The clinical pharmacist in drug research and development. Clinical research units.
Explore the source record for details and available documents.
Drug Evaluation↗
Biomedical subjects
T S Foster
Publications and source records attributed to T S Foster.
Pharmacologic evaluation of loratadine (SCH 29851), chlorpheniramine and placebo.
The antihistaminic effect of loratadine (160 mg) was compared in twenty-four normal male volunteers to chlorpheniramine maleate (4 mg) and placebo in a double blinded 3-way cross-over study of latin square design. After receiving single oral doses of each medication, the wheal response to serial 0.1 ml intradermal histamine (2 micrograms) and saline (control) injections were recorded over a 24-h period. The calculated wheal areas were compared to base-line measurements. The results were analyzed by analysis of variance. Loratadine exhibited a more pronounced inhibition of histamine wheal formation than placebo or chlorpheniramine maleate (p less than 0.003). In contrast to chlorpheniramine maleate which had a duration of action of only 3 h, loratadine inhibited the response for the entire observation period between 1 and 24 h post-dose. Although sedation was observed less frequently with loratadine (Placebo, n = 2; chlorpheniramine, n = 3; and loratadine, n = 1), the relative incidence were not statistically significant.
Adult↗
Retrograde spreading of hydrocortisone enema in inflammatory bowel disease.
A hydrocortisone suspension enema was radiolabeled with [99mTc]technetium sulfur colloid and administered to four normal subjects and eight patients with varying degrees of inflammatory bowel disease. The extent of enema spreading was monitored using external scintigraphy for a period of up to 4 hr after administration. Pretreatment of normal subjects with an evacuation enema resulted in spreading of the radiolabeled enema throughout the entire colon. In seven of the eight patients studied, the enema migrated a distance equal to or greater than the extent of disease involvement. An in vivo stability study with an indium-111-labeled enema, using the perturbed angular correlation technique, revealed that the enema retains its stability for up to 90 min after administration. These results indicate that the use of hydrocortisone enemas may not be restricted to distal bowel disease, but may also be effective in inflammatory bowel diseases involving proximal regions of the colon.
Colitis, Ulcerative↗
Patient-controlled analgesia in the terminally ill cancer patient.
Patient-controlled analgesia (PCA) is a relatively new therapeutic modality which has allowed postsurgical patients to safely and effectively self-administer doses of intravenous narcotics via a syringe pump and sequencing device. A pilot study was designed to evaluate PCA's safety and effectiveness in the terminally ill cancer patient. Eight patients whose chronic pain was not adequately controlled by oral narcotics were permitted to use PCA for a minimum of 48 hours. Respiratory rates, sedation rankings, and pain rankings indicated these patients achieved satisfactory analgesia with a minimum of sedation and experienced no respiratory depression. Three patients were switched to oral regimens using PCA dosing as a guide. Pain and sedation rankings were similar to those registered while exclusively on PCA. This self-dosing technique was judged to be safe, effective, and able to accommodate wide fluctuations in analgesic need when treating pain in the terminally ill cancer patient. The results obtained in these patients support further trials using PCA to individualize oral analgesic regimens.
Adult↗
The postoperative adverse effects of inhalational anesthetics.
Inhalational general anesthetics can contribute to postoperative morbidity (Table II). Postoperative effects of inhalational anesthetics on the central nervous system are speculative. The "toxic" effects of these agents during the postoperative period are most often an extension of their pharmacologic and physiochemical properties. Inhalational anesthetics may produce a number of varied changes in mental status after surgery such as headache, emergence excitement, and delirium. It is very important for health professionals to be aware of the risk of perioperative myocardial infarction in patients with preexisting heart disease if early detection and treatment are to occur. Relative to the common postoperative problems of atelectasis, pneumonia, and aspiration, inhalational agents may have a contributory role especially in patients with preexisting pulmonary disease. Postoperative nausea and vomiting are other common problems in which inhalational agents may have a role in their development. Although extensively investigated, suspected halothane hepatoxicity is a very rare complication if it exists at all. The renal effects of inhalational anesthetics are usually mild and transitory, although the use of methoxyflurane can produce direct nephrotoxicity. The evidence to support a clinically significant direct immunosuppressant effect of inhalational anesthetics after surgery is inconclusive. A concensus exists that any minor, short-lived effects are in all probability overshadowed by the nonspecific stress of surgery itself. By reducing this stress, anesthetics undoubtedly have a protective effect. There are probably no major mutagenic or carcinogenic effects of inhalational anesthetics under normal conditions. Inhalational anesthetics should be avoided during pregnancy because of their teratogenic potential and their effects on the uterus.(ABSTRACT TRUNCATED AT 250 WORDS)
Anesthesia, Inhalation↗
Patient-controlled high-dose morphine therapy in a patient with electrical burns.
Explore the source record for details and available documents.
Adult↗
Multicenter, double-blind, placebo-controlled trial of terfenadine in seasonal allergic rhinitis and conjunctivitis.
A multiclinic, double-blind, parallel and controlled study was conducted in the 1982 spring pollen season to evaluate and compare the effects of terfenadine, 60 mg bid with those of chlorpheniramine 4 mg tid and placebo for a treatment period of seven days in patients with seasonal allergic rhinitis and conjunctivitis. Of a total of 397 patients enrolled in the seven study centers, 345 patients were accepted for evaluation of efficacy and 393 patients for safety. The results show that based on the physicians' assessment of the overall efficacy, terfenadine was significantly superior to placebo and comparable to chlorpheniramine in the relief of allergic symptoms, with moderate to complete relief being observed in 60% (68/113) of the terfenadine-treated patients, in 60% (71/119) of the chlorpheniramine-treated patients, and in 30% (34/119) of the placebo-treated patients. The daily evaluation of severity of symptoms by the patients show that the effect of terfenadine and chlorpheniramine was evident on the first day after entry, reached a peak on the second day after entry, and persisted thereafter. Side effects were minor and infrequent in all treatment groups. There was no statistically significant difference in the incidence of sedation between the terfenadine (7.6%) and placebo (2.4%) groups whereas the incidence of sedation with chlorpheniramine (19%) was significantly higher. In conclusion, terfenadine is as effective as chlorpheniramine in the treatment of symptoms of seasonal allergic rhinitis and conjunctivitis with an incidence of sedation not significantly different from that with placebo and significantly less than with chlorpheniramine.
Adult↗
The adult respiratory distress syndrome.
The adult respiratory distress syndrome (ARDS) is a common form of acute respiratory failure that has been increasingly reported as associated with a wide variety of medical conditions. Unlike other identifiable pathological events causing severe lung injury, it is now recognized that ARDS is not a single disease, but a complex interaction of pathophysiological events that result in diffuse injury to lung parenchyma. Only through a thorough understanding of ARDS pathophysiology, pathogenesis, and clinical course can medical intervention be instituted in a judicious and timely manner. This review article is intended to provide an overview of the suspected precipitating causes, discrete pathophysiologic changes, and monitorable clinical events associated with ARDS. With mortality from ARDS high, significant attention is being given to improving therapeutic intervention with such conventional measures as mechanical ventilation, positive end-expiratory pressure, and fluid management, along with corticosteroids and several new experimental pharmacologic approaches.
Adult↗
Nifedipine stability in cardioplegic solution.
The stability of nifedipine in cardioplegic solution was studied. Cardioplegic solutions containing nifedipine at 275 and 500 micrograms/liter were stored in plastic bags covered in brown plastic wrappers (1) under normal room light at 25 degrees C and (2) in a dark refrigerator at 4 degrees C. Samples were removed periodically for 48 hours. Infusions of cardioplegic solution containing 275 micrograms/liter were simulated using tubing and flow rates of 100, 200, and 300 ml/min; bags were covered with aluminum foil, while tubing was exposed to normal room lighting or yellow lighting, which does not degrade nifedipine. Gas chromatography was used for nifedipine assays. Nifedipine degraded more rapidly at 25 degrees C than at 4 degrees C. However, even when protected from light and refrigerated, nifedipine concentrations declined to less than 90% of original potency by approximately six hours after preparation. There was no significant degradation during the simulated infusion regardless of light exposure or flow rate. Cardioplegic solutions containing nifedipine should be prepared immediately before the surgical procedure, refrigerated until use, and protected from light until administration.
Cardiovascular Agents↗
Nifedipine kinetics and bioavailability after single intravenous and oral doses in normal subjects.
Nifedipine kinetics have not been described in clinically relevant detail because of difficulties in formulating a stable preparation for intravenous use and lack of a specific and sensitive assay for plasma nifedipine. We recently developed a gas-chromatographic method and determined conditions in which nifedipine could be protected from photodegradation. Therefore, we evaluated the kinetics and bioavailability of nifedipine in 12 normal subjects after single intravenous (1 mg/5 min) and oral (10 mg) doses. After intravenous dosing, the drug was eliminated with a half-time of 1.77 +/- 0.25 hour, and total clearance was calculated at 0.62 +/- 0.09 liter/kg/hr. With oral drug administration, the elimination half-time was twice as long for the group; but within these subjects, marked variability in the rate of appearance of the drug in plasma was observed, giving profiles consistent with fast and slow absorption. In the latter group, peak plasma drug concentrations were only one third the level seen in those exhibiting a faster absorption profile, although the extent of drug absorption (as derived from areas under the plasma level-time curves) did not vary. Bioavailability was 0.45 +/- 0.08. Untoward effects resulting from the drug's pharmaco-subjects after intravenous administration (flushing).
Administration, Oral↗
Patient-controlled analgesia.
Patient-controlled analgesia is a relatively new and investigational technique that permits patients to treat pain by directly activating doses of intravenous narcotics. The technique was developed in response to the undertreatment of pain in hospitalized patients. Continuous narcotic infusion and intraspinal narcotic administrations also have the potential to provide continuous, uninterrupted analgesia, but do not allow simple dose attentuation to avoid overdosage. Patient-controlled analgesia is used to treat postoperative and labor pain and pain associated with terminal illness; it delivers analgesic more effectively with fewer side effects than conventional parenteral narcotic therapies. The technique is also an ideal investigative instrument for studying equianalgesic states. Several foreign-made devices are now being used under investigational sanctions in this country, and it is anticipated that several American manufacturers will be seeking regulatory approval to market the devices.
Administration, Oral↗
Patient-controlled analgesia: a new concept of postoperative pain relief.
This report concerns evaluation of patient-controlled analgesia (PCA) in the form of two preliminary investigations. In the first study, the patient-controlled analgesia device, which consists of a pump linked to a timer so that patients can activate intravenous administration of morphine sulfate to themselves during the postoperative period, was used in seven morbidly obese patients. The amount of morphine used during the first 36 hours was found to vary between 32 and 185 mg, with a significant difference in drug usage when related to weight as well as to body surface area. In the second study, morbidly obese patients undergoing gastric bypass operations were prospectively randomized into 12 patients who used the PCA device in the postoperative period and 12 patients who were given standard intramuscular dosages of morphine sulfate. An analgesia and sedation scale was then used to compare the two groups. The patients in the PCA group were able to maintain a state of adequate analgesia without sleep with a significantly greater frequency than were those in the intramuscular injection group. On the basis of answers to a questionnaire given to the patient after 60 hours of morphine analgesia, it was apparent that the PCA group was much more satisfied with that form of postoperative analgesia. It would appear that PCA is an efficacious and safe method of providing for postoperative pain relief.
Analgesia↗
Pharmacokinetics of theophylline in young and elderly subjects.
Theophylline kinetics were evaluated in 6 elderly (age 65-75 years) and 5 young (age 22-28 years), nonsmoking males following the oral administration of 200 mg of Elixophylline. Theophylline serum concentration in the postabsorptive phase declined in a monoexponential manner. Total body clearance, elimination half-life, volume of distribution and protein binding were determined. There were no statistically significant differences in these kinetic parameters between the elderly and young subjects. Therefore, advancing age should not be used as a sole factor in the adjustment of theophylline dosage.
Adult↗
Treatment of refractory ventricular arrhythmias. High dose parenteral and oral bretylium tosylate.
Explore the source record for details and available documents.
Administration, Oral↗
Pharmacist involvement in institutional review of clinical trials.
The establishment of an institutional review committee (IRC) for investigational clinical trials in a large community hospital is reported. After the need for an IRC was identified, the pharmacy and therapeutics committee charged the director of pharmacy with drafting a protocol for establishing an IRC. Following a literature review, guidelines were written for the IRC in the form of a committee manual. These guidelines were approved, and composition of the nine-member committee was set as follows: three members of the trustee medical education and research committee, three members of the medical staff, one member each of the clergy staff and the pharmacy staff, and one nonaffiliated community representative. The IRC reviews, approves or denies, and supervises all proposed clinical investigations. Risk/benefit ratios, purpose, recruitment and selection procedures, financial support, and informed consent documents of the proposed study are among the factors considered in the approval process. Guidelines for written policies and procedures governing IRC structure and activities are presented. The involvement of the pharmacist in the establishment and subsequent functions of the committee is described. IRC membership is an opportunity for the pharmacist to work with other professionals in protecting the rights and welfare of human research subjects.
Clinical Trials as Topic↗
Legal and ethical issues in clinical pharmacy research--informed consent, Part I.
The continued growth of hospital and clinical pharmacy should be paralleled by the development of sound research methods justifying innovative practices. Such research will, on occasion, require experimentation involving human subjects. The principal means of assuring that the welfare of research participants is not compromised is through the procurement of effective informed consent. Pharmacists, like many other health professionals, have had relatively little exposure to methodology involved in the writing of an informed consent instrument. A comprehensive document must not only conform to the requirements of federal regulatory agencies, but must also satisfy various institutional guidelines. Past instances of unethical human experimentation are discussed, and a format for preparation of an informed consent instrument is examined. Circumstances requiring informed consent and identification of the basic elements of consent are also explained.
Clinical Trials as Topic↗
Legal and ethical issues in clinical pharmacy research--informed consent, Part II.
Preparation of an effective informed consent document presents significant problems to those investigators not familiar with federal and institutional requirements. This article examines a detailed format for preparation of an informed consent instrument. Prepared by the authors and supplied to potential clinical investigators by a university institutional review committee, the guidelines incorporate Department of Health, Education, and Welfare regulations. An example consent form is provided.
Clinical Trials as Topic↗
Disulfiram-like reaction associated with a parenteral cephalosporin.
A disulfiram-like reaction attributed to cefoperazone, an investigational cephalosporin, is reported. Cefoperazone (T-1551, Pfizer Pharmaceuticals, Inc.), a semisynthetic, parenteral cephalosporin undergoing clinical trials in the United States, was administered in single 1-, 2-, and 3-g doses to 12 healthy volunteers. The drug was administered as a 5% solution by constant infusion over a five-minute period, and one week was allowed between doses. Approximately 25 hours after receiving the 3-g dose, one subject experienced facial flushing after drinking 12 fluid ounces of beer. A second ingestion of 24 ounces of beer eight hours later produced facial flushing, tachycardia, diaphoresis, and pounding headache; the symptoms lasted 1.5-2 hours. A subsequent rechallenge with beer five hours later produced an identical reaction, but the symptoms subsided rapidly. Further rechallenge 60 hours after receiving the drug produced no ill effects. No such reaction appears to have been reported previously as being associated with the administration of a cephalosporin.
Adult↗