bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of the Human Kidney to the Metabolic Clearance of Drugs
Authors: Vree Tom B. , Hekster Yechiel A. , Anderson Patricia G.
Published: January 2017

OBJECTIVE:

To demonstrate that the human kidney is capable not only of filtering and secreting drugs and their metabolites, but also of carrying out conjugation reactions such as acyl glucuronidation, N-glucuronidation, and glycination.

DATA SOURCES:

Plasma concentrations and renal excretion rates of drugs are measured and renal clearance is calculated in a series of selected pharmacokinetic studies in healthy human volunteers (some studies were conducted in the authors' laboratory and others were reported in the literature).

BACKGROUND THEORY:

It is generally agreed that the liver plays the dominant role in drug metabolism, and that the function of the kidneys is limited to excretion of parent drug and metabolites. This can be easily understood when a metabolite is present in both plasma and urine. When the metabolite is present in urine but is not measurable in plasma, then the possibility exists that the metabolite is formed by the kidneys.

RESULTS:

“Simple” excretion by the kidneys is demonstrated for sulfatroxazole/sulfamethoxazole. Ether glucuronides of codeine are formed in the liver, and the resulting glucuronide is excreted by the kidneys. Possible formation of N1- and N2-glucuronides by the kidneys is demonstrated for sulfadimethoxine, sulfametomidine, and sulfaphenazole. Acyl glucuronidation of probenecid and nalidixic acid is carried out by the kidneys. The acyl glucuronidation of probenecid shows a capacity-limited formation/excretion rate of 46 mg/h, which is subject dependent. During this process, the acyl glucuronidation of co-administered nalidixic acid is reduced from 53 to 16 percent compared with that of nalidixic acid alone. Probenecid and its acyl glucuronidation do not inhibit the ether glucuronidation of codeine in the liver, but only interfere with the active tubular secretion process. The acyl glucuronidation of the nonsteroidal antiinflammatory drug naproxen and its metabolite, O-desmethylnaproxen, may be carried out by the liver and kidneys. Glycination of benzoic acid and salicylic acid is carried out in both the liver and kidneys.

CONCLUSIONS:

It is difficult to recognize renal drug metabolism in the intact human body (in vivo); the glucuronides or conjugates must be measured via direct HPLC analysis. In cases where the metabolite is present in high concentrations in urine but not in blood, there may be an indication that the kidneys are responsible for the formation of the metabolite. Impaired kidney function not only affects renal excretion but may also affect renal metabolism.
Evaluation of the Reliability and Validity of a Measure of Anxiolytic Drug-Use Intensity for Pharmacoepidemiologic Studies
Authors: Ried L. Douglas , Johnson Richard E.
Published: January 2017

OBJECTIVE:

To assess the reliability and validity of a proposed new standard of drug-use intensity, the minimum marketed dose (MMD), using anxiolytic drugs as models.

DESIGN:

Retrospective, cohort design.

SETTING:

Staff model, nonprofit health maintenance organization.

PATIENTS/PARTICIPANTS:

Eighty-five patients who obtained one or more prescriptions for an anxiolytic, antidepressant, or sedative-hypnotic drug during three consecutive one-year time periods. Fifty-nine patients had a prescription filled during the year before the study.

RESULTS:

For anxiolytic drugs, the magnitude of the average correlation for the MMD measure of drug-use intensity was greater than the total number of prescriptions and the total number of dosage units. Discriminant validity was demonstrated because the MMD was not correlated with measures in unrelated therapeutic categories. Summed MMD units were shown to significantly predict physical impairment (criterion validity).

CONCLUSIONS:

The MMD measure of drug-use intensity was reliable and valid for anxiolytic drugs. These findings suggest that information gathered from automated prescription records may be a useful indicator of drug-use intensity in pharmacoepidemiologic studies.
Abnormal Platelet Aggregation Associated with Fluoxetine Therapy
Authors: Alderman Christopher P. , Moritz Claire K. , Ben-Tovim David I.
Published: January 2017

OBJECTIVE:

To document the development of abnormal hemostasis in a patient treated with fluoxetine.

CASE SUMMARY:

A 49-year-old man developed a release-type defect in platelet aggregation during treatment with fluoxetine. Abnormal platelet aggregation was observed during platelet viability testing, in which adenosine diphosphate, epinephrine, ristocetin, arachidonic acid, and collagen were used as agonists. Two days after the withdrawal of fluoxetine, platelet function returned to normal.

DISCUSSION:

Fluoxetine is an antidepressant that is thought to act through inhibition of serotonin reuptake in the central nervous system. Fluoxetine also inhibits the reuptake of serotonin in platelets, significantly decreasing granular storage and potentially influencing platelet aggregation characteristics. Clinical manifestations of abnormal platelet function have been reported in association with fluoxetine therapy.

CONCLUSIONS:

The rapid normalization of platelet aggregation after the withdrawal of fluoxetine in this patient does not conform to the known clinical pharmacokinetics of norfluoxetine. The half-life of fluoxetine is shorter, suggesting that the parent drug (rather than norfluoxetine) was the causative agent. Serum fluoxetine and norfluoxetine concentrations were not measured in this patient.
Dobutamine-Induced Fever
Authors: Robison-Strane Susan R. , Bubik Jane Simson
Published: January 2017

OBJECTIVE:

To report a case of dobutamine-induced fever.

PATIENT:

A 71-year-old woman with congestive heart failure who developed a fever after receiving dobutamine during two separate hospital admissions.

RESULTS:

Other possible causes of the fever during the first admission included relapse of staphylococcal sepsis and drug fever from vancomycin or metoclopramide. However, rechallenge with dobutamine on a subsequent admission demonstrated a highly probable relationship between dobutamine and fever.

CONCLUSIONS:

A strong temporal relationship between dobutamine and fever was noted during the patient's second admission and the case was not complicated by other new medications. No underlying infectious or noninfectious cause of the fever was found. Therefore, when patients receiving dobutamine become febrile, dobutamine should be considered as a possible cause.
Transient Hepatic Dysfunction in an Infant of an Epileptic Mother Treated with Carbamazepine during Pregnancy and Breastfeeding
Authors: Merlob Paul , Mor Naomi , Litwin Aviva
Published: January 2017

OBJECTIVE:

A case is reported of a carbamazepine (CBZ)-treated epileptic mother whose newborn presented with transient hepatic dysfunction characterized by direct hyperbilirubinemia and high concentrations of gamma-glutamyltransferase (GGT).

DATA SOURCES:

Information was obtained from case reports, clinical trials, and relevant bibliographic laboratory studies.

DATA EXTRACTION:

Data from case reports were evaluated and compared with those from our patient. The hepatotoxic reactions together with the microsomal enzymatic induction of CBZ were reviewed.

DATA SYNTHESIS:

A female infant bom to an epileptic mother treated with CBZ throughout pregnancy and breastfeeding presented with transient direct hyperbilirubinemia and high concentrations of GGT. The characteristics of her transient hepatic dysfunction were: early appearance (during the first day of life); discrepancy between the normal liver enzymes and high GGT concentrations; slow decrease of GGT, which nevertheless remained at above-normal concentrations even after the complete disappearance of direct hyperbilirubinemia; and spontaneous resolution in spite of only occasional breastfeeding. The possible explanations of this transient hepatic dysfunction (like enzymatic induction) are discussed.

CONCLUSIONS:

CBZ-induced hepatic dysfunction in neonates appears to have different clinical expressions. Infants of epileptic mothers treated with CBZ throughout pregnancy and breastfeeding should be carefully monitored for possible adverse effects.
Diazepam by Continuous Intravenous Infusion for Status Epilepticus in Anticonvulsant Hypersensitivity Syndrome
Authors: Bertz Richard J. , Howrie Denise L.
Published: January 2017

OBJECTIVE:

To report a case of status epilepticus in a patient with anticonvulsant hypersensitivity syndrome (AHS) that was controlled successfully using continuous intravenous infusion diazepam. AHS and alternatives for treatment of status epilepticus are also reviewed.

DESIGN:

Single case report.

SETTING:

217-bed children's university hospital.

PATIENT:

Four-year-old, 20-kg girl, diagnosed with idiopathic tonic-clonic epilepsy, who developed AHS to phenobarbital and phenytoin and status epilepticus unresponsive to lorazepam.

RESULTS:

Diazepam intravenous infusion at dosages titrated to 8 mg/h was used successfully to control seizures for eight days until signs and symptoms of AHS had resolved and maintenance therapy with valproic acid was started.

CONCLUSIONS:

Continuous intravenous infusion diazepam is a reasonable therapeutic choice for the management of status epilepticus in a patient with AHS when traditional therapy such as phenytoin and phenobarbital cannot be used.
Hypoglycemia Secondary to Trimethoprim/Sulfamethoxazole Administration in a Renal Transplant Patient
Authors: Johnson Jeffrey A. , Kappel Joanne E. , Sharif M. Nabi
Published: January 2017

OBJECTIVE:

To report a case of trimethoprim/sulfamethoxazole (TMP/SMX)-induced hypoglycemia in an immunosuppressed renal transplant patient.

DATA SOURCES:

English-language journal articles and reference texts identified via a MEDLINE search and a bibliographic review of pertinent data sources.

DATA SYNTHESIS:

Hypoglycemia resulting from the combination of sulfonylureas and sulfonamides is a recognized drug interaction. Hypoglycemia induced by sulfonamides alone may be encountered less frequently. Previously reported cases of TMP/SMX-induced hypoglycemia postulated that the sulfonamide mimics hypoglycemic sulfonylurea agents and stimulates pancreatic islet cells to secrete insulin. We report a case of hypoglycemia following the administration of high-dose TMP/SMX in a renal transplant patient. Elevated C-peptide concentrations following the hypoglycemic episode indicate that hypoglycemia resulted from increased endogenous insulin secretion.

CONCLUSIONS:

Hypoglycemia has been a rarely encountered result of TMP/SMX use. Patients receiving TMP/SMX, particularly those with impaired renal function and those receiving high doses, should be monitored closely for hypoglycemia.
Benzodiazepine Use in Older, Community-Dwelling Southern Californians: Prevalence and Clinical Correlates
Authors: Mayer-Oakes S. Allison , Kelman Greg , Beers Mark H. , De Jong Fred , Matthias Ruth , Atchison Kathryn A. , Lubben James E. , Schweitzer Stuart O.
Published: January 2017

OBJECTIVE:

To determine the use of benzodiazepines (BZDs) in an older, community-dwelling sample and to examine the sociodemographic and clinical correlates of BZD use.

DESIGN:

A cross-sectional study of 1752 elderly people (aged ≥65 y) who completed a mailed medication survey and a telephone health status survey.

PARTICIPANTS:

Participants were invited to participate in a large Medicare demonstration project on prevention by their private physicians, who were also enrolled in the larger study. Participants had to be English-speaking, could not have dementia or a terminal illness, and had to give informed consent to participate in the study.

MAIN OUTCOME MEASURES:

Sociodemographic and health status variables that predicted BZD use were examined. Sociodemographic variables included age, gender, ethnicity, education, and income. Health status variables included functional status, with measures of mental, social, and physical health. Influenza immunization status was used as an indicator for preventive health services use and self-reported chronic illness was used as a measure of comorbidity.

RESULTS:

Twenty percent of the participants used BZDs at least twice in the past year. We found that those who used BZDs were more than twice as likely to take ten or more drugs, two-and-a-half times more likely to have difficulty falling asleep, and over twice as likely to be depressed. BZD users were also more likely to be white, to have a college education, and to have received a recent influenza shot, but were not more likely to be women when controlled for health status.

CONCLUSIONS:

Further clinical research should explore the relationship between BZD use among older patients and the BZD-associated adverse clinical factors we observed, as well as the association between multiple drug use and potential adverse outcomes in older BZD users.
Clinical Rules for Phenytoin Dosing
Authors: Privitera Michael D.
Published: January 2017

OBJECTIVE:

To develop simple clinical rules for dosing phenytoin (PHT) using computer simulations, then to test the rules for accuracy and safety on actual patient data.

DESIGN:

Patients with steady-state PHT plasma concentrations at least two different PHT doses were identified from three separate sources of patient data. A computerized dosing program calculated pharmacokinetic parameters using Bayesian methodology, then predicted how many patients were likely to reach potentially toxic PHT plasma concentrations when their daily dosage was increased by 30, 50, or 100 mg. Dosing rules were developed to allow fewer than ten percent of resultant plasma concentrations to exceed 25 μg/mL. The dosing rules then were tested on dose/plasma concentration data from a separate group of patients.

SETTING:

All patients were being treated by neurologists either as outpatients or inpatients.

PATIENTS:

All patients were adults with epilepsy being treated with PHT; none had clinically significant renal or hepatic disease. Patients for the computer simulation were from three sources: (1) patients who had an initial PHT plasma concentration <10 μg/mL and required a dosage increase; (2) patients admitted to the hospital for PHT intoxication; and (3) patients who required consultations specifically for PHT dosing. Patients on whom the dosing rules were tested were part of a prospective, randomized trial of antiepileptic drug safety and efficacy.

MAIN OUTCOME MEASURES:

Successful dosing rules allowing fewer than ten percent of resulting plasma concentrations in the test group to exceed 25 μg/mL.

RESULTS:

The simulations used 167 actual dose/plasma concentration pairs from 45 patients. The resulting dosing rules were: increase the dosage by 100 mg/d if the initial plasma concentration was <7 μg/mL; increase the dosage by 50 mg/d if the initial plasma concentration is 7 to <12 μg/mL; increase the dosage by 30 mg/d if the initial plasma concentration is ≥12 μg/mL. The rules were tested on 129 50- or 100-mg dosage increases in 77 patients. All 53 dosage increases that were within the dosing rules produced plasma concentrations <25 μg/mL, whereas 36 percent (27 of 74) of the dosage increases that exceeded the dosing rules produced plasma concentrations >25 μg/mL.

CONCLUSIONS:

The proposed dosing rules are a simple method for clinicians to estimate PHT dosage changes and appear to be safe and accurate when applied retrospectively to actual patient data.
Endstage Liver Disease Associated with Nitrofurantoin Requiring Liver Transplantation
Authors: Hebert Mary F. , Roberts John P.
Published: January 2017

OBJECTIVE:

To report the apparent development of endstage liver disease secondary to nitrofurantoin administration.

PATIENT:

A 40-year-old woman developed hepatic failure after receiving nitrofurantoin 200 mg po bid for one month for prophylaxis against urinary-tract infections. Symptoms first occurred after two weeks of nitrofurantoin therapy. Other causes of hepatic failure (e.g., viral infection, autoimmune disorder, concomitant medications, cancer, Wilson's disease, ethanol abuse, pregnancy) were ruled out.

CONCLUSIONS:

Acute and chronic hepatic injury has previously been reported with the use of nitrofurantoin. The proposed mechanism may be immunoallergic or metabolic in origin. On evaluating concomitant diseases and medications in our patient as well as the temporal sequence of her signs and symptoms, it appears that she developed hepatic failure secondary to the use of nitrofurantoin, ultimately necessitating orthotopic liver transplantation. The potential for the development of such a severe adverse reaction warrants careful evaluation of symptoms that may potentially be caused by hepatic damage as well as immediate discontinuation of nitrofurantoin in patients presenting with jaundice.
Stability of Spironolactone in an Extemporaneously Prepared Suspension at Two Temperatures
Authors: Nahata Milap C. , Morosco Richard S. , Hippie Thomas F.
Published: January 2017

OBJECTIVE:

To determine the stability of spironolactone in an extemporaneously prepared suspension at 22 and 4°C over a three-month storage period.

DESIGN:

Spironolactone suspension (1 mg/mL) was prepared in syrup NF, carboxymethylcellulose, and purified water USP. The suspension was stored in ten amber glass prescription bottles; five were stored at 22°C and five at 4°C. Samples were drawn from each bottle and analyzed in duplicate (n=10) on days 0, 7, 14, 28, 42, 56, 70, and 91. Spironolactone concentrations were measured by a reproducible and stability-indicating HPLC method. Inspection of visual and pH changes also was performed on each study day.

RESULTS:

The mean concentration of spironolactone was always higher than 98 percent of its initial concentration. The pH and appearance of the suspension did not change substantially.

CONCLUSIONS:

Spironolactone was stable in a suspension containing syrup, carboxymethylcellulose, and purified water for three months during storage in amber glass bottles at both 22 and 4°C.
Enterococcus, an Emerging Pathogen
Authors: Tailor Sandra A.N. , Bailey Elaine M. , Rybak Michael J.
Published: January 2017

OBJECTIVE:

To review the bacterial genus Enterococcus with respect to its epidemiology, specific infections in humans, mechanisms of resistance and tolerance, and antimicrobial treatment.

DATA SOURCES:

A MEDLINE search of English-language journal articles published from 1977 to 1992 was completed. Articles published prior to 1977 were identified through Index Medicus and from references appearing in the bibliographies of other journal articles. Information also was acquired from abstracts, personal communication with infectious disease specialists with active research in the area of enterococcal infection, and conference proceedings.

STUDY SELECTION:

In vitro data; animal models of enterococcal infection; case reports; and case-controlled, cohort, and randomized controlled trials in humans were evaluated for relevant information.

DATA EXTRACTION:

Studies were evaluated by their methodologic strength (e.g., randomized controlled trial), reporting of clinically relevant outcomes (e.g., clinical response to antimicrobial therapy), statistical analyses, and accountability of all patients who entered the study.

DATA SYNTHESIS:

The incidence of enterococcal infections has increased in recent years and enterococci are now the second most frequently reported nosocomial pathogens. Enterococcus faecalis is the pathogen responsible for most enterococcal infections seen today; it has been implicated as an important cause of endocarditis, bacteremia, urinary tract infections, and intraabdominal infections.

CONCLUSIONS:

Enterococcal infection is of particular concern clinically because of its resistance to several antibiotics. Controlled comparative clinical trials of antimicrobial therapy in humans are lacking for several enterococcal infections. Therefore, the recommendations for antimicrobial therapy presented in this review are guidelines that reflect our current understanding of antibiotics used for enterococcal infection.
Hepatitis following Treatments with Famotidine and Then CimetIDINE
Authors: Hashimoto Fred , Davis Robin L. , Egli Douglas
Published: January 2017

OBJECTIVE:

To report a case of hepatitis induced by two histamine (H2)-receptor blockers, famotidine and cimetidine.

CASE SUMMARY:

A 51-year-old obese woman with a duodenal ulcer developed symptomatic, famotidine-induced hepatitis. Other causes for hepatitis were ruled out. Famotidine was discontinued and the patient took omeprazole for a month without incident. Cimetidine therapy was then initiated and shortly thereafter, the patient developed another episode of symptomatic hepatitis that resolved upon drug discontinuation. Two abdominal ultrasound examinations six months apart and an abdominal computed tomography scan obtained later showed what appeared to be a stable, fatty liver.

DISCUSSION:

This appears to be the first reported case of clinical hepatitis related to famotidine and the first reported case where clinical hepatitis followed the administration of two different H2-receptor blockers. The fatty liver probably was secondary to obesity and incidental to the hepatitis episodes.

CONCLUSIONS:

Famotidine can cause clinical hepatitis, and druginduced hepatitis can occur after the administration of two different H2-receptor blockers.
Creatinine Metabolism Impairment by an Anticonvulsant Drug, Phenacemide
Authors: Cahen Rémi , Martin Ambroise , Francois Bernard , Baltassat Pierre , Louisot Pierre
Published: January 2017

OBJECTIVE:

To report two cases of increased true serum creatinine (Ser) without renal failure caused by an anticonvulsant drug, phenacemide, and to discuss the possible mechanisms.

CASE SUMMARY:

Two patients treated with phenacemide were investigated for markedly increased Scr and decreased creatinine clearance (Clcr) values. Glomerular filtration rates, as determined by 125I-iothalamate clearance, were normal in both patients and analytical interferences with the Jaffé reaction were excluded. After discontinuation of the drug, phenacemide concentrations became undetectable within 2 days but it took 7–14 days for Scr and Clcr to return to normal values.

DISCUSSION:

The Scr increase with phenacemide (120–170 percent) was higher than that reported with cimetidine or trimethoprim (10–40 percent) and could not be explained solely by inhibition of the tubular secretion of creatinine. The hypothesis of an overproduction of creatinine caused by phenacemide was ruled out by experimental studies in rats. Creatinine increase in tissues was lower than that in the serum of rats given phenacemide. In vitro creatinine influx into red blood cells was inhibited in a dose-dependent way by phenacemide.

CONCLUSIONS:

Increased Scr concentrations in these patients could be related to an inhibition of transport and a decrease in creatinine volume of distribution. Creatinine concentrations should not be considered when dosage adjustments of renally eliminated drugs are being calculated for patients with such metabolic interferences.
Assessment of Cost-Effective Antibiotic Therapy in the Management of Infections in Cancer Patients
Authors: Cimino Michael A. , Rotstein Coleman M. , Moser Jason E.
Published: January 2017

OBJECTIVE:

To describe the economic benefits of a quality improvement effort directed at optimizing clinical outcome.

DESIGN:

A before—after observational design was used to evaluate the cost-effectiveness of a consensus approach to antimicrobial therapy.

SETTING:

The evaluation was conducted at a cancer research hospital.

PATIENTS:

Oncology patients requiring parenteral antibiotic therapy were consecutively observed.

MAIN OUTCOME MEASURES:

Outcome (clinical and microbiologic response), safety, and cost of therapy were assessed during a baseline period and compared to a period during which the consensus approach was used.

INTERVENTIONS:

The influence of a designated individual, in this case a clinical pharmacist, responsible for promotion of the consensus approach was explored.

RESULTS:

The consensus approach in combination with the promotional efforts of the clinical pharmacist was associated with a 13 percent increase in overall clinical response and a reduction of pathogen persistence from 22 to 11 percent. No difference in the average number of adverse effects per patient was observed over the two observation periods. These findings were associated with an estimated $22000/month cost savings. The consensus approach alone, without benefit of the clinical pharmacist, was not associated with improved therapeutic outcome or cost savings over the same observation periods.

CONCLUSIONS:

These data suggest that a consensus approach to antibiotic therapy can be cost-effective. An individual, such as a clinical pharmacist, may add significantly to quality improvement and cost-effective efforts in a hospital setting.
Drug Degradation during HPLC Analysis of Aztreonam: Effect on Pharmacokinetic Parameter Estimation
Authors: Friedrich Lawrence V. , White Roger L. , Kays Michael B. , Burgess David S.
Published: January 2017

OBJECTIVE:

To assess the impact of degradation of aztreonam, a beta-lactam antibiotic, during HPLC analysis on pharmacokinetic parameter estimates.

METHODS:

The baseline (B) serum concentration-time data from a published pharmacokinetic study of aztreonam were degraded using first-order equations and a degradation rate constant (0.014 h-1) determined from a preliminary degradation study. Samples were mathematically degraded for autosampler run times of 8–13 h (D1) to approximate a normal work day and for autosampler run times of 16–17 h (D2) and compared with B data. It was assumed that B data were nondegraded and that changes in chromatography were the result of degradation of azetreonam and not to any changes in chromatographic conditions. A two-compartment model was used to fit the data and pharmacokinetic parameters were calculated using standard equations. Statistical significance between all pharmacokinetic parameters for B and D1 and B and D2 was determined using the paired, two-tailed Student's t-test.

RESULTS:

Increased variability was noted for all pharmacokinetic parameters for D1 and D2 compared with B. Statistically significant differences were found for clearance (B <D1, p=0.0095 and B <D2, p=0.0194), steady-state volume of distribution (B D1, p=0.0497).

CONCLUSIONS:

Aztreonam degradation resulted in increased variability in pharmacokinetic parameter estimates. Investigators should be cognizant of this and preliminary studies should be performed to characterize degradation for the length of the expected autosampler run.
Difficulties in Diagnosing Narcotic Overdoses in Hospitalized Paitents
Authors: Whipple Julianne K. , Quebbeman Edward J. , Lewis Kelly S. , Gottlieb Mark S. , Ausman Robert K.
Published: January 2017

OBJECTIVE:

To describe the clinical presentation of narcotic overdose in hospitalized patients and to differentiate this circumstance from other conditions often misdiagnosed as overdose.

DESIGN:

Case series.

SETTING:

Two acute-care teaching hospitals.

PATIENTS:

Forty-three hospitalized patients who received naloxone for a clinically suspected narcotic overdose.

INTERVENTIONS:

Two investigators independently evaluated each incident to determine whether the patient had a narcotic overdose. The patients were judged to have had an overdose if caregivers documented an immediate improvementin mental status, respiratory rate, or blood pressure after naloxone administration.

MEASUREMENTS:

The clinical presentation of a narcotic overdose in hospitalized patients was defined. Conditions misdiagnosed as an overdose were determined.

MAIN RESULTS:

Symptoms improved rapidly with the administration of naloxone in 28 incidents (65 percent) and were designated overdose. In 15 other instances there was no improvement in symptoms; these patients were designated nonoverdose. Only half of the overdose patients had a respiratory rate <8 breaths/min immediately prior to naloxone administration. Only two of the overdose patients had the classic triad of symptoms (respiratory depression, coma, and pinpoint pupils). Other overdose patients had only one or two of the classic signs. The clinical presentation of narcotic overdoses in hospitalized patients did not include respiratory depression, hypotension, or coma in the majority of patients. All overdose patients showed a decrease in mental status. The majority of nonoverdose patients had pulmonary conditions that were misdiagnosed as a narcotic overdose.

CONCLUSIONS:

Narcotic overdoses in hospitalized patients seldom fit the classic description. The lack of respiratory depression does not mean the absence of a narcotic overdose. Patients who receive narcotics and develop a signficant decrease in mental status should be evaluated for a possible overdose. Pulmonary, neurologic, cardiovascular, and electrolyte abnormalities often are misdiagnosed as a narcotic overdose in hospitalized patients.
Cisapride: A Gastrointestinal Prokinetic Drug
Authors: Barone Joseph A. , Jessen Lois M. , Colaizzi John L. , Bierman Robert H.
Published: January 2017

OBJECTIVE:

To summarize the pharmacology, pharmacokinetics, efficacy, and safety of cisapride, and to evaluate its potential therapeutic role.

DATA SOURCES:

A computerized search of the MEDLINE database was used to identify English-language publications of cisapride data in humans. The MEDLINE search was supplemented by review article bibliographies. There was no attempt to limit the search to a specific gastrointestinal motility disorder.

STUDY SELECTION:

The MEDLINE search alone identified 165 citations. Because of the volume of available human cisapride data, the focus of the efficacy section is on complete published reports of controlled clinical studies. Abstracts and uncontrolled data are discussed only when other information is unavailable to address important aspects.

DATA EXTRACTION:

Information regarding study design, study population, results, and safety was recorded from each publication. The placebo response to gastrointestinal complaints in patients with motility disorders is high. Therefore, objective evidence of improvement was emphasized when documentation was available.

DATA SYNTHESIS:

Cisapride stimulates the motility of smooth muscle lining the esophagus, stomach, small intestine, and colon, and increases the tone of gut sphincters in vitro and in vivo. In controlled investigations, cisapride was superior to placebo in relieving symptoms associated with reflux esophagitis, nonulcer dyspepsia, and gastroparesis. Similar symptom and healing effects were observed with cisapride and histamine (H)2-antagonists in reflux esophagitis. Cisapride was either equal to or superior to metoclopramidein relieving reflux symptoms. However, metoclopramide was associated with significantly more central nervous system adverse effects. Cisapride was well tolerated, with adverse effects limited primarily to the gastrointestinal tract.

CONCLUSIONS:

Cisapride represents an attractive alternative to metoclopramidefor the treatment of a variety of motility disorders. Because it addresses a primary underlying cause of reflux esophagitis, cisapride may also prove to be an effective alternative to acid suppressants in the management of this disorder.
Medicaid Policies for HIV-Related Drug Therapies: Perspectives of the State Affiliates of the American Pharmaceutical Association
Authors: Buchanan Robert J. , Smith Scott R.
Published: January 2017

OBJECTIVES:

To determine how Medicaid prescription drug policies differ by state, and to assess how these policies affect pharmacies and the drug therapies available to Medicaid patients with HIV infection or tuberculosis.

EVALUATION PROCESS:

The state affiliates of the American Pharmaceutical Association (APhA) were surveyed to learn how state Medicaid policies impact the provision of prescription drugs to Medicaid patients within their state. The survey focused on Medicaid payment level incentives, Medicaid payments compared with private payments, Medicaid utilization policies, and incentives and disincentives in each state's Medicaid payment system.

RESULTS:

Approximately two-thirds of the APhA affiliates reported that the Medicaid payment levels in their states for drugs used to treat HIV-related illnesses were at least moderately below private payment levels; in 11 states these Medicaid payments were substantially below those of private payers. Many APhA affiliates responding to the survey stated that the Medicaid program in their state limited the number of reimbursed drugs that Medicaid patients can receive. Eight APhA affiliates reporting that these utilization limits created restrictions on the ability of Medicaid patients with AIDS and HIV-related infections to receive needed medications.

CONCLUSIONS:

With Medicaid programs becoming the major payers of AIDS-related healthcare, federal policies should standardize Medicaid coverage, payment, and utilization policies for prescription drugs needed by Medicaid recipients with HIV-related conditions. This would enable Medicaid patients to receive necessary and adequate drug therapies regardless of their state of residence. These federally mandated policies also would require an increased federal role in fimancing this expanded Medicaid drug coverage.
Estimation of Total Body and Extracellular Water Using Single-and Multiple-Frequency Bioimpedance
Authors: Patel Rakesh V. , Matthie James R. , Withers Paul O. , Peterson Edward L. , Zarowitz Barbara J.
Published: January 2017

OBJECTIVE:

To determine the precision and bias of single- and multiple-frequency bioimpedance estimates of total body water (TBW) and extracellular water (ECW) volumes in comparison with the true values for these volumes established by gold standard dilution techniques.

DESIGN:

Controlled, prospective, open-label investigation.

SETTING:

Private, not-for-profit university-affiliated, acute care hospital.

PARTICIPANTS:

Normal, healthy men (n=8) and women (n=6) volunteers, 25–46 years of age.

INTERVENTIONS:

A single oral dose of a mixture of deuterium oxide 10 g and bromine 30 mmol; bioimpedance analysis pre- and three hours postrnixture administration.

MAIN OUTCOME PARAMETERS:

TBW and ECW volumes established by deuterium oxide and bromine dilutional spaces (gold standards), respectively, and single- and multiple-frequency bioimpedance estimates of those same volumes.

RESULTS:

The mean multiple-frequency bioimpedance (MFB) and single frequency bioimpedance (SFB) estimates of TBW, 41.2 and 42.1 L, respectively, were not statistically different (NS) from the 41.2 L deuterium oxide value. Although the two methods had similar precision (NS), MFB was less biased. For ECW, the mean MFB and SFB values of 19.5 and 24.8 L, respectively, were significantly different from the bromine value of 18.8 L (p=0.013 and p=0.001, respectively). MFB was the more precise and less biased predictor of ECW.

CONCLUSIONS:

Compared with SFB, the MFB approach is a more precise and less biased predictor of TBW and ECW volumes in young, healthy adults, and may offer more accurate assessment in subjects with aberrant physiology.
Hypertension: Are Beta-Blockers and Diuretics Appropriate First-Line Therapies?
Authors: Wilson Marcus D. , Weart C. Wayne
Published: January 2017

OBJECTIVE:

To review the existing data on the use of diuretics or beta-blockers as first-line therapy for the treatment of mild to moderate hypertension, and to examine the issues surrounding the impact of these classes as well as the angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers (CCBs), alphablockers, and alpha-beta-blockers on cardiovascular risk factors and cardiovascular morbidity and mortality.

DATA SOURCES:

A MEDLINE search of applicable articles on antihypertensive therapies and their impact on morbidity and mortality. In addition, a MEDLINE search of relevant articles regarding cardiovascular risk factors and the influence of the various antihypertensive therapies on these parameters.

DATA SYNTHESIS:

The literature was evaluated with regard to outcome. Trials examining the impact of antihypertensive pharmacotherapy, primarily with diuretics and beta-blockers, have shown them to decrease the incidence of stroke by 33–50 percent. However, their effect on coronary heart disease has been disappointing, showing only a 14 ± 5 (mean ± SD) percent decrease. Examination of numerous clinical trials assessing the impact of the various antihypertensive therapies on cardiovascular risk factors, including blood pressure, plasma lipids, diabetic control/insulin sensitivity, and left ventricular hypertrophy was done. The classes included beta-blockers, diuretics, alpha-blockers, ACE inhibitors, and CCBs; the results show a diversity of effect. Diuretics and betablockers, tend to worsen cardiovascular risk status, whereas the alphablockers, ACE inhibitors, and CCBs all show a beneficial effect.

CONCLUSIONS:

Diuretics and beta-blockers can effectively reduce cerebrovascular morbidity and mortality, but have a limited effect on reducing cardiovascular disease, especially myocardial infarction. This may be explained, at least in part, by the negative, or lack of positive, effect on individual patients' overall cardiovascular risk status.
Update on the Management of Intestinal Cryptosporidiosis in AIDS
Authors: Ritchie David J. , Becker Evelyn S.
Published: January 2017

OBJECTIVE:

To update readers on the pharmacotherapeutic management of cryptosporidiosis in patientswith AIDS.

DATA SOURCES:

A MEDLINE search was used to identify pertinent literature. Additionally, programs and abstracts from the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy; the 1st International Conference on Macrolides, Azalides, and Streptogramins; the 93rd American Society for Microbiology Meeting; and the 6th and 7th International Conferenceson AIDS were used.

DATA EXTRACTION:

Available data from in vitro, animal, and human experiments were reviewed.

DATA SYNTHESIS:

Intestinal cryptosporidiosis in patients with AIDS can be a life-threatening opportunistic infection. However, there can be significant variability in disease expression, including spontaneous remission. Supportive care with hydration and nutritional supplementation remains a hallmark of therapy. Unfortunately, there is no proven specific pharmacotherapy of cryptosporidiosis in patients with AIDS. Numerous agents have been analyzed for in vitro activity and efficacy in experimental animal models and actual human cases of the infection, including paromomycin, azithromycin, c1arithromycin, octreotide, hyperimmune bovine colostrum, bovine transfer factor, and many others. Because limited numbers of controlled trials have been conducted with potential therapeutic agents, the majority of the information to date is preliminary in nature.

CONCLUSIONS:

Despite the availability of some evolving and potentially promising treatment modalities, further controlled clinical trials are necessary to evaluate the role of pharmacotherapy for intestinal cryptosporidiosis in patients with AIDS.
Antiulcer Prescribing Program in a State Correctional System
Authors: Keith Matthew R. , Cason Dick M. , Helling Dennis K.
Published: January 2017

OBJECTIVE:

To describe a formulary antiulcer agent prescribing program developed as the result of a drug use evaluation (DUE). Program implementation, methods. cost impact, and results of a follow-up DUE are provided.

BACKGROUND:

The institution is a 51 OOO-bed correctional system consisting of 40 separate units each containing an ambulatory care clinic. Medication orders are transmitted via mainframe computer system to one of four pharmacies, which collectively dispense an average of 4000 medication orders (30 days' supply) per day.

METHODS:

Results from the antiulcer agent (cimetidine, ranitidine, sucralfate) DUE revealed that the agents studied were prescribed in dosages and durations exceeding criteria developed by the Pharmacy and Therapeutics Committee. A program designed to reduce dosages to maintenance therapy after eight weeks at treatment dosage was developed by the Pharmacy and Therapeutics Committee with staff physician input. Antiulcer agent use and expenditures were followed and a follow-up DUE was completed seven months after program implementation. Antacid use and frequency of upper gastrointestinal studies that were ordered were followed.

RESULTS:

The follow-up DUE showed the mean daily dosage for prescribed histamine2-receptor antagonists decreased (Cimetidine from 694 to 454 mg, ranitidine from 280 to 183 mg) and the mean duration of therapy decreased from 14 to 10 months. The percentage of patients with potentially significant drug interactions decreased from 14.2 to 6.5 percent. The mean number of antiulcer agents dosage units dispensed per month decreased by 24461 units, resulting in a projected annual savings of $327 273. There were no identifiable clinically important changes in the use of antacid products or prescribing of upper gastrointestinal studies.

CONCLUSIONS:

A cost-savings program sponsored by the pharmacy and therapeutics committee decreased costs, corrected prescribing to more closely meet preset criteria, and produced no discernable unfavorable effect on patient care.
Preliminary Comparison of Predictive and Empiric Lithium Dosing: Impact on Patient Outcome
Authors: Marken Patricia A. , McCrary Kay E. , Lacombe Sylvia , Sommi Roger W. , Hornstra Robijn K. , Pierce Christine A. , Stanislav Steven W. , Evans R. Lee
Published: January 2017

OBJECTIVE:

To evaluate whether initiating lithium with predictive dosing compared with empiric dosing improves outcome in patients with manic symptoms.

DESIGN:

The study was a randomized, single-blind design and used the Modified Slattery predictive method.

SETTING AND PARTICIPANTS:

Eighteen inpatients at an urban psychiatric hospital with a Mania Rating Scale (MRS) score greater than or equal to 24 were enrolled.

OUTCOME MEASURES:

The study endpoint was defined as an MRS rating less than or equal to 14 or discharge from the hospital. Assessments (MRS, Brief Psychiatric Rating Scale, Clinical Global Impression, Systematic Assessment for Treatment of Emergent Events Scale, quality of life measures) were completed at baseline, on days 3 or 4 and 7 or 8, and weekly thereafter.

RESULTS:

The predictive group achieved a therapeutic concentration significantly sooner than did the empiric group (p=0.004); however, the mean serum lithium concentration at discharge did not differ between the groups. The predictive group was taking significantly higher dosages of antipsychotics in chlorpromazine equivalents on day 3 or 4 (p=0.05). Significantly fewer gastrointestinal/genitourinary adverse effects on day 3 or 4 were reported by patients in the predictive group (p=0.04). No difference was found between groups with any rating scale or other pharmacokinetic or medication item. Even though the difference did not meet statistical significance, the predictive group's length of stay in the acute unit was three days shorter than that of the empiric group, which may represent significant cost savings.

CONCLUSIONS:

The preliminary data do not suggest that patient outcome is improved by using Modified Slattery predictive dosing; however, the suggestion of a shorter length of stay in a restrictive unit merits further evaluation.
Possible Ciprofloxacin-Induced Acute Cholestatic Jaundice
Authors: Sherman Olga , Beizer Judith L.
Published: January 2017

OBJECTIVE:

To report a case of acute cholestatic jaundice in a patient who was receiving oral ciprofloxacin.

CASE SUMMARY:

An 84-year-old woman residing in a long-term care facility developed acute cholestatic jaundice while being treated with ciprofloxacin for a urinary tract infection. On day 6 of ciprofloxacin therapy, she was noted to have an erythematous, pruritic rash over her chest and abdomen. At this point ciprofloxacin treatment was discontinued, as an allergy was suspected. Three days later she was noted to have jaundiced sclera and skin, and liver function test results were markedly elevated. The plasma cholesterol concentration was increased substantially; there was no decrease in plasma albumin concentration or increase in prothrombin time. The patient was treated with intravenous fluids. Within the next month, the liver function test results decreased to near normal and the patient was asymptomatic. Follow-up liver test results three months later were normal.

DISCUSSION:

To our knowledge, there are only a few other case reports in the literature of a possible ciprofloxacin-induced liver injury. Enoxacin, a fluorinated quinolone antibiotic similar to ciprofloxacin, was reported to cause cholestatic liver injury in one patient. The exact mechanism by which fluoroquinolones may cause liver injury is unknown.

CONCLUSIONS:

We believe that this is only the second reported case of acute cholestatic jaundice resulting from ciprofloxacin therapy. Although this reaction seems to occur rarely, it is prudent to be alert for the signs and symptoms of cholestasis when administering ciprofloxacin.
Angina Pectoris Following Cisplatin, Etoposide, and Bleomycin in a Patient with Advanced Testicular Cancer
Authors: Rodriguez Jose , Collazos Julio , Gallardo Marisol , Hernando Gabriel
Published: January 2017

Objective:

To report a case of angina pectoris associated with chemotherapy for testicular cancer.

Case Summary:

An HIV-infected patient with massive retroperitoneal metastases of a mixed embryonal and undifferentiated teratocarcinoma was treated with cisplatin, etoposide, and bleomycin. While the patient was receiving the second course of chemotherapy, he developed several episodes of angina pectoris that responded to nitroglycerin. Coronary angiography excluded structural abnormalities in the coronary arteries. The patient was treated prophylactically with nifedipine during the 2 following courses of chemotherapy with no new ischemic events.

Discussion:

Coronary vasospasm seemed to be responsible for the angina in this patient. Several pathogenetic mechanisms that could explain these vascular events are discussed, including the possible role of bulky metastatic disease.

Conclusions:

The combination of cisplatin, etoposide, and bleomycin for testicular cancer, perhaps associated with bulky metastatic disease, can induce vasospastic phenomena that might be life-threatening.