Lack Of Systemic Side Effects Research Articles

Percutaneous auricular neuromodulation (nerve stimulation) for the treatment of pain following total knee arthroplasty: a randomized, double-masked, sham-controlled pilot study

BackgroundPercutaneous auricular nerve stimulation (neuromodulation) is an analgesic technique involving the percutaneous implantation of multiple leads at various points on/around the ear followed by the delivery of electric current using...

Comparison of Topical, Systemic, and Combined Therapy with Steroids on Idiopathic Granulomatous Mastitis: A Prospective Randomized Study.

Idiopathic granulomatous mastitis (IGM) is a benign disorder of the breast, for which the optimal treatment modality remains missing. A total of 124 patients with a histopathologically proven diagnosis of IGM were enrolled in a prospective, randomized parallel arm study. Patients were treated with topical steroids in Group T (n: 42), systemic steroids (0.8mg/kg/day peroral) in Group S (n: 42), and combined steroids (0.4mg/kg/day peroral + topical) in Group C (n: 40). Compliance with the therapy, response to the therapy, the duration of therapy, side effects and the recurrence rates were compared. Sixteen patients did not comply with the treatment, and the highest ratio of compliance with therapy was seen in Group T (p < 0.05). Complete clinical regression (CCR) was observed in 90 (83.3%) patients. Response to the treatment (RT) was evaluated radiologically and observed in 89.8% of the patients. There was no statistically significant difference between groups regarding CCR, RT and the recurrence rate. The longest duration of therapy was observed in Group T (22 ± 9.1-week), whereas the shortest was observed in Group S (11.7 ± 5.5-week) (p < 0.001). The systemic side effects were significantly lower in Group T in comparison with Groups S and C (2.4% vs. 38.2% and 30.3%, respectively) (p < 0.001). The efficiency of the treatment was similar for all groups, both clinically and radiologically. Although the duration of therapy was longer in Group T, the lack of systemic side effects increased the compliance of the patients with the therapy. Therefore, topical steroids would be among first-line treatment options of IGM.

The role of zinc in the treatment of acne: A review of the literature.

Acne vulgaris is a chronic disease of the pilosebaceous units presenting as inflammatory or noninflammatory lesions in individuals of all ages. The current standard of treatment includes topical formulations in the forms of washes, gels, lotions, and creams such as antibiotics, antibacterial agents, retinoids, and comedolytics. Additionally, systemic treatments are available for more severe or resistant forms of acne. Nevertheless, these treatments have shown to induce a wide array of adverse effects, including dryness, peeling, erythema, and even fetal defects and embolic events. Zinc is a promising alternative to other acne treatments owing to its low cost, efficacy, and lack of systemic side effects. In this literature review, we evaluate the effectiveness and side-effect profiles of various formulations of zinc used to treat acne.

‘Men don't need to know everything’: a field trial of a discreet, female-initiated, contraceptive barrier method (FemCap™) among Haitian-American women

Worldwide, women report the need for safe, non-hormonal, woman-initiated methods of family planning. Cervical barriers provide such technology but are under-researched and under-promoted. In the USA, there are few studies of cervical barriers among women at high unmet need for contraception. A feasibility study of the FemCap™ was conducted among US women of Haitian origin. Participants were heterosexual and seeking to avoid pregnancy. At first visit, participants completed baseline assessments, underwent group counselling and were fitted with FemCap™. Women were asked to insert or use the cap at home. The second visit (2–3 weeks) included an interviewer-administered questionnaire and a focus-group discussion. Participants (n = 20) were Haitian-born (70%), married (55%) and parous (85%). Their mean age was 32.6 years. Seventy percent reported recent unprotected sex. All women inserted the device at home and 9 women used it during intercourse, including 5 without prior partner negotiation. Of 20 women, 11 liked FemCap™ very much or somewhat; 7 considered it ‘OK’; 2 disliked it. Best-liked attributes were comfort, discreet wear and reusability. Difficulties with removal abated over time. Qualitative data revealed a high value placed on lack of systemic side effects. Use of FemCap™ was feasible and acceptable, supporting expansion of research, particularly among relevant populations with unmet need.

Luliconazole for the treatment of fungal infections: an evidence-based review.

Luliconazole is an imidazole antifungal agent with a unique structure, as the imidazole moiety is incorporated into the ketene dithioacetate structure. Luliconazole is the R-enantiomer, and has more potent antifungal activity than lanoconazole, which is a racemic mixture. In this review, we summarize the in vitro data, animal studies, and clinical trial data relating to the use of topical luliconazole. Preclinical studies have demonstrated excellent activity against dermatophytes. Further, in vitro/in vivo studies have also shown favorable activity against Candida albicans, Malassezia spp., and Aspergillus fumigatus. Luliconazole, although belonging to the azole group, has strong fungicidal activity against Trichophyton spp., similar to that of terbinafine. The strong clinical antifungal activity of luliconazole is possibly attributable to a combination of strong in vitro antifungal activity and favorable pharmacokinetic properties in the skin. Clinical trials have demonstrated its superiority over placebo in dermatophytosis, and its antifungal activity to be at par or even better than that of terbinafine. Application of luliconazole 1% cream once daily is effective even in short-term use (one week for tinea corporis/cruris and 2 weeks for tinea pedis). A Phase I/IIa study has shown excellent local tolerability and a lack of systemic side effects with use of topical luliconazole solution for onychomycosis. Further studies to evaluate its efficacy in onychomycosis are underway. Luliconazole 1% cream was approved in Japan in 2005 for the treatment of tinea infections. It has recently been approved by US Food and Drug Administration for the treatment of interdigital tinea pedis, tinea cruris, and tinea corporis. Topical luliconazole has a favorable safety profile, with only mild application site reactions reported occasionally.

Lack of Systemic Side Effects of Long-Term Inhaled Fluticasone Propionate Use in a Cohort of Asthmatic Children

Inhaled corticosteroids (ICS) are established as first-line therapy for persistent asthma in children. Fluticasone propionate (FP) has been used because it has equivalent efficacy when used at half-dose of older-generation ICS and has a comparable safety profile. However, concerns persist about the potential risk of adverse effects of long-term FP therapy on childhood growth, bone, adrenal function and immune system. To evaluate the potential adverse effects of FP, we analyzed growth, glucidic metabolism, hypothalamic-pituitary-adrenal axis, bone metabolism, bone mass density and immune system in a cohort of 19 children (average 102±18 months), with asthma who were in treatment with FP (average duration: 14 months, range: 11–17 months). Of these, 11 children homogenous for control of asthma symptoms, and compliance to therapy, were selected for a prospective study during which they were treated with FP250 mg/day for further 6 months (total period of treatment average duration: 22 months, range: 18–23 months). In all children, no alterations of growth, glucidic metabolism, hypothalamic-pituitary-adrenal axis, bone metabolism, bone mass density, immune system nor severe exacerbation of the disease were observed. Our study, showing that FP was able to control the symptoms of asthma and confirming the lack of systemic side effects at the recommended doses, supports its long-term use in children with asthma.

Lidocaine Eye Drops Attenuate Pain Associated with Ophthalmic Postherpetic Neuralgia

Topical lidocaine (LDC) treatment using a gel or patch preparation is effective in the treatment of postherpetic neuralgia (PHN), but neither is suited for the eye in patients with ophthalmic PHN. Herein, we examined the effect of LDC 4% eye drops on ophthalmic PHN pain. Twenty-four patients with ophthalmic PHN were randomized to receive 0.4 mL eye drops of either LDC 4% or saline placebo (PBO) in the painful eye. After a 7-day period, the patients were crossed over to receive the alternative eye drops. The pain in the eye and the forehead was assessed with a visual analog scale (VAS) before and 15 minutes after treatment. Patients used a descriptive scale to grade pain outcome and were asked to note whether the pain returned and how long after therapy it recurred. LDC significantly decreased the VAS score of persistent pain in the eye (baseline: 5.9 +/- 2.2 cm; 15 minutes after eye drops: 0.9 +/- 1.8 cm, mean +/- SD [P < 0.01]) and in the forehead (baseline: 6.3 +/- 2.0 cm; 15 minutes after eye drops: 2.6 +/- 2.7 cm [P < 0.01]). The delta change in these VAS scores between LDC and PBO was significant (P < 0.01). Moreover, pain was described as moderate or better by 23 patients after they received LDC and 4 patients of the PBO group. The effect of LDC persisted for a median of 36 hours (range, 8-96 hours) after application. This study suggests that LDC provides a significant improvement of ophthalmic PHN because of its prompt analgesia, lack of systemic side effects, and convenience of use.

Efficacy of a Metered-dose 8% Lidocaine Pump Spray for Patients with Post-herpetic Neuralgia

Topical lidocaine patch is effective in the treatment of post-herpetic neuralgia (PHN), but not suited for paroxysmal pain because of the long latency of analgesia. Here, we examined the efficacy of 8% lidocaine pump spray (Xylocaine pump spray, XPS) for PHN. Twenty-four patients with PHN were recruited into a randomized, double-blind, placebo-controlled, crossover study (study 1), and 100 patients with PHN were recruited into an open-labeled study (study 2). In study 1, patients were randomized to receive either XPS or saline placebo pump spray (PPS) applied to the painful skin areas. Following a 7-day period, patients were crossed over to receive the alternative treatment. In study 2, XPS was prescribed for patients who were advised to use the spray anytime, with a 2-hour gap between applications, for 2 weeks. The pain was assessed with a visual analogue scale (VAS). Details of use were noted in the diary. In study 1, greater decreases in VAS of persistent pain followed application of XPS (baseline: 6.1 +/- 1.7 cm, 15-minute post-spray: 2.3 +/- 2.5 cm, mean +/- SD) than with PPS (6.1 +/- 1.7 cm, 5.7 +/- 1.6 cm, [P < 0.01]). The effect persisted for a median of 4.5 hours (range, 2 to 24 hours) after application. In study 2, 13 of 100 patients discontinued the treatment because of mild local side effects or insufficient effect. In the remaining 87 patients, XPS maintained significant pain relief relative to baseline throughout the 2-week period. Satisfaction with the therapy was reported by 79% of patients. In both studies, XPS provided a significant improvement in PHN due to its prompt analgesia, lack of systemic side effects, and convenience of use.

The Analgesic Effect of a Metered-Dose 8% Lidocaine Pump Spray In Posttraumatic Peripheral Neuropathy: A Pilot Study

A topical lidocaine patch is effective in the treatment of posttraumatic peripheral neuropathy (PTPN), but it is not suited for breakthrough pain because of difficulty with an additional application. Here, we examined the effect of 8% lidocaine pump spray (Xylocaine pump spray, XPS) on peripheral neuropathic pain caused by surgery or injury. Thirty-one patients with PTPN were randomized to receive either XPS or saline placebo pump spray applied to painful skin areas. The optimal dose of up to 30 sprays (0.1 mL/single spray, 30 times) was individually determined as the dose which completely covered the painful site. After a 7-day period, the patients were crossed over to receive the optimal dose of the alternative spray. Pain was assessed with a visual analog scale. XPS, but not placebo pump spray, significantly decreased the visual analog scale for continuing pain and tactile allodynia. The effect persisted for a median of 5 h (range, 2-60 h) after application. Mild side effects were reported in three patients with XPS consisting of local irritation (n = 3) and local flare (n = 1). All adverse events disappeared without medication within a few hours. The present study suggests that XPS provides a significant improvement in PTPN due to its prompt analgesia, lack of systemic side effects and convenience.

Commercially Available Prostaglandin Analogs for the Reduction of Intraocular Pressure: Similarities and Differences

Over the last 12 years, the pharmacological management of glaucoma and ocular hypertension has significantly changed with the introduction of the prostaglandin analogs, specifically, latanoprost, bimatoprost, and travoprost. Their ability to effectively reduce intraocular pressure with once-per-day dosing, their comparable ocular tolerability with timolol, and their general lack of systemic side effects have made them the mainstay of pharmacological therapy for glaucoma and ocular hypertension in most parts of the world. A review of their pharmacology reveals that they are all prodrugs that are converted to their respective free acids within the eye to activate the prostanoid FP receptor and to reduce intraocular pressure by enhancing the uveoscleral and the trabecular meshwork outflow pathways. A review of numerous prospective, randomized comparative studies indicates that no clinically significant differences exist among these agents regarding their ability to lower intraocular pressure.

Desmopressin (DDAVP) and factor VIII: the tale as viewed from Milan (and Malmö)

Desmopressin (DDAVP) and factor VIII: the tale as viewed from Milan (and Malmö)

Topical Diclofenac Patch Relieves Minor Sports Injury Pain: Results of a Multicenter Controlled Clinical Trial

Sports-related soft tissue injuries, such as sprains, strains, and contusions, are a common painful condition. Current treatment includes oral nonsteroidal anti-inflammatory drugs (NSAIDs), which have a high incidence of intolerable gastrointestinal side effects. Topically applied drugs have the potential to act locally in the soft tissues without systemic effects. This study assessed the efficacy and safety of topical diclofenac (NSAID) patch applied directly to the painful injury site for the treatment of acute minor sports injury pain. Adult subjects ( N = 222) were recruited from two communities for a multicenter, randomized, placebo-controlled, parallel design study. All subjects had suffered a painful minor sports injury within the prior 72 hours of study entry. Either a diclofenac epolamine or placebo topical patch was applied directly to the skin overlying the painful injured site twice daily for 2 weeks. Measures of pain intensity were performed in a daily diary and at clinic visits on days 3, 7, and 14. Diclofenac patch was superior to placebo patch in relieving pain. Statistical significance was seen on clinic days 3 ( P = 0.036) and 14 ( P = 0.048), as well as the daily diary pain ratings at days 3, 7, and 14 ( P ≤ 0.044). No statistically significant differences were seen in any safety or side-effect measures with the diclofenac patch as compared to the placebo patch. Diclofenac epolamine patch is an effective and safe pain reliever for treatment of minor sports injury pain. The advantages of this novel therapy include its ease of use and lack of systemic side effects.

Endocrine effects and pharmacokinetic characteristics of a potent new gonadotropin-releasing hormone antagonist (Ganirelix) with minimal histamine-releasing properties: studies in postmenopausal women.

A potent and safe GnRH antagonist has been sought unsuccessfully for the last 2 decades. The recently developed GnRH antagonist RS-26306 or Ganirelix ([N-Ac-D-Nal(2)1,D-pClPhe2,D-Pal(3)3,D-hArg(Et2)6,L-++ +hArg(Et2)8,D-Ala10]GnRH ; Syntex Research, Palo Alto, CA), exhibited high antiovulatory potency and low histamine-releasing properties in preclinical studies. Therefore, we determined the extent to which single sc injections of three doses of RS-26306 (1, 3, and 6 mg) decreased serum concentrations of LH and FSH, the free alpha-subunit of LH/FSH/TSH, PRL, and testosterone in five healthy postmenopausal women. We also examined the pharmacokinetic characteristics of RS-26306 by quantifying serum levels of the drug by RIA. RS-26306 rapidly suppressed serum concentrations of LH, FSH, and free alpha-subunit. RS-26306 (6 mg) maximally decreased serum concentrations (mean +/- SEM) of LH, FSH, and free alpha-subunit by 70.1 +/- 3.6%, 42.3 +/- 2.5%, and 74.6 +/- 3.5%, respectively. RS-26306 also decreased serum testosterone, but not serum PRL, concentrations. RS-26306 concentrations reached peak serum levels at 1.2 +/- 0.3, 1.9 +/- 0.4, and 1.8 +/- 0.5 h, respectively, after 1-, 3-, and 6-mg sc injections. The mean serum half-life values based on the terminal portion of the disappearance curves were 22.8 +/- 2.5 and 26.9 +/- 1.0 h, respectively, after 3- and 6-mg s.c. doses. No systemic side-effects were noted after the administration of RS-26306. Our results demonstrate that the GnRH antagonist RS-26306 has favorable pharmacokinetic characteristics and is a potent suppressor of pituitary gonadotropin secretion in postmenopausal women. These attributes and the lack of systemic side-effects make RS-26306 a promising candidate for future clinical applications.

Topical anti-inflammatory activity of esters of steroid 21-OIC acids

Prednisolone derivatives, methyl 20 α- and 20 β-dihydroprednisolonate and methyl 17,20 α- and 17,20 β-acetonidodihydroprednisolonate have been evaluated for their topical anti-inflammatory activity in the croton oil induced ear edema test. The order of anti-inflammatory potency was prednisolone > methyl 17,20 α-acetonidodihydroprednisolonate > methyl 17,20 β-acetonidodihydroprednisolonate > methyl 20 β-dihydroprednisolonate > methyl 20 α-dihydroprednisolonate. This order was paralleled by the compounds' octanol-aqueous partition coefficients. Furthermore, after two consecutive days topical administration of an equipotent anti-inflammatory dose, only prednisolone significantly decreased plasma corticosterone levels and relative thymus weight, while the new steroid derivatives had no effect on these parameters, indicating their lack of systemic side effects.