- Comparison of pregabalin with doxepin in the management of uremic pruritus: a randomized single blind clinical trial. [JOURNAL ARTICLE]
- Hemodial Int 2016 Jul 11.
Introduction Pruritus is one of the frustrating skin manifestations of advanced renal failure. Many options have been used for the management of uremic pruritus (UP) such as pregabalin. There are some studies that reported beneficial effects of pregabalin in reducing UP; however, most of them did not have a comparator arm. Therefore, we designed this study to compare antipruritic effects of pregabalin with doxepin in the management of pruritus in hemodialysis patients. Methods Seventy-two patients suffering from UP were randomly assigned to receive pregabalin (50 mg every other day) or doxepin (10 mg per day) for 4 weeks. Severity of pruritus and its effect on quality of life were assessed by visual analog scale (VAS), 5-D itch scale and dermatology life quality index (DLQI) at baseline and after 1 week, 2 weeks and 4 weeks of the treatment. Findings Mean scores of the VAS decreased from 7.5± 1.4 and 7.1 ± 1.3 at baseline to 2.1 ± 2.6 and 4.2 ± 2.6 at the end of the study (P < 0.001) in the pregabalin and doxepin groups, respectively. Similarly, pregabalin significantly reduced mean scores of the 5-D itch scale and the DLQI compared to doxepin. The most reported side effect in each group was somnolence which occurred in similar rates in the both groups. Discussion Pregabalin was more effective than doxepin in reducing the severity of uremic pruritus and improving the quality of life of patients in this study, so we suggest that clinician can consider pregabalin prior to using antihistamine drugs in the management of severe itch in hemodialysis patients.
- [Pruritus in psoriasis : Profile and therapy]. [JOURNAL ARTICLE, ENGLISH ABSTRACT]
- Hautarzt 2016 Jul 4.
Psoriasis is a common chronic inflammatory disease with an incidence of about 0.5-3 %. Previously psoriasis was not primarily regarded to be associated with pruritus; however, this perception has changed in recent years. Meanwhile data conclusively show that between 64 and 97 % of patients report about pruritus that can be severe in a number of cases. Apart from suffering from psoriasis, the presence of pruritus causes additional stress and leads to a significant impairment of health-related quality of life. Neurogenic inflammation at least in part contributes to the development of pruritus in psoriasis skin lesions. A number of neuropeptides including substance P and calcitonin gene related peptide can act as pro-inflammatory mediators. There is evidence for a dysbalance between κ‑ and µ‑opioid receptors in lesional skin favoring inflammation and pruritus. After clearing of psoriasis lesions, pruritus is relieved as well. Therefore, specific treatment of pruritus is not necessary in general. In cases where severe pruritus is a prominent symptom, targeted therapy with mirtazapin or doxepin or neuroleptic compounds such as pregabalin or gabapentin or drugs affecting the κ‑ und µ‑opioid receptor balance can be administered. Today the importance of pruritus as a prominent symptom of psoriasis lesions has been widely accepted. In recent and running clinical trials with new drugs, pruritus at baseline and the effect of these drugs on pruritus is always assessed. This awareness also fuels basic research about pruritus in psoriasis.
- Ovariectomy changes the response to antidepressant drugs in tail suspension test in mice. [JOURNAL ARTICLE]
- Gynecol Endocrinol 2016 Jun 26.:1-5.
Depressive symptoms are very frequent over a lifetime, especially for women. Menopause is a period of higher depressive vulnerability. There are suggestive data that estrogen deficiency may increase the susceptibility for depression. We studied whether a bilateral ovariectomy (OVX) modifies mice behaviors and antidepressant drug effects through tail suspension test (TST). We evaluated behavioral changes at 1 week, 2 weeks, and up to 2 months after OVX. The behavior responses to doxepin, paroxetine, and venlafaxine at 1 week, 2 weeks, and 2 months after OVX were evaluated. No obvious difference was detected on the duration of immobility among control group, sham group, and OVX group in the TST at 1 week and 2 weeks after OVX. But the duration of immobility of OVX group was distinctly longer than that of both control group and sham operation group at 2 months after OVX. At 1 and 2 weeks after OVX, only the antidepressant response to venlafaxine was observed, while response to paroxetine increased 2 months after OVX. Response to antidepressant drugs was strongly modified in OVX mice. The present results suggest that not all antidepressant drugs are appropriate for depression with estrogen deficiency.
- Treatment of Fatigue in Parkinson Disease. [Comment, Journal Article]
- JAMA 2016 Jun 7; 315(21):2340-1.
Which pharmacological and nonpharmacological interventions are associated with improvement in general, physical, or mental fatigue and minimal adverse effects in patients with Parkinson disease (PD)?Rasagiline, modafinil, and doxepin are associated with improvement in fatigue and are not associated with increased risk of adverse effects in patients with PD. However, the quality of evidence is limited and does not provide a clear basis for treatment decisions.
- Topically applied mesoridazine exhibits the strongest cutaneous analgesia and minimized skin disruption among tricyclic antidepressants: The skin absorption assessment. [Journal Article]
- Eur J Pharm Biopharm 2016 Aug.:59-68.
Tricyclic antidepressants (TCAs) are found to have an analgesic action for relieving cutaneous pain associated with neuropathies. The aim of this study was to assess cutaneous absorption and analgesia of topically applied TCAs. Percutaneous delivery was investigated using nude mouse and pig skin models at both infinite and saturated doses. We evaluated the cutaneous analgesia in nude mice using the pinprick scores. Among five antidepressants tested in the in vitro experiment, mesoridazine, promazine and doxepin showed a superior total absorption percentage. The drug with the lowest total absorption percentage was found to be fluphenazine (<7%) either at an infinite dose or at saturated solubility. The follicular pathway was important for mesoridazine and promazine delivery. Mesoridazine showed stronger skin analgesia than the other TCAs although the in vivo skin absorption of mesoridazine (0.34nmol/mg) was less than that of promazine (0.80nmol/mg) and doxepin (0.74nmol/mg). Mesoridazine had a prolonged duration of pain relief (165min) compared to promazine (83min) and doxepin (17min). The skin irritation test demonstrated an evident barrier function deterioration and cutaneous erythema by promazine and doxepin treatment, whereas mesoridazine caused no obvious adverse effect by topical application for up to 7days.
- Antipruritic Effect of Cold-induced and Transient Receptor Potential-agonist-induced Counter-irritation on Histaminergic Itch in Humans. [JOURNAL ARTICLE]
- Acta Derm Venereol 2016 May 3.
A frequent empirical observation is that cold-induced counter-irritation may attenuate itch. The aim of this randomized, single-blinded, exploratory study was to evaluate the counter-irritation effects of cold-stimulation and topical application of transient receptor potential TRPA1/M8-agonists (trans-cinnamaldehyde/L-menthol, respectively), on histamine-induced itch, wheal and neurogenic inflammation in 13 healthy volunteers. Histamine 1% was applied to the volar forearms using skin prick-testing lancets. Recorded outcome-parameters were itch intensity, wheal reactions and neurogenic inflammation (measured by laser-speckle perfusion-imaging). Homotopic thermal counter-irritation was performed with 6 temperatures, ranging from 4°C to 37°C, using a 3 × 3-cm thermal stimulator. Chemical "cold-like" counter-irritation was conducted with 40% L-menthol and 10% trans-cinnamaldehyde, while 5% doxepin was used as a positive antipruritic control/comparator. Cold counter-irritation stimuli from 4°C to 22°C inhibited itch in a stimulus-intensity-dependent manner (p < 0.05) and, to a lesser extent, also wheal reactions and neurogenic inflammation. Chemical "cold-like" counter-irritation with both L-menthol and trans-cinnamaldehyde had antipruritic efficacy similar to doxepin (p < 0.05). Cold-induced counter-irritation had an inhibitory effect on histaminergic itch, suggesting that agonists of cold transduction receptors could be of potential antipruritic value.
- Electromembrane surrounded solid phase microextraction using electrochemically synthesized nanostructured polypyrrole fiber. [Journal Article]
- J Chromatogr A 2016 Apr 22.:75-82.
Electromembrane surrounded solid phase microextraction using conductive polymers as the sorbent is carried out for the first time for extraction of two antidepressants including amitriptyline (AMI) and doxepin (DOX), as model analytes. The polypyrrole coating was prepared and utilized as both cathode and SPME sorbent. Different variables such as the conditions for preparation of polypyrrole fiber, pH of the donor and the acceptor phases, applied voltage, and extraction time were optimized. Under the optimized conditions, figures of merit of the proposed method were investigated in human whole blood and urine samples. Intra- and inter-assay precisions ranged between 3.1-7.5% and 7.6-12.3%, respectively were obtained in different extraction media. Detection limits of 0.15 and 0.05 for AMI and 0.3 and 0.1ngmL(-1) for DOX were achieved in the urine and blood samples, respectively. Linearity of the method was studied up to 50.0ngmL(-1) for both analytes and coefficients of determination better than 0.9966 were achieved. Regardless of the high sample cleanup, which makes the proposed method suitable for analysis of drugs from complicated matrices, clean chromatograms were obtained. Finally, the proposed method was applied for analysis of AMI and DOX in different real samples and reasonable data were obtained.
- Pharmacological interventions for daytime sleepiness and sleep disorders in Parkinson's disease: Systematic review and meta-analysis. [Journal Article, Review]
- Parkinsonism Relat Disord 2016 Jun.:25-34.
Daytime sleepiness and sleep disorders are frequently reported in Parkinson's disease (PD). However, their impact on quality of life has been underestimated and few clinical trials have been performed.We aimed to assess the efficacy and safety of pharmacological interventions for daytime sleepiness and sleep disorders in PD.Systematic review of randomized controlled trials comparing any pharmacological intervention with no intervention or placebo for the treatment of daytime sleepiness and sleep problems in PD patients.Ten studies (n = 338 patients) were included. Four trials addressed interventions for excessive daytime sleepiness. Meta-analysis of the three trials evaluating modafinil showed a significant reduction in sleepiness, as assessed by the Epworth Sleepiness Scale (ESS) (- 2.24 points, 95% CI - 3.90 to - 0.57, p < 0.05). In one study, treatment with caffeine was associated with a non-significant improvement of 1.71 points in ESS (95% CI, - 3.57 to 0.13). The six remaining trials assessed interventions for insomnia and REM sleep Behaviour Disorder (RBD). Single study results suggest that doxepin and YXQN granules might be efficacious, while pergolide may be deleterious for insomnia and that rivastigmine may be used to treat RBD in PD patients. However, there is insufficient evidence to support or refute the efficacy of any of these interventions. No relevant side effects were reported.Whilst providing recommendations, this systematic review depicts the lack of a body of evidence regarding the treatment of sleep disorders in PD patients; hence, further studies are warranted.
- Spectroscopic, electrochemical and molecular docking studies of dothiepin and doxepin with bovine serum albumin and DNA base. [JOURNAL ARTICLE]
- Luminescence 2016 Mar 17.
The interaction of dothiepin (DOT) and doxepin (DOX) with bovine serum albumin (BSA) and a DNA base (adenine) was studied using UV-visible, fluorescence, attenuated total reflection-infra-red (ATR-IR), cyclic voltammetry and molecular docking methods. Strong fluorescence quenching was observed upon interaction of DOT and DOX with BSA/adenine and the mechanism suggested static quenching. Hydrophobic and hydrogen bonding interactions were the predominant intermolecular forces needed to stabilize the copolymer. Upon addition of the drugs: (i) the tautomeric equilibrium structure of the adenine was changed; and (ii) the oxidation and the reduction peaks of the adenine/BSA interaction shifted towards high and low potentials, respectively. In ATR-IR, the band shift of amides I and II indicated a change in secondary structure of BSA upon binding to DOT and DOX drugs. The reduction in voltammetric current in the presence of BSA/adenine was attributed to slow diffusion of BSA/adenine binding with DOX/DOT. The docking method indicated that the drug moiety interacted with the BSA molecule. Copyright © 2016 John Wiley & Sons, Ltd.
- Fatal toxicity index of medicinal drugs based on a comprehensive toxicology database. [JOURNAL ARTICLE]
- Int J Legal Med 2016 Mar 17.
The fatal toxicity index (FTI) is the absolute number of fatal poisonings caused by a particular drug divided by its consumption figure. Consequently, it is a useful measure in evaluating toxicity of the drug and its relevance in fatal poisonings. In this study, we assessed the FTI of medicinal drugs in 3 years (2005, 2009, and 2013) in Finland. As the measure of drug consumption, we used the number of defined daily doses (DDD) per population in each year. There were 70 medicinal drugs in Finland for which the mean FTI expressed as the number of deaths per million DDD over the three study years was higher or equal to 0.1. The Anatomical Therapeutic Chemical (ATC) classification system was used for the classification of the active ingredients of medicinal drugs according to the organ or system which they act on. Of these 70 drugs, 55 drugs (78.6 %) acted on the nervous system (denoted by ATC code N), 11 (15.7 %) on the cardiovascular system (C), three (4.3 %) on the alimentary tract and metabolism (A), and one (1.4 %) on the musculoskeletal system (M). The nervous system drugs consisted of 20 psycholeptics, (ATC code N05), 20 psychoanaleptics (N06), eight analgesics (N02), six antiepileptics (N03), and one other nervous system drug (N07). The highest individual FTIs were associated with the opioids methadone, dextropropoxyphene, oxycodone, tramadol, and morphine; the antipsychotics levomepromazine and chlorprothixene; and the antidepressants doxepin, amitriptyline, trimipramine, and bupropion. Buprenorphine was not included in the study, because most of the fatal buprenorphine poisonings were due to smuggled tablets. A clearly increasing trend in FTI was observed with pregabalin and possibly with bupropion, both drugs emerging as abused substances.