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Biomedical subjects

R E Small

Publications and source records attributed to R E Small.

At least 19 recordsLinked to original sources
PubMed1991

Current options for the treatment of systemic scleroderma.

The epidemiology, pathology, diagnosis, and clinical manifestations of systemic scleroderma (SSc) are described, and therapeutic options are discussed. SSc is a rare condition of unknown etiology that occurs in a subset of scleroderma patients. It is distinguished by involvement of the small arteries, microvessels, and diffuse connective tissue. The degree of internal organ involvement is the main determinant of morbidity and mortality. Management of SSc may entail supportive, palliative, remittive, and immunosuppressive therapies. Supportive therapy involves maintaining the affected extremities at warm temperatures and the use of emollient creams. Results of palliative treatment are mixed. Toxic reactions may be associated with many of these medications. Dermatologic manifestations have been treated with nonsteroidal anti-inflammatory agents, low-dose corticosteroids, dimethyl sulfoxide, and edetate disodium; peripheral and internal-organ vascular obstruction, with alpha-adrenergic blockers, angiotensin-converting-enzyme inhibitors, and calcium-channel blockers. Antacids with alginic acid, histamine H2-receptor antagonists, sucralfate, and cholinergic-acting agents may be used to relieve GI symptoms. Lung infections should be treated promptly with antibiotics. No drug therapy has been successful in reducing the incidence of fatal cardiac arrhythmias or in preventing cardiac fibrosis. Captopril and enalapril are essential in the control of SSc renal crisis. Penicillamine may hold promise as a remittive therapy. The immunosuppressive agents fluorouracil, cyclosporine, and methotrexate, which have shown limited effectiveness in preliminary studies, merit further investigation. No therapeutic agent has yet been shown to alter the course of SSc on a consistent or long-term basis. Toxicity and drug interactions remain a major concern in patient management, and aggressive monitoring is essential.

Adult↗
PubMed1990

Influence of H2 receptor antagonists on the disposition of flurbiprofen enantiomers.

The effect of oral cimetidine or ranitidine on the pharmacokinetics of the R and S enantiomers of the nonsteroidal anti-inflammatory drug flurbiprofen and its major metabolite, 4'-hydroxyflurbiprofen, was evaluated. Nine healthy volunteers participated in a randomized crossover design study with the following treatments: (A) flurbiprofen 200 mg; (B) flurbiprofen 200 mg plus ranitidine 150 mg bid for 7 days before and for 2 days after receiving flurbiprofen and (C) flurbiprofen 200 mg plus cimetidine 300 mg qid for 7 days before and for 2 days after receiving flurbiprofen. Blood and urine samples were collected at various intervals during a 48-hour period. These samples were assayed stereospecifically for flurbiprofen and its metabolite. Small but statistically significant differences in the terminal elimination rate constant (K), maximum peak serum drug concentration (Cmax), time to reach peak concentration (tmax), oral clearance (Cl/F) and area under the curve (AUC) were noted for flurbiprofen enantiomers. No significant treatment*isomer interactions were observed, indicating that neither cimetidine nor ranitidine interacted stereospecifically with flurbiprofen. Cimetidine, but not ranitidine, resulted in small (less than or equal to 15%) but statistically significant changes in flurbiprofen pharmacokinetic parameters. The interaction between H2-antagonists and flurbiprofen is unlikely to be clinically important.

Adult↗
PubMed1990

Liver function assessment by drug metabolism.

Liver function can be assessed by administering an exogenous substance to quantify changes in hepatic blood flow, uptake, biotransformation, and excretion. Characterization of drug half-life, clearance, and product formation rates are possible methods for measuring hepatic efficiency. Allopurinol and caffeine have been used to measure metabolite formation followed by renal elimination of both parent substance and metabolite. Sorbitol, a substance with high intrinsic clearance, can reflect liver blood flow, while trimethadione, a low-extraction drug, has been used to measure liver enzyme capacity. Metabolites from lidocaine, methacetin, and aminopyrine have been measured in serum, urine, and breath tests. Salivary clearance measurements of caffeine and antipyrine are reported as suitable for routine use. Genetic diversity of isoenzymes and the many metabolic processes used by hepatocytes make it extremely difficult to quantify functional changes with one substance. Combinations of model substrates have been suggested to assess the many hepatic processes.

Acetamides↗
PubMed1989

Diclofenac sodium.

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of diclofenac sodium are reviewed. Diclofenac, the first nonsteroidal anti-inflammatory agent (NSAID) to be approved that is a phenylacetic acid derivative, competes with arachidonic acid for binding to cyclo-oxygenase, resulting in decreased formation of prostaglandins. The drug has both analgesic and antipyretic activities. Diclofenac is efficiently absorbed from the gastrointestinal tract; peak plasma concentrations occur 1.5 to 2.0 hours after ingestion in fasting subjects. Even though diclofenac has a relatively short elimination half-life in plasma (1.5 hours), it persists in synovial fluid. The drug is metabolized in the liver and is eliminated by urinary and biliary excretion. In clinical trials, diclofenac was as effective as aspirin, diflunisal, indomethacin, sulindac, ibuprofen, ketoprofen, and naproxen in improving function and reducing pain in patients with rheumatoid arthritis. For treatment of osteoarthritis, diclofenac was equivalent in efficacy to aspirin, diflunisal, indomethacin, sulindac, ibuprofen, ketoprofen, naproxen, flurbiprofen, mefenamic acid, and piroxicam. Diclofenac was as effective as indomethacin or sulindac in treating ankylosing spondylitis. The most frequent adverse effects reported for diclofenac were gastrointestinal, but these effects were fewer and less serious than occurred with aspirin or indomethacin; in addition, diclofenac caused fewer central nervous system reactions than indomethacin. Diclofenac is administered in divided doses with meals. The recommended total daily dosage is 100 to 150 mg (osteoarthritis and ankylosing spondylitis) or 150 to 200 mg (rheumatoid arthritis). Diclofenac is effective, but no more so than other NSAIDs. It is structurally distinct and offers another choice in the treatment of rheumatological conditions.

Animals↗
PubMed1988

Sulindac-induced toxic epidermal necrolysis.

A case of sulindac-induced toxic epidermal necrolysis (TEN) is described; the etiology, symptoms, and treatment of TEN are reviewed; and sulindac's pharmacokinetic characteristics and other adverse effects are discussed. A 62-year-old black woman was given a prescription for sulindac 150 mg twice daily to relieve pain associated with degenerative joint disease. She also had a nine-year history of type II diabetes mellitus that was being managed with tolbutamide 500 mg once daily. After two weeks of sulindac therapy she developed a rash that spread over her entire body. Sulindac therapy was discontinued, and one day later the patient was admitted to the hospital with a temperature of 104.6 degrees F, conjunctivitis, and an erythematous macular rash over 60% of her body. Initially, therapy included prednisone 160 mg orally every day, applications of silver sulfadiazine cream four times daily for two days, and methylcellulose 0.5% ophthalmic solution (two drops four times daily) for the conjunctivitis. She also received intravenous hydration. By the fifth hospital day the patient's skin lesions and conjunctivitis had improved to the point that the prednisone dosage was tapered to 120 mg, then to 80 mg, and then to nothing over the following three days. Her diabetes was managed by short-term treatment with NPH insulin; however, before discharge, tolbutamide therapy was reinstituted, and insulin was discontinued. At follow-up four weeks after discharge, the patient's skin was largely clear. TEN has multiple etiologies, but the basic mechanism of injury is believed to be an immunological reaction directed at the basal cell layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1988

Pharmacokinetic and taste evaluation of ibuprofen (Motrin) 800 mg tablets in extemporaneous solution.

A 4-way crossover study was done to determine the pharmacokinetic and palatability characteristics of ibuprofen 800 mg tablets when given as a solution in various beverages. When compared to the tablet itself, no significant difference was noted for any variable measured for an orange juice solution. A delay in time-to-peak concentration (Tmax) was noted for a dilute cherry syrup solution. Changes in Tmax, peak concentration achieved and area-under-the-curve were noted with a Coca-Cola solution. The authors conclude Coca-Cola to be clearly inappropriate for this method, a dilute cherry syrup solution slightly better and orange juice to be the preferred option.

Adult↗
PubMed1987

Effect of antacid suspension on the pharmacokinetics of ibuprofen.

The effect of antacid administration on the pharmacokinetics of ibuprofen was evaluated in a randomized, crossover study of eight healthy volunteers. Doses of 62 mL of aluminum and magnesium hydroxide suspension and single doses of ibuprofen 400 mg were used. Subjects received each of the following treatments at one-week intervals: ibuprofen alone; ibuprofen administered concurrently with one dose of antacid; antacid administered one hour after the ibuprofen dose; and antacid administered concurrently with the ibuprofen dose, plus three more antacid doses given every five hours. Blood samples were taken at various time intervals up to 24 hours after the ibuprofen dose. Serum samples were assayed for ibuprofen content using high-performance liquid chromatography. Values for AUC, Cmax, tmax, and k were not significantly different among treatment groups. The ranges of mean (+/- S.D.) values were 113.97 +/- 21.5 to 127.53 +/- 29.3 micrograms.hr/mL for AUC, 35.30 +/- 6.40 to 41.00 +/- 10.00 micrograms/mL for Cmax, 0.95 +/- 0.30 to 1.28 +/- 0.54 hr for tmax, and 0.346 +/- 0.026 to 0.388 +/- 0.040 hr-1 for k. For the doses used, concurrent administration of aluminum and magnesium hydroxide suspension and ibuprofen does not alter ibuprofen pharmacokinetics.

Adult↗
PubMed1986

Spacer inhalers.

Explore the source record for details and available documents.

Administration, Intranasal↗
PubMed1986

Effects of cimetidine or ranitidine on the pharmacokinetics of flurbiprofen.

The effect of oral cimetidine or ranitidine on the pharmacokinetics of the nonsteroidal anti-inflammatory agent flurbiprofen was studied. Nine healthy volunteers participated in the study. The subjects were divided into three groups, and each group alternated therapy with each of the following treatments: flurbiprofen 200 mg (two 100-mg tablets), flurbiprofen 200 mg plus ranitidine 150 mg two times daily for seven days before and for two days after receiving flurbiprofen, and flurbiprofen 200 mg plus cimetidine 300 mg four times a day for seven days before and for two days after receiving flurbiprofen. Blood samples were collected at time zero and at various intervals during a 48-hour period. Serum flurbiprofen concentrations were determined by high-performance liquid chromatography. No significant differences in elimination rate constant, peak concentration, time to peak concentration, volume of distribution, or elimination half-life were noted among treatments. The difference in area under the curve (AUC) in subjects treated with flurbiprofen alone and in those treated with flurbiprofen plus cimetidine was significant. Two subjects experienced gastric upset; one case was apparently caused by cimetidine, and the other was likely caused by flurbiprofen. Although a significant increase in AUC was observed in subjects receiving flurbiprofen plus cimetidine, the interaction is probably not clinically important.

Adult↗
PubMed1986

Effect of ibuprofen on lithium plasma and red blood cell concentrations.

The effect of ibuprofen on steady-state lithium plasma and red blood cell concentrations was studied in 11 normal volunteers. During the seven-day control phase, sustained-release lithium carbonate 450 mg was administered every 12 hours. Lithium plasma and red blood cell concentrations were determined on days 5, 6, and 7. During the treatment phase (days 7-15), ibuprofen 400 mg was administered four times a day concurrently with lithium. Lithium plasma and red blood cell concentrations were obtained on days 14, 15, and 16. Multiple blood samples were obtained over a 12-hour period on days 6 and 15. Urine samples were collected from six subjects. The mean minimum lithium concentration increased 15% when ibuprofen was added. Mean maximum lithium concentration, area under the curve, red blood cell concentrations, and the lithium red blood cell to plasma ratio were significantly higher during the treatment phase. Mean lithium total body and renal clearance values were significantly lower during the treatment with ibuprofen. The administration of ibuprofen can increase steady-state plasma lithium concentrations and decrease lithium clearance.

Adult↗