Brown recluse spider bites: a complex problem wound. A brief review and case study.
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Brown recluse spiders (Loxosceles reclusa) are responsible for virtually all documented cases of spider bites leading to significant necrosis. The actual spider bite often goes unnoticed for as long as 4 to 6 hours, which makes diagnosis and, therefore, appropriate treatment, difficult. The spider bite generally results in either a necrotic wound or systemic symptoms that can lead to hemolysis. The patient described in this article experienced both complications. Dapsone and hyperbaric oxygen therapy brought the adverse response to the bite under control. The patient was hospitalized for 7 days during treatment for hemolysis and an extensive, necrotic wound. Efforts are underway to develop an assay to provide a definitive diagnosis for the brown recluse spider bite, but none is yet commercially available. Antivenom is scarce; capture of the offending spider appears to be most helpful in the diagnosis and proper treatment of spider bites. (+info)
Structural basis for inhibition of histamine N-methyltransferase by diverse drugs.
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In mammals, histamine action is terminated through metabolic inactivation by histamine N-methyltransferase (HNMT) and diamine oxidase. In addition to three well-studied pharmacological functions, smooth muscle contraction, increased vascular permeability, and stimulation of gastric acid secretion, histamine plays important roles in neurotransmission, immunomodulation, and regulation of cell proliferation. The histamine receptor H1 antagonist diphenhydramine, the antimalarial drug amodiaquine, the antifolate drug metoprine, and the anticholinesterase drug tacrine (an early drug for Alzheimer's disease) are surprisingly all potent HNMT inhibitors, having inhibition constants in the range of 10-100nM. We have determined the structural mode of interaction of these four inhibitors with HNMT. Despite their structural diversity, they all occupy the histamine-binding site, thus blocking access to the enzyme's active site. Near the N terminus of HNMT, several aromatic residues (Phe9, Tyr15, and Phe19) adopt different rotamer conformations or become disordered in the enzyme-inhibitor complexes, accommodating the diverse, rigid hydrophobic groups of the inhibitors. The maximized shape complementarity between the protein aromatic side-chains and aromatic ring(s) of the inhibitors are responsible for the tight binding of these varied inhibitors. (+info)
Intravenous administration of diphenhydramine reduces histamine-induced vasodilator effects in the retina and choroid.
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PURPOSE: Intravenous administration of histamine causes an increase in choroidal blood flow (ChBF) and retinal vessel diameters in healthy subjects. The receptor mediating this response has not yet been identified. The present study was undertaken to clarify whether H1 receptor blockade with diphenhydramine affects the hemodynamic response of histamine in the choroid and the retina. METHODS: A randomized, double-masked, placebo-controlled, two-way crossover study was performed in 18 healthy, male, nonsmoking subjects. Histamine (0.32 microg/kg per minute over 30 minutes) was infused intravenously in the absence (NaCl as placebo) or presence of the H1 blocker diphenhydramine (1.0 mg/min over 50 minutes). Ocular hemodynamic parameters, blood pressure, and intraocular pressure were measured before drug administration, after infusion of diphenhydramine or placebo, and after co-infusion of histamine. Subfoveal ChBF and fundus pulsation amplitude (FPA) were measured with laser Doppler flowmetry and laser interferometry, respectively. Retinal arterial and venous diameters were measured with a retinal vessel analyzer. Retinal blood velocity was assessed with bidirectional laser Doppler velocimetry. RESULTS: Administration of histamine caused a decrease in mean arterial pressure by -4% +/- 9% (ANOVA P = 0.01). This effect was blunted by coadministration of diphenhydramine (ANOVA, P = 0.04). Histamine significantly increased FPA and subfoveal ChBF. Coadministration of diphenhydramine significantly reduced this effect (ANOVA; FPA P = 0.001, ChBF P = 0.049). Histamine significantly increased retinal arterial diameter by +3.5% +/- 4.5% and retinal venous diameter by +3.7% +/- 2.8%. Again, coadministration of diphenhydramine significantly reduced the vasodilative effect to +0.3% +/- 5.5% in retinal arteries (ANOVA, P = 0.00006) and to +0.9% +/- 2.5% in retinal veins (ANOVA, P = 0.004). CONCLUSIONS: The present data confirm that histamine increases ChBF and retinal vessel diameters in healthy subjects. Administration of the H1 receptor blocker diphenhydramine significantly reduced histamine-induced changes in ocular perfusion parameters. These results strongly indicate that in the retina and choroid, H1 receptors are involved in the histamine-mediated hemodynamic effects in vivo. (+info)
A pharmacokinetic study of diphenhydramine transport across the blood-brain barrier in adult sheep: potential involvement of a carrier-mediated mechanism.
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The purpose of this study was to examine the disposition of diphenhydramine (DPHM) across the ovine blood-brain barrier (BBB). In six adult sheep, we characterized the central nervous system (CNS) pharmacokinetics of DPHM in brain extracellular fluid (ECF) and cerebrospinal fluid (CSF) using microdialysis in two experiments. In the first experiment, DPHM was administered via a five-step i.v. infusion (1.5, 5.5, 9.5, 13.5, and 17.5 microg/kg/min; 7 h per step). Average steady-state CNS/total plasma concentration ratios (i.e., [CNS]/[total plasma]) for steps 1 to 5 ranged from 0.4 to 0.5. However, average steady-state [CNS]/[free plasma] ratios ranged from 2 to 3, suggesting active transport of DPHM into the CNS. Plasma protein binding averaged 86.1 +/- 2.3% (mean +/- S.D.) and was not altered with increasing drug dose. Plasma, CSF, and ECF demonstrated biexponential pharmacokinetics with terminal elimination half-lives (t1/2beta) of 10.8 +/- 5.4, 3.6 +/- 1.0, and 5.3 +/- 4.2 h, respectively. The bulk flow of CSF and transport-mediated efflux of DPHM may explain the observed higher CNS clearances. In the second experiment, DPHM was coadministered with propranolol (PRN) to examine its effect on blood-brain CSF and blood-brain ECF DPHM relationships. Plasma total DPHM concentration decreased by 12.8 +/- 6.3% during PRN, whereas ECF and CSF concentrations increased (88.1 +/- 45.4 and 91.6 +/- 34.3%, respectively). This increase may be due to the inhibitory effect of PRN on a transporter-mediated efflux mechanism for DPHM brain elimination. (+info)
Effects of diphenhydramine and famotidine on lipid peroxidation and activities of antioxidant enzymes in different rat tissues.
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The potential antioxidant activity of diphenhydramine (histamine H1-receptor antagonist) and famotidine (histamine H2 receptor antagonist) was studied. Diphenhydramine inhibited the spontaneous, Fe(II)-induced and Fe(II)/ascorbate-induced lipid peroxidation, while famotidine showed a biphasic concentration-dependent effect on spontaneous lipid peroxidation (a stimulation by 1 mM and an inhibition by 5 mM) and increased Fe(II)-induced- and inhibited Fe(II)/ascorbate-induced lipid peroxidation in the rat liver and brain. Both drugs decreased *OH-provoked deoxyribose degradation in Fenton-type systems and inhibited O2- -provoked reduction of nitro-blue tetrazolium and ferrycytochrome C, but famotidine effect was stronger than that of diphenhydramine. The significant famotidine-induced inhibition of nitro-blue tetrazolium reduction might be underlain by the stimulation of superoxide dismutase activity. Famotidine and diphenhydramine did not alter the catalase activity in all tissue preparations, except for its concentration of 5 mM (a complete inhibition). The present results suggest a beneficial effect of histamine H1 and H2-blockers, especially famotidine, as antioxidants and/or metal chelators, which might be an additional explanation of their therapeutic action. (+info)
Acupuncture plus point-injection for 32 cases of obstinate urticaria.
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In order to observe the therapeutic effects of acupuncture plus point-injection for obstinate urticaria, 64 cases of obstinate urticaria were randomly divided into the following two groups. 32 cases in the treatment group were treated with acupuncture at the points of Quchi (LI11), Xuehai (SP10), Zusanli (ST 36), Sanyinjiao (SP6) and Fengchi (GB20) plus point-injection at the points of Zusanli (ST36) and Quchi (LI11). 32 cases in the control group were treated with antihistamines (such as Acrivastine, Cinnarizine or Ranitidine). The results showed that the therapeutic effect in the treatment group was obviously better than that in the control group (P < 0.05), with a much lower relapse rate in the former than that in the latter (P < 0.01). (+info)
Relationship between sedation and pupillary function: comparison of diazepam and diphenhydramine.
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AIMS: To examine the relationship between sedation and pupillary function by comparing the effects of diazepam and diphenhydramine on arousal and pupillary activity. METHODS: Fifteen male volunteers participated in three weekly sessions in which they received (i) diazepam 10 mg, (ii) diphenhydramine 75 mg and (iii) placebo, according to a balanced, double-blind protocol. Pupil diameter was measured with infrared pupillometry under four luminance levels. Alertness was assessed by visual analogue scales (VAS) and by critical flicker fusion frequency (CFFF). Blood pressure, heart rate and skin conductance were recorded by conventional methods. Data were analysed with analysis of variance (anova) with multiple comparisons. RESULTS: There were significant effects of ambient luminance (F3,42 = 305.7, P < 0.001) and treatment condition (F2,28 = 9.0, P < 0.01) on pupil diameter; diphenhydramine caused miosis at all luminance levels (P < 0.05). The light reflex response was not affected. Both active drugs reduced the pre-post treatment changes compared with placebo [mean difference from placebo (95% confidence interval)]: in CFFF (Hz), diazepam -0.73 (-1.63, 0.17), diphenhydramine -1.46 (-2.40, -0.52); and VAS alertness (mm), diazepam -11.49 (-19.19, -3.79), diphenhydramine -19.83 (-27.46, -12.20). There were significant effects of both session (F2,26 = 145.1, P < 0.001) and treatment (F2,26 = 5.5, P < 0.01) on skin conductance; skin conductance was reduced by both drugs (P < 0.05). CONCLUSIONS: The miosis by diphenhydramine and the reduction in skin conductance by both drugs may indicate central sympatholytic effects. A lack of a sympatholytic effect of diazepam on the pupil may be due to the masking of the miosis by mydriasis resulting from the inhibition of the parasympathetic output to the iris. (+info)
Effects of anti-vertigo drugs on medial vestibular nucleus neurons activated by horizontal rotation.
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The effects of anti-vertigo drugs on medial vestibular nucleus (MVN) neurons were examined to assess the site and mode of action using cats anesthetized with alpha-chloralose. Single neuron activity in the MVN was extracellularly recorded using a silver wire microelectrode attached along a seven-barreled micropipette, each of which was filled with diphenhydramine, diphenidol, betahistine, glutamate or NaCl. Type I of the MVN neurons were identified according to the responses obtained when the animal placed on a turn-table was rotated sinusoidally. The effects of the drugs were examined on type I neurons which received impulses primarily from the labyrinth and sent them to the oculomotor nuclei. The microiontophoretic application of diphenhydramine, diphenidol and betahistine inhibited rotation-induced firing of type I MVN neurons. Diphenhydramine and diphenidol were more potent than betahistine. These results suggest that these drugs directly act on MVN neurons to reduce the responsiveness to rotatory stimulation. (+info)