Bimatoprost – a review

Bimatoprost is a synthetic prostamide analog that is efficacious in the treatment of open-angle glaucoma, ocular hypertension and other forms of glaucoma. It reduces intraocular pressure (IOP) by increasing uveoscleral and trabecular outflow. When used as a 0.03% topical preparation once daily, it demonstrates sustained lowering of IOP of 7 – 8 mmHg over a 24-h period. The drug has been found to be more effective than timolol. In some studies it has shown greater ability to lower IOP when compared with other prostaglandin analogs; whereas in others all three clinically used prostaglandin analogs were found to be equally effective. It shows good IOP reduction when used in combination with other glaucoma medications. A common side effect includes mild conjunctival hyperemia, which is generally reversible. Other side effects include periorbital pigmentation, discomfort, ocular surface hyperemia and skin changes. Pharmacoeconomic data indicate that bimatoprost is cost effective in the treatment of open-angle glaucoma.     

Hydrogen sulfide prodrugs—a review

Hydrogen sulfide (H₂S) is recognized as one of three gasotransmitters together with nitric oxide (NO) and carbon monoxide (CO). As a signaling molecule, H₂S plays an important role in physiology and shows great potential in pharmaceutical applications. Along this line, there is a need for the development of H₂S prodrugs for various reasons. In this review, we summarize different H₂S prodrugs, their chemical properties, and some of their potential therapeutic applications.KEY WORDS: Hydrogen sulfide (H₂S), Gasotransmitters, H₂S prodrugs, H₂S-hybrid nonsteroidal anti-inflammatory drugs, Controllable H₂S prodrugs, Hydrolysis-based H₂S prodrugs     

Fragrance material review on β-methoxy-benzeneethanol

A toxicologic and dermatologic review of β-methoxy-benzeneethanol when used as a fragrance ingredient is presented. β-methoxy-benzeneethanol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for β-methoxy-benzeneethanol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, phototoxicity, and photoallergy data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al., 2012 for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances.     

Fragrance material review on α-methylbenzyl alcohol

A toxicologic and dermatologic review of α-methylbenzyl alcohol when used as a fragrance ingredient is presented. α-Methylbenzyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a secondary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for α-methylbenzyl alcohol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, toxicokinetics, repeated dose, genotoxicity, and carcinogenicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances.     

Lentiviral-mediated gene transfer – a patent review

Background: Lentiviral vectors are at the forefront of gene delivery systems for research and clinical applications. This special position is mainly due to their capacity to transduce slow dividing and non-dividing cells, to insert large genetic constructs in the host chromatin, and to sustain stable long-term transgene expression. Objective: To review the current literature and patents concerning the lentiviral system, the safety improvements, the production and purification of lentiviral vectors, pseudotyping and preclinical and clinical studies to provide expert opinion about the use of lentiviral vectors for gene therapy. Methods: The National Library of Medicine (PubMed) was searched for studies investigating the lentiviral system and the patents were searched at the World Intellectual Property Organization, European Patent Office and US Patent Office websites/databases. Results/conclusion: Based on the literature, several improvements have been performed regarding the safety, pseudotyping, vector production and purification on the lentivirus system. Clinical trials are underway for five different disorders.     

Fragrance material review on α-isobutylphenethyl alcohol

A toxicologic and dermatologic review of α-isobutylphenethyl alcohol when used as a fragrance ingredient is presented. α-Isobutylphenethyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a secondary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for α-isobutylphenethyl alcohol were evaluated then summarized and includes physical properties, skin sensitization, and repeated dose data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances.     

Fragrance material review on β-methylphenethyl alcohol

A toxicologic and dermatologic review of β-methylphenethyl alcohol when used as a fragrance ingredient is presented. β-Methylphenethyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for β-methylphenethyl alcohol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, toxicokinetics, repeated dose, and genotoxicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances.     

Bentonite toxicology and epidemiology – a review

Bentonite, a clay with numerous industrial and consumer applications, is mined and processed in many countries of the world. Its many beneficial uses also create the potential for widespread occupational and consumer exposure. The available studies on toxicity and epidemiology indicate that the principal exposure pathway of concern is inhalation of respirable dust by occupationally exposed cohorts. Bentonite itself is probably not more toxic than any other particulate not otherwise regulated and is not classified as a carcinogen by any regulatory or advisory body, but some bentonite may contain variable amounts of respirable crystalline silica, a recognized human carcinogen. Therefore, prudent management and adherence to occupational exposure limits is appropriate. This review summarizes the literature available on production, applications, exposure, toxicity, and epidemiology of bentonite and identifies data gaps and limitations.     

Fragrance material review on α-propylphenethyl alcohol

A toxicologic and dermatologic review of α-propylphenethyl alcohol when used as a fragrance ingredient is presented. α-Propylphenethyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a secondary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for α-propylphenethyl alcohol were evaluated then summarized and includes physical properties, acute toxicity, and genotoxicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances.     

Digoxin: Pharmacology and toxicology—A review

Digoxin is a cardiac glycoside used as drug in case of heart problems, including congestive heart failure, atrial fibrillation or flutter, and certain cardiac arrhythmias. It has a very narrow therapeutic window of the medication. Digoxin is toxic substance with well known cardiotoxic effect. In this work, pharmacology and toxicology of digoxin are summarized; Its pharmacokinetics, pharmacodynamics, available acute toxicity data (different species, different administration routes) are summarized in this article. Moreover, its treatment side effect and human poisonings are thoroughly discussed. Finally, appropriate therapy regimen is proposed.     

Treatment of Guillain-Barré syndrome: a review

Guillain-Barré syndrome is a frequently post-infectious, autoimmune acute inflammatory polyradiculoneuropathy affecting all age groups. It typically results in rapid-onset weakness symmetrically affecting proximal and distal muscles. Cranial muscles are not infrequently affected and respiratory muscle weakness requiring mechanical ventilation occurs in 25% of cases. The incidence is around 1-2 per 100,000/year. Various clinical, electrophysiological and immunological subtypes are described. Plasma exchanges (PE) and intravenous immunoglobulins (IVIg) represent the main treatment options. PE were shown to be effective on rate of recovery in randomized trials. Subsequently further trials have demonstrated the equivalence of IVIg. IVIg are frequently the preferred option for practical reasons. Treatment can result in reversible clinical fluctuations which need to be readily recognized. Although number of PE appears to be optimally of 4, except in mildly affected patients where only 2 may suffice, the dosage of IVIg conventionally administered (2 g/kg) may be sub-optimal in some patients. This may relate to a relationship between IVIg pharmacokinetics and clinical outcome. Studies are under way to evaluate the usefulness of a second IVIg course in severely-affected GBS patients. There is no evidence for use of corticosteroids in GBS. Both IVIg and PE are costly and despite their use and established effectiveness, there is still a need for new treatments to lessen disability. Further research is warranted in optimizing currently available therapies as well as finding others to effectively improve the management of this potentially devastating condition.     

α2C-adrenoceptor modulators: a patent review

INTRODUCTION: α2-Adrenoceptors (α2-ARs) are membrane proteins belonging to the superfamily of GPCRs. Detailed studies have shown three different subtypes, namely α2A, α2B and α2C. Although numerous α2-AR ligands exist, only a small set of compounds have shown even a degree of selectivity among the three α2-AR subtypes. Moreover, these compounds suffer from binding to receptor sites outside the α2-AR subfamily. Efforts made to understand the biological significance of each α2-AR subtype have greatly been assisted by genetically engineered mice. The main results obtained suggest that α2C-AR stimulation may represent a therapeutic strategy to get an analgesic response with reduced sedative effects and undesirable changes in blood pressure due to α2A-AR activation. AREAS COVERED: This review summarizes the patent literature about the development of α2C-AR modulators from 2000 to early 2010 and their therapeutic effects evoked by the interaction with this receptor subtype. EXPERT OPINION: Over 90 patents have been deposited in the last 10 years regarding different methods of α2C-AR modulation (use of agonists or antagonists, nucleic acids and polypeptides) for diagnosis, prognosis and treatment of disorders involving this receptor. Nevertheless, despite the numerous published patents, ligands highly selective for the α2C-AR subtype, which continues to be enigmatic, are lacking.     

Homotoxicology—a review of randomised clinical trials

Aim Homotoxicology is a form of therapy that uses homoeopathically diluted remedies with a view of eliminating toxins from the body. It is not a therapeutic method based on accepted scientific principles or biological plausibility. Yet numerous clinical studies have claimed efficacy. The aim of this systematic review is to summarise and critically evaluate the evidence from rigorous clinical trials of this form of therapy.Methods Seven electronic databases were searched for all studies of homotoxicological medicines for any human condition. To be included, trials had to be randomised and placebo-controlled. Data from such studies were validated and extracted according to pre-defined criteria. Their methodological quality was formally assessed using the Jadad score. Key data of all included trials were tabulated and summarised in narrative form.Results Seven trials met our inclusion criteria. Their Jadad scores indicated mostly a high methodological standard. The trials tested the efficacy of seven different medicines for seven different indications. The results were positive in all but one study. Important flaws were found in all trials. These render the results of the primary studies less reliable than their high Jadad scores might suggest.Conclusion Despite mostly positive findings and high ratings on the Jadad score, the placebo-controlled, randomised clinical trials of homotoxicology fail to demonstrate the efficacy of this therapeutic approach.     

Do practice guidelines augment drug utilisation review?

Drug utilisation review (DUR) or drug use evaluation (DUE) studies or programmes are intended to detect and/or correct inappropriate drug use. Appropriateness can be assessed at 3 levels: (i) whether any medication is warranted, or whether either no therapy or nondrug therapy is preferred (level 1); (ii) assuming drug therapy is indicated, which of several alternative drugs is the preferred choice? (level 2); and (iii) appropriateness of the drug regimen, including dosage, duration, type and frequency of monitoring, and drug interactions (level 3). The traditional approach to DUR/DUE has been to begin the appropriateness evaluation after a drug is prescribed. However, changes in healthcare organisation provide the basis for a disease-management or health-maintenance approach to DUR/DUE, and practice guidelines afford a possible source for guiding such studies. We hypothesised that the latter approach to DUR/DUE would be more likely to result in evaluation of level 1 drug-therapy issues than the traditional DUR/DUE approach. We tested this hypothesis by reviewing 56 practice guidelines involving drug therapy and also reviewed research studies published from 1992 to 1996. We found that studies that used the traditional DUR/DUE approach were most likely to examine level 3 drug-therapy issues, never addressed level 1 issues, and typically evaluated adherence to provider- or study team-developed guidelines rather than published guidelines. In contrast, the disease- or health-management approach nearly always examined level 1 issues, seldom addressed level 3 issues, and almost always evaluated adherence to a published practice guideline. Regardless of the DUR/DUE approach, about 40% of studies evaluated level 2 issues. The guidelines themselves were much more likely to include recommendations about level 1 and level 2 issues than about level 3 issues; however, even when a guideline included level 2 or level 3 issues, studies of adherence to the guideline rarely assessed anything beyond level 1 issues. This suggests that guideline recommendations about level 2 and level 3 issues may be too imprecise for use in evaluative studies. The drug-information compendia, on the other hand, provide detailed recommendations about level 3 issues. Revision of drug compendia may be warranted to include recommendations about all levels of drug-therapy issues. The results of intervention studies to improve drug-therapy compliance with guidelines suggest that information provided at the time of prescribing, information presented by local health professionals and information provided with a large amount of provider contact may be more likely to demonstrate significant improvements in drug therapy. We conclude that practice guidelines are a useful resource for augmenting DUR/DUE but that challenges to optimising their use include whether they can be kept current, acceptable and accessible to providers.     

Biologically active quinazoline derivatives — A patent review

Pharmaceutical Chemistry Journal -     

Does pharmacist-led medication review help to reduce hospital admissions and deaths in older people? A systematic review and meta-analysis

We set out to determine the effects of pharmacist-led medication review in older people by means of a systematic review and meta-analysis covering 11 electronic databases. Randomized controlled trials in any setting, concerning older people (mean age > 60 years), were considered, aimed at optimizing drug regimens and improving patient outcomes. Our primary outcome was emergency hospital admission (all cause). Secondary outcomes were mortality and numbers of drugs prescribed. We also recorded data on drug knowledge, adherence and adverse drug reactions. We retrieved 32 studies which fitted the inclusion criteria. Meta-analysis of 17 trials revealed no significant effect on all-cause admission, relative risk (RR) of 0.99 [95% confidence interval (CI) 0.87, 1.14, P  = 0.92], with moderate heterogeneity (I² = 49.5, P  = 0.01). Meta-analysis of mortality data from 22 trials found no significant benefit, with a RR of mortality of 0.96 (95% CI 0.82, 1.13, P  = 0.62), with no heterogeneity (I² = 0%). Pharmacist-led medication review may slightly decrease numbers of drugs prescribed (weighted mean difference = −0.48, 95% CI −0.89, −0.07), but significant heterogeneity was found (I² = 85.9%, P  < 0.001). Results for additional outcomes could not be pooled, but suggested that interventions could improve knowledge and adherence. Pharmacist-led medication review interventions do not have any effect on reducing mortality or hospital admission in older people, and can not be assumed to provide substantial clinical benefit. Such interventions may improve drug knowledge and adherence, but there are insufficient data to know whether quality of life is improved.     

Treatment–resistant panic disorder: a systematic review

Introduction: The prevalence of panic disorder (PD) in the population is high and these patients have work impairment, high unemployment rates, seek medical treatment more frequently and have more hospitalizations than people without panic symptoms. Despite the availability of pharmacological, psychological and combined treatments, approximately one-third of all PD patients have persistent panic attacks and other PD symptoms after treatment.

Areas covered: MEDLINE/Pubmed, CENTRAL, PsycINFO and Web of Science databases were searched for clinical trials in treatment–resistant PD. Only studies published between 1980 and 2015, in English, with human subjects, considered “journal articles” and clinical trial were included. We included trials recruiting only adult subjects with treatment–resistant PD, consistent with criteria from DSM-III to DSM5. We included all prospective experimental studies. Case, case series, retrospective studies or studies with <10 PD subjects were not included.

Expert opinion: Only 11 articles were included in this review. There were few quality studies, only two were randomized, controlled and double blind. Augmentation of the pharmacological treatment with cognitive-behavioral therapy demonstrated some short-term efficacy in treatment–resistant PD. There were also preliminary evidences of efficacy for monotherapy with reboxetine and olanzapine, and augmentation with pindolol, divalproex sodium, aripiprazole and olanzapine in short-term treatment.