective drug utilization review focusing on NSAIDs.

SETTING/PARTICIPANTS:

Members aged age⩾18 years of a 40 000-person southeastern Michigan health maintenance organization

MAIN OUTCOME MEASURES:

(1) Appropriateness of therapy using a four-level safety classification system for the NSAIDs developed by a consensus process; criteria based on safety under the assumption that any particular NSAID is equally likely to be effective when dosed appropriately; (2) evaluation of progression of NSAID therapy using the NSAID Therapy Progression Formula.

RESULTS:

For acute patients, almost half of the prescriptions were for ibuprofen and 33 percent were for naproxen. Ibuprofen usage accounted for 16 percent of total NSAID cost and naproxen agents accounted for over 50 percent of that cost. Potential cost savings of approximately $82 000 probably would have occurred had a 50 percent interchange rate for ibuprofen been acceptable. For chronic patients, 85 percent were treated with one or two NSAIDs; treatments were of reasonable high quality when compared by safety profiles. There was low use of ibuprofen in patients who only received one NSAID.

CONCLUSIONS:

NSAID usage assessment in a large population was achieved by developing a classification and scoring system based on NSAID safety; in this population, prescribing patterns were generally consistent with established criteria; however, when considering cost, improvement in initial NSAID selection for acute patients was possible.
Rapid Determination of Maintenance Heparin Infusion Rates with the Use of Non-Steady-State Heparin Concentrations
Authors: Kandrotas Robert J. , Gal Peter , Douglas Jean B. , Groce James B.
Published: January 2017

OBJECTIVE:

To compare heparin dosage adjustment using only activated partial thromboplastin time (APTT) with a method using non-steady-state heparin concentrations (HCs) to rapidly achieve and maintain an APTT ratio greater than or equal to 1.5 times baseline throughout the first 24 hours of therapy.

DESIGN:

Randomized, blind, parallel comparison of an empiric dosing method based only on APTT with a dosing method based on the calculation of heparin clearance using non-steady-state HCs.

SETTING:

A private community teaching hospital. The patient, physician, nurses, and investigators were blinded to the dosing method. Only the clinical staff pharmacist, who received the consult and made all dosage adjustments, was not blinded.

PATIENTS:

All patients requiring heparin for the treatment of thromboembolic disease were evaluated for potential inclusion in the study. Patients were enrolled in the study if they had a clinical diagnosis of deep venous thrombosis confirmed by objective means such as venography or ultrasonography. Patients were excluded if they had active bleeding, platelet dysfunction, thrombocytopenia, severe hepatic disease (total bilirubin >25.7 μmol/L), renal disease, or evidence of stroke. Patients were also excluded if they were receiving heparin prior to enrollment.

MAIN OUTCOME MEASURE:

Maintenance of an APTT ratio greater than or equal to 1.5 times baseline throughout the first 24 hours of heparin therapy.

RESULTS:

Thirty-four patients were enrolled in the study; 17 in each group. The groups were not significantly different with regard to gender, age, baseline APTT, or mean loading dose (p>0.5). Mean initial infusion rates for the control and HC groups were 1042 ± 194 and 1071 ± 143 units/h, respectively (p>0.5). After the first rate adjustment at 4 hours, the difference achieved significance at 1032 ± 232 and 1367 ± 317 units/h for the control and HC groups, respectively (p<0.01). At 12 hours, 18.8 percent of the patients in the control group were subtherapeutic; by 24 hours, 33.3 percent were subtherapeutic. No patients became subtherapeutic in the HCs group during the first 24 hours.

CONCLUSIONS:

This study demonstrates that, in contrast to standard heparin dosing methods, the use of non-steady-state HCs allows patients with deep venous thrombosis to rapidly achieve and maintain therapeutic APTT ratios throughout the critical first 24 hours of therapy.
Fluosol: Therapeutic Failure in severe Anemia
Authors: Kale Pramodini B. , Sklar Grant E. , Wesolowicz Laurie A. , DiLisio Ralph E.
Published: January 2017

OBJECTIVE:

To report the use of Fluosol in the management of a severe anemia and to review the literature regarding the use of Fluosol.

CASE REPORT:

A 40-year-old woman, at 40.5 weeks gestation, was admitted for induction of labor. Her hospital course was complicated by a postpartum hemorrhage and severe anemia. Because the patient was a Jehovah's Witness, she received non-blood products including hetastarch, iron dextran, and erythropoietin, and a total of 33 mL/kg of Fluosol, but she did not survive.

DISCUSSION:

Fluosol is an oxygen-carrying, perfluorochemical blood substitute. It was administered to our patient, who presented with the lowest hemoglobin (Hb) (11 g/L) and hematocrit (0.31 fraction of 1.00) of all reported cases. Almost all patients with an Hb <20 g/L do not survive.

CONCLUSIONS:

Although the use of Fluosol as a blood substitute appears theoretically promising, its use in the management of severe anemia cannot be recommended.
Fluvoxamine-Associated Manic Behavior: A Case Series
Authors: Dorevitch Abraham , Frankel Yehuda , Bar-Halperin Asher , Aronzon Rami , Zilberman Liana
Published: January 2017

OBJECTIVE:

To report cases of manic-like behavior induced by fluvoxamine, a selective serotonin-reuptake inhibitor; to review pertinent literature; and to encourage replication of our findings in larger patient samples.

DESIGN:

Description of a case series of fluvoxamine-induced, manic-like behavior.

PATIENTS:

Eight patients with depression or obsessive features who developed manic-like behavior after initiation of fluvoxamine therapy.

RESULTS:

Manic symptomatology resolved in all eight patients following dosage reduction or withdrawal of fluvoxamine. Four patients still are maintained on low-dose fluvoxamine without recurrent manic symptoms.

CONCLUSIONS:

Our case series suggests that fluvoxamine may have the ability to induce or unmask manic behavior in depressed patients. Clinicians are alerted to monitor for this “switching” effect, especially in patients previously or currently treated with neuroleptics or lithium, and in those patients exhibiting characteristics of obsessive-compulsive disorder.
Vesicular Eruptions following Acyclovir Administration
Authors: Buck Marcia L. , Vittone Sarah B. , Zaglul Horacio F.
Published: January 2017

OBJECTIVE:

To report the occurrence of vesicular lesions on the skin of a child receiving intravenous acyclovir therapy.

CASE SUMMARY:

A 12-year-old boy with presumed herpes simplex encephalitis developed cutaneous vesicular lesions following intravenous acyclovir administration. The lesions were initially thought to be herpetic. Further evaluation of the vesicle fluid and the temporal relationship of the development of the lesions with acyclovir administration led to the conclusion that the reaction was drug induced.

DISCUSSION:

Although inflammation and phlebitis are fairly common after acyclovir infusion, the development of vesicular lesions appears to be rare. Only two cases, both in adults, have been published in the medical literature. Although several theories have been proposed, including hypersensitivity, local drug toxicity, and tissue damage associated with extravasation, the mechanism of this reaction remains unclear.

CONCLUSIONS:

Vesicular eruption is a rare adverse reaction in patients receiving acyclovir. Careful evaluation is necessary to differentiate this reaction from herpetic lesions.
Treatment of Cryptosporidial Diarrhea in an AIDS Patient with Paromomycin
Authors: Danziger Larry H. , Kanyok Thomas P. , Novak Richard M.
Published: January 2017

OBJECTIVE:

To report a case of diarrhea caused by Cryptosporidium in an AIDS patient which was successfully treated with paromomycin.

CASE SUMMARY:

An AIDS patient with a 12-month history of Cryptosporidial diarrhea unresponsive to other treatment measures was treated with paromomycin 500 mg q6h for 14 days. Before initiating therapy, the patient was experiencing, on average, 20 bowel movements per day and had lost more than 25 kg. After therapy was initiated, the number of bowel movements dropped to 1–2 per day and the patient began to gain weight. The diarrhea recurred when therapy was discontinued. After retreatment for 14 days with paromomycin 500 mg q6h, the diarrhea stopped. The patient has not had a recurrence of Cryptosporidium diarrhea, stool cultures remain negative for Cryptosporidium oocysts, and the patient has regained most of the weight.

DISCUSSION:

Literature concerning the use of paromomycin for the treatment of cryptosporidiosis is discussed. A treatment algorithm for the management of cryptosporidiosis in AIDS patients is presented.

CONCLUSIONS:

We believe that we have presented a clear example of a case in which paromomycin was effective in treating and eradicating intestinal cryptosporidiosis in an AIDS patient. Paromomycin is the most effective agent available to date for the treatment of this devastating complication of AIDS.
Amiodarone-Clonazepam Interaction
Authors: Witt Daniel M. , Ellsworth Allan J. , Leversee John H.
Published: January 2017

OBJECTIVE:

To describe a potential drug interaction between amiodarone and clonazepam.

CASE SUMMARY:

A 78-year-old man with a history of congestive heart failure and coronary artery disease began taking amiodarone to suppress sustained ventricular tachycardia. Following the development of restless leg syndrome, therapy with clonazepam 0.5 mg qhs was initiated. Subsequently, the patient demonstrated signs and symptoms of benzodiazepine toxicity, which cleared following the discontinuation of clonazepam.

DISCUSSION:

Amiodarone is a Class III antiarrhythmic with an adverse-effect profile involving many different organ systems. It also has been shown to inhibit the metabolism of drugs cleared by oxidative microsomal enzymes. Clonazepam undergoes extensive hepatic metabolism, primarily by reduction and acetylation, and is therefore susceptible to altered disposition during concomitant administration of agents that inhibit hepatic microsomal enzymes. Hypothyroidism, occurring in up to 11 percent of patients treated with amiodarone, can also alter drug metabolism and sensitize the central nervous system, thus increasing the potential for toxicity. It is likely that a combination of these factors was responsible for the symptoms described in this patient.

CONCLUSIONS:

The complex pharmacologic profile of amiodarone and its effects on multiple organ systems necessitates close patient monitoring during concurrent administration of medications such as clonazepam, which are cleared by oxidative metabolism.
Ciprofloxacin-Induced Toxic Epidermal Necrolysis
Authors: Moshfeghi Mersedeh , Mandler Hilary D.
Published: January 2017

OBJECTIVE:

To report a case of probable ciprofloxacin-induced toxic epidermal necrolysis (TEN) in an adult with systemic lupus erythematosus (SLE).

CASE SUMMARY:

A 31-year-old woman with SLE developed a pruritic rash following her first dose of oral ciprofloxacin. She continued taking ciprofloxacin, and the rash progressively worsened, becoming painful and covering her entire body. She discontinued the ciprofloxacin six days later and presented to the hospital, where two days later, her rash began to desquamate with epidermal erosions and a positive Nikolsky's sign. Skin biopsy was positive for TEN. She then was transferred to a burn-treatment unit because of the severity of the skin involvement. The patient recovered following prolonged hospitalization and rehabilitation.

CONCLUSIONS:

Although TEN occurs rarely with ciprofloxacin, extensive postmarketing surveillance needs to be performed to determine other risk factors for its development and to establish the incidence of TEN and other severe cutaneous reactions caused by ciprofloxacin or the other fluoroquinolones.
ATOVAQUONE: A Review
Authors: Haile Lydia G. , Flaherty John F.
Published: January 2017

OBJECTIVE:

To review the chemistry, pharmacology, pharmacokinetics, clinical efficacy, and safety of atovaquone.

DATA IDENTIFICATION:

An English-language literature search using MEDLINE (1984-1993), programs and abstracts of the 30th, 31st, and 32nd Interscience Conferences on Antimicrobial Agents and Chemotherapy, program and abstracts of the VIII International Conference on AIDS, and unpublished information from Burroughs Wellcome, the manufacturer of atovaquone.

STUDY SELECTION:

All available pharmacokinetic and clinical trials were reviewed.

DATA EXTRACTION:

Study quality was assessed by a critical appraisal of study design and methods. Pharmacokinetic studies were evaluated for sampling, methods used to determine pharmacokinetic properties, and the presence of concentration-response and concentration-toxicity relationships. Clinical trials were assessed primarily for comparative efficacy and toxicity.

RESULTS:

Atovaquone is a novel hydroxynaphthoquinone with potent activity against Pneumocystis carinii and Toxoplasma gondii. Its pharmacokinetic properties are characterized by relatively poor bioavailability, excretion almost exclusively through the feces, lack of hepatic metabolism and urinary excretion, low steady-state plasma concentrations, high protein binding, and a long elimination half-life (50-70 h). Results from comparative clinical trials in AIDS patients with mild-to-moderate P. carinii pneumonia (PCP) reveal similar overall treatment success rates for atovaquone, trimethoprim/sulfamethoxazole (TMP/SMX), and pentamidine. Treatment failure because of lack of therapeutic response was significantly greater in patients who received atovaquone compared with those treated with TMP/SMX (p=0.002). More atovaquone-patients experienced treatment failure compared with their pentamidine-treated counterparts, although statistical significance was not achieved. Treatment failure secondary to drug toxicity was significantly higher in the TMP/SMX- and pentamidine-treated patients (p<0.01). Atovaquone has not been studied for PCP prophylaxis. Limited data exist on the use of atovaquone for toxoplasmic encephalitis (TE); however, results from an open trial reveal that the drug may be useful in treating this disorder. To date, atovaquone has been well tolerated by most patients administered the drug. The most common adverse effects include maculopapular rash, gastrointestinal disturbances, and fever. Atovaquone is considerably more costly than other oral agents used to treat PCP.

CONCLUSIONS:

Atovaquone appears to be better tolerated but less effective than TMP/SMX and pentamidine in the treatment of mild-to-moderate PCP. There is not enough information available on the use of atovaquone for PCP prophylaxis or the treatment of TE to definitively describe its efficacy. Comparative clinical trials are needed to assess its role in this clinical setting.
So Much Writing, So Little Science: A Review of 37 Years of Literature on Edetate Sodium Chelation Therapy
Authors: Grier Michael T. , Meyers David G.
Published: January 2017

OBJECTIVE:

To determine the safety and efficacy of edetate sodium (ethylenediamine tetraacetic acid; EDTA) chelation therapy for atherosclerosis.

METHODS:

Literature search using MEDLINE, encompassing 1966 through May 1993. Further references were obtained from articles and books, and from citations obtained from the American Academy of Medical Preventics.

RESULTS:

16 case reports or case series, 2 longitudinal studies, and 3 clinical trials were reviewed, along with testimonials cited in 19 books.

CONCLUSIONS:

Little valid scientific evidence is available. Although the postulated mechanisms of action for EDTA are biologically plausible and EDTA appears to be safe, it has not been proven effective. Indeed, the best evidence shows it to be ineffective. Therefore, EDTA chelation therapy should not be used in clinical practice to treat atherosclerosis.
Evaluation of The Pharmacokinetic Interaction Between Cemetidine or Famotidine and Cyclosporine in Healthy Men
Authors: Shaefer Mark S , Rossi Stephen J , Mcguire Timothy R , Schaaf Larry J , Collier Dean S , Stratta Robert J
Published: January 2017

Objective:

To investigate the potential interaction between cimetidine or famotidine and cyclosporine in healthy men.

Design:

All subjects received oral cyclosporine at baseline, after the first week of 1 histamine2 (H2)-blocker, and a third time after a 1-week washout plus 1 week of the second H2-blocker. Blood samples were collected just before each dose of cyclosporine and for up to 36 hours afterward for pharmacokinetic analysis.

Setting:

A college of pharmacy in a university teaching hospital.

Participants:

The study population consisted of 8 healthy men at least 19 years of age.

Main Outcome Measures:

Cyclosporine concentrations in whole blood were measured using a polyclonal fluorescence polarization immunoassay. Cyclosporine pharmacokinetic parameters during each of the 3 treatment periods were compared.

Results:

The average times to maximum cyclosporine concentrations were similar between baseline (3.2 h), cimetidine (2.9 h), and famotidine (3.6 h) dosing periods. There were no significant differences in area under the curve, half-life, or maximum concentration during the 3 dosing periods.

Conclusions:

Neither cimetidine or famotidine produced a significant change in the pharmacokinetics of single-dose oral cyclosporine in healthy men.
Difference Between the Measured and Ordered Dose of Catecholamine Infusions
Authors: Allen Elizabeth M , Boerum Don H Van , Olsen Alice F , Dean J Michael
Published: January 2017

Objective:

To measure the actual concentrations of dopamine, dobutamine, and epinephrine in infusates prepared for patients, and to compare these concentrations with those of the dopamine HCl, dobutamine, and epinephrine HCl infusates that had been prescribed to evaluate drug preparation accuracy.

Design:

Prospective, unblind study.

Setting:

Pediatric intensive care unit in a tertiary-care teaching hospital.

Participants:

All dopamine, dobutamine, and epinephrine infusions ordered for patients during the 2-month study period were eligible for inclusion in the study.

Measurements:

Daily samples of dopamine, dobutamine, and epinephrine infusates that were prepared for 41 pediatric patients were obtained; the infusate catecholamine concentration was measured by HPLC and compared with the ordered concentration. The concentration then was multiplied by the rate of infusion to determine the catecholamine dose.

Main Results:

There were significant differences between the measured doses of dopamine, dobutamine, and epinephrine and the dopamine HCl, dobutamine, and epinephrine HCl doses (p = 0.0001, p = 0.039, and p = 0.0009, respectively) that had been ordered because of preparation inaccuracies. Failure to account for the HCl salt in the stock drug accounted for some, but not all, of the inaccuracy of the dopamine HCl and epinephrine HCl infusates. There was a wide interday variability in the measured catecholamine dosage in patients receiving the same dose for 3 days or more.

Conclusions:

There are daily fluctuations in the preparation of dopamine, dobutamine, and epinephrine infusates that could alter the amount of drug actually delivered to critically ill patients and potentially contribute to their hemodynamic instability.
Compatibility of Ondansetron Hydrochloride with Meperidine Hydrochloride for Combined Administration
Authors: Xu Quanyun A , Trissel Lawrence A , Fox Janet L
Published: January 2017

Objective:

To determine the physical compatibility and chemical stability of ondansetron hydrochloride 0.1 and 1 mg/mL with meperidine hydrochloride 4 mg/mL admixed in NaCl 0.9% injection USP.

Design:

Triplicate test solutions of the drugs in NaCl 0.9% injection USP were prepared and stored at 4,22, and 32 °C. Samples were removed initially and at various time points over 31 days and were stored at −70 °C until they were analyzed. Physical compatibility was assessed by measuring solution turbidity with a color-correcting turbidimeter and particle content with a light-obscuration particle sizer/counter, as well as by visual assessment. Chemical stability of the drugs was determined using a stability-indicating HPLC analytic method. Duplicate determinations were performed on each sample to measure the concentration of each drug.

Results:

All admixtures were found to exhibit no visual or subvisual changes of consequence in turbidity or particle content at all observation points. Further, little or no loss of any of the drugs occurred in any concentration throughout the study.

Conclusions:

The physical compatibility and chemical stability of ondansetron hydrochloride with meperidine hydrochloride under the conditions of this study have been established for 7 days at 32 °C and 31 days at 4 and 22 °C.
Opioid-Induced Muscle Activity: Implications for Managing Chronic Pain
Authors: Sylvester Robert K , Levitt Ralph , Steen Preston D
Published: January 2017

Objective:

To increase awareness of opioid-induced involuntary muscle hyperactivity and to present management options.

Case Summary:

A ventilator-dependent 71-year-old man presented with pain caused by metastatic lung cancer. Transdermal fentanyl therapy was titrated to 200 μg/h. Two days later a continuous morphine infusion was initiated because of frequent administration of oral morphine solution for breakthrough pain. The patient became progressively less responsive and began exhibiting involuntary muscle hyperactivity thought to represent breakthrough pain. Despite the inability to assess pain control effectively in this unresponsive patient, the morphine infusion rate was increased from 22 to 717 mg/h within 7 days. No change in muscle hyperactivity was observed.

Discussion:

Over the last decade involuntary muscle hyperactivity has been documented as an adverse effect of chronic opioid therapy. The literature describing the incidence of this toxicity, possible risk factors for its development, and recommendations for its management are discussed.

Conclusions:

The occurrence of muscle hyperactivity in an unresponsive patient receiving chronic opioid therapy may represent opioid toxicity. Recommendations for managing opioid-induced muscle hyperactivity include reduction of the opioid dosage and/or administration of clonazepam therapy.
Pseudomonas Aeruginosa as a Cause of Infectious Diarrhea Successfully Treated with Oral Ciprofloxacin
Authors: Porco Frank V , Visconte Ernest B
Published: January 2017

Objective:

To describe an immunocompromised patient (without AIDS) with nosocomial infectious diarrhea caused by Pseudomonas aeruginosa. Oral ciprofloxacin therapy proved to be effective.

Case Summary:

An 80-year-old woman with type II diabetes mellitus and hypertension developed progressive renal insufficiency, was hospitalized because of uremia, and underwent hemodialysis. When the patient developed hematochezia, Duke's C sigmoid colon cancer was detected and successfully resected. She received broad-spectrum antibiotics in the perioperative period. The patient then developed profuse diarrhea associated with abdominal cramping, a low-grade fever, prostration, and headache. The patient then started to receive vancomycin 500 mg po qid empirically. Four days later, the diarrhea continued unabated, the Clostridium difficile titer was negative, and the vancomycin therapy was stopped. However, the stool culture was positive for heavy growth of P. aeruginosa sensitive to ciprofloxacin. The patient then began to receive ciprofloxacin 500 mg po bid. Within 3 days the diarrhea stopped. Oral ciprofloxacin therapy was continued for 10 days and the patient remained free of symptoms with formed stools thereafter.

Discussion:

Diarrhea following the use of broad-spectrum antibiotics implicates pseudomembranous colitis as the cause. The patient did not respond to oral vancomycin therapy and had a negative stool assay for C. difficile toxin. This patient was believed to have Pseudomonas enteritis, which was confirmed by 2 positive stool cultures. The administration of oral ciprofloxacin therapy stopped her diarrhea with a rapid resolution of symptoms.

Conclusions:

P. aeruginosa as a cause of infectious diarrhea is unusual. When it occurs, it usually represents a nosocomial infection in an immunocompromised host. This report illustrates that oral ciprofloxacin therapy is effective for Pseudomonas enteritis, with rapid resolution of symptoms.
Mechanism of Anaphylactoid Reactions: Improper Preparation of High-Dose Intravenous Cyclosporine Leads to Bolus Infusion of Cremophor El and Cyclosporine
Authors: Liau-Chu Merry , Theis Jochen GW , Koren Gideon
Published: January 2017

BACKGROUND:

During a Phase I/II trial of high-dose intravenous cyclosporine, a high incidence of anaphylactoid reactions was observed. Epidemiologic investigations revealed that the occurrence of anaphylactoid reactions was significantly associated with improper mixing during preparation of the infusions. It was hypothesized that improper mixing during the preparation of the infusion may have caused initial bolus infusions of the vehicle, Cremophor EL. These inadvertent bolus infusions may have caused the anaphylactoid reactions.

OBJECTIVE:

To investigate the effect of different mixing techniques on the distribution of the components of cyclosporine concentrate for infusion: cyclosporine, Cremophor EL, and ethanol in the infusions administered to the patients.

METHODS:

Infusions were prepared in a similar fashion as those administered to study patients enrolled in a high-dose cyclosporine therapy protocol. Samples were collected at defined time points of the infusions. Concentrations of cyclosporine and Cremophor EL were spectrophotometrically determined; ethanol concentrations were measured enzymatically.

RESULTS:

Cyclosporine and Cremophor EL concentrations were up to ninefold higher than intended during the first 10 minutes of the infusions that were not appropriately mixed. In contrast, the concentrations of cyclosporine and Cremophor EL were similar to the intended concentrations in all of the well-mixed infusions.

CONCLUSIONS:

Inappropriate mixing of high-dose cyclosporine infusions can lead to initial bolus infusion of cyclosporine and Cremophor EL. Bolus infusions of Cremophor EL have been associated with anaphylactoid reactions. Thus, thorough mixing of high-dose cyclosporine infusions may be important to reduce the possibility of life-threatening anaphylactoid reactions.
Formulation and Stability of Naltrexone Oral Liquid for Rapid Withdrawal from Methadone
Authors: Fawcett J Paul , Morgan Nicola C , Woods David J
Published: January 2017

OBJECTIVE:

To assess the stability of naltrexone oral liquid prepared from tablets and powder, and to evaluate its use in precipitating rapid withdrawal from methadone.

DESIGN:

Naltrexone 1 mg/mL oral liquids were prepared from tablets and powder and stored in the dark at 4, 25, and 70 °C. Similar formulations containing 5 mg/mL were stored at 70 °C. The 1-mg/mL formulation prepared from tablets was clinically evaluated in inducing rapid withdrawal in two drug-dependent individuals receiving methadone maintenance treatment using a naltrexone dose titration protocol.

SETTING:

A university pharmacy school and affiliated urban teaching hospital.

MAIN OUTCOME MEASURES:

Samples removed at six time points were analyzed for naltrexone concentration to assess decomposition over 90 days. An opioid withdrawal symptom checklist was used to assess the severity of the withdrawal symptoms prior to, and 30 minutes after, each dose of naltrexone.

RESULTS:

Decomposition of naltrexone in all formulations stored at 4 and 25 °C was not significant over 90 days. Both patients tolerated naltrexone 1 mg/mL oral liquid, but found it bitter and gritty. Withdrawal symptoms were experienced immediately after the first dose, but were resolving by the end of day 3 of naltrexone treatment, at which stage both patients were able to tolerate a 50-mg tablet of naltrexone as maintenance.

CONCLUSIONS:

Naltrexone 1 mg/mL oral liquids prepared from tablets or powder are stable when stored in the dark for 60 days at 4 °C and for 30 days at 25 °C. The formulation prepared from tablets provides flexible dosing in patients undergoing rapid withdrawal from methadone.