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Biomedical subjects

F Pucino

Publications and source records attributed to F Pucino.

30 records · Page 2Linked to original sources

Effects of alprazolam on respiratory drive, anxiety, and dyspnea in chronic airflow obstruction: a case study.

Alprazolam, an anxiolytic benzodiazepine, has a pharmacologic profile similar to that of diazepam. An intermediate half-life of 10-12 hours and a comparatively brief duration of activity relative to other anxiolytic benzodiazepines justified evaluation of a 0.5-mg test dose in an anxious patient with chronic obstructive lung disease. Subjective indexes, breath-by-breath respiratory drive response to hypercapnia, and blood alprazolam concentrations were determined before and after dosing. Subjective testing included a visual analog dyspnea scale, the state anxiety inventory, and subjective feelings visual analog scales (represented by alertness, calmness, and level of contentment). After dosing, the patient was better able to tolerate the rebreathing study technique. Statistically significant improvements in dyspnea (t - 10.20; p 0.0005), anxiety (t - 45.85; p less than 0.0001), alertness (t - 13.04; p less than 0.0001), cententedness (t - 12.27; p less than 0.0001), and calmness (t - 8.05; p less than 0.0001) occurred after alprazolam administration. Drive to breathe, as determined by mouth occlusion pressure and minute ventilation, was not statistically different before and after dosing. No adverse effects were reported or observed. Further study is warranted.

Alprazolam↗

Human infection with herpes zoster: etiology, pathophysiology, diagnosis, clinical course, and treatment.

Herpes zoster is a cutaneous vesicular eruption resulting from recrudescence of the chickenpox virus. It is mainly a disease of adults, with a predisposition for the elderly or immunocompromised. Although usually localized, the disease can disseminate to visceral organs. Diagnosis is often made based on the characteristic pattern of the lesion and clinical features. Tzanck smear, viral isolation, seroconversion, antibody titers, and monoclonal antibodies may further aid or confirm the diagnosis. Clinical features of herpes zoster may follow a progression through 3 stages, prodromal, acute, and chronic. The prodromal and acute phases seldom require more than symptomatic management. The chronic pain syndrome, postherpetic neuralgia (PHN), demands a more aggressive approach. Pharmacologic intervention, neuroaugmentation, and/or surgery may prevent or alleviate PHN, but universal response to any of these therapeutic approaches is unlikely. Tricyclic antidepressants remain the first choice in treating this pain syndrome. A trial of antiviral therapy may be warranted in patients with disseminated disease or in immunocompromised patients with localized disease. Of the antiviral agents, acyclovir is considered the drug of choice by most clinicians.

Acyclovir↗

Evaluation of creatinine clearance estimation in an elderly male population.

Thirty-one medically stable, elderly males (age 75 +/- 8.3 yrs) participated in a prospective study evaluating the accuracy of 16 methods of estimating creatinine clearance. Serum creatinine values were determined on the mornings of days 1, 4, and 5 to assure stable renal function. On the morning of day 3, a 24-hour urine collection was initiated. A statistically significant correlation existed between the measured and estimated clearance values for all 16 formulas. The correlation (r less than 0.65) was lower than that in previously published studies, however. Five of the formulas (1A, 5A, 5B, 7A, 7B) demonstrated no statistical difference between mean measured and estimated values. In this population, formula 2B was the least biased and formula 9B the most accurate. For all 16 methods, the bias was minimal and the relative accuracy of the estimated methods was comparable. The results support using methods to estimate creatinine clearance only as a rough bedside prediction of renal function in elderly males.

Aged↗

Patient tolerance to intravenous potassium chloride with and without lidocaine.

Hypokalemia is a common electrolyte abnormality. Intravenous repletion therapy with potassium chloride (KCl) in concentrations greater than 80-100 mEq/L is not recommended due to patient intolerance. Since this guideline at times may be clinically impractical, this study was designed to examine use of peripheral vein infusions of high concentration KCl therapy. Tolerance to KCl 20 mEq/65 ml iv with and without lidocaine 50 mg was evaluated in 18 hypokalemic subjects in a randomized, placebo-controlled, double-blind study. Subjective and objective assessments of adverse effects were determined throughout the infusion period. Pain was assessed by both verbal descriptor and visual analog scales and correlated significantly following infusion of KCl with or without lidocaine. Multivariant analysis demonstrated differences in pain perception between solutions, with significantly less pain following KCl with lidocaine versus KCl infusions. Transient adverse effects occurred in both groups, but the incidence was not statistically different. Use of concentrated iv KCl infusions may benefit hypokalemic patients with hypervolemia and/or severe potassium deficits. Addition of lidocaine clearly improves patient tolerance to intravenous KCl replacement.

Adolescent↗

Continuous nasogastric morphine infusion.

Morphine sulfate is the narcotic analgesic most commonly used for pain treatment in terminally ill patients. This case report demonstrates a new method of morphine administration. A 56-year-old terminally ill cancer patient with severe pain from metastatic adenocarcinoma of the lung required continuous nasogastric feeding and around-the-clock narcotic analgesics. The patient was safely and effectively converted from a continuous intravenous morphine infusion to continuous nasogastric morphine-enteral feedings. This method of administration may benefit patients receiving continuous enteral tube feedings who either require high-dose morphine therapy or are unable to use the oral administration route.

Humans↗

Pharmacogeriatrics.

The elderly comprise one of the fastest growing populations in the United States. By the year 2020, an estimated 45 million will be classified as elderly. Aging is a highly variable process as declines occur in physiologic functions. Alterations in cardiovascular, renal and hepatic function have the greatest effect on drug therapy. All pharmacokinetic and pharmacodynamic variables may be altered by age. Adverse drug reactions, drug interactions and poor compliance are frequent and may further complicate drug therapy. A review of those processes that commonly influence pharmacologic response and patient compliance to drug therapy is appropriate.

Aged↗

Evaluation of therapeutic drug monitoring in a long-term care facility: a pilot project.

The need for a therapeutic drug monitoring service was evaluated in a 150-bed long-term care facility. Thirty blood samples from 28 residents (mean age 87.9 years) were assayed to determine trough drug concentrations. All subjects were examined to determine pharmacodynamic effect. Pharmacokinetic consultations were written for serum drug concentrations outside accepted ranges. Fifty percent (15 of 30) of serum drug levels measured were subtherapeutic; the remaining levels were in the normal therapeutic range. Based on this sample data, it could be concluded that a minimum of 32 percent and as many as 68 percent of serum drug levels would be subtherapeutic following drug analysis in similar nursing home populations. Of 12 consultations, recommendations for seven (58 percent) were accepted by the subject's primary care physicians. Four of the consultations (33 percent) resulted in dosage modifications. These results support the need for further study.

Aged↗

Development of a questionnaire for detecting potential adverse drug reactions.

OBJECTIVE: To develop a comprehensive list of symptoms categorized by body system as part of a questionnaire for detecting potential adverse drug reactions. DATA SOURCES: A preliminary list of symptoms in lay terminology was extracted from the "Side Effects" section of all drug monographs contained in the United States Pharmacopeia Dispensing Information (USP DI) computerized database (Volume II, Advice for the Patient) using natural language processing software. The list was sorted alphabetically and duplicate terms were eliminated. Symptoms were then categorized by body system or anatomic region. A preferred term for each symptom was selected when multiple synonyms and related words were listed. Finally, all of the symptom terms were incorporated into a thesaurus from which the questionnaire was derived. RESULTS: The questionnaire will be used as part of a computer-assisted interview, developed to solicit information from patients regarding their medication regimens and to systematically query them regarding the presence of salient symptoms or complaints. The computer system will eventually interface with the USP DI database to identify drugs from a patient's regimen that may be associated with adverse symptoms. The symptom thesaurus will provide the link to the USP DI database. Preliminary experience with the questionnaire in a limited number of patients has been encouraging. CONCLUSIONS: The questionnaire can assist clinicians in identifying drug-related symptoms including unreported adverse clinical effects of newly marketed or investigational therapeutic agents. When the questionnaire is computerized and linked to a comprehensive database, it can be more widely used to alert healthcare providers of potential adverse drug reactions that may otherwise go undetected.

Adverse Drug Reaction Reporting Systems↗

Modified oral ondansetron regimen for cyclophosphamide-induced emesis in lupus nephritis.

OBJECTIVE: To evaluate the antiemetic efficacy of a modified regimen of oral ondansetron and dexamethasone in patients with lupus nephritis undergoing treatment with cyclophosphamide whose conventional antiemetic regimen had failed. DESIGN: A before-after prospective observational pilot project. SETTING: A federal research hospital. PATIENTS: Fourteen outpatients with lupus nephritis receiving intravenous cyclophosphamide 0.75-1.0 g/m2 had previously experienced chemotherapy-induced emetic events (vomiting or retching) while receiving a standard combination intravenous antiemetic regimen. The regimen consisted of four doses of thiethylperazine 10 mg and diphenhydramine 25 mg every 6 hours, and two doses of lorazepam 0.5 mg every 6 hours starting at 1 hour prior to cyclophosphamide. A subset of 8 patients previously completed a blinded study in which they received the intravenous formulation of ondansetron (4 doses of 4-16 mg q4h) administered orally beginning 30 minutes prior to the cyclophosphamide infusion. MAIN OUTCOME MEASURES: The number of emetic events and cost of drug administration were assessed for the modified ondansetron intervention and compared with those of the standard antiemetic regimen. The incidence of emetic events and visual analog nausea scores for the subset of eight patients were also evaluated. INTERVENTIONS: To account for the delayed onset of emesis associated with cyclophosphamide, patients received both ondansetron 8 mg orally every 4 hours (3 doses) and dexamethasone 10 mg orally (1 dose) beginning 4 hours after the cyclophosphamide infusion. This is different from the manufacturer's recommended dose schedule, in which ondansetron is administered prior to chemotherapy. RESULTS: No emetic events were observed following the administration of oral ondansetron/dexamethasone. The 95% confidence interval for the true rate of emesis was 0% to 19.3%. There was a significant difference in efficacy between ondansetron/dexamethasone and the triple antiemetic regimen (p < 0.0002). None of the patients experienced adverse effects while receiving the ondansetron/dexamethasone regimen. Cost comparisons (including admixture and nursing administration times) for standard combination therapy and oral ondansetron/dexamethasone were $109.09 and $70.24, respectively. No difference in emetic events or nausea ratings was observed between oral ondansetron/dexamethasone tablets and oral administration of ondansetron using the intravenous formula. CONCLUSIONS: This study suggests that a modified oral ondansetron/dexamethasone regimen is safe and efficacious, and costs less than alternative regimens to prevent cyclophosphamide-induced emesis in patients with lupus nephritis.

Administration, Oral↗

Effects of restricting levothyroxine dosage strength availability.

We conducted a prospective, randomized, controlled trial to assess whether hospital formulary restrictions involving limiting dosage strengths of levothyroxine affect physicians' ability to manage patients effectively and provide pharmacy cost savings in a tertiary care federal government research hospital. Thirty-three endocrinologists were randomly assigned to prescribe levothyroxine from a restrictive (dosage strengths of 25, 50, 100, 125, and 150 micrograms) or a nonrestrictive (dosage strengths of 25, 50, 75, 100, 112, 125, 150, 175, 200, and 300 micrograms) formulary through a central computer system. Their 241 respective outpatients' laboratory results and drug compliance were outcome measures. Achievement of treatment objectives was measured by thyroid function tests (free and total thyroxine, total triiodothyronine, thyrotropin), number of clinic visits, and compliance (survey method). Additional measures were drug distribution patterns, drug costs, and pharmacy inventory costs. Restriction of levothyroxine's dosage strength did not significantly alter therapeutic outcomes. However, the restricted formulary was associated with more complex dosing regimens, and resulted in no significant cost savings. It is not known whether such restriction would adversely affect the care of patients of nonspecialists. Prospective studies are required to verify presumed cost-containment measures before such measures are adopted for widespread application.

Adult↗

The pharmacokinetics and pharmacodynamics of fludarabine in rheumatoid arthritis.

STUDY OBJECTIVE: To describe the pharmacokinetics and pharmacodynamics of fludarabine in patients with rheumatoid arthritis (RA). DESIGN: Open-label, staggered trial conducted in conjunction with a phase I-II clinical trial. SETTING: Government research hospital. PATIENTS: Twenty-six patients with refractory RA. INTERVENTION: Fludarabine 20 or 30 mg/m2/day was administered as a 0.5-hour infusion for 3 consecutive days (1 cycle) for 6 months (1 cycle/mo). MEASUREMENTS AND MAIN RESULTS: Serial plasma samples were collected for pharmacokinetic analysis on day 2 of the first cycle of therapy. Relationships between pharmacokinetic parameters and hematologic and efficacy parameters were examined. The disposition of fludarabine was characterized by a two-compartment model. There were no differences in pharmacokinetics between the low- and high-dose groups. The mean+/-SD total clearance, volume of distribution at steady state, and beta-half-life were 13.68+/-5.1 L/hour, 170.08+/-86.5 L, and 10.9+/-3.1 hours, respectively. The volume of the peripheral compartment was approximately twice as large as the volume of the central compartment, indicating a significant amount of tissue distribution. No significant pharmacodynamic relationships were observed between pharmacokinetic parameters and hematologic and efficacy parameters. CONCLUSION: Fludarabine pharmacokinetics in patients with RA are characterized by an intermediate-length distribution phase (approximately 40 min), terminal half-life of 10.9 hours, and significant amount of tissue distribution.

Adult↗