Showing papers in "Annals of Pharmacotherapy in 1988"
TL;DR: Fibrin glue has been used in a variety of surgical procedures, and has been especially useful in heparinized patients undergoing cardiovascular procedures requiring extracorporeal circulation, as it does not require an intact hemostatic system to be effective.
Abstract: Fibrin glue is composed of two separate solutions of fibrinogen and thrombin. When mixed together, these agents mimic the last stages of the clotting cascade to form a fibrin clot. Fibrin glue is available in Europe but is not commercially available in the U.S.; therefore, investigators have extemporaneously compounded their own fibrin glue. Fibrinogen can be obtained from pooled, single-donor, and autologous blood donors and is usually isolated by the process of cryoprecipitation. The thrombin component is generally derived from commercial bovine sources. Some investigators have added calcium chloride and/or antifibrinolytics (i.e., aminocaproic acid, aprotinin) to their preparations. Fibrin glue can be applied using a double-barrel syringe or by spray application. Although fibrin glue has been used in a variety of surgical procedures, it has been especially useful in heparinized patients undergoing cardiovascular procedures requiring extracorporeal circulation, as it does not require an intact hemostatic system to be effective. Fibrin glue also has been evaluated in presealing woven or knitted Dacron vascular grafts. The major drawback to its use is the risk of transmitted serological disease from pooled and single-donor blood donors. The safest preparations use the patient's own blood to prepare fibrin glue. Overall, fibrin glue is a useful adjunct to other methods to control bleeding in selected surgical patients.
149 citations
TL;DR: Clinical pharmacists in this study hospital reported 1027 interventions in patient drug therapy over two time periods of three and two weeks, which had the potential to save $897 550 annually in hospital resources if all their interventions had been accepted and implemented.
Abstract: Clinical pharmacists in this study hospital reported 1027 interventions in patient drug therapy over two time periods of three and two weeks, respectively. These interventions were subjected to self and peer reviews and to cost-avoidance evaluation. The most frequent type of intervention was recommendations related to drug selection (29.6 percent). Recommendations were not implemented by physicians in only 10.2 percent of the cases. The perceived impact of these interventions on the quality, cost, or both was found by the peer reviewers to occur in 58.5, 16.1 and 25.6 percent of the cases, respectively. Also, when peer reviewed for clinical significance, 983 of these interventions were judged to improve drug therapy to an acceptable level based on the professional literature, and 36 were deemed very significant in terms of saving patients' lives or preserving major organ functions. Of the 983 interventions rendering drug therapy to an appropriate level, 398 were deemed to have cost-avoidance impact; of this number a 25 percent random sample was subjected to cost-avoidance evaluation. Realized cost-avoidance averaged $242 for each intervention implemented. When extrapolated annually, $364,900 was the net realized cost-avoidance after discounting for the cost of providing clinical pharmacy services. An average cost-avoidance of $860.50 was calculated for each intervention made by pharmacists, but not followed by physicians, for an annual potential cost-avoidance of $532,650. In all, clinical pharmacists had the potential to save $897,550 annually in hospital resources if all their interventions had been accepted and implemented.
147 citations
TL;DR: The illustrative meta-analysis confirmed previous traditional narrative literature reviews that Bendectin is not related to teratogenic outcomes in humans, and the corresponding chi-square values were not statistically significant at the p = 0.05 level.
Abstract: This article presents a stepwise approach for conducting a meta-analysis of epidemiological studies based on proposed guidelines. This systematic method is recommended for practitioners evaluating epidemiological studies in the literature to arrive at an overall quantitative estimate of the impact of a treatment. Bendectin is used as an illustrative example. Meta-analysts should establish a priori the purpose of the analysis and a complete protocol. This protocol should be adhered to, and all steps performed should be recorded in detail. To aid in developing such a protocol, we present methods the researcher can use to perform each of 22 steps in six major areas. The illustrative meta-analysis confirmed previous traditional narrative literature reviews that Bendectin is not related to teratogenic outcomes in humans. The overall summary odds ratio was 1.01 (χ2 = 0.05, p = 0.815) with a 95 percent confidence interval of 0.66–1.55. When the studies were separated according to study type, the summary odds rat...
120 citations
TL;DR: Clinical trials suggest that diclofenac has a favorable side-effect profile, excellent patient tolerability, and a lower patient dropout rate when compared with aspirin and other NSAID.
Abstract: Diclofenac sodium is a nonsteroidal antiinflammatory drug (NSAID) that has been used in 120 countries since its introduction in Japan in 1974. It is currently the eighth largest-selling drug and the most frequently used NSAID in the world. Diclofenac, a phenylacetic acid derivative, is a potent inhibitor of cyclooxygenase enzyme activity, and may also interact with the lipoxygenase enzyme pathway, and with the release and reuptake of arachidonic acid. Diclofenac is almost completely absorbed, highly protein-bound, penetrates well into synovial fluid, and is extensively metabolized. Comparative studies have shown that diclofenac is at least equivalent in efficacy to aspirin and other NSAID when used for the treatment of rheumatic diseases such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Diclofenac also possesses potent analgesic properties. Clinical trials suggest that diclofenac has a favorable side-effect profile, excellent patient tolerability, and a lower patient dropout rate when compared with aspirin and other NSAID.
114 citations
TL;DR: A formative method of documenting the clinical pharmacist's activities such as the PWDT must be functional on a daily basis in order to generate meaningful summative management reports.
Abstract: The profession of pharmacy has applied the term "documentation" to count activities that more closely approximate descriptive protocols or administrative reports. This extended nonclinical use of the term documentation has resulted in the profession losing sight of a necessary step in the development, justification, and successful implementation of clinical pharmacy services. An instrument that helps to standardize the documentation of a clinical pharmacist's database, patient-care activities, and therapeutic plans is presented. This process, the pharmacist's workup of drug therapy (PWDT), consists of the following six interrelated steps: (1) establish a comprehensive patient-specific database; (2) identify patient-specific, drug-related problems; (3) describe desired therapeutic outcomes; (4) list all therapeutic alternatives that might produce the desired outcomes; (5) select the drug recommendation(s) that most likely will result in the desired outcomes; and (6) establish a plan for therapeutic drug monitoring that documents that desired effects occur and undesired effects are minimized. A formative method of documenting the clinical pharmacist's activities such as the PWDT must be functional on a daily basis in order to generate meaningful summative management reports.
88 citations
TL;DR: Although 65 percent of the respondents were unwilling to pay an additional fee for the service, females and those who were 45–54 years and over 65 years old were significantly more willing to pay for the information.
Abstract: The extent of medication use and drug information preferences was surveyed randomly from patients at six different pharmacy health care systems. Following verbal consultation, each patient was given one or more modified United States Pharmacopoeia drug information leaflets corresponding to the verbal information and a self-addressed, stamped questionnaire to complete. Chi-square analysis was performed on 317 responses with overwhelming acceptance (96 percent) of the medication information provided. Although a majority of respondents (62 percent) preferred a combination of both written and oral information, specific information preferences (oral, written, or both) were significantly related to educational level, pharmacy attended, and prescription status. Nearly 45 percent of the respondents indicated the information was responsible for changing their medication use. Subjects who were elderly, taking cardiovascular medications, or getting refill prescriptions were significantly less likely to change as a result of the information provided. Although 65 percent of the respondents were unwilling to pay an additional fee for the service, females and those who were 45-54 years and over 65 years old were significantly more willing to pay for the information. In addition, the willingness to pay tended to increase as the number of daily medications taken increased. Consideration of socioeconomic and prescription variables may help define subgroups with specific information preferences and counseling activities that may be directly reimbursable.
58 citations
TL;DR: Sixty-two serum concentrations were obtained from 12 infected patients enrolled in a vancomycin pharmacokinetic study and both unbound and total serum vancomYcin concentrations were measured using ultrafiltration and a commercial fluorescent polarization immunoassay.
Abstract: Sixty-two serum concentrations were obtained from 12 infected patients enrolled in a vancomycin pharmacokinetic study Both unbound and total serum vancomycin concentrations were measured using ultrafiltration and a commercial fluorescent polarization immunoassay Ultrafiltrates were obtained by centrifugation at 1000 X g for ten minutes at room temperature and their assay indicated a range in protein binding from 79 to 71 percent The mean protein binding (mean +/- SD) was 4195 +/- 1415 percent No measurable adsorption of vancomycin onto the ultrafiltration membrane was noted Orthogonal regression of unbound versus total vancomycin concentrations was described by the equation y = 0597x-0362 with a correlation coefficient of 0948
52 citations
TL;DR: The data suggest that for patients free of preexisting renal and cardiac disease, rapid AB infusions are well tolerated and produce adverse reactions similar in nature and severity to slower infusions.
Abstract: Our objective was to prospectively study febrile and chill reactions associated with two amphotericin B (AB) infusion rates, slow (2-hour) versus rapid (45 minute). Seventeen consenting bone marrow transplant recipients in whom AB was to be initiated for documented or suspected fungal infections were recruited. After standardized premedication, patients received eight daily AB infusions (0.5 mg/kg/d, concentration 0.25 mg/ml). Rate was assigned using a randomized, crossover pair design. Axillary temperature, chills, and meperidine dose required to resolve chills were monitored for each infusion. For the first pair of infusions, fever (defined as a rise of 1 degree C) occurred frequently, in 12 of 17 (70.5 percent) and 13 of 17 patients (76.4 percent), with a mean rise of 1.7 degrees C (range 1.1-3.7) and 1.7 degrees C (1.1-3.5) degrees for the 45-minute and 2-hour infusions, respectively (p greater than 0.10). Chills were observed in 15 of 17 (88.2 percent) and 14 of 17 (82.3 percent) recipients of the 45-minute and 2-hour infusions, respectively. The time of onset (p greater than 0.10) and the duration of chills (p = 0.08) were similar for both infusion rates. Meperidine requirements for rapid and slow infusions were similar as well (p = 0.12). These data suggest that for patients free of preexisting renal and cardiac disease, rapid AB infusions are well tolerated and produce adverse reactions (fever and chills) similar in nature and severity to slower infusions.
49 citations
TL;DR: Data presented here suggest that other antibiotics, such as vancomycin and tobramycin, can be used successfully in polymethylmethacrylate beads and provide preliminary facts for future investigations of such applications.
Abstract: Over the past several years there has been a growing interest in the use of locally implanted beads containing antibiotics for the treatment of chronic osteomyelitis. This method has been popularized in Europe and, with few exceptions, gentamicin has been the only antibiotic used. There have been only a few reports from the U.S. and there is little information regarding the pharmacokinetics of antibiotics used in this fashion. To our knowledge this is the first report using vancomycin. Three patients with chronic osteomyelitis were treated with vancomycin and/or tobramycin polymethylmethacrylate beads. These beads were extemporaneously compounded and implanted for up to six weeks. From the site of bead implantation local fluid aliquots were collected for the measurement of antibiotic concentrations. In two patients, initial tobramycin concentrations exceeded 400 mg/L. In one patient receiving vancomycin, initial localized concentrations were approximately 100 mg/L. In all three patients therapeutic concentrations of localized antibiotic were maintained with immeasurable systemic concentrations throughout the period of bead placement. Localized antibiotic therapy for the management of chronic osteomyelitis represents a potential therapeutic alternative to long-term parenteral therapy. Data presented here suggest that other antibiotics, such as vancomycin and tobramycin, can be used successfully in polymethylmethacrylate beads and provide preliminary facts for future investigations of such applications.
46 citations
TL;DR: Neuroleptic malignant syndrome is associated with essentially all of the currently available antipsychotic agents and the signs and symptoms are hyperpyrexia, define.
Abstract: Neuroleptic malignant syndrome (NMS) is associated with essentially all of the currently available antipsychotic agents. The signs and symptoms associated with the syndrome are hyperpyrexia, defined by body temperature greater than 38 degrees C; extreme muscle rigidity, with or without elevated creatine phosphokinase or hyperreflexia; and other symptoms such as altered level of consciousness and/or autonomic dysfunction as manifested by labile blood pressure, tachycardia, tachypnea, urinary or fecal incontinence, pallor, or diaphoresis. This potentially fatal syndrome complicates the treatment of patients with recurrent psychotic symptoms because of the possibility for recurrence of the NMS. A case of recurrent NMS is presented in which the patient was rechallenged with an antipsychotic agent. In addition, 41 reported cases of antipsychotic rechallenge after NMS are reviewed. The results of the review suggest that neuroleptic rechallenge following NMS is associated with an acceptable risk of recurrence in most patients. However, close monitoring for NMS and careful selection of patients for antipsychotic rechallenge is mandatory. A minimal time period of five days before rechallenge may also reduce the risk of recurrent NMS. Recurrence was not associated with patient age or gender, nor the antipsychotic agent used.
46 citations
TL;DR: This article presents a review of the literature on the development and prevention of stress ulcer disease and investigates such alternative prophylactic agents as sucralfate and prostaglandins that do not alter the normal gastric acidity.
Abstract: Stress-related gastrointestinal bleeding is known to occur in approximately 25 percent of untreated seriously ill patients, but with appropriate prophylaxis is largely preventable. Since the treatment of stress bleeding is generally unsatisfactory and has a high mortality, routine prophylaxis should be instituted for susceptible patients. Multiple mechanisms contribute to stress ulcer formation, the most important of which appear to be mucosal ischemia and the inability to control back-diffused hydrogen. Antacids and histamine2-blocking agents are presently the cornerstone of effective prophylaxis, but because they have been implicated as contributors to nosocomial pneumonias due to bacterial overgrowth in the stomach, investigation is ongoing into such alternative prophylactic agents as sucralfate and prostaglandins that do not alter the normal gastric acidity. This article presents a review of the literature on the development and prevention of stress ulcer disease.
TL;DR: Literature has recently begun to appear describing the therapeutic activities of long-acting somatostatin analog octreotide and the first steps to understanding their clinical pharmacology are being taken.
Abstract: The somatostatins represent endogenous substances that serve a diversity of functions in the body. These activities are just beginning to be understood and could have major implications in the treatment of human disease. Their chief pharmacologic activities lie in the modification or modulation of protein hormone synthesis of the gastrointestinal system; a great many other systems may be involved as well. Since the discovery of the therapeutic potentials of naturally isolated somatostatins, attempts have been made to design newer analogs more conducive to practical use. Such an example is long-acting somatostatin analog octreotide. Literature has recently begun to appear describing the therapeutic activities of this and other similar compounds and the first steps to understanding their clinical pharmacology are being taken. Surprising activity has been found in the palliative treatment of a wide variety of formerly resistant gastrointestinal syndromes and endocrine tumors. These activities may have considerable future impact on the treatment of disease involving hormonal imbalance or inappropriate secretion.
TL;DR: Possible mechanisms involved in the blood pressure elevation as well as treatment approaches that have been employed are discussed and further research efforts are needed to clarify conflicting information.
Abstract: Use of the immunosuppressive agent cyclosporine has been associated with an increased incidence of hypertension. The incidence, onset, duration, and severity of the associated blood pressure elevation varies greatly depending on the therapeutic indication for cyclosporine use. This paper reviews the disparity in the reports of cyclosporine-associated hypertension and the factors evaluated for possible association. Possible mechanisms involved in the blood pressure elevation as well as treatment approaches that have been employed are discussed. Further research efforts are needed to clarify conflicting information regarding mechanisms, associated factors, and rational treatment.
TL;DR: In this era of program evaluation and justification, the process of encouraging other health professionals to review pharmacists' contribution to patient care should not be overlooked.
Abstract: Clinical pharmacists in this study hospital reported 1027 interventions in patient drug therapy over two time periods of three and two weeks each. When peer-reviewed for clinical significance, 36 of these interventions were deemed significant in terms of saving patients' lives or preserving major organ functions; 983 were judged to improve drug therapy to an acceptable level based on standards of the professional literature (8 recommendations were informational i.e., not clinically significant).These 36 interventions were subjected to an independent, blind review by three practicing physicians who were given the same ranking system for clinical relevance as the one used by the peer reviewers. The physicians independently concurred with the peer reviewers on the two interventions initially ranked as 6 (lifesaving in nature). Of the interventions ranked 5 (preserving major organ functions) by the peer-review group, 53 percent were given a rank of 5 by the physicians. However, the remaining 47 percent were g...
TL;DR: This paper addresses the relative potential for weight gain with the monoamine oxidase inhibitors and suggests that phenelzine is the MAOI most likely to induce weight gain; reports of isocarboxazid-induced weight gain are less common.
Abstract: Weight gain associated with antidepressant therapy is a common problem that often results in noncompliance. Some authors suggest that monoamine oxidase inhibitors (MAOI) are less likely to produce weight gain than tricyclic antidepressants. This paper addresses the relative potential for weight gain with the MAOI. Assessing the potential for antidepressant-induced weight gain necessitates separating the weight changes associated with alterations in mood disorders from those due to drug-induced alterations in appetite control. The mechanisms of appetite control are reviewed briefly followed by proposed mechanisms by which the MAOI may alter this control. A literature review suggests that phenelzine is the MAOI most likely to induce weight gain; reports of isocarboxazid-induced weight gain are less common. There are no cases of tranylcypromine-induced weight gain in the literature that are clearly associated with the drug. The MAOI probably have different effects on the mechanisms of appetite control.
TL;DR: A 26-year-old hemophiliac patient with acquired immunodeficiency syndrome and cryptosporidiosis whose diarrhea improved with continuous intravenous administration of a long-acting somatostatin analog, octreotide, should be considered for patients with secretory diarrhea refractory to other forms of therapy.
Abstract: Cryptosporidiosis commonly causes severe diarrhea in immunosuppressed patients. There currently are no antiparasitic drugs consistently effective for this infection. This case describes a 26-year-old hemophiliac patient with acquired immunodeficiency syndrome and cryptosporidiosis whose diarrhea improved with continuous intravenous administration of a long-acting somatostatin analog, octreotide. Somatostatin has a variety of inhibitory effects on gastrointestinal hormones as well as a possible nonspecific effect on gastrointestinal mucosal fluid and electrolyte secretion. The somatostatin analog should be considered for patients with secretory diarrhea refractory to other forms of therapy.
TL;DR: The strengths and limitations of the major pharmacoepidemiologic methodologies employed in postmarketing drug surveillance are described and the current status of the U.S. surveillance system is described.
Abstract: This article describes and discusses the strengths and limitations of the major pharmacoepidemologic methodologies employed in postmarketing drug surveillance and describes the current status of the U.S. surveillance system. The main methodologies employed in postmarketing drug surveillance include controlled clinical trials, observational epidemiologic studies (cohort, case-control, cross-sectional), demographic methods, drug utilization surveys, spontaneous reports, and automated databases linking medications and disease. Examples of pharmacoepidemiologic studies using each of these methodologies are presented. When a question arises about the efficacy and/or safety of a marketed drug, typically a mixture of these study methodologies is employed. The article concludes with a brief discussion of the role of the Food and Drug Administration, pharmaceutical manufactures, and academic institutions in initiating and conducting postmarketing drug studies.
TL;DR: Postmarketing surveillance could benefit from more attention to identifying and solving the problems associated with record linkage studies, including postmarketing drug surveillance.
Abstract: Large automated databases are the source of information for many record linkage studies, including postmarketing drug surveillance. Despite this reliance on prerecorded data, there have been few attempts to assess data quality and validity. This article presents some of the basic data quality and validity issues in applying record linkage methods to postmarketing surveillance. Studies based on prerecorded data, as in most record linkage studies, have all the inherent problems of the data from which they are derived. Sources of threats to the validity of record linkage studies include the completeness of data, the ability to accurately identify and follow the records of individuals through time and place, and the validity of data. This article also describes techniques for evaluating data quality and validity. Postmarketing surveillance could benefit from more attention to identifying and solving the problems associated with record linkage studies.
TL;DR: Two cases of reversible mental confusion in elderly patients with mild renal insufficiency following intravenous famotidine therapy are reported, possibly explained by an increased permeability of the blood-brain barrier in patients with decreased renal function.
Abstract: Central nervous system effects, such as mental confusion and hallucinations, have been reported with both cimetidine and ranitidine. Elderly patients with renal or hepatic dysfunction are more susceptible to these adverse reactions. We report two cases of reversible mental confusion in elderly patients with mild renal insufficiency following intravenous famotidine therapy, possibly explained by an increased permeability of the blood-brain barrier in patients with decreased renal function.
TL;DR: The two-stage intervention can be used to effect virtually any modification in prescribing trends deemed appropriate by an institution and is especially well suited for hospitals with a transient prescribing population for whom episodic forms of intervention are not effective.
Abstract: prescriber antagonism has been encountered. Cost savings for one year have been approximately $55 000. Based on acceptance by prescribers and success of the above intervention, usage reviews have been conducted to identify other drugprescribing problems that may be amenable to intervention. In 1986-87, over $117000 was spent on parenteral metronidazole at this institution. Metronidazole also possesses characteristics that permit extended (12-hour) intervals of administration.' A review of 216 written inpatient orders revealed that 94 percent of treatment courses during a 14-weekperiod involved dosage intervals of eight hours or less. Only 4 percent of treatment courses involved 12-hour dosage intervals. In June 1987, an identical two-stage intervention was used to convert metronidazole from q8h to ql2h regimens. Again, both stages had a significant impact on prescribing ~abit~. Aft.er the persuasive stage was initiated, 27 percent of all written mpatient orders were for 12-hour dosage intervals; this increased to an average of 94 percent for 18weeks following implementation of the second sta~e of the intervention. An average of 59 percent of total orders were written by the prescriber for extended intervals. The bal~nce were s~cc~ss fully converted by therapeutic interchange. Contmuous momto~m.g shows no deviation from the above trends. To our knowledge, this IS the first report of such an intervention to increase metronidazole dosage intervals to 12 hours. Cost savings are estimated to be $24 000 in the first year of the program. The two-stage intervention was implemented in October 1986 to convert tobramycin written inpatient orders to gentamicin (except in critical care areas where pseudomonal infections warrant tobramycin usage). Annual cost savings achieved as a result of this inter~ention have been $34 000. Clindamycin will be added to the program m early 1988. This is another antibiotic for which extended (eight-hour) dosage intervals are possible and can result in a savings of $30 000 per year at this hospital. The design of this program does not permit us to evaluate whether physicians modified their prescribing behavior as a consequence of the rationale supporting extended interval dosing or in anticipation of the therapeutic interchange stage. However, the fact that prescribers had the option of requesting no substitution and did so infrequently suggests that the rationale was generally accepted and extended-interval prescribing was adopted. Perhaps prescribers would have resisted the change if therapeutic interchange had been initiated without a preceding persuasive stage. Such other factors as peer-group endorsement and the presence of preprinted orders in the patient's health record when an interchange was required may have increased compliance. Our assessments were not designed to determine the impact of each factor, but to measure the overall effectiveness of the two stages of intervention. In our institution, the combined effect of persuasive and power strategies has proved successful. Continued prescriber acceptance is demonstrated by the percentage of orders in which no interchange is required to comply with appropriate use guidelines, and by minimal use of the' 'no substitute" clause. This two-stage intervention can be used to effect virtually any modification in prescribing trends deemed appropriate by an institution. It is especially well suited for hospitals with a transient prescribing population for whom episodic forms of intervention are not effective.
TL;DR: Perceived importance of medication information and the kind of information provided to patients in an outpatient setting and less than half the time was information considered highly important by patients provided by their physicians are shown.
Abstract: A study was done to determine perceived importance of medication information and the kind of information provided to patients in an outpatient setting. A scale describing 14 points of medication information was used prior to the physician's visit in one study phase and afterwards in the second phase. Results showed that patients perceived all 14 items to be important but rated precautions to observe, drug interactions, and adverse effects most highly. Also, less than half the time was information considered highly important by patients provided by their physicians.
TL;DR: A clinical pharmacy service providing blood cholesterol testing and consultation was implemented in a community pharmacy and patients expressed strong satisfaction with various aspects of the service, and the amount that they were willing to pay increased significantly.
Abstract: A clinical pharmacy service providing blood cholesterol testing and consultation was implemented in a community pharmacy. In this pilot study, 27 patients each paid $10 to have a serum cholesterol determination. All subjects completed a questionnaire to determine attitude toward such a service, intention to use it in the future, and willingness to pay for its use. A posttest patient satisfaction questionnaire was completed after blood-level results were reported and discussed with the patient.All subjects stated that they were strongly in favor of such a service, that they would use it, and that they would pay an average of $11.60 for the test. On the posttest questionnaire, patients expressed strong satisfaction with various aspects of the service, and the amount that they were willing to pay increased significantly to $14.35.It is recommended that community pharmacies implement such patient-oriented services.
TL;DR: Although often described as a mucolytic, its function is probably that of mucoregulation, which results in physical changes in accumulated secretions that are favorable in terms of clearance.
Abstract: Carbocysteine is prescribed for conditions characterized by the accumulation of excessive mucus. Although often described as a mucolytic, its function is probably that of mucoregulation, which results in physical changes in accumulated secretions that are favorable in terms of clearance. The chemistry, pharmacology, pharmacokinetics, clinical applications, and toxicology of carbocysteine are reviewed.
TL;DR: TMP-SMX therapy should be instituted with extreme caution in patients with AIDS who have demonstrated a prior hypersensitivity reaction to the drug, including a severe anaphylactoid reaction associated with pulmonary edema and rhabdomyolysis.
Abstract: A patient with acquired immunodeficiency syndrome (AIDS) developed rash, fever, neutropenia, and elevated liver function tests during an initial course of trimethoprim-sulfamethoxazole (TMP-SMX) therapy Upon reexposure to the drug, the patient experienced a severe anaphylactoid reaction associated with pulmonary edema and rhabdomyolysis Reactions associated with TMP-SMX rechallenge in this patient population have been previously reported but have not been associated with this degree of severity TMP-SMX therapy should be instituted with extreme caution in patients with AIDS who have demonstrated a prior hypersensitivity reaction to the drug
TL;DR: It is difficult to recommend the drug of choice for producing sedation in children undergoing diagnostic procedures because most available studies have not compared these drugs in a controlled and blind manner, and the data have often been collected retrospectively.
Abstract: Sedation is routinely used in pediatric patients undergoing diagnostic procedures. Meperidine with promethazine and chlorpromazine; meperidine with pentobarbital; and meperidine, morphine, pentobarbital, thiopental, methohexital, chloral hydrate, and benzodiazepines as single agents have been used at different doses in patients for various procedures including computed tomography, endoscopy, electroencephalography, and bone marrow biopsies. Most available studies, however, have not compared these drugs in a controlled and blind manner, and the data have often been collected retrospectively. In addition, the degree and duration of sedation required may depend on the procedure. Thus, it is difficult to recommend the drug of choice for producing sedation. Serious cardiac and respiratory effects and excessive sedation have been associated with these drugs, even when normal doses were used. Controlled studies and specific guidelines are needed for optimal use and monitoring of these drugs in pediatric patients.
TL;DR: Carboplatin will be most useful in patients with decreased renal function and those who cannot tolerate high-volume hydration regimens, and patients at higher risk for development of cisplatin-related ototoxicity or neurotoxicity may be ideal candidates for carboplatin as initial therapy.
Abstract: Carboplatin, a new antineoplastic agent with a spectrum of antitumor activity similar to cisplatin, has shown appreciable activity in patients with ovarian carcinoma, head and neck cancer, and small-cell lung cancer. This platinum complex is less nephrotoxic, ototoxic, and neurotoxic than cisplatin. Myelosuppression may be severe and dose-limiting. Carboplatin distributes into a volume approximating total body water, and is slowly bound to plasma proteins; its elimination is a biphasic process. Renal clearance of free platinum from carboplatin correlates highly with creatinine clearance in patients with normal or impaired renal function. The recommended iv dose of carboplatin as a single agent in previously untreated patients is 400-500 mg/m2; dosage must be reduced in patients with decreased renal function, low initial platelet count, or extensive prior chemotherapy or radiation therapy. Carboplatin will be most useful in patients with decreased renal function and those who cannot tolerate high-volume hydration regimens. Patients at higher risk for development of cisplatin-related ototoxicity or neurotoxicity (e.g., patients expected to receive cumulative cisplatin doses exceeding 600-800 mg/m2) may be ideal candidates for carboplatin as initial therapy. Large-scale comparative trials are needed before carboplatin can be recommended as a replacement for cisplatin.
TL;DR: Prolonged duration of action of lisinopril allows once daily dosing, unlike captopril for which dosing is required every 8–12 hours or enalapril which may necessitate twice daily doses.
Abstract: Lisinopril is a new, nonsulfhydryl angiotensin-converting enzyme inhibitor approved for the treatment of hypertension. After oral administration, 25-29 percent of the dose is absorbed intact; biotransformation is not required for pharmacological activity. Onset of action occurs one to two hours after administration, with effects still present 24 hours later. The major route of elimination is through renal excretion and an elimination half-life of 12.6 hours has been reported in normotensive individuals. In patients with impaired renal function (creatinine clearance less than or equal to 30 ml/min) a longer half-life and accumulation have been observed. Lisinopril 20-80 mg/d has been shown to be as effective as hydrochlorothiazide, nifedipine, and beta-blocking agents in the treatment of essential hypertension. Its efficacy in renovascular hypertension has also been demonstrated. In congestive heart failure (CHF) doses of 2.5-20 mg/d appear to provide hemodynamic effects comparable to those of captopril. Dizziness and cough have been the most frequently reported side effects; rash and proteinuria have also been reported in a small number of patients. Interactions with diuretics, potassium supplements, and possibly with nonsteroidal antiinflammatory agents may occur. Lisinopril appears to be similar in efficacy to other antihypertensive agents in the treatment of essential hypertension and to captopril in the treatment of CHF. Whether lisinopril is safer or more effective than captopril or enalapril in the treatment of hypertension or CHF requires further investigation. Prolonged duration of action of lisinopril allows once daily dosing, unlike captopril for which dosing is required every 8-12 hours or enalapril which may necessitate twice daily dosing.
TL;DR: Within 36 hours of discontinuing naproxen, the meningitis-like symptoms markedly improved, and a thorough drug history, including that of recent or intermittent NSAID use, should be obtained.
Abstract: A rare complication of nonsteroidal antiinflammatory drug (NSAID) use, particularly in patients with collagen vascular or autoimmune diseases, is aseptic meningitis. A healthy 21-year-old man receiving naproxen for muscle spasm was admitted with a chief complaint of severe headache. Approximately one week after beginning naproxen, the patient developed headache, fever (T 38.8°C), shaking chills, and nuchal rigidity with occasional nausea and vomiting resulting in a 15-lb weight loss. Findings from a cerebrospinal fluid examination revealed polymorphonuclear pleocytosis and elevated protein, but no evidence of infection with bacteria, fungi, mycobacteria, or viral agents was noted. Within 36 hours of discontinuing naproxen, the meningitis-like symptoms markedly improved. Rechallenge with naproxen was not performed. In patients exhibiting meningitis-like symptoms, a thorough drug history, including that of recent or intermittent NSAID use, should be obtained.
TL;DR: Trials evaluating the clinical utility of octreotide indicate efficacy in the management of symptoms associated with acromegaly and hypersecretory neuroendocrine tumors, and in the control of nontumoral secretory diarrheas.
Abstract: Octreotide is an investigational synthetic peptide exhibiting actions similar to those of endogenous somatostatin It has a longer half-life than the native hormone and can be administered by subcutaneous injection Octreotide inhibits the secretion of growth hormone and numerous regulatory peptides of the gastroenteropancreatic system Trials evaluating the clinical utility of octreotide indicate efficacy in the management of symptoms associated with acromegaly and hypersecretory neuroendocrine tumors, and in the control of nontumoral secretory diarrheas Octreotide therapy is well tolerated This agent should prove useful in the symptomatic control of a number of rare hypersecretory disorders
TL;DR: A simple noncomputer method was developed to allow individuals to estimate caffeine plasma concentrations based on personal intake habits, and changes in the time courses due to smoking, oral contraceptive use, and liver disease, all of which alter caffeine pharmacokinetics were examined.
Abstract: Multiple dosage regimens for therapeutic agents are commonly comprised of a constant dosing interval and a constant dose size. This is not true for the ingestion of a pharmacologically active agent that is a component in a dietary source. Caffeine is contained in foods and beverages that are regular components of the diet for many people. Because daily intake is unsystematic, a computer program was written to simulate caffeine plasma concentration-time courses following ingestion of variable amounts on irregular schedules. Literature values for caffeine pharmacokinetics, for the caffeine content in various foods and beverages, and for consumer habits were employed to simulate various caffeine plasma concentration-time courses. By searching for predictable traits in a wide variety of plasma concentration-time courses representing normal adults, a simple noncomputer method was developed to allow individuals to estimate caffeine plasma concentrations based on personal intake habits. Changes in the time cours...