Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant human GH (hGH) combined with a permeation enhancer for the nasal mucosa, sodium tauro-24,25-dihydrofusidate (STDHF), was administered intranasally (in) in six patients with classical GH deficiency. Three different doses were tested (0.2, 0.4, and 0.8 IU/kg BW). The concentration of STDHF was 1% in all doses. As a comparison, all patients received a sc injection of hGH (0.1 IU/kg BW). Blood samples were obtained at frequent intervals for up to 8 h (in doses) or 24 h (sc dose) and analyzed for the plasma concentration of hGH. All three i.n. doses gave a rapid increase in hGH with peak maxima (Cmax) at 20-30 min, and a decline to baseline within 2-3 h. In contrast, the sc dose resulted in a Cmax 2-3 h after the injection, followed by a plateau phase for 2-3 h. The baseline was reached 12-14 h after administration. The uptake [area under the curve (AUC)] was considerably lower for all three in doses, i.e. 1.6-3% of the AUC obtained with the sc dose. However, the Cmax varied between 5.7 +/- 1.4% (0.8 IU/kg BW) and 15.8 +/- 2.1% (0.4 IU/kg BW) of the maximal peak with the sc dose. Of the in doses, 0.4 IU/kg BW resulted in the highest AUC and Cmax. A self-rating protocol was also used to estimate nasal sensations for up to 2 h after dosing. All sensations (itching, burning, sneezing, and running of the nose) were transient and tolerable. This study demonstrates that hGH can be administered intranasally in combination with STDHF. The in dosing results in a plasma peak of hGH very similar to the physiological endogenous peak. No side-effects were noted, other than a transient nasal irritation. Therefore, the nasal route for hGH administration offers a more physiological and more convenient alternative to injections for the treatment of GH deficiency.
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PMID:Intranasal administration of human growth hormone (hGH) in combination with a membrane permeation enhancer in patients with GH deficiency: a pharmacokinetic study. 847 11

The term ocular allergy encompasses a group of diseases in which there is a high frequency of atopy, ocular itching, stringy discharge and a papillary conjunctival reaction. Conditions confined to the lids and conjunctiva (e.g. seasonal allergic conjunctivitis) have a good prognosis but those involving the cornea may result in visual impairment (e.g. atopic keratoconjunctivitis). Mast cell and eosinophil mechanisms are important in al the ocular allergies, but T cell inflammation is prominent only in vernal keratoconjunctivitis, atopic keratoconjunctivitis and giant papillary conjunctivitis. Therapy involves the use of antigen avoidance (where possible), nonspecific medical therapy (e.g. cold compresses, artificial tears), specific medical therapy and, in certain situations, immunotherapy and surgery. Topical antihistamines (often in combination with a vasoconstrictor) and oral antihistamines are widely used in perennial and seasonal conjunctivitis. Levocabastine is a new preparation which is more rapid and potent. Mast cell inhibitors [e.g. sodium cromoglycate (cromolyn sodium)] have a proven track record as safe and effective therapy for all ocular allergic diseases and the newer, more potent nedocromil and lodoxamide are now available. Topical steroids are only indicated in sight-threatening disease due to their serious adverse effects and other therapy should be continued to minimise the dose required. There is a lack of intermediate potency and high potency but safe topical preparations. A number of future possibilities exist, some of which have been partially explored. Cyclo-oxygenase inhibitors have proved of limited use, but inhibitors of lipoxygenase and kinin pathways are awaited. Although results with HEPP have been disappointing, other modulators of mast cell function (e.g. picumast, beta-agonists and phosphodiesterase inhibitors) may prove useful in the future. So far, results with topical cyclosporin in serious disease are very encouraging. Future developments in the manipulation of eosinophilic products, cytokines and adhesion molecules may also be relevant. However, the current situation for those with serious ocular allergy remains a disturbing dependence upon topical steroids, with all the attendant risks.
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PMID:Therapeutic options in ocular allergic disease. 852 55

A randomized clinical trial was conducted to compare diclofenac sodium 0.1% ophthalmic solution to placebo in relieving ocular signs and symptoms in patients with acute seasonal allergic conjunctivitis. Twenty patients (10 per treatment) qualified for this two week, double-masked study with moderate itching, bulbar conjunctival injection and a positive skin test. Diclofenac was statistically and clinically superior in the physician's global evaluation (p = 0.03) and the primary composite score [itching + bulbar/palpebral conjunctival injection (p = 0.037)] after two weeks of treatment. Four patients experienced some transient ocular burning/stinging with diclofenac. Diclofenac sodium appears to be effective for relieving the ocular signs and symptoms associated with acute seasonal allergic conjunctivitis.
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PMID:Safety and efficacy of diclofenac sodium 0.1% ophthalmic solution in acute seasonal allergic conjunctivitis. 859 Feb 68

Fosphenytoin sodium, a phosphate ester prodrug of phenytoin, was developed as a replacement for parenteral phenytoin sodium. Unlike phenytoin, fosphenytoin is freely soluble in aqueous solutions, including standard i.v. solutions, and is rapidly absorbed by the i.m. route. Fosphenytoin is metabolized (conversion half-life of 8 to 15 min) to phenytoin by endogenous phosphatases. Therapeutic free (unbound) and total plasma phenytoin concentrations are consistently attained after i.m. or i.v. administration of fosphenytoin loading doses. Fosphenytoin has fewer local adverse effects (e.g., pain, burning, and itching at the injection site) after i.m. or i.v. administration than parenteral phenytoin. Systemic effects related to the CNS are similar for both preparations, but transient paresthesias are more common with fosphenytoin.
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PMID:Pharmacology and pharmacokinetics of fosphenytoin. 864 12

The pathogenesis of allergic rhinitis is complex, involving not only histamine and mast cell-derived tryptase, but also eosinophil- and neutrophil-derived mediators, cytokines, and intercellular cell adhesion molecules (ICAM-1). It is surprising that antihistamines, which block only one component of the process, have proved so effective in the management of allergic rhinitis. Research has therefore focused on whether antihistamines have additional pharmacological activities. In vitro studies have shown that high concentrations of second generation antihistamines can block inflammatory mediator release from basophils and mast cells, and reduce ICAM-1 expression in epithelial cell lines. In vivo studies have also shown an effect on the allergen-induced inflammatory reaction; both oral and intranasal antihistamines cause a reduction in nasal symptoms and inflammatory cell influx. Oral terfenadine and cetirizine and intranasal levocabastine and azelastine have also demonstrated a lowering of ICAM-1 expression on epithelial cells. With regard to clinical efficacy, topical levocabastine (0.5 mg/mL eye drop solution and 0.5 mg/mL nasal spray) was shown to be more effective than oral terfenadine (60 mg twice daily) in relieving ocular itch (P = 0.02) and reducing nasal symptoms in allergic rhinoconjunctivitis. In a further study, levocabastine eye drops were as effective and well tolerated as sodium cromoglycate in seasonal allergic rhinitis. Intranasal azelastine (0.28 mg twice daily) showed a trend for superior relief of rhinorrhoea and nasal obstruction compared with oral terfenadine (60 mg twice daily). In addition, intranasal azelastine (0.28 mg twice daily) resulted in significant reductions in sneezing, nasal obstruction, rhinorrhoea and itching in perennial rhinitis, compared with the lower efficacy of beclomethasone dipropionate (0.1 mg twice daily). As well as benefits in efficacy, topical administration is associated with improved safety. Some antihistamines, particularly those metabolized in the liver, are associated with occasional reports of severe side-effects. It is therefore logical to administer antihistamines directly to the target organ.
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PMID:Antihistamines: topical vs oral administration. 873 53

The purpose of this study concerns a novel method for preclinical assessment of rectal irritation caused by suppositories introduced into the rectum. Rectal irritation was assessed by the balloon method in fasting conscious rats. This method is based on measuring rectal contractions due to possible irritation caused by the presence of drugs and adjuvants in the suppository. In control experiments (vehicle only), significant rectal contractions were not observed in a range of pH 1.5-11.0 and osmotic pressure 70-2000 mOsm kg-1 H2O, respectively. On the other hand, strong contractions were observed after rectal administration of an aqueous solution of 50% glycerin, 100 mM sodium caprate or 25 mM sodium cholate. The intensity of contraction after rectal administration of sodium caprate or sodium cholate was dependent on the concentration in the dosing solution. In addition, the effect of sodium caprate and sodium cholate on rat rectal mucosa was investigated by optical light microscopy. Although slight or moderate alteration such as the presence of mucinous substance in lumen and congestion, oedema and haemorrhage of the rectal membrane 20 min after rectal administration, there was no major damage to the rectal mucosa. There was a correlation between the median score for mucinous substance in lumen and mean intensity of rectal contraction. For comparative purposes, defecating sensations, pain, itch, burning sensations, and awareness of the presence of a foreign body after administration of suppositories containing 0, 1, 2 and 4% sodium caprate were examined in eight healthy volunteers. The defecating sensation in the human subjects correlated with the intensity of rectal contraction in rats. The results suggest that rectal contraction in conscious rats could be a useful index for prediction of a defecating sensation in man.
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PMID:A novel method for the preclinical assessment of rectal irritation. 873 60

A 28-year-old woman with a previous atopic history had been complaining of itching and burning erythematous plaques or blister eruptions on her face and neck for the last 2 years. These lesions became red-brown and then disappeared in 1-2 weeks. However, the site of two of them had remained heavily pigmented after resolution. Sometimes, vesicular lesions affected the oral mucosa causing a burning sensation. She had noticed that these eruptions reappeared in the same location and related to menstruation (when she used to take naproxen sodium because of dysmenorrhea). Furthermore, pigmented sites became red-brown, elevated and itchy. These findings suggested a fixed drug eruption (FDE) due to naproxen, a sporadic clinical event previously reported only once. Patch tests were performed on the back (normal skin) with a series of NSAIDs, and with naproxen both on the back and on previous FDE sites. The test were negative on the back, and on previous FDE sites the skin got dark. The value of this result as a diagnostic tool was unclear so we performed an oral challenge test with naproxen which proved the diagnosis definitely.
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PMID:Cutaneous reaction to naproxen. 893 96

Progressive familial intrahepatic cholestasis (PFIC) occurs in many communities and races. A form of PFIC in five children from two consanguineous marriages in an Irish kindred is described. In addition, a review of clinical information from the records of three deceased members of the kindred strongly implies that they also suffered from PFIC. The children had a history of neonatal diarrhoea, sepsis, and intermittent jaundice that ultimately became permanent. They suffered intractable pruritus and growth retardation. Despite evidence of severe cholestasis, serum gamma-glutamyl transferase and cholesterol were normal in these children. Sweat sodium concentration were raised in three children. Liver histology showed severe intrahepatic cholestasis and hepatocellular injury. Urinary bile acid analysis revealed a non-specific pattern consistent with chronic cholestasis. These children suffer from a form of PFIC remarkably similar to that occurring in members of the Byler kindred.
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PMID:Byler-like familial cholestasis in an extended kindred. 937 Sep 14

Fosphenytoin is a phosphate ester prodrug of phenytoin developed as a replacement for standard injectable sodium phenytoin. After absorption, phenytoin is cleaved (conversion half-life 8-15 min) from fosphenytoin. Unlike phenytoin, fosphenytoin is freely soluble in aqueous solutions (including standard intravenous solutions) and rapidly absorbed by the intramuscular route. Fosphenytoin has been tested successfully for three indications in humans: intramuscular maintenance dosing, intramuscular loading dose administration, and intravenous treatment of status epilepticus. Local toxicity (pain, burning, itching) is less by the intramuscular or intravenous route for fosphenytoin than for standard injectable sodium phenytoin. Systemic toxicity is similar with both preparations except that hypotension is less common and paresthesias are more common with fosphenytoin.
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PMID:Fosphenytoin (Cerebyx). 903 68

To investigate the spinal processing of cutaneous pruritic and algesic stimuli, single-unit recordings were made from wide-dynamic-range-type lumbar spinal dorsal horn neurons in pentobarbital-sodium-anesthetized rats. Neuronal responses were recorded to mechanical and noxious thermal stimuli, as well as to microinjection (1 microl) of histamine (0.01-10% = 9 x 10(-1)-9 x 10(-4) M), capsaicin (0.1% = 3.3 x 10(-3) M), or other algesic chemicals into skin within the receptive field via intracutaneously placed needles. Most (84%) of the 89 neurons responded to intracutaneous (i.c.) microinjection of histamine with a brief phasic discharge followed by an afterdischarge of variable (s to min) duration. Ten minutes after i.c. microinjection of histamine (but not NaCl), there was a significant increase in the mean area of the low-threshold (but not high-threshold) portion of unit mechanical receptive fields. However, responses to graded pressure stimuli were not significantly affected after histamine. Responses did not exhibit significant tachyphylaxis when histamine microinjections were repeated at 5- or 10-min intervals. Unit responses significantly increased in a dose-related manner to microinjection of histamine at concentrations ranging across 4 orders of magnitude. Within 30 s after i.c. microinjection of the H1 antagonist cetirizine, unit responses to i.c. histamine delivered at the same skin site were significantly attenuated. Unit responses to histamine, as well as to noxious thermal stimulation, were significantly reduced after systemic administration of morphine (3.5 mg/kg i.p.) in a naloxone-reversible manner. Application of a mechanical rub, scratch, or a noxious heat stimulus during the unit's ongoing response to i.c. histamine produced a brief and marked excitation, often followed by a period of reduced ongoing discharge. Unit responses to histamine were markedly suppressed by electrical stimulation in the midbrain periaqueductal gray. Most (79%) histamine-responsive units tested also responded to i.c. microinjection of capsaicin. After the initial microinjection of capsaicin, subsequent responses to histamine and capsaicin microinjections were significantly reduced. Units also responded to i.c. ethanol (capsaicin vehicle) in a dose-related manner, and showed tachyphylaxis to repeated i.c. ethanol at 80% but not at 8%. The mean response to 80% ethanol was significantly smaller than to 0.1% capsaicin. All units tested also responded to topical application of mustard oil (50%) and i.c. serotonin (30 microg). The results are discussed in terms of theories that attempt to reconcile psychophysical and clinical observations of pain and itch sensation.
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PMID:Responses of rat spinal dorsal horn neurons to intracutaneous microinjection of histamine, capsaicin, and other irritants. 916 72


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