Role of Acetyl-L-Carnitine in the Treatment of Diabetic Peripheral Neuropathy

2008 ◽  
Vol 42 (11) ◽  
pp. 1686-1691 ◽  
Author(s):  
Jeffery D Evans ◽  
Tibb F Jacobs ◽  
Emily W Evans

Objective: To examine the role of acetyl-L-carnitine (ALC) in the treatment of diabetic peripheral neuropathy (DPN). Data Sources: A MEDLINE search (1966–April 2008) of the English-language literature was performed using the search terms carnitine, diabetes, nerve, and neuropathy. Studies identified were then cross-referenced for their citations. Study Selection and Data Extraction: The search was limited to clinical trials, meta-analyses, and reviews addressing the use of ALC for the treatment of DPN. Studies that included other disease states that could cause peripheral neuropathy were excluded. Two large clinical studies that used ALC for the treatment of DPN were identified. No case studies were identified. Data Synthesis: The results from 2 published clinical trials Involving 1679 subjects were included. Subjects who received at least 2 g daily of ALC showed decreases in pain scores. One study showed improvements in electrophysiologic factors such as nerve conduction velocities, while the other did not. Patients who had neuropathic pain reported reductions in pain using a visual analog scale. Nerve regeneration was documented in one trial. The supplement was well tolerated, A proprietary form of ALC was used in both studies. Conclusions: Data on treatment of DPN with ALC support its use. It should be recommended to patients early in the disease process to provide maximal benefit. Further studies should be conducted to determine the effectiveness of ALC in the treatment and prevention of the worsening symptoms of DPN.

1993 ◽  
Vol 27 (7-8) ◽  
pp. 898-903 ◽  
Author(s):  
Julie S. Larsen ◽  
Edward P. Acosta

OBJECTIVE: To familiarize readers with a potentially new class of compounds for treating asthma. Background information on leukotrienes is provided in addition to an indepth review of pertinent clinical trials. DATA SOURCES: Information was obtained from controlled clinical trials, abstracts, and review articles identified through a MEDLINE search of English-language articles. STUDY SELECTION: Emphasis was placed on early clinical trials that showed some benefit with these compounds as well as more recent studies using newer agents that produced more promising results. DATA EXTRACTION: Information regarding leukotriene biochemistry was extracted from basic science research and data from human studies were evaluated by the authors according to patient selection, study design, methodology, and therapeutic response. DATA SYNTHESIS: Leukotrienes have a pathophysiologic role in asthma. Two distinct but pharmacologically similar classes of leukotriene inhibitors are currently being clinically evaluated. These are leukotriene receptor antagonists and 5-lipoxygenase inhibitors. Early clinical trials with these agents yielded unfavorable results primarily because of lack of drug potency and selectivity, poor patient tolerance, and possibly the route of administration. Subsequent studies with more potent and selective agents have further implicated leukotrienes as biochemical mediators in asthma and, consequently, have shown promising clinical outcomes with respect to pulmonary function testing and patient tolerance. CONCLUSIONS: Advancements in the pathogenesis of asthma are beginning to define a role for the leukotrienes. Although more studies are needed to assess the efficacy of leukotriene inhibitors, recent clinical trials using leukotriene-receptor antagonists and 5-lipoxygenase inhibitors indicate a potential for the expansion of therapeutic regimens currently used in the treatment of asthma.


1996 ◽  
Vol 7 (3) ◽  
pp. 183-194 ◽  
Author(s):  
Alice Tseng ◽  
Michelle Foisy

OBJECTIVE: To review the pharmacology and pharmacokinetics of intravenous, oral and intraocular ganciclovir, and to discuss the role of these various formulations in the management of cytomegalovirus (CMV) retinitis in AIDS patients.DATA SOURCES: A MEDLINE search (1987 through November 1995) of English-language literature using the main medical subject headings ‘ganciclovir’ and ‘cytomegalovirus’, and the subheading ‘acquired immunodeficiency syndrome’. Relevant articles were also selected from references of identified articles. Abstracts from recent medical conferences of infectious diseases, pharmacology and human immunodeficiency virus were screened for additional data.STUDY SELECTION AND DATA EXTRACTION: All articles and abstracts discussing the use of ganciclovir for the management or prophylaxis of CMV retinitis in AIDS patients were considered for inclusion. Pertinent information, as judged by the authors, was selected and synthesized for discussion.DATA SYNTHESIS: Ganciclovir has demonstrated virustatic activity against CMV, and is often administered 5 mg/kg intravenously every 12 h as first-line therapy for CMV retinitis. Intravenous maintenance therapy at 5 mg/kg daily is usually effective at delaying retinitis progression for approximately 60 to 70 days. Neutropenia and thrombocytopenia are observed frequently, often necessitating interruption or discontinuation of therapy. Local drug administration may delay disease progression even further, and may be considered for patients who are intolerant to or failing intravenous therapy. However, systemic ganciclovir should be encouraged to reduce the risk of developing contralateral eye or end-organ CMV disease. Oral ganciclovir at 1 g tid is almost as effective as intravenous ganciclovir 5 mg/kg/day in delaying retinitis progression and is associated with fewer line-related complications. Absorption, drug interactions, cost and compliance should also be considered.CONCLUSIONS: Until recently, ganciclovir was available only for intravenous use. Recent developments allow for intraocular and oral administration of this agent. A clear understanding of the advantages and disadvantages of these new formulations is required in order to select the most appropriate product for managing CMV retinitis in AIDS patients.


2017 ◽  
Vol 34 (2) ◽  
pp. 92-99 ◽  
Author(s):  
Shaila Perveen ◽  
Mir Azimuddin Ahmed

Objective: To evaluate role of probiotics in human physiology, metabolism, health, immunity and GI disorders.It is important for gastroenterologists to improve their understanding of the mechanisms of probiotics and the evidence that support their use in clinical practice.Data Sources: A medline search (1948-December 2014) was conducted using GI diseases and probiotics as terms for identifying pertinent studies. Search limits included English language. Additional information was obtained from bibliographies.Data Selection And Data Extraction: The information provided is based on review of primary literature from randomized controlled trials (RCTs), meta-analyses, expert consensus panel recommendations and society-based practice recommendations. References are provided for more reading and figure summarizes key information about their mechanism of action.Data Synthesis: The need for objective, evidence-based guidance on the role of probiotics is becoming increasingly important as public awareness grows. This consensus is intended as a practical reference to help physicians make appropriate, evidence-based recommendations to patients who might benefit from probiotic treatment. Overall, the randomised, placebo-controlled trials included in this article support, with a high evidence level, the therapeutic effects of probiotic agents for several disorders including antibiotic or Clostridium difficile-associated diarrhea, irritable bowel syndrome, and the inflammatory bowel diseases. Although probiotic research is a rapidly evolving field, there are sufficient data to justify a trial of probiotics for treatment or prevention of some of these conditions. However, the capacity of probiotics to modify disease symptoms is likely to be modest and varies among probiotic strains and not all probiotics are right for all diseases. The goal of this review is to provide clinicians with an overview of the rationale and data which support or refute the role of probiotics for treating commonly encountered gastrointestinal disorders.J Bangladesh Coll Phys Surg 2016; 34(2): 92-99


2018 ◽  
Vol 53 (2) ◽  
pp. 186-194 ◽  
Author(s):  
Alexandra L. Bixby ◽  
Amy VandenBerg ◽  
Jolene R. Bostwick

Objective: This nonsystematic review describes risk of bleeding in treatment with serotonin reuptake inhibitors (SRIs) and provide recommendations for the management of patients at risk of bleeding. Data Sources: Articles were identified by English-language MEDLINE search published prior to June 2018 using the terms SRI, serotonin and noradrenaline reuptake inhibitors, OR antidepressive agents, AND hemorrhage OR stroke. Study Selection and Data Extraction: Meta-analyses were utilized to identify information regarding risk of bleeding with antidepressants. Individual studies were included if they had information regarding bleeding risk with specific SRIs, timing of risk, or risk with medications of interest. Data Synthesis: SRIs increase risk of bleeding by 1.16- to 2.36-fold. The risk is synergistic between SRIs and nonsteroidal anti-inflammatory drugs (NSAIDs; odds ratio [OR] range between studies 3.17-10.9). Acid-reducing medications may mitigate risk of gastrointestinal bleeds in chronic NSAIDs and SRI users (OR range between studies 0.98-1.1). Antidepressants with low or no affinity for the serotonin transporter, such as bupropion or mirtazapine, may be appropriate alternatives for patients at risk of bleeding. Relevance to Patient Care and Clinical Practice: This review includes data regarding bleeding risk for specific antidepressants, concomitant medications, and risk related to duration of SRI use. Considerations and evidence-based recommendations are provided for management of SRI users at high bleeding risk. Conclusions: Clinicians must be aware of the risk of bleeding with SRI use, especially for patients taking NSAIDs. Patient education is prudent for those prescribed NSAIDs and SRIs concurrently.


2012 ◽  
Vol 46 (10) ◽  
pp. 1349-1357 ◽  
Author(s):  
Victor Tuan Giam Chuang ◽  
Manabu Suno

Objective: To comprehensively review the literature regarding the efficacy, safety, and costs associated with the use of levoleucovorin in cancer treatment and to assess whether levoleucovorin would be a reasonable alternative to the use of racemic leucovorin. Data Sources: A MEDLINE search was conducted for English-language human studies published between January 1980 and April 2012 using the terms I-LV. levoleucovorin, d,I-LV, leucovorin, folinic acid, tolinate, 5-formyltetrahydrofolate, folic acid, folates, methotrexate, 5-fluorouracil, and clinical trials. Study Selection and Data Extraction: Articles pertinent to clinical trials (Phase 1, 2, 3) related to evaluating the efficacy, interchangeability, and safety of levoleucovorin were collected and their contents reviewed. Data Synthesis: From these pharmacokinetics and clinical studies, information on the use of levoleucovorin as a modulator of fluorouracil as well as when combined with other antitumor agents were scrutinized and extracted for comparison with leucovorin whenever possible. Two randomized Phase 3 clinical studies comparing the efficacy and adverse effect profiles of leucovorin and levoleucovorin demonstrated that levoleucovorin is as effective as leucovorin in terms of response, toxicity, and survival. Six randomized Phase 3 clinical studies demonstrated the safety and efficacy of levoleucovorin as a modulator of fluorouracil in combination with/without other antitumor agents in colorectal cancer patients. Levoleucovorin has been studied in other cancers. These clinical Phase 1/2/3 studies demonstrated efficacy and safety of levoleucovorin in combination chemotherapeutic regimens comprising fluorouracil and other antitumor agents. Conclusions: The results of the clinical studies suggest that levoleucovorin is efficacious and can be used safely in combination with fluorouracil and other antitumor agents. Levoleucovorin can be used interchangeably with leucovorin for modulating fluorouracil. The current shortage of the supply of leucovorin centered in North America renders levoleucovorin a reasonable alternative in terms of efficacy and toxicity profile, but from the perspective of cost, leucovorin remains the drug of choice.


1992 ◽  
Vol 26 (1) ◽  
pp. 46-55 ◽  
Author(s):  
Neeta Bahal ◽  
Milap C. Nahata

OBJECTIVE: To review the chemistry, antimicrobial spectrum, pharmacokinetics, clinical trials, adverse effects, and drug interactions of four new macrolide antibiotics: Azithromycin, clarithromycin, dirithromycin, and roxithromycin. DATA SOURCES: Information was obtained from comparative clinical trials, abstracts, conference proceedings, and review articles. Indexing terms included azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, and macrolide antibiotics. STUDY SELECTION: Emphasis was placed on comparative clinical trials involving the new macrolide antibiotics. DATA EXTRACTION: Data from human studies published in the English language were evaluated. Trials were assessed by sample size, macrolide dosage regimen, and therapeutic response. DATA SYNTHESIS: The erythromycins have gained widespread use in treating a variety of infections. Although they are effective, limitations include the need to administer four times a day and the intolerable adverse gastrointestinal effects. Four of the more extensively studied agents, azithromycin, clarithromycin, dirithromycin, and roxithromycin, are currently being studied in patients. Based on the studies to date, the newer macrolides may offer several advantages over erythromycin, including: (1) greater antimicrobial activity against certain organisms; (2) longer elimination half-life, thus allowing less frequent administration; and (3) lower incidence of adverse gastrointestinal effects. CONCLUSIONS: The new macrolide antibiotics appear to offer an improvement over erythromycin. Definitive conclusions about the role of these drugs should await completion of ongoing clinical studies.


1993 ◽  
Vol 27 (1) ◽  
pp. 61-67 ◽  
Author(s):  
Shawn M. Borcherding ◽  
Suzanne G. Meeves ◽  
Neil E. Klutman ◽  
Patricia A. Howard

OBJECTIVE: To critically evaluate the current literature regarding the role of calcium-channel antagonists in preventing atherosclerosis. DATA SOURCES: English language clinical studies, abstracts, conference proceedings, and review articles pertaining to calcium-channel antagonists and atherosclerosis. STUDY SELECTION: Relevant animal and human studies examining the role of calcium-channel antagonists in atherosclerosis prevention and treatment. DATA EXTRACTION: Potential mechanisms for the development of atherosclerosis and the use of calcium antagonists for preventing and treating coronary artery disease are discussed. Animal studies are summarized; next, significant data from human clinical studies are presented. DATA SYNTHESIS: Available studies are described and discussed. CONCLUSIONS: Results from animal and clinical trials in humans suggest that calcium antagonists may retard the development and progression of atherosclerosis. However, most clinical trials to date have been conducted in patients with proven atherosclerotic plaques. Further studies examining the role of calcium-channel antagonists in preventing and treating atherosclerosis are needed, but may be difficult to conduct because of the large numbers of patients required, long trial duration, and associated costs.


1997 ◽  
Vol 31 (5) ◽  
pp. 625-632 ◽  
Author(s):  
Bob L Lobo ◽  
William L Greene

OBJECTIVE: TO review the literature that compares Zolpidem with triazolam, with an emphasis on efficacy and safety in humans. DATA SOURCES: Information was retrieved from a MEDLINE search (1983–1996) of the English-language literature using the terms triazolam and zolpidem. STUDY SELECTION: Reports of clinical trials comparing the safety and efficacy of zolpidem and triazolam were included in this review. DATA EXTRACTION: Data were evaluated according to study design, efficacy, and adverse effects. Pertinent information was selected and the data synthesized into a review format. DATA SYNTHESIS: Zolpidem and triazolam have similar pharmacokinetic and pharmacodynamic effects in humans. Clinical trials have shown that usually recommended, equipotent dosages of zolpidem and triazolam do not differ with respect to pharmacokinetics, efficacy, tolerability, residual effects, memory impairment, rebound insomnia, abuse potential, or other adverse effects. CONCLUSIONS: Zolpidem offers no distinct therapeutic advantage over triazolam for the treatment of insomnia.


2018 ◽  
Vol 52 (12) ◽  
pp. 1238-1249 ◽  
Author(s):  
Joseph E. Cruz ◽  
Tania Ahuja ◽  
Mary Barna Bridgeman

Objective: To review the role of the sodium-glucose cotransporter-2 (SGLT2) inhibitors in the management of type 2 diabetes (T2DM), including the effects on renal and cardiovascular (CV) outcomes. Data Sources: A literature search of MEDLINE databases (1964 through May 2018) was conducted utilizing key words sodium-glucose co-transporter-2 inhibitors, SGLT2 inhibitors, and diabetes; additional limits for drug names were added. Study Selection and Data Extraction: Available English-language data from reviews, abstracts, presentations, and clinical trials of use of SGLT2 therapy specifically detailing outcomes on CV and renal disease in humans were reviewed. Data Synthesis: This review will explore the role of the SGLT2 inhibitors on CV and renal outcomes in patients with T2DM. Relevance to Patient Care and Clinical Practice: A paradigm shift regarding the regulation of medications for the treatment of T2DM has resulted in the need for CV outcomes data as part of the drug approval process. Reduction of major CV events and progression of nephropathy in patients with T2DM represent major outcomes of clinical significance. Few medications have been able to establish a reduction in these end points; data for the use of SGLT2 inhibitors are favorable in this regard. Conclusion: The SGLT2 inhibitors represents a class of medications that reduce glucose levels via a novel and complementary mechanism. Emerging evidence suggests a plausible explanation for the observed reduction in adverse renal and CV outcomes in recent clinical trials. Questions remain whether these agents reduce renal disease risk greater than achievement of the same glycemic goals as other antidiabetics and whether CV and renal benefits are reproducible in high-risk patients with chronic kidney disease.


1996 ◽  
Vol 30 (5) ◽  
pp. 507-513 ◽  
Author(s):  
Marie A Chisholm ◽  
Anthony L Mulloy ◽  
A Thomas Taylor

OBJECTIVE: TO review the pathogenesis and pharmacologic treatment of acute hypercalcemia associated with malignancy. DATA SOURCES: A MEDLINE search (1966 to 1995) of the English-language literature pertaining to acute hypercalcemia was performed. Additional literature was obtained from reference lists of articles identified through the search. STUDY SELECTION AND DATA EXTRACTION: All articles discussing the etiology and medical management of cancer-related acute hypercalcemia were considered in the review. Clinical trials reporting efficacy and safety of antihypercalcemic agents were also included. Information selected in the review was based on the discretion of the authors. DATA SYNTHESIS: Hypercalcemia is a life-threatening disorder associated with malignancy. It occurs in approximately 10–20% of patients with cancer. A variety of medications have been used in the management of hypercalcemia including bisphosphonates, calcitonin, furosemide, gallium nitrate, glucocorticoids, NaCl 0.9%, and plicamycin. Each of these agents has been reviewed with consideration of pharmacologic mechanism of action, evaluation of clinical trials, recommended dosages, efficacy, safety, cost, and role in treating cancer-related acute hypercalcemia. CONCLUSIONS: Immediate management of cancer-related acute hypercalcemia to prevent death and provide symptomatic relief is warranted. Severity determined by symptoms, calcium concentrations, and the overall status of the patient are important considerations in selecting appropriate therapy. Although the specific role of individual agents may vary, hydration remains the cornerstone of therapy. NaCl 0.9%, calcitonin, and Pamidronate disodium have established roles as dominant first-line agents for the management of acute hypercalcemia associated with malignancy.


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