Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potassium salt of a chemically stabilized dipeptide, {1-[4-(1 H-tetrazol-5-yl)butyl]indol-3-yl}carbonyl-Hyp-Nal-N(methyl)-Bzl , (Hyp = (R)-4-hydroxy-L-proline; Nal = 3-L-(beta-naphthyl)-alanine), S18523, is described as a new water-soluble, potent and selective NK1 receptor antagonist. The low molecular weight antagonist (M(r) = 736) displays nanomolar potency (pA2 = 9.6) in the rabbit vena cava (NK1) bioassay and nanomolar affinity (pKi = 9.1) on the human NK1 receptor expressed by lymphoblastoma cells. It is devoid of mu-opiate affinity (Ki > 10(-4) M with respect to tritiated Tyr-DAla-Gly-MePhe-Gly-ol), has negligible calcium-channel affinity (estimated Ki = 2.6 x 10(-5) M, with respect to isradipine) and does not cause peritoneal mast-cell degranulation. S18523 has strong antinociceptive effects in three classical pain tests in vivo both by i.v. and p.o. routes. The dipeptide potently antagonizes bronchoconstriction provoked by exogenous substance P in the guinea-pig and acts longer than the non-peptide antagonist CP99994, when administered as aerosol. Finally, S18523 displays antiinflammatory properties, since it dose-dependently inhibits substance P-induced plasma extravasation both in the bladder (ID50 = 0.18 mg/kg i.v.) and bronchi (ID50 = 0.14 mg/kg i.v.) of the guinea-pig.
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PMID:A water-soluble, stable dipeptide NK1 receptor-selective neurokinin receptor antagonist with potent in vivo pharmacological effects: S18523. 888 65

Dexketoprofen trometamol is a water-soluble salt of the dextrorotatory enantiomer of the nonsteroidal anti-inflammatory drug (NSAID) ketoprofen. Racemic ketoprofen is used as an analgesic and an anti-inflammatory agent, and is one of the most potent in vitro inhibitors of prostaglandin synthesis. This effect is due to the S(+)-enantiomer (dexketoprofen), while the R(-)-enantiomer is devoid of such activity. The pharmacokinetic profile of ketoprofen and its enantiomers was assessed in several animals species and in human volunteers. In humans, the relative bioavailability of oral dexketoprofen trometamol (12.5 and 25 mg, respectively) is similar to that of oral racemic ketoprofen (25 and 50 mg, respectively), as measured in all cases by the area under the concentration-time curve values for S(+)-ketoprofen. Dexketoprofen trometamol, given as a tablet, is rapidly absorbed, with a time to maximum plasma concentration (tmax) of between 0.25 and 0.75 hours, whereas the tmax for the S-enantiomer after the racemic drug, administered as tablets or capsules prepared with the free acid, is between 0.5 and 3 hours. Peak plasma concentrations of 1.4 and 3.1 mg/L are reached after administration of dexketoprofen trometamol 12.5 and 25 mg, respectively. From 70 to 80% of the administered dose is recovered in the urine during the first 12 hours, mainly as the acyl-glucuronoconjugated parent drug. No R(-)-ketoprofen is found in the urine after administration of dexketoprofen [S(+)-ketoprofen], confirming the absence of bioinversion of the S(+)-enantiomer in humans. in animal studies, the anti-inflammatory potency of dexketoprofen was always equivalent to that demonstrated by twice the dose of ketoprofen. Similarly, animal studies showed a high analgesic potency for dexketoprofen trometamol. The R(-)-enantiomer demonstrated a much lower potency, its analgesic action being apparent only in conditions where the metabolic bioinversion to the S(+)-enantiomer was significant. The gastric ulcerogenic effect of dexketoprofen at various oral doses (1.5 to 6 mg/kg) in the rat do not differ from those of the corresponding double doses (3 to 12 mg/kg) of racemic ketoprofen. Repeated (5-day) oral administration of dexketoprofen as the trometamol salt causes less gastric ulceration than was observed after the acid form of both dexketoprofen and the racemate. In addition, single dose dexketoprofen as the free acid at 10 to 20 mg/kg does not show a significant intestinal ulcerogenic effect in rats, while racemic ketoprofen 20 or 40 mg/kg is clearly ulcerogenic to the small intestine. The analgesic efficacy of oral dexketoprofen trometamol 10 to 20 mg is superior to that of placebo and similar to that of ibuprofen 400 mg in patients with moderate to serve pain after third molar extraction. The time to onset of pain relief appeared to be shorter in patients treated with dexketoprofen trometamol than in those treated with ibuprofen 400 mg. Dexketoprofen trometamol was well tolerated, with a reported incidence of adverse events similar to that of placebo.
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PMID:Preclinical and clinical development of dexketoprofen. 892 55

The therapeutic effect of most immunosuppressive agents is unspecific and therefore often limited by an increased risk of infection by viral, bacterial or fungal organisms as well as by an increased incidence of malignant neoplasms. This short review includes the most commonly used immunosuppressants such as corticosteroids, azathioprine, methotrexate, cyclophosphamide and cyclosporine. The most common risks of long-term corticosteroid treatment are Cushing-like changes, decreased glucose tolerance and the usually benign steroid diabetes. Also clinically important is osteoporosis, since it can be prevented by physical training, calcium supplementation and treatment with vitamin D if necessary. Although there is still no proof of a significantly increased risk of peptic ulcer during steroid therapy, patients may develop gastrointestinal hemorrhage and even perforation without producing pain while being treated with corticosteroids. Mineralocorticoid effects, such as salt and water retention, are seen only with hydrocortisone and prednisone, whereas with synthetic steroids such as dexamethasone, sodium retention is absent despite their strong antiphlogistic activity. The most important side effect of the cytotoxic agents azathioprine, methotrexate and cyclophosphamide is marrow suppression. Due to the high turnover of neutrophils, patients most frequently suffer neutropenia rather than thrombocytopenia or anemia. Neutropenia, as well as impaired humoral and cellular immune mechanisms, are responsible for increased susceptibility to bacterial, viral or parasitic diseases during immunosuppressive therapy. Hepatotoxicity has been reported among patients receiving azathioprine (cholestatic hepatitis) and methotrexate (elevated AST levels and, rarely, liver fibrosis or cirrhosis). Cyclophosphamide causes hemorrhagic cystitis in a substantial proportion of patients, as well as an increased incidence of urothelial neoplasms. Both these side effects may be prevented by Mesna. The most important side effects of cyclosporine are acute and chronic nephrotoxicity usually associated with significantly elevated plasma levels of the drug. It must be borne in mind that severe nephrotoxicity may occur in patients receiving cyclosporine and ketoconazole together, since the latter may inappropriately increase the plasma cyclosporine level.
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PMID:[Immunosuppression--a tightrope walk between iatrogenic harm and therapy]. 892 65

The ocular effects of topical prostaglandin F2 alpha (PGF2 alpha) were studied in normotensive human eyes. PGF2 alpha as tromethamine salt, 100 micrograms, was applied to one eye of 23 normotensive subjects, intraocular pressure (IOP) and pupil size were measured, objective and subjective findings recorded during the first 24 h. Tonography was performed in 10 subjects. As compared with the baseline, PGF2 alpha caused a significant IOP reduction between 1 and 24 h (p < 0.001), being maximal (4.9 +/- 0.5 mm Hg, mean +/- SEM, p < 0.001) between 4 and 8 h. As compared with the contralateral control eyes, which received 50 microliters of saline, treated eyes exhibited significant IOP reduction between 1 and 24 h (p < 0.001), being maximal (4.2 +/- 0.4 mm Hg, mean +/- SEM, p < 0.001) at 4 h. PGF2 alpha caused marked conjunctival hyperemia in all eyes. Pupillary diameter was not altered. Aqueous flare and cellular response were not seen. Half of the subjects complained of ocular smarting, mild ocular pain or headache. Total outflow facility did not change (p > 0.05).
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PMID:Effects of topically applied prostaglandin F2 alpha on normotensive human eyes. 903 93

Prostaglandin F2 alpha (PGF2 alpha) as its tromethamine salt was topically applied, and hypotensive and other ocular effects were studied, in glaucomatous human eyes. After baseline intraocular pressure (IOP) measurements, 100 micrograms PGF2 alpha tromethamine salt dissolved in 50 milligrams saline was applied to 23 glaucomatous eyes of 20 patients. The pretreatment diurnal IOP values of the same eye served as control group. It was found that in comparison with baseline values, PGF2 alpha caused significant but transient elevation in IOP in the first half-hour (mean 1.95 mm Hg, p < 0.01), but it decreased below baseline values at the first hour. A significant decrease in IOP from baseline was observed at the 2nd hour (p < 0.05), which became more prominent between the 4th and 24th hours (p < 0.001). PGF2 alpha produced a maximal IOP reduction of 10.21 mm Hg at the 12th hour (p < 0.001). The IOP differences between PGF2 alpha-treated and control groups were significant between the 4th and 24th hours (p < 0.001), with the maximal IOP difference of 9.21 mm Hg at the 12th hour (p < 0.001). PGF2 alpha caused marked conjunctival hyperaemia in all eyes. Aqueous flare and cellular response were not seen in any of the eyes. Half of the patients experienced ocular smarting or a foreign-body sensation, periocular pain and headache. PGF2 alpha reduced IOP effectively in glaucomatous human eyes.
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PMID:Effects of topically applied prostaglandin F2 alpha tromethamine salt on glaucomatous human eyes. 906 56

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of gemcitabine are reviewed. Gemcitabine is a deoxycytidine-analogue antimetabolite with activity against some solid tumors. Gemcitabine is phosphorylated intracellularly to difluorodeoxycytidine triphosphate, which terminates DNA-chain elongation and competitively inhibits DNA polymerase and ribonucleotide reductase. After i.v. administration, gemcitabine is rapidly distributed into total body water. The drug is deaminated in the plasma to inactive difluorodeoxyuridine; both gemcitabine and difluorodeoxyuridine are primarily renally eliminated. In clinical studies, gemcitabine reduced pain and improved function in patients with advanced pancreatic cancer. Gemcitabine has shown some activity against non-small-cell lung cancer, particularly when combined with cisplatin or ifosfamide. The agent has also shown modest activity against advanced ovarian and breast cancer. Adverse effects include dose-limiting myelosuppression, flu-like symptoms, nausea, vomiting, and rash. Gemcitabine has FDA-approved labeling for use in the treatment of locally advanced and metastatic pancreatic cancer. The recommended dosage for this indication is 1000 mg/m2 (as the hydrochloride salt) i.v. given over 30 minutes weekly for seven weeks, followed after one week of rest by 1000 mg/ m2 i.v. given over 30 minutes weekly for three weeks every four weeks. Gemcitabine palliates symptoms in patients with advanced or metastatic pancreatic cancer. More study is needed to determine gemcitabine's role in the treatment of non-small-cell lung cancer, ovarian cancer, and breast cancer.
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PMID:Gemcitabine: a cytidine analogue active against solid tumors. 911 4

Zinc is concentrated in the dorsal horn of the spinal cord and has been proposed to alter excitability of primary afferent C-fibers, structures believed to be important in nociceptive transmission. Based on the inhibitory effect of zinc on the activity of various other neurotransmitters that play a role in nociception, we tested the hypothesis that zinc modulates pain transmission. To test this, we examined the effect of exogenous zinc, administered intrathecally (i.t.), on nociception in the mouse. We also assessed the impact of decreased concentrations of endogenously occurring zinc in the extracellular fluid brought about by an i.t. injection of either ethylenediaminetetraacetic acid disodium-calcium salt (Ca++EDTA), a calcium-saturated, membrane-impermeable chelator of divalent cations, or of dipicolinic acid, a zinc chelator. Injection of zinc produced a dose-related antinociceptive effect, optimal at 90 min in the writhing assay, but had no effect on tail-flick response latencies. In contrast, injection of either Ca++EDTA or dipicolinic acid produced a dose-related hyperalgesia in the tail-flick assay at 90 min after injection. Responses induced in the writhing assay were unaffected by Ca++EDTA. Although zinc had no effect on thermal nociception, the hyperalgesic effect of Ca++EDTA was antagonized by coadministration of Ca++EDTA with zinc. Similarly, the antinociceptive effect of zinc on writhing responses was attenuated when coadministered with Ca++EDTA. Zinc also inhibited primary afferent C-fiber activity because 10 ng of zinc i.t. inhibited the behavioral response induced by injection i.t. of 1 nmol of capsaicin. Neither zinc nor Ca++EDTA altered writhing or tail-flick latencies, respectively, when injected intracerebroventricularly. These findings support the hypothesis that endogenous zinc, localized in the dorsal horn of the spinal cord, plays a role in the regulation of pain.
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PMID:Manipulations of zinc in the spinal cord, by intrathecal injection of zinc chloride, disodium-calcium-EDTA, or dipicolinic acid, alter nociceptive activity in mice. 931 41

The use of freezing temperatures for the therapeutic destruction of tissue began in England in 1845-51 when James Arnott described the use of iced salt solutions (about-20 degrees C) to freeze advanced cancers in accessible sites, producing reduction in tumor size and amelioration of pain. Improved freezing techniques were possible early in the 1990s when solidified carbon dioxide came into use and later when liquid nitrogen and nitrous oxide became available. Nevertheless, cryotherapy was a minor technique, used only for the accessible lesions of skin and mucosa. With the development of modern cryosurgical apparatus by Cooper in 1961, a resurgence of interest in cryosurgery was initiated and techniques for diverse clinical conditions, including visceral cancer, evolved, After the initial widespread clinical trials matured in the 1970s, some applications of the technique fell into disuse while others became standard treatment. Late in the 1980s, further improvements in apparatus and imaging techniques have permitted increased clinical use in neoplastic disease, including visceral cancer.
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PMID:History of cryosurgery. 949 80

Acanthamoeba species are an important cause of microbial keratitis that may cause severe ocular inflammation and visual loss. The first cases were recognized in 1973, but the disease remained very rare until the 1980s, when an increase in incidence mainly associated with contact lens wear was reported. There is an increased risk when contact lens rinsing and soaking solutions are prepared with nonsterile water and salt tablets. The clinical picture is often characterized by severe pain with an early superficial keratitis that is often treated as herpes simplex infection. Subsequently a characteristic radial perineural infiltration may be seen, and ring infiltration is common. Limbitis and scleritis are frequent. Laboratory diagnosis is primarily by culture of epithelial samples inoculated onto agar plates spread with bacteria. Direct microscopy of samples using stains for the cyst wall or immunostaining may also be employed. A variety of topically applied therapeutic agents are thought to be effective, including propamidine isethionate, clotrimazole, polyhexamethylene biguanide, and chlorhexidine. Various combinations of these and other agents have been employed, often resulting in medical cure, especially if treatment is commenced early in the course of the disease. Penetrating keratoplasty is preferably avoided in inflamed eyes, but may be necessary in severe cases to preserve the globe or, when the infection has resolved, to restore corneal clarity for optical reasons.
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PMID:Acanthamoeba keratitis. 963

The primary care physician has a responsibility not only to recognize and treat acute stone passage but to ensure that the patient with recurrent stones has metabolic evaluation and appropriate preventive care. Renal colic is typically severe, radiates to the groin, is associated with hematuria, and may cause ileus. About 90% of stones that cause renal colic pass spontaneously. The patient with acute renal colic should be treated with fluids and analgesics and should strain the urine to recover stone for analysis. Highgrade obstruction or failure of oral analgesics to relieve pain may require hospitalization; a urinary tract infection in the setting of an obstruction is a urologic emergency requiring immediate drainage, usually with a ureteral stent. Several approaches are available when stones do not pass spontaneously, including extracorporeal shock wave lithotripsy, percutaneous lithotripsy, and ureteroscopic laser lithotripsy. Calcium stone disease has a lifetime prevalence of 10% in men and causes significant morbidity. Renal failure is unusual. Stone types include calcium oxalate, uric acid, struvite, and cystine. Stone analysis is particularly important when a noncalcareous constituent is identified. The majority of patients with nephrolithiasis will have recurrence, so prevention is a high priority. High fluid intake is a mainstay of prevention. Metabolic evaluation will indicate other appropriate preventive measures, which may include dietary salt and protein restriction, and use of thiazide diuretics, neutral phosphate, potassium citrate, allopurinol, and magnesium salts. Dietary calcium restriction may worsen oxaluria and negative calcium balance (osteoporosis).
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PMID:Nephrolithiasis: acute management and prevention. 965 69


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