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Biomedical subjects

J T DiPiro

Publications and source records attributed to J T DiPiro.

At least 55 records · Page 3Linked to original sources
PubMed1990

Assessment of cefazolin and cefuroxime tissue penetration by using a continuous intravenous infusion.

A continuous intravenous infusion was used to assess the tissue penetration of cefazolin (14 subjects) and cefuroxime (15 subjects) in orthopedic surgery patients. Subjects were randomly assigned to receive a continuous intravenous infusion of cefazolin (mean, 178.6 mg/h) or cefuroxime (mean, 330.0 mg/h) at a rate estimated to achieve a target steady-state total concentration of 50 micrograms/ml in serum. The infusion was initiated 12 to 14 h before surgery, and blood and muscle tissue samples were collected intraoperatively at the times of incision and wound closure. Although there was a significant difference between the free concentrations of cefazolin (at incision, 9.3 micrograms/ml; at closure, 9.2 micrograms/ml) and cefuroxime in serum (at incision, 26.9 micrograms/ml; at closure, 31.8 micrograms/ml), there was no difference in the total concentrations in muscle at either surgical incision (cefazolin, 6.1 micrograms/g; cefuroxime, 5.6 micrograms/g) or wound closure (cefazolin, 7.7 micrograms/g; cefuroxime, 7.4 micrograms/g). There was a significant correlation between the pooled free serum and total muscle concentrations for cefazolin (P = 0.001); however, there was no correlation between these variables with the pooled cefuroxime data (P = 0.403). These findings indicate that the free drug concentration in serum alone is not consistently predictive of the total concentration of cephalosporin in muscle.

Cefazolin↗
PubMed1990

Pathophysiology and treatment of gram-negative sepsis.

The pathogenesis, clinical presentation, and complications of gram-negative bacterial sepsis are described, and the implications for therapy are reviewed. The sepsis syndrome is a clinically defined condition that involves the physiologic alterations and clinical consequences of the presence of microorganisms or their toxins in the bloodstream or tissues. Gram-negative bacteria produce sepsis and septic shock via the release of the cell-wall component known as endotoxin (lipopolysaccharide). The lipid A moiety, common to gram-negative bacteria, is immunogenic and appears to account for many of the biologic effects of endotoxin. A variety of mediators, including tumor-necrosis factor, are released in response to endotoxin, with resultant diverse effects on host tissues, including organ dysfunction and shock. Adequate treatment requires prompt recognition of infection, especially endotoxemia and sepsis, and the early institution of appropriate therapy. Corticosteroids offer little benefit, and the efficacy of naloxone and nonsteroidal anti-inflammatory drugs has not been determined. Although suitable antimicrobial therapy is necessary to eliminate the offending organisms, antimicrobial agents do not inhibit the effects of the bacterial toxins that are present in sepsis. The outcome of sepsis may be favorably influenced in the future by the use of newer methods of detection and newer treatment modalities, including monoclonal antibodies directed against endotoxin or inhibitors of inflammatory mediators.

Bacterial Infections↗
PubMed1989

Controlling drug effects through improved oral formulations. The pharmacokinetics of the prazosin gastrointestinal therapeutic system.

Influences that determine a drug's effects include pharmacokinetic factors (the serum concentrations of drug as determined by the drug dose, absorption, distribution, and excretion) and pharmacodynamic factors (the intensity of drug effect). Most assessments of drug effect focus on the therapeutic range, i.e., the serum concentrations below which therapeutic effects are unlikely and above which toxic effects may be seen. A goal for many treatment regimens is to maintain serum drug concentrations within the therapeutic range. Maintenance of drug concentrations within the therapeutic range can be difficult with many traditional oral dosage formulations. Soon after administration of standard tablets, capsules, or liquids, a pronounced peak level is observed in serum. At the end of a dosage interval, serum concentrations are frequently below those needed to exert therapeutic effect. One reason for the wide range in serum concentrations with standard oral formulations is that these products usually exhibit first-order drug absorption, in which the rate of absorption from the gastrointestinal tract continually varies following a dose (from high to low) and is directly determined by the amount of drug remaining in the gastrointestinal tract. First-order absorption, therefore, results in changing absorption rates, wide swings in serum drug concentrations, a relatively short duration of action, and often, inconsistent drug effects over a dosage interval. One way to address the problems with standard oral products that have first-order absorption is to produce products that control drug release and absorption. A large number of controlled-release oral products are now on the market and use a variety of technologies. The ideal controlled-release formulation would result in zero-order drug absorption, in which the rate of drug absorption from the gastrointestinal tract would be constant and not determined by the amount of drug in the gastrointestinal tract. Zero-order absorption, therefore, results in an unchanging absorption rate, consistent serum levels, a longer duration of action, and more steady drug effect. Zero-order absorption is particularly preferable in situations that require a consistent, long-term therapeutic effect, e.g., in patients with hypertension, asthma, or arrhythmias. Of all the controlled-release preparations on the market, however, very few exhibit zero-order absorption; most can be categorized somewhere between first- and zero-order kinetics. An advanced-technology tablet has been invented to produce zero-order drug absorption for prazosin and nifedipine.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1989

Relationship of plasma clonidine to growth hormone concentrations in children and adolescents.

The relationships of plasma clonidine to increases in growth hormone, blood pressure response and degree of sedation were studied in nine children with short stature after a 0.15 mg/m2 oral clonidine tolerance test. A direct correlation was found between the peak plasma clonidine concentration and the increase in plasma growth hormone (P = 0.055). The patients experienced varying degrees of blood pressure reduction and sedation that were unrelated to age. No correlation was found between the plasma clonidine concentration and degree of blood pressure reduction or degree of sedation. The half-life of oral clonidine ranged from 1.75 to 2.38 hours, which is significantly less than that for adults.

Adolescent↗
PubMed1989

A comparison of monobactam antibiotics in surgical infections.

The introduction of gentamicin almost 20 years ago provided an effective option for the treatment of gram-negative bacillary infections. During the past few years, the availability of aztreonam (a monobactam), imipenem (a carbapenem), and newer cephalosporins within vitro activities comparable with aminoglycosides against many gram-negative bacilli, has stimulated a reassessment of the role of aminoglycosides in treating these infections. When determining the role of new antimicrobials as potential replacements for more established agents, the clinical focus should be on three factors: comparative efficacy, safety, and cost. Consideration of cost is relevant only when efficacy and safety are equivalent. Other factors, such as comparative in vitro antimicrobial activity, pharmacokinetics, and effect on normal flora can also influence the selection of an antimicrobial regimen. A new class of antimicrobials, the monobactams, is the focus of this review. The only member of this class currently in clinical use is aztreonam. A comparison with aminoglycosides is particularly relevant because aztreonam is active against aerobic gram-negative bacilli. This review will discuss the acknowledged concerns with aminoglycoside use and compare the characteristics of aztreonam and currently marketed aminoglycosides.

Aminoglycosides↗
PubMed1989

Single-dose cefmetazole versus multiple dose cefoxitin for prophylaxis in abdominal surgery.

One hundred and ninety-five patients undergoing abdominal surgical procedures completed a multicentre, randomized, open-label study comparing the safety and efficacy of cefmetazole and cefoxitin for the prevention of postoperative wound infection. Cefmetazole was administered iv in a single 2 g dose given within 90 min of the operation. Cefoxitin was administered in a single 2 g, similarly timed, preoperative dose and two additional doses given at 6 h intervals after surgery. For operations that exceeded 2-4 h duration an additional dose of each agent was administered. Patients undergoing colorectal operations received oral neomycin and erythromycin as bowel preparation. Colorectal operations were performed most frequently (49% of patients) followed by cholecystectomies (26%) and gastroduodenal procedures (21%). The operative site infection rate was 6.5% for cefmetazole and 7.7% for cefoxitin (P greater than 0.05). Serious drug related adverse effects were not observed. This study demonstrates that administration of single-dose cefmetazole is as effective as a standard three dose regimen of cefoxitin for prophylaxis with abdominal operations.

Abdomen↗
PubMed1989

Comparative intraoperative concentrations of two cephalosporins with activity against anaerobic bacteria.

We determined the intraoperative concentrations of cefmetazole and cefoxitin in serum and muscle from the wound of 30 patients who were undergoing cholecystectomies. The study employed an open-label design in which all patients randomly received cefoxitin sodium (30 mg/kg) or cefmetazole sodium (15 or 30 mg/kg) intravenously with the induction of anesthesia. Total serum and wound-muscle concentrations achieved with cefmetazole 30 mg/kg were significantly greater than those achieved with a similar dose of cefoxitin. Cefmetazole in a 15 mg/kg dose was comparable with cefoxitin 30 mg/kg in achieved concentrations. The elimination half-life for cefoxitin was much shorter than that for cefmetazole (41 min v. 64-68 min, respectively) and this relates to a shorter duration of action for the former. The choice of agent for surgical prophylaxis should incorporate factors relating to drug pharmacokinetic properties as well as microbiological factors.

Adolescent↗
PubMed1989

Pharmacokinetics of gentamicin in neonates on extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) has been used in more than 1,000 infants in 50 centers in the United States. The extracorporeal circuit contains approximately 400 ml of blood, an amount exceeding the blood volume of most full-term neonates. The effect of this additional blood volume on drug disposition is unknown. In this study, we determined the pharmacokinetic parameters of gentamicin in 10 infants on ECMO. Gentamicin concentrations were determined by a fluorescence polarization immunoassay. Pharmacokinetic parameters were determined from these concentrations by using a two-compartment model. Our study demonstrated a mean steady-state volume of distribution of 0.51 +/- 0.11 liters/kg, a figure similar to that in previous studies of full-term infants. The elimination half-life was found to be prolonged (mean, 573 +/- 263 min). The creatinine level in the plasma of the infants was found to be a statistically significant predictor of elimination half-life. Recommendations regarding initial dosing levels of gentamicin in infants on ECMO are made.

Blood Urea Nitrogen↗
PubMed1988

Use of serum drug concentrations in surgical patients.

Surgical patients frequently require drug treatments that can be assessed with serum drug concentrations. Of the agents for which serum drug concentrations are routinely available, the aminoglycosides theophylline, vancomycin, digoxin, and phenytoin are used most frequently in surgical patients. When using serum drug concentrations, the clinician should have an understanding of the relationships (or lack of) between drug concentrations and therapeutic or toxic effects. When blood is collected for serum concentration determinations, the exact timing of the sample in relation to the dose must be considered. For some drugs, (such as the aminoglycosides, it is necessary to determine peak and trough concentrations, whereas for other agents, like theophylline, the average or mid-dose level may be more important to consider. There are many factors that affect serum drug concentrations. Among these are various disease states, obesity, fluid imbalances, the drug dosage form used, and concurrent drug use. Not all patients require serum drug concentration monitoring; however, with each drug there are high-risk patients who may benefit. When used properly, serum drug concentrations may be helpful in maximizing therapeutic benefits, minimizing or diagnosing drug toxicity, and assessing patient compliance with drug regimens.

Aminoglycosides↗
PubMed1988

Effect of antimicrobial therapy on bowel flora.

The known patterns and functions of gastrointestinal flora and antimicrobial effects on flora are described, and the clinical implications of altered bowel flora are described. A major role of the normal endogenous intestinal flora is to inhibit gastrointestinal colonization and overgrowth by potentially pathogenic bacteria. Serious disruption of this protective mechanism may occur after the administration of various antimicrobial agents. Alteration of bacterial flora by antimicrobials is often the result of incomplete absorption after oral administration or of high concentrations in saliva, bile, or secretions from the intestinal flora. Suppression of endogeneous microflora after antimicrobial administration may permit overgrowth of pathogenic strains in the gastrointestinal tract, development or selection of antimicrobial-agent-resistant strains, and disruption of colonization resistance. The disruption of normal bowel flora can result in diarrhea, pseudomembranous colitis, and systemic infections or sepsis in immunocompromised patients. Agents that are well absorbed and have minimal biliary excretion should minimize the detrimental effects from altered flora. The choice of an antimicrobial agent that has a narrow spectrum, is specific for the infection, is not appreciably excreted in the bile, and is completely absorbed if given orally appears to be the most appropriate practice for preventing or minimizing alteration of bowel flora.

Anti-Bacterial Agents↗
PubMed1988

Use of cephalosporins with enhanced anti-anaerobic activity for treatment and prevention of anaerobic and mixed infections.

The microbiology, adverse-effect profiles, pharmacokinetics, published results of comparative clinical trials, and costs of cephalosporins with enhanced antianaerobic activity are reviewed. Cefoxitin, ceftizoxime, cefotetan, and moxalactam have been used as single agents in the treatment or prophylaxis of anaerobic or mixed aerobic and anaerobic infections, including intra-abdominal, female genital tract, and soft-tissue infections. None of these agents is as active against Bacteroides species as is clindamycin or metronidazole, but differences among the four cephalosporins do not appear to be clinically important. These agents differ somewhat in their activity against gram-positive and gram-negative bacteria. The majority of adverse reactions to these agents are immunological; disulfiram-like reactions and alterations in normal hemostasis have also been observed with cefotetan and moxalactam. All of these agents are well absorbed after intramuscular injection and produce serum concentrations adequate to treat most infections. Only ceftizoxime and moxalactam produce cerebrospinal fluid concentrations adequate for treatment of gram-negative meningitis. The primary route of elimination is renal, and each agent requires dosage adjustments in patients with renal impairment. Major differences exist among the elimination half-lives of the agents in patients with normal renal function. The decision to use a cephalosporin for treatment of anaerobic infections should be based on the results of clinical trials that have demonstrated the efficacy of the agent. Data are available to support the use of cefoxitin, ceftizoxime, and moxalactam in the treatment of intra-abdominal infections; cefoxitin and moxalactam to prevent infection of traumatic injury to the abdomen; all four agents in the treatment of female genital tract infections; and all four agents for prophylactic use in surgical procedures that may involve enteric anaerobes, especially B. fragilis. Cephalosporins with enhanced antianaerobic activity appear to have similar in vitro microbiological activity and have efficacy similar to that of combination regimens for the treatment and prophylaxis of intra-abdominal infections, abdominal contamination, obstetric and gynecological infections, and soft-tissue infections.

Bacteria, Anaerobic↗
PubMed1987

Drug interactions in surgical patients.

Drug interactions, defined as when the administration of a single substance (drug, nutrient, or tobacco) modifies the response to a drug, occur relatively frequently in surgical patients and may result in increased morbidity and lengthened hospital stay. Drug interactions also account for some instances of drug ineffectiveness or exaggerated pharmacologic response. There are many types of drug interactions. However, most of them are related to altered drug pharmacokinetic properties, where there are alterations in drug absorption, distribution, metabolism, or elimination; or altered drug pharmacodynamic actions, where two agents may have synergistic, additive, or antagonistic pharmacologic effects. The term, drug interaction, usually refers to pairs of drug substances administered concurrently, but more than two agents may be involved. When patients are taking a large number of different medications, there may be multiple drug interactions with additive or antagonistic effects, the overall effects of which are difficult to predict. There are hundreds of reported drug interactions, and some may be of important clinical consequence. In surgical patients, the majority of drug interactions involve histamine-2 blockers (particularly cimetidine), digoxin, warfarin, or a variety of agents that may be administered during anesthesia. Recognition of the potential for adverse drug interactions is of primary importance in minimizing their effects. Usually, potentially interacting drugs may be administered concurrently as long as appropriate patient or laboratory assessments are performed. For some agents, such as digoxin or theophylline, serum drug concentrations may aid in the avoidance of adverse drug interactions.

Anesthesia↗
PubMed1987

Effect of hemorrhagic shock on cefazolin and gentamicin pharmacokinetics in dogs.

The physiologic response to traumatic injury may alter the disposition of drugs and thereby affect their therapeutic or toxic potential. A study was conducted in 10 mongrel dogs to determine the effect of experimental hemorrhagic shock with resuscitation on the pharmacokinetics of gentamicin and cefazolin. Single simultaneous intravenous doses of gentamicin (3 mg/kg) and cefazolin (25 mg/kg) were administered to each animal on an initial study day, after which serial blood and urine collections were performed. After 1 week, a standard hemorrhagic shock model was applied to each animal. Shock was continued for 1 h, after which the animal was resuscitated with either whole blood or saline. After stabilization for 20 min, a second dose of gentamicin and cefazolin was administered, and blood and urine were again collected. Drug clearance was not significantly altered, except for that of cefazolin after saline resuscitation, for which there was a significant increase in drug clearance. After both methods of resuscitation an increase in the volume of distribution was noted for cefazolin and gentamicin. Drug half-life was noted to be increased after shock for cefazolin by both resuscitation methods and for gentamicin after shock by saline resuscitation. Although alterations of pharmacokinetic parameters were noted, mean concentrations of gentamicin and cefazolin in serum were similar for pre- and postshock phases.

Animals↗
PubMed1987

Stability of terbutaline sulfate repackaged in disposable plastic syringes.

The stability of terbutaline sulfate injection repackaged in disposable plastic syringes and stored for a 60-day period under one of three conditions, dark at 4 degrees C, dark at 25 degrees C, and light at 25 degrees C, was studied. Terbutaline sulfate from 1-mg/mL ampuls was repackaged into 63 3-mL polypropylene syringes. Twenty-one syringes were protected from light by storage in ultraviolet-light-inhibiting bags in a dark cabinet. Twenty-one syringes were exposed to continuous fluorescent light at room temperature, and the remaining syringes were stored in the dark under refrigeration. Samples were visually inspected and assayed on days 0, 1, 4, 7, 14, 28, and 60 after repackaging. Drug concentrations were determined by a stability-indicating high-performance liquid chromatographic method. Terbutaline concentrations ranged from 89.2% to 98.5% of initial concentration. The contents of the light-exposed syringes had yellowed by day 60. Terbutaline sulfate in polypropylene syringes is stable for 60 days under refrigeration and at room temperature when protected from light, but substantial degradation and discoloration of the drug can occur when the syringes are not protected from light.

Drug Packaging↗
PubMed1987

Polyethylene glycol electrolyte lavage solution (PEG-ELS). A rapid, safe mechanical bowel preparation for colorectal surgery.

The use of polyethylene glycol electrolyte lavage solution (PEG-ELS) as a whole-bowel irrigation for colorectal surgery is retrospectively evaluated in 65 consecutive patients. Sixty-three (97%) of the patients were able to complete the lavage. Fifty-five (85%) of these tolerated the preparation without event. Unpleasant reactions of nausea, vomiting, or fullness resolved in most patients by decreasing the rate of ingestion. Twenty-seven patients had associated medical illnesses that may have been aggravated by volume overload, but none of these experienced any adverse effects from the lavage. Most patients completed the total lavage ingestion of 4 L in 4 hours, which resulted in a 1-day preparation prior to operation. There were no wound or septic complications in any of the lavage patients. This clinical review indicates that PEG-ELS is a safe, rapid, and effective mechanical bowel preparation that should be able to reduce in-hospital preparation time for most patients undergoing colorectal surgery.

Adolescent↗