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Systemic Side Effects (systemic + side_effects)

Distribution by Scientific Domains

Medical Sciences	87%

Selected Abstracts

Transdermal Clonidine Skin Reactions

JOURNAL OF CLINICAL HYPERTENSION, Issue 2 2002
L. Michael Prisant MD
The clonidine transdermal therapeutic system is being used as a therapy for blood pressure treatment. Systemic side effects seem to be fewer than with oral clonidine. However, localized skin reactions occur frequently and the incidence increases with the dose and duration of use. Common signs include erythema, scaling, vesiculation, excoriation, and induration. Allergic contact dermatitis is less frequent but common. Hyperpigmentation and depigmentation also occur. Pretreatment with 0.5% hydrocortisone is associated with less skin irritation and higher blood levels. Although oral clonidine is no longer widely used in the management of hypertension, awareness of these reactions to the transdermal delivery of this agent is important. [source]

Local oropharyngeal side effects of inhaled corticosteroids in patients with asthma

ALLERGY, Issue 5 2006
R. Buhl
The widespread use of inhaled corticosteroids (ICS) for the treatment of persistent asthma, although highly effective, may be associated with both systemic and local side effects. Systemic side effects of ICS have been extensively studied. In contrast, relatively few studies have been performed to specifically evaluate local side effects of ICS. These local side effects , including oropharyngeal candidiasis, dysphonia, pharyngitis, and cough , are generally viewed as minor complications of therapy. However, they can be clinically significant, affect patient quality of life, hinder compliance with therapy, and mask symptoms of more serious disease. Local side effects result from deposition of an active ICS in the oropharynx during administration of the drug. Numerous factors can influence the proportion of an inhaled dose that is deposited in the oropharyngeal cavity, including the ICS formulation, type of delivery system, and patient compliance with administration instructions. Therefore, the incidence of local side effects can vary widely. The goal in developing a new ICS is to include key pharmacologic characteristics that reduce oropharyngeal exposure to active drug while maintaining efficacy comparable with currently available ICS. [source]

Paired comparison of bathwater versus oral delivery of 8-methoxypsoralen in psoralen plus ultraviolet A therapy for chronic palmoplantar psoriasis

PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 1 2006
A. Hofer
Background: Both bath psoralen plus ultraviolet A (PUVA) and oral PUVA with 8-methoxypsoralen (8-MOP) have been successfully used for the treatment of recalcitrant palmoplantar psoriasis. This trial was designed to assess the efficacy and side effects of the different treatment modalities in a randomized half-side comparison. Methods: Eight patients with moderate-to-severe psoriasis on soles (n=6) and/or palms (n=8) were randomly assigned to receive bath PUVA treatment on one side and oral PUVA on the other. Initial treatment dose was 50% of the minimal phototoxic dose evaluated for bath PUVA and oral PUVA. Treatment was given three times a week for 4 weeks. Before treatment and every week a severity index (SI) was assessed by summing the scores of erythema, infiltration, scaling and vesicles evaluated on a scale from 0 to 4. After 4 weeks of treatment the half-side trial was finished and the treatment was continued on both sides with the more effective treatment regimen. Results: Both bath PUVA and oral PUVA achieved a reduction of the mean initial SI from 5.9 (95% confidence intervals (CI) 4.5,8.0) to 3.3 (1.8,6.0) (44% SI reduction, P<0.005, Student's paired t -test) and 6.0 (5.0,7.8) to 2.9 (1.8,4.0) (52% SI reduction; P<0.005), respectively. The statistical comparison of the entire 4-week study period revealed a significant better effect in lesions treated with oral PUVA compared with bath PUVA (P=0.033). However, at 4 weeks, there was no significant difference between the achieved SI reduction of oral PUVA and bath PUVA. Systemic side effects (nausea and/or dizziness) were only observed after oral PUVA. Conclusion: This study gives evidence that in the first 4 treatment weeks oral PUVA is slightly more effective than bath PUVA but the former has more systemic side effects. [source]

Continuous local intrahippocampal delivery of adenosine reduces seizure frequency in rats with spontaneous seizures

EPILEPSIA, Issue 9 2010
Annelies Van Dycke
Summary Purpose:, Despite different treatment options for patients with refractory epilepsy such as epilepsy surgery and neurostimulation, many patients still have seizures and/or drug-related cerebral and systemic side effects. Local intracerebral delivery of antiepileptic compounds may represent a novel strategy with specific advantages such as the option of higher local doses and reduced side effects. In this study we evaluate the antiepileptic effect of local delivery of adenosine in the kainic acid rat model, a validated model for temporal lobe epilepsy. Methods:, Fifteen rats, in which intraperitoneal kainic acid injection had induced spontaneous seizures, were implanted with a combination of depth electrodes and a cannula in both hippocampi. Cannulas were connected to osmotic minipumps to allow continuous hippocampal delivery. Rats were freely moving and permanently monitored by video-EEG (electroencephalography). Seizures were scored during 2 weeks of local hippocampal delivery of saline (baseline), followed by 2 weeks of local adenosine (6 mg/ml) (n = 10) or saline (n = 5) delivery (0.23 ,l/h) (treatment). In 7 of 10 adenosine-treated rats, saline was also delivered during a washout period. Results:, During the treatment period a mean daily seizure frequency reduction of 33% compared to the baseline rate was found in adenosine-treated rats (p < 0.01). Four rats had a seizure frequency reduction of at least 50%. Both nonconvulsive and convulsive seizures significantly decreased during the treatment period. In the saline-control group, mean daily seizure frequency increased with 35% during the treatment period. Conclusions:, This study demonstrates the antiseizure effect of continuous adenosine delivery in the hippocampi in rats with spontaneous seizures. [source]

Intracutaneous injection of the macrophage-activating lipopeptide-2 (MALP-2) which accelerates wound healing in mice , a phase I trial in 12 patients

EXPERIMENTAL DERMATOLOGY, Issue 12 2008
Margarete Niebuhr
Abstract:, Chronic skin ulcers, such as leg ulcers, pressure sores and diabetic foot ulcers, are a challenge to physicians and medical personnel and a cause of tremendous discomfort and ensuing loss of quality of life to the patients. Wound healing involves production and action of various growth factors. A novel approach, distinct from the application of single growth factors, is the administration of the macrophage stimulator macrophage-activating lipopeptide-2 (MALP-2). The rationale is based on the finding that macrophages are the main source of several growth factors required for wound healing, which are sequentially released during this process. MALP-2 has previously been shown to be effective in an established animal model with diabetic mice. The purpose of the present phase I study was to establish tolerability of MALP-2 when applied into small cutaneous wounds in human beings. Twelve patients (six females and six males; mean age 66.8 years; range 52,87 years) with different diagnoses were enrolled into the study. An artificial wound was created with a 2-mm diameter skin biopsy punch and a volume of 30 ,l MALP-2 (0.125,1 ,g) or vehicle control, respectively, was injected intracutaneously into the wound and closed with a water-resistant transparent adhesive. Photos were taken daily from every patient up to 6 days, and skin biopsies were performed after 1 week from six patients. We could show in the present study for the first time that MALP-2 caused a transient erythema and was tolerated without any systemic side effects up to a dose of 1 ,g per wound in human beings. In healthy as well as in diabetic patients, MALP-2 induced local inflammation that faded after 48 h. The effectiveness of MALP-2 in the healing of chronic wounds in humans, e.g. in chronic skin ulcers, such as leg ulcers, pressure sores and diabetic foot ulcers, could now be addressed in further studies. [source]

Insight into the molecular mechanisms of glucocorticoid receptor action promotes identification of novel ligands with an improved therapeutic index

EXPERIMENTAL DERMATOLOGY, Issue 8 2006
Heike Schäcke
Abstract:, Glucocorticoids are highly effective in the therapy of inflammatory and autoimmune disorders. Their beneficial action is restricted because of their adverse effects upon prolonged usage. Topical glucocorticoids that act locally have been developed to significantly reduce systemic side effects. Nonetheless, undesirable cutaneous effects such as skin atrophy persist from the use of topical glucocorticoids. There is therefore a high medical need for drugs as effective as glucocorticoids but with a reduced side-effect profile. Glucocorticoids function by binding to and activating the glucocorticoid receptor that positively or negatively regulates the expression of specific genes. Several experiments suggest that the negative regulation of gene expression by the glucocorticoid receptor accounts for its anti-inflammatory action. This occurs through direct or indirect binding of the receptor to transcription factors such as activator protein-1, nuclear factor- ,B or interferon regulatory factor-3 that are already bound to their regulatory sites. The positive action of the receptor occurs through homodimer binding of the receptor to discrete nucleotide sequences and this possibly contributes to some of the adverse effects of the hormone. Glucocorticoid receptor ligands that promote the negative regulatory action of the receptor with reduced positive regulatory function should therefore show improved therapeutic potential. A complete separation of the positive from the negative regulatory activities of the receptor has so far not been possible because of the interdependent nature of the two regulatory processes. Nevertheless, considerable improvement in the therapeutic action of glucocorticoid receptor ligands is being achieved through the use of key molecular targets for screening novel glucocorticoid receptor ligands. [source]

Effect of inhaled corticosteroids on risk of development of cataract: a meta-analysis

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2006
Anup Uboweja
Abstract The objective of this study was to quantify the risk of cataract among users of inhaled corticosteroids (ICS). Studies that examined the association of ICS use with risk of cataract were identified through computerized (MEDLINE, EMBASE), manual searches using Index Medicus, and checking cross-references to recover all published articles and scientific session abstracts. Pooled odds ratio (OR) with 95% confidence intervals (CI) were estimated using two methods, fixed effects Mantel,Haenszel model and random effects DerSimonian,Laird model. Four studies satisfied all the inclusion/exclusion criteria and were included in the analysis. The pooled OR (95% CI) by the Mantel,Haenszel method was 1.48 (1.39,1.57) and by the DerSimonian,Laird method was 1.48 (1.30,1.68). The test for heterogeneity was not significant. A total number of nine negative studies would be required to make the results of our meta-analysis non-significant. Number needed to harm is 16 with 95% CI of 13,19. Contrary to popular belief, inhaled ICS may be associated with systemic side effects like cataract as shown by this meta-analysis. The risk of increased cataract shown in our analysis needs to be weighted against the benefits of ICS. Further evaluations are required to clarify the causal association between the dosage and duration of drug use. [source]

Ophthalmically Administered , Blockers and Their Cardiopulmonary Effects

JOURNAL OF CLINICAL HYPERTENSION, Issue 3 2001
Domenic A. Sica MD
Early clinical studies revealed that timolol and other topical , blockers were effective in reducing intra-ocular pressure, without the side effects associated with other antiglaucoma agents. However, because persons with cardiovascular or respiratory diseases were generally excluded from many of these early studies, the risk of serious cardiovascular and respiratory side effects was seriously underestimated. Once these drugs were made available to the general population, reports of systemic side effects began to proliferate. Very quickly, adverse effects from topical , blockade became "old news." Despite this recognition, many treating physicians remained unaware of the potential for systemic , blockade from topically applied , blockers. A significant portion of a topically administered dose of a , blocker can be absorbed and thereby affect systemic , blockade. Sensitivity to systemic , blockade can be quite dramatic in certain highly susceptible patients, particularly those with either cardiac or pulmonary abnormalities. Careful review of patients' medications will generally lessen, but not completely eliminate, the risk of undesired complications attributable to topical P blockade. [source]

Intertriginous epidermal dysmaturation from pegylated liposomal doxorubicin

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2003
Joseph C. English III
Background:, A new formulation of doxorubicin (pegylated liposomal doxorubicin) has been developed to attenuate the systemic side effects produced by this agent. Although pegylated liposomal doxorubicin has a much lower risk for cardiotoxicity, it has been associated with cutaneous side effects that differ from, and may also be more frequent than, those produced by the free form of the drug. Methods:, We report a case of interface dermatitis with keratinocyte dysmaturation, limited to the intertriginous areas, in a patient who received pegylated liposomal doxorubicin, and we review the literature. Results:, It is possible that the enhanced delivery of doxorubicin in liposomal form promotes cutaneous side effects of the drug. We consider the possible mechanisms for keratinocyte dysmaturation produced by this form of doxorubicin. Conclusions:, Our findings further suggest that inflammatory changes seen on biopsy may not always allow a reliable histopathologic distinction between this chemotherapy effect and graft-versus-host disease. [source]

Dosage regimens for inhaled therapy in children should be reconsidered

JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 2 2002
JH Wildhaber
Abstract: In current asthma guidelines, dosage regimens for inhalation therapy in children are based on adult doses and are generally titrated per kilogram of bodyweight or per square metre of body surface area. However, these recommendations do not correspond well with current knowledge of aerosol therapy in childhood. Lung deposition of the aerosolised drug is the key determinant for clinical efficacy and for systemic side effects of inhalation therapy. Lung deposition increases with age, whereas lung deposition expressed as a percentage per kilogram bodyweight is age-independent. This finding is explained by the self-regulating effect of age-dependent airway anatomy on lung deposition. Therefore, it is more likely that adult doses translate into paediatric doses only by virtue of the differences in self-limiting pulmonary deposition when using the same absolute nominal doses of the medication. Adapting the adult dose to a paediatric dose calculated on body size might be unnecessary and could lead to insufficient pulmonary deposition of medication. These findings suggest that dosage regimens for inhalation therapy for children may have to be reconsidered, and should be determined from dose-ranging studies rather than calculated from adult doses based on body size. [source]

Design of anticancer prodrugs for reductive activation

MEDICINAL RESEARCH REVIEWS, Issue 1 2009
Yu Chen
Abstract Anticancer prodrugs designed to target specifically tumor cells should increase therapeutic effectiveness and decrease systemic side effects in the treatment of cancer. Over the last 20 years, significant advances have been made in the development of anticancer prodrugs through the incorporation of triggers for reductive activation. Reductively activated prodrugs have been designed to target hypoxic tumor tissues, which are known to overexpress several endogenous reductive enzymes. In addition, exogenous reductive enzymes can be delivered to tumor cells through fusion with tumor-specific antibodies or overexpressed in tumor cells through gene delivery approaches. Many anticancer prodrugs have been designed to use both the endogenous and exogenous reductive enzymes for target-specific activation and these prodrugs often contain functional groups such as quinones, nitroaromatics, N-oxides, and metal complexes. Although no new agents have been approved for clinical use, several reductively activated prodrugs are in various stages of clinical trial. This review mainly focuses on the medicinal chemistry aspects of various classes of reductively activated prodrugs including design principles, structure-activity relationships, and mechanisms of activation and release of active drug molecules. © 2008 Wiley Periodicals, Inc. Med Res Rev, 29, No. 1, 29,64, 2009 [source]

Intravenous Magnesium for Complex Regional Pain Syndrome Type 1 (CRPS 1) Patients: A Pilot Study

PAIN MEDICINE, Issue 5 2009
Susan Collins MSc
ABSTRACT Objectives., To explore the feasibility of intravenous magnesium administration as a potential candidate intervention for a large size trial in Complex Regional Pain Syndrome Type 1 (CRPS 1). Design., Randomized clinical trial. Setting., Outpatient pain clinic. Patients., Ten CRPS 1 patients. Interventions., Eight patients received 70 mg/kg magnesium sulphate infusions in 4 hours for 5 days. For blinding purposes, 2 patients received equal amount NaCl 0.9% solutions (data not analyzed or presented). Interventions were accompanied by standardized physical therapy. Outcome Measures., Pain was assessed using an 11-point Box scale (three times daily for a week) and the McGill Pain Questionnaire. Skin sensitivity was measured with the Semmes Weinstein Monofilaments, (other) impairments with the Impairment Level Sumscore. In addition, functional limitations (Radboud Skills Questionnaire, questionnaire rising and sitting down) and quality of life (Short Form-36 [SF-36], EuroQol) were evaluated. Assessments were performed at baseline, 1, 3, 6, and 12 weeks after intervention. Results., Mild systemic side effects were experienced and the infusions were locally well tolerated. Pain was significantly reduced at all follow up compared with baseline (T1: P = 0.01, T3: P = 0.04, T6: P = 0.02, T12: P = 0.02). McGill sensory subscale improved significantly at T1 (number of words chosen: P = 0.03 and pain rating index: P = 0.03). Impairment level (P = 0.03) and quality of life (EuroQol P = 0.04, SF-36 physical P = 0.01) were significantly improved at T12. No improvement was found for skin sensitivity and functional limitations. Conclusion., Intravenous magnesium significantly improved pain, impairment and quality of life and was well tolerated. The results of this pilot study are encouraging and suggest that magnesium IV as a treatment in CRPS 1 should be further explored in a large size formal trial design. [source]

Paired comparison of bathwater versus oral delivery of 8-methoxypsoralen in psoralen plus ultraviolet A therapy for chronic palmoplantar psoriasis

A Novel Technique for Loading of Paclitaxel-PLGA Nanoparticles onto ePTFE Vascular Grafts

BIOTECHNOLOGY PROGRESS, Issue 3 2007
Hyun Jung Lim
The major cause of hemodialysis vascular access dysfunction (HVAD) is the occurrence of stenosis followed by thrombosis at venous anastomosis sites due to the aggressive development of venous neointimal hyperplasia. Local delivery of antiproliferative drugs may be effective in inhibiting hyperplasia without causing systemic side effects. We have previously demonstrated that paclitaxel-coated expanded poly(tetrafluoroethylene) (ePTFE) grafts, by a dipping method, could prevent neointimal hyperplasia and stenosis of arteriovenous (AV) hemodialysis grafts, especially at the graft-venous anastomoses; however, large quntities of initial burst release have remained a problem. To achieve controlled drug release, paclitaxel (Ptx)-loaded poly(lactic- co -glycolic acid) (PLGA) nanoparticles (Ptx-PLGA-NPs) were prepared by the emulsion-solvent evaporation method and then transferred to the luminal surface and inner part of ePTFE vascular grafts through our micro tube pumping and spin penetration techniques. Scanning electron microscope (SEM) images of various stages of Ptx-PLGA-NPs unequivocally showed that micro tube pumping followed by spin penetration effectively transferred Ptx-PLGA-NPs to the inner part, as well as the luminal surface, of an ePTFE graft. In addition, the in vitro release profiles of paclitaxel demonstrated that this new system achieved controlled drug delivery with a reduced initial burst release. These results suggest that loading of Ptx-PLGA-NPs to the luminal surface and the inner part of an ePTFE graft is a promising strategy to ultimately inhibit the development of venous neointimal hyperplasia. [source]

Non-viral strategies of intra-ocular gene delivery

ACTA OPHTHALMOLOGICA, Issue 2009
F BEHAR-COHEN
Purpose Systemic anti TNF strategies are efficient to treat intraocular inflammation but require repeated injections and are associated to severe systemic side effects. Our aim was to develop a non viral gene transfer method to produce locally anti-inflammatory proteins in a sustained and minimally invasive manner in the ocular media. For this purpose, we have transformed the ciliary muscle into a bioreactor, using an electrically assisted gene transfer technique. Methods Electrotransfer (ET) of plasmids, encoding for different variants of TNF alpha soluble receptors, was performed in the ciliary muscle cells. Using toptimized conditions, soluble receptors were dosed in the ocular media up to 8 months after a single treatment. The technique has been applied in two models of intraocular inflammation: Endotoxin-Induced Uveitis (EIU) and auto immune experimental uveitis (EAU) in rats. Results When performed 8 days or 3 months before the LPS challenge, ET significantly reduced both clinical and histological signs of EIU. Particularly, iNOS, IL6 and TNF were down regulated while IL10 was upregulated. Importantly, systemic TNF alpha was not decreased demonstrating a local effect of the treatment. In EAU, ET significantly delayed the onset of EAU and deceased its severity. Similarly, a switch towards a Th2 cytokines profile was observed in the ocular media without any effect on systemic TNF alpha. Conclusion - ET is a safe and efficient non viral method to produce locally TNF alpha soluble receptors. - Local anti TNF allows for a local intraocular immunomodulation, without affecting systemic TNF. ET could therefore be used to reduce systemic side effects of anti TNF and prevent repeated injections. [source]