Prophylaxis of migraine headaches with riboflavin: A systematic review.

WHAT IS KNOWN AND OBJECTIVE: Migraine headache is a relatively common, debilitating condition that costs our healthcare system over 78 billion dollars per year. Riboflavin has been advocated as a safe, effective prophylactic therapy for the prevention of migraines. The purpose of this study was to provide a systematic review of the current role of riboflavin in the prophylaxis of migraine headache. METHODS: A MEDLINE literature search inclusive of the dates 1966-2016 was performed using the search terms: riboflavin and migraine disorders. Excerpta Medica was searched from 1980 to 2016 using the search terms: riboflavin and migraine. Additionally, Web of Science was searched using the terms riboflavin and migraine inclusive of 1945-2016. Bibliographies of all relevant papers were reviewed for additional citations. We utilized the PRISMA guidelines to select English language, human, clinical trials of riboflavin as a single entity or in combination, review articles, and supporting pharmacokinetic and pharmacogenomic data assessing the efficacy and mechanism of riboflavin therapy in the prophylactic treatment of migraine headache. RESULTS AND DISCUSSION: A total of 11 clinical trials reveal a mixed effect of riboflavin in the prophylaxis of migraine headache. Five clinical trials show a consistent positive therapeutic effect in adults; four clinical trials show a mixed effect in paediatric and adolescent patients, and two clinical trials of combination therapy have not shown benefit. Adverse reactions with riboflavin have generally been mild. WHAT IS NEW AND CONCLUSION: Riboflavin is well tolerated, inexpensive and has demonstrated efficacy in the reduction of adult patient's migraine headache frequency. Additional data are needed, however, to resolve questions involving pharmacokinetic issues and pharmacogenomic implications of therapy.

Systematic review of topical amitriptyline for the treatment of neuropathic pain.

WHAT IS KNOWN AND OBJECTIVE: Neuropathic pain is a common disorder for which patients seek treatment. The most common causes of neuropathic pain are diabetes, herpetic infection and chemotherapy-induced neuropathy. Oral administration of amitriptyline has traditionally been used for treating neuropathic pain; however, it has dose-related anticholinergic effects, which may limit its use in some individuals. Pharmacotherapeutic agents that are commonly used to treat neuropathic pain include antidepressants, anticonvulsants, opioids and opioid-like substances, and topical medications. The objective of this paper is to review the effectiveness of topical amitriptyline in patients with neuropathic pain. METHODS: We utilized the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to provide a systematic and transparent reporting method. The literature search was performed using PubMed (1966 through October 2014) applying the MeSH 'amitriptyline' and 'drug administration, topical' and 'neuropathy'. Web of Science (1945 through October 2014) was searched using the text words 'amitriptyline' and 'neuropathy'. Bibliographies of retrieved articles were scanned for relevant articles. Cochrane databases were also searched for methods to treat neuropathic pain. Broad subject headings, including 'neuropathic pain', were used to search the database for review articles. All data sources in English and in humans were considered for inclusion. RESULTS AND DISCUSSION: Topical application of amitriptyline has the theoretical advantage of local effects with fewer systemic side effects. The clinical trials and case reports describing the use of topical amitriptyline we reviewed show mixed results concerning the efficacy and the presence of adverse reactions. Controlled clinical trials reveal that topical amitriptyline is not effective in treating neuropathic pain. The uncontrolled clinical trials did support efficacy of topical amitriptyline; however, the data from these trials may be biased due to the nature of the study design. Finally, there have been several case reports that claim patients achieved pain relief with the use of topical amitriptyline. Data from these cases are limited due to the fact that there were no controls to which the amitriptyline treatments could be compared, and the majority of the patients in these cases were on other analgesics. WHAT IS NEW AND CONCLUSION: Although there are reports that describe the benefits of topical amitriptyline for neuropathic pain, data from evidence-based controlled clinical trials do not support efficacy in patients who use topical amitriptyline for neuropathic pain control.

Psychopathy: clinical features, developmental basis and therapeutic challenges.

WHAT IS KNOWN AND OBJECTIVE: Psychopathy is a personality disorder characterized by deficits in personality and behaviour. Personality deficits are marked by interpersonal and affective facets, including pathological lying, grandiose sense of self-worth, lack of remorse and callousness. Behavioural deficits are defined by lifestyle and antisocial deficits, including impulsivity, parasitic lifestyle and poor behavioural controls. The objective of this review is to provide clinicians with (i) an appreciation of the clinical features of psychopathy, (ii) an understanding of the structural and functional derangements and the genetic and environmental factors which serve as the basis for the development of psychopathy and (iii) a summary of published reports of pharmacological approaches to the management of this disorder. METHODS: A literature search of MEDLINE/PubMed (1966-present) was conducted using the MeSH search terms psychopathy and antisocial personality disorder alone and in combination with the subheading drug therapy. Additional databases included Web of Science (1945-present) and International Pharmaceutical Abstracts (1970-present) using the text words psychopath and antisocial personality were searched. A search of Amazon books using the search terms psychopathy and sociopathy was also performed. Bibliographies of relevant articles were searched for additional citations. All data sources in English were considered for inclusion. For background information, broad subject headings were searched for review articles first. Human and animal drug therapy articles were evaluated giving preference to those papers using a controlled trial methodology. RESULTS AND DISCUSSION: Psychopathy is a personality disorder characterized by a lack of conscience, pathologic lying, manipulative behaviour and often superficial charm. The incidence of psychopathy in the general population is generally considered to be 0·6-4% with a higher proportion of males to females. Brain imaging studies of psychopaths suggest a smaller and less active amygdala and prefrontal cortex. There also appear to be physiological derangements in psychopathy, including alterations/dysregulation in neurotransmitter homeostasis (dopamine and serotonin), altered endocrine responses (testosterone and cortisol) and altered autonomic responses to emotional stimuli and stressors. Although both genetic and environmental factors likely contribute to the developmental basis of psychopathy, these factors are poorly understood at present. To date, limited studies with pharmacologic interventions in psychopathy are available and there are insufficient trials to determine efficacy. WHAT IS NEW AND CONCLUSION: Psychopathy is a serious personality disorder with profound negative effects on individuals and society. To design rational therapeutic strategies for this disorder, additional research is needed to discover the specific pathological and pathophysiological basis of psychopathy and to further elucidate the genetic and environmental factors responsible for psychopathic development. There is emerging evidence of phenotypic variants in psychopathy, including successful and unsuccessful types. It is important for clinicians to be cognizant of the psychopathic personality.

Retinoic acid syndrome: a review.

The retinoic acid syndrome (RAS) is an unpredictable but frequent complication which may develop after administration of all-trans retinoic acid (ATRA) most commonly in patients with acute promyelocytic leukaemia (APL). In this review, we describe the incidence, predictive factors, clinical course, outcome and treatment of RAS in patients with APL treated with ATRA. The incidence of RAS in patients receiving ATRA is about 14-16%, with an associated mortality of about 2%. Initial high white blood cell (WBC) count, rapidly increasing WBC count and/or the presence of the CD 13 expression on leukaemic cells may help in identifying patients likely to develop RAS. Concurrent chemotherapy will probably decrease the risk of developing RAS but often exacerbates bleeding, leading to leucocytosis, thrombocytopenia, disseminated intravascular coagulation and fibrinolysis. Prophylactic steroids are not recommended but prompt administration of steroids at the first sign of unexplained dyspnea, fever, weight gain or pulmonary infiltrate, is critical. Liposomal ATRA is being investigated to induce haematological cure in APL without chemotherapy and to reduce the incidence of RAS but further validation of its usefulness is necessary.

Prussian blue for treatment of radiocesium poisoning.

Prussian blue is a crystal lattice that exchanges potassium for cesium at the surface of the crystal. When given orally, it binds cesium that is secreted in the gut before it can be reabsorbed. Data suggest that in humans, Prussian blue can reduce cesium's half-life by approximately 43% and reduce total body burdens. Prussian blue is well tolerated at a dosage of 3 g/day with appropriate monitoring of serum potassium levels and observing for signs of constipation. Clinical data on the efficacy of Prussian blue in the management of radiocesium poisoning were evaluated. Articles published in English describing distribution and elimination of cesium in both humans and animals were reviewed, along with articles describing administration of Prussian blue in clinical toxicology.

Identification and Etiology of Visible Quiescent Infections of Monilinia fructicola and Botrytis cinerea in Sweet Cherry Fruit.

Visible quiescent infections were detected as small (<1 mm) necrotic flecks on green cv. Bing cherry fruit and as reddish halos surrounding tannish spots (1 to 2 mm) on immature, yellow-pink cv. Rainier cherry fruit in commercial orchards in California. Monilinia fructicola or Botrytis cinerea, the fungal pathogens causing brown rot and gray mold of cherry fruit, respectively, were isolated from most of the viable infections. M. fructicola was isolated more frequently from quiescent infections than B. cinerea in two years of the study, whereas similar isolation frequencies for both fungi were obtained in the other two years of sampling from one commercial Rainier cherry orchard. Using immature-pink Bing fruit that were inoculated in the laboratory, significantly more visible quiescent infections than active decay were reproduced in 6-, 9-, or 12-h wetness-period treatments after inoculation as compared to 18- or 24-h wetness periods where more active decay developed. Non-visible quiescent infections of M. fructicola or B. cinerea of immature Bing and Rainier fruit collected 2 weeks before harvest were identified on surface-sterilized, paraquat-treated fruit. In both years of the study, significantly more brown rot and gray mold occurred on the surface-sterilized, paraquat-treated fruit than on the non-treated or surface-sterilized fruit, indicating the presence of non-visible quiescent infections by these fungi in cherry fruit. Thus, for the first time, we demonstrated the presence of visible quiescent infections caused by M. fructicola and B. cinerea and we confirmed the occurrence of non-visible quiescent infections in sweet cherry fruit in California.

Drug-induced nightmares.

OBJECTIVE: To compile and assess the English-language literature on drug-induced nightmares, excluding nightmares secondary to drug withdrawal or drug-associated night terrors. DATA SOURCES: Published articles, letters, case reports, and abstracts in English were identified by MEDLINE (1966-May 1998) searches using the search term nightmares, chemically induced. Additional articles were obtained from bibliographies of retrieved articles. DATA EXTRACTION: All case reports of drug-induced nightmares were evaluated using the Naranjo algorithm for causality. Clinical studies of drugs that reported nightmares as an adverse effect were assessed for frequency of occurrence. DATA SYNTHESIS: Nightmares, defined as nocturnal episodes of intense anxiety and fear associated with a vivid, emotionally charged dream experience, are generally classified as a parasomnia. Possible pharmacologic mechanisms for drug-induced nightmares, such as REM suppression and dopamine receptor stimulation, are reviewed. However, the vast majority of therapeutic agents implicated in causing nightmares have no obvious pharmacologic mechanism. CONCLUSIONS: Assessing causality with an event such as a nightmare is difficult because of the high incidence of nightmares in the healthy population. Using qualitative, quantitative, and possible pharmacologic mechanism criteria, it appears that sedative/hypnotics, beta-blockers, and amphetamines are the therapeutic modalities most frequently associated with nightmares. These drug classes have a plausible pharmacologic mechanism to explain this effect. Dopamine agonists also have evidence of causality, with dopamine receptor stimulation as a possible pharmacologic mechanism.

The addition of antibiotics to fibrin glue.

Fibrin glue is composed of two separate solutions of fibrinogen and thrombin. When mixed together, these two solutions mimic the final stages of the clotting cascade to form a fibrin clot. Because the resulting fibrin patch is a good medium for microbial growth, the addition of antibiotics to one of the components of fibrin glue has been shown to reduce postoperative infections. Seventeen different antibiotics have been investigated in vitro. Of the 17, cefotaxime, mezlocillin, gentamicin, neomycin, and polymixin B, when added to fibrin glue, can decrease the rate of clot formation or the strength of the resultant fibrin clot. Further work is necessary to characterize the effect the addition of antibiotics has on the rate and strength of fibrin clotting and to determine what effect low systemic levels of antibiotics might have on antibiotic resistance patterns.

Drug-induced hiccups.

Pharmacotherapeutic agents are uncommonly associated with hiccups. Corticosteroids and benzodiazepines have been the drug classes mentioned most frequently in the literature as being associated with the development of hiccups. However, by using a strict criterion, there is currently insufficient evidence for any drug to be considered causative in the etiology of hiccups.

Drug-induced pure red cell aplasia.

Pure red cell aplasia (PRCA) is an uncommon hematologic disorder characterized by the absence of erythroblasts in otherwise normal bone marrow. It is commonly an autoimmune disorder sometimes associated with a congenital error. It may also be acquired in association with thymomas, hematologic malignancies, human parvovirus B19 infection, drugs, and other disease states. Thirty drugs have been implicated as causative in PRCA, but most literature reports describe only one or two patients. Data evaluating possible mechanisms of drug-induced PRCA are extremely limited, with conflicting results from different investigators. The criteria we used were at least five patients reported, reports from at least three separate investigators, and a minimum of one case of probable causality or better using a published assessment scale. With these criteria, phenytoin, azathioprine, and isoniazid had sufficient evidence of causality. All three are documented causes of PRCA and should be considered in any case of selective erythrocyte aplasia.

Publication rates in U.S. schools and colleges of pharmacy, 1976-1992.

To establish publication rates of U.S. schools and colleges of pharmacy (SCOP) for 1976-1992, we obtained data from the Science Citation Index (SCI) Corporate Index. The SCI data base covers the top 4500 journals in the technical and scientific fields. Citations were counted without regard to publication type (letter, abstract, review, etc.). Duplicative publications were eliminated. Faculty counts were obtained from the American Association of Colleges of Pharmacy Roster of Faculty and Staff for the inclusive years. Total publications for all schools increased over 100% from 1976 to 1992, and the number of faculty members increased by 40% during that time. However, only 12 (16%) of the SCOP averaged 50 or more publications/year, whereas 43 (59%) averaged fewer than 20. Data were also normalized by full-time faculty members. Only 13 (18%) SCOP averaged 1.0 or more publication/faculty/year, and 38 (52%) averaged fewer than 0.5. Publication rates were greater for medical center-based than for nonmedical center-based SCOP (p < 0.05), and for public than for private SCOP (p < 0.05). These data suggest that over half of the existing SCOP are minimally productive, generating less than 20 publications/year or 0.5 publication/faculty/year.

Local analgesia with opioid drugs.

These data suggest the presence of peripheral opioid receptors that are involved in the clinical perception of pain. This is a radical change in our traditional thinking of opioid pharmacology and pain management. Most clinicians have been taught that opioids work through the central nervous system. These new data depart from this traditionally held view of an exclusively central site of action. Further data, specifically, additional dose-response data with varying amounts of morphine, additional studies in pain syndromes other than knee arthroscopy, and the development and pharmacology of orally active opioid compounds that do not cross the central nervous system, are necessary to confirm and expand the present findings. The possibility of providing opioid pain relief free of central nervous system adverse effects is an exciting prospect. Additional studies of topical opioid preparations also would be of interest.

Opiate antagonists for the treatment of schizophrenia.

Numerous studies suggest that opiate antagonists may have antipsychotic properties. A review of the literature describing the use of naloxone to treat schizophrenic patients has shown mixed results. The three studies on naltrexone have found no benefit in controlling auditory hallucinations. We present a synopsis of these studies.

Drug-induced lichen planus.

Lichen planus is a relatively common skin disorder of unknown etiology. A wide variety of drugs have been implicated in its cause. Using five or more cases of drug-induced lichen planus reported in at least three separate reports with at least one case of probable cause by the scale of Naranjo et al as criteria, sufficient evidence exists that beta-blockers, methyldopa, penicillamine, quinidine, and quinine play a role in this disorder. Evidence is insufficient for angiotensin-converting enzyme inhibitors, sulfonylurea agents, carbamazepine, gold, lithium, and a host of miscellaneous drugs. Given available epidemiologic evidence, nonsteroidal antiinflammatory agents probably should also be considered causative. Differentiating drug-induced lichen planus from the idiopathic disorder is difficult; most evidence is based on the dechallenge and rechallenge with the drug when these data are available.

Dexrazoxane in the prevention of doxorubicin-induced cardiotoxicity.

OBJECTIVE: To review doxorubicin-induced cardiotoxicity and to evaluate the use of dexrazoxane in its prevention. DATA SOURCES: All animal and human reports involving doxorubicin-induced cardiac adverse effects were searched using MEDLINE combined with a fan search of relevant papers. DATA EXTRACTION: Animal, in vitro cellular, and human data are thoroughly reviewed with particular emphasis on doxorubicin-induced cardiotoxicity, including clinical manifestations, risk factors, and mechanisms of toxicity. The role of dexrazoxane in the prevention of doxorubicin-induced cardiotoxicity is reviewed, including mechanism of effect, animal data, and human trials. DATA SYNTHESIS: Anthracyclines are associated with a cumulative, dose-dependent, irreversible cardiomyopathy that can lead to congestive heart failure and death. The incidence of cardiotoxicity rises sharply at a total lifetime dose of more than 550 mg/m2. Through its semiquinone metabolite, doxorubicin appears to generate superoxide anion and superhydroxide free radicals with iron as a cofactor. Because of poor myocardial concentrations of superoxide dismutase, catalase, and glutathione peroxidase, these free radicals cause extensive lipid peroxidation and mitochondrial destruction. CONCLUSIONS: Dexrazoxane is hydrolyzed to its active form intracellularly and binds iron to prevent the formation of superhydroxide radicals, thus preventing mitochondrial destruction. The effect of dexrazoxane on the prevention of doxorubicin-induced cardiotoxicity is impressive in both animal and human studies. Further research is needed to clearly demonstrate the effect dexrazoxane has on the antitumor effects of combination chemotherapy while defining optimal dosing strategies to minimize myelosuppression and maximize cardioprotection.