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Sample records for acute drug administration

  1. An example of US Food and Drug Administration device regulation: medical devices indicated for use in acute ischemic stroke.

    PubMed

    Peña, Carlos; Li, Khan; Felten, Richard; Ogden, Neil; Melkerson, Mark

    2007-06-01

    The Food and Drug Administration has established requirements for protecting the public health by assuring the safety and effectiveness of a variety of medical products including drugs, devices, and biological products, and for promoting public health by expediting the approval of treatments that are safe and effective. The Center for Devices and Radiological Health is the center within the agency that is responsible for pre- and postmarket regulation of medical devices. In this article, we review current regulation of medical devices, research and development programs, pre- and postmarket perspectives, and future considerations of medical devices, particularly as they relate to devices targeting acute ischemic stroke as an example of the process. We also review the Center for Devices and Radiological Health's historical perspective of acute ischemic stroke trials and clinical trial design considerations used in prior studies that have led to US market clearance as they are related to currently marketed devices indicated for acute ischemic stroke.

  2. Acute Administration of Dopaminergic Drugs has Differential Effects on Locomotion in Larval Zebrafish

    PubMed Central

    Irons, T.D.; Kelly, P.; Hunter, D.L.; MacPhail, R.C.; Padilla, S.

    2013-01-01

    Altered dopaminergic signaling causes behavioral changes in mammals. In general, dopaminergic receptor agonists increase locomotor activity, while antagonists decrease locomotor activity. In order to determine if zebrafish (a model organism becoming popular in pharmacology and toxicology) respond similarly, the acute effects of drugs known to target dopaminergic receptors in mammals were assessed in zebrafish larvae. Larvae were maintained in 96-well microtiter plates (1 larva/well). Non-lethal concentrations (0.2–50 µM) of dopaminergic agonists (apomorphine, SKF-38393, and quinpirole) and antagonists (butaclamol, SCH-23390, and haloperidol) were administered at 6 days post-fertilization (dpf). An initial experiment identified the time of peak effect of each drug (20–260 minutes post-dosing, depending on the drug). Locomotor activity was then assessed for 70 minutes in alternating light and dark at the time of peak effect for each drug to delineate dose-dependent effects. All drugs altered larval locomotion in a dose-dependent manner. Both the D1- and D2-like selective agonists (SKF-38393 and quinpirole, respectively) increased activity, while the selective antagonists (SCH-23390 and haloperidol, respectively) decreased activity. Both selective antagonists also blunted the response of the larvae to changes in lighting conditions at higher doses. The nonselective drugs had biphasic effects on locomotor activity: apomorphine increased activity at the low dose and at high doses, while butaclamol increased activity at low to intermediate doses, and decreased activity at high doses. This study demonstrates that (1) larval zebrafish locomotion can be altered by dopamine receptor agonists and antagonists, (2) receptor agonists and antagonists generally have opposite effects, and (3) drugs that target dopaminergic receptors in mammals appear, in general, to elicit similar locomotor responses in zebrafish larvae. PMID:23274813

  3. Drug Education for Administrators

    ERIC Educational Resources Information Center

    Hackett, Peter; McKeon, Thomas L.

    1976-01-01

    The formulation of a drug policy and the implementation of that policy in a firm but fair manner are the responsibility of the school administrator. Authors give serious consideration to this responsibility. (Editor/RK)

  4. Food and Drug Administration

    MedlinePlus

    ... blog post. April 11, 2017 ‘Organs-on-Chips’ Technology: FDA Testing Groundbreaking Science More FDA Voice Blog ... FEAR Act Site Map Nondiscrimination Website Policies U.S. Food and Drug Administration 10903 New Hampshire Avenue Silver ...

  5. Drug Enforcement Administration.

    ERIC Educational Resources Information Center

    Department of Justice, Washington, DC.

    This fact sheet contains information relating to drug abuse and abusers; drug traffic legislation; law enforcement; and descriptions of commonly used narcotics, stimulants, depressants, and hallucinogens. Also included is a short but explicit listing of audiovisual aids, an annotated bibliography, and drug identification pictures. The booklet…

  6. Healthcare professionals’ views of the use and administration of two salvage therapy drugs for acute ulcerative colitis: a nested qualitative study within the CONSTRUCT trial

    PubMed Central

    Clement, Clare; Rapport, Frances; Seagrove, Anne; Alrubaiy, Laith; Williams, John

    2017-01-01

    Objectives Insight into healthcare professionals’ views and experiences of the use of ciclosporin and infliximab as salvage therapies for acute ulcerative colitis (UC) and how this may affect participation in a comparison trial is lacking. The study aimed to capture views and opinions of healthcare professionals about the two drugs within the CONSTRUCT trial. Design An interview-based qualitative study using Framework Analysis embedded within an open-label, pragmatic randomised trial. Setting National Health Service Health Boards and Trusts, including large teaching and district hospitals in England, Scotland and Wales. Participants Principal Investigators (PIs) for trial sites (who were all consultant gastroenterologists) and nurses responsible for administering and monitoring the salvage therapy drugs across trial sites. 15 PIs and 8 nurses recruited from a range of sites stratified by site recruitment rates were interviewed. Results Interviews revealed that professionals made judgements regarding the salvage therapies largely based on experience of giving the two drugs and perceptions of effectiveness and adverse side effects. A clear preference for infliximab among nurses was revealed, largely based on experiences of administration and drug handling, with some doctors strongly favouring infliximab based on experience of prescribing the drug as well as patient views and the existing evidence base. Most doctors were more equivocal, and all were prepared to suspend preferences and wait for evidence of effectiveness and safety from the CONSTRUCT trial. PIs also questioned guidelines around drug use and restrictions placed on personal autonomy in delivering best patient care. Conclusions Findings highlight healthcare professionals’ preference for the salvage treatment, infliximab in treating steroid-resistant UC, largely based on resource intensive nursing requirements of intravenous administration of ciclosporin. Not all doctors expressed this preference, being

  7. Food and Drug Administration

    MedlinePlus

    ... Reportable Food Registry Report an Emergency Report Suspected Criminal Activity For Industry: Drugs and Therapeutic Biologics News & ... FDA Organization FDA Basics Advisory Committees International Programs Criminal Investigations Emergency Preparedness & Response Working at FDA Training/ ...

  8. Acute stroke therapy with tissue plasminogen activator (tPA) since it was approved by the U.S. Food and Drug Administration (FDA).

    PubMed

    Zivin, Justin A

    2009-07-01

    Tissue plasminogen activator (tPA) for acute ischemic stroke was approved by the U.S. Food and Drug Administration (FDA) in 1996. Since then it has been severely underutilized. At the time when most practitioners were first being exposed to the literature concerning tPA, there were many concerns about safety and the restrictions on use were quite onerous. Since then a good deal of further work has been done to loosen the restrictions and allay concerns about the risks. The true risk to benefit ratio is far better than is generally realized. Now it is mostly economic problems related to the costs of constantly supplying emergency care that is limiting access. Furthermore, in the current litigious environment, failure to treat is likely to be a more hazardous course of action than legal exposure due to poor outcomes. It must be emphasized that the drug is quite safe and highly effective, and current utilization rates are unacceptably low. Ann Neurol 2009;66:6-10.

  9. Drugs and drug administration in extreme environments.

    PubMed

    Küpper, Thomas E A H; Schraut, Bettina; Rieke, Burkhard; Hemmerling, Arnica-Verena; Schöffl, Volker; Steffgen, Juergen

    2006-01-01

    Emergency medicine must often cope with harsh climates far below freezing point or high temperatures, and sometimes, an alternative to the normal route of drug administration is necessary. Most of this information is not yet published. Therefore, we summarized the information about these topics for most drugs used in medical emergencies by combining literature research with extensive personal communications with the heads of the drug safety departments of the companies producing these drugs. Most drugs can be used after temperature stress of limited duration. Nevertheless, we recommend replacing them at least once per year or after extreme heat. Knowledge about drugs used in extreme environments will be of increasing importance for medical personnel because in an increasingly mobile society, more and more people, and especially elderly -often with individual medical risks-travel to extreme regions such as tropical or arctic regions or to high altitude, and some of them need medical care during these activities. Because of this increasing need to use drugs in harsh climates (tourism, expeditions, peace corps, military, etc) the actual International Congress of Harmonization recommendations should be added with stability tests at +50 degrees C, freezing and oscillating temperatures, and UV exposure to simulate the storage of the drugs at "outdoor conditions."

  10. 77 FR 61417 - Guidance for Industry on Acute Bacterial Sinusitis: Developing Drugs for Treatment; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-09

    ...: Developing Drugs for Treatment; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice... entitled ``Acute Bacterial Sinusitis: Developing Drugs for Treatment.'' This guidance addresses FDA's... an indication for the treatment of acute bacterial sinusitis (ABS). This guidance finalizes...

  11. Mass drug administration for malaria

    PubMed Central

    Poirot, Eugenie; Skarbinski, Jacek; Sinclair, David; Kachur, S Patrick; Slutsker, Laurence; Hwang, Jimee

    2013-01-01

    Background Mass drug administration (MDA), defined as the empiric administration of a therapeutic antimalarial regimen to an entire population at the same time, has been a historic component of many malaria control and elimination programmes, but is not currently recommended. With renewed interest in MDA and its role in malaria elimination, this review aims to summarize the findings from existing research studies and program experiences of MDA strategies for reducing malaria burden and transmission. Objectives To assess the impact of antimalarial MDA on population asexual parasitaemia prevalence, parasitaemia incidence, gametocytaemia prevalence, anaemia prevalence, mortality and MDA-associated adverse events. Search methods We searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE+, EMBASE, to February 2013. We also searched CABS Abstracts, LILACS, reference lists, and recent conference proceedings. Selection criteria Cluster-randomized trials and non-randomized controlled studies comparing therapeutic MDA versus placebo or no MDA, and uncontrolled before-and-after studies comparing post-MDA to baseline data were selected. Studies administering intermittent preventive treatment (IPT) to sub-populations (for example, pregnant women, children or infants) were excluded. Data collection and analysis Two authors independently reviewed studies for inclusion, extracted data and assessed risk of bias. Studies were stratified by study design and then subgrouped by endemicity, by co-administration of 8-aminoquinoline plus schizonticide drugs and by plasmodium species. The quality of evidence was assessed using the GRADE approach. Main results Two cluster-randomized trials, eight non-randomized controlled studies and 22 uncontrolled before-and-after studies are included in this review. Twenty-two studies (29 comparisons) compared MDA to placebo or no intervention of which two comparisons were

  12. 76 FR 82311 - Food and Drug Administration Transparency Initiative: Food and Drug Administration Report on Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-30

    ... and Drug Administration Report on Good Guidance Practices: Improving Efficiency and Transparency... announcing the availability of a report entitled ``Food and Drug Administration Report on Good Guidance... Office of the Commissioner prepared a report entitled ``Food and Drug Administration Report on...

  13. Effects of acute caffeine administration on adolescents.

    PubMed

    Temple, Jennifer L; Dewey, Amber M; Briatico, Laura N

    2010-12-01

    Acute caffeine administration has physiological, behavioral, and subjective effects. Despite its widespread use, few studies have described the impact of caffeine consumption in children and adolescents. The purpose of this study was to investigate the effects of acute caffeine administration in adolescents. We measured cardiovascular responses and snack food intake after acute administration of 0 mg, 50 mg, 100 mg, and 200 mg of caffeine. We also compared usual food intake and subjective effects of caffeine between high- and low-caffeine consumers. Finally, we conducted a detailed analysis of caffeine sources and consumption levels. We found main effects of caffeine dose on heart rate (HR) and diastolic blood pressure (DBP), with HR decreasing and DBP increasing with increasing caffeine dose. There were significant interactions among gender, caffeine use, and time on DBP. High caffeine consumers (>50 mg/day) reported using caffeine to stay awake and drinking coffee, tea, soda, and energy drinks more than low consumers (<50 mg/day). Boys were more likely than girls to report using getting a rush, more energy, or improved athletic performance from caffeine. Finally, when we examined energy and macronutrient intake, we found that caffeine consumption was positively associated with laboratory energy intake, specifically from high-sugar, low-fat foods and also positively associated with protein and fat consumption outside of the laboratory. When taken together, these data suggest that acute caffeine administration has a broad range of effects in adolescents and that the magnitude of these effects is moderated by gender and chronic caffeine consumption.

  14. 78 FR 69133 - Drug Enforcement Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-18

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug... renewal to the Drug Enforcement Administration (DEA) to be registered as a bulk manufacturer of the following basic classes of controlled substances: Drug Schedule Tetrahydrocannabinols (7370) I...

  15. Effect of solcoseryl on antitumour action and acute toxicity of some antineoplastic drugs.

    PubMed

    Danysz, A; Sołtysiak-Pawluczuk, D; Czyzewska-Szafran, H; Jedrych, A; Jastrzebski, Z

    1991-01-01

    The in vivo effect of Solcoseryl on the antitumour activity and acute toxicity of some antineoplastic drugs was examined. It was found that Solcoseryl does not inhibit the antineoplastic effectiveness of the drugs against transplantable P 388 leukaemia in mice. Studies of the effect of Solcoseryl on acute toxicity of selected antineoplastic drugs in mice revealed that the biostimulator could exert a modifying influence. The prior administration of Solcoseryl significantly decreases the acute toxicity of methotrexate but has no effect on acute toxicity of 5-fluorouracil, increases the acute toxicity of bleomycin and vinblastine and has no effect on acute toxicity of methotrexate and mitoxantron. On the other hand, Solcoseryl administered simultaneously with the antineoplastic drugs increases acute toxicity of 5-fluorouracil, bleomycin and mitoxantron. The protective effect of the biostimulator noted exclusively against acute toxicity of 5-fluorouracil was also observed after multiple administration of this anticancer drug.

  16. The effects of heroin administration and drug cues on impulsivity.

    PubMed

    Jones, Jermaine D; Vadhan, Nehal P; Luba, Rachel R; Comer, Sandra D

    2016-08-01

    Drug addiction is a chronic relapsing disorder characterized by compulsive drug seeking and continued use despite negative consequences. Behavioral impulsivity is a strong predictor of the initiation and maintenance of drug addiction. Preclinical data suggest that heroin may exacerbate impulsive characteristics in an individual but this has yet to be assessed in clinical samples. The current secondary data analysis sought to investigate the effects of heroin on impulsivity along with the effects of exposure to drug cues. Using the current data set, we also tentatively assessed the etiological relationship between impulsivity and heroin abuse. Sixteen heroin-dependent participants were recruited to complete Immediate Memory Task/Delayed Memory Task (IMT/DMT) and GoStop tasks following repeated heroin administration, following acute heroin administration, and following a drug cue exposure session. Four preceding days of active heroin availability, compared to four preceding days of placebo drug availability, increased impulsivity assessed using the IMT and DMT. Presentation of drug cues similarly acted to increase impulsivity assessments on all three tasks. It also appears that heavier users were more susceptible to the influence of drug cues on impulsivity. The present study represents a step toward a more comprehensive understanding of the interaction between opioid abuse and impulsivity. A better understanding of these factors could provide critical insight into the maintenance of heroin use and relapse.

  17. 75 FR 22599 - Draft Guidance for Industry and Food and Drug Administration Staff; Food and Drug Administration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-29

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration Staff; Food and Drug Administration and Industry Procedures for Section 513(g) Requests for Information Under the Federal Food, Drug, and Cosmetic Act AGENCY: Food and Drug Administration, HHS. ACTION:...

  18. Acute immune-mediated thrombocytopenia due to oxaliplatin administration: a case report.

    PubMed

    Pietrantonio, Filippo; Di Bartolomeo, Maria; Buzzoni, Roberto; Bajetta, Emilio

    2010-01-01

    Drug-induced acute thrombocytopenia is an extremely rare side effect that may occur immediately after oxaliplatin infusion. This potentially fatal reaction is immune mediated and can be anticipated by mild hemorrhagic signs during previous administrations. This is the first report of acute thrombocytopenia occurring during adjuvant treatment of colorectal cancer with oxaliplatin. Clinicians should be aware of this adverse event in order to prevent possible serious consequences and stop further oxaliplatin administration.

  19. Despite Federal Legislation, Shortages Of Drugs Used In Acute Care Settings Remain Persistent And Prolonged.

    PubMed

    Chen, Serene I; Fox, Erin R; Hall, M Kennedy; Ross, Joseph S; Bucholz, Emily M; Krumholz, Harlan M; Venkatesh, Arjun K

    2016-05-01

    Early evidence suggests that provisions of the Food and Drug Administration Safety and Innovation Act of 2012 are associated with reductions in the total number of new national drug shortages. However, drugs frequently used in acute unscheduled care such as the care delivered in emergency departments may be increasingly affected by shortages. Our estimates, based on reported national drug shortages from 2001 to 2014 collected by the University of Utah's Drug Information Service, show that although the number of new annual shortages has decreased since the act's passage, half of all drug shortages in the study period involved acute care drugs. Shortages affecting acute care drugs became increasingly frequent and prolonged compared with non-acute care drugs (median duration of 242 versus 173 days, respectively). These results suggest that the drug supply for many acutely and critically ill patients in the United States remains vulnerable despite federal efforts.

  20. 78 FR 63220 - Guidance for Industry on Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-23

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Acute Bacterial Skin and Skin... guidance for industry entitled ``Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for... drugs to treat acute bacterial skin and skin structure infections (ABSSSI). This guidance finalizes...

  1. Drug induced acute pancreatitis: incidence and severity.

    PubMed Central

    Lankisch, P G; Dröge, M; Gottesleben, F

    1995-01-01

    To determine the incidence and severity of drug induced acute pancreatitis, data from 45 German centres of gastroenterology were evaluated. Among 1613 patients treated for acute pancreatitis in 1993, drug induced acute pancreatitis was diagnosed in 22 patients (incidence 1.4%). Drugs held responsible were azathioprine, mesalazine/sulfasalazine, 2',3'-dideoxyinosine (ddI), oestrogens, frusemide, hydrochlorothiazide, and rifampicin. Pancreatic necrosis not exceeding 33% of the organ was found on ultrasonography or computed tomography, or both, in three patients (14%). Pancreatic pseudocysts did not occur. A decrease of arterial PO2 reflecting respiratory insufficiency, and an increase of serum creatinine, reflecting renal insufficiency as complications of acute pancreatitis were seen in two (9%) and four (18%) patients, respectively. Artificial ventilation was not needed, and dialysis was necessary in only one (5%) case. Two patients (9%) died of AIDS and tuberculosis, respectively; pancreatitis did not seem to have contributed materially to their death. In conclusion, drugs rarely cause acute pancreatitis, and drug induced acute pancreatitis usually runs a benign course. PMID:7489946

  2. Orbitofrontal response to drug-related stimuli after heroin administration.

    PubMed

    Walter, Marc; Denier, Niklaus; Gerber, Hana; Schmid, Otto; Lanz, Christian; Brenneisen, Rudolf; Riecher-Rössler, Anita; Wiesbeck, Gerhard A; Scheffler, Klaus; Seifritz, Erich; McGuire, Philip; Fusar-Poli, Paolo; Borgwardt, Stefan

    2015-05-01

    The compulsion to seek and use heroin is frequently driven by stress and craving during drug-cue exposure. Although previous neuroimaging studies have indicated that craving is mediated by increased prefrontal cortex activity, it remains unknown how heroin administration modulates the prefrontal cortex response. This study examines the acute effects of heroin on brain function in heroin-maintained patients. Using a crossover, double-blind, placebo-controlled design, 27 heroin-maintained patients performed functional magnetic resonance imaging 20 minutes after the administration of heroin or placebo (saline) while drug-related and neutral stimuli were presented. Images were processed and analysed with statistical parametric mapping. Plasma concentrations of heroin and its main metabolites were assessed using high-performance liquid chromatography. Region of interest analyses showed a drug-related cue-associated blood-oxygen-level-dependent activation in the orbitofrontal cortex (OFC) in heroin-dependent patients during both treatment conditions (heroin and placebo). This activation of the OFC was significantly higher after heroin than after placebo administration. These findings may indicate the importance of OFC activity for impulse control and decision-making after regular heroin administration and may emphasize the benefit of the heroin-assisted treatment in heroin dependence.

  3. 21 CFR 20.107 - Food and Drug Administration manuals.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Food and Drug Administration manuals. 20.107... Administration manuals. (a) Food and Drug Administration administrative staff manuals and instructions that affect a member of the public are available for public disclosure. An index of all such manuals...

  4. Glutamatergic Mechanisms of Comorbidity Between Acute Stress and Cocaine Self-administration

    PubMed Central

    Garcia-Keller, Constanza; Kupchik, Yonatan; Gipson, Cassandra D; Brown, Robyn M; Spencer, Sade; Bollati, Flavia; Esparza, Maria A; Roberts-Wolfe, Doug; Heinsbroek, Jasper; Bobadilla, Ana-Clara; Cancela, Liliana M; Kalivas, Peter W

    2015-01-01

    There is substantial comorbidity between stress disorders and substance use disorders (SUDs), and acute stress augments the locomotor stimulant effect of cocaine in animal models. Here we endeavor to understand the neural underpinnings of comorbid stress disorders and drug use by determining if the glutamatergic neuroadaptations that characterize cocaine self-administration are induced by acute stress. Rats were exposed to acute (2 h) immobilization stress and 3 weeks later the nucleus accumbens core was examined for changes in glutamate transport, glutamate mediated synaptic currents, and dendritic spine morphology. We also determined if acute stress potentiated the acquisition of cocaine self-administration. Acute stress produced an enduring reduction in glutamate transport, and potentiated excitatory synapses on medium spiny neurons. Acute stress also augmented the acquisition of cocaine self-administration. Importantly, by restoring glutamate transport in the accumbens core with ceftriaxone the capacity of acute stress to augment the acquisition of cocaine self-administration was abolished. Similarly, ceftriaxone treatment prevented stress-induced potentiation of cocaine-induced locomotor activity. However, ceftriaxone did not reverse stress-induced synaptic potentiation, indicating that this effect of stress exposure did not underpin the increased acquisition of cocaine self-administration. Reversing acute stress-induced vulnerability to self-administer cocaine by normalizing glutamate transport poses a novel treatment possibility for reducing comorbid SUDs in stress disorders. PMID:26821978

  5. 77 FR 71803 - Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-04

    ... HUMAN SERVICES Food and Drug Administration Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug Products--Questions and Answers; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing...

  6. Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice

    PubMed Central

    Amin, Bahareh; Nakhsaz, Alireza; Hosseinzadeh, Hossein

    2015-01-01

    Objective: The present study was designed to investigate the putative antidepressant effects of crocin and crocetin, two major active ingredients of Crocus sativus L. (saffron) using mice in two different regimens of acute and sub-acute administration. Material and Methods: In acute treatment, antidepressant-like activities of crocin and crocetin (10, 20 and 40 mg/kg, i.p.) were evaluated using forced swim test (FST). In sub-acute study (21 times with 24-h intervals), antidepressant-like effects of oral administration of drugs were examined using FST and tail suspension test (TST). Locomotor activity and motor coordination were studied using open field and rotarod tests, respectively. Results: Acute treatment with crocin (40 mg/kg) and crocetin (20 and 40 mg/kg) produced antidepressant-like effect in FST without affecting the baseline locomotion in mice. Sub-acute oral administration of crocin significantly decreased immobility time only at the highest dose (100 mg/kg). Crocetin (12.5, 25 and 50 mg/kg) was able to decrease immobility time in FST and TST. Locomotor activity and coordination of mice were not affected by crocin or crocetin. Conclusion: Since higher doses of crocin was required to show antidepressant effects, more efficacy of crocetin may be concluded. This observation provides further support for metabolism of crocin to crocetin following oral administration. PMID:26468466

  7. The Use of Drugs to Reduce Hearing Loss Following Acute Acoustic Trauma

    DTIC Science & Technology

    2013-10-15

    1 AD_________________ Award Number: W81XWH-10-1-0485 TITLE: The Use of Drugs to Reduce Hearing Loss Following Acute Acoustic...Final 25 June 2010 – 24 October 2013 3. DATES COVERED 4. TITLE AND SUBTITLE The Use of Drugs to Reduce Hearing Loss Following Acute Acoustic Trauma...was to apply the same drug administration protocol to groups of animals exposed to a lower level continuous noise. Data from the treated and control

  8. 21 CFR 20.107 - Food and Drug Administration manuals.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Food and Drug Administration manuals. 20.107 Section 20.107 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.107 Food and...

  9. 21 CFR 20.107 - Food and Drug Administration manuals.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Food and Drug Administration manuals. 20.107 Section 20.107 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.107 Food and...

  10. 21 CFR 20.107 - Food and Drug Administration manuals.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Food and Drug Administration manuals. 20.107 Section 20.107 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.107 Food and...

  11. Adverse Drug Events caused by Serious Medication Administration Errors

    PubMed Central

    Sawarkar, Abhivyakti; Keohane, Carol A.; Maviglia, Saverio; Gandhi, Tejal K; Poon, Eric G

    2013-01-01

    OBJECTIVE To determine how often serious or life-threatening medication administration errors with the potential to cause patient harm (or potential adverse drug events) result in actual patient harm (or adverse drug events (ADEs)) in the hospital setting. DESIGN Retrospective chart review of clinical events that transpired following observed medication administration errors. BACKGROUND Medication errors are common at the medication administration stage for hospitalized patients. While many of these errors are considered capable of causing patient harm, it is not clear how often patients are actually harmed by these errors. METHODS In a previous study where 14,041 medication administrations in an acute-care hospital were directly observed, investigators discovered 1271 medication administration errors, of which 133 had the potential to cause serious or life-threatening harm to patients and were considered serious or life-threatening potential ADEs. In the current study, clinical reviewers conducted detailed chart reviews of cases where a serious or life-threatening potential ADE occurred to determine if an actual ADE developed following the potential ADE. Reviewers further assessed the severity of the ADE and attribution to the administration error. RESULTS Ten (7.5% [95% C.I. 6.98, 8.01]) actual adverse drug events or ADEs resulted from the 133 serious and life-threatening potential ADEs, of which 6 resulted in significant, three in serious, and one life threatening injury. Therefore 4 (3% [95% C.I. 2.12, 3.6]) serious and life threatening potential ADEs led to serious or life threatening ADEs. Half of the ten actual ADEs were caused by dosage or monitoring errors for anti-hypertensives. The life threatening ADE was caused by an error that was both a transcription and a timing error. CONCLUSION Potential ADEs at the medication administration stage can cause serious patient harm. Given previous estimates of serious or life-threatening potential ADE of 1.33 per 100

  12. Exploring network theory for mass drug administration.

    PubMed

    Chami, Goylette F; Molyneux, David H; Kontoleon, Andreas A; Dunne, David W

    2013-08-01

    Network theory is a well-established discipline that uses mathematical graphs to describe biological, physical, and social systems. The topologies across empirical networks display strikingly similar organizational properties. In particular, the characteristics of these networks allow computational analysis to contribute data unattainable from examining individual components in isolation. However, the interdisciplinary and quantitative nature of network analysis has yet to be exploited by public health initiatives to distribute preventive chemotherapies. One notable application is the 2012 World Health Organization (WHO) Roadmap for Neglected Tropical Diseases (NTDs) where there is a need to upscale distribution capacity and to target systematic noncompliers. An understanding of local networks for analysing the distributional properties of community-directed treatment may facilitate sustainable expansion of mass drug-administration (MDA) programs.

  13. Drugs under preclinical and clinical study for treatment of acute and chronic lymphoblastic leukemia

    PubMed Central

    Jacob, Joe Antony; Salmani, Jumah Masoud Mohammad; Chen, Baoan

    2016-01-01

    Targeted therapy has modernized the treatment of both chronic and acute lymphoblastic leukemia. The introduction of monoclonal antibodies and combinational drugs has increased the survival rate of patients. Preclinical studies with various agents have resulted in positive outputs with Phase III trial drugs and monoclonal antibodies entering clinical trials. Most of the monoclonal antibodies target the CD20 and CD22 receptors. This has led to the approval of a few of these drugs by the US Food and Drug Administration. This review focuses on the drugs under preclinical and clinical study in the ongoing efforts for treatment of acute and chronic lymphoblastic leukemia. PMID:27382259

  14. The Clinical Course of a Drug-induced Acute Dystonic Reaction in the Emergency Room

    PubMed Central

    Marano, Massimo; di Biase, Lazzaro; Salomone, Gaetano; Di Santo, Alessandro; Montiroli, Annalisa; Di Lazzaro, Vincenzo

    2016-01-01

    Background Acute dystonic reactions following the administration of safe, reliable drugs can occur and must be promptly recognized and treated in the emergency room. Phenomenology Shown The entire clinical course of an acute dystonic reaction due to metoclopramide, from early motor signs to full-blown clinical symptoms and resolution. Educational Value Providing elements for early recognition of a drug-induced movement disorder phenomenology. PMID:28105387

  15. Altered prefrontal connectivity after acute heroin administration during cognitive control.

    PubMed

    Schmidt, André; Borgwardt, Stefan; Gerber, Hana; Schmid, Otto; Wiesbeck, Gerhard A; Riecher-Rössler, Anita; Bendfeldt, Kerstin; Smieskova, Renata; Lang, Undine E; Rubia, Katya; Walter, Marc

    2014-09-01

    Neuroimaging studies have reported reduced activity in a broad network of brain regions during response inhibition in heroin-dependent patients. However, how heroin in an acute dose modulates the neural correlates of response inhibition and the underlying brain connectivity has not yet been investigated. In this double-blind placebo-controlled study, we used functional magnetic resonance imaging to examine whether acute heroin administration changed whole brain activity during response inhibition in 26 heroin-dependent patients. We then applied dynamic causal modelling to investigate the effect of an acute dose of heroin on the functional interactions between the dorsal anterior cingulate cortex (dACC) and the bilateral inferior frontal gyri (IFG). Heroin acutely reduced dACC activity, as well as the inhibition-induced modulation of connectivity from the dACC to the right IFG compared with placebo. Furthermore, dACC activity was positively related to false alarm rates after placebo but not heroin administration. These results suggest that acute heroin administration impairs cognitive control in dependent patients by reducing the activity in the dACC activity and the functional connectivity from the dACC to the right IFG.

  16. 75 FR 14448 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-25

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical Practices; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. SUMMARY: The Food and Drug Administration (FDA) Los...

  17. 77 FR 49448 - Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-16

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The Food and Drug Administration (FDA), Baltimore District Office,...

  18. 77 FR 10537 - Food and Drug Administration/Xavier University Global Medical Device Conference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-22

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration/Xavier University Global Medical Device Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. SUMMARY: The Food and Drug Administration (FDA) Cincinnati District, in cosponsorship with...

  19. 77 FR 20826 - Guidance for Industry and Food and Drug Administration Staff; Food and Drug Administration and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-06

    ... the Federal Food, Drug, and Cosmetic Act; Availability AGENCY: Food and Drug Administration, HHS... Procedures for Section 513(g) Requests for Information under the Federal Food, Drug, and Cosmetic Act.'' This... Section 513(g) Requests for Information under the Federal Food, Drug, and Cosmetic Act'' to the...

  20. [Anatomophysiological bases of drug administration. Dosage forms and routes of administration].

    PubMed

    Carillo Norte, Juan Antonio; Gañán Presmanes, Yolanda

    2010-12-01

    The administration of the right dose to the right patient is of paramount importance to obtain an optimal drug response within the scope of clinical pharmacology and tailored medicine. The marketing of safer and more efficient drug entities, along with the development of new drug administration devices provide a major boost for the diagnosis and treatment of diseases, beyond our imagination. However dose adjustment is not enough to produced the desired effect, and drug therapy should include an appropriate route of drug administration. Currently, there are many different and sophisticated methods to incorporate drugs into the patients that nurses should be familiar with. When there is no contraindication, oral route of drug administration is of choice and most frequently used as a physiological pathway of drug intake.

  1. A review of human drug self-administration procedures

    PubMed Central

    Jones, Jermaine D.; Comer, Sandra D.

    2014-01-01

    Drug self-administration procedures in laboratory settings allow us to closely model drug-taking behavior in real-world settings. This review provides an overview of many of the common self-administration methods used in human laboratory research. Typically, self-administration studies provide a quantifiable measure of the reinforcing effect of a drug, which is believed to be predictive of its potential for abuse. Several adaptations of the self-administration paradigm exist, the simplest of which allows participants free access to the drug under investigation. Free-access procedures allow investigators to observe patterns of drug self-administration and drug effects in a controlled setting. Allowing participants to choose between two simultaneously available reinforcers (choice procedures) is another well-established method of assessing the reinforcing effects of a drug. Offering a choice between two reinforcers (e.g. two different doses of the same drug, two different drugs, or drug and nondrug reinforcers) provides researchers with a point of comparison (e.g. between a drug of known abuse potential and a novel drug). When combined with other endpoints, such as subjective effects ratings, physiological responses, and cognitive performance, human self-administration paradigms have contributed significantly to our understanding of the factors that contribute to, maintain, and alter drug-taking behavior including: craving, positive subjective effects, toxicity, drug interactions and abstinence. This area of research has also begun to incorporate other techniques such as imaging and genetics to further understand the multifaceted nature of substance abuse. The present paper summarizes the different self-administration techniques that are commonly used today and the application of other procedures that may complement interpretation of the drug PMID:23839027

  2. Animal models of social contact and drug self-administration.

    PubMed

    Strickland, Justin C; Smith, Mark A

    2015-09-01

    Social learning theories of drug abuse propose that individuals imitate drug use behaviors modeled by social peers, and that these behaviors are selectively reinforced and/or punished depending on group norms. Historically, animal models of social influence have focused on distal factors (i.e., those factors outside the drug-taking context) in drug self-administration studies. Recently, several investigators have developed novel models, or significantly modified existing models, to examine the role of proximal factors (i.e., those factors that are immediately present at the time of drug taking) on measures of drug self-administration. Studies using these newer models have revealed several important conclusions regarding the effects of social learning on drug abuse: 1) the presence of a social partner influences drug self-administration, 2) the behavior of a social partner determines whether social contact will increase or decrease drug intake, and 3) social partners can model and imitate specific patterns of drug self-administration. These findings are congruent with those obtained in the human laboratory, providing support for the cross-species generality and validity of these preclinical models. This mini-review describes in detail some of the preclinical animal models used to study social contact and drug self-administration to guide future research on social learning and drug abuse.

  3. 77 FR 11553 - Draft Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-27

    ... good manufacturing practices (CGMP) for PET drugs. The procedures were finalized and an implementation... HUMAN SERVICES Food and Drug Administration Draft Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug Products--Questions and Answers; Availability AGENCY: Food and...

  4. 78 FR 48691 - Food and Drug Administration Patient Network Annual Meeting; Demystifying Food and Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-09

    ...; Demystifying Food and Drug Administration: An Exploration of Drug Development Hosted by the Food and Drug... registration fee for this conference. Early registration is suggested because space is limited. The...

  5. United States Food and Drug Administration Product Label Changes

    PubMed Central

    Sung, Julie C.; Stein-Gold, Linda; Goldenberg, Gary

    2016-01-01

    Once a drug has been approved by the United States Food and Drug Administration and is on the market, the Food and Drug Administration communicates new safety information through product label changes. Most of these label changes occur after a spontaneous report to either the drug manufacturing companies or the Food and Drug Administration MedWatch program. As a result, 400 to 500 label changes occur every year. Actinic keratosis treatments exemplify the commonality of label changes throughout the postmarket course of a drug. Diclofenac gel, 5-fluorouracil cream, imiquimod, and ingenol mebutate are examples of actinic keratosis treatments that have all undergone at least one label revision. With the current system of spontaneous reports leading to numerous label changes, each occurrence does not necessarily signify a radical change in the safety of a drug. PMID:26962391

  6. United States Food and Drug Administration Product Label Changes

    PubMed Central

    Sung, Julie C.; Stein-Gold, Linda; Goldenberg, Gary

    2017-01-01

    Once a drug has been approved by the United States Food and Drug Administration and is on the market, the Food and Drug Administration communicates new safety information through product label changes. Most of these label changes occur after a spontaneous report to either the drug manufacturing companies or the Food and Drug Administration MedWatch program. As a result, 400 to 500 label changes occur every year. Actinic keratosis treatments exemplify the commonality of label changes throughout the postmarket course of a drug. Diclofenac gel, 5-fluorouracil cream, imiquimod, and ingenol mebutate are examples of actinic keratosis treatments that have all undergone at least one label revision. With the current system of spontaneous reports leading to numerous label changes, each occurrence does not necessarily signify a radical change in the safety of a drug. PMID:28367259

  7. United States Food and Drug Administration Product Label Changes.

    PubMed

    Kircik, Leon; Sung, Julie C; Stein-Gold, Linda; Goldenberg, Gary

    2017-02-01

    Once a drug has been approved by the United States Food and Drug Administration and is on the market, the Food and Drug Administration communicates new safety information through product label changes. Most of these label changes occur after a spontaneous report to either the drug manufacturing companies or the Food and Drug Administration MedWatch program. As a result, 400 to 500 label changes occur every year. Actinic keratosis treatments exemplify the commonality of label changes throughout the postmarket course of a drug. Diclofenac gel, 5-fluorouracil cream, imiquimod, and ingenol mebutate are examples of actinic keratosis treatments that have all undergone at least one label revision. With the current system of spontaneous reports leading to numerous label changes, each occurrence does not necessarily signify a radical change in the safety of a drug.

  8. United States Food and Drug Administration Product Label Changes.

    PubMed

    Kircik, Leon; Sung, Julie C; Stein-Gold, Linda; Goldenberg, Gary

    2016-01-01

    Once a drug has been approved by the United States Food and Drug Administration and is on the market, the Food and Drug Administration communicates new safety information through product label changes. Most of these label changes occur after a spontaneous report to either the drug manufacturing companies or the Food and Drug Administration MedWatch program. As a result, 400 to 500 label changes occur every year. Actinic keratosis treatments exemplify the commonality of label changes throughout the postmarket course of a drug. Diclofenac gel, 5-fluorouracil cream, imiquimod, and ingenol mebutate are examples of actinic keratosis treatments that have all undergone at least one label revision. With the current system of spontaneous reports leading to numerous label changes, each occurrence does not necessarily signify a radical change in the safety of a drug.

  9. 38 CFR 52.180 - Administration of drugs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2014-07-01 2014-07-01 false Administration of drugs... of drugs. The program management must assist with the management of medication and have a system for disseminating drug information to participants and program staff. (a) Procedures. (1) The program...

  10. 38 CFR 52.180 - Administration of drugs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Administration of drugs... of drugs. The program management must assist with the management of medication and have a system for disseminating drug information to participants and program staff. (a) Procedures. (1) The program...

  11. 38 CFR 52.180 - Administration of drugs.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2013-07-01 2013-07-01 false Administration of drugs... of drugs. The program management must assist with the management of medication and have a system for disseminating drug information to participants and program staff. (a) Procedures. (1) The program...

  12. 38 CFR 52.180 - Administration of drugs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2012-07-01 2012-07-01 false Administration of drugs... of drugs. The program management must assist with the management of medication and have a system for disseminating drug information to participants and program staff. (a) Procedures. (1) The program...

  13. 38 CFR 52.180 - Administration of drugs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Administration of drugs... of drugs. The program management must assist with the management of medication and have a system for disseminating drug information to participants and program staff. (a) Procedures. (1) The program...

  14. Drugs on the College Campus. A Guide for College Administrators.

    ERIC Educational Resources Information Center

    Nowlis, Helen H.

    This guide to drugs on the college campus provides accurate information to help administrators and other college officials understand and cope with the use of drugs by college students. The problem is defined, and facts about drugs, and the implications and issues occasioned by their use, are presented. Information is also offered in the following…

  15. Methamphetamine Self-Administration Acutely Decreases Monoaminergic Transporter Function

    PubMed Central

    McFadden, Lisa M.; Stout, Kristen A.; Vieira-Brock, Paula L.; Allen, Scott C.; Nielsen, Shannon M.; Wilkins, Diana G.; Hanson, Glen R.; Fleckenstein, Annette E.

    2014-01-01

    Numerous pre-clinical studies have demonstrated that non-contingent methamphetamine (METH) administration rapidly decreases both dopamine (DA) transporter (DAT) and vesicular monoamine-2 transporter (VMAT-2) function. Because of the importance of transporter function to the abuse and neurotoxic liabilities of METH, and previous research indicating that the effects of non-contingent METH treatment do not necessarily predict effects of contingent exposure, the present study examined the acute impact of METH self-administration on these transporters. Results revealed that five days of METH self-administration (4 h/session; 0.06 mg/infusion) decreased DAT and VMAT-2 activity, as assessed in synaptosomes and vesicles, respectively, prepared from striatal tissue 1 h after the final self-administration session. METH self-administration increased core body temperatures as well. Brain METH and amphetamine (AMPH) levels, assessed 1 h after the final self-administration session, were approximately twice greater in high-pressing rats compared to low-pressing rats despite similar changes in DAT function. In conclusion, the present manuscript is the first to describe transporter function and METH/AMPH levels after self-administration in rodents. These data provide a foundation to investigate complex questions including how the response of dopaminergic systems to METH self-administration contributes to contingent-related processes such as dependence. PMID:22120988

  16. Methamphetamine self-administration acutely decreases monoaminergic transporter function.

    PubMed

    McFadden, Lisa M; Stout, Kristen A; Vieira-Brock, Paula L; Allen, Scott C; Nielsen, Shannon M; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

    2012-03-01

    Numerous preclinical studies have demonstrated that noncontingent methamphetamine (METH) administration rapidly decreases both dopamine (DA) transporter (DAT) and vesicular monoamine-2 transporter (VMAT-2) function. Because of the importance of transporter function to the abuse and neurotoxic liabilities of METH, and previous research indicating that the effects of noncontingent METH treatment do not necessarily predict effects of contingent exposure, the present study examined the acute impact of METH self-administration on these transporters. Results revealed that five days of METH self-administration (4 h/session; 0.06 mg/infusion) decreased DAT and VMAT-2 activity, as assessed in synaptosomes and vesicles, respectively, prepared from striatal tissue 1 h after the final self-administration session. METH self-administration increased core body temperatures as well. Brain METH and amphetamine (AMPH) levels, assessed 1 h after the final self-administration session, were approximately twice greater in high-pressing rats compared to low-pressing rats despite similar changes in DAT function. In conclusion, the present manuscript is the first to describe transporter function and METH/AMPH levels after self-administration in rodents. These data provide a foundation to investigate complex questions including how the response of dopaminergic systems to METH self-administration contributes to contingent-related processes such as dependence.

  17. Evaluation of drug administration errors in a teaching hospital

    PubMed Central

    2012-01-01

    Background Medication errors can occur at any of the three steps of the medication use process: prescribing, dispensing and administration. We aimed to determine the incidence, type and clinical importance of drug administration errors and to identify risk factors. Methods Prospective study based on disguised observation technique in four wards in a teaching hospital in Paris, France (800 beds). A pharmacist accompanied nurses and witnessed the preparation and administration of drugs to all patients during the three drug rounds on each of six days per ward. Main outcomes were number, type and clinical importance of errors and associated risk factors. Drug administration error rate was calculated with and without wrong time errors. Relationship between the occurrence of errors and potential risk factors were investigated using logistic regression models with random effects. Results Twenty-eight nurses caring for 108 patients were observed. Among 1501 opportunities for error, 415 administrations (430 errors) with one or more errors were detected (27.6%). There were 312 wrong time errors, ten simultaneously with another type of error, resulting in an error rate without wrong time error of 7.5% (113/1501). The most frequently administered drugs were the cardiovascular drugs (425/1501, 28.3%). The highest risks of error in a drug administration were for dermatological drugs. No potentially life-threatening errors were witnessed and 6% of errors were classified as having a serious or significant impact on patients (mainly omission). In multivariate analysis, the occurrence of errors was associated with drug administration route, drug classification (ATC) and the number of patient under the nurse's care. Conclusion Medication administration errors are frequent. The identification of its determinants helps to undertake designed interventions. PMID:22409837

  18. 77 FR 49449 - Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-16

    ... drugs, devices, and biologics; as well as inspections of clinical investigators, IRBs, and research... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice; Public Workshop AGENCY: Food and Drug Administration, HHS....

  19. Retention of drug administration skills after intensive teaching.

    PubMed

    Wheeler, D W; Degnan, B A; Murray, L J; Dunling, C P; Whittlestone, K D; Wood, D F; Smith, H L; Gupta, A K

    2008-04-01

    We have identified deficiencies in medical students' drug administration skills, and we attempted to address them with interactive online teaching modules and simulated critical incident scenarios. Short-term improvements have been evident with this intensive effort, but medium-term retention of skills has not been measured. A drug administration lecture, an online module and a simulated emergency scenario were offered to final year clinical students. None of the teaching was compulsory but participation was recorded, along with students' simulator performances and marks in an objective structured practical examination 9 months later. A poor simulator score predicted a poor performance in the later examination. Participation in the simulated scenario only significantly improved examination scores when supplemented by online teaching (p = 0.002). Intensive drug administration teaching using an online module and high fidelity simulation improves drug administration skills in the medium term. Students found simulation much more engaging than online teaching.

  20. Empowering Malaria Vaccination by Drug Administration

    DTIC Science & Technology

    2010-01-01

    response with drugs that neutralize suppressive functions and potentiate protective responses. Chloroquine may be a first attractive candidate...However, sterile immunity is never observed in natura lly exposed popu- lations; adults living in e ndemic areas often harbor para- si tes albeit ar low ...NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND

  1. 78 FR 9928 - Food and Drug Administration Drug Shortages Task Force and Strategic Plan; Request for Comments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Drug Shortages Task Force and Strategic Plan; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION: Notice; request for comments. SUMMARY: To assist the Food and Drug Administration (FDA or Agency) in drafting a strategic...

  2. 78 FR 15019 - Food and Drug Administration Prescription Drug User Fee Act V Benefit-Risk Plan; Request for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-08

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Prescription Drug User Fee Act V Benefit-Risk Plan; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION: Notice, request for comments. SUMMARY: The Food and Drug Administration (FDA or the Agency) is announcing...

  3. Gaps in Drug Dosing for Obese Children: A Systematic Review of Commonly Prescribed Acute Care Medications

    PubMed Central

    Rowe, Stevie; Siegel, David; Benjamin, Daniel K.

    2015-01-01

    Purpose Approximately 1 out of 6 children in the United States is obese. This has important implications for drug dosing and safety, as pharmacokinetic (PK) changes are known to occur in obesity due to altered body composition and physiology. Inappropriate drug dosing can limit therapeutic efficacy and increase drug-related toxicity for obese children. Few systematic reviews examining PK and drug dosing in obese children have been performed. Methods We identified 25 acute care drugs from the Strategic National Stockpile and Acute Care Supportive Drugs List and performed a systematic review for each drug in 3 study populations: obese children (2–18 years of age), normal weight children, and obese adults. For each study population, we first reviewed a drug’s Food and Drug Administration (FDA) label, followed by a systematic literature review. From the literature, we extracted drug PK data, biochemical properties, and dosing information. We then reviewed data in 3 age subpopulations (2–7 years, 8–12 years, and 13–18 years) for obese and normal weight children and by route of drug administration (intramuscular, intravenous, by mouth, and inhaled). If sufficient PK data were not available by age/route of administration, a data gap was identified. Findings Only 2/25 acute care drugs (8%) contained dosing information on the FDA label for each obese children and adults compared with 22/25 (88%) for normal weight children. We found no sufficient PK data in the literature for any of the acute care drugs in obese children. Sufficient PK data were found for 7/25 acute care drugs (28%) in normal weight children and 3/25 (12%) in obese adults. Implications Insufficient information exists to guide dosing in obese children for any of the acute care drugs reviewed. This knowledge gap is alarming, given the known PK changes that occur in the setting of obesity. Future clinical trials examining the PK of acute care medications in obese children should be prioritized. PMID

  4. 21 CFR 20.107 - Food and Drug Administration manuals.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Section 20.107 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... affect a member of the public are available for public disclosure. An index of all such manuals is... Information Public Reading Room, located in rm. 1050, at the same address. The index and all manuals...

  5. Acute neuropsychological effects of MDMA and ethanol (co-)administration in healthy volunteers

    PubMed Central

    Wezenberg, E.; Valkenberg, M. M. G. J.; de Jong, C. A. J.; Buitelaar, J. K.; van Gerven, J. M. A.; Verkes, R. J.

    2008-01-01

    Rationale In Western societies, a considerable percentage of young people expose themselves to 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”). Commonly, ecstasy is used in combination with other substances, in particular alcohol (ethanol). MDMA induces both arousing as well as hallucinogenic effects, whereas ethanol is a general central nervous system depressant. Objective The aim of the present study is to assess the acute effects of single and co-administration of MDMA and ethanol on executive, memory, psychomotor, visuomotor, visuospatial and attention function, as well as on subjective experience. Materials and methods We performed a four-way, double-blind, randomised, crossover, placebo-controlled study in 16 healthy volunteers (nine male, seven female) between the ages of 18–29. MDMA was given orally (100 mg) and blood alcohol concentration was maintained at 0.6‰ by an ethanol infusion regime. Results Co-administration of MDMA and ethanol was well tolerated and did not show greater impairment of performance compared to the single-drug conditions. Impaired memory function was consistently observed after all drug conditions, whereas impairment of psychomotor function and attention was less consistent across drug conditions. Conclusions Co-administration of MDMA and ethanol did not exacerbate the effects of either drug alone. Although the impairment of performance by all drug conditions was relatively moderate, all induced significant impairment of cognitive function. PMID:18305926

  6. Acute caffeine administration affects zebrafish response to a robotic stimulus.

    PubMed

    Ladu, Fabrizio; Mwaffo, Violet; Li, Jasmine; Macrì, Simone; Porfiri, Maurizio

    2015-08-01

    Zebrafish has been recently proposed as a valid animal model to investigate the fundamental mechanisms regulating emotional behavior and evaluate the modulatory effects exerted by psychoactive compounds. In this study, we propose a novel methodological framework based on robotics and information theory to investigate the behavioral response of zebrafish exposed to acute caffeine treatment. In a binary preference test, we studied the response of caffeine-treated zebrafish to a replica of a shoal of conspecifics moving in the tank. A purely data-driven information theoretic approach was used to infer the influence of the replica on zebrafish behavior as a function of caffeine concentration. Our results demonstrate that acute caffeine administration modulates both the average speed and the interaction with the replica. Specifically, zebrafish exposed to elevated doses of caffeine show reduced locomotion and increased sensitivity to the motion of the replica. The methodology developed in this study may complement traditional experimental paradigms developed in the field of behavioral pharmacology.

  7. FDA reform signed into law. Food and Drug Administration.

    PubMed

    James, J S

    1997-12-05

    The laws under which the Food and Drug Administration (FDA) operates have been changed by bipartisan Congressional efforts. The FDA Modernization Act of 1997, signed into law on November 21, 1997 modifies the mission of the FDA to include a goal of speeding research, innovation and access to care. The legislation allows fast track review for the most important drugs. It also allows drug companies to promote off label use of already-approved pharmaceuticals for other purposes. The controversial issue allows drug companies to provide physicians with documentation on the effectiveness of their drugs in treating other conditions. The industry supports the change since the revenue growth for off label use of drugs is especially important for smaller biotechnical companies, while consumer groups fear that it is a loophole for selling unproven drugs. The bill also renews the Prescription Drug User Fee Act (PDUFA), regulating the current practice of compounding, and monitoring medical devices and health care claims for foods.

  8. Stroke Code Improves Intravenous Thrombolysis Administration in Acute Ischemic Stroke

    PubMed Central

    Chen, Chih-Hao; Tang, Sung-Chun; Tsai, Li-Kai; Hsieh, Ming-Ju; Yeh, Shin-Joe; Huang, Kuang-Yu; Jeng, Jiann-Shing

    2014-01-01

    Background and Purpose Timely intravenous (IV) thrombolysis for acute ischemic stroke is associated with better clinical outcomes. Acute stroke care implemented with “Stroke Code” (SC) may increase IV tissue plasminogen activator (tPA) administration. The present study aimed to investigate the impact of SC on thrombolysis. Methods The study period was divided into the “pre-SC era” (January 2006 to July 2010) and “SC era” (August 2010 to July 2013). Demographics, critical times (stroke symptom onset, presentation to the emergency department, neuroimaging, thrombolysis), stroke severity, and clinical outcomes were recorded and compared between the two eras. Results During the study period, 5957 patients with acute ischemic stroke were admitted; of these, 1301 (21.8%) arrived at the emergency department within 3 h of stroke onset and 307 (5.2%) received IV-tPA. The number and frequency of IV-tPA treatments for patients with an onset-to-door time of <3 h increased from the pre-SC era (n = 91, 13.9%) to the SC era (n = 216, 33.3%) (P<0.001). SC also improved the efficiency of IV-tPA administration; the median door-to-needle time decreased (88 to 51 min, P<0.001) and the percentage of door-to-needle times ≤60 min increased (14.3% to 71.3%, P<0.001). The SC era group tended to have more patients with good outcome (modified Rankin Scale ≤2) at discharge (49.5 vs. 39.6%, P = 0.11), with no difference in symptomatic hemorrhage events or in-hospital mortality. Conclusion The SC protocol increases the percentage of acute ischemic stroke patients receiving IV-tPA and decreases door-to-needle time. PMID:25111200

  9. Nurses' medication administration practices at two Singaporean acute care hospitals.

    PubMed

    Choo, Janet; Johnston, Linda; Manias, Elizabeth

    2013-03-01

    This study examined registered nurses' overall compliance with accepted medication administration procedures, and explored the distractions they faced during medication administration at two acute care hospitals in Singapore. A total of 140 registered nurses, 70 from each hospital, participated in the study. At both hospitals, nurses were distracted by personnel, such as physicians, radiographers, patients not under their care, and telephone calls, during medication rounds. Deviations from accepted medication procedures were observed. At one hospital, the use of a vest during medication administration alone was not effective in avoiding distractions during medication administration. Environmental factors and distractions can impact on the safe administration of medications, because they not only impair nurses' level of concentration, but also add to their work pressure. Attention should be placed on eliminating distractions through the use of appropriate strategies. Strategies that could be considered include the conduct of education sessions with health professionals and patients about the importance of not interrupting nurses while they are administering medications, and changes in work design.

  10. Difficulties experienced during preparation and administration of oral drugs

    PubMed Central

    Boztepe, Handan; Özdemir, Handan; Karababa, Çiğdem; Yıldız, Özlem

    2014-01-01

    Aim: It was aimed to determine the difficulties experienced by pediatric nurses working in the wards of a university hospital during preparation and administration of drugs and to determine solution recommendations. Material and Methods: One hundred and eight nurses who accepted to participate in the study constituted the sample of the study. Open-ended questions were asked in order to obtain detailed information about the attitudes and views of the participants and face to face interview was used. The problems experienced during preparation and administration of drugs were collected using the data collection form prepared by the investigators. Institution approval, ethics committee approval (HEK12/193) and written informed consent from the nurses who wished to participate in the study were obtained to conduct the study. The data obtained were expressed as figures and percentages. Results: The most commonly reported problems in preparation of drugs included incomplete dissolution of tablets or non-homogeneous distribution in fluids (54.6%) and difficulty in breaking tablets in appropriate doses (45.3%). The most commonly reported problem experienced during administration of drugs was rejection of drugs which tasted bad by babies/children or spitting out the drug (75.9%). In our study, the nurses also mentioned the problems related with drug administration equipment. These problems included fear of injectors (25.9%), escape of the drugs into the respiratory way (15.7%) and lack of appropriate equipment for administering the drugs (7.4%). Conclusions: In our study, it was found that all nurses experienced difficulty in preparing and administering drugs. The problems experienced by the nurses and solution recommendations for these problems were reported to the hospital administration. PMID:26078668

  11. The formulation of drug for ocular administration.

    PubMed

    Aiache, J M; el Meski, S; Beyssac, E; Serpin, G

    1997-01-01

    The different barriers that slow the penetration of active ingredients administered by the ocular route are described, and some novel dosage forms designed for this route are discussed. Both precorneal and corneal factors considerably restrict ocular penetration. The low bioavailability of classical ophthalmic dosage forms can be improved by several approaches, particularly by increasing the time the active ingredients remain in contact with the eye tissues. The new dosage forms are reviewed according to their type and their drug release mechanisms. The characteristics, advantages, and limitations of each are outlined. The potential of these dosage forms can be expected to enhance development. They offer prolonged effectiveness, reproducibility, fewer unwanted side effects, and improved tolerance.

  12. Acute d-Amphetamine Pretreatment Does Not Alter Stimulant Self-Administration in Humans

    PubMed Central

    Stoops, William W.; Vansickel, Andrea R.; Lile, Joshua A.; Rush, Craig R.

    2007-01-01

    Recent clinical research indicates that d-amphetamine is effective in treating cocaine and methamphetamine dependence. There is concern, however, with the use of d-amphetamine as a pharmacotherapy because acute administration of d-amphetamine decreases inhibition in cocaine-using individuals and may increase drug-taking behavior. The purpose of the present experiment was to determine whether acute d-amphetamine pretreatment would alter the reinforcing, subject-rated, and cardiovascular effects of d-amphetamine. To this end, 7 human volunteers first sampled doses of oral d-amphetamine (0, 8, and 16 mg). These doses engender moderate drug taking and were selected to avoid a ceiling or floor effect. Volunteers were then allowed to self-administer these sampled doses using a modified-progressive ratio procedure in two sessions in which they received pretreatments with either 0 or 15 mg oral d-amphetamine 2 hours prior to completing the modified progressive-ratio procedure. d-Amphetamine produced prototypical stimulant-like effects (e.g., increased ratings of stimulated, elevated blood pressure) and maintained responding on the modified progressive-ratio schedule. Pretreatment with 15 mg oral d-amphetamine also produced prototypical stimulant-like effects, but failed to alter break points for d-amphetamine on the modified progressive-ratio procedure relative to placebo pretreatment. These results indicate that acute d-amphetamine pretreatment does not increase stimulant self-administration. PMID:17490738

  13. Overview of the 2014 Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee meeting regarding cangrelor.

    PubMed

    Lhermusier, Thibault; Baker, Nevin C; Waksman, Ron

    2015-04-15

    Landmark clinical trials have established the benefit of P2Y12 inhibitors in the setting of acute coronary syndrome and percutaneous coronary intervention. On February 12, 2014, the Medicines Company (Sponsor) presented efficacy and safety data regarding cangrelor to the Food and Drug Administration (FDA) Cardiovascular and Renal Drugs Advisory Committee. The Sponsor sought approval for 2 indications: (1) in the setting of percutaneous coronary intervention for the reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with coronary artery disease and (2) in the setting of bridging therapy in patients with acute coronary syndrome or with stents who are at increased risk for thrombotic events (such as stent thrombosis) when oral P2Y12 therapy is interrupted because of surgery. The following is a summary of the data presented to the FDA by the Sponsor, the FDA's clinical review of cangrelor.

  14. 76 FR 56770 - Food and Drug Administration/Xavier University Global Outsourcing Conference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-14

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration/Xavier University Global...: The Food and Drug Administration (FDA) Cincinnati District, in cosponsorship with Xavier University, is announcing a public conference entitled ``FDA/Xavier University Global Outsourcing...

  15. 76 FR 72951 - Guidance for Industry and Food and Drug Administration Staff; Establishing the Performance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-28

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff... Differentiation of Human Papillomaviruses; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice... Differentiation of Human Papillomaviruses.'' This guidance document provides industry and Agency staff...

  16. 77 FR 5027 - Food and Drug Administration Transparency Initiative: Exploratory Program To Increase Access to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-01

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Transparency Initiative... announcing the availability of a report entitled ``Food and Drug Administration Transparency Initiative... Transparency Initiative. This report includes eight initiatives adopted by the Commissioner of Food and...

  17. Effects of acute and chronic administration of venlafaxine and desipramine on extracellular monoamine levels in the mouse prefrontal cortex and striatum.

    PubMed

    Higashino, Kosuke; Ago, Yukio; Umehara, Masato; Kita, Yuki; Fujita, Kazumi; Takuma, Kazuhiro; Matsuda, Toshio

    2014-04-15

    Prefrontal catecholamine neurotransmission plays a key role in the therapeutic actions of drugs for attention-deficit/hyperactivity disorder (ADHD). We have recently shown that serotonin/noradrenaline reuptake inhibitors and the noradrenaline reuptake inhibitor desipramine attenuated horizontal hyperactivity in spontaneously hypertensive rats, an animal model of ADHD, and that these drugs are potential pharmacotherapeutics for ADHD. In this study, we used in vivo microdialysis to study the effects of acute and chronic (once daily for 3 weeks) administration of the serotonin/noradrenaline reuptake inhibitor venlafaxine and the noradrenaline reuptake inhibitor desipramine on noradrenaline, dopamine, and serotonin levels, and the expression of the neuronal activity marker c-Fos in the mouse prefrontal cortex and striatum. Both acute and chronic venlafaxine administration increased prefrontal noradrenaline, dopamine, and serotonin levels and striatal noradrenaline and serotonin levels. Both acute and chronic desipramine administration increased prefrontal noradrenaline and dopamine levels and striatal noradrenaline levels, with chronic administration yielding stronger increase. Chronic desipramine did not affect striatal dopamine and serotonin levels. Both acute and chronic venlafaxine administration increased the expression of c-Fos in the prefrontal cortex, whereas chronic, but not acute, desipramine administration increased the expression of c-Fos in the prefrontal cortex. Both acute and chronic venlafaxine administration increased the striatal c-Fos expression to some degree, whereas desipramine administration did not. These results suggest that acute and chronic venlafaxine and chronic desipramine administration maximally activate the prefrontal adrenergic and dopaminergic systems without affecting striatal dopaminergic systems in mice.

  18. 77 FR 23485 - Food and Drug Administration Patient Network Annual Meeting; Input Into Food and Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-19

    ... perspective is discussed outside of a specific product's marketing application review. The medical product... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Patient Network Annual Meeting... regulatory process related to the medical product life cycle, analyze where in the process patient input...

  19. 78 FR 59038 - Mobile Medical Applications; Guidance for Industry and Food and Drug Administration Staff...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-25

    ... and Drug Administration Staff; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice..., and other entities about how the FDA intends to apply its regulatory authorities to select...

  20. 76 FR 789 - Guidance for Industry and Food and Drug Administration Staff; Section 905(j) Reports...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-06

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...: Demonstrating Substantial Equivalence for Tobacco Products.'' In general, the Federal Food, Drug, and...

  1. 77 FR 26768 - Food and Drug Administration/International Society for Pharmaceutical Engineering Cosponsorship...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-07

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration/International Society for..., and Sustaining a Culture of Compliance AGENCY: Food and Drug Administration, HHS. ] ACTION: Notice of public workshop. The Food and Drug Administration (FDA) Center for Drug Evaluation and Research,...

  2. 75 FR 17143 - Draft Guidance for Industry and Food and Drug Administration Staff; Medical Devices; Neurological...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-05

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA... six of them from the premarket notification requirements of the Federal Food, Drug, and Cosmetic...

  3. 76 FR 50740 - Draft Guidance for Industry and Food and Drug Administration Staff; Procedures for Handling...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-16

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is... Federal Food, Drug, and Cosmetic Act (the FD&C Act), procedural information on how to fulfill section...

  4. 76 FR 61103 - Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-03

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA... Food, Drug, and Cosmetic Act (FD&C Act), also known as the de novo classification process. FDA...

  5. 78 FR 11654 - Draft Guidance for Industry and Food and Drug Administration Staff; Providing Information About...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-19

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... Food, Drug, and Cosmetic Act; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the draft...

  6. The runway model of drug self-administration

    PubMed Central

    Ettenberg, Aaron

    2009-01-01

    Behavioral scientists have employed operant runways as a means of investigating the motivational impact of incentive stimuli for the better part of the past 100 years. In this task, the speed with which a trained animal traverses a long straight alley for positive incentive stimuli, like food or water, provides a reliable index of the subject’s motivation to seek those stimuli. The runway is therefore a particularly appropriate tool for investigating the drug-seeking behavior of animals working for drugs of abuse. The current review describes our laboratory’s work over the past twenty years developing and implementing an operant runway model of drug self-administration. Procedures are described that methodologically dissociate the antecedent motivational processes that induce an animal to seek a drug, from the positive reinforcing consequences of actually earning the drug. Additional work is reviewed on the use of the runway method as a means of modeling the factors that often result in a “relapse” of drug self-administration after a period of abstinence (i.e., a response reinstatement test), as are runway studies that revealed the presence of opposing positive and negative consequences of self-administered cocaine. This body of work suggests that the runway method has served as a powerful behavioral tool for the study of the behavioral and neurobiological basis of drug self-administration. PMID:19032964

  7. Formulation approaches in mitigating toxicity of orally administrated drugs.

    PubMed

    Kadiyala, Irina; Tan, Elijah

    2013-01-01

    This paper provides an overview of current formulation approaches to mitigate toxicity of orally administrated drugs. The formulation approaches are characterized by their intended impact on a drug's pharmacokinetic parameters, pharmacological properties or metabolic pathways. Regulatory opportunities and constraints with focus on U.S. regulations in optimizing a drug's safety or efficacy profile are reviewed. The following formulation approaches are described: (i) pharmacokinetic-modulating and (ii) pharmacodynamic-modulating. In the pharmacokinetic-modulating approach, the pharmacokinetic profile of drug release is modified by, for example, a reduction in peak drug plasma concentration while preserving or improving AUC, thereby potentially reducing toxic effects that may be related to C(max). In the pharmacodynamic-modulating approach, the drug is co-dosed with pharmacologically active or nonpharmacologically active agent or agents intended for mitigation of the drug's toxicity. The pharmacodynamic-modulating approach requires information on the specificity of drug interactions with other compounds and also on metabolic pathways. Examples demonstrating successful formulation work in reducing drug toxicity are provided. The in-depth knowledge of the drug's PK and PD properties combined with a greater understanding of the biology of diseases are necessary for successful drug product formulation leading to optimized in vivo exposure and minimized toxicity.

  8. Drugs and acute porphyrias: reasons for a hazardous relationship.

    PubMed

    Roveri, Giulia; Nascimbeni, Fabio; Rocchi, Emilio; Ventura, Paolo

    2014-11-01

    The porphyrias are a group of metabolic diseases caused by inherited or acquired enzymatic deficiency in the metabolic pathway of heme biosynthesis. Simplistically, they can be considered as storage diseases, because the partial enzymatic defect gives rise to a metabolic "bottleneck" in the biosynthetic pathway and hence to an accumulation of different metabolic intermediates, potentially toxic and responsible for the various (cutaneous or neurovisceral) clinical manifestations observed in these diseases. In the acute porphyrias (acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and the very rare delta-aminolevulinic acid dehydratase ALAD-d porphyria), the characteristic severe neurovisceral involvement is mainly ascribed to a tissue accumulation of delta-aminolevulinic acid, a neurotoxic nonporphyrin precursor. Many different factors, both endogenous and exogenous, may favor the accumulation of this precursor in patients who are carriers of an enzymatic defect consistent with an acute porphyria, thus contributing to trigger the serious (and potentially fatal) clinical manifestations of the disease (acute porphyric attacks). To date, many different drugs are known to be able to precipitate an acute porphyric attack, so that the acute porphyrias are also considered as pharmacogenetic or toxygenetic diseases. This article reviews the different biochemical mechanisms underlying the capacity of many drugs to precipitate a porphyric acute attack (drug porphyrogenicity) in carriers of genetic mutations responsible for acute porphyrias, and addresses the issue of prescribing drugs for patients affected by these rare, but extremely complex, diseases.

  9. [Behavioral correlations of gradual forced administration of psychoactive drugs].

    PubMed

    Shabanov, P D; Lebedev, A A

    2011-01-01

    The study was aimed at evaluating the behavioral correlations of the forced administration of psychoactive drugs. Wistar rats received the following drugs in elevated doses (over 4 days, i. p.): (i) physiological saline (control; 0.1-0.2-0.4-0.8 ml/rat), (ii) psychostimulant amphetamine (0.5-1.0--2.0-4.0 mg/kg); (iii) opioid analgetic fentanyl (0.00625-0.0125--0.025-0.05 mg/kg), (iv) ethanol 40% solution (0.5-1.0--2.0-4.0 g/kg), (v) barbiturate sodium ethaminal (2.5-5--10-20 mg/kg); and(vi) synthetic glucocorticoid dexamethasone (0.5-1.0--2.0-4.0 mg/kg). The forced regime of drug administration led to gradual load of the organism and prevented drug tolerance. The dynamics of self-stimulation reaction of the lateral hypothalamus was registered every day over drug administration period and revealed the following regularities: (I) dose-dependent effect of psychostimulant amphetamine and opioid analgetic fentanyl; (II) dexamethasone modulated self-stimulation, increasing (2 day, 1 mg/kg) or decreasing it (3 day, 2 mg/kg); (III) ethanol (1-2 g/kg) activated self-stimulation slightly; (IV) sodium ethaminal slightly inhibited self-stimulation and increased the thresholds of self-stimulation. In 24 h and 72 h after the last administration of drugs, the rat behavior was assessed in open field, elevated plus maze, resident-intruder paradigm, and Porsolt's test. In the open field, significant signs of post-intoxication exposure of psychoactive drugs were revealed, which were registered for 24-72 h after drug withdrawal. The withdrawal of drugs was accompanied with reduction (in 24 h) and subsequent recovery (in 72 h) of the vertical motor activity, exploration behavior, and emotionality. The anxiety indexes were increased up to the 3rd day after withdrawal. The antidepressant effect was also increased. The system of aggression-defense was restored only in rats treated with ethanol. The indexes of individual behavior and communicability in the post-intoxication period were

  10. Cerebral blood flow effects of acute intravenous heroin administration.

    PubMed

    Kosel, Markus; Noss, Roger S; Hämmig, Robert; Wielepp, Peter; Bundeli, Petra; Heidbreder, Rebeca; Kinser, Jane A; Brenneisen, Rudolf; Fisch, Hans-Ulrich; Kayser, Sarah; Schlaepfer, Thomas E

    2008-04-01

    We examined acute effects of intravenous diacetylmorphine (heroin) administration - which induces a characteristic biphasic response: A short rush-sensation associated with intense pleasurable feelings followed by a subjectively different period of euphoria on cerebral blood flow. This was assessed in nine male heroin dependent patients participating in a heroin maintenance program in a setting resembling everyday pattern of heroin abuse. 99mTc-HMPAO was administered 45 s (rush) and 15 min (euphoria) after administration of i.v. heroin and 45 s after administration of saline (placebo). Plasma concentration of diacetylmorphine and its metabolites were measured with high-pressure liquid chromatography (HPLC). Compared to the euphoria condition, rush was associated with blood flow increase in the left posterior cerebellar lobe, left anterior cingulate gyrus and right precuneus. Our results are in line with recent reports indicating that the cerebellum is an important component in functional brain systems subserving sensory and motor integration, learning, modulation of affect, motivation and social behaviour, which all play important roles in reinforcing properties of opioids.

  11. Acute coronary vasospasm in a patient with eosinophilic granulomatosis with polyangiitis following NSAID administration

    PubMed Central

    Benallegue, Naïl; Lozach, Pierre; Belizna, Cristina; Lavigne, Christian; Urbanski, Geoffrey

    2016-01-01

    Abstract Eosinophilic with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome) is a rare systemic disease characterized by a small-vessel necrotizing vasculitis. Cardiac manifestations are broad-ranging and are associated with a poor prognosis. Coronary vasospasm is uncommon. Here, we report a case of an acute coronary vasospasm in a patient with EGPA after corticosteroids withdrawal and nonsteroidal antiinflammatory drug (NSAID) introduction. This patient was initially misdiagnosed as bradykinin-mediated angioedema. A 30-year-old man presented with recurrence of abdominal pain and acute dyspnea. NSAID administration for pain during a flare was followed by coronary vasospasms leading to cardiac arrest. Corticosteroid treatment was recently interrupted by the patient. This case reports a rare cardiac complication of EGPA. NSAID might contribute to coronary vasospasm by eosinophilic degranulation in EGPA. Moreover, corticosteroid compliance must be emphasized among patients who display EGPA with high cardiac risk to prevent fatal issues. PMID:27893661

  12. Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods.

    PubMed

    Reese, Jessica A; Li, Xiaoning; Hauben, Manfred; Aster, Richard H; Bougie, Daniel W; Curtis, Brian R; George, James N; Vesely, Sara K

    2010-09-23

    Drug-induced immune thrombocytopenia (DITP) is often suspected in patients with acute thrombocytopenia unexplained by other causes, but documenting that a drug is the cause of thrombocytopenia can be challenging. To provide a resource for diagnosis of DITP and for drug safety surveillance, we analyzed 3 distinct methods for identifying drugs that may cause thrombocytopenia. (1) Published case reports of DITP have described 253 drugs suspected of causing thrombocytopenia; using defined clinical criteria, 87 (34%) were identified with evidence that the drug caused thrombocytopenia. (2) Serum samples from patients with suspected DITP were tested for 202 drugs; drug-dependent, platelet-reactive antibodies were identified for 67 drugs (33%). (3) The Food and Drug Administration's Adverse Event Reporting System database was searched for drugs associated with thrombocytopenia by use of data mining algorithms; 1444 drugs had at least 1 report associated with thrombocytopenia, and 573 (40%) drugs demonstrated a statistically distinctive reporting association with thrombocytopenia. Among 1468 drugs suspected of causing thrombocytopenia, 102 were evaluated by all 3 methods, and 23 of these 102 drugs had evidence for an association with thrombocytopenia by all 3 methods. Multiple methods, each with a distinct perspective, can contribute to the identification of drugs that can cause thrombocytopenia.

  13. Impact of administrative technology on acute care bed need.

    PubMed Central

    Martin, J B; Dahlstrom, G A; Johnston, C M

    1985-01-01

    This article reports an evaluation of the impact of three administrative technologies--Admission Scheduling (AS) Systems, Outpatient Surgery (OPS) Programs, and Preadmission Testing (PAT) Programs--on the number of acute care beds required by a hospital. The evaluation mechanism reported here is called the ADTECH Computerized Planning Model. ADTECH uses parameters of each technology, identified from previous literature and discussions with health care professionals, to predict the changes in bed requirements resulting from implementation of these programs. Data from eight hospitals of various characteristics and sizes were run to test the ADTECH model. The results from these test runs indicate that the proper implementation of AS, OPS, and PAT can significantly influence a hospital's required bed complement. PMID:3988530

  14. Improving Drugs Administration Safety in Pediatric Resuscitation Using Mobile Technology.

    PubMed

    Hagberg, Hamdi; Siebert, Johan; Gervaix, Alain; Daehne, Peter; Lovis, Christian; Manzano, Sergio; Ehrler, Frederic

    2016-01-01

    The fast preparation of drugs during pediatric resuscitation is of utmost importance. The influence of the patient's weight on the drug doses requires to perform complex calculations and is a source of errors. A technological solution could be a real help in avoiding these kinds of mistakes. Relying on a user centered approach we have developed an application supporting drug preparation. It has been tested in simulations with predefined scenario. The developed tool consists of a screen displaying a list of drug that can be administered. When the user select a drug, the instructions regarding its preparation are displayed with all dosage precisely calculated. The tool has demonstrated a significant reduction of errors associated to administration, a speeding up the overall process and has been well received by the nurses.

  15. Behavioral economics of drug self-administration and drug abuse policy.

    PubMed

    Hursh, S R

    1991-09-01

    The concepts of behavioral economics have proven useful for understanding the environmental control of overall levels of responding for a variety of commodities, including reinforcement by drug self-administration. These general concepts are summarized for application to the analysis of drug-reinforced behavior and proposed as the basis for future applications. This behavioral agenda includes the assessment of abuse liability, the assay of drug-reinforcer interactions, the design of drug abuse interventions, and the formulation of drug abuse public policy. These separate domains of investigation are described as part of an overall strategy for designing model projects to control drug use and testing public policy initiatives.

  16. Food and Drug Administration Drug Approval Process: A History and Overview.

    PubMed

    Williams, Christopher Ty

    2016-03-01

    In this article, the processing of investigational and new drug applications is described and the standard and expedited review processes are examined. The efforts of the US Food and Drug Administration to ensure greater agency transparency and fiscal responsibility and intensify oversight during the drug development and approval process are reviewed. Often attributed to a decrease in the number of uninsured adults, both the increase in prescription drug sales and the high costs associated with bringing a new drug to market highlight the necessity for a streamlined and cost-effective process to deliver these drugs safely and effectively.

  17. Food and Drug Administration Evaluation and Cigarette Smoking Risk Perceptions

    ERIC Educational Resources Information Center

    Kaufman, Annette R.; Waters, Erika A.; Parascandola, Mark; Augustson, Erik M.; Bansal-Travers, Maansi; Hyland, Andrew; Cummings, K. Michael

    2011-01-01

    Objectives: To examine the relationship between a belief about Food and Drug Administration (FDA) safety evaluation of cigarettes and smoking risk perceptions. Methods: A nationally representative, random-digit-dialed telephone survey of 1046 adult current cigarette smokers. Results: Smokers reporting that the FDA does not evaluate cigarettes for…

  18. Cyproheptadine resembles clozapine in vivo following both acute and chronic administration in rats.

    PubMed

    Goudie, Andrew J; Cooper, Gillian D; Cole, Jon C; Sumnall, Harry R

    2007-03-01

    Cyproheptadine is a cheap, widely available anti-allergy drug with a broad receptor binding profile which resembles that of clozapine. In rats discriminating clozapine from vehicle cyproheptadine mimicked clozapine very closely. Acutely it induced full generalization in the absence of response suppression, as observed with clozapine. Chronic administration of clozapine and cyproheptadine induced tolerance and cross-tolerance respectively to the clozapine stimulus. This was characterized by circa 3.5-fold parallel shifts to the right in the clozapine generalization curves. Such tolerance and cross-tolerance was spontaneously reversible, suggesting that it was pharmacodynamic, and that clozapine and cyproheptadine induce similar neuroadaptations when administered chronically. Administration of chlordiazepoxide at a very high dose induced no cross-tolerance to the clozapine stimulus showing the pharmacological specificity of tolerance. The clozapine stimulus is a compound cue involving actions at various receptors, and various clozapine-like antipsychotic (APD) drugs generalize fully to it. These data demonstrate that in vivo cyproheptadine resembles clozapine both acutely and chronically. Our findings, in conjunction with other actions of cyproheptadine -- induction of weight gain, alleviation of clozapine withdrawal, anxiolytic actions, alleviation of 'typical' APD-induced motoric side effects, and some preliminary clinical findings -- suggest that further study of cyproheptadine in conjunction with a 'typical' APD for the possible treatment of schizophrenia is merited at both pre-clinical and clinical levels.

  19. 75 FR 25271 - Guidance for Industry and Food and Drug Administration Staff; Enforcement Policy Concerning...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-07

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff... Smokeless Tobacco; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the guidance entitled...

  20. 75 FR 13766 - Food and Drug Administration and Process Analytical Technology for Pharma Manufacturing: Food and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-23

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration and Process Analytical Technology for Pharma Manufacturing: Food and Drug Administration--Partnering With Industry; Public Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. The Food and...

  1. 76 FR 38666 - Food and Drug Administration (FDA) and Marine Environmental Sciences Consortium/Dauphin Island...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-01

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration (FDA) and Marine Environmental Sciences Consortium/Dauphin Island Sea Lab Collaboration (U19) AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of...

  2. 75 FR 73951 - Amendments to General Regulations of the Food and Drug Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 14, and 17 RIN 0910-AG55 Amendments to General Regulations of the Food and Drug Administration AGENCY: Food and Drug Administration, HHS. ACTION: Direct final rule. SUMMARY: The Food and Drug Administration (FDA) is amending certain of its...

  3. 75 FR 73984 - Amendments to General Regulations of the Food and Drug Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 14, and 17 RIN 0910-AG55 Amendments to General Regulations of the Food and Drug Administration AGENCY: Food and Drug Administration, HHS. ACTION: Proposed rule. SUMMARY: The Food and Drug Administration (FDA) is proposing to amend certain of its...

  4. 76 FR 570 - Draft Guidance for Industry and Food and Drug Administration Staff; Establishing the Performance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-05

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... Antibodies to Borrelia Burgdorferi; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the draft...

  5. 76 FR 27331 - Draft Guidance for Industry and Food and Drug Administration Staff; Establishing the Performance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-11

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... Trachomatis and/or Neisseria Gonorrhoeae: Screening and Diagnostic Testing; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing...

  6. 75 FR 73107 - Guidance for Industry and Food and Drug Administration Staff; Blood Lancet Labeling; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-29

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff; Blood Lancet Labeling; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the guidance...

  7. 75 FR 47603 - Draft Guidance for Industry and Food and Drug Administration Staff; Recommendations for Premarket...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-06

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA... zonisamide assays. This draft guidance is not final nor is it in effect at this time. DATES: Although you...

  8. 76 FR 36542 - Draft Guidance for Industry and Food and Drug Administration Staff: The Content of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-22

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... Glucose Suspend Device Systems; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the draft...

  9. 77 FR 67379 - Draft Guidance for Industry and Food and Drug Administration Staff; Highly Multiplexed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-09

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... Devices; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the draft guidance entitled...

  10. 75 FR 57963 - Draft Guidance for Industry and Food and Drug Administration Staff; Establishing the Performance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-23

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... Helicobacter pylori; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the draft guidance...

  11. 76 FR 43689 - Draft Guidance for Industry and Food and Drug Administration Staff; Mobile Medical Applications...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-21

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration Staff; Mobile Medical Applications; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the...

  12. 75 FR 73106 - Draft Guidance for Industry and Food and Drug Administration Staff; Establishing the Performance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-29

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... Clostridium difficile; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the draft guidance...

  13. 76 FR 40921 - Draft Guidance for Industry and Food and Drug Administration Staff; Enforcement Policy for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-12

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... Radiology Devices; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the draft guidance...

  14. 76 FR 569 - Draft Guidance for Industry and Food and Drug Administration Staff; Establishing the Performance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-05

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... Staphylococcus aureus; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. ] SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the draft guidance...

  15. 78 FR 4417 - Draft Guidance for Industry and Food and Drug Administration Staff; Submissions for Postapproval...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-22

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... Marketing Applications; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry...

  16. Serotonin and suicidality: the impact of acute fluoxetine administration. I: Serotonin and suicide.

    PubMed

    King, R A; Segman, R H; Anderson, G M

    1994-01-01

    The general enhancement of central serotonin (5-HT) neurotransmission following long-term administration of serotonin-selective reuptake inhibitors (SSRIs) appears to play an important role in these drugs' anti-depressant efficacy. Because suicide and/or aggression appear linked to diminished levels of brain 5-HT and its metabolites, it has been suggested that SSRIs may be particularly effective in reducing suicidality. Case reports of increased or new suicidal ideation following administration of fluoxetine and other SSRIs, however, raise questions about how these potential side effects may relate to the SSRI's acute effects on 5-HT transmission. Part I of this review examines fluoxetine's effects on suicidality and related behaviors and reviews the relationship of suicidality to serotonergic dysregulation.

  17. Acute symptoms of drug hypersensitivity (urticaria, angioedema, anaphylaxis, anaphylactic shock).

    PubMed

    Limsuwan, Ticha; Demoly, Pascal

    2010-07-01

    Drug hypersensitivity reactions (HSRs) are the adverse effects of drugs which, when taken at doses generally tolerated by normal subjects, clinically resemble allergy. Immediate-reaction of drug HSRs are those that occur less than 1 hour after the last drug intake, usually in the form of urticaria, angioedema, rhinitis, conjunctivitis, bronchospasm, and anaphylaxis or anaphylactic shock. Acute urticarial and angioedema reactions are common clinical problems frequently encountered by internists and general practitioners. They are not specific to drug allergic reaction, and can be caused by various pathogenic mechanisms. Despite the benign course of urticaria and angioedema, a mucocutaneous swelling of the upper respiratory tract could be life-threatening by itself or a feature of anaphylaxis. This article reviews acute symptoms of drug HSR-related urticaria, angioedema, anaphylaxis, and anaphylactic shock, and how clinicians should approach these problems.

  18. 77 FR 14403 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-09

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Norovirus Serological Reagents; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA)...

  19. 77 FR 18828 - Guidance for Industry and Food and Drug Administration Staff; Factors To Consider When Making...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-28

    ... Novo Classifications; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the guidance document... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration...

  20. 21 CFR 20.20 - Policy on disclosure of Food and Drug Administration records.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Administration records. (a) The Food and Drug Administration will make the fullest possible disclosure of records... Administration records. 20.20 Section 20.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Administration records shall be made available for public disclosure. (c) Except as provided in paragraph (d)...

  1. 21 CFR 7.45 - Food and Drug Administration-requested recall.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Industry Responsibilities § 7.45 Food and Drug Administration-requested recall. (a) The Commissioner of... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Food and Drug Administration-requested recall. 7.45 Section 7.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  2. 21 CFR 20.30 - Food and Drug Administration Freedom of Information Staff.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Food and Drug Administration Freedom of Information Staff. 20.30 Section 20.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION General Policy § 20.30 Food and Drug Administration Freedom...

  3. 21 CFR 20.120 - Records available in Food and Drug Administration Public Reading Rooms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Records available in Food and Drug Administration Public Reading Rooms. 20.120 Section 20.120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF....120 Records available in Food and Drug Administration Public Reading Rooms. (a) The Food and...

  4. 21 CFR 20.120 - Records available in Food and Drug Administration Public Reading Rooms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Records available in Food and Drug Administration Public Reading Rooms. 20.120 Section 20.120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF....120 Records available in Food and Drug Administration Public Reading Rooms. (a) The Food and...

  5. 21 CFR 20.120 - Records available in Food and Drug Administration Public Reading Rooms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Records available in Food and Drug Administration Public Reading Rooms. 20.120 Section 20.120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF....120 Records available in Food and Drug Administration Public Reading Rooms. (a) The Food and...

  6. 21 CFR 20.120 - Records available in Food and Drug Administration Public Reading Rooms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Records available in Food and Drug Administration Public Reading Rooms. 20.120 Section 20.120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF....120 Records available in Food and Drug Administration Public Reading Rooms. (a) The Food and...

  7. 21 CFR 20.120 - Records available in Food and Drug Administration Public Reading Rooms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Records available in Food and Drug Administration Public Reading Rooms. 20.120 Section 20.120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF....120 Records available in Food and Drug Administration Public Reading Rooms. (a) The Food and...

  8. 21 CFR 10.90 - Food and Drug Administration regulations, recommendations, and agreements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Food and Drug Administration regulations, recommendations, and agreements. 10.90 Section 10.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Procedures § 10.90 Food and Drug Administration regulations, recommendations, and agreements. (a)...

  9. 21 CFR 10.90 - Food and Drug Administration regulations, recommendations, and agreements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Food and Drug Administration regulations, recommendations, and agreements. 10.90 Section 10.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Procedures § 10.90 Food and Drug Administration regulations, recommendations, and agreements. (a)...

  10. 21 CFR 5.1105 - Chief Counsel, Food and Drug Administration.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Chief Counsel, Food and Drug Administration. 5.1105 Section 5.1105 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ORGANIZATION Organization § 5.1105 Chief Counsel, Food and Drug Administration. The...

  11. Anticataleptic activity of cathinone and MDMA (Ecstasy) upon acute and subchronic administration in rat.

    PubMed

    Banjaw, Mehret Yerdaw; Mayerhofer, Andreas; Schmidt, Werner J

    2003-09-15

    It was recently demonstrated that acute administration of 3,4-methylenedioxymethamphet-amine (MDMA, "Ecstasy") is capable of counteracting haloperidol-induced catalepsy in rats. The present study was done with another psychostimulant, S-(-)-cathinone. In these experiments, 32 male Sprague-Dawley rats, 225 +/- 25 g, were used. They were divided into three groups. All groups received 0.5 mg/kg haloperidol in normal saline (s.c.) as a first injection. Then 30 min later each group received either isotonic phosphate-buffered saline, 1 mg/kg S-(-)-cathinone, or 2.5 mg/kg (RS)-MDMA (s.c.) as a second injection. The results of descent latency on both the horizontal bar and vertical grid showed that S-(-)-cathinone or (RS)-MDMA upon acute administration induces a strong anticataleptic activity (P < 0.0001) compared to rats treated with haloperidol plus vehicle. The effect of both drugs was later masked upon subchronic administration (days 2-7, 26-29). This is probably due to sensitization of cataleptic behavior. However, when the same groups of rats were tested on day 8 in a different task, i.e., open-field, they showed a significant difference (P < 0.05). The detailed mechanism of the observed strong anticataleptic activity of S-(-)-cathinone (which is considered a potent dopamine releaser) requires further investigation.

  12. Potential of nanoparticulate drug delivery systems by intranasal administration.

    PubMed

    Ali, Javed; Ali, Mushir; Baboota, Sanjula; Sahani, Jasjeet Kaur; Ramassamy, Charles; Dao, Lé; Bhavna

    2010-05-01

    Due to number of problems related with oral, parenteral, rectal and other routes of drug administration, the interest of pharmaceutical scientists has increased towards exploring the possibilities of intranasal delivery of various drugs. Nasal drug delivery system is commonly known for the treatment of local ailments like cold, cough, rhinitis, etc. Efforts have been made to deliver various drugs, especially peptides and proteins, through nasal route for systemic use; utilizing the principles and concepts of various nanoparticulate drug delivery systems using various polymers and absorption promoters. The incorporation of drugs into nanoparticles might be a promising approach, since colloidal formulations have been shown to protect them from the degrading milieu in the nasal cavity and facilitate their transport across the mucosal barriers. The use of nanoparticles for vaccine delivery provides beneficial effect, by achieving good immune responses. This could be due to the fact that small particles can be transported preferentially by the lymphoid tissue of the nasal cavity (NALT). The brain gets benefited through the intranasal delivery as direct olfactory transport bypasses the blood brain barrier and nanoparticles are taken up and conveyed along cell processes of olfactory neurons through the cribriform plate to synaptic junctions with neurons of the olfactory bulb. The intranasal delivery is aimed at optimizing drug bioavailability for systemic drugs, as absorption decreases with increasing molecular weight, and for drugs, which are susceptible to enzymatic degradation such as proteins and polypeptides. This review discusses the potential benefits of using nanoparticles for nasal delivery of drugs and vaccines for brain, systemic and topical delivery. The article aims at giving an insight into nasal cavity, consideration of factors affecting and strategies to improve drug absorption through nasal route, pharmaceutical dosage forms and delivery systems with

  13. Acute water intoxication during military urine drug screening.

    PubMed

    Tilley, Molly A; Cotant, Casey L

    2011-04-01

    Random mandatory urine drug screening is a routine practice in the military. The pressure to produce a urine specimen creates a temptation to consume large volumes of water, putting those individuals at risk of acute water intoxication. This occurs when the amount of water consumed exceeds the kidney's ability to excrete it, resulting in hyponatremia owing to excess amount of water compared to serum solutes. The acute drop in serum osmolality leads to cerebral edema, causing headaches, confusion, seizures, and death. There has been increasing awareness of the danger of overhydration among performance athletes, but dangers in other groups can be underappreciated. We present the case of a 37-year-old male Air Force officer who developed acute water intoxication during urine drug screening. Our case demonstrates the need for a clear Air Force policy for mandatory drug testing to minimize the risk of developing this potentially fatal condition.

  14. Intravenous drug administration: a skill for student nurses?

    PubMed

    Morris, Ruth

    2006-04-01

    This article explores issues related to children's nursing students learning about preparation and administration of IV drugs, considering professional and organisational issues. The competencies required for safe practice are discussed, and the question of who is in the best position to teach and assess students in this skill is considered. Organisations need to ensure that clear guidelines exist for student nurses' involvement in IV therapy.

  15. Food and Drug Administration regulation and evaluation of vaccines.

    PubMed

    Marshall, Valerie; Baylor, Norman W

    2011-05-01

    The vaccine-approval process in the United States is regulated by the Center for Biologics Evaluation and Research of the US Food and Drug Administration. Throughout the life cycle of development, from preclinical studies to after licensure, vaccines are subject to rigorous testing and oversight. Manufacturers must adhere to good manufacturing practices and control procedures to ensure the quality of vaccines. As mandated by Title 21 of the Code of Regulations, licensed vaccines must meet stringent criteria for safety, efficacy, and potency.

  16. 75 FR 4982 - Redelegation of Functions; Delegation of Authority to Drug Enforcement Administration Official

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-01

    ... Enforcement Administration Official AGENCY: Drug Enforcement Administration (DEA), Department of Justice... Administration (DEA), Department of Justice, is amending the appendix to the Justice Department regulations to... Substances Act and subsequently delegated to the Administrator of DEA. DATES: Effective Dates: This...

  17. Acute and subacute drug-induced movement disorders.

    PubMed

    Burkhard, Pierre R

    2014-01-01

    Many pharmacological agents may induce a variety of movement disorders, including dystonia, tremor, parkinsonism, myoclonus and dyskinesia, with an acute, subacute or more chronic time course. Motor symptoms may be isolated or part of a more extensive cerebral or systemic condition, such as the neuroleptic malignant syndrome or the serotonin syndrome. Drug-induced movement disorders share a number of features that should make them easy to identify, including a clear temporal relationship between medication initiation and symptom onset, a dose-effect, and, with the exception of tardive syndromes, complete resolution after discontinuation of the offending agent. Diagnosis relies on a thorough medication history. Medications commonly involved include dopamine receptor blockers, antidepressants and anti-epileptics, among many others. Mechanisms underlying drug-induced movement disorders involve blockade, facilitation or imbalance of dopamine, serotonin, noradrenaline and cholinergic neurotransmission in the basal ganglia. The present review focuses on drug-induced movement disorders that typically develop as an acute (hours to days) or subacute (days to weeks) event, including acute dystonic reactions, akathisia, drug-induced parkinsonism, neuroleptic malignant syndrome, serotonin syndrome, parkinsonism-hyperpyrexia syndrome, drug-induced tremor, drug-induced hyperkinesias and movement disorders associated with the use of recreational drugs.

  18. Oral Administration of Peptide-Based Drugs: Beyond Lipinski's Rule.

    PubMed

    Santos, Gabriela B; Ganesan, A; Emery, Flavio S

    2016-10-19

    The use of peptides in therapy presents several limitations, from physicochemical characteristics to inadequate pharmacokinetic profiles for oral absorption. As peptides are gaining importance in the therapeutic arsenal, there is an increasing need to rationalize the main characteristics of this compound class in the market. Therefore, we performed an extensive analysis of all known peptide drugs and clinical candidates based on their peptide features, physicochemical and structural properties, and correlated these with their administration route and therapeutic classes. Peptide drugs are widely distributed across drug and pharmacological space, covering several therapeutic areas with structural diversity and complexity, distributed between groups of cyclic and linear compounds. Although structural and physicochemical properties are clear within these groups, we counter the consensus that cyclic peptides have better oral availability than linear peptides, as most of the orally administrated peptides have linear structures. This study and review furnishes information that could support peptide drug design, with a new cutoff of known descriptors that go beyond the Rule of Five.

  19. 28 CFR 0.157 - Federal Bureau of Investigation-Drug Enforcement Administration Senior Executive Service.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Federal Bureau of Investigation-Drug... Administrative Matters § 0.157 Federal Bureau of Investigation—Drug Enforcement Administration Senior Executive... within the Federal Bureau of Investigation (FBI) and the Drug Enforcement Administration (DEA) to...

  20. 28 CFR 0.157 - Federal Bureau of Investigation-Drug Enforcement Administration Senior Executive Service.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Federal Bureau of Investigation-Drug... Administrative Matters § 0.157 Federal Bureau of Investigation—Drug Enforcement Administration Senior Executive... within the Federal Bureau of Investigation (FBI) and the Drug Enforcement Administration (DEA) to...

  1. 28 CFR 0.157 - Federal Bureau of Investigation-Drug Enforcement Administration Senior Executive Service.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Federal Bureau of Investigation-Drug... Administrative Matters § 0.157 Federal Bureau of Investigation—Drug Enforcement Administration Senior Executive... within the Federal Bureau of Investigation (FBI) and the Drug Enforcement Administration (DEA) to...

  2. 78 FR 13348 - Science Board to the Food and Drug Administration Advisory Committee; Amendment of Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-27

    ... HUMAN SERVICES Food and Drug Administration Science Board to the Food and Drug Administration Advisory... Administration (FDA) is announcing an amendment to the notice of meeting of the Science Board to the Food and... that a meeting of the Science Board to the Food and Drug Administration would be held on February...

  3. 78 FR 35937 - Food and Drug Administration Decisions for Investigational Device Exemption Clinical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-14

    ... revised and is being reissued for comment because the Food and Drug Administration Safety and Innovation... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Decisions for Investigational Device Exemption Clinical Investigations; Draft Guidance for Industry and Food and Drug...

  4. 75 FR 17418 - Memorandum of Understanding Between the Food and Drug Administration, United States Department of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-06

    ... HUMAN SERVICES Food and Drug Administration Memorandum of Understanding Between the Food and Drug... Health AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is providing notice of a memorandum of understanding (MOU) between the Food and...

  5. 75 FR 3238 - Draft Guidance for Industry and Food and Drug Administration Staff; Heart Valves...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-20

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration...; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug... for heart valves. This draft guidance document is not final, nor is it in effect at this time....

  6. 76 FR 6685 - Draft Guidance for Industry and Food and Drug Administration Staff; Recommended Warning for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-07

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration...; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug... about the potential adverse health effects from the use of powder on medical gloves and is...

  7. Expand classical drug administration ways by emerging routes using dendrimer drug delivery systems: a concise overview.

    PubMed

    Mignani, Serge; El Kazzouli, Saïd; Bousmina, Mosto; Majoral, Jean-Pierre

    2013-10-01

    Drugs are introduced into the body by numerous routes such as enteral (oral, sublingual and rectum administration), parenteral (intravascular, intramuscular, subcutaneous and inhalation administration), or topical (skin and mucosal membranes). Each route has specific purposes, advantages and disadvantages. Today, the oral route remains the preferred one for different reasons such as ease and compliance by patients. Several nanoformulated drugs have been already approved by the FDA, such as Abelcet®, Doxil®, Abraxane® or Vivagel®(Starpharma) which is an anionic G4-poly(L-lysine)-type dendrimer showing potent topical vaginal microbicide activity. Numerous biochemical studies, as well as biological and pharmacological applications of both dendrimer based products (dendrimers as therapeutic compounds per se, like Vivagel®) and dendrimers as drug carriers (covalent conjugation or noncovalent encapsulation of drugs) were described. It is widely known that due to their outstanding physical and chemical properties, dendrimers afforded improvement of corresponding carried-drugs as dendrimer-drug complexes or conjugates (versus plain drug) such as biodistribution and pharmacokinetic behaviors. The purpose of this manuscript is to review the recent progresses of dendrimers as nanoscale drug delivery systems for the delivery of drugs using enteral, parenteral and topical routes. In particular, we focus our attention on the emerging and promising routes such as oral, transdermal, ocular and transmucosal routes using dendrimers as delivery systems.

  8. Resveratrol: A medical drug for acute pancreatitis

    PubMed Central

    Ma, Zhen-Hua; Ma, Qing-Yong

    2005-01-01

    Accumulating evidence demonstrates that resveratrol, a natural polyphenolic compound extracted from plants, inhibit inflammation when administered. It has direct effects on suppression of platelet coagulation and cytokines production in many experimental models. Because microcirculation occlusion and cytokines over-production is involved in many diseases such as acute pancreatitis (AP), the discovery of resveratrol as platelet and cytokines inhibitors has shed light on the treatment of AP, which still has significant mortality and morbidity. It is anticipated that this natural polyphenol could serve as a therapeutic compound in managing AP through different pathways. PMID:15929163

  9. Sequential drug verification errors resulting in wrong drug administration during caesarean section.

    PubMed

    Calderbank, S; Uncles, D R; Burns, N; Kariyawasam, H K C D; Allan, G D L

    2011-01-01

    An intravenous bolus of phentolamine was inadvertently given to a parturient during an emergency caesarean section following delivery of her infant when the intention had been to give an intravenous bolus of 5 IU Syntocinon. Root cause analysis identified a series of errors originating in the hospital pharmacy when one drug package was mistakenly issued in place of another. Subsequent checks failed to detect the original mistake. The final and most important check immediately before intravenous administration was also at fault. This case highlights a systems failure that permitted issue, transportation and administration of the wrong drug to a parturient. Robust measures to ensure avoidance of drug administration errors should be evaluated and introduced where possible.

  10. Is tobacco a drug? Administrative agencies as common law courts.

    PubMed

    Sunstein, C R

    1998-04-01

    Professor Cass Sunstein argues that the FDA has the authority to regulate tobacco products. He considers the text of the Federal Food, Drug, and Cosmetic Act, which supports the FDA assertion, and the context of its enactment, which argues against the FDA. He resolves the tension between text and context in favor of FDA jurisdiction by turning to the emerging role of administrative agencies. In modern government, he contends, administrative agencies have become America's common law courts, with the power to adapt statutory regimes to new facts and new values when the underlying statute is ambiguous. Professor Sunstein's Article, like the other pieces in this volume, was written after the United States District Court for the Middle District of North Carolina decided Coyne Beahm v. FDA, but before a three judge panel of the United States Court of Appeals for the Fourth Circuit reversed that decision in Brown & Williamson Tobacco Corp. v. FDA. In Coyne Beahm, the District Court held that the Federal Food, Drug, and Cosmetic Act authorized the FDA to regulate tobacco products, but not tobacco advertising. The Fourth Circuit rejected the District Court's jurisdictional ruling and invalidated the FDA's regulations in their entirety. The Clinton Administration has since requested an en banc rehearing before the Fourth Circuit.

  11. Acute Neuroactive Drug Exposures alter Locomotor Activity in Larval Zebrafish

    EPA Science Inventory

    As part of the development of a rapid in vivo screen for prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae by assessing the acute effects of prototypic drugs that act on the central nervous system. Initially,...

  12. [Intravesical therapy with mitomycin through electromotive drug administration].

    PubMed

    Verri, Cristian; Liberati, Emanuele; Celestino, Francesco; De Carlo, Francesco; Torelli, Fiammetta; Di Stasi, Savino M

    2013-01-01

    In the management of non-muscle invasive bladder cancer (NMIBC), high-level evidence supports the widespread practice of intravesical therapy with mitomycin-C (MMC). Randomized trials showed a significant reduction in short-term recurrence compared with transurethral resection of bladder tumor (TURBT) alone, but little effect on long-term and no impact at all in preventing progression. Electromotive drug administration (EMDA®) offers a means of controlling and enhancing the tissue transport of certain drugs, in order to increase their efficacy. In both laboratory and clinical studies, intravesical electromotive drug administration (EMDA) increases MMC bladder uptake, resulting in an improved clinical efficacy in NMIBC without systemic side effects. New frameworks for treatment of NMIBC - e.g., sequential intravesical BCG and EMDA/MMC, as well as intravesical EMDA/MMC immediately before TURBT - have provided promising preliminary results with higher remission rates and longer remission times, and they are a priority to minimise the costs of disease management. These findings suggest EMDA-enhanced MMC efficacy against urothelial cancer could be a major therapeutic breakthrough in the treatment of NMIBC.

  13. Neuroendocrine and neurochemical effects of acute ibogaine administration: a time course evaluation.

    PubMed

    Ali, S F; Newport, G D; Slikker, W; Rothman, R B; Baumann, M H

    1996-10-21

    Ibogaine (IBO) is an indole alkaloid that is reported to facilitate drug abstinence in substance abusers. Despite considerable investigation, the mechanism of IBO action in vivo and its suitability as a treatment for drug addiction remains unclear. The present study was designed to evaluate the time-course effects of acute IBO on neuroendocrine and neurochemical indices. Adult male rats were treated with i.p. saline or 50 mg/kg IBO and sacrificed 15, 30, 60, 120 min and 24 h later. Trunk blood was collected for hormone measures and brains were dissected for neurochemical analyses. IBO produced a rapid elevation in plasma prolactin that declined to control levels by 60 min. Corticosterone levels increased 15 min after drug administration, continued to increase for 120 min, but returned to control levels 24 h after dosing. IBO decreased dopamine (DA) concentrations in the striatum and frontal cortex at 30, 60 and 120 min after injection while DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were elevated over the same time period. 24 h after IBO, DOPAC concentrations in striatum and HVA levels in the frontal cortex were below control values. Serotonin (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA) were decreased at 60 min after IBO administration only in the striatum. These data indicate that a single injection of IBO produces a spectrum of effects that includes: (1) elevation of plasma prolactin and corticosterone, (2) short- and long-term effects on DA neurotransmission, and (3) modest, transient effects of 5-HT neurotransmission. The effects of IBO reported herein may have relevance to the anti-addictive properties of this drug, and this proposal warrants further investigation.

  14. Drug-induced pulmonary edema and acute respiratory distress syndrome.

    PubMed

    Lee-Chiong, Teofilo; Matthay, Richard A

    2004-03-01

    Noncardiogenic pulmonary edema, and, to a lesser extent, acute respiratory distress syndrome (ARDS), are common clinical manifestations of drug-induced lung diseases. Clinical features and radiographic appearances are generally indistinguishable from other causes of pulmonary edema and ARDS. Typical manifestations include dyspnea, chest discomfort, tachypnea, and hypoxemia. Chest radiographs commonly reveal interstitial and alveolar filling infiltrates. Unlike pulmonary edema that is due to congestive heart failure, cardiomegaly and pulmonary vascular redistribution are generally absent in cases that are drug-related. Rare cases of drug-induced myocarditis with heart failure and pulmonary edema have been described. Results from laboratory evaluation and respiratory function tests are nonspecific.

  15. Multiple routes of drug administration and HIV risk among injecting drug users.

    PubMed

    Vorobjov, Sigrid; Uusküla, Anneli; Des Jarlais, Don C; Abel-Ollo, Katri; Talu, Ave; Rüütel, Kristi

    2012-06-01

    This study assesses relationships between drug administration routes and HIV serostatus, drug use, and sexual behaviors among current injecting drug users (IDUs) in Tallinn, Estonia. We recruited 350 IDUs for a cross-sectional risk behavior survey. Adjusted odds ratios (AORs) were calculated to explore injection risk behavior, sexual behavior, and HIV serostatus associated with multiple route use. Focus groups explored reasons why injectors might use non-injecting routes of administration. Those reporting multiple drug administration routes were less likely to be HIV seropositive (AOR = 0.49, 95% confidence interval [CI] = 0.25-0.97) and had almost twice the odds of having more than one sexual partner (AOR = 1.90, 95% CI = 1.01-3.60) and of reporting having sexually transmitted diseases (AOR = 2.38, 95% CI = 1.02-5.59). IDUs who engage in noninjecting drug use may be reducing their risk of acquiring HIV though sharing injection equipment, but if infected may be a critical group for sexual transmission of HIV to people who do not inject drugs.

  16. [Internet and nursing: development of a site on drug administration].

    PubMed

    da Silva, F B; Cassiani, S H; Zem-Mascarenhas, S H

    2001-01-01

    This study identified existent sites in the internet about Administration of Medications and developed and evaluated a specific site of this thematic. Of the 158 existent and available sites in the database of the Alta Vista search, 17 of these presented some relationship with pharmacology, marketing and information about drugs, technologies and rules of the medication. After that a site was developed and named The process of Administration of Medications in focus which goal was to present investigations conducted by a group about the following topics: errors, technology, complications, study group and the team. The evaluation of this site was made by 2 analyst of systems, 2 computer science technicians and 4 nursing professors and it showed that the quality of the pages, the time of answer, the link, images and content were considered between excellent and satisfactory.

  17. How the US Food and Drug Administration Can Solve the Prescription Drug Shortage Problem

    PubMed Central

    2013-01-01

    Drug shortages are threatening care quality and cost-containment efforts. I describe the pharmaceutical marketplace changes that have caused the problem, and propose new policies to solve it, through changing incentives for producers and purchasers. I propose a grading scheme for the Food and Drug Administration when it inspects manufacturing facilities in the United States and abroad. The inspections’ focus would change from closing unsafe plants to improving production process quality, reducing the likelihood that plants will be closed—the most frequent cause of drug shortages. PMID:23488502

  18. Mode of inhibitory actions of acute and chronic chloroquine administration on the electrically stimulated mouse diaphragm in vitro.

    PubMed Central

    Okwuasaba, F. K.; Otubu, J. A.; Udoh, F. V.

    1990-01-01

    1. The effects of bath applied chloroquine (Chlo) and of acute and chronic Chlo administration on skeletal muscle reactivity to electrical stimulation and to drugs have been studied on mouse hemidiaphragm preparations in vitro. 2. Chlo (0.15-150 micrograms) produced a concentration-dependent inhibition twitch and tetanic contractions due to direct muscle stimulation (MS). Acute and chronic administration of Chlo (45 mg kg-1, i.p. daily, for 3-28 days) progressively shifted the concentration-response curve to bath-applied Chlo to the right, with maximum effect occurring from day 14 of Chlo pretreatment. 3. Acute and chronic administration of Chlo decreased the twitch and tetanus tension, raised the minimal fusion frequency (MFR) for tetanic contraction to occur and did not alter the twitch/tetanus tension ratio. Tetanus tension unlike twitch tension was not significantly decreased on day 3. 4. Caffeine (5-500 microM)--and isoprenaline (0.001-0.8 microM)-induced potentiations of twitch contraction were attenuated in a concentration-dependent manner by bath-applied Chlo and by acute and chronic administration of Chlo. Higher concentrations of caffeine (0.1-5 microM) and KCl (10 mM-130 mM) produced contracture of the muscle which was sensitive to inhibition by Chlo (50-150 microM). Moreover, the spike contractions superimposed on caffeine contracture were more sensitive to the inhibitory effect of Chlo than the contracture. 5. The inhibitory effects of dantrolene sodium and (+)-tubocurarine on MS and on indirectly stimulated hemidiaphragm respectively were not significantly altered by acute and chronic administration of Chlo. In contrast, the inhibitory concentration-response curve to procaine was shifted to the right.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2282456

  19. Food and drug administration regulation of drugs that raise blood pressure.

    PubMed

    Blankfield, Robert P; Iftikhar, Imran H

    2015-01-01

    Although it is recognized that a systolic blood pressure (SBP) increase ≥ 2 mm Hg or a diastolic blood pressure (DBP) increase ≥ 1 mm Hg increases the risk of heart attacks and strokes in middle-aged adults, the Food and Drug Administration (FDA) lacks an adequate policy for regulating medications that increase blood pressure (BP). Some FDA reviewers consider a clinically significant increase in BP to occur only if a drug raises SBP ≥ 20 mm Hg or if a drug raises DBP ≥ 10 to 15 mm Hg. In recent years, numerous drugs have been regulated or taken off the market due to cardiovascular safety concerns. The list includes rofecoxib (Vioxx), valdecoxib (Bextra), nonselective nonsteroidal anti-inflammatory drugs, sibutramine (Meridia), and phenylpropanolamine. It is probable that the hypertensive effect of these drugs explains why they increase the risk of adverse cardiovascular events. Other drugs, notably serotonin-norepinephrine reuptake inhibitors and drugs used to treat attention deficit hyperactivity disorder, were approved without cardiovascular safety data despite the fact that they raise BP comparable to valdecoxib and sibutramine. It is the responsibility of the FDA to ensure that drugs are properly labeled regarding risk. Even if a drug raises BP only modestly, FDA guidelines for new drug approvals should include a requirement for cardiovascular safety data. However, such guidelines will not address the problem of how to obtain cardiovascular safety data for the many already approved drugs that increase BP. The FDA should play a role in obtaining cardiovascular safety data for such drugs.

  20. Drug Administration Errors in Hospital Inpatients: A Systematic Review

    PubMed Central

    Berdot, Sarah; Gillaizeau, Florence; Caruba, Thibaut; Prognon, Patrice; Durieux, Pierre; Sabatier, Brigitte

    2013-01-01

    Context Drug administration in the hospital setting is the last barrier before a possible error reaches the patient. Objectives We aimed to analyze the prevalence and nature of administration error rate detected by the observation method. Data Sources Embase, MEDLINE, Cochrane Library from 1966 to December 2011 and reference lists of included studies. Study Selection Observational studies, cross-sectional studies, before-and-after studies, and randomized controlled trials that measured the rate of administration errors in inpatients were included. Data Extraction Two reviewers (senior pharmacists) independently identified studies for inclusion. One reviewer extracted the data; the second reviewer checked the data. The main outcome was the error rate calculated as being the number of errors without wrong time errors divided by the Total Opportunity for Errors (TOE, sum of the total number of doses ordered plus the unordered doses given), and multiplied by 100. For studies that reported it, clinical impact was reclassified into four categories from fatal to minor or no impact. Due to a large heterogeneity, results were expressed as median values (interquartile range, IQR), according to their study design. Results Among 2088 studies, a total of 52 reported TOE. Most of the studies were cross-sectional studies (N=46). The median error rate without wrong time errors for the cross-sectional studies using TOE was 10.5% [IQR: 7.3%-21.7%]. No fatal error was observed and most errors were classified as minor in the 18 studies in which clinical impact was analyzed. We did not find any evidence of publication bias. Conclusions Administration errors are frequent among inpatients. The median error rate without wrong time errors for the cross-sectional studies using TOE was about 10%. A standardization of administration error rate using the same denominator (TOE), numerator and types of errors is essential for further publications. PMID:23818992

  1. 78 FR 42381 - Administrative Detention of Drugs Intended for Human or Animal Use

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-15

    ... July 15, 2013 Part IV Department of Health and Human Services Food and Drug Administration 21 CFR Parts... / Proposed Rules#0;#0; ] DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1 and 16 Administrative Detention of Drugs Intended for Human or Animal Use AGENCY: Food and...

  2. 76 FR 37820 - Proyecto Informar: Food and Drug Administration Hispanic Outreach Initiative (U01)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-28

    ... HUMAN SERVICES Food and Drug Administration Proyecto Informar: Food and Drug Administration Hispanic Outreach Initiative (U01) AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and... cooperative agreement for the National Alliance for Hispanic Health. The goal of the Food and...

  3. 75 FR 36425 - Guidance for Industry and Food and Drug Administration Staff; In Vitro Diagnostic Studies...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-25

    ... HUMAN SERVICES Food and Drug Administration (formerly Docket No. 2007D-0387) Guidance for Industry and Food and Drug Administration Staff; In Vitro Diagnostic Studies--Frequently Asked Questions; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

  4. 75 FR 22412 - Food and Drug Administration/Xavier University Global Outsourcing Conference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-28

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration/Xavier University Global...: The Food and Drug Administration (FDA), Cincinnati District, in co-sponsorship with Xavier University, is announcing a public conference entitled ``FDA/Xavier University Global Outsourcing...

  5. 78 FR 76842 - Food and Drug Administration/American Academy of Ophthalmology Workshop on Developing Novel...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Food and Drug Administration/American Academy of Ophthalmology Workshop on Developing Novel Endpoints for Premium Intraocular Lenses; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION:...

  6. 76 FR 68767 - Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-07

    ... entitled ``Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification...] [FR Doc No: 2011-28766] DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0689] Draft Guidance for Industry and Food and Drug Administration Staff; De...

  7. 76 FR 36543 - Draft Guidance for Industry and Food and Drug Administration Staff: Applying Human Factors and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-22

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA... and Food and Drug Administration Staff: Applying Human Factors and Usability Engineering to...

  8. Modeling of Corneal and Retinal Pharmacokinetics after Periocular Drug Administration

    PubMed Central

    Amrite, Aniruddha C.; Edelhauser, Henry F.; Kompella, Uday B.

    2012-01-01

    .99) with the observed values in the SD rat corneas. Similar pharmacokinetics models explain drug delivery to the cornea in rat and rabbit animal models. Retinal pharmacokinetics after periocular drug administration can be explained with a four-compartment (periocular space, choroid-containing transfer compartment, retina, and distribution compartment) model with elimination from the periocular space, retina, and choroid compartment. Inclusion of a dissolution–release step before the drug is available for absorption or elimination better explains retinal tmax. Good fits were obtained in both the BN (r = 0.99) and SD (r = 0.99) rats for retinal celecoxib using the same model; however, the parameter estimates differed. Conclusions Corneal and retinal pharmacokinetics of small lipophilic molecules after periocular administration can be described by compartment models. The modeling analysis shows that (1) leak-back from the site of administration most likely contributes to the apparent lack of an increase phase in corneal concentrations; (2) elimination via the conjunctival or periocular blood and lymphatic systems contributes significantly to drug clearance after periocular injection; (3) corneal pharmacokinetics of small lipophilic molecules can be explained by using similar models in rats and rabbits; and (4) although there are differences in some retinal pharmacokinetics parameters between the pigmented and nonpigmented rats, the physiological basis of these differences has yet to be ascertained. PMID:18172109

  9. Effects of acute and 2-week administration of oral salbutamol on exercise performance and muscle strength in athletes.

    PubMed

    Hostrup, M; Kalsen, A; Auchenberg, M; Bangsbo, J; Backer, V

    2016-01-01

    Our objective was to investigate effects of acute and 2-week administration of oral salbutamol on repeated sprint ability, exercise performance, and muscle strength in elite endurance athletes. Twenty male elite athletes [VO2max: 69.4 ± 1.8 (Mean ± SE) mL/min/kg], aged 25.9 ± 1.4 years, were included in a randomized, double-blinded and placebo-controlled parallel study. At baseline, after acute administration, and again after 2-week administration of the study drugs (8 mg salbutamol or placebo), subjects' maximal voluntary contraction (MVC) of m. quadriceps and isometric endurance of m. deltoideus were measured, followed by three repeated Wingate tests. Exercise performance at 110% of VO2max was determined on a bike ergometer. Acute administration of salbutamol increased peak power during first Wingate test by 4.1 ± 1.7% (P < 0.05). Two-week administration of salbutamol increased (P < 0.05) peak power during first and second Wingate test by 6.4 ± 2.0 and 4.2 ± 1.0%. Neither acute nor 2-week administration of salbutamol had any effect on MVC, exercise performance at 110% of VO2max or on isometric endurance. No differences were observed in the placebo group. In conclusion, salbutamol benefits athletes' sprint ability. Thus, the present study supports the restriction of oral salbutamol in competitive sports.

  10. 28 CFR 0.103a - Delegations respecting claims against the Drug Enforcement Administration.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Delegations respecting claims against the Drug Enforcement Administration. 0.103a Section 0.103a Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE Drug Enforcement Administration § 0.103a Delegations...

  11. 21 CFR 20.31 - Retention schedule of requests for Food and Drug Administration records.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Retention schedule of requests for Food and Drug Administration records. 20.31 Section 20.31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION General Policy § 20.31 Retention schedule of requests for...

  12. 21 CFR 20.32 - Disclosure of Food and Drug Administration employee names.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Disclosure of Food and Drug Administration employee names. 20.32 Section 20.32 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION General Policy § 20.32 Disclosure of Food and...

  13. 21 CFR 20.29 - Prohibition on withdrawal of records from Food and Drug Administration files.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Prohibition on withdrawal of records from Food and Drug Administration files. 20.29 Section 20.29 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION General Policy § 20.29 Prohibition...

  14. 77 FR 41415 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... HUMAN SERVICES Food and Drug Administration Single-Ingredient, Immediate-Release Drug Products... AGENCY: Food and Drug Administration, HHS. ACTION: Notice; correction. SUMMARY: The Food and Drug... such products in interstate commerce. The document was published with an incorrect Web link....

  15. 21 CFR 874.5220 - Ear, nose, and throat drug administration device.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5220 Ear, nose, and throat drug administration device. (a) Identification. An ear, nose, and throat drug... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ear, nose, and throat drug administration...

  16. 21 CFR 874.5220 - Ear, nose, and throat drug administration device.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5220 Ear, nose, and throat drug administration device. (a) Identification. An ear, nose, and throat drug... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ear, nose, and throat drug administration...

  17. Reform at FDA: faster access to promising drugs? Food and Drug Administration.

    PubMed

    Baker, R

    1995-06-01

    The Food and Drug Administration (FDA), the government agency responsible for ensuring that drugs, vaccines, and medical devices are safe and effective, is under hot debate by Congress, the Clinton administration, and the AIDS community. The Clinton/Gore proposal favors excluding drug and biologic manufacturers from requirements for more environmental assessments and only indirectly addresses drug development. Oregon Democratic Congressman Ron Wyden introduced an FDA reform bill which calls for the FDA to use expert panels, independent testing organizations, and institutional review boards (IRB) to help speed new drugs and devices through the approval process. The bill calls for the use of the IRB for the approval (or denial) of applications for Phase I review of new drugs. Not surprisingly, the AIDS community has differing views on the reform at the FDA. The Treatment Action Group (TAG), whose members hold key positions in well-known AIDS groups, supports the status quo at FDA and is lobbying AIDS organizations across the country to sign on to its FDA Reform Principles. Other AIDS treatment activists, such as members of ACT UP, favor local IRB jurisdiction over Phase I research.

  18. GABAergic modulation of human social interaction in a prisoner's dilemma model by acute administration of alprazolam.

    PubMed

    Lane, Scott D; Gowin, Joshua L

    2009-10-01

    Recent work in neuroeconomics has used game theory paradigms to examine neural systems that subserve human social interaction and decision making. Attempts to modify social interaction through pharmacological manipulation have been less common. Here we show dose-dependent modification of human social behavior in a prisoner's dilemma model after acute administration of the γ-aminobutyric acid (GABA)-A modulating benzodiazepine alprazolam. Nine healthy adults received doses of placebo, 0.5, 1.0, and 2.0 mg alprazolam in a counterbalanced within-subject design, while completing multiple test blocks per day on an iterated prisoner's dilemma game. During test blocks in which peak subjective effects of alprazolam were reported, cooperative choices were significantly decreased as a function of dose. Consistent with previous reports showing that high acute doses of GABA-modulating drugs are associated with violence and other antisocial behavior, our data suggest that at sufficiently high doses, alprazolam can decrease cooperation. These behavioral changes may be facilitated by changes in inhibitory control facilitated by GABA. Game theory paradigms may prove useful in behavioral pharmacology studies seeking to measure social interaction, and may help inform the emerging field of neuroeconomics.

  19. Bioequivalence of generic drugs: a simple explanation for a US Food and Drug Administration requirement.

    PubMed

    Andrade, Chittaranjan

    2015-06-01

    There is a widespread misconception that for a generic drug to be deemed bioequivalent to a branded drug, it must contain 80%-125% of the active ingredient that is present in the branded version. More correctly, bioequivalence is studied in randomized crossover trials that compare the generic drug with the reference agent, and the relevant outcome measures are pharmacokinetic (PK) parameters such as peak drug concentration and area under the curve, which describe the rate and extent of absorption of the drug. The ratio of each PK characteristic of the generic drug to the reference drug is computed; the ideal value of this ratio is 1:1, or just 1.00 (indicating a perfect match, or perfect bioequivalence). Because this ideal is probably unattainable, the US Food and Drug Administration requires that the 90% confidence interval of the PK ratio should lie between 0.80 and 1.25. For the entire 90% confidence interval to meet this requirement, the mean PK value of the generic product should actually lie quite close to that of the reference standard. Therefore, the variation between the generic and the reference is actually small. These concepts are explained in this article with the help of simple, easy-to-understand examples.

  20. Acute adverse event signalling scheme using the Saskatchewan Administrative health care utilization datafiles: results for two benzodiazepines.

    PubMed

    Rawson, N S; Rawson, M J

    1999-01-01

    Linked administrative health care utilization databases offer potential benefits for postmarketing surveillance. The value of the Saskatchewan datafiles in an acute adverse event signalling scheme has been evaluated using two benzodiazepines. The first 20,000 patients dispensed lorazepam and the first 8525 patients dispensed alprazolam were followed through the datafiles over the year after their initial prescription of the relevant drug, and all medical services occurring during treatment were recorded. The most frequent adverse drug reactions to benzodiazepines are drowsiness, depression, impaired intellectual function and memory, lethargy, impaired coordination, dizziness, nausea and/or vomiting, skin rash, and respiratory disturbance. Data from our study showed that sleep disorders, depressive disorders, dizziness and/or vertigo, respiratory symptoms, esophagus and stomach disorders, and inflammatory skin conditions occurred significantly more often in the first 30 days after the initial prescription than in the succeeding six months in both drug groups, indicating that they are important adverse events. There are several limitations to the methodology; however, the results of the analysis indicate that the use of administrative health care utilization datafiles in a systematic assessment to signal potential acute adverse drug reactions is a feasible proposition, but further studies are required to assess whether events are real adverse reactions.

  1. Drug-Induced Acute Interstitial Nephritis with Nifedipine

    PubMed Central

    Golbin, Léonard; Dolley-Hitze, Thibault; Lorcy, Nolwenn; Rioux-Leclercq, Nathalie; Vigneau, Cécile

    2016-01-01

    Background. Acute interstitial nephritis (AIN) is a frequent cause of Acute Kidney Injury (AKI). Drug hypersensitivity is the most common etiology and the list of drugs that can induce AIN is not exhaustive yet. Case Report. Here, we describe the case of a 43-year-old man who was treated with nifedipine (Adalate®) for Raynaud's syndrome. After nifedipine introduction, serum creatininemia progressively increased from 91 to 188 μmol/L in a few months and AKI was diagnosed. Laboratory work-up results indicated the presence of tubular proteinuria and nonspecific inflammatory syndrome. Histological analysis found granulomatous interstitial nephropathy without necrosis in 20% of the kidney biopsy without immunofluorescent deposit. Nifedipine was stopped and corticosteroid treatment was started with a rapid but incomplete reduction of serum creatininemia level to 106 μmol/L. Conclusion. This is the first case of AIN caused by nifedipine. PMID:26955492

  2. Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity

    PubMed Central

    Tiradentes, R.V.; Pires, J.G.P.; Silva, N.F.; Ramage, A.G.; Santuzzi, C.H.; Futuro, H.A.

    2014-01-01

    Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central. PMID:25003632

  3. Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity.

    PubMed

    Tiradentes, R V; Pires, J G P; Silva, N F; Ramage, A G; Santuzzi, C H; Futuro Neto, H A

    2014-07-01

    Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33 ± 4.7 and -31 ± 5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35 ± 5.4 and -31 ± 5.5%, respectively, with an increase in blood pressure +26.3 ± 2.5; 3 mg/kg sertraline reduced RSNA by -59.4 ± 8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central.

  4. The corporate assault on the Food and Drug Administration.

    PubMed

    Nixon, R

    1996-01-01

    Current "regulatory reform" in the U.S. Congress is seeking to eliminate the Food and Drug Administration. The author discusses the forces behind this reform and traces the impact of campaign contributions from various industries opposed to FDA regulations, stock held by members of Congress in companies regulated by the FDA, and a variety of organizations with ties to House Speaker Newt Gingrich that have received donations from industries that Gingrich has helped in their efforts to loosen FDA regulations. The article also examines the myth that the FDA is an overzealous watchdog imposing unnecessary burdens on the companies that it regulates. The controversy over the cow hormone rBGH is given as an example.

  5. US Food and Drug Administration Perspectives on Clinical Mass Spectrometry.

    PubMed

    Lathrop, Julia Tait; Jeffery, Douglas A; Shea, Yvonne R; Scholl, Peter F; Chan, Maria M

    2016-01-01

    Mass spectrometry-based in vitro diagnostic devices that measure proteins and peptides are underutilized in clinical practice, and none has been cleared or approved by the Food and Drug Administration (FDA) for marketing or for use in clinical trials. One way to increase their utilization is through enhanced interactions between the FDA and the clinical mass spectrometry community to improve the validation and regulatory review of these devices. As a reference point from which to develop these interactions, this article surveys the FDA's regulation of mass spectrometry-based devices, explains how the FDA uses guidance documents and standards in the review process, and describes the FDA's previous outreach to stakeholders. Here we also discuss how further communication and collaboration with the clinical mass spectrometry communities can identify opportunities for the FDA to provide help in the development of mass spectrometry-based devices and enhance their entry into the clinic.

  6. Administrative detention of drugs intended for human or animal use. Final rule.

    PubMed

    2014-05-29

    The Food and Drug Administration (FDA or the Agency) is implementing administrative detention authority with respect to drugs intended for human or animal use as authorized by amendments made to the Federal Food, Drug, and Cosmetic Act (the FD&C Act) by the Food and Drug Administration Safety and Innovation Act (FDASIA). FDA's administrative detention authority with respect to drugs allows FDA to better protect the integrity of the drug supply chain. Specifically, FDA is able to administratively detain drugs encountered during an inspection that an authorized FDA representative conducting an inspection has reason to believe are adulterated or misbranded. This authority is intended to protect the public by preventing distribution or subsequent use of drugs encountered during inspections that are believed to be adulterated or misbranded, until FDA has had time to consider what action it should take concerning the drugs, and to initiate legal action, if appropriate.

  7. 76 FR 78530 - Applications for Food and Drug Administration Approval To Market a New Drug; Revision of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-19

    ...The Food and Drug Administration (FDA or the Agency) is issuing an interim final rule amending its postmarketing reporting regulations implementing certain provisions of the Federal Food, Drug and Cosmetic Act. The provisions of the Federal Food, Drug and Cosmetic Act require manufacturers who are the sole manufacturers of certain drug products to notify FDA at least 6 months before......

  8. A multifunctional pipette for localized drug administration to brain slices.

    PubMed

    Ahemaiti, Aikeremu; Ainla, Alar; Jeffries, Gavin D M; Wigström, Holger; Orwar, Owe; Jesorka, Aldo; Jardemark, Kent

    2013-10-15

    We have developed a superfusion method utilizing an open-volume microfluidic device for administration of pharmacologically active substances to selected areas in brain slices with high spatio-temporal resolution. The method consists of a hydrodynamically confined flow of the active chemical compound, which locally stimulates neurons in brain slices, applied in conjunction with electrophysiological recording techniques to analyze the response. The microfluidic device, which is a novel free-standing multifunctional pipette, allows diverse superfusion experiments, such as testing the effects of different concentrations of drugs or drug candidates on neurons in different cell layers with high positional accuracy, affecting only a small number of cells. We demonstrate herein the use of the method with electrophysiological recordings of pyramidal cells in hippocampal and prefrontal cortex brain slices from rats, determine the dependence of electric responses on the distance of the superfusion device from the recording site, document a multifold gain in solution exchange time as compared to whole slice perfusion, and show that the device is able to store and deliver up to four solutions in a series. Localized solution delivery by means of open-volume microfluidic technology also reduces reagent consumption and tissue culture expenses significantly, while allowing more data to be collected from a single tissue slice, thus reducing the number of laboratory animals to be sacrificed for a study.

  9. 76 FR 22903 - Draft Guidance for Industry and Food and Drug Administration Staff; Establishing That a Tobacco...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-25

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... Request AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug... February 15, 2007'' to the Center for Tobacco Products, Food and Drug Administration, 9200 Corporate...

  10. 78 FR 9701 - Draft Joint Food and Drug Administration/Health Canada Quantitative Assessment of the Risk of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-11

    ... HUMAN SERVICES Food and Drug Administration Draft Joint Food and Drug Administration/Health Canada... and Canada AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA or we) is announcing the availability of a draft ``Joint Food and Drug...

  11. Assessment of substance abuse liability in rodents: self-administration, drug discrimination, and locomotor sensitization.

    PubMed

    Paterson, Neil E

    2012-09-01

    Assessing abuse liability is a crucial step in the development of a novel chemical entity (NCE) with central nervous system (CNS) activity or with chemical or pharmacological properties in common with known abused substances. Rodent assessment of abuse liability is highly attractive due to its relatively low cost and high predictive validity. Described in this unit are three rodent assays commonly used to provide data on the potential for abuse liability based on the acute effects of NCEs: specifically, self-administration, drug discrimination, and locomotor sensitization. As these assays provide insight into the potential abuse liability of NCEs as well as in vivo pharmacological mechanism(s) of action, they should form a key part of the development process for novel therapeutics aimed at treating CNS disorders.

  12. 28 CFR 16.102 - Exemption of Drug Enforcement Administration and Immigration and Naturalization Service Joint...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Administration and Immigration and Naturalization Service Joint System of Records. 16.102 Section 16.102 Judicial... Systems Under the Privacy Act § 16.102 Exemption of Drug Enforcement Administration and Immigration and..., the Immigration and Naturalization Service or the Drug Enforcement Administration will...

  13. 28 CFR 16.102 - Exemption of Drug Enforcement Administration and Immigration and Naturalization Service Joint...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Administration and Immigration and Naturalization Service Joint System of Records. 16.102 Section 16.102 Judicial... Systems Under the Privacy Act § 16.102 Exemption of Drug Enforcement Administration and Immigration and..., the Immigration and Naturalization Service or the Drug Enforcement Administration will...

  14. 28 CFR 16.102 - Exemption of Drug Enforcement Administration and Immigration and Naturalization Service Joint...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Administration and Immigration and Naturalization Service Joint System of Records. 16.102 Section 16.102 Judicial... Systems Under the Privacy Act § 16.102 Exemption of Drug Enforcement Administration and Immigration and..., the Immigration and Naturalization Service or the Drug Enforcement Administration will...

  15. 77 FR 43846 - Food and Drug Administration Pediatric Medical Devices Workshop; Notice of Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-26

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Pediatric Medical Devices... Administration's (FDA) Office of Orphan Products Development is announcing the following workshop: FDA Pediatric Medical Devices Workshop. This meeting is intended to focus on challenges in pediatric device...

  16. 75 FR 17423 - Memorandum of Understanding Between the Food and Drug Administration, United States Department of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-06

    ... HUMAN SERVICES Food and Drug Administration Memorandum of Understanding Between the Food and Drug... Profession Schools, Inc. AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and... opportunities for socio-economically disadvantaged students. DATES: The agreement became effective January...

  17. 21 CFR 874.5220 - Ear, nose, and throat drug administration device.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ear, nose, and throat drug administration device... SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5220 Ear, nose, and throat drug administration device. (a) Identification. An ear, nose, and throat...

  18. 21 CFR 874.5220 - Ear, nose, and throat drug administration device.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Ear, nose, and throat drug administration device... SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5220 Ear, nose, and throat drug administration device. (a) Identification. An ear, nose, and throat...

  19. 21 CFR 874.5220 - Ear, nose, and throat drug administration device.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ear, nose, and throat drug administration device... SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5220 Ear, nose, and throat drug administration device. (a) Identification. An ear, nose, and throat...

  20. Acute hepatopathy associated with mitotane administration in a dog.

    PubMed

    Webb, Craig B; Twedt, David C

    2006-01-01

    An adult dog with a persistent elevation in alkaline phosphatase enzyme activity was started on mitotane for suspected hyperadrenocorticism. One month later, the dog was presented for intermittent anorexia and acute icterus. The dog's liver enzyme activities and total bilirubin were markedly elevated, prothrombin time was prolonged, and blood urea nitrogen and glucose were low. Histopathology revealed marked, centrilobular, hepatocellular loss. After discontinuation of the mitotane, the dog recovered with supportive care and was normal 3 months later, which was consistent with mitotane-associated hepatic failure.

  1. Cannabis and tolerance: acute drug impairment as a function of cannabis use history

    PubMed Central

    Ramaekers, J. G.; van Wel, J. H.; Spronk, D. B.; Toennes, S. W.; Kuypers, K. P. C.; Theunissen, E. L.; Verkes, R. J.

    2016-01-01

    Cannabis use history as predictor of neurocognitive response to cannabis intoxication remains subject to scientific and policy debates. The present study assessed the influence of cannabis on neurocognition in cannabis users whose cannabis use history ranged from infrequent to daily use. Drug users (N = 122) received acute doses of cannabis (300 μg/kg THC), cocaine HCl (300 mg) and placebo. Cocaine served as active control for demonstrating neurocognitive test sensitivity. Executive function, impulse control, attention, psychomotor function and subjective intoxication were significantly worse after cannabis administration relative to placebo. Cocaine improved psychomotor function and attention, impaired impulse control and increased feelings of intoxication. Acute effects of cannabis and cocaine on neurocognitive performance were similar across cannabis users irrespective of their cannabis use history. Absence of tolerance implies that that frequent cannabis use and intoxication can be expected to interfere with neurocognitive performance in many daily environments such as school, work or traffic. PMID:27225696

  2. Cannabis and tolerance: acute drug impairment as a function of cannabis use history.

    PubMed

    Ramaekers, J G; van Wel, J H; Spronk, D B; Toennes, S W; Kuypers, K P C; Theunissen, E L; Verkes, R J

    2016-05-26

    Cannabis use history as predictor of neurocognitive response to cannabis intoxication remains subject to scientific and policy debates. The present study assessed the influence of cannabis on neurocognition in cannabis users whose cannabis use history ranged from infrequent to daily use. Drug users (N = 122) received acute doses of cannabis (300 μg/kg THC), cocaine HCl (300 mg) and placebo. Cocaine served as active control for demonstrating neurocognitive test sensitivity. Executive function, impulse control, attention, psychomotor function and subjective intoxication were significantly worse after cannabis administration relative to placebo. Cocaine improved psychomotor function and attention, impaired impulse control and increased feelings of intoxication. Acute effects of cannabis and cocaine on neurocognitive performance were similar across cannabis users irrespective of their cannabis use history. Absence of tolerance implies that that frequent cannabis use and intoxication can be expected to interfere with neurocognitive performance in many daily environments such as school, work or traffic.

  3. Zohydro approval by food and drug administration: controversial or frightening?

    PubMed

    Manchikanti, Laxmaiah; Atluri, Sairam; Candido, Kenneth D; Boswell, Mark V; Simopoulos, Thomas T; Grider, Jay S; Falco, Frank J E; Hirsch, Joshua A

    2014-01-01

    The actions and regulations of the Food and Drug Administration (FDA) are crucial to the entire population of the U.S., specifically the public who take a multitude of drugs and providers who prescribe drugs and devices. Further, the FDA is relevant to investors, specifically in regards to biotech and pharmaceutical companies involved in developing new drugs. The FDA has been criticized for a lack of independence on the one hand and excessive regulatory and expanding authority without evidence and consistency of the actions on the other hand. The FDA approved a single-entity, long-acting, hydrocodone product (Zohydro, Zogenix, San Diego, CA) on October 25, 2013, against the recommendation of the FDA's own appointed scientific advisory panel, which voted 11 to 2 against the approval of Zohydro. Subsequent to the approval, multiple consumer safety organizations, health care agencies, addiction treatment providers, professional organizations, and other groups on the frontline of the opioid addiction epidemic have expressed concern. In addition, the US Congress and various state attorneys general raised serious concerns about the approval of Zohydro, which is highly addictive and may enhance the opioid addiction epidemic. Supporters of Zohydro contend that it is necessary and essential to manage chronic pain and improve functional status with no additional risk. Over the past 15 years, prescriptions for opioids have skyrocketed with the United States consuming more than 84% of the global oxycodone and more than 99% of the hydrocodone supply. The sharp increase in opioid prescribing has led to parallel increases in opioid addiction and overdose deaths, surpassing motor vehicle injuries in the U.S. Recent studies assessing the trends of medical use and misuse of opioid analgesics from 2000 to 2011 have concluded that the present trend of the continued increase in the medical use of opioid analgesics appears to contribute to increasing misuse, resulting in multiple health

  4. Caregivers' perception of drug administration safety for pediatric oncology patients.

    PubMed

    Harris, Nariman; Badr, Lina Kurdahi; Saab, Raya; Khalidi, Aziza

    2014-01-01

    Medication errors (MEs) are reported to be between 1.5% and 90% depending on many factors, such as type of the institution where data were collected and the method to identify the errors. More significantly, the risk for errors with potential for harm is 3 times higher for children, especially those receiving chemotherapy. Few studies have been published on averting such errors with children and none on how caregivers perceive their role in preventing such errors. The purpose of this study was to evaluate pediatric oncology patient's caregivers' perception of drug administration safety and their willingness to be involved in averting such errors. A cross-sectional design was used to study a nonrandomized sample of 100 caregivers of pediatric oncology patients. Ninety-six of the caregivers surveyed were well informed about the medications their children receive and were ready to participate in error prevention strategies. However, an underestimation of potential errors uncovered a high level of "trust" for the staff. Caregivers echoed their apprehension for being responsible for potential errors. Caregivers are a valuable resource to intercept medication errors. However, caregivers may be hesitant to actively communicate their fears with health professionals. Interventions that aim at encouraging caregivers to engage in the safety of their children are recommended.

  5. Vaccines, Pharmaceutical Products, and Bioterrorism: Challenges for the U.S. Food and Drug Administration

    DTIC Science & Technology

    1999-08-01

    plague (Yersinia pestis), tularemia (Francisella tularensis), brucellosis ( Brucella abortus, B. melitensis , B. suis, B. canis), Q fever (Coxiella...Special Issue 20011029 090 Vaccines, Pharmaceutical Products, and Bioterrorism: Challenges for the U.S. Food and Drug Administration Kathryn C...Zoon U.S. Food and Drug Administration, Rockville, Maryland, USA In regards to bioterrorism, the goal of the U.S. Food and Drug Administration (FDA

  6. Drug Enforcement Administration Western Lab wins EPA Federal Green Challenge award for electronics recycling

    EPA Pesticide Factsheets

    SAN FRANCISCO - Today, the U.S. Environmental Protection Agency Regional Administrator Jared Blumenfeld presented the Federal Green Challenge award to the Drug Enforcement Administration (DEA) Western Laboratory for increasing its electronics recycling mor

  7. Approved drugs and their problems in patient care: routes of administration and dosing.

    PubMed

    Cook, Stuart D

    2007-08-15

    Problems in patient care with regard to route of administration and dosing of currently approved drugs are reviewed. Dose, frequency and route of administration can make a difference in efficacy, side effects, quality of life, antigenicity, cost, and compliance.

  8. Dosage Form Developments of Nanosuspension Drug Delivery System for Oral Administration Route.

    PubMed

    Chen, Ang; Shi, Ye; Yan, Zhiqiang; Hao, Hongxun; Zhang, Yong; Zhong, Jian; Hou, Huiming

    2015-01-01

    A large amount of new drug candidates are practically insoluble in aqueous solvents and are even simultaneously poorly soluble in organic solvents. Nanosuspension drug delivery system (DDS) was firstly developed in 1994 and has attracted more and more attention as a formation solution for the poorly soluble drugs. By nansizing the poorly soluble drugs, nanosuspensions have several outstanding advantages for drug delivery. Among many administration routes of drug delivery, oral administration is the most preferred route due to its advantages such as ease of ingestion, versatility to accommodate various types of drug candidates, low production cost, high safety, good patient compliance, and pain avoidance. Current marketed pharmaceutical nanosuspension DDS products are mostly for oral administration. This review is to systematically summarize the nanosuspension DDS dosage form developments of poorly soluble drugs for oral administration use.

  9. 75 FR 69089 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Federal Register 2010, 2011, 2012, 2013, 2014

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    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff... for the Topical Approximation of Skin; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the...

  10. 76 FR 20992 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

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    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff... AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA... subject to comment in accordance with the Agency's good guidance practices. DATES: Submit...

  11. 78 FR 102 - Guidance for Industry and Food and Drug Administration Staff; eCopy Program for Medical Device...

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  13. 76 FR 19373 - The 14th Annual Food and Drug Administration-Orange County Regulatory Affairs Educational...

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  14. 77 FR 52744 - Food and Drug Administration/European Medicines Agency Orphan Product Designation and Grant Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Food and Drug Administration/European Medicines Agency Orphan Product Designation and Grant Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of meeting. The Food and Drug Administration's...

  15. 76 FR 64228 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

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    2011-10-17

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  16. 76 FR 44935 - Draft Guidance for Industry and Food and Drug Administration Staff; 510(k) Device Modifications...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-27

    ...] [FR Doc No: 2011-18923] DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0453] Draft Guidance for Industry and Food and Drug Administration Staff; 510(k... AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration...

  17. 76 FR 20688 - Guidance for Industry and Food and Drug Administration Staff; 30-Day Notices, 135-Day Premarket...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-13

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff... Supplements for Manufacturing Method or Process Changes; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability...

  18. 77 FR 37058 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-20

    ...] [FR Doc No: 2012-15025] DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA 2012-D-0304] Draft Guidance for Industry and Food and Drug Administration Staff; Class II...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA)...

  19. 75 FR 21632 - Draft Guidance for Industry and Food and Drug Administration Staff; Total Product Life Cycle...

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  1. 76 FR 78670 - Draft Guidance for Industry and Food and Drug Administration Staff; Evaluation of Sex Differences...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-19

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing... adequately addressed in clinical trials. This draft guidance is not final nor is it in effect at this...

  2. 75 FR 59726 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-28

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... Assays; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the draft guidance entitled ``Class...

  3. 77 FR 63837 - Draft Guidance for Industry and Food and Drug Administration Staff; eCopy Program for Medical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-17

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration Staff; eCopy Program for Medical Device Submissions; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability...

  4. 21 CFR 21.20 - Procedures for notice of Food and Drug Administration Privacy Act Record Systems.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Administration Privacy Act Record Systems. 21.20 Section 21.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROTECTION OF PRIVACY Food and Drug Administration Privacy Act Record Systems § 21.20 Procedures for notice of Food and Drug Administration Privacy Act...

  5. 21 CFR 21.20 - Procedures for notice of Food and Drug Administration Privacy Act Record Systems.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Administration Privacy Act Record Systems. 21.20 Section 21.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROTECTION OF PRIVACY Food and Drug Administration Privacy Act Record Systems § 21.20 Procedures for notice of Food and Drug Administration Privacy Act...

  6. 21 CFR 21.20 - Procedures for notice of Food and Drug Administration Privacy Act Record Systems.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Administration Privacy Act Record Systems. 21.20 Section 21.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROTECTION OF PRIVACY Food and Drug Administration Privacy Act Record Systems § 21.20 Procedures for notice of Food and Drug Administration Privacy Act...

  7. 21 CFR 21.20 - Procedures for notice of Food and Drug Administration Privacy Act Record Systems.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Administration Privacy Act Record Systems. 21.20 Section 21.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROTECTION OF PRIVACY Food and Drug Administration Privacy Act Record Systems § 21.20 Procedures for notice of Food and Drug Administration Privacy Act...

  8. Effects of Acute Administration of Ketorolac on Mammalian Vestibular Sensory Evoked Potentials

    PubMed Central

    Gaines, G Christopher; Jones, Timothy A

    2013-01-01

    The nonsteroidal antiinflammatory drug (NSAID) ketorolac is a candidate for use as a supplemental analgesic during major surgery in anesthetized rodents. The use of ketorolac during surgery is believed to reduce the anesthetic dose required to achieve and maintain an adequate surgical plane, thus improving the physiologic condition and survival of animals during long experimental procedures. Ketorolac has reported side effects that include dizziness, ear pain, hearing loss, tinnitus, and vertigo in humans, but ketorolac has not been reported to affect the vestibular system in animals. To investigate this possibility, we evaluated the acute effects of ketorolac on vestibular compound action potentials in C57BL/6 mice. Linear vestibular sensory-evoked potentials (VsEP) were recorded during the administration of ketorolac at doses 3 to 14 times the effective analgesic dose. VsEP results for ketorolac were compared with those from a control group maintained under anesthesia for the same period. Ketorolac did not significantly affect the temporal profiles of response latencies and amplitudes or the rate of change in response measures over time between controls and ketorolac-treated mice. These findings demonstrate that ketorolac can be used as an analgesic to supplement anesthesia in mice without concerns of modifying the amplitudes and latencies of the linear VsEP. PMID:23562034

  9. Effects of acute administration of ketorolac on mammalian vestibular sensory evoked potentials.

    PubMed

    Gaines, G Christopher; Jones, Timothy A

    2013-01-01

    The nonsteroidal antiinflammatory drug (NSAID) ketorolac is a candidate for use as a supplemental analgesic during major surgery in anesthetized rodents. The use of ketorolac during surgery is believed to reduce the anesthetic dose required to achieve and maintain an adequate surgical plane, thus improving the physiologic condition and survival of animals during long experimental procedures. Ketorolac has reported side effects that include dizziness, ear pain, hearing loss, tinnitus, and vertigo in humans, but ketorolac has not been reported to affect the vestibular system in animals. To investigate this possibility, we evaluated the acute effects of ketorolac on vestibular compound action potentials in C57BL/6 mice. Linear vestibular sensory-evoked potentials (VsEP) were recorded during the administration of ketorolac at doses 3 to 14 times the effective analgesic dose. VsEP results for ketorolac were compared with those from a control group maintained under anesthesia for the same period. Ketorolac did not significantly affect the temporal profiles of response latencies and amplitudes or the rate of change in response measures over time between controls and ketorolac-treated mice. These findings demonstrate that ketorolac can be used as an analgesic to supplement anesthesia in mice without concerns of modifying the amplitudes and latencies of the linear VsEP.

  10. Pilot study of the safety of starting administration of low-dose aspirin and cilostazol in acute ischemic stroke.

    PubMed

    Fujita, Keishi; Komatsu, Yoji; Sato, Naoaki; Higuchi, Osamu; Kujiraoka, Yuji; Kamezaki, Takao; Suzuki, Kensuke; Matsumura, Akira

    2011-01-01

    Progressive stroke is a serious problem due to the associated morbidity and mortality. Aspirin is recommended for acute ischemic stroke, but does not reduce the frequency of stroke progression. No standard treatment has been approved for the prevention of stroke progression. Cilostazol, which reduces platelet aggregation about 3 hours after single administration, does not increase the frequency of bleeding events when compared with aspirin or a placebo. Moreover, the combination of 100 mg aspirin and 200 mg cilostazol does not increase the frequency of bleeding events compared with only 100 mg aspirin, and thus is expected to prevent stroke progression with a high degree of safety. The present study investigated the safety of this combination of two drugs administered at the above concentrations in 54 patients with acute ischemic stroke within 48 hours of stroke onset. Modified National Institutes of Health Stroke Scale (NIHSS) measurements were performed at baseline and again on day 4 to 7. Progressive stroke was defined as an increase greater than or equal to 1 point on NIHSS. Patient scores on the modified Rankin Scale (mRS) were evaluated at baseline and 3 months after enrollment. Stroke progression occurred in 11.1% of the patients. The percentages of patients with mRS score from 0 to 2 were 42.6% and 75% at baseline and 3 months, respectively. No symptomatic intracranial hemorrhage or major extracranial hemorrhage occurred. These results suggest that administration of aspirin and cilostazol is safe for acute ischemic stroke.

  11. 76 FR 44594 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-26

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff...; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...'s good guidance practices. DATES: Submit either electronic or written comments on this guidance...

  12. 75 FR 69449 - Draft Guidance for Industry and Food and Drug Administration Staff on Dear Health Care Provider...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-12

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration...; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug... manufacturer or distributor of a human drug or biologic, or from FDA--intended to alert physicians and...

  13. 78 FR 9396 - Draft Guidance for Industry and Food and Drug Administration Staff; Civil Money Penalties for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-08

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  14. Shortage of Peritoneal Dialysis Solution and the Food and Drug Administration's Response.

    PubMed

    Jensen, Valerie; Throckmorton, Douglas C

    2015-08-07

    Although the number of new drug shortages has been lower in recent years than in the past, severe shortages have occurred that have affected large numbers of patients. A new law entitled the Food and Drug Administration Safety and Innovation Act was enacted in July of 2012, which requires companies to notify the Food and Drug Administration of anticipated shortages. This notification requirement has allowed the Food and Drug Administration to work closely with manufacturers earlier to mitigate and, often, prevent shortages. However, not all shortages are able to be prevented, and the shortage of peritoneal dialysis solution is one that has had a significant effect on patients. The Food and Drug Administration continues to use all available tools to address this shortage with manufacturers, including temporary availability of imported peritoneal dialysis solution from Ireland. Mitigating shortages is a top priority for the Food and Drug Administration, and communication with all stakeholders is essential.

  15. Acute oral administration of low doses of methylphenidate targets calretinin neurons in the rat septal area

    PubMed Central

    García-Avilés, Álvaro; Albert-Gascó, Héctor; Arnal-Vicente, Isabel; Elhajj, Ebtisam; Sanjuan-Arias, Julio; Sanchez-Perez, Ana María; Olucha-Bordonau, Francisco

    2015-01-01

    Methylphenidate (MPD) is a commonly administered drug to treat children suffering from attention deficit hyperactivity disorder (ADHD). Alterations in septal driven hippocampal theta rhythm may underlie attention deficits observed in these patients. Amongst others, the septo-hippocampal connections have long been acknowledged to be important in preserving hippocampal function. Thus, we wanted to ascertain if MPD administration, which improves attention in patients, could affect septal areas connecting with hippocampus. We used low and orally administered MPD doses (1.3, 2.7 and 5 mg/Kg) to rats what mimics the dosage range in humans. In our model, we observed no effect when using 1.3 mg/Kg MPD; whereas 2.7 and 5 mg/Kg induced a significant increase in c-fos expression specifically in the medial septum (MS), an area intimately connected to the hippocampus. We analyzed dopaminergic areas such as nucleus accumbens and striatum, and found that only 5 mg/Kg induced c-fos levels increase. In these areas tyrosine hydroxylase correlated well with c-fos staining, whereas in the MS the sparse tyrosine hydroxylase fibers did not overlap with c-fos positive neurons. Double immunofluorescence of c-fos with neuronal markers in the septal area revealed that co-localization with choline acethyl transferase, parvalbumin, and calbindin with c-fos did not change with MPD treatment; whereas, calretinin and c-fos double labeled neurons increased after MPD administration. Altogether, these results suggest that low and acute doses of methylphenidate primary target specific populations of caltretinin medial septal neurons. PMID:25852493

  16. Effect of acute thioacetamide administration on rat brain phospholipid metabolism

    SciTech Connect

    Osada, J.; Aylagas, H.; Miro-Obradors, M.J.; Arce, C.; Palacios-Alaiz, E.; Cascales, M. )

    1990-09-01

    Brain phospholipid composition and the ({sup 32}P)orthophosphate incorporation into brain phospholipids of control and rats treated for 3 days with thioacetamide were studied. Brain phospholipid content, phosphatidylcholine, phosphatidylethanolamine, lysolecithin and phosphatidic acid did not show any significant change by the effect of thioacetamide. In contrast, thioacetamide induced a significant decrease in the levels of phosphatidylserine, sphingomyelin, phosphatidylinositol and diphosphatidylglycerol. After 75 minutes of intraperitoneal label injection, specific radioactivity of all the above phospholipids with the exception of phosphatidylethanolamine and phosphatidylcholine significantly increased. After 13 hours of isotope administration the specific radioactivity of almost all studied phospholipid classes was elevated, except for phosphatidic acid, the specific radioactivity of which did not change and for diphosphatidylglycerol which showed a decrease in specific radioactivity. These results suggest that under thioacetamide treatment brain phospholipids undergo metabolic transformations that may contribute to the hepatic encephalopathy induced by thioacetamide.

  17. Neurocognitive performance following acute mephedrone administration, with and without alcohol.

    PubMed

    de Sousa Fernandes Perna, E B; Papaseit, E; Pérez-Mañá, C; Mateus, J; Theunissen, E L; Kuypers, Kpc; de la Torre, R; Farré, M; Ramaekers, J G

    2016-12-01

    Recreational use of mephedrone, alone and in combination with alcohol, has increased over the past years. Pharmacological properties of mephedrone share similarities with methylenedioxymethamphetamine (MDMA), but its effect on neurocognitive function has not been well established in humans. The present study assessed the effect of mephedrone alone and after co-administration with alcohol on neurocognitive function. It was hypothesised that mephedrone would improve psychomotor performance but impair memory performance, when administered alone. Neurocognitive performance was expected to be impaired following mephedrone when combined with alcohol. Eleven participants received single doses of 200 mg mephedrone or placebo combined with 0.8 g/kg alcohol or placebo. Neurocognitive performance was assessed at baseline (T0), at one hour (T1) and four hours after (T2) mephedrone administration, by means of the Divided Attention Task (DAT), Critical Tracking Task (CTT), and the Spatial Memory Test (SMT). Mephedrone intoxication impaired short-term spatial memory at T1 and improved critical tracking performance at T2 Mephedrone alone did not affect divided attention, but did show an interaction with alcohol on reaction time at T2 Reaction time decreased when mephedrone was combined with alcohol as compared to alcohol alone. Alcohol intoxication impaired both short- and long-term spatial memory at T1 and divided attention at T1 and T2 Critical tracking performance was not affected by alcohol intoxication. The current findings support the hypothesis that mephedrone improves psychomotor performance, impairs spatial memory and does not affect divided attention performance. Stimulatory effects of mephedrone were not sufficient to compensate for the impairing effects of alcohol on most performance parameters.

  18. Behavioural antecedents to pro re nata psychotropic medication administration on acute psychiatric wards.

    PubMed

    Stewart, Duncan; Robson, Deborah; Chaplin, Robert; Quirk, Alan; Bowers, Len

    2012-12-01

    This study examined the antecedents to administration of pro re nata (PRN) psychotropic medication on acute psychiatric wards, with a particular focus on its use in response to patient aggression and other conflict behaviours. A sample of 522 adult in-patients was recruited from 84 acute psychiatric wards in England. Data were collected from nursing and medical records for the first 2  weeks of admission. Two-thirds of patients received PRN medication during this period, but only 30% of administrations were preceded by patient conflict (usually aggression). Instead, it was typically administered to prevent escalation of patient behaviour and to help patients sleep. Overall, no conflict behaviours or further staff intervention occurred after 61% of PRN administrations. However, a successful outcome was less likely when medication was administered in response to patient aggression. The study concludes that improved monitoring, review procedures, training for nursing staff, and guidelines for the administration of PRN medications are needed.

  19. Drug-eluting stent thrombosis: the Kounis hypersensitivity-associated acute coronary syndrome revisited.

    PubMed

    Chen, Jack P; Hou, Dongming; Pendyala, Lakshmana; Goudevenos, John A; Kounis, Nicholas G

    2009-07-01

    The advent of drug-eluting stents (DES) has revolutionized the field of interventional cardiology. Their dramatic and persistent restenotic and target lesion revascularization advantages are unquestioned. However, concerns over the rare but potentially catastrophic risk of stent thrombosis (ST) have tempered universal acceptance of these devices. Although the precise mechanism of DES ST is undoubtedly multifactorial and as yet not fully elucidated, delayed or incomplete endothelial healing clearly plays a pivotal role. Detailed histopathological data have implicated a contributory allergic or hypersensitivity component, as verified by the Food and Drug Administration's Manufacturer and User Device Experience Center and the Research on Adverse Drug/device events And Reports (RADAR) project. These findings thus suggest a potential connection with the Kounis syndrome, the concurrence of acute coronary events with allergic, hypersensitivity, anaphylactic, or anaphylactoid reactions. Potential culprits responsible for this phenomenon include: arachidonic acid metabolites such as leukotrienes and thromboxane, proteolytic enzymes such as chymase and tryptase, histamine, cytokines, and chemokines. Additionally, inflammatory cells such as macrophages, T-lymphocytes, and mast cells are probably also contributory. Autopsy-confirmed infiltrates of various inflammatory cells including lymphocytes, plasma cells, macrophages, and eosinophils have been reported in all 3 vascular wall layers and are reminiscent of those associated with the Kounis syndrome. Although the concurrence of acute coronary syndromes with hypersensitivity reactions has been long established, the specific association with DES ST remains unproven. Potential incorporation of hypersensitivity suppressive agents might represent a promising paradigm shift from efficacy to safety in future DES designs.

  20. Brain and Muscle Redox Imbalance Elicited by Acute Ethylmalonic Acid Administration

    PubMed Central

    Schuck, Patrícia Fernanda; Milanez, Ana Paula; Felisberto, Francine; Galant, Leticia Selinger; Machado, Jéssica Luca; Furlanetto, Camila Brulezi; Petronilho, Fabricia; Dal-Pizzol, Felipe; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2015-01-01

    Ethylmalonic acid (EMA) accumulates in tissues and biological fluids of patients affected by short-chain acyl-CoA dehydrogenase deficiency (SCADD) and ethylmalonic encephalopathy, illnesses characterized by neurological and muscular symptoms. Considering that the mechanisms responsible for the brain and skeletal muscle damage in these diseases are poorly known, in the present work we investigated the effects of acute EMA administration on redox status parameters in cerebral cortex and skeletal muscle from 30-day-old rats. Animals received three subcutaneous injections of EMA (6 μmol/g; 90 min interval between injections) and were killed 1 h after the last administration. Control animals received saline in the same volumes. EMA administration significantly increased thiobarbituric acid-reactive substances levels in cerebral cortex and skeletal muscle, indicating increased lipid peroxidation. In addition, carbonyl content was increased in EMA-treated animal skeletal muscle when compared to the saline group. EMA administration also significantly increased 2’,7’-dihydrodichlorofluorescein oxidation and superoxide production (reactive species markers), and decreased glutathione peroxidase activity in cerebral cortex, while glutathione levels were decreased only in skeletal muscle. On the other hand, respiratory chain complex I-III activity was altered by acute EMA administration neither in cerebral cortex nor in skeletal muscle. The present results show that acute EMA administration elicits oxidative stress in rat brain and skeletal muscle, suggesting that oxidative damage may be involved in the pathophysiology of the brain and muscle symptoms found in patients affected by SCADD and ethylmalonic encephalopathy. PMID:26010931

  1. Brain and muscle redox imbalance elicited by acute ethylmalonic acid administration.

    PubMed

    Schuck, Patrícia Fernanda; Milanez, Ana Paula; Felisberto, Francine; Galant, Leticia Selinger; Machado, Jéssica Luca; Furlanetto, Camila Brulezi; Petronilho, Fabricia; Dal-Pizzol, Felipe; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2015-01-01

    Ethylmalonic acid (EMA) accumulates in tissues and biological fluids of patients affected by short-chain acyl-CoA dehydrogenase deficiency (SCADD) and ethylmalonic encephalopathy, illnesses characterized by neurological and muscular symptoms. Considering that the mechanisms responsible for the brain and skeletal muscle damage in these diseases are poorly known, in the present work we investigated the effects of acute EMA administration on redox status parameters in cerebral cortex and skeletal muscle from 30-day-old rats. Animals received three subcutaneous injections of EMA (6 μmol/g; 90 min interval between injections) and were killed 1 h after the last administration. Control animals received saline in the same volumes. EMA administration significantly increased thiobarbituric acid-reactive substances levels in cerebral cortex and skeletal muscle, indicating increased lipid peroxidation. In addition, carbonyl content was increased in EMA-treated animal skeletal muscle when compared to the saline group. EMA administration also significantly increased 2',7'-dihydrodichlorofluorescein oxidation and superoxide production (reactive species markers), and decreased glutathione peroxidase activity in cerebral cortex, while glutathione levels were decreased only in skeletal muscle. On the other hand, respiratory chain complex I-III activity was altered by acute EMA administration neither in cerebral cortex nor in skeletal muscle. The present results show that acute EMA administration elicits oxidative stress in rat brain and skeletal muscle, suggesting that oxidative damage may be involved in the pathophysiology of the brain and muscle symptoms found in patients affected by SCADD and ethylmalonic encephalopathy.

  2. Revocation of Office of Generic Drug's interim policy statement on inactive ingredients. Food and Drug Administration, HHS. Notice.

    PubMed

    1999-04-30

    The Food and Drug Administration (FDA) is revoking an interim policy statement on inactive ingredients in parenteral, ophthalmic, otic, and topical generic drug products (Interim Inactive Ingredient Policy). These generic drug products are the subjects of abbreviated new drug applications (ANDA's). The Interim Inactive Ingredient Policy was issued as a memorandum from the Acting Director of the Center for Drug Evaluation and Research's (CDER's) Office of Generic Drugs, FDA, to CDER's Associate Director for Science and Medical Affairs, FDA. FDA is taking this action because the Interim Inactive Ingredient Policy no longer represents current agency policy.

  3. Food and Drug Administration (FDA) drug approval end points for chronic cutaneous ulcer studies.

    PubMed

    Eaglstein, William H; Kirsner, Robert S; Robson, Martin C

    2012-01-01

    The rising costs of caring for chronic cutaneous ulcers (CCUs) and recent appreciation of the mortality of CCUs have led to consideration of the reasons for the failure to have new drug therapies. No new chemical entities to heal CCUs have been approved by the Food and Drug Administration (FDA) in over a decade, in part due to an inability to reach the FDA accepted end point of "complete wound closure." The frequent failure to reach the complete closure end point brings forward the question of the relevance of other healing end points such as improved quality of life, or partial healing. Because CCUs carry a prognosis and mortality rate worse than many cancers, it is reasonable to compare the FDA trial end points for cancer drug approval with those for CCUs. And the difference is quite striking. While there is only one end point for CCUs, there are five surrogate and three direct end points for cancers. In contrast to cancer, surrogate end points and partial healing are not acceptable for therapies aimed at CCUs. For example, making tumors smaller is an acceptable end point, but making CCUs smaller is not and improvement in the signs and symptoms of cancer is an acceptable end point for cancers but not CCUs. As CCUs carry a prognosis and mortality rate worse than many cancers, we believe a reconsideration of end points for CCUs is highly warranted.

  4. 78 FR 6762 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules To Establish Standards...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-31

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 16, 106, 110, 112, 114, 117, 120, 123, 129, 179, and 211 Food and Drug Administration Food Safety Modernization Act: Proposed Rules To Establish... Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for Human...

  5. 78 FR 10107 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules To Establish Standards...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-13

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 16, 106, 110, 112, 114, 117, 120, 123, 129, 179, and 211 Food and Drug Administration Food Safety Modernization Act: Proposed Rules To Establish... Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for Human...

  6. 75 FR 11893 - Food and Drug Administration Transparency Task Force; Request for Comments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-12

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Transparency Task Force... transparent, collaborative, and participatory government. FDA has formed an internal Transparency Task Force..., the Task Force has held two public meetings, on June 24, 2009, and November 3, 2009, and established...

  7. 77 FR 31026 - Requirements for Importing Food and Drug Administration Regulated Products Into the United States

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-24

    ... respect to importing pharmaceutical products, medical devices, food products, as well as technology which... No: 2012-12592] DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Requirements for Importing Food and Drug Administration Regulated Products Into the...

  8. 77 FR 38173 - Agreements and Memoranda of Understanding Between the Food and Drug Administration and Other...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-27

    ... AGENCY: Food and Drug Administration, HHS. ACTION: Direct final rule; withdrawal. SUMMARY: The Food and Drug Administration (FDA) published in the Federal Register of March 23, 2012 (77 FR 16923), a direct final rule making technical changes to update a requirement that many of its written agreements...

  9. 75 FR 15439 - Food and Drug Administration/Xavier University Global Medical Device Conference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-29

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration/Xavier University Global... University, is announcing a public conference entitled ``FDA/Xavier University Global Medical Device... public conference will be held on the campus of Xavier University, 3800 Victory Pkwy., Cincinnati,...

  10. 78 FR 15957 - Food and Drug Administration/Xavier University Global Medical Device Conference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-13

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration/Xavier University Global... University, is announcing a public conference entitled ``FDA/Xavier University Global Medical Device... public conference will be held on the campus of Xavier University, 3800 Victory Pkwy., Cincinnati,...

  11. 77 FR 21784 - Science Board to the Food and Drug Administration; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-11

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Science Board to the Food and Drug Administration; Notice of... provides advice to the Agency on keeping pace with technical and scientific evolutions in the fields...

  12. 76 FR 61366 - Food and Drug Administration Transparency Initiative: Draft Proposals for Public Comment to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-04

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Transparency Initiative: Draft Proposals for Public Comment to Increase Transparency By Promoting Greater Access to the Agency's Compliance... availability; request for comments. SUMMARY: As part of the Transparency Initiative, the Food and...

  13. 76 FR 55927 - Draft Guidance for Industry and Food and Drug Administration Staff; Demonstrating the Substantial...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-09

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration Staff; Demonstrating the Substantial Equivalence of a New Tobacco Product: Responses to Frequently Asked... the Substantial Equivalence of a New Tobacco Product: Responses to Frequently Asked Questions.''...

  14. 78 FR 5185 - Guidance for Industry and Food and Drug Administration Staff; Humanitarian Use Device (HUD...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-24

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff... the industry and FDA staff entitled ``Humanitarian Use Device (HUD) Designations.'' Devices are... HUD designations may be eligible for marketing approval under the Humanitarian Device Exemption...

  15. 76 FR 78931 - Food and Drug Administration Rare Disease Patient Advocacy Day; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-20

    ... Disorders, and the Genetic Alliance. FDA encourages all attendees to also plan on attending the NIH Rare... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Food and Drug Administration Rare Disease Patient...

  16. TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE AFTER ACUTE ORAL ADMINISTRATION

    EPA Science Inventory

    TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE
    AFTER ACUTE ORAL ADMINISTRATION

    Michael F. Hughes, Ph.D., Brenda C. Edwards, Carol T. Mitchell and Elaina M. Kenyon, Ph.D. United States Environmental Protection Agency, Office of Research and Development, Nation...

  17. The effects of acute alcohol administration on the human brain: insights from neuroimaging.

    PubMed

    Bjork, James M; Gilman, Jodi M

    2014-09-01

    Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for development and maintenance of addiction. These in vivo neuroimaging studies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same structures, where some elements of these decrements normalize with extended sobriety. In this review, we will summarize recent findings about acute human brain responses to alcohol using neuroimaging techniques, and how they might explain behavioral effects of alcohol intoxication. We then briefly address how chronic alcohol intoxication (as inferred from cross-sectional differences between various drinking populations and controls) may yield individual brain differences between drinking subjects that may confound interpretation of acute alcohol administration effects. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'.

  18. Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models

    PubMed Central

    Li, Minmin; Lu, Chengwen; Zhang, Leiming; Zhang, Jianqiao; Du, Yuan; Duan, Sijin; Wang, Tian; Fu, Fenghua

    2015-01-01

    The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP) induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2) and cyclooxygenase- (COX-) 2. In CLP model, low dose of escin ameliorates endotoxin induced liver injury and intestinal mucosal injury and increases the expression of tight junction protein claudin-5 in mice. These findings suggest that escin effectively inhibits acute inflammation and reduces intestinal mucosal injury in animal models. PMID:26199634

  19. Association of Geographical Factors With Administration of Tissue Plasminogen Activator for Acute Ischemic Stroke

    PubMed Central

    Kunisawa, Susumu; Morishima, Toshitaka; Ukawa, Naoto; Ikai, Hiroshi; Otsubo, Tetsuya; Ishikawa, Koichi B.; Yokota, Chiaki; Minematsu, Kazuo; Fushimi, Kiyohide; Imanaka, Yuichi

    2013-01-01

    Background Intravenous tissue plasminogen activator (tPA) is an effective treatment for acute ischemic stroke if administered within a few hours of stroke onset. Because of this time restriction, tPA administration remains infrequent. Ambulance use is an effective strategy for increasing tPA administration but may be influenced by geographical factors. The objectives of this study are to investigate the relationship between tPA administration and ambulance use and to examine how patient travel distance and population density affect tPA utilization. Methods and Results We analyzed administrative claims data from 114 194 acute ischemic stroke cases admitted to 603 hospitals between July 2010 and March 2012. Mixed‐effects logistic regression models of patients nested within hospitals with a random intercept were generated to analyze possible predictive factors (including patient characteristics, ambulance use, and driving time from home to hospital) of tPA administration for different population density categories to investigate differences in these factors in various regional backgrounds. Approximately 5.1% (5797/114 194) of patients received tPA. The composition of baseline characteristics varied among the population density categories, but adjustment for covariates resulted in all factors having similar associations with tPA administration in every category. The administration of tPA was associated with patient age and severity of stroke symptoms, but driving time showed no association. Ambulance use was significantly associated with tPA administration even after adjustment for covariates. Conclusion The association between ambulance use and tPA administration suggests the importance of calling an ambulance for suspected stroke. Promoting ambulance use for acute ischemic stroke patients may increase tPA use. PMID:24045119

  20. 28 CFR 0.103a - Delegations respecting claims against the Drug Enforcement Administration.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... claims against the Drug Enforcement Administration. (a) The Administrator of DEA is authorized to... lawful activities of DEA personnel in an amount not to exceed $50,000.00 in any one case. (b) Notwithstanding the provisions of 28 CFR 0.104, the Administrator of DEA is authorized to redelegate the power...

  1. 28 CFR 0.103a - Delegations respecting claims against the Drug Enforcement Administration.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... claims against the Drug Enforcement Administration. (a) The Administrator of DEA is authorized to... lawful activities of DEA personnel in an amount not to exceed $50,000.00 in any one case. (b) Notwithstanding the provisions of 28 CFR 0.104, the Administrator of DEA is authorized to redelegate the power...

  2. 28 CFR 0.103a - Delegations respecting claims against the Drug Enforcement Administration.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... claims against the Drug Enforcement Administration. (a) The Administrator of DEA is authorized to... lawful activities of DEA personnel in an amount not to exceed $50,000.00 in any one case. (b) Notwithstanding the provisions of 28 CFR 0.104, the Administrator of DEA is authorized to redelegate the power...

  3. 76 FR 43332 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-20

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff...; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug... subject to comment in accordance with the Agency's good guidance practices. DATES: Submit...

  4. 76 FR 64354 - Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-18

    ... HUMAN SERVICES Food and Drug Administration Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small Business; Extension of Comment Period AGENCY: Food and Drug... Drug Administration Food Safety Modernization Act Fee Amounts on Small Business; Request for...

  5. 76 FR 16425 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-23

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff...; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug... document is immediately in effect as the special control for the ovarian adnexal mass assessment score...

  6. 77 FR 60126 - Guidance for Industry on Acute Bacterial Otitis Media: Developing Drugs for Treatment; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-02

    ...; Formerly 2008N-0004] Guidance for Industry on Acute Bacterial Otitis Media: Developing Drugs for Treatment... Media: Developing Drugs for Treatment.'' This guidance addresses FDA's current thinking regarding the... treatment of acute bacterial otitis media (ABOM). This guidance finalizes the revised draft guidance of...

  7. Role of US military research programs in the development of US Food and Drug Administration--approved antimalarial drugs.

    PubMed

    Kitchen, Lynn W; Vaughn, David W; Skillman, Donald R

    2006-07-01

    US military physicians and researchers helped identify the optimum treatment dose of the naturally occurring compound quinine and collaborated with the pharmaceutical industry in the development and eventual US Food and Drug Administration approval of the synthetic antimalarial drugs chloroquine, primaquine, chloroquine-primaquine, sulfadoxine-pyrimethamine, mefloquine, doxycycline, halofantrine, and atovaquone-proguanil. Because malaria parasites develop drug resistance, the US military must continue to support the creation and testing of new drugs to prevent and treat malaria until an effective malaria vaccine is developed. New antimalarial drugs also benefit civilians residing in and traveling to malarious areas.

  8. The influence of the time of antidotal treatment administration on the potency of newly developed oximes to counteract acute toxic effects of tabun in mice.

    PubMed

    Kassa, Jirí

    2005-01-01

    (1) The influence of the time of administration of antidotal treatment consisting of anticholinergic drug (atropine) and newly developed oxime (K027 or K048) on its effectiveness to eliminate tabun-induced lethal toxic effects was studied in mice. (2) The therapeutic efficacy of antidotal treatment of tabun-induced acute poisoning depends on the time of its administration regardless of the choice of the oxime. (3) Our results show that both oximes studied (K027, K048) are able to sufficiently eliminate lethal effects of tabun. Nevertheless, their efficacy significantly decreases when they were administered 5 min after tabun poisoning. (4) The findings support the hypothesis that both newly developed oximes appear to be suitable oximes to counteract acute toxicity of tabun although their ability to eliminate lethal toxic effects of tabun significantly decreases with prolonged time interval between tabun challenge and antidotal treatment administration.

  9. The administration of sulfonamide drugs to adult salmon

    USGS Publications Warehouse

    Amend, D.F.; Fryer, J.L.

    1968-01-01

    Mass treatment is the most convenient way to combat fish diseases. For example, drugs can be administered per os in diets, or chemicals can be added to the water. These methods are mostly ineffective in treating systemic infections of adult salmon because mature salmon do not feed, and many fish diseases cannot be controlled by chemical baths. Thus, effective treatment would require administering drugs to each individual.

  10. Antiallodynic Activity of Ceftriaxone and Clavulanic Acid in Acute Administration is Associated with Serum TNF-α Modulation and Activation of Dopaminergic and Opioidergic Systems.

    PubMed

    Ochoa-Aguilar, A; Sotomayor-Sobrino, M A; Jaimez, R; Rodríguez, R; Plancarte-Sánchez, R; Ventura-Martinez, R

    2017-03-26

    Preclinical Research The aim of this study was to determine the antiallodynic effect of acute administration of the β-lactam antimicrobials, ceftriaxone (CFX) and clavulanic acid (CLAV), for the control of established pain on a model of neuropathic pain (NP). We also investigated the involvement of dopaminergic and opioidergic pathways as well as alterations in serum concentrations of TNF-α in the antiallodynic actions of these drugs. CFX, CLAV, or gabapentin (GAP), a reference drug, were administered i.p. twelve days after constriction of the sciatic nerve in rats. Mechanic and cold allodynia were evaluated for 3 h and alterations in serum concentration of TNF-α determined. Both CFX and CLAV had antiallodynic effects in response to mechanical and cold stimulation, similar to GAP. The antiallodynic effects of CFX and CLAV were blocked by haloperidol (HAL), a D2 receptor antagonist, and by naloxone (NLX), an opioid receptor antagonist. Additionally, serum TNF-α levels were attenuated following CFX and CLAV administration. These results suggest that acute administration of CFX and CLAV may represent a promising approach for treating the acute allodynia of NP, and that the mechanisms involved in these effects involve activation of dopaminergic and opioidergic pathways as well as modulation of TNF-α production. Drug Dev Res, 2017. © 2017 Wiley Periodicals, Inc.

  11. Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm).

    PubMed

    Kennedy, D O; Scholey, Andrew B; Tildesley, N T J; Perry, E K; Wesnes, K A

    2002-07-01

    Melissa officinalis (lemon balm) is a traditional herbal medicine, which enjoys contemporary usage as a mild sedative, spasmolytic and antibacterial agent. It has been suggested, in light of in vitro cholinergic binding properties, that Melissa extracts may effectively ameliorate the cognitive deficits associated with Alzheimer's disease. To date, no study has investigated the effects on cognition and mood of administration of Melissa to healthy humans. The present randomised, placebo-controlled, double-blind, balanced-crossover study investigated the acute effects on cognition and mood of a standardised extract of M. officinalis. Twenty healthy, young participants received single doses of 300, 600 and 900 mg of M. officinalis (Pharmaton) or a matching placebo at 7-day intervals. Cognitive performance was assessed using the Cognitive Drug Research (CDR) computerised test battery and two serial subtraction tasks immediately prior to dosing and at 1, 2.5, 4 and 6 h thereafter. In vitro IC(50) concentrations for the displacement of [3H]-(N)-nicotine and [3H]-(N)-scopolamine from nicotinic and muscarinic receptors in human occipital cortex tissue were also calculated. Results, utilising the cognitive factors previously derived from the CDR battery, included a sustained improvement in Accuracy of Attention following 600 mg of Melissa and time- and dose-specific reductions in both Secondary Memory and Working Memory factors. Self-rated "calmness," as assessed by Bond-Lader mood scales, was elevated at the earliest time points by the lowest dose, whilst "alertness" was significantly reduced at all time points following the highest dose. Both nicotinic and muscarinic binding were found to be low in comparison to the levels found in previous studies.

  12. Effects of acute and chronic administration of methylprednisolone on oxidative stress in rat lungs* **

    PubMed Central

    Torres, Ronaldo Lopes; Torres, Iraci Lucena da Silva; Laste, Gabriela; Ferreira, Maria Beatriz Cardoso; Cardoso, Paulo Francisco Guerreiro; Belló-Klein, Adriane

    2014-01-01

    Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO) and total reactive antioxidant potential (TRAP), in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.); acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methylprednisolone in drinking water (6 mg/kg per day for 30 days); and chronic control, comprising rats receiving normal drinking water. Results: The levels of TRAP were significantly higher in the acute treatment group rats than in the acute control rats, suggesting an improvement in the pulmonary defenses of the former. The levels of lung LPO were significantly higher in the chronic treatment group rats than in the chronic control rats, indicating oxidative damage in the lung tissue of the former. Conclusions: Our results suggest that the acute use of corticosteroids is beneficial to lung tissue, whereas their chronic use is not. The chronic use of methylprednisolone appears to increase lung LPO levels. PMID:25029646

  13. Chick embryo chorioallantoic membrane (CAM): an alternative predictive model in acute toxicological studies for anti-cancer drugs

    PubMed Central

    KUE, Chin Siang; TAN, Kae Yi; LAM, May Lynn; LEE, Hong Boon

    2015-01-01

    The chick embryo chorioallantoic membrane (CAM) is a preclinical model widely used for vascular and anti-vascular effects of therapeutic agents in vivo. In this study, we examine the suitability of CAM as a predictive model for acute toxicology studies of drugs by comparing it to conventional mouse and rat models for 10 FDA-approved anticancer drugs (paclitaxel, carmustine, camptothecin, cyclophosphamide, vincristine, cisplatin, aloin, mitomycin C, actinomycin-D, melphalan). Suitable formulations for intravenous administration were determined before the average of median lethal dose (LD50) and median survival dose (SD50) in the CAM were measured and calculated for these drugs. The resultant ideal LD50 values were correlated to those reported in the literature using Pearson’s correlation test for both intravenous and intraperitoneal routes of injection in rodents. Our results showed moderate correlations (r2=0.42 − 0.68, P<0.005–0.05) between the ideal LD50 values obtained using the CAM model with LD50 values from mice and rats models for both intravenous and intraperitoneal administrations, suggesting that the chick embryo may be a suitable alternative model for acute drug toxicity screening before embarking on full toxicological investigations in rodents in development of anticancer drugs. PMID:25736707

  14. 28 CFR Appendix B to Part 61 - Drug Enforcement Administration Procedures Relating to the Implementation of the National...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR IMPLEMENTING THE NATIONAL.... This part applies to all organizational elements of the Drug Enforcement Administration . 2....

  15. 21 CFR 320.34 - Requirements for batch testing and certification by the Food and Drug Administration.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug...

  16. Technology assessment and the Food and Drug Administration

    NASA Technical Reports Server (NTRS)

    Kaplan, A. H.; Becker, R. H.

    1972-01-01

    The statutory standards underlying the activities of the FDA, and the problems the Agency faces in decision making are discussed from a legal point of view. The premarketing clearance of new drugs and of food additives, the two most publicized and criticized areas of FDA activity, are used as illustrations. The importance of statutory standards in technology assessment in a regulatory setting is developed. The difficulties inherent in the formulation of meaningful standards are recognized. For foods, the words of the statute are inadequate, and for drugs, a statutory recognition of the various other objectives would be useful to the regulator and the regulated.

  17. Drug-induced Pneumonitis Following the Administration of TAS-102

    PubMed Central

    Hasegawa, Yoshikazu; Ota, Takayo; Tsukuda, Hiroshi; Suzumura, Tomohiro; Fukuoka, Masahiro

    2016-01-01

    A 59-year-old woman, diagnosed with advanced rectal cancer, presented with a low-grade fever and dyspnea on exertion after the 2nd cycle of TAS-102. TAS-102 has promising efficacy in patients with metastatic colorectal cancer. A CT scan revealed mosaic patterns with bilateral ground-glass opacities. The drug lymphocyte stimulation test for TAS-102 was strongly positive and serum β-D glucan level was elevated. The clinical course was compatible with TAS-102-induced pneumonitis combined with pneumocystis pneumonia (PCP). We herein report a rare case of drug-induced pneumonitis in a patient receiving TAS-102 in combination with PCP. PMID:27725548

  18. Teen Involvement for Drug Abuse Prevention. Administrator's Guide.

    ERIC Educational Resources Information Center

    Conroy, Gladys E.; Brayer, Herbert O.

    The Teen Involvement program is implemented primarily by youth, with guidance and direction from qualified, concerned adults. It aims at preventing substance abuse by utilizing positive youth-to-youth communications. Junior and senior high school students are trained to discusses causes of drug abuse and ways of preventing it with students in…

  19. Both acute and prolonged administration of EPO reduce cerebral and systemic vascular conductance in humans.

    PubMed

    Rasmussen, Peter; Kim, Yu-Sok; Krogh-Madsen, Rikke; Lundby, Carsten; Olsen, Niels V; Secher, Niels H; van Lieshout, Johannes J

    2012-03-01

    Administration of erythropoietin (EPO) has been linked to cerebrovascular events. EPO reduces vascular conductance, possibly because of the increase in hematocrit. Whether EPO in itself affects the vasculature remains unknown; here it was evaluated in healthy males by determining systemic and cerebrovascular variables following acute (30,000 IU/d for 3 d; n=8) and chronic (5000 IU/week for 13 wk; n=8) administration of EPO, while the responsiveness of the vasculature was challenged during cycling exercise, with and without hypoxia. Prolonged administration of EPO increased hematocrit from 42.5 ± 3.7 to 47.6 ± 4.1% (P<0.01), whereas hematocrit was unaffected following acute EPO administration. Yet, the two EPO regimes increased arterial pressure similarly (by 8±4 and 7±3 mmHg, respectively; P=0.01) through reduced vascular conductance (by 7±3 and 5±2%; P<0.05). Also, both EPO regimes widened the arterial-to-jugular O(2) differences at rest as well as during normoxic and hypoxic exercise (P<0.01), which indicated reduced cerebral blood flow despite preserved dynamic cerebral autoregulation, and an increase in middle cerebral artery mean blood flow velocity (P<0.05), therefore, reflected vasoconstriction. Thus, administration of EPO to healthy humans lowers systemic and cerebral conductance independent of its effect on hematocrit.

  20. 78 FR 32390 - Food and Drug Administration Safety and Innovation Act (FDASIA): Request for Comments on the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-30

    ... HUMAN SERVICES Office of the Secretary Food and Drug Administration Safety and Innovation Act (FDASIA... Information Technology AGENCY: Office of the National Coordinator for Health Information Technology...: The Food and Drug Administration (FDA), Office of the National Coordinator for Health...

  1. 76 FR 19998 - Supplemental Funding Under the Food and Drug Administration Pediatric Device Consortia Grant Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-11

    ... Service (HFA-500), Food and Drug Administration, 5630 Fishers Lane, rm.1079, Rockville, MD 20857, 301-827... Acquisition & Grant Services, 5630 Fishers Lane, Rm. 1079, Rockville, MD 20857, 301-827-7177. Dated: April...

  2. 21 CFR 7.45 - Food and Drug Administration-requested recall.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Industry Responsibilities § 7.45 Food and Drug Administration-requested recall. (a) The Commissioner of... agency action is necessary to protect the public health and welfare. (b) The Commissioner or his...

  3. 21 CFR 20.28 - Food and Drug Administration determinations of confidentiality.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SERVICES GENERAL PUBLIC INFORMATION General Policy § 20.28 Food and Drug Administration determinations of... held in confidence and will not be available for public disclosure shall be made only in the form of...

  4. 77 FR 125 - Draft Guidance for Industry and Food and Drug Administration Staff; Medical Device Classification...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-03

    ... Staff; Medical Device Classification Product Codes; Availability AGENCY: Food and Drug Administration... of the draft guidance entitled ``Medical Device Classification Product Codes.'' The purpose of the... classification product codes for medical devices regulated by the Center for Devices and Radiological...

  5. 76 FR 31345 - Cooperative Arrangement Between the United States Food and Drug Administration and the Inter...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-31

    ... Drug Administration and the Inter-American Institute for Cooperation in Agriculture AGENCY: Food and... notice of a cooperative arrangement between FDA and the Inter-American Institute for Cooperation...

  6. 77 FR 39498 - Guidances for Industry and Food and Drug Administration Staff: Computer-Assisted Detection...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-03

    ...--Premarket Notification (510(k)) Submissions; and Clinical Performance Assessment: Considerations for... Approval and Premarket Notification (510(k)) Submissions; Availability AGENCY: Food and Drug Administration... Applied to Radiology Images and Radiology Device Data--Premarket Notification (510(k)) Submissions''...

  7. 76 FR 14030 - Extension of Memorandum of Understanding Between the Food and Drug Administration and Servicio...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-15

    ... and Drug Administration and Servicio Nacional de Sanidad, Inocuidad y Calidad Agroalimentaria of the... Sanidad, Inocuidad y Calidad Agroalimentaria of the United Mexican States. The purpose of the MOU is...

  8. Rectal drug administration in adults: how, when, why.

    PubMed

    Lowry, Michael

    Administering medication per rectum can be the most appropriate route for some patients may not always be considered by health professionals. Cultural sensitivities, as well as misinformation regarding insertion methods, may be barriers to the practice. This article explains how the rectal route functions in drug absorption, clarifies when this route is appropriate to use and outlines the steps nurses should follow to prepare patients adequately and safely to carry out the procedure.

  9. Antidepressant-like activity of EMD 386088, a 5-HT6 receptor partial agonist, following systemic acute and chronic administration to rats.

    PubMed

    Jastrzębska-Więsek, Magdalena; Siwek, Agata; Partyka, Anna; Szewczyk, Bernadeta; Sowa-Kućma, Magdalena; Wasik, Anna; Kołaczkowski, Marcin; Wesołowska, Anna

    2015-10-01

    The study was designed to examine the potency of EMD 386088, a 5-HT6 receptor partial agonist, to exert antidepressant-like properties in animal models following acute and chronic intraperitoneal administration to rats. The modified rat forced swim test (FST) was utilized to examine a potential antidepressant effect of EMD 386088 after acute treatment (30 min before the test) and three times in a 24-h administration scheme (24 h, 5 h, and 30 min prior to the FST). The olfactory bulbectomy (OB) model was used to assess its antidepressant-like properties after chronic treatment (the drug was administered once daily for 14 days). EMD 386088 showed an antidepressant-like effect in all conducted tests. Its activity in FST after its acute administration (5 mg/kg) was blocked by the selective 5-HT6 receptor antagonist SB 271046. The obtained results seem to be specific, as there was no observed locomotor stimulation by the drug given at a lower/antidepressant dose. In the three times in the 24-h treatment scheme, EMD 386088 (2.5 mg/kg) exerted antidepressant properties in FST as well as increased locomotor activity in the open field test. Chronic administration of EMD 386088 (2.5 mg/kg) significantly improved the learning deficit in OB rats without affecting performance in Sham-operated (SH) animals in the passive avoidance test, and reduced OB-related rats' locomotor hyperactivity, but did not change the number of rearing + peeping episodes. The obtained findings suggest that EMD 386088 produces antidepressant-like activity after systemic acute and chronic administration which may result from direct stimulation of 5-HT6 receptors.

  10. Radium Ra 223 dichloride injection: U.S. Food and Drug Administration drug approval summary.

    PubMed

    Kluetz, Paul G; Pierce, William; Maher, V Ellen; Zhang, Hui; Tang, Shenghui; Song, Pengfei; Liu, Qi; Haber, Martin T; Leutzinger, Eldon E; Al-Hakim, Ali; Chen, Wei; Palmby, Todd; Alebachew, Elleni; Sridhara, Rajeshwari; Ibrahim, Amna; Justice, Robert; Pazdur, Richard

    2014-01-01

    On May 15, 2013, the U.S. Food and Drug Administration (FDA) approved radium Ra 223 dichloride (Ra-223; Xofigo injection; Bayer HealthCare Pharmaceuticals Inc.) for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no known visceral metastatic disease. The FDA review was based on clinical trial BC1-06, which randomly allocated patients (2:1) to either Ra-223 plus best standard of care (BSoC) or placebo plus BSoC. The primary endpoint was overall survival (OS) with a key secondary endpoint of time to first symptomatic skeletal event (SSE). A statistically significant improvement in OS was demonstrated [HR, 0.70; 95% confidence interval, 0.55-0.88, P = 0.0019]. At the prespecified interim analysis, the median OS durations were 14.0 and 11.2 months in the Ra-223 and placebo arms, respectively. The improvement in OS was supported by a delay in time to first SSE favoring the Ra-223 arm. The most common (>10%) adverse reactions in patients receiving Ra-223 were nausea, diarrhea, vomiting, and peripheral edema. The most common (>10%) hematologic laboratory abnormalities were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia. Ra-223 is the first α-emitting radiotherapeutic and the first radiopharmaceutical to demonstrate an OS advantage in metastatic prostate cancer.

  11. The Food and Drug Administration and pragmatic clinical trials of marketed medical products.

    PubMed

    Anderson, Monique L; Griffin, Joseph; Goldkind, Sara F; Zeitler, Emily P; Wing, Liz; Al-Khatib, Sana M; Sherman, Rachel E

    2015-10-01

    Pragmatic clinical trials can help answer questions of comparative effectiveness for interventions routinely used in medical practice. Pragmatic clinical trials may examine outcomes of one or more marketed medical products, and they are heterogeneous in design and risk. The Food and Drug Administration is charged with protecting the rights, safety, and welfare of individuals enrolled in clinical investigations, as well as assuring the integrity of the data upon which approval of medical products is made. The Food and Drug Administration has broad jurisdiction over drugs and medical devices (whether or not they are approved for marketing), and as such, clinical investigations of these products are subject to applicable Food and Drug Administration regulations. While many pragmatic clinical trials will meet the criteria for an exemption from the requirements for an investigational new drug application or investigational device exemption, in general, all clinical investigations of medical products that fall under Food and Drug Administration jurisdiction must adhere to regulations for informed consent and review by an institutional review board. We are concerned that current Food and Drug Administration requirements for obtaining individual informed consent may deter or delay the conduct of pragmatic clinical trials intended to develop reliable evidence of comparative safety and effectiveness of approved medical products that are regulated by the Food and Drug Administration. Under current regulations, there are no described mechanisms to alter or waive informed consent to make it less burdensome or more practicable for low-risk pragmatic clinical trials. We recommend that the Food and Drug Administration establish a risk-based approach to obtaining informed consent in pragmatic clinical trials that would facilitate the conduct of pragmatic clinical trials without compromising the protection of enrolled individuals or the integrity of the resulting data.

  12. Novel drugs for older patients with acute myeloid leukemia.

    PubMed

    Montalban-Bravo, G; Garcia-Manero, G

    2015-04-01

    Acute myeloid leukemia (AML) is the second most common form of leukemia and the most frequent cause of leukemia-related deaths in the United States. The incidence of AML increases with advancing age and the prognosis for patients with AML worsens substantially with increasing age. Many older patients are ineligible for intensive treatment and require other therapeutic approaches to optimize clinical outcome. To address this treatment gap, novel agents with varying mechanisms of action targeting different cellular processes are currently in development. Hypomethylating agents (azacitidine, decitabine, SGI-110), histone deacetylase inhibitors (vorinostat, pracinostat, panobinostat), FMS-like tyrosine kinase receptor-3 inhibitors (quizartinib, sorafenib, midostaurin, crenolanib), cytotoxic agents (clofarabine, sapacitabine, vosaroxin), cell cycle inhibitors (barasertib, volasertib, rigosertib) and monoclonal antibodies (gentuzumab ozogamicin, lintuzumab-Ac225) represent some of these promising new treatments. This review provides an overview of novel agents that have either completed or are currently in ongoing phase III trials in patients with previously untreated AML for whom intensive treatment is not an option. Other potential drugs in earlier stages of development will also be addressed in this review.

  13. 78 FR 51732 - The Food and Drug Administration/European Medicines Agency Orphan Product Designation and Grant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-21

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration The Food and Drug Administration/European Medicines Agency Orphan Product Designation and Grant Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The Food and...

  14. 76 FR 28688 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-18

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 866 Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: In Vitro Diagnostic Devices for Bacillus Species Detection AGENCY: Food and Drug Administration, HHS. ACTION: Notice of...

  15. 76 FR 50483 - Draft Guidance for Industry and Food and Drug Administration Staff; Factors to Consider When...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-15

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration Staff; Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Review; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

  16. 77 FR 14404 - Guidance for the Public, Food and Drug Administration (FDA) Advisory Committee Members, and FDA...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-09

    ... HUMAN SERVICES Food and Drug Administration Guidance for the Public, Food and Drug Administration (FDA) Advisory Committee Members, and FDA Staff: Public Availability of Advisory Committee Members' Financial.... SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a guidance for...

  17. 21 CFR 19.10 - Food and Drug Administration Conflict of Interest Review Board.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Management and Operations on any matter arising under the conflict of interest laws, except a determination... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Food and Drug Administration Conflict of Interest... HUMAN SERVICES GENERAL STANDARDS OF CONDUCT AND CONFLICTS OF INTEREST General Provisions § 19.10...

  18. 76 FR 55928 - Food and Drug Administration Health Professional Organizations Conference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-09

    ... Organizations Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. The... Professional Organizations. Dr. Margaret Hamburg, Commissioner of the Food and Drugs, and Dr. Janet Woodcock... organization, address, and telephone number. There is no registration fee for this conference....

  19. 77 FR 19425 - Prescription Drugs Not Administered During Treatment; Update to Administrative Cost for Calendar...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-30

    ... AFFAIRS Prescription Drugs Not Administered During Treatment; Update to Administrative Cost for Calendar... purposes of calculating VA's charges for prescription drugs that were not administered during treatment but... administered during treatment for: (1) A nonservice-connected disability for which the veteran is entitled...

  20. Drug Administration Errors in an Institution for Individuals with Intellectual Disability: An Observational Study

    ERIC Educational Resources Information Center

    van den Bemt, P. M. L. A.; Robertz, R.; de Jong, A. L.; van Roon, E. N.; Leufkens, H. G. M.

    2007-01-01

    Background: Medication errors can result in harm, unless barriers to prevent them are present. Drug administration errors are less likely to be prevented, because they occur in the last stage of the drug distribution process. This is especially the case in non-alert patients, as patients often form the final barrier to prevention of errors.…

  1. Effects of chronic administration of drugs of abuse on impulsive choice (delay discounting) in animal models.

    PubMed

    Setlow, Barry; Mendez, Ian A; Mitchell, Marci R; Simon, Nicholas W

    2009-09-01

    Drug-addicted individuals show high levels of impulsive choice, characterized by preference for small immediate over larger but delayed rewards. Although the causal relationship between chronic drug use and elevated impulsive choice in humans has been unclear, a small but growing body of literature over the past decade has shown that chronic drug administration in animal models can cause increases in impulsive choice, suggesting that a similar causal relationship may exist in human drug users. This article reviews this literature, with a particular focus on the effects of chronic cocaine administration, which have been most thoroughly characterized. The potential mechanisms of these effects are described in terms of drug-induced neural alterations in ventral striatal and prefrontal cortical brain systems. Some implications of this research for pharmacological treatment of drug-induced increases in impulsive choice are discussed, along with suggestions for future research in this area.

  2. Drug specificity in extended access cocaine and heroin self-administration.

    PubMed

    Lenoir, Magalie; Guillem, Karyn; Koob, George F; Ahmed, Serge H

    2012-11-01

    Increased drug availability can precipitate a rapid escalation of drug consumption in both vulnerable humans and laboratory animals. Drug intake escalation is observed across a broad spectrum of drugs of abuse, including stimulants, opiates, ethanol and phencyclidine. Whether and to what extent the processes underlying escalated levels of drug intake vary across different substances is poorly understood. The present study sought to address this question in rats self-administering both cocaine and heroin-two addictive drugs with both common and different neurobiological effects. In experiment 1, we determined how cocaine intake is initially related to heroin intake in non-escalated rats with a limited access to both drugs. In experiment 2, two groups of rats were initially allowed to self-administer either cocaine or heroin for 1 hour per day and then after behavioral stabilization, for 6 hours per day to precipitate drug intake escalation. In each group, dose-injection functions for cocaine and heroin self-administration were generated. In experiment 1, regardless of the dose, rats with a high intake of one drug did not necessarily have a high intake of the alternate drug. In experiment 2, escalated levels of heroin or cocaine self-administration did not generalize to the other drug. This outcome was confirmed in a third drug substitution experiment following different access lengths to cocaine self-administration (i.e. 1, 4 and 8 hours). The processes underlying spontaneous and escalated drug overconsumption appear thus to vary across different drugs of abuse. More research should be devoted in the future to these differences.

  3. 21 CFR 20.108 - Agreements between the Food and Drug Administration and other departments, agencies, and...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Food and Drug Administration Web site at http://www.fda.gov once finalized. (c) Agreements and... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Agreements between the Food and Drug Administration and other departments, agencies, and organizations. 20.108 Section 20.108 Food and Drugs FOOD...

  4. 21 CFR 20.108 - Agreements between the Food and Drug Administration and other departments, agencies, and...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Agreements between the Food and Drug Administration and other departments, agencies, and organizations. 20.108 Section 20.108 Food and Drugs FOOD AND... Specific Categories of Records § 20.108 Agreements between the Food and Drug Administration and...

  5. 21 CFR 20.108 - Agreements between the Food and Drug Administration and other departments, agencies, and...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Food and Drug Administration Web site at http://www.fda.gov once finalized. (c) Agreements and... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Agreements between the Food and Drug Administration and other departments, agencies, and organizations. 20.108 Section 20.108 Food and Drugs FOOD...

  6. Drug administration in animal studies of cardiac arrest does not reflect human clinical experience

    PubMed Central

    Reynolds, Joshua C.; Rittenberger, Jon C.; Menegazzi, James J.

    2007-01-01

    Introduction To date, there is no evidence showing a benefit from any advanced cardiac life support (ACLS) medication in out-of-hospital cardiac arrest (OOHCA), despite animal data to the contrary. One explanation may be a difference in the time to first drug administration. Our previous work has shown the mean time to first drug administration in clinical trials is 19.4 minutes. We hypothesized that the average time to drug administration in large animal experiments occurs earlier than in OOHCA clinical trials. Methods We conducted a literature review between 1990 and 2006 in MEDLINE using the following MeSH headings: swine, dogs, resuscitation, heart arrest, EMS, EMT, ambulance, ventricular fibrillation, drug therapy, epinephrine, vasopressin, amiodarone, lidocaine, magnesium, and sodium bicarbonate. We reviewed the abstracts of 331 studies and 197 full manuscripts. Exclusion criteria included: non-peer reviewed, all without primary animal data, and traumatic models. From these, we identified 119 papers that contained unique information on time to medication administration. The data are reported as mean, ranges, and 95% confidence intervals. Mean time to first drug administration in animal laboratory studies and clinical trials was compared with a t-test. Regression analysis was performed to determine if time to drug predicted ROSC. Results Mean time to first drug administration in 2378 animals was 9.5 minutes (range 3.0–28.0; 95% CI around mean 2.78, 16.22). This is less than the time reported in clinical trials (19.4 min, p<0.001). Time to drug predicted ROSC (Odds Ratio 0.844; 95% CI 0.738, 0.966). Conclusion Shorter drug delivery time in animal models of cardiac arrest may be one reason for the failure of animal studies to translate successfully into the clinical arena. PMID:17360097

  7. Is albumin administration in the acutely ill associated with increased mortality? Results of the SOAP study

    PubMed Central

    Vincent, Jean-Louis; Sakr, Yasser; Reinhart, Konrad; Sprung, Charles L; Gerlach, Herwig; Ranieri, V Marco

    2005-01-01

    Introduction Albumin administration in the critically ill has been the subject of some controversy. We investigated the use of albumin solutions in European intensive care units (ICUs) and its relationship to outcome. Methods In a cohort, multicenter, observational study, all patients admitted to one of the participating ICUs between 1 May and 15 May 2002 were followed up until death, hospital discharge, or for 60 days. Patients were classified according to whether or not they received albumin at any time during their ICU stay. Results Of 3,147 admitted patients, 354 (11.2%) received albumin and 2,793 (88.8%) did not. Patients who received albumin were more likely to have cancer or liver cirrhosis, to be surgical admissions, and to have sepsis. They had a longer length of ICU stay and a higher mortality rate, but were also more severely ill, as manifested by higher simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) scores than the other patients. A Cox proportional hazard model indicated that albumin administration was significantly associated with decreased 30-day survival. Moreover, in 339 pairs matched according to a propensity score, ICU and hospital mortality rates were higher in the patients who had received albumin than in those who had not (34.8 versus 20.9% and 41.3 versus 27.7%, respectively, both p < 0.001). Conclusion Albumin administration was associated with decreased survival in this population of acutely ill patients. Further prospective randomized controlled trials are needed to examine the effects of albumin administration in sub-groups of acutely ill patients. PMID:16356223

  8. Evaluation of physicochemical incompatibilities during parenteral drug administration in a paediatric intensive care unit.

    PubMed

    Gikic, M; Di Paolo, E R; Pannatier, A; Cotting, J

    2000-06-01

    Patients in paediatric intensive care units (PICU) often receive numerous medications by the parenteral route. Frequently two or more drugs are delivered simultaneously through the same line and the risk of physicochemical incompatibilities is thus important. The objectives of this study were 1) to identify prospectively the combinations of injectable drugs administered in the PICU of our university hospital and 2) to analyze them according to information found in the literature. The data were collected by a pharmacist over a 30-day period and classified in three categories: compatible, incompatible and undocumented. Nineteen patients were included in the study with a median age of 3.2 years. The mean number (+/- SD) of injectable drugs per patient and per day was 6.5 (+/- 2.8), for a total of 26 drugs and 7 solutes. 64 combinations of drugs were observed with 2 (31.3%), 3 (45.3%), 4 (10.9%) or 5 (12.5%) drugs. 81 drug-drug and 94 drug-solute combinations were recorded. Among these, 151 (86.3%) were compatible, 6 (3.4%) incompatible and 18 (10.3%) undocumented. The incompatibilities included furosemide (Lasix), a drug in alkaline solution and Vamina-Glucose, a total parenteral nutrition solution. No clinical consequences resulting from drug incompatibilities were shown in this study. We suggest that in vitro compatibility tests on standard drug combinations, as well as a training program for nurses on drug incompatibility problems would sensitively increase the security of parenteral drug administration.

  9. Development of a standardized knowledge base to generate individualized medication plans automatically with drug administration recommendations

    PubMed Central

    Send, Alexander F J; Al-Ayyash, Adel; Schecher, Sabrina; Rudofsky, Gottfried; Klein, Ulrike; Schaier, Matthias; Pruszydlo, Markus G; Witticke, Diana; Lohmann, Kristina; Kaltschmidt, Jens; Haefeli, Walter E; Seidling, Hanna M

    2013-01-01

    Aims We aimed to develop a generic knowledge base with drug administration recommendations which allows the generation of a dynamic and comprehensive medication plan and to evaluate its comprehensibility and potential benefit in a qualitative pilot study with patients and physicians. Methods Based on a literature search and previously published medication plans, a prototype was developed and iteratively refined through qualitative evaluation (interviews with patients and focus group discussions with physicians). To develop the recommendations for safe administration of specific drugs we screened the summary of product characteristics (SmPC) of different exemplary brands, allocated the generated advice to groups with brands potentially requiring the same advice, and reviewed these allocations regarding applicability and appropriateness of the recommendations. Results For the recommendations, 411 SmPCs of 140 different active ingredients including all available galenic formulations, routes of administrations except infusions, and administration devices were screened. Finally, 515 distinct administration recommendations were included in the database. In 926 different generic groups, 29 879 allocations of brands to general advice, food advice, indications, step-by-step instructions, or combinations thereof were made. Thereby, 27 216 of the preselected allocations (91.1%) were confirmed as appropriate. In total, one third of the German drug market was labelled with information. Conclusions Generic grouping of brands according to their active ingredient and other drug characteristics and allocation of standardized administration recommendations is feasible for a large drug market and can be integrated in a medication plan. PMID:24007451

  10. Safeguarding the process of drug administration with an emphasis on electronic support tools

    PubMed Central

    Seidling, Hanna M; Lampert, Anette; Lohmann, Kristina; Schiele, Julia T; Send, Alexander J F; Witticke, Diana; Haefeli, Walter E

    2013-01-01

    Aims The aim of this work is to understand the process of drug administration and identify points in the workflow that resulted in interventions by clinical information systems in order to improve patient safety. Methods To identify a generic way to structure the drug administration process we performed peer-group discussions and supplemented these discussions with a literature search for studies reporting errors in drug administration and strategies for their prevention. Results We concluded that the drug administration process might consist of up to 11 sub-steps, which can be grouped into the four sub-processes of preparation, personalization, application and follow-up. Errors in drug handling and administration are diverse and frequent and in many cases not caused by the patient him/herself, but by family members or nurses. Accordingly, different prevention strategies have been set in place with relatively few approaches involving e-health technology. Conclusions A generic structuring of the administration process and particular error-prone sub-steps may facilitate the allocation of prevention strategies and help to identify research gaps. PMID:24007450

  11. Acute Coronary Syndromes, Gastrointestinal Protection, and Recommendations Regarding Concomitant Administration of Proton-Pump Inhibitors (Omeprazol/Esomeprazole) and Clopidogrel.

    PubMed

    Lozano, Iñigo; Sanchez-Insa, Esther; de Leiras, Sergio Rodríguez; Carrillo, Pilar; Ruiz-Quevedo, Valeriano; Pinar, Eduardo; Gopar-Gopar, Silvia; Bayon, Jeremías; Mañas, Pilar; Lasa, Garikoitz; CruzGonzalez, Ignacio; Hernandez, Felipe; Fernandez-Portales, Javier; Fernandez-Fernandez, Javier; Pérez-Serradilla, Ana; de la Torre Hernandez, José M; Gomez-Jaume, Alfredo

    2016-02-01

    The Food and Drug Administration and the European Medicines Agency sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. The purpose is to know the gastroprotective approach in patients with acute coronary syndrome (ACS) and the level of follow-up of the alert. In 17 hospitals with catheterization laboratory in Spain, 1 per region, we studied 25 consecutive patients per hospital whose diagnosis of discharge since October 1, 2013, had been any type of ACS. We analyzed their baseline clinical profile, the gatroprotective agents at admission and discharge and the antiplatelet therapy at discharge. The number of patients included was 425: age 67.2 ± 12.5 years, women 29.8%, diabetes 36.5%. The patients presented unstable angina in 21.6%, non-ST-elevation myocardial infarction in 35.3% and ST-elevation myocardial infarction in 43.1%. Conservative approach was chosen in 17.9%, bare-metal stents 32.2%, ≥ 1 drug-eluting stent 48.5%, and surgery 1.4%. Aspirin was indicated in 1.9%, aspirin + clopidogrel 73.6%, aspirin + prasugrel 17.6%, and aspririn + ticagrelor 6.8%. Gastroprotective agents were present in 40.2% patients at admission and this percentage increased to 93.7% at discharge. Of the 313 (73.6%) on clopidogrel in 96 (30.6%) was combined with omeprazole and 3 (0.95%) with esomeprazole, whereas the most commonly used was pantoprazole with 190 patients (44.7%). In conclusion, almost the totality of the patients with an ACS receive gastroprotective agents at the moment of discharge, most of them with proton-pump inhibitors. In one every 3 cases of the patients who are on clopidogrel, the recommendation of the Food and Drug Administration and the European Medicines Agency is not followed.

  12. Basics of PK-PD using QEEG: acute/repetitive administration, interactions. Focus on anxiolytics with different neurochemical mechanisms as examples.

    PubMed

    Barbanoj, M J; Riba, J; Morte, A; Antonijoan, R M; Jané, F

    2002-01-01

    Utilizing computer-assisted quantitative analysis of the electroencephalogram (EEG) in combination with certain statistical procedures and under specific design conditions, it is possible to objectively evaluate the functional bioavailability of psychotropic substances in the target organ: the human brain. Specifically, one may determine whether a drug is active in the central nervous system (CNS) compared with placebo in humans, the dose effect (including nonmonotonic drug effects along the continuum range of concentrations) and the time effect (including time-dependent pharmacodynamic phenomena as tolerance and sensitization), as well as its activity in relation to the formulation and route of application. Methodological aspects are introduced, discussing the usefulness of evaluating different treatments, doses, time points, states, target variables, electrodes and even different groups. Several issues are raised in relation to acute vs. repetitive administration, particularly those dealing with statistical comparisons when making conclusions about acute, repetitive or superimposed effects, and in relation to human psychotropic interactions, such as mechanistic drug-drug interaction descriptions, drug metabolites and enantiomers, as well as the importance of acquiring drug plasma concentrations, elapse of time and topographic distributions to accurately identify its occurrence. PK-PD modeling is introduced as a tool to enlarge the scope of inferences that can be derived when using pharmaco-EEG. The examples presented in order to develop the arguments are mainly focused on anxiolytic compounds belonging to the different neurochemical groups, benzodiazepines and azaspirones. Questions that have yet to been resolved are also addressed.

  13. A systematic review of acute pancreatitis as an adverse event of type 2 diabetes drugs: from hard facts to a balanced position.

    PubMed

    Giorda, C B; Nada, E; Tartaglino, B; Marafetti, L; Gnavi, R

    2014-11-01

    The question whether antidiabetes drugs can cause acute pancreatitis dates back to the 1970s. Recently, old concerns have re-emerged following claims that use of incretins, a new class of drugs for type 2 diabetes, might increase the relative risk of acute pancreatitis up to 30-fold. Given that diabetes is per se a potent risk factor for acute pancreatitis and that drug-related acute pancreatitis is rare and difficult to diagnose, we searched the medical databases for information linking acute pancreatitis and type 2 diabetes drugs. Among the biguanides, both phenformin and metformin (the latter in patients with renal insufficiency) have been cited in case reports as a potential cause of acute pancreatitis. Sulphonylureas, as both entire class and single compound (glibenclamide), have also been found in cohort studies to increase its risk. No direct link was found between pancreatic damage and therapy with metaglinide, acarbose, pramlintide or SGLT-2 inhibitors. In animal models, thiazolinediones have demonstrated proprieties to attenuate pancreatic damage, opening perspectives for their use in treating acute pancreatitis in humans. Several case reports and the US Food and Drug Administration pharmacovigilance database indicate an association between acute pancreatitis and incretins, dipeptidyl peptidase-4 (DPP-4) inhibitors, and GLP-1 receptor agonists. To date, however, a clear-cut odds ratio for this association has been reported in only one of eight pharmacoepidemiological studies. Finally, none of the intervention trials investigating these compounds, including two large randomized controlled trials with cardiovascular endpoints, confirmed the purportedly increased risk of acute pancreatitis with incretin use.

  14. [Albuminuria after acute oral administration of proteins in patients with renovascular hypertension].

    PubMed

    Stríbrná, J; Růzicka, M; Englis, M; Peregrín, J; Lánská, V

    1993-02-05

    In a group of 19 patients with renovascular hypertension the effect of a morning snack comprising meat (1 g protein per 1 kg body weight) on urinary albumin excretion was assessed. Concurrently the plasma creatinine concentration (Pcr) was examined which varied between normal and 260 mumol/l and the creatinine clearance (Ccr). After administration of an acute protein load the mean Ccr value increased by 23%. The albumin excretion, however, did not change substantially, as compared with the previous collection period (mean 17 and 18 micrograms/min). Microalbuminuria was recorded in 31% of the patients and its prevalence was directly related to the increasing Pcr value. The results revealed that an acute protein load did not increase albuminuria although the rise of Ccr was significant. The variability of albumin excretion in the course of the day is, however, influenced also by other factors and for assessment of microalbuminuria therefore examination of 24-hour urine samples should be preferred.

  15. Effect of acute ethanol administration on zebrafish tail-beat motion.

    PubMed

    Bartolini, Tiziana; Mwaffo, Violet; Butail, Sachit; Porfiri, Maurizio

    2015-11-01

    Zebrafish is becoming a species of choice in neurobiological and behavioral studies of alcohol-related disorders. In these efforts, the activity of adult zebrafish is typically quantified using indirect activity measures that are either scored manually or identified automatically from the fish trajectory. The analysis of such activity measures has produced important insight into the effect of acute ethanol exposure on individual and social behavior of this vertebrate species. Here, we leverage a recently developed tracking algorithm that reconstructs fish body shape to investigate the effect of acute ethanol administration on zebrafish tail-beat motion in terms of amplitude and frequency. Our results demonstrate a significant effect of ethanol on the tail-beat amplitude as well as the tail-beat frequency, both of which were found to robustly decrease for high ethanol concentrations. Such a direct measurement of zebrafish motor functions is in agreement with evidence based on indirect activity measures, offering a complementary perspective in behavioral screening.

  16. Acute effects of nicotine administration during prospective memory, an event related fMRI study.

    PubMed

    Rusted, Jennifer; Ruest, Torsten; Gray, Marcus A

    2011-07-01

    We previously demonstrated that stimulating neuronal nicotinic acetylcholine receptors modulates prospective memory (PM), the ability to remember and implement a prior intention. Here we used fMRI to explore the neuronal correlates of acute nicotinic (1mg) modulation during PM, employing a double blind, valence-matched placebo-controlled design, and a solely event-related analysis. Eight healthy adults completed on two occasions (1 week washout) a simple attentional task containing infrequent PM trials. PM activated bilateral parietal, prefrontal (BA10) and anterior cingulate, and deactivated genual cingulate and medial prefrontal regions. Further, acute nicotine administration decreased activity within a largely overlapping right parietal region. This data validates a purely event-related approach to exploring PM, and suggests procholinergic modulation of PM by parietal rather than BA10/frontal regions.

  17. Corticosteroid Administration and Outcome of Adolescents and Adults With Acute Bacterial Meningitis: A Meta-analysis

    PubMed Central

    Assiri, Abdullah M.; Alasmari, Faisal A.; Zimmerman, Valerie A.; Baddour, Larry M.; Erwin, Patricia J.; Tleyjeh, Imad M.

    2009-01-01

    OBJECTIVE: To systematically assess the effect of the adjunctive administration of corticosteroids in the treatment of acute bacterial meningitis. METHODS: We performed a systematic review and meta-analysis by searching several databases for reports (published from January 1966 through February 2008) of placebo-controlled randomized trials of corticosteroid use in the treatment of adolescents and adults with acute bacterial meningitis. We used random-effects models. Sources of heterogeneity were explored by preplanned subgroup analyses. RESULTS: The 4 eligible trials (published between 1999 and 2007) were of high methodological quality and included 1261 adult patients. Overall, the short-term mortality rate associated with corticosteroid administration was not significantly lower than that associated with placebo (relative risk [RR], 0.81; 95% confidence interval [CI], 0.54-1.20; I2=54%). A significant interaction was found between the effect of corticosteroids and the income status of the country (P=.02) and the prevalence of infection with human immunodeficiency virus (HIV) among study populations (P=.03). The administration of corticosteroids resulted in a lower short-term mortality rate than did the administration of placebo in high-income countries (pooled RR, 0.5; 95% CI, 0.27-0.92; I2=0%) and in the studies with a low prevalence of infection with HIV (RR, 0.66; 95% CI, 0.44-0.99; I2=0%). In studies from high-income countries, the number needed to treat with corticosteriods to prevent 1 death and 1 neurologic sequela was 12.5 (95% CI, 7.1-100.0) and 11.0 (95% CI, 5.6-100.0), respectively. CONCLUSION: Our meta-analysis suggests that the adjunctive administration of corticosteroids is beneficial in the treatment of adolescents and adults with bacterial meningitis in patient populations similar to those seen in high-income countries and in areas with a low prevalence of HIV infection. PMID:19411436

  18. Factors Influencing Drug Uptake during Mass Drug Administration for Control of Lymphatic Filariasis in Rural and Urban Tanzania

    PubMed Central

    Kisoka, William J.; Simonsen, Paul E.; Malecela, Mwelecele N.; Tersbøl, Britt P.; Mushi, Declare L.; Meyrowitsch, Dan W.

    2014-01-01

    Background In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission interruption within reasonable time. The present study aimed to identify predictors and barriers to individual drug uptake during MDA implementation by the National LF Elimination Programme in Tanzania. Methods A questionnaire based cross sectional household survey was carried out in two rural and two urban districts in Lindi and Morogoro regions shortly after the 2011 MDA. 3279 adults (≥15 years) were interviewed about personal characteristics, socio-economic status, MDA drug uptake among themselves and their children, reasons for taking/not taking drugs, and participation in previous MDA activities for LF control. Findings The overall drug uptake rate was 55.1% (range of 44.5–75.6% between districts). There was no overall major difference between children (54.8%) and adults (55.2%) or between females (54.9%) and males (55.8%), but the role of these and other predictors varied to some extent between study sites. Major overall predictors of drug uptake among the interviewed adults were increasing age and history of previous drug uptake. Being absent from home during drug distribution was the main reason for not taking the drugs (50.2%) followed by clinical contraindications to treatment (10.8%), missing household visits of drug distributors (10.6%), and households not being informed about the distribution (9.0%). Conclusion Drug uptake relied more on easily modifiable provider-related factors than on individual perceptions and practices in the target population. Limited investments in appropriate timing, dissemination of accurate timing information to recipients and motivation of drug distributors to visit all households (repeatedly when residents are absent) are likely to have

  19. Strain Differences in Delay Discounting between Lewis and Fischer 344 Rats at Baseline and Following Acute and Chronic Administration of d-Amphetamine

    PubMed Central

    Huskinson, Sally L.; Krebs, Christopher A.; Anderson, Karen G.

    2012-01-01

    Stimulant drugs have been shown either to increase or decrease rates of delay discounting (impulsive choice). These mixed findings may result from genetic, neurochemical, or environmental factors. Lewis (LEW) and Fischer 344 (F344) rats have neurochemical and behavioral differences that may be relevant to delay discounting and were used to examine effects of acute and chronic administration of d-amphetamine (d-AMP) on impulsive choice using a within-session delay-discounting procedure. Male LEW (n=8) and F344 (n=8) rats chose between one food pellet delivered immediately and three food pellets delivered after an increasing delay. Saline and d-AMP (0.1, 0.3, 1.0, and 1.7 mg/kg) were tested acutely and during chronic d-AMP exposure. Choice for the larger reinforcer decreased as the delay to its presentation increased for both strains at baseline. LEW rats made more impulsive choices than F344 rats as indicated by shorter indifference points, and this is consistent with previous research. Acute administration of d-AMP dose dependently increased larger-reinforcer choice and area under the curve (AUC) for LEW, but not F344 rats. During chronic exposure to d-AMP, larger-reinforcer choice and AUC increased relative to acute administration for F344 rats responding in shorter delay series, but not for F344 rats responding in longer delay series or for LEW rats. Differential effects of acute and chronic administration of d-AMP on impulsive choice in LEW and F344 rats may be a result of various factors, including genetic, neurochemical, and environmental variables. Future research should attempt to tease apart the relative contribution of each of these factors on impulsive choice. PMID:22342664

  20. Acute drug prescribing to children on chronic antiepilepsy therapy and the potential for adverse drug interactions in primary care

    PubMed Central

    Novak, Philipp H; Ekins-Daukes, Suzie; Simpson, Colin R; Milne, Robert M; Helms, Peter; McLay, James S

    2005-01-01

    Aims To investigate the extent of acute coprescribing in primary care to children on chronic antiepileptic therapy, which could give rise to potentially harmful drug–drug interactions. Design Acute coprescribing to children on chronic antiepileptic drug therapy in primary care was assessed in 178 324 children aged 0–17 years for the year 1 November 1999 to 31 October 2000. Computerized prescribing data were retrieved from 161 representative general practices in Scotland. Setting One hundred and sixty-one general practices throughout Scotland. Results During the study year 723 (0.41%) children chronically prescribed antiepileptic therapy were identified. Fourteen antiepileptic agents were prescribed, with carbamazepine, sodium valproate and lamotrigine accounting for 80% of the total. During the year children on chronic antiepileptic therapy were prescribed 4895 acute coprescriptions for 269 different medicines. The average number of acute coprescriptions for non-epileptic drug therapy were eight, 11, six, and six for the 0–1, 2–4, 5–11, and 12–17-year-olds, respectively. Of these acute coprescriptions 72 (1.5%) prescribed to 22 (3.0%) children were identified as a potential source of clinically serious interactions. The age-adjusted prevalence rates for potentially serious coprescribing were 86, 26, 22, and 33/1000 children chronically prescribed antiepileptic therapy in the 0–1, 2–4, 5–11, and 12–17-year-old age groups, respectively. The drugs most commonly coprescribed which could give rise to such interactions were antacids, erythromycin, ciprofloxacin, theophylline and the low-dose oral contraceptive. For 10 (45.5%0 of the 20 children identified at risk of a potentially clinically serious adverse drug interaction, the acute coprescription was prescribed off label because of age or specific contraindication/warning. Conclusions In primary care, 3.0% of children on chronic antiepileptic therapy are coprescribed therapeutic agents, which could

  1. Differential Modulation of Thresholds for Intracranial Self-Stimulation by mGlu5 Positive and Negative Allosteric Modulators: Implications for Effects on Drug Self-Administration

    PubMed Central

    Cleva, Richard M.; Watterson, Lucas R.; Johnson, Meagan A.; Olive, M. Foster

    2011-01-01

    Pharmacological manipulation of the type 5 metabotropic glutamate (mGlu5) receptor alters various addiction related behaviors such as drug self-administration and the extinction and reinstatement of drug-seeking behavior. However, the effects of pharmacological modulation of mGlu5 receptors on brain reward function have not been widely investigated. We examined the effects of acute administration of positive and negative allosteric modulators (PAMs and NAMs, respectively) on brain reward function by assessing thresholds for intracranial self-stimulation (ICSS). In addition, when acute effects were observed, we examined changes in ICSS thresholds following repeated administration. Male Sprague-Dawley rats were implanted with bipolar electrodes into the medial forebrain bundle and trained to respond for ICSS, followed by assessment of effects of mGlu5 ligands on ICSS thresholds using a discrete trials current–intensity threshold determination procedure. Acute administration of the selective mGlu5 NAMs MTEP (0, 0.3, 1, or 3 mg/kg) and fenobam (0, 3, 10, or 30 mg/kg) dose-dependently increased ICSS thresholds (∼70% at the highest dose tested), suggesting a deficit in brain reward function. Acute administration of the mGlu5 PAMs CDPPB (0, 10, 30, and 60 mg/kg) or ADX47273 (0, 10, 30, and 60 mg/kg) was without effect at any dose tested. When administered once daily for five consecutive days, the development of tolerance to the ability of threshold-elevating doses of MTEP and fenobam to increase ICSS thresholds was observed. We conclude that mGlu5 PAMs and NAMs differentially affect brain reward function, and that tolerance to the ability of mGlu5 NAMs to reduce brain reward function develops with repeated administration. These brain reward deficits should be taken into consideration when interpreting acute effects of mGlu5 NAMs on drug self-administration, and repeated administration of these ligands may be an effective method to reduce these deficits. PMID

  2. The role of human drug self-administration procedures in the development of medications.

    PubMed

    Comer, S D; Ashworth, J B; Foltin, R W; Johanson, C E; Zacny, J P; Walsh, S L

    2008-07-01

    The purpose of this review is to illustrate the utility and value of employing human self-administration procedures in medication development, including abuse liability assessments of novel medications and evaluation of potential pharmacotherapies for substance use disorders. Traditionally, human abuse liability testing has relied primarily on subjective reports describing drug action by use of questionnaires; similarly, drug interactions between putative treatment agents and the drugs of abuse have relied on these measures. Subjective reports are highly valued because they provide qualitative and quantitative information about the characteristics of central and peripheral pharmacodynamic effects as well as safety and tolerability. However, self-administration procedures directly examine the behavior of interest-that is, drug taking. The present paper (1) reviews the most commonly used human self-administration procedures, (2) discusses the concordance of subjective reports and self-administration within the context of medications development for substance use disorders, focusing primarily on illustrative examples from development efforts with opioid and cocaine dependence, and (3) explores the utility of applying self-administration procedures to assess the abuse liability of novel compounds, including "abuse-deterrent" formulations (ADFs). The review will focus on opioid and cocaine dependence because a rich database from both clinical laboratory and clinical trial research exists for these two drug classes. The data reviewed suggest that drug-induced changes in self-administration and subjective effects are not always concordant. Therefore, assessment of self-administration in combination with subjective effects provides a more comprehensive picture that may have improved predictive validity for translating to the clinical setting.

  3. The role of human drug self-administration procedures in the development of medications

    PubMed Central

    Comer, SD; Ashworth, JB; Foltin, RW; Johanson, CE; Zacny, JP; Walsh, SL

    2008-01-01

    The purpose of this review is to illustrate the utility and value of employing human self-administration procedures in medication development, including abuse liability assessments of novel medications and evaluation of potential pharmacotherapies for substance use disorders. Traditionally, human abuse liability testing has relied primarily on subjective reports describing drug action by use of questionnaires; similarly, drug interactions between putative treatment agents and the drugs of abuse have relied on these measures. Subjective reports are highly valued because they provide qualitative and quantitative information about the characteristics of central and peripheral pharmacodynamic effects as well as safety and tolerability. However, self-administration procedures directly examine the behavior of interest – that is, drug taking. The present paper 1) reviews the most commonly used human self-administration procedures, 2) discusses the concordance of subjective reports and self-administration within the context of medications development for substance use disorders, focusing primarily on illustrative examples from development efforts with opioid and cocaine dependence, and 3) explores the utility of applying self-administration procedures to assess the abuse liability of novel compounds, including “abuse deterrent” formulations (ADFs). The review will focus on opioid and cocaine dependence because a rich database from both clinical laboratory and clinical trial research exists for these two drug classes. The data reviewed suggest that drug-induced changes in self-administration and subjective effects are not always concordant. Therefore, assessment of self-administration in combination with subjective effects provides a more comprehensive picture that may have improved predictive validity for translating to the clinical setting. PMID:18436394

  4. The Compendium of Pharmaceuticals and Specialties as a Drug Information Resource for Treatment of Acute Drug Overdose

    PubMed Central

    Parker, William A.

    1979-01-01

    A study was undertaken to determine the extent to which family physicians consult the Compendium of Pharmaceuticals and Specialties (CPS) as an information resource for acute drug ingestions and to evaluate the scope and consistency of the informational content contained in the CPS Product monographs. Ninety percent of family physicians were found to consult the CPS as their first resource in a suspected acute drug ingestion. Although the CPS is a useful reference because of its universal distribution and annual updating, standardization of informational content and consistency between product monographs are necessary. Presently, major inconsistencies exist and some information is outdated.

  5. U.s. Food and Drug Administration approval: carfilzomib for the treatment of multiple myeloma.

    PubMed

    Herndon, Thomas M; Deisseroth, Albert; Kaminskas, Edvardas; Kane, Robert C; Koti, Kallappa M; Rothmann, Mark D; Habtemariam, Bahru; Bullock, Julie; Bray, Jeffrey D; Hawes, Jessica; Palmby, Todd R; Jee, Josephine; Adams, William; Mahayni, Houda; Brown, Janice; Dorantes, Angelica; Sridhara, Rajeshwari; Farrell, Ann T; Pazdur, Richard

    2013-09-01

    The U.S. Food and Drug Administration (FDA) review leading to accelerated approval of carfilzomib is described. A single-arm trial enrolled 266 patients with multiple myeloma refractory to the most recent therapy who had received prior treatment with bortezomib and an immunomodulatory agent (IMID). Patients received carfilzomib by intravenous infusion over 2 to 10 minutes at a dose of 20 mg/m2 on days 1, 2, 8, 9, 15, and 16 of the 28 days of cycle 1, and at a dose of 27 mg/m2 on the same schedule in cycle 2 and subsequent cycles. The primary efficacy endpoint was overall response rate (ORR) as determined by an independent review committee using International Myeloma Working Group Uniform Response Criteria. The safety of carfilzomib was evaluated in 526 patients with multiple myeloma treated with various dosing regimens. The ORR was 23%. The median duration of response was 7.8 months. The most common adverse reactions associated with carfilzomib infusion were fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, and fever. The most common serious adverse events were pneumonia, acute renal failure, fever, and congestive heart failure. Infusion reactions to carfilzomib could be reduced by pretreatment with dexamethasone and intravenous fluids. On July 20, 2012, the FDA granted accelerated approval of carfilzomib for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an IMID and who have shown disease progression while on therapy or within 60 days of completion of the last therapy.

  6. Acute intrastriatal administration of quinolinic acid affects the expression of the coat protein AP-2 and its interaction with membranes.

    PubMed

    Borgonovo, Janina; Seltzer, Alicia; Sosa, Miguel Angel

    2009-10-01

    Clathrin-coated vesicle endocytosis is thought to be crucial for the maintenance of synaptic transmission and for the cell plasticity at the nervous system. In this study, we demonstrated that acute intrastriatal administration of quinolinic acid (QUIN), an agonist of the N-methyl-D: -aspartate receptor, induces a decrease of the coat protein AP-2 expression and affects their interaction with membranes. By western blot analysis we observed that at 24 h after QUIN intrastriatal injection, alpha1 subunit of AP-2 and alpha2, at lesser extent, were reduced in the striatal membranes. The decrease of both subunits expression was extended to 48 h after treatment, although the soluble proteins were mostly affected. Other areas of the brain were not affected by the treatment, except the cerebellum, where a significant increase of soluble AP-2 (both subunits) was observed at 48 h after injection. Another coat protein, as the phosphoprotein AP-180, was not affected by the injection of QUIN. We also confirmed that QUIN injection causes increasing loss of striatal neurons after the administration of the toxin. We concluded that QUIN may affect the endocytotic machinery of the striatum, by inducing changes in the AP-2 behaviour. Consequently, the internalization of NMDAR and/or AMPAR may be affected, by QUIN, contributing to the excitotoxic effect of the drug.

  7. Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts.

    PubMed

    Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

    2013-09-01

    This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest.

  8. Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts

    PubMed Central

    Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

    2014-01-01

    This double-blind, placebo-controlled study investigated effects of oral morphine (0, 45, 135 mg/70kg) and oral oxycodone (0, 15, 45 mg/70kg) in buprenorphine-maintained opioid addicts. Since a 3:1 morphine:oxycodone dose ratio had yielded equivalent subjective and physiological effects in non-dependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures, i.e. a drug vs. money and a drug vs. drug procedure, were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater compared to high-dose morphine. The study demonstrated that a 3:1 dose ratio of morphine:oxycodone was not equipotent in buprenorphine-dependent subjects. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest. PMID:23839029

  9. A New Approach to the Oral Administration of Insulin and Other Peptide Drugs

    NASA Astrophysics Data System (ADS)

    Saffran, Murray; Sudesh Kumar, G.; Savariar, Celin; Burnham, Jeffrey C.; Williams, Frederick; Neckers, Douglas C.

    1986-09-01

    The oral administration of peptide drugs is well known to be precluded by their digestion in the stomach and small intestine. As a new approach to oral delivery, peptide drugs were coated with polymers cross-linked with azoaromatic groups to form an impervious film to protect orally administered drugs from digestion in the stomach and small intestine. When the azopolymer-coated drug reached the large intestine, the indigenous microflora reduced the azo bonds, broke the cross-links, and degraded the polymer film, thereby releasing the drug into the lumen of the colon for local action or for absorption. The ability of the azopolymer coating to protect and deliver orally administered peptide drugs was demonstrated in rats with the peptide hormones vasopressin and insulin.

  10. The use of sonophoresis in the administration of drugs throughout the skin.

    PubMed

    Escobar-Chávez, José Juan; Bonilla-Martínez, Dalia; Villegas-González, Martha Angélica; Rodríguez-Cruz, Isabel Marlen; Domínguez-Delgado, Clara Luisa

    2009-01-01

    Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injection. However, the stratum corneum acts as a barrier that limits the penetration of substances through the skin. Application of ultrasound to the skin increases its permeability (sonophoresis) and enables the delivery of various substances into and through the skin. Ultrasound has been used extensively for medical diagnostics and to a certain extent in medical therapy (physiotherapy, ultrasonic surgery, hyperthermia). Nevertheless, it has only recently become popular as a technique to enhance drug release from drug delivery systems. A number of studies suggest the use of ultrasound as an external mean of delivering drugs at increased rates and at desired times. This review presents the main findings in the field of sonophoresis, namely transdermal drug delivery and transdermal monitoring. Particular attention is paid to proposed enhancement mechanisms and trends in the field of topical and transdermal delivery.

  11. Prescription Drug Promotion from 2001-2014: Data from the U.S. Food and Drug Administration

    PubMed Central

    Sullivan, Helen W.; Aikin, Kathryn J.; Chung-Davies, Eunice; Wade, Michael

    2016-01-01

    The volume of prescription drug promotion over time is often measured by assessing changes in ad spending. However, this method obscures the fact that some types of advertising are more expensive than others. Another way to measure the changes in prescription drug promotion over time is to assess the number of promotional pieces submitted to the U.S. Food and Drug Administration (FDA). Form FDA 2253 collects information such as the date submitted and the type of material submitted. We analyzed data from Forms FDA 2253 received from 2001–2014. We examined the frequency of submissions by audience (consumer and healthcare professional) and type of promotional material. There was a noted increase in prescription drug promotion submissions across all media in the early 2000s. Although non-Internet promotion submissions have since plateaued, Internet promotion continued to increase. These results can help public health advocates and regulators focus attention and resources. PMID:27149513

  12. Food and Drug Administration process for development and approval of drugs and radiopharmaceuticals: treatments in urologic oncology.

    PubMed

    Ning, Yang-Min; Maher, V Ellen

    2015-03-01

    Regulatory advice and assessment play an important role in the successful development of new drugs and radiopharmaceuticals for the treatment of urologic malignancies. Cooperation between the US Food and Drug Administration (FDA) and the pharmaceutical industry has led to the approval of more than 20 new urologic oncology products in the last 2 decades. Despite these advances, more effective treatments need to be developed and approved for the treatment of urologic malignancies. This review provides general information about the FDA's role in the development of investigational new drugs, with an emphasis on the regulatory process and the requirements for marketing approval. In addition, this review summarizes the products for the treatment of urologic malignancies that were approved by the FDA in the last 30 years and the key issues concerning urologic oncology products that were discussed publicly at Oncologic Drug Advisory Committee meetings in the past 10 years.

  13. The role of excessive versus acute administration of erythropoietin in attenuating hepatic ischemia-reperfusion injury.

    PubMed

    Pappo, Orit; Ben-Ari, Ziv; Shevtsov, Evgeni; Avlas, Orna; Gassmann, Max; Ravid, Amiram; Cheporko, Yelena; Hochhauser, Edith

    2010-12-01

    Ischemia-reperfusion injury (I/R) is the main cause of primary graft nonfunction. Our aim was to evaluate the effect of excessive versus acute administration of erythropoietin (EPO) in attenuating the hepatic injury induced by I/R in mice. The effect of segmental (70%) hepatic ischemia was evaluated in a transgenic mouse line with constitutive overexpression of human EPO cDNA and in wild-type (WT) mice. Mice were randomly allocated to 5 main experimental groups: (i) WT-sham, (ii) WT ischemia, (iii) WT ischemia + recombinant human erythropoietin (rhEPO), (iv) transgenic-sham, and (v) transgenic ischemia. The EPO-pretreated mice showed a significant reduction in liver enzyme levels and intrahepatic caspase-3 activity and fewer apoptotic hepatocytes (p < 0.05 for all) compared with the WT untreated I/R group. EPO decreased c-Jun N-terminal kinase (JNK) phosphorylation and nuclear factor-κB (NF-κB) expression during I/R. In transgenic I/R livers, baseline histology showed diffused hepatic injury, and no significant beneficial effect was noted between the WT untreated and the transgenic I/R mice. In conclusion, acute pretreatment with EPO in WT mice attenuated in vivo I/R liver injury. However, in excessive EPO overexpression, the initial liver injury abolished the beneficial effect of EPO. These findings have important implications for the potential use of acute EPO in I/R injury during liver transplantation.

  14. Nanocarriers and the delivered drug: effect interference due to intravenous administration.

    PubMed

    Vlasova, Maria A; Rytkönen, Jussi; Riikonen, Joakim; Tarasova, Olga S; Mönkäre, Juha; Kovalainen, Miia; Närvänen, Ale; Salonen, Jarno; Herzig, Karl-Heinz; Lehto, Vesa-Pekka; Järvinen, Kristiina

    2014-10-15

    Intravenously administered nanocarriers are widely studied to improve the delivery of various therapeutic agents. However, recent in vivo studies have demonstrated that intravenously administered nanocarriers that do not contain any drug may affect cardiovascular function. Here we provide an example where the drug and the nanocarrier both affect the same cardiovascular parameters following intravenous administration. The peptide ghrelin antagonist (GhA) increases arterial pressure, while thermally hydrocarbonized porous silicon nanoparticles (THCPSi) transiently decrease it, as assessed with radiotelemetry in conscious rats. As a result, intravenous administration of GhA-loaded THCPSi nanoparticles partially antagonized GhA activity: arterial pressure was not increased. When the cardiovascular effects of GhA were blocked with atenolol pretreatment, GhA-loaded nanoparticles reduced arterial pressure to similar extent as drug-free nanoparticles. These data indicate that the biological activity of a drug delivered within a nanocarrier may be obscured by the biological responses induced by the nanocarrier itself.

  15. Local drug delivery - the early Berlin experience: single drug administration versus sustained release.

    PubMed

    Speck, Ulrich; Scheller, Bruno; Rutsch, Wolfgang; Laule, Michael; Stangl, Verena

    2011-05-01

    Our initial investigations into restenosis inhibition by local drug delivery were prompted by reports on an improved outcome of coronary interventions, including a lower rate of target lesion revascularisation, when the intervention was performed with an ionic instead of non-ionic contrast medium. Although this was not confirmed in an animal study, the short exposure of the vessel wall to paclitaxel dissolved in contrast agent or coated on balloons proved to be efficacious. A study comparing three methods of local drug delivery to the coronary artery in pigs indicated the following order of efficacy in inhibiting neointimal proliferation: paclitaxel-coated balloons > sirolimus-eluting stents, sustained drug release > paclitaxel in contrast medium. Cell culture experiments confirmed that cell proliferation can be inhibited by very short exposure to the drug. Shorter exposure times require higher drug concentrations. Effective paclitaxel concentrations in porcine arteries are achieved when the drug is dissolved in contrast medium or coated on balloons. Paclitaxel is an exceptional drug in that it stays in the treated tissue for a long time. This may explain the long-lasting efficacy of paclitaxel-coated balloons, but does not disprove the hypothesis that the agent blocks a process initiating long-lasting excessive neointimal proliferation, which occurs early after vessel injury.

  16. Acute Clinical Worsening after Steroid Administration in Cervical Myelitis May Reveal a Subdural Arteriovenous Fistula

    PubMed Central

    Rain, Silvia; Udding, Jan; Broere, Daniel

    2016-01-01

    Subdural arteriovenous fistula (SDAVF) is a rare condition characterized by clinical manifestations ranging from mild bilateral sensory deficits to quadriplegia. The diagnosis is often delayed due to unspecific neurological symptoms, initially diagnosed as polyneuropathy or myelopathy. The diagnosis can be delayed for as long as 1–15 years. The following report describes a cervical SDAVF case initially misdiagnosed as myelitis transversa and treated with intravenous steroids. A 56-year-old male presented with sensory deficits and mild leg and right arm weakness. Cervical MRI showed a central medullary hyperintense lesion with contrast enhancement. After metabolic, infectious, and malignant causes were excluded, myelitis transversa was presumed and the patient was treated intravenously with methylprednisolone. Shortly after that, he developed quadriplegia. Cervical MRI imaging showed engorged cervical perimedullary vessels, which were not visible on the initial MRI. The diagnosis was revised and a SDAVF identified. Prompt surgical treatment led to a complete recovery. The effect of intravenous steroids in SDAVF is controversial. Acute clinical worsening after steroid administration is previously reported in several publications; however, due to the paucity of clinical studies on SDAVF, this effect remains mostly overlooked or unknown. The findings in this patient support the causative relation between SDAVF clinical worsening and steroid administration. We propose that acute clinical worsening under steroids in patients initially diagnosed with myelitis should raise suspicion of an SDAVF. PMID:27920716

  17. Acute kidney function and morphology following topload administration of recombinant hemoglobin solution.

    PubMed

    Martucci, Alexandre Fabricio; Abreu Martucci, Ana Carolina Carvalho Ferreira; Cabrales, Pedro; Nascimento, Paulo do; Intaglietta, Marcos; Tsai, Amy G; Castiglia, Yara Marcondes Machado

    2017-02-01

    There is a 0.138% incidence of adverse reactions related to blood transfusion. Transfusion-related acute lung injury, immunosuppression, fever, pathogen transmission, and hemolytic transfusion reactions are the most common ones. Synthetic oxygen carriers have been developed to deal with blood shortages and for use in the field where stored blood was not available. They were also designed to be pathogen free, including unknown viruses. In this study, we used Male Golden Syrian Hamsters implemented with a dorsal window chamber to determine how infusion of three different, genetically crosslinked recombinant acellular hemoglobin (rHb) solutions with different oxygen affinities and nitric oxide kinetics affect mean arterial pressure (MAP), heart rate (HR), kidney function, and kidney structure. We found that the administration of all three rHb solutions caused mild hypertension and bradycardia 30 minutes after infusion. However, acute changes in glomerular filtration rate (GFR) were not detected, even though histological analysis was performed 72 hours after treatment revealed some structural changes. All the rHb solutions resulted in hypertension 30 minutes after a 10% topload administration. Regardless of their properties, the presence of acellular Hb causes significant alterations to kidney tissue.

  18. Combined administration of hyperbaric oxygen and hydroxocobalamin improves cerebral metabolism after acute cyanide poisoning in rats.

    PubMed

    Hansen, M B; Olsen, N V; Hyldegaard, O

    2013-11-01

    Hyperbaric oxygen therapy (HBOT) or intravenous hydroxocobalamin (OHCob) both abolish cyanide (CN)-induced surges in interstitial brain lactate and glucose concentrations. HBOT has been shown to induce a delayed increase in whole blood CN concentrations, whereas OHCob may act as an intravascular CN scavenger. Additionally, HBOT may prevent respiratory distress and restore blood pressure during CN intoxication, an effect not seen with OHCob administration. In this report, we evaluated the combined effects of HBOT and OHCob on interstitial lactate, glucose, and glycerol concentrations as well as lactate-to-pyruvate ratio in rat brain by means of microdialysis during acute CN poisoning. Anesthetized rats were allocated to three groups: 1) vehicle (1.2 ml isotonic NaCl intra-arterially); 2) potassium CN (5.4 mg/kg intra-arterially); 3) potassium CN, OHCob (100 mg/kg intra-arterially) and subsequent HBOT (284 kPa in 90 min). OHCob and HBOT significantly attenuated the acute surges in interstitial cerebral lactate, glucose, and glycerol concentrations compared with the intoxicated rats given no treatment. Furthermore, the combined treatment resulted in consistent low lactate, glucose, and glycerol concentrations, as well as in low lactate-to-pyruvate ratios compared with CN intoxicated controls. In rats receiving OHCob and HBOT, respiration improved and cyanosis disappeared, with subsequent stabilization of mean arterial blood pressure. The present findings indicate that a combined administration of OHCob and HBOT has a beneficial and persistent effect on the cerebral metabolism during CN intoxication.

  19. Effect of acute and chronic cobalt administration on carotid body chemoreceptors responses.

    PubMed

    Morelli, L; Di Giulio, C; Iezzi, M; Data, P G

    1994-06-30

    Chronic cobalt exposure leads to release and production of erythropoietin and consequently to polycythemia. Accordingly, cellular elements sensitive to oxygen in the carotid body, would manifest responses during acute and chronic cobalt administration. The carotid body, detects gas changes (PO2, PCO2/pH) in the arterial blood and regulates ventilation and circulation by the afferent nerve discharge. We hypothesized that cobalt interacts with an oxygen sensitive mechanism in the carotid chemoreception and in erythropoietin producing cells. Twelve cats were anesthetized, paralysed and artificially ventilated; few fiber preparation of carotid sinus nerve were recorded during close intraarterial injection of cobalt. In another protocol, 12 rats received an intraperitoneal dose of CoCl2 (10 mg/kg) daily for 6 weeks. At the end, the carotid body was fixed in situ by superfusion. Ultrastructural and morphometric studies were made. Acute administration (0.08-2.3 mumol) promptly stimulated the chemoreceptor afferents. Type I cells increased significantly along with erythropoiesis in the chronic cobalt treated rats. The stimulatory effects of cobalt on the carotid body chemoreceptor showed that sensitive mechanisms in the kidney and in the carotid body are similar, and cobalt interacts with the physiological responses of oxygen.

  20. 78 FR 17611 - Provisions of the Food and Drug Administration Safety and Innovation Act Related to Medical Gases...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-22

    ... On July 9, 2012, President Obama signed the Food and Drug Safety and Innovation Act (FDASIA) (Pub. L... HUMAN SERVICES Food and Drug Administration 21 CFR Part Chapter 1 Provisions of the Food and Drug Administration Safety and Innovation Act Related to Medical Gases; Request for Comments Regarding...

  1. 21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (CONTINUED) FOOD ADDITIVES Premarket Notifications § 170.105 The Food and Drug Administration's (FDA's... 21 Food and Drugs 3 2014-04-01 2014-04-01 false The Food and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective....

  2. A Novel Method of Drug Administration to Multiple Zebrafish (Danio rerio) and the Quantification of Withdrawal

    PubMed Central

    Holcombe, Adam; Schalomon, Melike; Hamilton, Trevor James

    2014-01-01

    Anxiety testing in zebrafish is often studied in combination with the application of pharmacological substances. In these studies, fish are routinely netted and transported between home aquaria and dosing tanks. In order to enhance the ease of compound administration, a novel method for transferring fish between tanks for drug administration was developed. Inserts that are designed for spawning were used to transfer groups of fish into the drug solution, allowing accurate dosing of all fish in the group. This increases the precision and efficiency of dosing, which becomes very important in long schedules of repeated drug administration. We implemented this procedure for use in a study examining the behavior of zebrafish in the light/dark test after administering ethanol with differing 21 day schedules. In fish exposed to daily-moderate amounts of alcohol there was a significant difference in location preference after 2 days of withdrawal when compared to the control group. However, a significant difference in location preference in a group exposed to weekly-binge administration was not observed. This protocol can be generalized for use with all types of compounds that are water-soluble and may be used in any situation when the behavior of fish during or after long schedules of drug administration is being examined. The light/dark test is also a valuable method of assessing withdrawal-induced changes in anxiety. PMID:25407925

  3. Biomarker qualification pilot process at the US Food and Drug Administration.

    PubMed

    Goodsaid, Federico; Frueh, Felix

    2007-03-23

    New biomarkers of safety and efficacy are becoming powerful tools in drug development. Their application can be accelerated if a consensus can be reached about their qualification for regulatory applications. This consensus requires a review structure within the US Food and Drug Administration (FDA) that can evaluate qualification data for these biomarkers and determine whether these biomarkers can be qualified. A pilot process and corresponding Biomarker Qualification Review Team have been developed to test how the FDA can work on biomarker qualification.

  4. Differential peptidomics assessment of strain and age differences in mice in response to acute cocaine administration.

    PubMed

    Romanova, Elena V; Rubakhin, Stanislav S; Ossyra, John R; Zombeck, Jonathan A; Nosek, Michael R; Sweedler, Jonathan V; Rhodes, Justin S

    2015-12-01

    Neurochemical differences in the hypothalamic-pituitary axis between individuals and between ages may contribute to differential susceptibility to cocaine abuse. This study measured peptide levels in the pituitary gland (Pit) and lateral hypothalamus (LH) in adolescent (age 30 days) and adult (age 65 days) mice from four standard inbred strains, FVB/NJ, DBA/2J, C57BL/6J, and BALB/cByJ, which have previously been characterized for acute locomotor responses to cocaine. Individual peptide profiles were analyzed using mass spectrometric profiling and principal component analysis. Sequences of assigned peptides were verified by tandem mass spectrometry. Principal component analysis classified all strains according to their distinct peptide profiles in Pit samples from adolescent mice, but not adults. Select pro-opiomelanocortin-derived peptides were significantly higher in adolescent BALB/cByJ and DBA/2J mice than in FVB/NJ or C57BL/6J mice. A subset of peptides in the LH, but not in the Pit, was altered by cocaine in adolescents. A 15 mg/kg dose of cocaine induced greater peptide alterations than a 30 mg/kg dose, particularly in FVB/NJ animals, with larger differences in adolescents than adults. Neuropeptides in the LH affected by acute cocaine administration included pro-opiomelanocortin-, myelin basic protein-, and glutamate transporter-derived peptides. The observed peptide differences could contribute to differential behavioral sensitivity to cocaine among strains and ages. Peptides were measured using mass spectrometry (MALDI-TOF) in individual lateral hypothalamus and pituitary samples from four strains and two ages of inbred mice in response to acute cocaine administration. Principal component analyses (PCA) classified the strains according to their peptide profiles from adolescent mice, and a subset of peptides in the lateral hypothalamus was altered by cocaine in adolescents.

  5. Use of Bioimpedance to Assess Changes in Hemodynamics During Acute Administration of CPAP

    PubMed Central

    Digby, Genevieve C.; Driver, Helen S.; Fitzpatrick, Michael; Ropchan, Glorianne; Parker, Christopher M.

    2011-01-01

    Background Attempts to investigate the mechanisms by which continuous positive airway pressure (CPAP) therapy improves heart function in patients with obstructive sleep apnea (OSA) have been limited by the lack of non-invasive methods to assess cardiac performance. We used transthoracic electrical bioimpedance (TEB) to assess acute hemodynamic changes including heart rate (HR), stroke volume (SV), cardiac output (CO) and cardiac index (CI) during PAP titration in (1) post-operative cardiac surgery patients, (2) patients with severe OSA, and (3) normal healthy volunteers. Methods Post-operative cardiac surgery patients were studied via TEB and pulmonary artery catheter (PAC) during acute titration of positive end-expiratory pressure (PEEP) while mechanically ventilated. Patients with severe OSA were studied non-invasively by TEB during acute CPAP titration in supine stage 2 sleep, and normal subjects while awake and recumbent. Results In post-operative cardiac surgery patients (n = 3), increasing PEEP to 18 cmH2O significantly reduced SV and CI relative to baseline. There was no difference between TEB and PAC in terms of ability to assess variations in hemodynamic parameters. In patients with severe OSA (n = 3), CPAP titration to optimal pressure to alleviate obstructive apneas reduced HR, SV, CO and CI significantly compared to without CPAP. In three healthy subjects, maximal tolerated CPAP reduced SV and CO significantly compared to baseline. Conclusions Acute administration of CPAP causes a decrease in CO and CI, apparently a consequence of a reduction in SV. TEB appears to be an accurate and reproducible non-invasive method of detecting changes in hemodynamics.

  6. Acute caffeine administration effect on brain activation patterns in mild cognitive impairment.

    PubMed

    Haller, Sven; Montandon, Marie-Louise; Rodriguez, Cristelle; Moser, Dominik; Toma, Simona; Hofmeister, Jeremy; Sinanaj, Indrit; Lovblad, Karl-Olof; Giannakopoulos, Panteleimon

    2014-01-01

    Previous studies showed that acute caffeine administration enhances task-related brain activation in elderly individuals with preserved cognition. To explore the effects of this widely used agent on cognition and brain activation in early phases of cognitive decline, we performed a double-blinded, placebo-controlled functional magnetic resonance imaging (fMRI) study during an n-back working memory task in 17 individuals with mild cognitive impairment (MCI) compared to 17 age-matched healthy controls (HC). All individuals were regular caffeine consumers with an overnight abstinence and given 200 mg caffeine versus placebo tablets 30 minutes before testing. Analyses included assessment of task-related activation (general linear model), functional connectivity (tensorial-independent component analysis, TICA), baseline perfusion (arterial spin labeling, ASL), grey matter density (voxel-based morphometry, VBM), and white matter microstructure (tract-based spatial statistics, TBSS). Acute caffeine administration induced a focal activation of the prefrontal areas in HC with a more diffuse and posteromedial activation pattern in MCI individuals. In MCI, TICA documented a significant caffeine-related enhancement in the prefrontal cortex, supplementary motor area, ventral premotor and parietal cortex as well as the basal ganglia and cerebellum. The absence of significant group differences in baseline ASL perfusion patterns supports a neuronal rather than a purely vascular origin of these differences. The VBM and TBSS analyses excluded potentially confounding differences in grey matter density and white matter microstructure between MCI and HC. The present findings suggest a posterior displacement of working memory-related brain activation patterns after caffeine administration in MCI that may represent a compensatory mechanism to counterbalance a frontal lobe dysfunction.

  7. Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial

    PubMed Central

    Xiao, Guomin; Wei, Jing; Yan, Weiqi; Wang, Weimin; Lu, Zhenhui

    2008-01-01

    injury were lower in the progesterone group than in the placebo group, but there was no statistical significance between the two groups (P > 0.05). Instances of complications and adverse events associated with the administration of progesterone were not found. Conclusion Our data suggest that acute severe TBI patients with administration of progesterone hold improved neurologic outcomes for up to 6 months. These results provide information important for further large and multicenter clinical trials on progesterone as a promising neuroprotective drug. Trial Registration ACTRN12607000545460. PMID:18447940

  8. Nicotine and cocaine self-administration using a multiple schedule of intravenous drug and sucrose reinforcement in rats.

    PubMed

    Stairs, Dustin J; Neugebauer, Nichole M; Bardo, Michael T

    2010-05-01

    There appears to be a relatively narrow range of contingencies in which intravenous (i.v) infusions of nicotine will maintain responding in rats. The schedule of reinforcement typically used when investigating i.v. nicotine self-administration is a simple fixed-ratio (FR) schedule. This study determined if responding in rats could be established using a multiple schedule of either i.v. cocaine or nicotine and sucrose reinforcement. Following training of individual components with each reinforcer, rats were placed on an FR15 60-s timeout multiple schedule of cocaine (0.3 mg/kg/infusion) and sucrose (45 mg pellets) reinforcement or an FR5 60-s timeout multiple schedule of nicotine (0.03 mg/kg/infusion) and sucrose (45 mg pellets) reinforcement. Both cocaine and nicotine maintained significant levels of responding under the multiple schedule. Pretreatment with the dopamine D1 antagonist SCH 23390 increased cocaine-maintained responding, but not sucrose responding. Acute pretreatment with the nicotinic antagonist mecamylamine or SCH 23390 specifically decreased nicotine self-administration. Extinction of the individual nicotine and sucrose components resulted in decreases in responding in each component under extinction. These results indicate that i.v. nicotine maintains responding under a multiple schedule. This procedure may be useful when studying the specificity of drug pretreatments on nicotine self-administration.

  9. Epidemiology of acute drug poisoning in a tertiary center from Iasi County, Romania.

    PubMed

    Sorodoc, Victorita; Jaba, Irina M; Lionte, Catalina; Mungiu, Ostin C; Sorodoc, Laurentiu

    2011-12-01

    The aim of this retrospective epidemiological study was to investigate the demographical, etiological and clinical characteristics of acute drug poisonings in Iasi County, Romania. All patients were referred and admitted in the Toxicology Clinic of "Sf. Ioan" Emergency Clinic Hospital Iasi, Romania. Between 2003 and 2009, 811 cases of acute drug poisonings were recorded, counting for 28.43% from the total number of poisonings. The majority of these poisonings resulted in mild (51.94%) and medium (28.35%) clinical forms, while 19.71% were coma situations. In all, 63.51% of patients originated from urban areas, 39.94% were unemployed and the patients were predominantly women (66.46%). A high percentage (97.27%) were suicide attempts, using only one type of drug (65.88%) and the 21-30 years group (29.8%) records the highest incidence, for both women and men. The most frequently involved drugs were benzodiazepines 13.69%, anticonvulsive drugs 8.63%, barbiturates 8.51% and cardiovascular drugs 5.92%. Drugs combinations were recorded in 32.92% of cases and 1.2% were combinations between drugs and other substances. Mortality was the outcome in 0.3% of the total registered number of acute drug poisonings. This study underlines that in order to provide a proper management of these situations, a Regional Poison Information Center is absolutely necessary.

  10. Key Findings from Preclinical and Clinical Drug Interaction Studies Presented in New Drug and Biological License Applications Approved by the Food and Drug Administration in 2014.

    PubMed

    Yu, Jingjing; Ritchie, Tasha K; Zhou, Zhu; Ragueneau-Majlessi, Isabelle

    2016-01-01

    Regulatory approval documents contain valuable information, often not published, to assess the drug-drug interaction (DDI) profile of newly marketed drugs. This analysis aimed to systematically review all drug metabolism, transport, pharmacokinetics, and DDI data available in the new drug applications and biologic license applications approved by the U.S. Food and Drug Administration in 2014, using the University of Washington Drug Interaction Database, and to highlight the significant findings. Among the 30 new drug applications and 11 biologic license applications reviewed, 35 new molecular entities (NMEs) were well characterized with regard to drug metabolism, transport, and/or organ impairment and were fully analyzed in this review. In vitro, a majority of the NMEs were found to be substrates or inhibitors/inducers of at least one drug metabolizing enzyme or transporter. In vivo, when NMEs were considered as victim drugs, 16 NMEs had at least one in vivo DDI study with a clinically significant change in exposure (area under the time-plasma concentration curve or Cmax ratio ≥2 or ≤0.5), with 6 NMEs shown to be sensitive substrates of cytochrome P450 enzymes (area under the time-plasma concentration curve ratio ≥5 when coadministered with potent inhibitors): paritaprevir and naloxegol (CYP3A), eliglustat (CYP2D6), dasabuvir (CYP2C8), and tasimelteon and pirfenidone (CYP1A2). As perpetrators, seven NMEs showed clinically significant inhibition involving both enzymes and transporters, although no clinically significant induction was observed. Physiologically based pharmacokinetic modeling and pharmacogenetics studies were used for six and four NMEs, respectively, to optimize dosing recommendations in special populations and/or multiple impairment situations. In addition, the pharmacokinetic evaluations in patients with hepatic or renal impairment provided useful quantitative information to support drug administration in these fragile populations.

  11. Co-administration of a Tumor-Penetrating Peptide Enhances the Efficacy of Cancer Drugs

    PubMed Central

    Sugahara, Kazuki N.; Teesalu, Tambet; Karmali, Priya Prakash; Kotamraju, Venkata Ramana; Agemy, Lilach; Greenwald, Daniel R.; Ruoslahti, Erkki

    2010-01-01

    Poor penetration of anti-cancer drugs into tumors can be an important factor limiting their efficacy. Studying mouse tumor models, we show that a previously characterized tumor-penetrating peptide, iRGD (CRGDK/RGPD/EC), increased vascular and tissue permeability in a tumor-specific and neuropilin-1-dependent manner, allowing co-administered drugs to penetrate into extravascular tumor tissue. Importantly, this effect did not require the drugs to be chemically conjugated to the peptide. Systemic injection with iRGD improved the therapeutic index of drugs of various compositions including a small molecule (doxorubicin), nanoparticles (nab-paclitaxel and doxorubicin liposomes), and a monoclonal antibody (trastuzumab). Thus, co-administration of iRGD may be a valuable way to enhance the efficacy of anti-cancer drugs while reducing their side effects, a primary goal of cancer therapy research. PMID:20378772

  12. Lethal acute lung injury and hypoglycemia after subcutaneous administration of monochloroacetic acid.

    PubMed

    Kato, Junko; Dote, Tomotaro; Shimizu, Hiroyasu; Shimbo, Yukari; Fujihara, Michiko; Kono, Koichi

    2006-06-01

    Hypoglycemia is suspected in the acute lethal toxicity induced by cutaneous exposure to monochloroacetic acid (MCA). Although it has been shown that hepato-renal dysfunction is involved, the mechanism and the target organs that directly affect mortality remain to be determined. We suspected respiratory failure as a main cause of death in some reported cases. We investigated dose-response effects, hypoglycemia, and lung injury in rats exposed to MCA. Serum glucose, blood gases, and parameters of alveolar injury in bronchoalveolar lavage fluid (BALF) were analysed 2 and 4 h after subcutaneous administration of MCA (108, 135 or 163 mg/kg). Apparent pulmonary injury and hypoglycemia were not identified 2 h after administration, but lactate dehydrogenase (LDH) and total cells in BALF were dose-dependently increased; and severe hypoglycemia was identified 4 h after administration. Blood gas analysis showed remarkable alveolar gas dysfunction as exchange in the 163 mg/kg group. Thus, hypoglycemia and lung injury appear to cause death in response to MCA exposure.

  13. Improved memory for reward cues following acute buprenorphine administration in humans.

    PubMed

    Syal, Supriya; Ipser, Jonathan; Terburg, David; Solms, Mark; Panksepp, Jaak; Malcolm-Smith, Susan; Bos, Peter A; Montoya, Estrella R; Stein, Dan J; van Honk, Jack

    2015-03-01

    In rodents, there is abundant evidence for the involvement of the opioid system in the processing of reward cues, but this system has remained understudied in humans. In humans, the happy facial expression is a pivotal reward cue. Happy facial expressions activate the brain's reward system and are disregarded by subjects scoring high on depressive mood who are low in reward drive. We investigated whether a single 0.2mg administration of the mixed mu-opioid agonist/kappa-antagonist, buprenorphine, would influence short-term memory for happy, angry or fearful expressions relative to neutral faces. Healthy human subjects (n38) participated in a randomized placebo-controlled within-subject design, and performed an emotional face relocation task after administration of buprenorphine and placebo. We show that, compared to placebo, buprenorphine administration results in a significant improvement of memory for happy faces. Our data demonstrate that acute manipulation of the opioid system by buprenorphine increases short-term memory for social reward cues.

  14. 76 FR 43690 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-21

    ... Administration (FDA) is announcing the availability of the guidance entitled ``Class II Special Controls Guidance Document: Electrocardiograph Electrodes.'' The special controls identify the following risks to health... Drug Administration Staff; Class II Special Controls Guidance Document: Electrocardiograph...

  15. 78 FR 277 - Food and Drug Administration Actions Related to Nicotine Replacement Therapies and Smoking...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-03

    ... goals: (1) Total abstinence from tobacco use, (2) reductions in consumption of tobacco, and (3... Tobacco Dependence; Public Hearing; Extension of Comment Period AGENCY: Food and Drug Administration, HHS... innovative products and treatments for tobacco dependence. The Agency is taking this action to...

  16. 27 CFR 17.136 - Compliance with Food and Drug Administration requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... products manufactured solely for export or for uses other than internal human consumption (e.g. tobacco... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Compliance with Food and Drug Administration requirements. 17.136 Section 17.136 Alcohol, Tobacco Products and Firearms...

  17. 28 CFR 0.157 - Federal Bureau of Investigation-Drug Enforcement Administration Senior Executive Service.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... within the Federal Bureau of Investigation (FBI) and the Drug Enforcement Administration (DEA) to be known as the FBI-DEA Senior Executive Service (FBI-DEA SES). (b) Pursuant to 5 U.S.C. 3151(b)(2)(B), a... the position of Deputy Director of the FBI (which remains subject to the exclusive authority of...

  18. 77 FR 8886 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-15

    ... of public workshop. SUMMARY: The Food and Drug Administration (FDA) Detroit District Office, in co... District Office, 300 River Pl., Suite 5900, Detroit, MI 48207, 313-393-8143, Fax: 313- 393-8139, email... 13.3 Continuing Education Credits for SoCRA CE and Nurse CNE. SoCRA designates this live activity...

  19. 76 FR 78933 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-20

    .... ACTION: Notice of public workshop. The Food and Drug Administration (FDA), Los Angeles District Office... continuing nurse education (CNE). SOCRA designates this educational activity for a maximum of 13.3 American.... SoCRA is an approved provider of CNE by the Pennsylvania State Nurses Association (PSNA),...

  20. 76 FR 51040 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    .... ACTION: Notice of public workshop. The Food and Drug Administration (FDA) Philadelphia District Office..., Philadelphia District, 900 U.S. Customhouse, Second & Chestnut Streets, Philadelphia, PA 19106, 215-597-4390... Continuing Education Credits for SoCRA CE and Nurse CNE. SOCRA designates this live activity for a maximum...

  1. 76 FR 17138 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-28

    .... ACTION: Notice of public workshop. The Food and Drug Administration (FDA) Denver District Office, in co... activity for a maximum of 13.3 Continuing Education (CE) Credits for SoCRA CE and Nurse CNE. SoCRA... nursing education by the Pennsylvania State Nurses Association (PSNA), an accredited approver by...

  2. Program Administrator's Handbook. Strategies for Preventing Alcohol and Other Drug Problems. The College Series.

    ERIC Educational Resources Information Center

    CSR, Inc., Washington, DC.

    This handbook is for administrators of programs in higher education settings which deal with alcohol and other drug (AOD) related problems. Chapter 1, "Defining the Problem, Issues, and Trends" examines the problem from various perspectives and presents the latest statistics on the extent of AOD use on campuses, specific problems affecting…

  3. 78 FR 13070 - Guidance for Clinical Investigators, Industry, and Food and Drug Administration Staff: Financial...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-26

    ... HUMAN SERVICES Food and Drug Administration (formerly 1999D-4396) Guidance for Clinical Investigators... recommendations made by the Office of the Inspector General (OIG), Department of Health and Human Services, in... represents FDA's current thinking on this topic. It does not create or confer any rights for or on any...

  4. 77 FR 16923 - Agreements and Memoranda of Understanding Between the Food and Drug Administration and Other...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-23

    ...-ROM submissions): Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers... document, into the ``Search'' box and follow the prompts and/or go to the Division of Dockets Management... Register of March 22, 1977 (42 FR 15616 at 15625). Consumers, industry, professional groups,...

  5. 77 FR 16971 - Agreements and Memoranda of Understanding Between the Food and Drug Administration and Other...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-23

    ... Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852... and/or go to the Division of Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. FOR... 20.108) in the Federal Register of March 22, 1977 (42 FR 15616 at 15625). Consumers,...

  6. 76 FR 41803 - Guidance for Industry and Food and Drug Administration Staff; Establishing the Performance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-15

    ... Differentiation of Influenza Viruses; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice... Differentiation of Influenza Viruses.'' FDA is issuing this guidance to inform industry and Agency staff of its... diagnostic devices intended for the detection or detection and differentiation of influenza viruses....

  7. 78 FR 15370 - Draft Guidance for Industry and Food and Drug Administration Staff: Recommendations for Labeling...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-11

    ... Container Is Not Made With Natural Rubber Latex; Availability AGENCY: Food and Drug Administration, HHS... to include in the labeling of a medical product to convey that natural rubber latex was not used as a... for inclusion in medical product labeling such as ``latex-free,'' ``does not contain natural...

  8. 76 FR 12563 - Amendments to General Regulations of the Food and Drug Administration; Confirmation of Effective...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-08

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 14, and 17 RIN 0910-AG55 Amendments to... certain general regulations of FDA to include tobacco products, where appropriate, in light of FDA's authority to regulate these products under the Family Smoking Prevention and Tobacco Control Act,...

  9. 76 FR 50484 - Draft Guidance for Industry, Clinical Investigators, and Food and Drug Administration Staff...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-15

    ... Food and Drug Administration Staff; Design Considerations for Pivotal Clinical Investigations for... Considerations for Pivotal Clinical Investigations for Medical Devices.'' This document is intended to provide... to fulfill premarket clinical data requirements. This draft guidance is not final nor is it in...

  10. Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early-stage Alzheimer's disease.

    PubMed

    Schneider, Lon S

    2014-03-01

    The February 2013 Food and Drug Administration (FDA) draft guidance for developing drugs for early-stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale - the Clinical Dementia Rating Scale in particular - for the primary outcome for prodromal AD clinical trials. In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence-based clinical research practices are still evolving.

  11. In vitro and in vivo evaluation of self-nanoemulsifying drug delivery systems of cilostazol for oral and parenteral administration.

    PubMed

    Mahmoud, Dina B; Shukr, Marwa H; Bendas, Ehab R

    2014-12-10

    The current investigation was aimed to improve the solubility of poorly soluble drug, cilostazol (CLZ). Self-nanoemulsifying drug delivery system (SNEDDS) composed of oil, surfactant and co-surfactant for both oral and parenteral administration of CLZ was formulated. The components for SNEDDS were identified by solubility studies, and pseudo-ternary phase diagrams were plotted to identify the efficient self-emulsification regions. The optimum formula, composed of Capryol 90 as an oil phase, Cremophor EL as a surfactant, and Transcutol HP as a co-surfactant in a ratio of 19.8:30.5:49.7 by weight, was able to solubilize CLZ 2000 times higher than its solubility in water. This formula was able to form grade "A" nanoemulsion when diluted with water, resulted in emulsification time of 50±1.1 s, particle size of 14.3 nm, PDI of 0.5 and % transmittance was 97.40%±0.65. It showed excellent in vitro dissolution of 93.1% and 81.5% after 5 min in 0.3% sodium lauryl sulphate solution and phosphate buffer pH 6.4, respectively when compared with the marketed tablet formulation and drug suspension as the tablets showed only 44.3% and 9.9% while CLZ suspension showed 33.9% and 8.8% in 0.3% sodium lauryl sulphate solution and phosphate buffer pH 6.4, respectively. It was found to be robust to dilution, thermodynamically stable with low viscosity values of 14.20±0.35 cP. In vivo study revealed significant increase in bioavailability of CLZ in rabbits to 3.94 fold compared with the marketed tablet formulation after oral administration. This formula could be sterilized by autoclaving and did not cause significant hemolysis to human blood which indicates its safety for intravenous administration with a 1.12 fold increase in bioavailability compared with its oral administration. Our study illustrated the potential use of SNEDDS of poorly soluble CLZ orally, and its successful administration of parenterally when required in acute cases of myocardial and cerebral infarction.

  12. Finding, evaluating, and managing drug-related risks: approaches taken by the US Food and Drug Administration (FDA).

    PubMed

    Weaver, Joyce; Grenade, Lois La; Kwon, Hyon; Avigan, Mark

    2009-01-01

    Marketed pharmaceuticals are evaluated for safety by the US Food and Drug Administration (FDA) throughout the life cycle of the products. The FDA uses data from controlled clinical trials, from postmarketing case reports reported to the FDA's Adverse Event Reporting System, from epidemiological studies, and from registries to evaluate the safety of approved products. For some products, including some products used in dermatologic medicine, risks become apparent during the postmarketing period that require additional measures beyond product labeling and routine pharmacovigilance. The FDA continues to seek additional tools to assess risk, including pharmacogenomic biomarkers for adverse drug reactions and the use of large medical record and epidemiological databases for the systematic detection and characterization of drug-associated safety outcomes.

  13. 76 FR 46303 - Guidance for Industry and Food and Drug Administration Staff: Investigational New Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-02

    .... We acknowledge that there will be cord blood banks that are not able to achieve licensure by October... Blood Intended for Hematopoietic Reconstitution for Specified Indications; Availability AGENCY: Food and... Drug Applications (INDs) for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord...

  14. 78 FR 20664 - Society of Clinical Research Associates-Food and Drug Administration: Food and Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-05

    ... authority of FDA and to facilitate interaction with FDA representatives. The program will focus on the... provide those engaged in FDA-regulated (human) clinical trials with information on a number of topics... community a high priority to help ensure the quality of FDA-regulated drugs and devices. The workshop...

  15. 21 CFR 20.105 - Testing and research conducted by or with funds provided by the Food and Drug Administration.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Testing and research conducted by or with funds provided by the Food and Drug Administration. 20.105 Section 20.105 Food and Drugs FOOD AND DRUG... Categories of Records § 20.105 Testing and research conducted by or with funds provided by the Food and...

  16. 21 CFR 20.105 - Testing and research conducted by or with funds provided by the Food and Drug Administration.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Testing and research conducted by or with funds provided by the Food and Drug Administration. 20.105 Section 20.105 Food and Drugs FOOD AND DRUG... Categories of Records § 20.105 Testing and research conducted by or with funds provided by the Food and...

  17. 21 CFR 20.105 - Testing and research conducted by or with funds provided by the Food and Drug Administration.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Testing and research conducted by or with funds provided by the Food and Drug Administration. 20.105 Section 20.105 Food and Drugs FOOD AND DRUG... Categories of Records § 20.105 Testing and research conducted by or with funds provided by the Food and...

  18. 21 CFR 20.105 - Testing and research conducted by or with funds provided by the Food and Drug Administration.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Testing and research conducted by or with funds provided by the Food and Drug Administration. 20.105 Section 20.105 Food and Drugs FOOD AND DRUG... Categories of Records § 20.105 Testing and research conducted by or with funds provided by the Food and...

  19. 21 CFR 20.105 - Testing and research conducted by or with funds provided by the Food and Drug Administration.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Testing and research conducted by or with funds provided by the Food and Drug Administration. 20.105 Section 20.105 Food and Drugs FOOD AND DRUG... Categories of Records § 20.105 Testing and research conducted by or with funds provided by the Food and...

  20. 76 FR 5387 - Guidance for Industry and Food and Drug Administration Staff; “`Harmful and Potentially Harmful...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-31

    ... Food, Drug, and Cosmetic Act''; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice... Section 904(e) of the Federal Food, Drug, and Cosmetic Act.'' This guidance provides written guidance to... Tobacco Products as Used in Section 904(e) of the Federal Food, Drug, and Cosmetic Act.'' The...

  1. Prohibited or regulated? LSD psychotherapy and the United States Food and Drug Administration.

    PubMed

    Oram, Matthew

    2016-09-01

    Over the 1950s and early 1960s, the use of the hallucinogenic drug lysergic acid diethylamide (LSD) to facilitate psychotherapy was a promising field of psychiatric research in the USA. However, during the 1960s, research began to decline, before coming to a complete halt in the mid-1970s. This has commonly been explained through the increase in prohibitive federal regulations during the 1960s that aimed to curb the growing recreational use of the drug. However, closely examining the Food and Drug Administration's regulation of LSD research in the 1960s will reveal that not only was LSD research never prohibited, but that the administration supported research to a greater degree than has been recognized. Instead, the decline in research reflected more complex changes in the regulation of pharmaceutical research and development.

  2. 75 FR 18219 - Drug and Medical Device Forum on Food and Drug Administration Drug and Device Requirements and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-09

    ... related to the production and marketing of drugs and/or devices. Topics for discussion include the following: Regulating Medical Products in the Global Environment FDA Revitalization Efforts--Top 10 Drug... Case Studies--Supplier Controls Supplier Quality in a Global Economy--Consensus Standards...

  3. 75 FR 32953 - Guidance for Industry and Food and Drug Administration Staff; Use of “Light,” “Mild,” “Low,” or...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-10

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry and Food and Drug Administration Staff... Tobacco Products; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the guidance entitled ``Use...

  4. Immunomodulatory Drugs: Immune Checkpoint Agents in Acute Leukemia

    PubMed Central

    Knaus, Hanna A.; Kanakry, Christopher G.; Luznik, Leo; Gojo, Ivana

    2016-01-01

    Intrinsic immune responses to acute leukemia are inhibited by a variety of mechanisms, such as aberrant antigen expression by leukemia cells, secretion of immunosuppressive cytokines and expression of inhibitory enzymes in the tumor microenvironment, expansion of immunoregulatory cells, and activation of immune checkpoint pathways, all leading to T cell dysfunction and/or exhaustion. Leukemic cells, similar to other tumor cells, hijack these inhibitory pathways to evade immune recognition and destruction by cytotoxic T lymphocytes. Thus, blockade of immune checkpoints has emerged as a highly promising approach to augment innate anti-tumor immunity in order to treat malignancies. Most evidence for the clinical efficacy of this immunotherapeutic strategy has been seen in patients with metastatic melanoma, where anti-CTLA-4 and anti-PD-1 antibodies have recently revolutionized treatment of this lethal disease with otherwise limited treatment options. To meet the high demand for new treatment strategies in acute leukemia, clinical testing of these promising therapies is commencing. Herein, we review the biology of multiple inhibitory checkpoints (including CTLA-4, PD-1, TIM-3, LAG-3, BTLA, and CD200R) and their contribution to immune evasion by acute leukemias. In addition, we discuss the current state of preclinical and clinical studies of immune checkpoint inhibition in acute leukemia, which seek to harness the body’s own immune system to fight leukemic cells. PMID:25981611

  5. Immunomodulatory Drugs: Immune Checkpoint Agents in Acute Leukemia.

    PubMed

    Knaus, Hanna A; Kanakry, Christopher G; Luznik, Leo; Gojo, Ivana

    2017-01-01

    Intrinsic immune responses to acute leukemia are inhibited by a variety of mechanisms, such as aberrant antigen expression by leukemia cells, secretion of immunosuppressive cytokines and expression of inhibitory enzymes in the tumor microenvironment, expansion of immunoregulatory cells, and activation of immune checkpoint pathways, all leading to T cell dysfunction and/or exhaustion. Leukemic cells, similar to other tumor cells, hijack these inhibitory pathways to evade immune recognition and destruction by cytotoxic T lymphocytes. Thus, blockade of immune checkpoints has emerged as a highly promising approach to augment innate anti-tumor immunity in order to treat malignancies. Most evidence for the clinical efficacy of this immunotherapeutic strategy has been seen in patients with metastatic melanoma, where anti-CTLA-4 and anti-PD-1 antibodies have recently revolutionized treatment of this lethal disease with otherwise limited treatment options. To meet the high demand for new treatment strategies in acute leukemia, clinical testing of these promising therapies is commencing. Herein, we review the biology of multiple inhibitory checkpoints (including CTLA-4, PD-1, TIM-3, LAG-3, BTLA, and CD200R) and their contribution to immune evasion by acute leukemias. In addition, we discuss the current state of preclinical and clinical studies of immune checkpoint inhibition in acute leukemia, which seek to harness the body's own immune system to fight leukemic cells.

  6. Effects of Acute and Repeated Administration of Oxycodone and Naloxone-Precipitated Withdrawal on Intracranial Self-Stimulation in Rats

    PubMed Central

    Wiebelhaus, Jason M.; Walentiny, D. Matthew

    2016-01-01

    Incidence of prescription opioid abuse and overdose, often led by oxycodone, continues to increase, producing twice as many overdose deaths as heroin. Surprisingly, preclinical reports relevant to oxycodone’s abuse-related effects are relatively sparse considering its history and patient usage. The goal of this study was to characterize dose- and time-dependent effects of acute and repeated oxycodone administration in a frequency-rate intracranial self-stimulation (ICSS) procedure, an assay often predictive of drug-related reinforcing effects, in male Sprague-Dawley rats. We hypothesized that oxycodone would produce a biphasic profile of rate-increasing and rate-decreasing effects maintained by ICSS similar to μ-opioid receptor agonists. Oxycodone (0.03, 0.3, 1, and 3 mg/kg, s.c.) produced dose- and time-dependent alterations on ICSS, with the predicted biphasic profile of rate-increasing effects at lower stimulation frequencies followed by rate-decreasing effects at higher frequencies. Peak effects were observed between 30 and 60 minutes, which were reversed by naloxone pretreatment (30 minutes). Tolerance to rate-decreasing effects was observed over a 5-day period when rats were treated with 1 mg/kg oxycodone twice a day. Subsequently, the dosing regimen was increased to 3 mg/kg twice a day over 10 days, although further marked tolerance did not develop. When then challenged with 10 mg/kg naloxone, a significant suppression below baseline levels of ICSS-maintained responding occurred indicative of dependence that recovered to baseline within 5 hours. The results of this study provide the first report of acute and chronic effects of oxycodone on responding maintained by ICSS presentation and the use of ICSS-maintained responding to characterize its tolerance and dependence effects. PMID:26491062

  7. Effects of Acute and Repeated Administration of Oxycodone and Naloxone-Precipitated Withdrawal on Intracranial Self-Stimulation in Rats.

    PubMed

    Wiebelhaus, Jason M; Walentiny, D Matthew; Beardsley, Patrick M

    2016-01-01

    Incidence of prescription opioid abuse and overdose, often led by oxycodone, continues to increase, producing twice as many overdose deaths as heroin. Surprisingly, preclinical reports relevant to oxycodone's abuse-related effects are relatively sparse considering its history and patient usage. The goal of this study was to characterize dose- and time-dependent effects of acute and repeated oxycodone administration in a frequency-rate intracranial self-stimulation (ICSS) procedure, an assay often predictive of drug-related reinforcing effects, in male Sprague-Dawley rats. We hypothesized that oxycodone would produce a biphasic profile of rate-increasing and rate-decreasing effects maintained by ICSS similar to μ-opioid receptor agonists. Oxycodone (0.03, 0.3, 1, and 3 mg/kg, s.c.) produced dose- and time-dependent alterations on ICSS, with the predicted biphasic profile of rate-increasing effects at lower stimulation frequencies followed by rate-decreasing effects at higher frequencies. Peak effects were observed between 30 and 60 minutes, which were reversed by naloxone pretreatment (30 minutes). Tolerance to rate-decreasing effects was observed over a 5-day period when rats were treated with 1 mg/kg oxycodone twice a day. Subsequently, the dosing regimen was increased to 3 mg/kg twice a day over 10 days, although further marked tolerance did not develop. When then challenged with 10 mg/kg naloxone, a significant suppression below baseline levels of ICSS-maintained responding occurred indicative of dependence that recovered to baseline within 5 hours. The results of this study provide the first report of acute and chronic effects of oxycodone on responding maintained by ICSS presentation and the use of ICSS-maintained responding to characterize its tolerance and dependence effects.

  8. Effects of acute ethanol administration on nocturnal pineal serotonin N-acetyltransferase activity

    SciTech Connect

    Creighton, J.A.; Rudeen, P.K.

    1988-01-01

    The effect of acute ethanol administration on pineal serotonin N-acetyltransferase (NAT) activity, norepinephrine and indoleamine content was examined in male rats. When ethanol was administered in two equal doses (2 g/kg body weight) over a 4 hour period during the light phase, the nocturnal rise in NAT activity was delayed by seven hours. The nocturnal pineal norepinephrine content was not altered by ethanol except for a delay in the reduction of NE with the onset of the following light phase. Although ethanol treatment led to a significant reduction in nocturnal levels of pineal serotonin content, there was no significant effect upon pineal content of 5-hydroxyindoleacetic acid (5-HIAA). The data indicate that ethanol delays the onset of the rise of nocturnal pineal NAT activity.

  9. Effects of acute administration of brotizolam in subjects with disturbed sleep

    PubMed Central

    Roehrs, T.; Zorick, F.; Koshorek, G. L.; Wittig, R.; Roth, T.

    1983-01-01

    1 Effects of ingestion of brotizolam (0.25 and 0.50 mg) over 1-3 days on polysomnographic measures of sleep were assessed in patients complaining of insomnia. 2 Brotizolam reduced latency to sleep, number of awakenings and wake during sleep, and increased total sleep time. It also increased stage 2 sleep and decreased slow wave and rapid eye movement sleep. 3 Increasing the dose from 0.25 to 0.50 mg increased hypnotic efficacy, and there was a more consistent and reliable effect. 4 Discontinuation of brotizolam had minimal effects on sleep compared with placebo over the 3 nights after acute administration. 5 No side-effects or disruption of daytime function was found using questionnaires and objective tests of performance. PMID:6661383

  10. Behavioral consequences of chelator administration in acute cadmium toxicity (journal version)

    SciTech Connect

    Peele, D.B.; Farmer, J.D.; MacPhail, R.C.

    1988-01-01

    The conditioned flavor-aversion paradigm was used to assess the toxicity of acutely administered cadmium and the interaction of cadmium with the heavy-metal chelating agents dimercaprol (BAL) and dimercaptosuccinic acid (DMSA). Shortly after consuming saccharin, rats received cadmium either alone or in combination with BAL or DMSA. When compared to rats receiving either nothing or the vehicle, rats receiving cadmium displayed significant reductions in saccharin preference (i.e., conditioned flavor aversions). BAL and DMSA were also capable of producing conditioned flavor aversions when given alone. Rats receiving cadmium in combination with either BAL or DMSA displayed significant, but not complete, attenuations of conditioned flavor aversions when compared to rats receiving cadmium alone. Chelator-induced blockade of cadmium-induced flavor-aversion conditioning was not obtained when BAL or DMSA administration was delayed by 4 hrs.

  11. A mathematical model for long-term effect of diethylcarbamazine-albendazole mass drug administration on lymphatic filariasis

    NASA Astrophysics Data System (ADS)

    Tasman, H.; Supali, T.; Supriatna, A. K.; Nuraini, N.; Soewono, E.

    2015-03-01

    In this paper we discuss a mathematical model for the transmission of lymphatic filariasis disease. The human population is divided into susceptible, latent, acute and chronic subpopulations. Treatment is carried out within the scheme of mass drug administration (MDA) by giving the diethylcarbamazine (DEC) and albendazole (ALB) to all individuals. In the model, we assume that the treatments have direct killing effect to microfilariae, increase of immune-mediated effect. The treated individuals are assumed to remain susceptible to the disease. This is due to the fact that the treatment is only partially effective against macrofilaria. Simulations of the model reveals that DEC-ALB treatment does give significant reduction of acute and chronic compartments at the end of the treatment period and slow down the growth after the treatment before eventually tend to the endemic state. It showed that repeated treatment during MDA is effective to decrease the transmission. This suggests that terminating MDA program after a long period of its application may still effective in controlling the disease.

  12. Liver necrosis induced by acute intraperitoneal ethanol administration in aged rats.

    PubMed

    Giavarotti, Leandro; D'Almeida, Vania; Giavarotti, Karin A S; Azzalis, Ligia A; Rodrigues, Luciano; Cravero, Amerys A M; Videla, Luis A; Koch, Osvaldo R; Junqueira, Virginia B C

    2002-03-01

    It is generally agreed that the deleterious pathophysiological effects of ethanol are caused, at least partially by an increase in free radical production. However, little attention has been directed to the effects of ethanol upon elderly organisms. Male Wistar rats at ages 3, 6, 12, 18 and 24 months were treated either with a single i.p. dose of 35% ethanol (v/v) at 3 g ethanol/kg body weight or an isovolumetric amount of 0.9% saline solution. We then assessed the plasma levels of transaminases and hepatic levels of oxidative stress-related parameters, followed by liver histological evaluation. The younger rats (3 months old) were not affected by the treatment with ethanol with respect to any of the studied parameters except for a lowering of total hepatic GSH and an increase in hepatic thiobarbituric acid reactants (TBARS) formation, while animals older than 3 months were increasingly more affected by the treatment. Acute ethanol treatment elicited the similar responses to those in the 3 months-old group, plus a decrease in the hepatic and plasma levels of beta-carotene and the plasma level of alpha-tocopherol, as well as an increase in the activity of plasma transaminases. In the 12,18 and 24 months old groups, there was increasing liver necrosis. These findings suggest that liver damage induced by acute ethanol administration in elderly rats may involve a lack of antioxidants.

  13. Central nervous insulin administration does not potentiate the acute glucoregulatory impact of concurrent mild hyperinsulinemia.

    PubMed

    Ott, Volker; Lehnert, Hendrik; Staub, Josefine; Wönne, Kathrin; Born, Jan; Hallschmid, Manfred

    2015-03-01

    Experiments in rodents suggest that hypothalamic insulin signaling essentially contributes to the acute control of peripheral glucose homeostasis. Against this background, we investigated in healthy humans whether intranasal (IN) insulin, which is known to effectively reach the brain compartment, impacts systemic glucose metabolism. Twenty overnight-fasted healthy, normal-weight men were IN administered 210 and 420 international units [IU] (10 and 20 IU every 15 min) of the insulin analog aspart (ins-asp) and placebo, respectively, during experimental sessions lasting 6 h. The use of ins-asp rather than human insulin enabled us to disentangle exogenous and endogenous insulin kinetics. IN insulin dose-dependently decreased plasma glucose concentrations while reducing C-peptide and attenuating endogenous insulin levels. However, we also observed a slight dose-dependent permeation of ins-asp into the circulation. In control experiments mimicking the systemic but not the central nervous uptake of the IN 210 IU dose via intravenous infusion of ins-asp at a dose of 0.12 IU/kg/24 h (n = 10), we obtained essentially identical effects on fasting plasma glucose concentrations. This pattern indicates that sustained IN insulin administration to the human brain to enhance central nervous insulin signaling does not acutely alter systemic glucose homeostasis beyond effects accounted for by concurrent mild hyperinsulinemia.

  14. Changes in cerebral neurotransmitters and metabolites induced by acute donepezil and memantine administrations: a microdialysis study.

    PubMed

    Shearman, E; Rossi, S; Szasz, B; Juranyi, Z; Fallon, S; Pomara, N; Sershen, H; Lajtha, A

    2006-03-31

    Cholinesterase inhibitors including donepezil, rivastigmine, and galantamine and the N-methyl-D-aspartate (NMDA) antagonist, memantine are the medications currently approved for the treatment of Alzheimer's disease (AD). In addition to their beneficial effects on cognitive and functional domains typically disrupted in AD, these agents have also been shown to slow down the emergence of behavioral and psychotic symptoms associated with this disease. However, the underlying mechanisms for these therapeutic effects remain poorly understood and could involve effects of these medications on non-cholinergic or non-glutamatergic neurotransmitter systems respectively. These considerations prompted us to initiate a series of investigations to examine the acute and chronic effects of donepezil (Aricept (+/-)-2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-1 hydrochloride and memantine (1-amino-3,5-dimethyladamantane hydrochloride C12H21N.HCl)). The present study focuses on the acute effects of donepezil and memantine on brain extracellular levels of acetylcholine, dopamine, serotonin, norepinephrine and their metabolites. We assayed changes in the ventral and dorsal hippocampus and the prefrontal and medial temporal cortex by microdialysis. Memantine resulted in significant increases in extracellular dopamine (DA), norepinephrine (NE), and their metabolites, in the cortical regions, and in a reduction of DA in the hippocampus. Donepezil produced an increase in extracellular DA in the cortex and in the dorsal hippocampus. Norepinephrine increased in the cortex; with donepezil it increased in the dorsal hippocampus and the medial temporal cortex, and decreased in the ventral hippocampus. Interestingly both compounds decreased extracellular serotonin (5HT) levels. The metabolites of the neurotransmitters were increased in most areas. We also found an increase in extracellular acetylcholine (ACh) by memantine in the nucleus accumbens and the

  15. Cyberpharmacies and the role of the US Food And Drug Administration

    PubMed Central

    2001-01-01

    The sale of consumer products over the Internet has grown rapidly, including the sale of drugs. While the growth in online drug sales by reputable pharmacies is a trend that may provide benefits to consumers, online drug sales also present risks to purchasers and some unique challenges to regulators, law enforcement officials and policy makers. The Food and Drug Administration (FDA or the Agency) is concerned about the public health implications of Internet drug sales, and we are responding to these concerns as part of our overall goal of developing and implementing risk-based strategies to protect public health and safety. Although other products regulated by the Agency, such as medical devices, medical test products, foods, dietary supplements and animal drugs also are sold online, this paper focuses on online drug sales. We discuss the advantages and risks of online drug sales, outline FDA's authority and enforcement activities in this area, and describe new initiatives we are taking to better respond to the regulatory challenges we face. PMID:11720945

  16. Clinical review: Drug metabolism and nonrenal clearance in acute kidney injury

    PubMed Central

    Vilay, A Mary; Churchwell, Mariann D; Mueller, Bruce A

    2008-01-01

    Decreased renal drug clearance is an obvious consequence of acute kidney injury (AKI). However, there is growing evidence to suggest that nonrenal drug clearance is also affected. Data derived from human and animal studies suggest that hepatic drug metabolism and transporter function are components of nonrenal clearance affected by AKI. Acute kidney injury may also impair the clearance of formed metabolites. The fact that AKI does not solely influence kidney function may have important implications for drug dosing, not only of renally eliminated drugs but also of those that are hepatically cleared. A review of the literature addressing the topic of drug metabolism and clearance alterations in AKI reveals that changes in nonrenal clearance are highly complicated and poorly studied, but they may be quite common. At present, our understanding of how AKI affects drug metabolism and nonrenal clearance is limited. However, based on the available evidence, clinicians should be cognizant that even hepatically eliminated drugs and formed drug metabolites may accumulate during AKI, and renal replacement therapy may affect nonrenal clearance as well as drug metabolite clearance. PMID:19040780

  17. Mortality due to acute adverse drug reactions in Galicia: 1997-2011.

    PubMed

    Miguel-Arias, Domingo; Pereiro Gómez, César; Bermejo Barrera, Ana M; López de Abajo Rodríguez, Benito; Sobrido Prieto, María

    2016-03-02

    The aim of this research is to study all people who died in the Autonomous Community of Galicia from acute death after drugconsumption (ADR) in which there was judicial intervention during the period from 1997 to 2011, according to inclusion and exclusión criteria established by the National Drug Plan for the entire national territory. Sociodemographic and clinical characteristics of deceased subjects were studied, in order to identify key risk factors and/or vulnerable populations.A total of 805 deaths were recorded. The distribution by provinces and municipalities corresponds to the areas of greatest population, incidence of consumption and proximity to the coast. The average age of these patients was 34.34 years, with a gradual increase over years. Most of them were male (91.2%) and single (47.7). 43.5% of the deceased habitually used the parenteral route of administration and 36.4% had positive HIV serology. The most frequently-detected substances corresponded to opiates (heroin: 61.3%, methadone: 35.6%), followed by cocaine (53.7%), although the most common pattern was that of poly-consumption. ADR mortality figures remain relatively stable throughout the study period. The predominant pattern is that of males, opiates and a long history of consumption.

  18. [Therapeutic drug monitoring of 6-thioguanine nucleotides in paediatric acute lymphoblastic leukaemia: interest and limits].

    PubMed

    Fakhoury, May; de Beaumais, Tiphaine; Médard, Yves; Jacqz-Aigrain, Evelyne

    2010-01-01

    6-mercaptopurine, a key drug for the treatment of acute lymphoblastic leukaemia in children, is a prodrug metabolized into 6-thioguanine (6-TGN) which are the active compounds and into methylated metabolites, primary by thiopurine S-methyltransferase enzyme (TPMT). This enzyme displays important inter subject variability linked to a genetic polymorphism: when treated with standard doses of thiopurine, TPMT-deficient and heterozygous patients are at great risk for developing severe and potentially life-threatening toxicity (hematopoietic, hepatic, mucositis...) but show a better survival rate while patients with high TPMT activity (wild type) present lower peripheral red blood cells 6-TGN concentrations and a higher risk of leukemia relapse. Genotyping remains crucial before 6-MP administration at diagnosis to identify patients with homozygous mutant TPMT genotype and therefore prevent severe and life-threatening toxicity, and to individualize therapy according to TMPT genotype. Follow-up of ALL treatment should preferentially be based on repeated determinations of intracellular active metabolites (6-thioguanine nucleotides) and methylated metabolites in addition to haematological surveillance.

  19. Using Chemoinformatics, Bioinformatics, and Bioassay to Predict and Explain the Antibacterial Activity of Nonantibiotic Food and Drug Administration Drugs.

    PubMed

    Kahlous, Nour Aldin; Bawarish, Muhammad Al Mohdi; Sarhan, Muhammad Arabi; Küpper, Manfred; Hasaba, Ali; Rajab, Mazen

    2017-03-27

    Discovering of new and effective antibiotics is a major issue facing scientists today. Luckily, the development of computer science offers new methods to overcome this issue. In this study, a set of computer software was used to predict the antibacterial activity of nonantibiotic Food and Drug Administration (FDA)-approved drugs, and to explain their action by possible binding to well-known bacterial protein targets, along with testing their antibacterial activity against Gram-positive and Gram-negative bacteria. A three-dimensional virtual screening method that relies on chemical and shape similarity was applied using rapid overlay of chemical structures (ROCS) software to select candidate compounds from the FDA-approved drugs database that share similarity with 17 known antibiotics. Then, to check their antibacterial activity, disk diffusion test was applied on Staphylococcus aureus and Escherichia coli. Finally, a protein docking method was applied using HYBRID software to predict the binding of the active candidate to the target receptor of its similar antibiotic. Of the 1,991 drugs that were screened, 34 had been selected and among them 10 drugs showed antibacterial activity, whereby drotaverine and metoclopramide activities were without precedent reports. Furthermore, the docking process predicted that diclofenac, drotaverine, (S)-flurbiprofen, (S)-ibuprofen, and indomethacin could bind to the protein target of their similar antibiotics. Nevertheless, their antibacterial activities are weak compared with those of their similar antibiotics, which can be potentiated further by performing chemical modifications on their structure.

  20. Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs.

    PubMed

    Zhou, Xiaobing; Ma, Ben; Lin, Zhi; Qu, Zhe; Huo, Yan; Wang, Jufeng; Li, Bo

    2014-10-01

    As kidney is a major target organ affected by drug toxicity, early detection of renal injury is critical in preclinical drug development. In past decades, a series of novel biomarkers of drug-induced nephrotoxicity were discovered and verified in rats. However, limited data regarding the performance of novel biomarkers in non-rodent species are publicly available. To increase the applicability of these biomarkers, we evaluated the performance of 4 urinary biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), clusterin, total protein, and N-acetyl-β-D-glucosaminidase (NAG), relative to histopathology and traditional clinical chemistry in beagle dogs with acute kidney injury (AKI) induced by gentamicin. The results showed that urinary NGAL and clusterin levels were significantly elevated in dogs on days 1 and 3 after administration of gentamicin, respectively. Gene expression analysis further provided mechanistic evidence to support that NGAL and clusterin are potential biomarkers for the early assessment of drug-induced renal damage. Furthermore, the high area (both AUCs=1.000) under receiver operator characteristics (ROC) curve also indicated that NGAL and clusterin were the most sensitive biomarkers for detection of gentamicin-induced renal proximal tubular toxicity. Our results also suggested that NAG may be used in routine toxicity testing due to its sensitivity and robustness for detection of tissue injury. The present data will provide insights into the preclinical use of these biomarkers for detection of drug-induced AKI in non-rodent species.

  1. Effects of systemic administration of sitafloxacin on subgingival microflora and antimicrobial susceptibility profile in acute periodontal lesions.

    PubMed

    Tomita, Sachiyo; Kasai, Shunsuke; Ihara, Yuichiro; Imamura, Kentaro; Kita, Daichi; Ota, Koki; Kinumatsu, Takashi; Nakagawa, Taneaki; Saito, Atsushi

    2014-01-01

    The aim of this study was to assess the effect(s) of systemic administration of sitafloxacin on subgingival microbial profiles of acute periodontal lesions. Antimicrobial susceptibility of clinical isolates was also investigated. Patients with acute phases of chronic periodontitis were subjected to clinical examination and microbiological assessment of their subgingival plaque samples by culture technique. Sitafloxacin was then administered (100 mg/day for 5 days) systemically. The clinical and microbiological examinations were repeated 6-8 days after administration. Susceptibilities of clinical isolates to various antimicrobials were determined using the broth and agar dilution methods. From the sampled sites in 30 participants, a total of 355 clinical isolates (34 different bacterial species) were isolated and identified. Parvimonas micra, Prevotella intermedia and Streptococcus mitis were the most prevalent cultivable bacteria in acute sites. Systemic administration of sitafloxacin yielded a significant improvement in clinical and microbiological parameters. Among the antimicrobials tested, sitafloxacin was the most potent against the clinical isolates with an MIC90 of 0.12 μg/ml at baseline. After administration, most clinical isolates were still highly susceptible to sitafloxacin although some increase in MICs was observed. The results suggest that systemic administration of sitafloxacin is effective against subgingival bacteria isolated from acute periodontal lesions.

  2. Relations among acute and chronic nicotine administration, short-term memory, and tactics of data analysis.

    PubMed

    Kangas, Brian D; Branch, Marc N

    2012-09-01

    Emerging evidence suggests that nicotine may enhance short-term memory. Some of this evidence comes from nonhuman primate research using a procedure called delayed matching-to-sample, wherein the monkey is trained to select a comparison stimulus that matches some physical property of a previously presented sample stimulus. Delays between sample stimulus offset and comparison stimuli onset are manipulated and accuracy is measured. The present research attempted to systematically replicate these enhancement effects with pigeons. In addition, the effects of nicotine were assessed under another, more dynamic, memory task called titrating-delay matching-to-sample. In this procedure, the delay between sample offset and comparison onset adjusts as a function of the subject's performance. Correct matches increase the delay, mismatches decrease the delay, and titrated delay values serve as the primary dependent measure. Both studies examined nicotine's effects under acute and chronic administration. Neither provided clear or compelling evidence of memory enhancement following nicotine administration despite reliable and systematic dose-related changes in response latency measures. A modest dose-related effect on accuracy was found, but the magnitude of the effect appears to be directly related to tactics of data analysis involving best-dose analyses of a very circumscribed subset of trial types.

  3. Evaluation of acute and sub-chronic oral toxicity study of Baker Cleansers Bitters - a polyherbal drug on experimental rats

    PubMed Central

    Patrick-Iwuanyanwu, K.C.; Amadi, U.; Charles, I. A.; Ayalogu, E.O.

    2012-01-01

    Baker Cleanser Bitters (BCB) - a polyherbal formula commonly used in the treatment of diabetes, liver cirrhosis, kidney failure, rheumatism and arthritis was evaluated in an acute and sub-chronic toxicity study in Wistar albino rats. A single administration of BCB was given orally at the highest dose level of 2000 mg/kg body weight in the acute toxicity study. Signs of toxicity were observed every hour for the first 6 h and every day for 7 days. In the sub-chronic oral toxicity study, BCB was administered to rats at doses of 50, 100 and 200 mg/kg body weight for 28 days. Mortalities, clinical signs, body weight changes, biochemical and haematological parameters were monitored during the study period. There were no mortalities or clinical signs observed in rats in the acute toxicity study. In the sub-chronic study in rats, daily oral administration of BCB at the dose of 200 mg/kg body weight resulted in a drop in percentage increase in body weight at the end of the 4th week. Alanine amino transferase (ALT), aspartate amino transferase (AST), fasting blood sugar and packed cell volume (PCV) decreased significantly (p≤0.05) whereas alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and platelets increased significantly (p≤0.05) when compared to control. The high no-observed adverse effects level (NOAEL) value of 2000 mg/kg body weight implies that the drug could be safe. The study also revealed that the polyherbal drug may have good hypoglycemic effects and favourable reducing effects on the cardiovascular risk factors and explains the basis for the continual use of this plant by traditional medical practitioners. PMID:27847451

  4. The effect of acute stress and long-term corticosteroid administration on plasma metabolites in an urban and desert songbird.

    PubMed

    Davies, Scott; Rodriguez, Natalie S; Sweazea, Karen L; Deviche, Pierre

    2013-01-01

    In response to stressful stimuli, animals activate the hypothalamic-pituitary-adrenal axis, which can result in transition to the "emergency life history stage." A key adaptive characteristic of this life history stage is the mobilization of energy stores. However, few data are available on the metabolic response to acute stress in wild-caught, free-ranging birds. We quantified the effect of acute capture and restraint stress on plasma glucose, free fatty acid, and uric acid in free-ranging Abert's towhees Melozone aberti. Furthermore, birds were caught from urban and desert localities of Phoenix, Arizona, to investigate potential effects of urban versus desert habitats on the corticosterone (CORT) and metabolic response to acute stress. Complementing work on free-ranging birds, captive towhees received CORT-filled Silastic capsules to investigate the response of urban and desert conspecifics to long-term CORT administration. We quantified the effect of CORT administration on baseline plasma glucose and uric acid, liver and pectoralis muscle glycogen stores, kidney phosphoenolpyruvate carboxykinase (PEPCK-C, a key gluconeogenic enzyme), and body mass. Acute stress increased plasma CORT and glucose and decreased plasma uric acid but had no effect on plasma free fatty acid. There was no difference between urban and desert localities in body mass, fat scores, and the response to acute stress. CORT administration decreased body mass but had no effect on glucose and uric acid, pectoral muscle glycogen, or kidney PEPCK-C. However, liver glycogen of CORT-treated urban birds increased compared with corresponding controls, whereas glycogen decreased in CORT-treated desert birds. This study suggests that Abert's towhees principally mobilize glucose during acute stress but urban and desert towhees do not differ in their CORT and metabolic response to acute stress or long-term CORT administration.

  5. Delayed administration of darbepoetin or erythropoietin protects against ischemic acute renal injury and failure.

    PubMed

    Johnson, D W; Pat, B; Vesey, D A; Guan, Z; Endre, Z; Gobe, G C

    2006-05-01

    Administration of human recombinant erythropoietin (EPO) at time of acute ischemic renal injury (IRI) inhibits apoptosis, enhances tubular epithelial regeneration, and promotes renal functional recovery. The present study aimed to determine whether darbepoetin-alfa (DPO) exhibits comparable renoprotection to that afforded by EPO, whether pro or antiapoptotic Bcl-2 proteins are involved, and whether delayed administration of EPO or DPO 6 h following IRI ameliorates renal dysfunction. The model of IRI involved bilateral renal artery occlusion for 45 min in rats (N = 4 per group), followed by reperfusion for 1-7 days. Controls were sham-operated. Rats were treated at time of ischemia or sham operation (T0), or post-treated (6 h after the onset of reperfusion, T6) with EPO (5000 IU/kg), DPO (25 mug/kg), or appropriate vehicle by intraperitoneal injection. Renal function, structure, and immunohistochemistry for Bcl-2, Bcl-XL, and Bax were analyzed. DPO or EPO at T0 significantly abrogated renal dysfunction in IRI animals (serum creatinine for IRI 0.17 +/- 0.05 mmol/l vs DPO-IRI 0.08 +/- 0.03 mmol/l vs EPO-IRI 0.04 +/- 0.01 mmol/l, P = 0.01). Delayed administration of DPO or EPO (T6) also significantly abrogated subsequent renal dysfunction (serum creatinine for IRI 0.17 +/- 0.05 mmol/l vs DPO-IRI 0.06 +/- 0.01 mmol/l vs EPO-IRI 0.03 +/- 0.03 mmol/l, P = 0.01). There was also significantly decreased tissue injury (apoptosis, P < 0.05), decreased proapoptotic Bax, and increased regenerative capacity, especially in the outer stripe of the outer medulla, with DPO or EPO at T0 or T6. These results reaffirm the potential clinical application of DPO and EPO as novel renoprotective agents for patients at risk of ischemic acute renal failure or after having sustained an ischemic renal insult.

  6. Effect of early administration of exogenous basic fibroblast growth factor on acute edematous pancreatitis in rats

    PubMed Central

    Yan, Qiang; Yao, Xing; Dai, Li-Cheng; Zhang, Guo-Lei; Ping, Jin-Liang; He, Jian-Fang; Han, Chun-Fan

    2006-01-01

    AIM: To observe the therapeutic effect of early administration of exogenous Basic fibroblast growth factor (bFGF) on acute edematous pancreatitis (AEP) in rats. METHODS: Thirty male Sprague-Dawley rats were randomly divided into three (n = 10): normal control group (group I), AEP group (group II) and AEP with bFGF treatment group (group III). AEP was induced by subcutaneous injection of cerulein (5.5 μg/kg and 7.5 μg/kg) at 1 h interval into rats of groups II and III. Three hours after induction of AEP, 100 μg/kg bFGF was administrated intraperitoneally for 1h to group III rats. For test of DNA synthesis in acinar cells, 5-bromo-2’-deoxyuridine (BrdU) labeling solution was intraperitoneally injected into the rats of groups II and III 24 h after bFGF treatment. The changes in serum amylase, lipase, pancreatic tissue wet/dry ratio were detected. RESULTS: In bFGF treatment group, there was a significant decrease in the volume of serum amylase, lipase and the pancreatic wet/dry weight ratio(1383.0 ± 94.6 U/L, 194.0 ± 43.6 U/L, 4.32 ± 0.32) compared to AEP group (3464 ± 223.7 U/L, 456 ±68.7 U/L, 6.89 ± 0.47) (P < 0.01), and no significant difference was found between bFGF treatment and control group (1289 ± 94.0 U/L, 171 ± 23.4 U/L, 4.12 ± 0.26, P > 0.05). The inflammatory changes such as interstitial edema, polymorphonuclear neutrophils (PMNs) and vacuolization were significantly ameliorated compared to AEP group (P < 0.01). A small number of BrdU-labeled nuclei were observed in acinar cells of AEP rats (1.8 ± 0.3 nuclei/microscopic field, n = 10) while diffuse BrdU-labeled nuclei were found in bFGF-treated rats (18.9 ± 1.4 nuclei/microscopic field, n = 10) (P < 0.01). Immunohistochemical study showed increased DNA synthesis in pancreatic acinar cells. CONCLUSION: Early administration of exogenous bFGF has significant therapeutic effect on cerulein-induced acute edematous pancreatitis in rats. Its mechanism is related to the amelioration of inflammation

  7. Dramatyping: a generic algorithm for detecting reasonable temporal correlations between drug administration and lab value alterations

    PubMed Central

    2016-01-01

    According to the World Health Organization, one of the criteria for the standardized assessment of case causality in adverse drug reactions is the temporal relationship between the intake of a drug and the occurrence of a reaction or a laboratory test abnormality. This article presents and describes an algorithm for the detection of a reasonable temporal correlation between the administration of a drug and the alteration of a laboratory value course. The algorithm is designed to process normalized lab values and is therefore universally applicable. It has a sensitivity of 0.932 for the detection of lab value courses that show changes in temporal correlation with the administration of a drug and it has a specificity of 0.967 for the detection of lab value courses that show no changes. Therefore, the algorithm is appropriate to screen the data of electronic health records and to support human experts in revealing adverse drug reactions. A reference implementation in Python programming language is available. PMID:27042396

  8. Design and development of a modified runway model of mouse drug self-administration

    PubMed Central

    Pandy, Vijayapandi; Khan, Yasmin

    2016-01-01

    The present study established a novel mouse model of a runway drug self-administration in our laboratory. The operant runway apparatus consisted of three long runways arranged in a zig-zag manner. The methodology consisted of six distinct phases: habituation, preconditioning, conditioning, post-conditioning, extinction and reinstatement. The effects of saline were compared with escalating doses of either ethanol (0.5–4.0 g/kg, i.p), heroin (5–40 mg/kg, i.p), or nicotine (0.1–0.5mg/kg, i.p) administered in the goal box during the conditioning phase (day 1 to day 5). A significant decrease in the time of trained (conditioned) mice to reach the goal box confirmed the subjects’ motivation to seek those drugs on day 6 (expression). The mice were then subjected to non-rewarded extinction trials for 5 days over which run times were significantly increased. After 5 days of abstinence, a priming dose of ethanol or heroin (1/5th of maximum dose used in conditioning) significantly reinstated the drug-seeking behavior. These results suggest that the modified runway model can serve as a powerful behavioral tool for the study of the behavioral and neurobiological bases of drug self-administration and, as such, is appropriate simple but powerful tool for investigating the drug-seeking behavior of laboratory mice. PMID:26902717

  9. Design and development of a modified runway model of mouse drug self-administration.

    PubMed

    Pandy, Vijayapandi; Khan, Yasmin

    2016-02-23

    The present study established a novel mouse model of a runway drug self-administration in our laboratory. The operant runway apparatus consisted of three long runways arranged in a zig-zag manner. The methodology consisted of six distinct phases: habituation, preconditioning, conditioning, post-conditioning, extinction and reinstatement. The effects of saline were compared with escalating doses of either ethanol (0.5-4.0 g/kg, i.p), heroin (5-40 mg/kg, i.p), or nicotine (0.1-0.5mg/kg, i.p) administered in the goal box during the conditioning phase (day 1 to day 5). A significant decrease in the time of trained (conditioned) mice to reach the goal box confirmed the subjects' motivation to seek those drugs on day 6 (expression). The mice were then subjected to non-rewarded extinction trials for 5 days over which run times were significantly increased. After 5 days of abstinence, a priming dose of ethanol or heroin (1/5th of maximum dose used in conditioning) significantly reinstated the drug-seeking behavior. These results suggest that the modified runway model can serve as a powerful behavioral tool for the study of the behavioral and neurobiological bases of drug self-administration and, as such, is appropriate simple but powerful tool for investigating the drug-seeking behavior of laboratory mice.

  10. Endotoxin administration to humans inhibits hepatic cytochrome P450-mediated drug metabolism.

    PubMed Central

    Shedlofsky, S I; Israel, B C; McClain, C J; Hill, D B; Blouin, R A

    1994-01-01

    In experimental animals, injection of gram-negative endotoxin (LPS) decreases hepatic cytochrome P450-mediated drug metabolism. To evaluate this phenomenon in a human model of gram-negative sepsis, LPS was administered on two consecutive days to healthy male volunteers during which time a cocktail of antipyrine (AP-250 mg), hexobarbital (HB-500 mg), and theophylline (TH-150 mg) was ingested and the apparent oral clearance of each drug determined. Each subject had a control drug clearance study with saline injections. In the first experiment, six subjects received the drug cocktail 0.5 h after the first dose of LPS. In the second experiment, another six subjects received the drug cocktail 0.5 h after the second dose of LPS. In both experiments, LPS caused the expected physiologic responses of inflammation including fever with increases in serum concentrations of TNF alpha, IL-1 beta, IL-6, and acute phase reactants. In the first experiment, only minor decreases in clearances of the probe drugs were observed (7-12%). However in the second experiment, marked decreases in the clearances of AP (35, 95% CI 18-48%), HB (27, 95% CI 14-34%), and TH (22, 95% CI 12-32%) were seen. The decreases in AP clearance correlated with initial peak values of TNF alpha (r = 0.82) and IL-6 (r = 0.86). These data show that in humans the inflammatory response to even a very low dose of LPS significantly decreases hepatic cytochrome P450-mediated drug metabolism and this effect evolves over a 24-h period. It is likely that septic patients with much higher exposures to LPS have more profound inhibition of drug metabolism. PMID:7989576

  11. A drug-paired taste cue elicits withdrawal and predicts cocaine self-administration.

    PubMed

    Nyland, Jennifer E; Grigson, Patricia S

    2013-03-01

    Addiction is a chronic disease where periods of abstinence are riddled with instances of craving, withdrawal, and eventual relapse to escalated drug use. Cues previously associated with drug use can have a deleterious effect on this cycle by precipitating withdrawal symptoms. Here we focus specifically on the relationship between avoidance of a drug-paired taste cue and the ability of the drug-paired cue to elicit withdrawal and, ultimately, drug seeking and taking. We used a rat model of drug addiction and naloxone-induced loss of body weight to test whether a taste cue elicits withdrawal in anticipation of drug availability. Experiment 1 investigated the ability of a taste cue to elicit signs of withdrawal when it predicted experimenter-administered morphine (15 mg/kg, i.p.). In Experiment 2, a saccharin taste cue was paired with the opportunity to actively self-administer cocaine (0.167 mg/infusion, i.v.). The results show that presentation of a morphine- or cocaine-paired taste cue is sufficient to elicit naloxone-induced withdrawal symptoms, and greater withdrawal predicts greater cocaine self-administration in rats.

  12. Gender-based differences in the toxicity of pharmaceuticals--the Food and Drug Administration's perspective.

    PubMed

    Miller, M A

    2001-01-01

    Women experience more adverse reactions to treatment with therapeutic drugs than men. Theories proposed to explain this include overdosing, different pharmacokinetics and pharmacodynamics, women are more likely to report adverse events than men, or women take more medications than men. Food and Drug Administration (FDA) Office of Women's Health (OWH) funds research to promote including women in clinical trials and understanding the biology of sex-related differences in the safety of FDA-regulated products. Including women in clinical trials advances the understanding of drug efficacy and safety in women by providing information on drug dosing, pharmacokinetics, and pharmacodynamics. A Baysian statistical analysis of sex differences in adverse events showed that although about the same number of adverse events were reported for men and women, those reported for women were more serious. One example of a sex difference in the toxicity of pharmaceuticals is the drug-induced cardiac arrhythmia, torsades de point. OWH funded studies in animals and humans to investigate the mechanism behind this sex difference. These studies demonstrated that shortening the QT interval increases the risk of developing torsades and that androgens protect against torsades by slowing cardiac repolarization and prolonging the QT interval. Understanding the mechanisms behind other reported sex-related differences in adverse drug effects requires additional research. The preliminary studies conducted to date suggest that this sex-related difference is likely to be a multifactorial problem requiring information from several fields of study. Ideally, individuals at risk for developing an adverse event should be identified prior to therapeutic intervention. The OWH plans to fund more studies to investigate the role of hormonal variations on drug metabolism and drug-drug interactions. Animal and in vitro model systems are needed to fully understand the mechanism of how gender influences drug

  13. [Administration of Palonosetron and Phenotropil for Prophylaxis of the N-V-D Stage of Acute Radiation Syndrome].

    PubMed

    Drachouv, I S; Bykov, V N; Seleznev, A B

    2016-01-01

    Experiments on small (rats) and large (dogs) animals have shown that a sequential administration of Palonosetron and Phenotropil decreases the intensity of the main manifestations of the N-V-D stage of acute radiation syndrome. These data show the appropriateness of a combined administration of Palonosetron and Phenotropil to prevent a reduced work capacity in the individuals participating in elimination of the consequences of accidents associated with overexposure to radiation.

  14. US Food and Drug Administration Web Site: A Primer for Pharmacists

    PubMed Central

    Baker, Danial E.

    2015-01-01

    The US Food and Drug Administration (FDA) Web site includes a vast amount of information, but it can be difficult to navigate. Despite frequently asked question (FAQ)–type pages within the Web site, it may not be easy for first-time users to find drug information. This article presents some examples of common questions, provides the locations of the answers on the FDA Web site, and gives a brief description of some of the many resources the FDA provides for health care professionals. Additionally, a newer project being undertaken by the FDA, Snapshot, is introduced. PMID:27621506

  15. US Food and Drug Administration Web Site: A Primer for Pharmacists.

    PubMed

    Leonard, James; Baker, Danial E

    2015-11-01

    The US Food and Drug Administration (FDA) Web site includes a vast amount of information, but it can be difficult to navigate. Despite frequently asked question (FAQ)-type pages within the Web site, it may not be easy for first-time users to find drug information. This article presents some examples of common questions, provides the locations of the answers on the FDA Web site, and gives a brief description of some of the many resources the FDA provides for health care professionals. Additionally, a newer project being undertaken by the FDA, Snapshot, is introduced.

  16. 75 FR 60767 - Office of the Commissioner; Request for Comments on the Food and Drug Administration Fiscal Year...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-01

    ... HUMAN SERVICES Food and Drug Administration Office of the Commissioner; Request for Comments on the Food... Global Supply Chain, (3) Strengthen Compliance and Enforcement Activities to Support Public Health, and... AGENCY: Food and Drug Administration, HHS. ACTION: Notice; request for comments. SUMMARY: The Food...

  17. 77 FR 45357 - Draft Guidance for Industry and Food and Drug Administration Staff; Acceptance and Filing Review...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-31

    ... and Research. This draft guidance is not final nor is it in effect at this time. DATES: Although you... Development (HFM-40), Center for Biologics Evaluation and Research, Food and Drug Administration, 1401..., Center for Biologics Evaluation and Research (HFM-17), Food and Drug Administration, 1401 Rockville...

  18. 76 FR 22905 - Guidance for Food and Drug Administration Staff and Tobacco Retailers on Civil Money Penalties...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Guidance for Food and Drug Administration Staff and Tobacco... regulation (21 CFR 10.115). The guidance represents the Agency's current thinking on ``Civil Money...

  19. 77 FR 11550 - Draft Guidance for Industry on Notification to Food and Drug Administration of Issues That May...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-27

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Notification to Food and Drug..., directing FDA to use all available administrative tools to expand the Agency's efforts to combat the problem... required nutrition, or to address other serious medical conditions. Other shortages force providers...

  20. 77 FR 41418 - Statement of Cooperation Between the Food and Drug Administration and the Secretaria of Health of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... HUMAN SERVICES Food and Drug Administration Statement of Cooperation Between the Food and Drug Administration and the Secretaria of Health of the United Mexican States: Safety and Sanitary Quality of Fresh and Frozen Molluscan Shellfish Exported From Mexico to the United States AGENCY: Food and...

  1. 77 FR 20825 - Guidance for Industry and Food and Drug Administration Staff; User Fees for 513(g) Requests for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-06

    ...; User Fees for 513(g) Requests for Information; Availability AGENCY: Food and Drug Administration, HHS... guidance entitled ``Guidance for Industry and Food and Drug Administration Staff; User Fees for 513(g) Requests for Information.'' This guidance document describes the user fees associated with 513(g)...

  2. 40 CFR 23.10 - Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act. 23.10 Section 23.10 Protection of Environment ENVIRONMENTAL... action under the Federal Food, Drug, and Cosmetic Act. Unless the Administrator otherwise...

  3. 40 CFR 23.10 - Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act. 23.10 Section 23.10 Protection of Environment ENVIRONMENTAL... action under the Federal Food, Drug, and Cosmetic Act. Unless the Administrator otherwise...

  4. 40 CFR 23.10 - Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act. 23.10 Section 23.10 Protection of Environment ENVIRONMENTAL... action under the Federal Food, Drug, and Cosmetic Act. Unless the Administrator otherwise...

  5. 40 CFR 23.10 - Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act. 23.10 Section 23.10 Protection of Environment ENVIRONMENTAL... action under the Federal Food, Drug, and Cosmetic Act. Unless the Administrator otherwise...

  6. 40 CFR 23.10 - Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act. 23.10 Section 23.10 Protection of Environment ENVIRONMENTAL... action under the Federal Food, Drug, and Cosmetic Act. Unless the Administrator otherwise...

  7. 77 FR 24721 - The 15th Annual Food and Drug Administration-Orange County Regulatory Affairs Educational...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration The 15th Annual Food and Drug Administration--Orange County... announcing the following conference: The 15th Annual Educational Conference cosponsored with the...

  8. 76 FR 77542 - Draft Guidance for Industry and Food and Drug Administration Staff on Humanitarian Use Device...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-13

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration... guidance for industry and FDA staff entitled ``Humanitarian Use Device (HUD) Designations.'' Devices are... HUD designation may be eligible for marketing approval under the Humanitarian Device Exemption...

  9. Pharmacokinetics of a New Carbapenem, DA-1131, after Intravenous Administration to Rats with Uranyl Nitrate-Induced Acute Renal Failure

    PubMed Central

    Kim, So H.; Shim, Hyun J.; Kim, Won B.; Lee, Myung G.

    1998-01-01

    Because the physiological changes that occur in patients with acute renal failure could alter the pharmacokinetics of the drugs used to treat the disease, the pharmacokinetics of DA-1131, a new carbapenem antibiotic, were investigated after 1-min intravenous administration of the drug (50 mg/kg of body weight) to control rats and rats with uranyl nitrate-induced acute renal failure (U-ARF rats). The impaired kidney function was observed in U-ARF rats on the basis of physiological parameters observed by microscopy of the kidney and obtained by chemical analysis of the plasma. After a 1-min intravenous infusion of DA-1131, the concentrations in plasma and the total area under the plasma concentration-time curve from time zero to time infinity increased significantly in U-ARF rats compared with those in control rats (13,000 versus 4,400 μg · min/ml). This was due to the significantly slower total body clearance (CL) of DA-1131 (3.84 versus 11.4 ml/min/kg) from U-ARF rats than from control rats. The significantly slower CL of DA-1131 from U-ARF rats was due to both significantly slower renal clearance (0.000635 versus 4.95 ml/min/kg because of a significant decrease in the 8-h urinary excretion of unchanged DA-1131 [1.54 versus 43.8% of the intravenous dose] due to impaired kidney function, as proved by the significant decrease in creatinine clearance [0.0159 versus 4.29 ml/min/kg]) and significantly slower nonrenal clearance (3.80 versus 6.34 ml/min/kg because of a significant decrease in the metabolism of DA-1131 in the kidney) in U-ARF rats. The amounts of DA-1131 recovered from all tissues studied (except the kidneys) were significantly higher for U-ARF rats than for control rats; however, the ratios of the amount in tissue to the concentration in plasma (except those for the kidney, small intestine, and spleen) were not significantly different between the two groups of rats, indicating that the affinity of DA-1131 for rat tissues was not changed considerably in

  10. Symptoms and danger signs in acute drug hypersensitivity.

    PubMed

    Bircher, Andreas J

    2005-04-15

    Early and rapid recognition of severe adverse drug reactions is essential. Prompt withdrawal of the offending drug is the most important action to minimize morbidity and mortality. Dependent on the type of reaction, e.g. in immediate type reactions instant withdrawal and therapy are mandatory, whereas in delayed reactions diagnosis as early as possible may be life-saving. The skin is an important herald organ and may early signal a severe evolution of a cutaneous reaction or involvement of circulating blood cells or internal organs. A synthesis considering all factors should be made to obtain an early and correct diagnosis.

  11. Acute and subacute IL-1β administrations differentially modulate neuroimmune and neurotrophic systems: possible implications for neuroprotection and neurodegeneration

    PubMed Central

    2013-01-01

    Background In Alzheimer’s disease, stroke and brain injuries, activated microglia can release proinflammatory cytokines, such as interleukin (IL)-1β. These cytokines may change astrocyte and neurotrophin functions, which influences neuronal survival and induces apoptosis. However, the interaction between neuroinflammation and neurotrophin functions in different brain conditions is unknown. The present study hypothesized that acute and subacute elevated IL-1β differentially modulates glial and neurotrophin functions, which are related to their role in neuroprotection and neurodegeneration. Method Rats were i.c.v. injected with saline or IL-1β for 1 or 8 days and tested in a radial maze. mRNA and protein expressions of glial cell markers, neurotrophins, neurotrophin receptors, β-amyloid precursor protein (APP) and the concentrations of pro- and anti-inflammatory cytokines were measured in the hippocampus. Results When compared to controls, memory deficits were found 4 days after IL-1 administrations, however the deficits were attenuated by IL-1 receptor antagonist (RA). Subacute IL-1 administrations increased expressions of APP, microglial active marker CD11b, and p75 neurotrophin receptor, and the concentration of tumor necrosis factor (TNF)-α and IL-1β, but decreased expressions of astrocyte active marker glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and TrK B. By contrast, up-regulations of NGF, BDNF and TrK B expressions were found after acute IL-1 administration, which are associated with the increase in both glial marker expressions and IL-10 concentrations. However, TrK A was down-regulated by acute and up-regulated by subacute IL-1 administrations. Subacute IL-1-induced changes in the glial activities, cytokine concentrations and expressions of BDNF and p75 were reversed by IL-1RA treatment. Conclusion These results indicate that acute and subacute IL-1 administrations induce different changes toward neuroprotection

  12. Tramadol hydrochloride: pharmacokinetics, pharmacodynamics, adverse side effects, co-administration of drugs and new drug delivery systems.

    PubMed

    Vazzana, M; Andreani, T; Fangueiro, J; Faggio, C; Silva, C; Santini, A; Garcia, M L; Silva, A M; Souto, E B

    2015-03-01

    Tramadol hydrochloride (TrHC) is a synthetic analgesic drug exhibiting opioid and non-opioid properties, acting mainly on the central nervous system. It has been mostly used to treat pain, although its use to treat anxiety and depression has also been documented. These properties arise from the fact that they inhibit serotonin (5-HT) reuptake augmenting 5-HT concentration on the synaptic cleft. Despite this, TrHC has also been described to have several side effects which are mainly due to its fast metabolization and excretion which in turn requires multiple doses per day. To surpass this limitation, new pharmaceutical formulations are being developed intending the protection, target and sustained delivery as well as a reduction on daily dose aiming a reduction on the side effects. In the present work we have revised the efficacy, safety, biological and adverse effects of TrHC, and the added value of developing a novel drug delivery system for topical administration.

  13. Effect of delay on self-administration of remifentanil under a drug versus drug choice procedure in rhesus monkeys.

    PubMed

    Maguire, David R; Gerak, Lisa R; France, Charles P

    2013-12-01

    Drug abuse can be conceptualized as excessive choice of drug over other reinforcers, and factors that affect drug taking can be examined experimentally using choice procedures. This study examined the impact of reinforcer delay on self-administration of the μ-opioid receptor agonist remifentanil in rhesus monkeys (n = 4) lever pressing under a concurrent fixed-ratio 30 schedule. Responding on either lever delivered an intravenous infusion of either remifentanil or saline. Dose-effect curves were first determined when responding on one lever delivered remifentanil and responding on a second lever delivered saline. Monkeys then chose between two doses of remifentanil, and delay to delivery of the large dose was varied systematically. Responding for remifentanil (0.01-1.0 µg/kg/infusion) increased dose-dependently when the alternative was saline or a dose of remifentanil. Delaying delivery of the large dose of remifentanil by 30, 60, 120, or 240 seconds increased responding for smaller, immediately available doses (0.01-0.1 µg/kg/infusion) and, in some cases, increased responding for doses of remifentanil that did not maintain responding when the alternative was saline. These data demonstrate that delaying the delivery of an opioid receptor agonist can significantly affect its reinforcing effectiveness. The imposition of a delay reduces the effectiveness of large doses of drug to maintain responding and increases the effectiveness of immediately available commodities, including smaller doses of drug. Increased reinforcing effectiveness of smaller doses of drug in the context of other delayed reinforcers might contribute to the development and maintenance of opioid abuse.

  14. Acute neuroactive drug exposures alter locomotor activity in larval zebrafish

    EPA Science Inventory

    In an effort to develop a rapid in vivo screen for EPA's prioritization of toxic chemicals, we are characterizing the locomotor activity of zebrafish (Danio rerio) larvae after exposure to prototypic drugs that act on the central nervous system. MPTP (1-methyl-4phenyl- 1 ,2,3,6-...

  15. The Food and Drug Administration advisory committees and panels: how they are applied to the drug regulatory process.

    PubMed

    Ciociola, Arthur A; Karlstadt, Robyn G; Pambianco, Daniel J; Woods, Karen L; Ehrenpreis, Eli D

    2014-10-01

    Food and Drug Administration (FDA) advisory panels and committees play a critical role in advising the FDA on the safety and efficacy of medical devices and drugs marketed in the US. Advisory panel recommendations are used by the FDA to make decisions regarding medical products. Currently, the FDA utilizes over 50 advisory panels that serve the three major FDA centers, including the Centers for Biologics, Drugs and Device Products. Members of an advisory panel typically include academicians, clinicians, consumers, patients, and industry representatives. The FDA establishes the schedules for advisory panel meetings on an annual basis and a panel usually meets several times a year for two consecutive days in Washington, DC. Typically, the advisory panel discusses issues highlighted by the FDA and is then asked to vote a response to the questions posed in advance by the FDA. Advisory panel recommendations have a strong influence on FDA's decision to approve a product, as evidenced by the 214 Advisory Panels FDA convened between January 2008 to November 2012, during which advisory panel members voted to approve the product (or use of the product) ∼74% of the time, with FDA ultimately approving the medical product (or use of the product) ∼79% of the time. The ACG membership are encouraged to consider serving the public's interest by participating in an FDA advisory panel utilizing their expertise for the evaluation of a new drug or medical device, and providing advice about whether the product should be sold in the US.

  16. Evolution of the Food and Drug Administration approach to liver safety assessment for new drugs: current status and challenges.

    PubMed

    Senior, John R

    2014-11-01

    Prompted by approval in 1997 of troglitazone and bromfenac, two drugs that promptly began to show serious and sometimes fatal liver toxicity, we began at the Food and Drug Administration (FDA) a series of annual conferences in 1999 to consider issues of drug-induced liver injury (DILI). First inviting reviewers of new drug applications we opened the audiences in 2001 to pharmaceutical industry and academic consultants to industry and FDA, and slides shown at the meetings were posted on the internet to be available at the website of the American Association for the Study of Liver Diseases (AASLD)-go to ( http://www.aasld.org/dili/Pages/default.aspx ). Observations by Dr. Hyman J. Zimmerman that "drug-induced hepatocellular jaundice is a serious lesion" with possible mortality formed a basis for developing a computer program to plot peak serum values for alanine aminotransferase (ALT) and total bilirubin (TBL) in an x-y log-log graph for all subjects enrolled in clinical trials. This program had the capability to show the time course of all liver tests for individuals who had both hepatocellular injury and reduced whole liver function, plus clinical narratives to diagnose the severity and most likely cause of the abnormalities. We called the program eDISH (for evaluation of Drug-Induced Serious Hepatotoxicity), and began in 2004 to use it to assess DILI in clinical trial subjects. From 2008, comments made by the presenters at the conferences about their slides and ensuing discussions have been added to the website. All this has raised awareness of the problem, and since 1997, the FDA has not had to withdraw a single drug because of post-marketing hepatotoxicity. Many issues still remain to be resolved; among the most controversial is the best method to estimate likelihood that a given liver injury was actually caused by the drug in question. On November 9, 2012, a workshop was convened to discuss the best practices for the assessment of drug-induced liver injury

  17. Assessing candidacy for acute hepatitis C treatment among active young injection drug users: a case-series report.

    PubMed

    Asher, Alice; Lum, Paula J; Page, Kimberly

    2012-01-01

    Treatment for acute hepatitis C virus (HCV) infection has significantly better outcomes than treatment for chronic infection. The short window of the acute period poses challenges for young injection drug users (IDU), who are at highest risk of HCV infection, to demonstrate treatment candidacy. We recruited patients with acute HCV from a prospective cohort study to examine clinical and behavioral issues related to treatment candidacy. We report on outcomes and how nursing case management affected candidacy. All five acutely-infected participants reported daily drug use at baseline. All established primary care and decreased their drug use. None received treatment for their acute infection; one was treated within 12 months of infection. Establishing treatment candidacy for young IDU in the acute phase involves various health domains. An acute infection's short period poses many challenges to establishing candidacy, but it is a window of opportunity to engage young IDU in health care.

  18. The Food and Drug Administration's initiative for safe design and effective use of home medical equipment.

    PubMed

    Weick-Brady, Mary; Singh, Simran

    2014-06-01

    Although home-use medical devices provide significant benefits, including improved quality of life and cost savings, they are associated with unique risks. These risks result from interactions among the user, the use environment, and the device, and they can greatly impact user and patient safety. This article describes measures being taken by the Food and Drug Administration to address safe use of medical equipment by trained and untrained people outside of clinical facilities.

  19. Effect of chronic estradiol administration on the acute pressor response to aortic coarctation in conscious rats.

    PubMed

    Salgado, M C; Castania, J A; Ballejo, G; Salgado, H C

    1995-08-01

    We investigated the effect of chronic estradiol administration on the pressor response elicited by acute (45 min) partial aortic constriction in conscious Wistar rats and on vascular reactivity to angiotensin II and vasopressin in vitro. Estradiol (10 micrograms kg-1 day-1, sc) or vehicle was administered for 7 days to young castrated male and female rats and to female rats that had stopped cycling (14-16 months of age). In the acute experiment of aortic coarctation in conscious rats, carotid pressure was monitored continuously before and for 45 min after partial abdominal aortic coarctation. In ovariectomized females the mean carotid pressure and heart rate before aortic coarctation were significantly lower in estradiol-treated animals (107 +/- 3 vs 119 +/- 3 mmHg and 360 +/- 31 vs 494 +/- 12 bpm). Estradiol did not affect the pressor response (145-150 mmHg) to aortic coarctation of castrated male rats or ovariectomized female rats but blunted the reflex bradycardia of ovariectomized rats. The onset of the pressor response to aortic coarctation was delayed in aged female rats as compared to the other groups. While estradiol treatment significantly accelerated the onset of hypertension in aged rats, it did not affect the pressor response of castrated animals. Full dose-response curves to angiotensin II and vasopressin were constructed in vitro in the isolated mesenteric arterial bed obtained from similarly treated groups. Estradiol did not affect the vasopressin sensitivity or responsiveness of any group, but caused a significant increase in angiotensin II sensitivity in ovariectomized rats only.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Albumin Administration in Acute Ischemic Stroke: Safety Analysis of the ALIAS Part 2 Multicenter Trial

    PubMed Central

    Hill, Michael D.; Martin, Renee H.; Palesch, Yuko Y.; Moy, Claudia S.; Tamariz, Diego; Ryckborst, Karla J.; Jones, Elizabeth B.; Weisman, David; Pettigrew, Creed; Ginsberg, Myron D.

    2015-01-01

    Background Albumin treatment of ischemic stroke was associated with cardiopulmonary adverse events in previous studies and a low incidence of intracranial hemorrhage. We sought to describe the neurological and cardiopulmonary adverse events in the ALIAS Part 2 Multicenter Trial. Methods Ischemic stroke patients, aged 18–83 and a baseline NIHSS ≥ 6, were randomized to treatment with ALB or saline control within 5 hours of stroke onset. Neurological adverse events included symptomatic intracranial hemorrhage, hemicraniectomy, neurological deterioration and neurological death. Cardiopulmonary adverse events included pulmonary edema/congestive heart failure, acute coronary syndromes, atrial fibrillation, pneumonia and pulmonary thromboembolism. Results Among 830 patients, neurological and cardiopulmonary adverse events were not differentially associated with poor outcome between ALB and saline control subjects. The rate of symptomatic intracranial hemorrhage in the first 24h was low overall (2.9%, 24/830) but more common in the ALB treated subjects (RR = 2.4, CI95 1.01–5.8). The rate of pulmonary edema/CHF in the first 48h was 7.9% (59/830) and was more common among ALB treated subjects (RR = 10.7, CI95 4.3–26.6); this complication was expected and was satisfactorily managed with mandated diuretic administration and intravenous fluid guidelines. Troponin elevations in the first 48h were common, occurring without ECG change or cardiac symptoms in 52 subjects (12.5%). Conclusions ALB therapy was associated with an increase in symptomatic ICH and pulmonary edema/congestive heart failure but this did not affect final outcomes. Troponin elevation occurs routinely in the first 48 hours after acute ischemic stroke. Trial Registration ClincalTrials.gov NCT00235495 PMID:26325387

  1. Efficacy of Intravenous Administration of Landiolol in Patients With Acute Heart Failure and Supraventricular Tachyarrhythmia

    PubMed Central

    Kiuchi, Shunsuke; Aikawa, Hiroto; Hisatake, Shinji; Kabuki, Takayuki; Oka, Takashi; Dobashi, Shintaro; Fujii, Takahiro; Ikeda, Takanori

    2017-01-01

    Background Patients with acute heart failure (HF) complicated by supraventricular tachyarrhythmia (SVT) often receive continuous intravenous infusion of landiolol or diltiazem for rate control. It is unclear whether the interval from initiation of infusion to commencement of oral beta-blocker (BB) therapy differs for these two drugs. Methods From January 2013 to July 2015, 94 consecutive patients were hospitalized for acute HF complicated by SVT. After 35 patients were excluded, the remaining 59 were divided into groups treated with diltiazem or landiolol. We investigated the blood pressure, heart rate, New York Heart Association classification, brain natriuretic peptide, chest X-ray film, echocardiographic findings (ejection fraction (EF)), time until commencement of oral BB therapy, and hospital stay. Results There were no significant between-group differences of heart rate, blood pressure, or the severity of HF. The time until commencing oral BB therapy was significantly shorter in the landiolol group compared with the diltiazem group (median: 2 vs. 4 days, P = 0.002), but there was no significant difference in hospital stay. This interval was significantly shorter in patients with a reduced EF in the landiolol group (median: 2 days) compared with those with a reduced EF in the diltiazem group (median: 5 days, P = 0.008), and patients with a preserved EF in the landiolol group tended to have a shorter interval (median: 2 days) than those with a preserved EF in the diltiazem group (median: 4 days, P = 0.092). Conclusions Switching to oral BBs was accomplished earlier with landiolol than with diltiazem. PMID:28392863

  2. Effects of Gelam and Acacia honey acute administration on some biochemical parameters of Sprague Dawley rats

    PubMed Central

    2014-01-01

    Background Since ancient times, honey has been used for medicinal purposes in many cultures; it is one of the oldest and most enduring substances used in wound management. Scientific evidence for its efficacy is widely studied, but systemic safety studies are still lacking. It is essential to study the impact of consumption of honey on the health and proper development of the consumer. Therefore, the present study was designed to observe the effects of acute administration (14 days) of Gelam honey (GH), a wild harvesting honey and Acacia honey (AH), a beekeeping honey, on male and female Sprague Dawley (SD) rats. Methods An acute oral study was performed following OECD test guideline 423, with minor modifications. In the study, GH, AH and sucrose (S) were administered at 2000 mg/kg body weight. Animals were observed for the next 14 days. Gross pathology was performed at the end of the study. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Clinical biochemistry, gross pathology, relative organ weight and histopathological examination were performed. Results Rats fed with honey did not exhibit any abnormal signs or deaths. Results showed a decrease in weight gain and energy efficiency, but significantly increased in total food intake and total calories in female rats fed with GH, compared to control (p < 0.05). Nevertheless, a significant increase in body weight was observed in male rats in all honey-treated groups. Male rats fed with AH significantly decreased in total food intake, total calories and energy efficiency. Both male and female rats fed with GH displayed a significant decrease in triglycerides compared to control group. Hepatic and renal function levels were within acceptable range. The gross necropsy analysis did not reveal changes in any of the organs examined. Conclusions Our results suggest that acute consumption of GH and AH at 2000 mg/kg body weight of male and female SD rats has some discrepancy

  3. Mass administration of the antimalarial drug mefloquine to Guantánamo detainees: a critical analysis.

    PubMed

    Nevin, Remington L

    2012-10-01

    Recently, evidence has emerged from an unusual form of mass drug administration practised among detainees held at US Naval Station Guantánamo Bay, Cuba ('Guantánamo'), ostensibly as a public health measure. Mefloquine, an antimalarial drug originally developed by the US military, whose use is associated with a range of severe neuropsychiatric adverse effects, was administered at treatment doses to detainees immediately upon their arrival at Guantánamo, prior to laboratory testing for malaria and irrespective of symptoms of disease. In this analysis, the history of mefloquine's development is reviewed and the indications for its administration at treatment doses are discussed. The stated rationale for the use of mefloquine among Guantánamo detainees is then evaluated in the context of accepted forms of population-based malaria control. It is concluded that there was no plausible public health indication for the use of mefloquine at Guantánamo and that based on prevailing standards of care, the clinical indications for its use are decidedly unclear. This analysis suggests the troubling possibility that the use of mefloquine at Guantánamo may have been motivated in part by knowledge of the drug's adverse effects, and points to a critical need for further investigation to resolve unanswered questions regarding the drug's potentially inappropriate use.

  4. 75 FR 32952 - Draft Guidance for Industry and Food and Drug Administration Staff; “‘Harmful and Potentially...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-10

    ... the Federal Food, Drug, and Cosmetic Act''; Availability AGENCY: Food and Drug Administration, HHS... Products as Used in Section 904(e) of the Federal Food, Drug, and Cosmetic Act.'' This draft guidance... Cosmetic Act.'' This draft guidance, when finalized, will discuss the meaning of the term ``harmful...

  5. Acute effect of potassium canrenoate administration on renin-angiotensin, kallikrein-kinin and prostaglandin systems.

    PubMed

    Lahera, V; Cachofeiro, V; Duran, F; Cañizo, F J; Rodriguez, F J; Tresguerres, J A

    1988-01-01

    1. To investigate the possible effects of potassium canrenoate (PC) on plasma renin activity (PRA) and on renal prostaglandins (PGS) and kinins under elevated sodium and/or potassium intakes, a single dose of PC was administered to four groups of Wistar male rats. 2. They were fed a normal diet (C), a diet supplemented with 4% of NaCl, (Na), with 1% of KCl: (K) or both supplements (NaK). 3. PRA and urinary PGS excretion did not show changes after PC administration, but total urinary kinins showed higher values after the treatment in all groups. 4. A diuretic but not natriuretic effect was observed only in C animals. 5. In conclusion, the single dose of PC was able to stimulate urinary kinins and to spare potassium independently of dietary electrolyte supplements that were able to block the diuretic effect of the drug.

  6. Acute and chronic administration of gold nanoparticles cause DNA damage in the cerebral cortex of adult rats.

    PubMed

    Cardoso, Eria; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rodriguez, Juan Carlos Ortiz; Benavides, Roberto; da Silva, Luciano; Andrade, Vanessa M; da Silva Paula, Marcos Marques

    2014-01-01

    The use of gold nanoparticles is increasing in medicine; however, their toxic effects remain to be elucidated. Studies show that gold nanoparticles can cross the blood-brain barrier, as well as accumulate in the brain. Therefore, this study was undertaken to better understand the effects of gold nanoparticles on rat brains. DNA damage parameters were evaluated in the cerebral cortex of adult rats submitted to acute and chronic administration of gold nanoparticles of two different diameters: 10 and 30nm. During acute administration, adult rats received a single intraperitoneal injection of either gold nanoparticles or saline solution. During chronic administration, adult rats received a daily single injection for 28 days of the same gold nanoparticles or saline solution. Twenty-four hours after either single (acute) or last injection (chronic), the rats were euthanized by decapitation, their brains removed, and the cerebral cortices isolated for evaluation of DNA damage parameters. Our study showed that acute administration of gold nanoparticles in adult rats presented higher levels of damage frequency and damage index in their DNA compared to the control group. It was also observed that gold nanoparticles of 30nm presented higher levels of damage frequency and damage index in the DNA compared to the 10nm ones. When comparing the effects of chronic administration of gold nanoparticles of 10 and 30nm, we observed that occurred significant different index and frequency damage, comparing with control group. However, there is no difference between the 10 and 30nm groups in the levels of DNA damage for both parameters of the Comet assay. Results suggest that gold nanoparticles for both sizes cause DNA damage for chronic as well as acute treatments, although a higher damage was observed for the chronic one.

  7. Alpha and beta EEG power reflects L-dopa acute administration in parkinsonian patients

    PubMed Central

    Melgari, Jean-Marc; Curcio, Giuseppe; Mastrolilli, Francesca; Salomone, Gaetano; Trotta, Laura; Tombini, Mario; di Biase, Lazzaro; Scrascia, Federica; Fini, Rita; Fabrizio, Emma; Rossini, Paolo Maria; Vernieri, Fabrizio

    2014-01-01

    Aim: To evaluate the effect of an acute L-dopa administration on eye-closed resting state electroencephalographic (EEG) activity of cognitively preserved Parkinsonian patients. Methods: We examined 24 right-handed patients diagnosed as uncomplicated probable Parkinson’s disease (PD). Each patient underwent Unified Parkinson’s Disease Rating Scale (UPDRS)-part-III evaluation before and 60 min after an oral load of L-dopa-methyl-ester/carbidopa 250/25 mg. Resting condition eyes-closed EEG data were recorded both pre- and post L-dopa load. Absolute EEG power values were calculated at each scalp derivation for Delta, Theta, Alpha and Beta frequency bands. UPDRS scores (both global and subscale scores) and EEG data (power values of different frequency bands for each scalp derivation) were submitted to a statistical analysis to compare Pre and Post L-Dopa conditions. Finally, a correlation analysis was carried out between EEG spectral content and UPDRS scores. Results: Considering EEG power spectral analysis, no statistically significant differences arose on Delta and Theta bands after L-dopa intake. Conversely, Alpha and Beta rhythms significantly increased on centro-parietal scalp derivations, as a function of L-dopa administration. Correlation analysis indicated a significant negative correlation between Beta power increase on centro-parietal areas and UPDRS subscores (Rigidity of arms and Bradykinesia). A minor significant negative correlation was also found between Alpha band increase and resting tremor. Conclusions: Assuming that a significant change in EEG power spectrum after L-dopa intake may be related to dopaminergic mechanisms, our findings are consistent with the hypothesis that dopaminergic defective networks are implicated in cortical oscillatory abnormalities at rest in non-demented PD patients. PMID:25452725

  8. Effects of acute cortisol administration on perceptual priming of trauma-related material.

    PubMed

    Holz, Elena; Lass-Hennemann, Johanna; Streb, Markus; Pfaltz, Monique; Michael, Tanja

    2014-01-01

    Intrusive memories are a hallmark symptom of posttraumatic stress disorder (PTSD). They reflect excessive and uncontrolled retrieval of the traumatic memory. Acute elevations of cortisol are known to impair the retrieval of already stored memory information. Thus, continuous cortisol administration might help in reducing intrusive memories in PTSD. Strong perceptual priming for neutral stimuli associated with a "traumatic" context has been shown to be one important learning mechanism that leads to intrusive memories. However, the memory modulating effects of cortisol have only been shown for explicit declarative memory processes. Thus, in our double blind, placebo controlled study we aimed to investigate whether cortisol influences perceptual priming of neutral stimuli that appeared in a "traumatic" context. Two groups of healthy volunteers (N = 160) watched either neutral or "traumatic" picture stories on a computer screen. Neutral objects were presented in between the pictures. Memory for these neutral objects was tested after 24 hours with a perceptual priming task and an explicit memory task. Prior to memory testing half of the participants in each group received 25 mg of cortisol, the other half received placebo. In the placebo group participants in the "traumatic" stories condition showed more perceptual priming for the neutral objects than participants in the neutral stories condition, indicating a strong perceptual priming effect for neutral stimuli presented in a "traumatic" context. In the cortisol group this effect was not present: Participants in the neutral stories and participants in the "traumatic" stories condition in the cortisol group showed comparable priming effects for the neutral objects. Our findings show that cortisol inhibits perceptual priming for neutral stimuli that appeared in a "traumatic" context. These findings indicate that cortisol influences PTSD-relevant memory processes and thus further support the idea that administration

  9. Glutathione Depletion and Recovery After Acute Ethanol Administration in the Aging Mouse

    PubMed Central

    Vogt, Barbara L.; Richie, John P.

    2007-01-01

    Glutathione (GSH) plays an important role in the detoxification of ethanol (EtOH) and acute EtOH administration leads to GSH depletion in the liver and other tissues. Aging is also associated with a progressive decline in GSH levels and impairment in GSH biosynthesis in many tissues. Thus, the present study was designed to examine the effects of aging on EtOH-induced depletion and recovery of GSH in different tissues of the C57Bl/6NNIA mouse. EtOH (2-5 g/kg) or saline was administered i.p. to mice of ages 6 mo (young), 12 mo (mature), and 24 mo (old); and GSH and cyst(e)ine concentrations were measured 0-24 hours thereafter. EtOH administration (5g/kg) depleted hepatic GSH levels >50% by 6 hr in all animals. By 24 hr, levels remained low in both young and old mice, but recovered to baseline levels in mature mice. At 6 hr, the decrease in hepatic GSH was dose-dependent up to 3 g/kg EtOH, but not at higher doses. The extent of depletion at the 3 g/kg dose was dependent upon age, with old mice demonstrating significantly lower GSH levels than mature mice (P<0.001). Altogether these results indicate that aging was associated with a greater degree of EtOH and fasting-induced GSH depletion and subsequent impaired recovery in liver. An impaired ability to recover was also observed in young animals. Further studies are required to determine if an inability to recover from GSH depletion by EtOH is associated with enhanced toxicity. PMID:17343832

  10. Microglia activation and cell death in response to diethyl-dithiocarbamate acute administration.

    PubMed

    Zucconi, Gigliola Grassi; Laurenzi, Maria Assunta; Semprevivo, Massimo; Torni, Federica; Lindgren, Jan Ake; Marinucci, Eva

    2002-04-29

    An increasing body of evidence suggests a role for activated microglia in the pathogenesis of neurodegenerative disorders. Hence, it would be useful to have a better understanding of the significance of microglial activation for neuronal damage. Unfortunately, most models of microglial activation use invasive or long-lasting insults, which make it difficult to evaluate the role played by microglia. We have instead developed a model for microglial activation by using brief exposure to the widely available neurotoxin diethyl-dithiocarbamate (DDTC). Despite evidence for the neurotoxic nature of this substance, microglia involvement has not been hitherto investigated. After acute i.p. administration of DDTC at two different doses, microglia were already activated in selected areas of the rat brain (hippocampal dentate gyrus, entorhinal-pyriform cortex and hypothalamus) after 1 hour, reaching a peak at 3-6 hours and subsided within 6-48 hours, depending on the brain region. Microglia activation was associated with interleukin-1 beta immunopositivity between 3 and 6 hours and with up-regulation of major histocompatibility complex class II expression between 24 and 48 hours. No significant changes in astrocyte immunostaining were detected between 6 hours and 6 days. The TUNEL procedure revealed the death of a limited number of cells in the above-mentioned structures that peaked at 6h and then declined rapidly. Cell death was detected in sites with major, minor, or no microglial activation, indicating that these two events can occur concomitantly or independently. The study shows that the administration of DDTC provides a useful model for studying the implications of region-specific reactivity of microglia and its differential interaction with neuronal damage.

  11. Redox state and energy metabolism during liver regeneration: alterations produced by acute ethanol administration.

    PubMed

    Gutiérrez-Salinas, J; Miranda-Garduño, L; Trejo-Izquierdo, E; Díaz-Muñoz, M; Vidrio, S; Morales-González, J A; Hernández-Muñoz, R

    1999-12-01

    Ethanol metabolism can induce modifications in liver metabolic pathways that are tightly regulated through the availability of cellular energy and through the redox state. Since partial hepatectomy (PH)-induced liver proliferation requires an oversupply of energy for enhanced syntheses of DNA and proteins, the present study was aimed at evaluating the effect of acute ethanol administration on the PH-induced changes in cellular redox and energy potentials. Ethanol (5 g/kg body weight) was administered to control rats and to two-thirds hepatectomized rats. Quantitation of the liver content of lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, and adenine nucleotides led us to estimate the cytosolic and mitochondrial redox potentials and energy parameters. Specific activities in the liver of alcohol-metabolizing enzymes also were measured in these animals. Liver regeneration had no effect on cellular energy availability, but induced a more reduced cytosolic redox state accompanied by an oxidized mitochondrial redox state during the first 48 hr of treatment; the redox state normalized thereafter. Administration of ethanol did not modify energy parameters in PH rats, but this hepatotoxin readily blocked the PH-induced changes in the cellular redox state. In addition, proliferating liver promoted decreases in the activity of alcohol dehydrogenase (ADH) and of cytochrome P4502E1 (CYP2E1); ethanol treatment prevented the PH-induced diminution of ADH activity. In summary, our data suggest that ethanol could minimize the PH-promoted metabolic adjustments mediated by redox reactions, probably leading to an ineffective preparatory event that culminates in compensatory liver growth after PH in the rat.

  12. Acute tubulointerstitial nephritis/drug induced acute kidney injury; an experience from a single center in Pakistan

    PubMed Central

    Naqvi, Rubina; Mubarak, Muhammad; Ahmed, Ejaz; Akhtar, Fazal; Naqvi, Anwar; Rizvi, Adib

    2016-01-01

    Introduction: There is no information in literature specifically on the prevalence and clinicopathological characteristics of acute tubulointerstitial nephritis/drug induced acute kidney injury (AKI) from Pakistan. Objectives: We aim to report a series of cases from patients developing AKI after exposure to some medications or finding of interstitial nephritis on histopathology. Patients and Methods: This is an observational study of patients identified as having AKI after exposure to medications. AKI was defined according to RIFLE criteria and all patients fell from risk to loss category on arrival. On ultrasonography, all patients had normal size non-obstructed kidneys. Renal biopsy findings were consistent with tubule interstitial nephritis. Results: Mean age of patients was 36.41 ± 17.40 years. Among total of 155, 80 were male and 75 female. Regarding drugs, most common was exposure to aminoglycoside in 34 (22%) followed by use of non-steroidal anti-inflammatory analgesics in 28, contrast induced agents in 11. Renal biopsy was performed in 58 patients. In half of these, insulting agent was not known and in rest either multiple medications were ingested or there was denial to substance use or recovery was delayed despite discontinuation of responsible medication. Renal replacement therapy was required on arrival in 119/155 (hemodialysis = 115, peritoneal dialysis = 4) cases. Complete renal recovery was observed in 71%, while 7.7% expired during acute phase, partial renal recovery was seen in 15% and 5% disappeared after first discharge from the hospital. Conclusion: Tubulointerstitial nephritis may occur with many drugs of common use. Early and intensive efforts must be made to consider and then timely correct the injury to the kidney. PMID:27069962

  13. Acute ethanol administration affects zebrafish preference for a biologically inspired robot.

    PubMed

    Spinello, Chiara; Macrì, Simone; Porfiri, Maurizio

    2013-08-01

    Preclinical animal models constitute a cornerstone against which the reward processes involved in drug addiction are often studied and dissected. While rodents have traditionally represented the species of choice, a growing body of literature indicates that zebrafish are emerging as a valuable model organism. Specifically, several studies demonstrate that the effects of ethanol at the level of emotional- and cognitive-related domains can be reliably investigated using zebrafish. The rapidly evolving nature of these efforts allows substantial room for the development of novel experimental paradigms suited to this freshwater species. The field of ethorobotics may prove particularly beneficial, due to its ability to convey fully controllable and easily reproducible experimental tools. In this study, we addressed the possibility of using a biologically inspired robot to investigate the emotionally related properties of ethanol in a preference task in zebrafish. To this aim, we evaluated wild-type zebrafish preference toward a robotic stimulus and addressed whether ethanol administration (0.25% and 1.00% ethanol/water concentration) may alter such preferences. In accordance with our previous studies, we observed that zebrafish exhibit a natural attraction toward the robot. Additionally, in agreement with our predictions, we showed that ethanol administration abolishes such preferences. This work is the first to demonstrate that robotic stimuli can be used in zebrafish to investigate the reward-related properties of alcohol.

  14. Personalized Cardiovascular Medicine Today: A Food and Drug Administration/Center for Drug Evaluation and Research Perspective.

    PubMed

    Blaus, Alison; Madabushi, Rajanikanth; Pacanowski, Michael; Rose, Martin; Schuck, Robert N; Stockbridge, Norman; Temple, Robert; Unger, Ellis F

    2015-10-13

    Over the past decade, personalized medicine has received considerable attention from researchers, drug developers, and regulatory agencies. Personalized medicine includes identifying patients most likely to benefit and those most likely to experience adverse reactions in response to a drug, and tailoring therapy based on pharmacokinetics or pharmacodynamic response, as well. Perhaps most exciting is finding ways to identify likely responders through genetic, proteomic, or other tests, so that only likely responders will be treated. However, less precise methods such as identifying historical, demographic, or other indicators of increased or reduced responsiveness are also important aspects of personalized medicine. The cardiovascular field has not used many genetic or proteomic markers, but has regularly used prognostic variables to identify likely responders. The development of biomarker-based approaches to personalized medicine in cardiovascular disease has been challenging, in part, because most cardiovascular therapies treat acquired syndromes, such as acute coronary syndrome and heart failure, which develop over many decades and represent the end result of several pathophysiological mechanisms. More precise disease classification and greater understanding of individual variations in disease pathology could drive the development of targeted therapeutics. Success in designing clinical trials for personalized medicine will require the selection of patient populations with attributes that can be targeted or that predict outcome, and the use of appropriate enrichment strategies once such attributes are identified. Here, we describe examples of personalized medicine in cardiovascular disease, discuss its impact on clinical trial design, and provide insight into the future of personalized cardiovascular medicine from a regulatory perspective.

  15. Acute but not chronic administration of pioglitazone promoted behavioral and neurochemical protective effects in the MPTP model of Parkinson's disease.

    PubMed

    Barbiero, Janaína K; Santiago, Ronise M; Lima, Marcelo M S; Ariza, Deborah; Morais, Lívia H; Andreatini, Roberto; Vital, Maria A B F

    2011-01-01

    The present study investigated the neurochemical, motor and cognitive effects of pioglitazone in a rat model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the first experiment, we administered MPTP, and 1h later administered a single oral dose of pioglitazone (5, 15 and 30 mg/kg). The following day, we performed the open-field test and neurochemical dose response curve. We demonstrated that 30 mg/kg of pioglitazone was capable of restoring striatal dopamine (DA) concentrations and motor behaviors. A second experiment was conducted to test the effects of two protocols (acute and chronic) of pioglitazone (30 mg/kg) administration in the open-field test, two-way active avoidance task and in the DA and metabolites levels. The acute protocol consisted of a single oral administration 1 h after MPTP, whereas the chronic protocol was performed with daily administrations starting 1 h after MPTP and ending 22 days after that. Results showed that neither protocol was able to reverse the cognitive impairment promoted by MPTP. We also demonstrated that acute treatment generated some level of neuroprotection, as confirmed by the absence of DA reduction in the group treated with pioglitazone in comparison to the sham group. By contrast, chronic treatment leaded to a reduction of striatal DA, close to MPTP administration alone. These findings suggest that acute administration of pioglitazone (30 mg/kg) was more efficient in generating beneficial effects on motor behaviors and in striatal DA levels. Nevertheless, we failed to demonstrate that pioglitazone administration improved performance on a dopamine-related cognitive task after MPTP.

  16. Effects of acute and repeated administration of salvinorin A on dopamine function in the rat dorsal striatum

    PubMed Central

    Chefer, Vladimir I.; Shippenberg, Toni S.

    2013-01-01

    Rationale Acute systemic administration of salvinorin A, a naturally occurring κ-opioid receptor (KOPr) agonist, decreases locomotion and striatal dopamine (DA) overflow. Objectives Conventional and quantitative microdialysis techniques were used to determine whether salvinorin A infusion into the dorsal striatum (DSTR) decreases DA overflow by altering DA uptake or release. The influence of repeated salvinorin A administration on basal DA dynamics and cocaine-evoked alterations in DA overflow and locomotion was also assessed. Materials and methods Salvinorin A was administered via the dialysis probe (0; 20–200 nM) or via intraperitoneal (i.p.) injection (1.0 or 3.2 mg/kg per day×5 days). The effects of a challenge dose of cocaine were examined 48 h after repeated salvinorin treatment. Results Retrodialysis of salvinorin A produced a dose-related, KOPr antagonist reversible, decrease in DA levels. Extracellular DA levels were decreased whereas DA extraction fraction, which provides an estimate of DA uptake, was unaltered. In contrast to its acute administration, repeated salvinorin A administration did not modify dialysate DA levels. Similarly, neither basal extracellular DA levels nor DA uptake was altered. Unlike synthetic KOPr agonists, prior repeated administration of salvinorin A did not attenuate the locomotor activating effects of an acute cocaine (20 mg/kg, i.p.) challenge. However, cocaine-evoked DA overflow was enhanced. Conclusions These data demonstrate that acute, but not repeated, salvinorin A administration decreases mesostriatal neurotransmission and that activation of DSTR KOPr is sufficient for this effect. Differences in the interaction of salvinorin and synthetic KOPr agonists with cocaine suggest that the pharmacology of these agents may differ. PMID:18246329

  17. Prescription drugs; revocation of final guideline patient package inserts and withdrawal of draft guideline patient package inserts--Food and Drug Administration. Notice.

    PubMed

    1982-09-07

    The Food and Drug Administration (FDA) is revoking the final guideline patient package inserts for 5 classes of drugs and is withdrawing the draft guideline patient package inserts for 5 other classes of drugs. Elsewhere in this issue of the Federal Register, the agency is revoking the regulations that established general requirements for the preparation and distribution of patient package inserts for prescription drug products. Those regulations had established a pilot program that would have been applied to 10 classes of drugs for 3 years. This notice revokes the draft and final guidelines which described how manufactures might comply with the regulations with respect to affected classes of drug.

  18. Antibiotic treatment for acute haematogenous osteomyelitis of childhood: moving towards shorter courses and oral administration.

    PubMed

    Pääkkönen, M; Peltola, H

    2011-10-01

    Acute haematogenous osteomyelitis (AHOM) of childhood usually affects the long bones of the lower limbs. Although almost any agent may cause AHOM, Staphylococcus aureus is the most common bacterium, followed by Streptococcus pneumoniae and, in some countries, Salmonella spp. and Kingella kingae. Magnetic resonance imaging (MRI) has improved the diagnostic accuracy of traditional radiography and scintigraphy. Except for the pre-treatment diagnostic sample from bone before the institution of antibiotic therapy, no other surgery is usually required. Traditionally, non-neonatal AHOM has been treated with a 1-3-month course of antibiotics, including an intravenous (i.v.) phase for the first weeks, but recent prospective randomised studies challenge this approach. For most uncomplicated cases, a course of 20 days including an i.v. period of 2-4 days suffices, provided large enough doses of a well-absorbed agent (clindamycin or a first-generation cephalosporin, local resistance permitting) are used, administration is four times daily and most symptoms and signs subside within a few days. Serum C-reactive protein (CRP) is a good guide in monitoring the course of illness, and the antimicrobial can usually be discontinued if CRP has decreased to <20 mg/L. Newer and costly agents, such as linezolid, should be reserved for cases due to resistant S. aureus strains. AHOM in neonates and immunocompromised patients probably requires a different approach. Because sequelae may develop slowly, follow-up for at least 1 year post hospitalisation is recommended.

  19. Prevention of reflex natriuresis after acute unilateral nephrectomy by neonatal administration of MSG

    SciTech Connect

    Lin, S.Y.; Wiedemann, E.; Deschepper, C.F.; Alper, R.H.; Humphreys, M.H.

    1987-02-01

    Acute unilateral nephrectomy (AUN) results in natriuresis from the remaining kidney through reflex pathways involving the central nervous system and requiring an intact pituitary gland. The natriuresis is accompanied by an increase in the plasma concentration of a peptide or peptides derived from the N-terminal fragment (NTF) of proopiomelanocortin. The authors measured plasma immunoreactive NTF-like material (IR-NTF) by radioimmunoassay, before and after AUN in control rats and rats treated neonatally with monosodium glutamate (MSG), a procedure that produces neuroendocrine dysfunction by destroying cell bodies in the hypothalamic arcuate nucleus, median eminence, and other brain regions. In control rats, IR-NTF increased from 85.8 +/- 54.9 (SD) to 207 +/- 98.1 fmol/ml after AUN as sodium excretion (U/sub Na/V) doubled. In MSG-treated rats, AUN produced no change in plasma IR-NTF concentration, nor did U/sub Na/V increase. Tissue content of IR-NTF was reduced in the arcuate nucleus and anterior lobe of pituitaries from MSG-treated rats compared with controls, but was no different in the neurointermediate lobe. These results indicate that the hypothalamic lesion produced by neonatal administration of MSG prevents both the increase in plasma IR-NTF concentration and the natruiuresis after AUN, and therefore lend further support to the concept of a casual relationship between these two consequences of AUN.

  20. Acute toxicity, histopathology, and coagulopathy in American kestrels (Falco sparverius) following administration of the rodenticide diphacinone.

    PubMed

    Rattner, Barnett A; Horak, Katherine E; Warner, Sarah E; Day, Daniel D; Meteyer, Carol U; Volker, Steven F; Eisemann, John D; Johnston, John J

    2011-05-01

    The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be over 20 times greater in American kestrels (Falco sparverius; median lethal dose 96.8 mg/kg body weight) compared with Northern bobwhite (Colinus virginianus) and mallards (Anas platyrhynchos). Modest evidence of internal bleeding was observed at necropsy, although histological examination of heart, liver, kidney, lung, intestine, and skeletal muscle revealed hemorrhage over a wide range of doses (35.1-675 mg/kg). Residue analysis suggests that the half-life of diphacinone in the liver of kestrels that survived was relatively short, with the majority of the dose cleared within 7 d of exposure. Several precise and sensitive clotting assays (prothrombin time, Russell's viper venom time, thrombin clotting time) were adapted for use in this species, and oral administration of diphacinone at 50 mg/kg increased prothrombin time and Russell's viper venom time at 48 and 96 h postdose compared with controls. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and generally corresponded with the onset of overt signs of toxicity and lethality. In view of the toxicity and risk evaluation data derived from American kestrels, the involvement of diphacinone in some raptor mortality events, and the paucity of threshold effects data following short-term dietary exposure for birds of prey, additional feeding trials with captive raptors are warranted to characterize more fully the risk of secondary poisoning.

  1. Acute toxicity, histopathology, and coagulopathy in American kestrels (Falco sparverius) following administration of the rodenticie diphacinone

    USGS Publications Warehouse

    Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Day, Daniel D.; Meteyer, Carol U.; Voler, Steven F.; Eisemann, John D.; Johnston, John J.

    2011-01-01

    The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be over 20 times greater in American kestrels (Falco sparverius; median lethal dose 96.8 mg/kg body weight) compared with Northern bobwhite (Colinus virginianus) and mallards (Anas platyrhynchos). Modest evidence of internal bleeding was observed at necropsy, although histological examination of heart, liver, kidney, lung, intestine, and skeletal muscle revealed hemorrhage over a wide range of doses (35.1-675 mg/kg). Residue analysis suggests that the half-life of diphacinone in the liver of kestrels that survived was relatively short, with the majority of the dose cleared within 7 d of exposure. Several precise and sensitive clotting assays (prothrombin time, Russell's viper venom time, thrombin clotting time) were adapted for use in this species, and oral administration of diphacinone at 50 mg/kg increased prothrombin time and Russell?s viper venom time at 48 and 96 h postdose compared with controls. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and generally corresponded with the onset of overt signs of toxicity and lethality. In view of the toxicity and risk evaluation data derived from American kestrels, the involvement of diphacinone in some raptor mortality events, and the paucity of threshold effects data following short-term dietary exposure for birds of prey, additional feeding trials with captive raptors are warranted to characterize more fully the risk of secondary poisoning.

  2. Design of a RESTful web information system for drug prescription and administration.

    PubMed

    Bianchi, Lorenzo; Paganelli, Federica; Pettenati, Maria Chiara; Turchi, Stefano; Ciofi, Lucia; Iadanza, Ernesto; Giuli, Dino

    2014-05-01

    Drug prescription and administration processes strongly impact on the occurrence of risks in medical settings for they can be sources of adverse drug events (ADEs). A properly engineered use of information and communication technologies has proven to be a promising approach to reduce these risks. In this study, we propose PHARMA, a web information system which supports healthcare staff in the secure cooperative execution of drug prescription, transcription and registration tasks. PHARMA allows the easy sharing and management of documents containing drug-related information (i.e., drug prescriptions, medical reports, screening), which is often inconsistent and scattered across different information systems and heterogeneous organization domains (e.g., departments, other hospital facilities). PHARMA enables users to access such information in a consistent and secure way, through the adoption of REST and web-oriented design paradigms and protocols. We describe the implementation of the PHARMA prototype, and we discuss the results of the usability evaluation that we carried out with the staff of a hospital in Florence, Italy.

  3. Time Dependent Antinociceptive Effects of Morphine and Tramadol in the Hot Plate Test: Using Different Methods of Drug Administration in Female Rats

    PubMed Central

    Gholami, Morteza; Saboory, Ehsan; Mehraban, Sogol; Niakani, Afsaneh; Banihabib, Nafiseh; Azad, Mohamad-Reza; Fereidoni, Javid

    2015-01-01

    Morphine and tramadol which have analgesic effects can be administered acutely or chronically. This study tried to investigate the effect of these drugs at various times by using different methods of administration (intraperitoneal, oral, acute and chronic). Sixty adult female rats were divided into six groups. They received saline, morphine or tramadol (20 to 125 mg/Kg) daily for 15 days. A hot plate test was performed for the rats at the 1st, 8th and 15th days. After drug withdrawal, the hot plate test was repeated at the 17th, 19th, and 22nd days. There was a significant correlation between the day, drug, group, and their interaction (P<0.001). At 1st day (d1), both morphine, and tramadol caused an increase in the hot plate time comparing to the saline groups (P<0.001), while there was no correlation between drug administration methods of morphine and/or tramadol. At the 8th day (d8), morphine and tramadol led to the most powerful analgesic effect comparing to the other experimental days (P<0.001). At the 15th day (d15), their effects diminished comparing to the d8. After drug withdrawal, analgesic effect of morphine, and tramadol disappeared. It can be concluded that the analgesic effect of morphine and tramadol increases with the repeated use of them. Thereafter, it may gradually decrease and reach to a level compatible to d1. The present data also indicated that although the analgesic effect of morphine and tramadol is dose-and-time dependent, but chronic exposure to them may not lead to altered nociceptive responses later in life. PMID:25561936

  4. Long-term drug administration in the adult zebrafish using oral gavage for cancer preclinical studies

    PubMed Central

    Dang, Michelle; Henderson, Rachel E.; Garraway, Levi A.

    2016-01-01

    ABSTRACT Zebrafish are a major model for chemical genetics, and most studies use embryos when investigating small molecules that cause interesting phenotypes or that can rescue disease models. Limited studies have dosed adults with small molecules by means of water-borne exposure or injection techniques. Challenges in the form of drug delivery-related trauma and anesthesia-related toxicity have excluded the adult zebrafish from long-term drug efficacy studies. Here, we introduce a novel anesthetic combination of MS-222 and isoflurane to an oral gavage technique for a non-toxic, non-invasive and long-term drug administration platform. As a proof of principle, we established drug efficacy of the FDA-approved BRAFV600E inhibitor, Vemurafenib, in adult zebrafish harboring BRAFV600E melanoma tumors. In the model, adult casper zebrafish intraperitoneally transplanted with a zebrafish melanoma cell line (ZMEL1) and exposed to daily sub-lethal dosing at 100 mg/kg of Vemurafenib for 2 weeks via oral gavage resulted in an average 65% decrease in tumor burden and a 15% mortality rate. In contrast, Vemurafenib-resistant ZMEL1 cell lines, generated in culture from low-dose drug exposure for 4 months, did not respond to the oral gavage treatment regimen. Similarly, this drug treatment regimen can be applied for treatment of primary melanoma tumors in the zebrafish. Taken together, we developed an effective long-term drug treatment system that will allow the adult zebrafish to be used to identify more effective anti-melanoma combination therapies and opens up possibilities for treating adult models of other diseases. PMID:27482819

  5. Effects of sharing information on drug administration errors in pediatric wards: a pre–post intervention study

    PubMed Central

    Chua, Siew-Siang; Choo, Sim-Mei; Sulaiman, Che Zuraini; Omar, Asma; Thong, Meow-Keong

    2017-01-01

    Background and purpose Drug administration errors are more likely to reach the patient than other medication errors. The main aim of this study was to determine whether the sharing of information on drug administration errors among health care providers would reduce such problems. Patients and methods This study involved direct, undisguised observations of drug administrations in two pediatric wards of a major teaching hospital in Kuala Lumpur, Malaysia. This study consisted of two phases: Phase 1 (pre-intervention) and Phase 2 (post-intervention). Data were collected by two observers over a 40-day period in both Phase 1 and Phase 2 of the study. Both observers were pharmacy graduates: Observer 1 just completed her undergraduate pharmacy degree, whereas Observer 2 was doing her one-year internship as a provisionally registered pharmacist in the hospital under study. A drug administration error was defined as a discrepancy between the drug regimen received by the patient and that intended by the prescriber and also drug administration procedures that did not follow standard hospital policies and procedures. Results from Phase 1 of the study were analyzed, presented and discussed with the ward staff before commencement of data collection in Phase 2. Results A total of 1,284 and 1,401 doses of drugs were administered in Phase 1 and Phase 2, respectively. The rate of drug administration errors reduced significantly from Phase 1 to Phase 2 (44.3% versus 28.6%, respectively; P<0.001). Logistic regression analysis showed that the adjusted odds of drug administration errors in Phase 1 of the study were almost three times that in Phase 2 (P<0.001). The most common types of errors were incorrect administration technique and incorrect drug preparation. Nasogastric and intravenous routes of drug administration contributed significantly to the rate of drug administration errors. Conclusion This study showed that sharing of the types of errors that had occurred was significantly

  6. Acute Thrombocytopenia: An Unusual Complication Occurring After Drug-Eluting Microspheres Transcatheter Hepatic Chemoembolization

    SciTech Connect

    Poggi, Guido; Quaretti, Pietro; Montagna, Benedetta Sottotetti, Federico Tagliaferri, Barbara Pozzi, Emma Amatu, Alessio Pagella, Chiara; Bernardo, Giovanni

    2011-02-15

    Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma and liver metastases from neuroendocrine tumors, colorectal carcinomas, and uveal melanomas. Although the technique is relatively safe, it has been associated with several complications. We report the cases of two patients with colorectal liver metastases who developed acute thrombocytopenia a few hours after TACE. To our knowledge, acute thrombocytopenia occurring after TACE with drug-eluting microspheres has not yet been reported. Here we discuss the hypothetical etiopathogenetic mechanisms.

  7. Acute and chronic administration of ibogaine to the rat results in astrogliosis that is not confined to the cerebellar vermis.

    PubMed

    O'Callaghan, J P; Rogers, T S; Rodman, L E; Page, J G

    1996-10-31

    Acute administration of high doses of ibogaine (IBG) to the male rat results in degeneration of Purkinje cells and reactive gliosis in the cerebellar vermis. We examined whether acute and chronic administration of IBG to male and female rats results in gliosis as determined by quantification of the astroglial intermediate filament protein, glial fibrillary acidic protein (GFAP). After acute administration of IBG, rats of both sexes showed dose-related increases in GFAP that were not confined to the cerebellar vermis. After chronic administration of IBG, female, but not male rats, showed large (as much as 200% of control), dose-related increases in GFAP in hippocampus, olfactory bulbs, brain stem and striatum, but not cerebellum. In hippocampus, the cytoskeletal proteins, neurofilament 68 (NF-68) and beta-tubulin were increased in females treated chronically with IBG, findings consistent with a damage-induced sprouting response. Together, the data indicate that IBG damages areas of the brain outside the cerebellum and that the sites damaged are dependent on sex and dosage regimen.

  8. Serotonin-2C receptors in the basolateral nucleus of the amygdala mediate the anxiogenic effect of acute imipramine and fluoxetine administration.

    PubMed

    Vicente, Maria Adrielle; Zangrossi, Helio

    2012-04-01

    A growing body of evidence indicates that facilitation of serotonin-2C receptor (5-HT2CR)-mediated neurotransmission in the basolateral nucleus of the amygdala (BLA) is involved in anxiety generation. We investigated here whether BLA 5-HT2CRs exert a differential role in the regulation of defensive behaviours related to generalized anxiety (inhibitory avoidance) and panic (escape) disorders. We also evaluated whether activation of BLA 5-HT2CRs accounts for the anxiogenic effect caused by acute systemic administration of the antidepressants imipramine and fluoxetine. Male Wistar rats were tested in the elevated T-maze after intra-BLA injection of the endogenous agonist 5-HT, the 5-HT2CR agonist MK-212 or the 5-HT2CR antagonist SB-242084. This test allows the measurement of inhibitory avoidance acquisition and escape expression. We also investigated whether intra-BLA administration of SB-242084 interferes with the acute anxiogenic effect caused by imipramine and fluoxetine in the Vogel conflict test, and imipramine in the elevated T-maze. While intra-BLA administration of 5-HT and MK-212 facilitated inhibitory avoidance acquisition, suggesting an anxiogenic effect, SB-242084 had the opposite effect. None of these drugs affected escape performance. Intra-BLA injection of a sub-effective dose of SB-242084 fully blocked the anxiogenic effect caused either by the local microinjection of 5-HT or the systemic administration of imipramine and fluoxetine. Our findings indicate that 5-HT2CRs in BLA are selectively involved in the regulation of defensive behaviours associated with generalized anxiety, but not panic. The results also provide the first direct evidence that activation of BLA 5-HT2CRs accounts for the short-term aversive effect of antidepressants.

  9. The argument for integrating vector control with multiple drug administration campaigns to ensure elimination of lymphatic filariasis

    PubMed Central

    Burkot, TR; Durrheim, DN; Melrose, WD; Speare, R; Ichimori, K

    2006-01-01

    Background There is a danger that mass drug administration campaigns may fail to maintain adequate treatment coverage to achieve lymphatic filariasis elimination. Hence, additional measures to suppress transmission might be needed to ensure the success of the Global Program for the Elimination of Lymphatic Filariasis. Discussion Vector control successfully eliminated lymphatic filariasis when implemented alone or with mass drug administration. Challenges to lymphatic filariasis elimination include uncertainty of the exact level and duration of microfilarial suppression required for elimination, the mobility of infected individuals, consistent non-participation of some infected individuals with mass drug administration, the possible development of anti-filarial drug resistance and treatment strategies in areas co-endemic with loasis. Integration of vector control with mass drug administration can address some of these challenges. The potential benefits of vector control would include: (1) the ability to suppress filariasis transmission without the need to identify all individual 'foci of infection'; (2) minimizing the risk of reestablishment of transmission from imported microfilaria positive individuals; and (3) decreasing the risk of dengue or malaria transmission where, respectively, Aedes or Anopheles are lymphatic filariasis vectors. Summary With adequate sustained treatment coverage, mass drug administration should meet the criteria for elimination of lymphatic filariasis. However, it may be difficult to sustain sufficiently high mass drug administration coverage to achieve lymphatic filariasis elimination in some areas, particularly, where Aedes species are the vectors. Since vector control was effective in controlling and even eliminating lymphatic filariasis transmission, integration of vector control with mass drug administration will ensure the sustainability of transmission suppression and thereby better ensure the success of national filariasis

  10. Medical devices; revocation of cardiac pacemaker registry. Food and Drug Administration, HHS. Final rule.

    PubMed

    1999-11-24

    The Food and Drug Administration (FDA) is issuing a final rule to revoke a regulation requiring a cardiac pacemaker registry. The registry, which was mandated by the Deficit Reduction Act of 1984, requires any physician and any provider of services who requests or receives Medicare payment for an implantation, removal, or replacement of permanent cardiac pacemaker devices and pacemaker leads to submit certain information to the registry. The information is used by FDA to track the performance of permanent cardiac pacemakers and pacemaker leads and by the Health Care Finance Administration (HCFA) to administer its Medicare payment program for these devices. This action is being taken to implement an act to Repeal An Unnecessary Medical Device Reporting Requirement passed by Congress in 1996 to remove the cardiac pacemaker registry to eliminate duplicative and unnecessary reporting.

  11. Intravesical electromotive drug administration for the treatment of non-infectious chronic cystitis.

    PubMed

    Riedl, C R; Knoll, M; Plas, E; Stephen, R L; Pflüger, H

    1997-01-01

    Seventeen patients with non-infectious chronic cystitis (NICC) (9 with interstitial cystitis, 6 patients with radiation cystitis, 1 with chemocystitis and 1 with lupoid cystitis) were treated with electromotive administration of intravesical lidocaine and dexamethasone followed by hydrodistension of the bladder. Complete resolution of symptoms for an average of 7.5 months was observed in 11 patients (65%), partial improvement in 4 (23.5%). In this series no complications occurred. Electromotive drug administration (EMDA) and cystodistension were well tolerated by all patients. The treatment was performed on an outpatient basis, thus reducing therapeutic costs. The results presented demonstrate that the combination of EMDA and bladder hydrodistension is an effective first-line treatment for NICC patients.

  12. Are we nearly there yet? Coverage and compliance of mass drug administration for lymphatic filariasis elimination.

    PubMed

    Alexander, Neal D E

    2015-03-01

    Lymphatic filariasis has been targeted for elimination by 2020, and a threshold of 65% coverage of mass drug administration (MDA) has been adopted by the Global Programme to Eliminate Lymphatic Filariasis (GPELF). A recent review by Babu and Babu of 36 studies of MDA for lymphatic filariasis in India found that coverage, defined as receipt of tablets, ranged from 48.8 to 98.8%, while compliance, defined as actual ingestion of tablets, was 22% lower on average. Moreover, the denominator for these coverage figures is the eligible, rather than total, population. By contrast, the 65% threshold, in the original modelling study, refers to ingestion of tablets in the total population. This corresponds to GPELF's use of 'epidemiological drug coverage' as a trigger for the Transmission Assessment Surveys (TAS), which indicate whether to proceed to post-MDA surveillance. The existence of less strict definitions of 'coverage' should not lead to premature TAS that could impair MDA's sustainability.

  13. Regulatory aspects of teratology: role of the Food and Drug Administration

    SciTech Connect

    Kelsey, F.O.

    1982-04-01

    The Food and Drug Administration is a scientific regulatory agency whose consumer protection activities cover a wide range of products including foods and additives, and pesticide residues on foods; drugs; cosmetics; medical devices; and radiation-emitting electronic products. Amongst its concerns is the possible teratogen effects of regulated products to which the pregnant woman is exposed. The policies and programs of the agency directed toward reducing such risks to the unborn are reviewed. These measures include guidelines for animal reproduction studies and for clinical trials involving women to childbearing potential; labeling of products to disclose known or possible harm to the fetus or embryo; surveillance procedures designed to detect previously unsuspected adverse effects of marketed products; research activities designed to develop better understanding of developmental toxicology and improved techniques for detecting embryocidal and embryotoxic effects; and educational efforts directed both to professionals and the public regarding hazards to the unborn of agency-regulated products.

  14. Regulatory aspects of teratology: role of the Food and Drug Administration.

    PubMed

    Kelsey, F O

    1982-04-01

    The Food and Drug Administration is a scientific regulatory agency whose consumer protection activities cover a wide range of products including foods and additives, and pesticide residues on foods; drugs; cosmetics; medical devices; and radiation-emitting electronic products. Amongst its concerns is the possible teratogen effects of regulated products to which the pregnant woman is exposed. The policies and programs of the agency directed toward reducing such risks to the unborn are reviewed. These measures include guidelines for animal reproduction studies and for clinical trials involving women to childbearing potential; labeling of products to disclose known or possible harm to the fetus or embryo; surveillance procedures designed to detect previously unsuspected adverse effects of marketed products; research activities designed to develop better understanding of developmental toxicology and improved techniques for detecting embryocidal and embryotoxic effects; and educational efforts directed both to professionals and the public regarding hazards to the unborn of agency-regulated products.

  15. Will mass drug administration eliminate lymphatic filariasis? Evidence from northern coastal Tanzania.

    PubMed

    Parker, Melissa; Allen, Tim

    2013-07-01

    This article documents understandings and responses to mass drug administration (MDA) for the treatment and prevention of lymphatic filariasis among adults and children in northern coastal Tanzania from 2004 to 2011. Assessment of village-level distribution registers, combined with self-reported drug uptake surveys of adults, participant observation and interviews, revealed that at study sites in Pangani and Muheza districts the uptake of drugs was persistently low. The majority of people living at these highly endemic locations either did not receive or actively rejected free treatment. A combination of social, economic and political reasons explain the low uptake of drugs. These include a fear of treatment (attributable, in part, to a lack of trust in international aid and a questioning of the motives behind the distribution); divergence between biomedical and local understandings of lymphatic filariasis; and limited and ineffective communication about the rationale for mass treatment. Other contributory factors are the reliance upon volunteers for distribution within villages and, in some locations, strained relationships between different groups of people within villages as well as between local leaders and government officials. The article also highlights a disjuncture between self-reported uptake of drugs by adults at a village level and the higher uptake of drugs recorded in official reports. The latter informs claims that elimination will be a possibility by 2020. This gives voice to a broader problem: there is considerable pressure for those implementing MDA to report positive results. The very real challenges of making MDA work are pushed to one side - adding to a rhetoric of success at the expense of engaging with local realities. It is vital to address the kind of issues raised in this article if current attempts to eliminate lymphatic filariasis in mainland coastal Tanzania are to achieve their goal.

  16. US Food and Drug Administration international collaborations for cellular therapy product regulation

    PubMed Central

    2012-01-01

    Cellular therapy products are an emerging medical product class undergoing rapid scientific and clinical innovation worldwide. These products pose unique regulatory challenges both for countries with existing regulatory frameworks and for countries where regulatory frameworks for cellular therapy products are under development. The United States Food and Drug Administration (US FDA) has a history of productive working relationships with international regulatory authorities, and seeks to extend this to the cellular therapy field. The US FDA and its global regulatory counterparts are engaged in collaborations focused on the convergence of scientific and regulatory approaches, and the education of scientists, clinicians, regulators, and the public at large on the development of cellular therapies. PMID:23021082

  17. Food and Drug Administration: Insufficient Planning for Field Laboratory Consolidation Decisions.

    DTIC Science & Technology

    1987-12-04

    t ’c . ~ I~S %i Executive Summairy Purpose The Food and Drug Administration’s (FDA’s) mission is to protect andpromote the public health and the well...Objectives, Scope, and Methodology 14 Chapter 2 18 Limited Evaluation FDA’s Evaluation Focused Mainly on Physical Facilities 18 Criteria Used to Other...Contents Tables Table 2.1: Factors and Categories FDA Used to Evaluate 20 - Laboratories Table 2.2: Laboratory Rankings and Scores 21 Table 2.3

  18. Of specialty interest: the Food and Drug Administration: a partner in safe practice.

    PubMed

    Baker, Karen

    2003-01-01

    Have you ever wondered what really goes on at the United States Food and Drug Administration (FDA)? At each meeting of the Society of Otorhinolaryngology and Head-Neck Nurses (SOHN) and the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) the FDA is repeatedly mentioned, and not always favorably! This article discusses the process of bringing new medical devices to market and explains how ORL (or ENT) nurses can contribute to the protection of the public health by providing medical device adverse event information to FDA.

  19. United States Food and Drug Administration Regulation of Gene and Cell Therapies.

    PubMed

    Bailey, Alexander M; Arcidiacono, Judith; Benton, Kimberly A; Taraporewala, Zenobia; Winitsky, Steve

    2015-01-01

    The United States (US) Food and Drug Administration (FDA) is a regulatory agency that has oversight for a wide range of products entering the US market, including gene and cell therapies. The regulatory approach for these products is similar to other medical products within the United States and consists of a multitiered framework of statutes, regulations, and guidance documents. Within this framework, there is considerable flexibility which is necessary due to the biological and technical complexity of these products in general. This chapter provides an overview of the US FDA regulatory oversight of gene and cell therapy products.

  20. G-749, a novel FLT3 kinase inhibitor, can overcome drug resistance for the treatment of acute myeloid leukemia

    PubMed Central

    Lee, Hee Kyu; Kim, Hong Woo; Lee, In Yong; Lee, Jungmi; Lee, Jaekyoo; Jung, Dong Sik; Lee, Sang Yeop; Park, Sung Ho; Hwang, Haejun; Choi, Jang-Sik; Kim, Jung-Ho; Kim, Se Won; Kim, Jung Keun; Cools, Jan; Koh, Jong Sung

    2014-01-01

    Aberrant activations of Fms-like tyrosine receptor kinase (FLT) 3 are implicated in the pathogenesis of 20% to 30% of patients with acute myeloid leukemia (AML). G-749 is a novel FLT3 inhibitor that showed potent and sustained inhibition of the FLT3 wild type and mutants including FLT3-ITD, FLT3-D835Y, FLT3-ITD/N676D, and FLT3-ITD/F691L in cellular assays. G-749 retained its inhibitory potency in various drug-resistance milieus such as patient plasma, FLT3 ligand surge, and stromal protection. Furthermore, it displayed potent antileukemic activity in bone marrow blasts from AML patients regardless of FLT3 mutation status, including those with little or only minor responses to AC220 or PKC412. Oral administration of G-749 yielded complete tumor regression and increased life span in animal models. Thus, G-749 appears to be a promising next-generation drug candidate for the treatment of relapsed and refractory AML patients with various FLT3-ITD/FLT3-TKD mutants and further shows the ability to overcome drug resistance. PMID:24532805

  1. 77 FR 44256 - Draft Guidance for Industry and Food and Drug Administration Staff; Safety Considerations for 510...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-27

    ...-Bore Connectors Intended for Enteral Applications; Availability AGENCY: Food and Drug Administration... Misconnections with Small- bore Connectors Intended for Enteral Applications.'' The use of common connector... Risks of Misconnections With Small-Bore Connectors Intended for Enteral Applications'' to the...

  2. 76 FR 81510 - Draft Guidance for Industry and Food and Drug Administration Staff; the 510(k) Program...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-28

    ... Staff; the 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications ; Availability... and Drug Administration Staff; The 510(k) Program: Evaluating Substantial Equivalence in Premarket... reviews premarket notification (510(k)) submissions as well as on the Special and Abbreviated...

  3. 76 FR 29251 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls; Guidance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-20

    ...; Class II Special Controls; Guidance Document: Topical Oxygen Chamber for Extremities; Availability... Drug Administration Staff; Class II Special Controls Guidance Documents: Topical Oxygen Chamber for... Guidance Document: Topical Oxygen Chamber for Extremities'' to the Division of Small...

  4. National Veterans Health Administration inpatient risk stratification models for hospital-acquired acute kidney injury

    PubMed Central

    Cronin, Robert M; VanHouten, Jacob P; Siew, Edward D; Eden, Svetlana K; Fihn, Stephan D; Nielson, Christopher D; Peterson, Josh F; Baker, Clifton R; Ikizler, T Alp; Speroff, Theodore

    2015-01-01

    Objective Hospital-acquired acute kidney injury (HA-AKI) is a potentially preventable cause of morbidity and mortality. Identifying high-risk patients prior to the onset of kidney injury is a key step towards AKI prevention. Materials and Methods A national retrospective cohort of 1,620,898 patient hospitalizations from 116 Veterans Affairs hospitals was assembled from electronic health record (EHR) data collected from 2003 to 2012. HA-AKI was defined at stage 1+, stage 2+, and dialysis. EHR-based predictors were identified through logistic regression, least absolute shrinkage and selection operator (lasso) regression, and random forests, and pair-wise comparisons between each were made. Calibration and discrimination metrics were calculated using 50 bootstrap iterations. In the final models, we report odds ratios, 95% confidence intervals, and importance rankings for predictor variables to evaluate their significance. Results The area under the receiver operating characteristic curve (AUC) for the different model outcomes ranged from 0.746 to 0.758 in stage 1+, 0.714 to 0.720 in stage 2+, and 0.823 to 0.825 in dialysis. Logistic regression had the best AUC in stage 1+ and dialysis. Random forests had the best AUC in stage 2+ but the least favorable calibration plots. Multiple risk factors were significant in our models, including some nonsteroidal anti-inflammatory drugs, blood pressure medications, antibiotics, and intravenous fluids given during the first 48 h of admission. Conclusions This study demonstrated that, although all the models tested had good discrimination, performance characteristics varied between methods, and the random forests models did not calibrate as well as the lasso or logistic regression models. In addition, novel modifiable risk factors were explored and found to be significant. PMID:26104740

  5. Chronic smoking, but not acute nicotine administration, modulates neural correlates of working memory

    PubMed Central

    Ross, Thomas J.; Shakleya, Diaá M.; Huestis, Marilyn A.; Stein, Elliot A.

    2010-01-01

    Rationale Beyond the amelioration of deprivation-induced impairments, and in contrast to effects on attentional processes, the cognitive-enhancing properties of nicotine on working memory (WM) operations remain unclear. Objectives In an effort to elucidate potential enhancing effects, we explored the impact of transdermal nicotine on neural functioning in minimally deprived smokers and, in addition, assessed differences between smokers and non-smokers using a mixed block/event-related fMRI design that attempted to isolate specific central executive operations (attentional switch events) within general WM function (task blocks). Methods In task blocks, participants performed a continuous counting paradigm that required the simultaneous maintenance of, and frequent switching of attentional focus between, two running tallies in WM on some trials. Cigarette smokers (n=30) were scanned twice, once each with a nicotine and placebo patch, while non-smokers (n=27) were scanned twice with no patch. Results Across both groups, task blocks were associated with bilateral activation, notably in medial and lateral prefrontal cortex (PFC), anterior insula, and parietal regions, whereas individual attentional switch trials were associated with activation in a similar, but predominantly left-lateralized network. Within the smoker group, although nicotine increased heart rate, altered performance and mood, and reduced tobacco cravings, no acute drug (state-like) effect on brain activity was detected for either the task or switch effects. However, relative to non-smokers, smokers showed greater tonic activation in medial superior frontal cortex, right anterior insula, and bilateral anterior PFC throughout task blocks (trait-like effect). Conclusions These data suggest smokers require recruitment of additional WM and supervisory control operations during task performance. PMID:20862456

  6. An evaluation process for an electronic bar code medication administration information system in an acute care unit.

    PubMed

    Bargren, Michelle; Lu, Der-Fa

    2009-01-01

    The purpose of this case study is to present an evaluation process and recommendations for addressing the gaps found with the implementation of a new bar code medication administration (BCMA) technology in a busy acute care hospital unit. The case study analyzes workflow procedures associated with administration of medications in an inpatient labor and delivery care unit before and one year after implementation of BCMA technology. The comparison reveals a twofold increase in workflow procedures for nursing staff because of the new technology. System gaps are identified from a nursing user's perspective, and recommendations are offered to close those gaps.

  7. Effect of an acute intraluminal administration of capsaicin on oesophageal motor pattern in GORD patients with ineffective oesophageal motility.

    PubMed

    Grossi, L; Cappello, G; Marzio, L

    2006-08-01

    Ineffective oesophageal motility (IOM) is a functional disorder affecting about 50% of gastro-oesophageal reflux disease (GORD) patients. This disease in a severe form limits the clearing ability of the oesophagus and is considered one of the predictive factors for poorer GORD resolution. Capsaicin, the active compound of red pepper, exerts a prokinetic effect on oesophageal motility in healthy subjects by increasing the amplitude of body waves, even if no evidence exists on its possible role in situations of reduced motility. The aim of the study was to evaluate the effect of an acute administration of capsaicin on the oesophageal motor pattern in a group of GORD patients affected by severe IOM. Twelve GORD patients with severe IOM received an intra-oesophageal administration of 2 mL of a red pepper-olive oil mixture and 2 mL of olive oil alone serving as a control during a stationary manometry. The motor patterns of the oesophageal body and lower oesophageal sphincter (LOS) were analysed at baseline and after the infusion of the two stimuli. The administration of capsaicin induced a significant improvement in oesophageal body contractility when compared with baseline. The velocity of propagation of waves and the LOS basal tone remained unchanged. The motor pattern was unaltered by the administration of olive oil alone. An acute administration of capsaicin seems to improve the motor performance of the oesophageal body in patients with ineffective motility. Whether this could represent the basis for further therapeutic approaches of GORD patients needs further study.

  8. Effects of Ketamine on Levels of Inflammatory Cytokines IL-6, IL-1β, and TNF-α in the Hippocampus of Mice Following Acute or Chronic Administration.

    PubMed

    Li, Yanning; Shen, Ruipeng; Wen, Gehua; Ding, Runtao; Du, Ao; Zhou, Jichuan; Dong, Zhibin; Ren, Xinghua; Yao, Hui; Zhao, Rui; Zhang, Guohua; Lu, Yan; Wu, Xu

    2017-01-01

    Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile, ketamine has been shown to modulate the levels of inflammatory cytokines. We hypothesized that the effects of ketamine on the central nervous system are associated with inflammatory cytokines. Therefore, we set out to establish acute and chronic ketamine administration models in C57BL/6 mice, to evaluate spatial recognition memory and emotional response, to analyze the changes in the levels of the inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the mouse hippocampus, employing behavioral tests, Western blot, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Our results showed that ketamine at the dose of 60 mg/kg induced spatial recognition memory deficit and reduced anxiety-like behaviors in mice after chronic administration. Moreover, we found that ketamine increased the hippocampal levels of IL-6 and IL-1β after single, multiple and long-term administration in a dose-dependent manner. However, the expression level of TNF-α differed in the mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α, whereas multiple and long-term administration decreased it significantly. We considered that TNF-α expression could be controlled by a bi-directional regulatory pathway, which was associated with the dose and duration of ketamine administration. Our results suggest that the alterations in the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α may be involved in the neurotoxicity of ketamine.

  9. Effects of Ketamine on Levels of Inflammatory Cytokines IL-6, IL-1β, and TNF-α in the Hippocampus of Mice Following Acute or Chronic Administration

    PubMed Central

    Li, Yanning; Shen, Ruipeng; Wen, Gehua; Ding, Runtao; Du, Ao; Zhou, Jichuan; Dong, Zhibin; Ren, Xinghua; Yao, Hui; Zhao, Rui; Zhang, Guohua; Lu, Yan; Wu, Xu

    2017-01-01

    Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile, ketamine has been shown to modulate the levels of inflammatory cytokines. We hypothesized that the effects of ketamine on the central nervous system are associated with inflammatory cytokines. Therefore, we set out to establish acute and chronic ketamine administration models in C57BL/6 mice, to evaluate spatial recognition memory and emotional response, to analyze the changes in the levels of the inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the mouse hippocampus, employing behavioral tests, Western blot, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Our results showed that ketamine at the dose of 60 mg/kg induced spatial recognition memory deficit and reduced anxiety-like behaviors in mice after chronic administration. Moreover, we found that ketamine increased the hippocampal levels of IL-6 and IL-1β after single, multiple and long-term administration in a dose-dependent manner. However, the expression level of TNF-α differed in the mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α, whereas multiple and long-term administration decreased it significantly. We considered that TNF-α expression could be controlled by a bi-directional regulatory pathway, which was associated with the dose and duration of ketamine administration. Our results suggest that the alterations in the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α may be involved in the neurotoxicity of ketamine. PMID:28373844

  10. Dose-response relationship of an environmental mixture of pyrethroids following an acute oral administration in the rat

    EPA Science Inventory

    Dose-response relationship of an environmental mixture of pyrethroids following an acute oral administration in the rat M.F. Hughes1, D.G. Ross1, J.M. Starr1, E.J. Scollon1,2, M.J. Wolansky1,3, K.M. Crofton1, M.J. DeVito1,4 1U.S. EPA, ORD, Research Triangle Park, NC, 2U.S. EPA,...

  11. Antidiabetic-drug combination treatment for glucose intolerance in adult female rats treated acutely with olanzapine.

    PubMed

    Boyda, Heidi N; Procyshyn, Ric M; Asiri, Yahya; Wu, Claire; Wang, Cathy K; Lo, Ryan; Pang, Catherine C Y; Honer, William G; Barr, Alasdair M

    2014-01-03

    Second generation antipsychotic drugs are routinely used as treatment for psychotic disorders. Many of these compounds, including olanzapine, cause metabolic side-effects such as impaired glucose tolerance and insulin resistance. Individual antidiabetic drugs can help control elevated glucose levels in patients treated with antipsychotics, but the effects of combining antidiabetics, which routinely occurs with Type 2 diabetes mellitus patients, have never been studied. Presently, we compared the effects of the three different antidiabetics metformin (500mg/kg, p.o.), rosiglitazone (30mg/kg, p.o.) and glyburide (10mg/kg, p.o.) on metabolic dysregulation in adult female rats treated acutely with olanzapine. In addition, dual combinations of each of these antidiabetics were compared head-to-head against each other and the individual drugs. The animals received two daily treatments with antidiabetics and were then treated acutely with olanzapine (10mg/kg, i.p.). Fasting glucose and insulin levels were measured, followed by a 2h glucose tolerance test. Olanzapine caused a large and highly significant glucose intolerance compared to vehicle treated rats. Rosiglitazone decreased glucose levels non-significantly, while both metformin and glyburide significantly decreased glucose levels compared to olanzapine-only treated animals. For antidiabetic dual-drug combinations, the rosiglitazone-metformin group showed an unexpected increase in glucose levels compared to all of the single antidiabetic drugs. However, both the metformin-glyburide and rosiglitazone-glyburide groups showed significantly greater reductions in glucose levels following olanzapine than with single drug treatment alone for metformin or rosiglitazone, bringing glucose levels down to values equivalent to vehicle-only treated animals. These findings indicate that further study of antidiabetic dual-drug combinations in patients treated with antipsychotic drugs is warranted.

  12. 75 FR 52755 - Draft Guidance for Industry on Acute Bacterial Skin and Skin Structure Infections: Developing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-27

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Acute Bacterial Skin and Skin... guidance for industry entitled ``Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for... the development of antimicrobial drugs for the treatment of acute bacterial skin and skin...

  13. Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs

    SciTech Connect

    Zhou, Xiaobing; Ma, Ben; Lin, Zhi; Qu, Zhe; Huo, Yan; Wang, Jufeng; Li, Bo

    2014-10-01

    As kidney is a major target organ affected by drug toxicity, early detection of renal injury is critical in preclinical drug development. In past decades, a series of novel biomarkers of drug-induced nephrotoxicity were discovered and verified in rats. However, limited data regarding the performance of novel biomarkers in non-rodent species are publicly available. To increase the applicability of these biomarkers, we evaluated the performance of 4 urinary biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), clusterin, total protein, and N-acetyl-β-D-glucosaminidase (NAG), relative to histopathology and traditional clinical chemistry in beagle dogs with acute kidney injury (AKI) induced by gentamicin. The results showed that urinary NGAL and clusterin levels were significantly elevated in dogs on days 1 and 3 after administration of gentamicin, respectively. Gene expression analysis further provided mechanistic evidence to support that NGAL and clusterin are potential biomarkers for the early assessment of drug-induced renal damage. Furthermore, the high area (both AUCs = 1.000) under receiver operator characteristics (ROC) curve also indicated that NGAL and clusterin were the most sensitive biomarkers for detection of gentamicin-induced renal proximal tubular toxicity. Our results also suggested that NAG may be used in routine toxicity testing due to its sensitivity and robustness for detection of tissue injury. The present data will provide insights into the preclinical use of these biomarkers for detection of drug-induced AKI in non-rodent species. - Highlights: • Urinary NGAL, clusterin and NAG levels were significantly elevated in canine AKI. • NGAL and clusterin gene expression were increased following treatment with gentamicin. • NGAL and clusterin have high specificity and sensitivity for detection of AKI.

  14. Influence of drugs of abuse and alcohol upon patients admitted to acute psychiatric wards: physician's assessment compared to blood drug concentrations.

    PubMed

    Mordal, Jon; Medhus, Sigrid; Holm, Bjørn; Mørland, Jørg; Bramness, Jørgen G

    2013-06-01

    In acute psychiatric services, rapid and accurate detection of psychoactive substance intake may be required for appropriate diagnosis and intervention. The aim of this study was to investigate the relationship between (a) drug influence as assessed by physicians and (b) blood drug concentrations among patients admitted to acute psychiatric wards. We also explored the possible effects of age, sex, and psychotic symptoms on physician's assessment of drug influence. In a cross-sectional study, the sample comprised 271 consecutive admissions from 2 acute psychiatric wards. At admission, the physician on call performed an overall judgment of drug influence. Psychotic symptoms were assessed with the positive subscale of the Positive and Negative Syndrome Scale. Blood samples were screened for a wide range of psychoactive substances, and quantitative results were used to calculate blood drug concentration scores. Patients were judged as being under the influence of drugs and/or alcohol in 28% of the 271 admissions. Psychoactive substances were detected in 56% of the blood samples. Altogether, 15 different substances were found; up to 8 substances were found in samples from 1 patient. Markedly elevated blood drug concentration scores were estimated for 15% of the patients. Physician's assessment was positively related to the blood drug concentration scores (r = 0.52; P < 0.001), to symptoms of excitement, and to the detection of alcohol, cannabis, and amphetamines. The study demonstrates the major impact of alcohol and drugs in acute psychiatric settings and illustrates the challenging nature of the initial clinical assessment.

  15. Clinical Risk Factors for In-Hospital Adverse Cardiovascular Events After Acute Drug Overdose

    PubMed Central

    Manini, Alex F.; Hoffman, Robert S.; Stimmel, Barry; Vlahov, David

    2015-01-01

    Objectives It was recently demonstrated that adverse cardiovascular events (ACVE) complicate a high proportion of hospitalizations for patients with acute drug overdoses. The aim of this study was to derive independent clinical risk factors for ACVE in patients with acute drug overdoses. Methods This prospective cohort study was conducted over 3 years at two urban university hospitals. Patients were adults with acute drug overdoses enrolled from the ED. In-hospital ACVE was defined as any of myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest. Results There were 1,562 patients meeting inclusion/exclusion criteria (mean age, 41.8 years; female, 46%; suicidal, 38%). ACVE occurred in 82 (5.7%) patients (myocardial injury, 61; shock, 37; dysrhythmia, 23; cardiac arrests, 22) and there were 18 (1.2%) deaths. On univariate analysis, ACVE risk increased with age, lower serum bicarbonate, prolonged QTc interval, prior cardiac disease, and altered mental status. In a multivariable model adjusting for these factors as well as patient sex and hospital site, independent predictors were: QTc > 500 msec (3.8% prevalence, odds ratio [OR] 27.6), bicarbonate < 20 mEql/L (5.4% prevalence, OR 4.4), and prior cardiac disease (7.1% prevalence, OR 9.5). The derived prediction rule had 51.6% sensitivity, 93.7% specificity, and 97.1% negative predictive value; while presence of two or more risk factors had 90.9% positive predictive value. Conclusions The authors derived independent clinical risk factors for ACVE in patients with acute drug overdose, which should be validated in future studies as a prediction rule in distinct patient populations and clinical settings. PMID:25903997

  16. [Influence of iron nanoparticles on cardiac performance and hemodynamics in rabbits after intravenous administration in acute experiment].

    PubMed

    Doroshenko, A M

    2014-01-01

    Iron nanoparticles are possessed by high potential in the creation of effective and safe antianemic drugs due to the enhanced biological activity of metal nanoparticles. As a step of intravenous dosage form development the study of short-term effects of iron nanoparticles on the cardiovascular system is important. Dose-dependent changes of systemic hemodynamics' parameters were established in acute experiment on rabbits after several intravenous injections of zero-valent iron nanoparticles solution.

  17. The Food and Drug Administration's role in the canned salmon recalls of 1982.

    PubMed Central

    Hayes, A H

    1983-01-01

    The Alaska salmon industry conducted 9 recalls of 7 3/4-oz cans of salmon in 1982 after a 7 3/4-oz can of Alaskan salmon was implicated in illness and one death in Belgium from Clostridium botulinum type E toxin. By the code number on the can, the Food and Drug Administration (FDA), Seattle District, traced it to a specific salmon packer. Subsequently, the FDA received a report about a defect in the can. Investigation of the salmon packer's plant by the Agency revealed that the equipment used at the plant to reform the cans--which arrived at the cannery in a nearly flattened state--might have been responsible for the defect. The death and illness in Belgium, combined with the results of the FDA inspection of the plant implicated in the Belgian incident, provided strong evidence of the existence of a hazardous situation that might have widespread adverse health effects. The Food and Drug Administration therefore requested the firm to recall its 1980 and 1981 production of salmon packaged in 7 3/4-oz cans. The Agency then began an investigation of all U.S. salmon packed inn cans of this size that had been reformed on the equipment implicated in the can defect. Of 300,000 cans examined, 22 with the defect were found. As additional firms were identified as having used the defective cans, subsequent recalls were initiated. PMID:6414026

  18. Quantum Dot-Loaded Liposomes to Evaluate the Behavior of Drug Carriers after Oral Administration.

    PubMed

    Tahara, Kohei; Fujimoto, Shiho; Fujii, Fumihiko; Tozuka, Yuichi; Jin, Takashi; Takeuchi, Hirofumi

    2013-01-01

    We have developed submicron-sized liposomes modified with a mucoadhesive polymer to enhance peptide drug absorption after oral administration. Liposomal behavior in the gastrointestinal tract is a critical factor for effective peptide drug delivery. The purpose of this study was to prepare quantum dot- (QD-) loaded submicron-sized liposomes and examine liposomal behavior in the body after oral administration using in vivo fluorescence imaging. Two types of CdSe/CdZnS QDs with different surface properties were used: hydrophobic (unmodified) QDs and hydrophilic QDs with glutathione (GSH) surface modifications. QD- and GSH-QD-loaded liposomes were prepared by a thin film hydration method. Transmission electron microscopy revealed that QDs were embedded in the liposomal lipid bilayer. Conversely, GSH-QDs were present in the inner aqueous phase. Some of the GSH-QDs were electrostatically associated with the lipid membrane of stearylamine-bearing cationic liposomes. QD-loaded liposomes were detected in Caco-2 cells after exposure to the liposomes, and these liposomes were not toxic to the Caco-2 cells. Furthermore, we evaluated the in vivo bioadhesion and intestinal penetration of orally administered QD-loaded liposomes by observing the intestinal segment using confocal laser scanning microscopy.

  19. Quantum Dot-Loaded Liposomes to Evaluate the Behavior of Drug Carriers after Oral Administration

    PubMed Central

    Tahara, Kohei; Fujimoto, Shiho; Fujii, Fumihiko; Tozuka, Yuichi; Jin, Takashi; Takeuchi, Hirofumi

    2013-01-01

    We have developed submicron-sized liposomes modified with a mucoadhesive polymer to enhance peptide drug absorption after oral administration. Liposomal behavior in the gastrointestinal tract is a critical factor for effective peptide drug delivery. The purpose of this study was to prepare quantum dot- (QD-) loaded submicron-sized liposomes and examine liposomal behavior in the body after oral administration using in vivo fluorescence imaging. Two types of CdSe/CdZnS QDs with different surface properties were used: hydrophobic (unmodified) QDs and hydrophilic QDs with glutathione (GSH) surface modifications. QD- and GSH-QD-loaded liposomes were prepared by a thin film hydration method. Transmission electron microscopy revealed that QDs were embedded in the liposomal lipid bilayer. Conversely, GSH-QDs were present in the inner aqueous phase. Some of the GSH-QDs were electrostatically associated with the lipid membrane of stearylamine-bearing cationic liposomes. QD-loaded liposomes were detected in Caco-2 cells after exposure to the liposomes, and these liposomes were not toxic to the Caco-2 cells. Furthermore, we evaluated the in vivo bioadhesion and intestinal penetration of orally administered QD-loaded liposomes by observing the intestinal segment using confocal laser scanning microscopy. PMID:26555997

  20. Gender-related differences in pulmonary arterial hypertension targeted drugs administration.

    PubMed

    Marra, Alberto M; Benjamin, Nicola; Eichstaedt, Christina; Salzano, Andrea; Arcopinto, Michele; Gargani, Luna; D Alto, Michele; Argiento, Paola; Falsetti, Lorenzo; Di Giosia, Paolo; Isidori, Andrea M; Ferrara, Francesco; Bossone, Eduardo; Cittadini, Antonio; Grünig, Ekkehard

    2016-12-01

    During the last 15 years, a real "paradigm-shift" occurred, due to the development of PAH-targeted drugs, leading to crucial improvements in symptoms, exercise capacity, hemodynamics and outcome of PAH patients. In order to describe differences regarding epidemiology and therapy in PAH according to gender, we performed a review of the available literature in "PubMed" and "Web of Science" databases. In order to find relevant articles, we combined each of the following the keywords "pulmonary arterial hypertension", "gender", "sex", "men", "woman", "male", "female", "phosphodiesterase inhibitors", "endothelin receptor antagonists", "prostanoids". While there is a substantial agreement among epidemiological studies in reporting an increased prevalence of pulmonary arterial hypertension (PAH) among women, male PAH patients are affected by a higher impairment of the right ventricular function and consequently experience poorer outcomes. With regards to PAH-targeted drug administration, endothelin receptor antagonists (ERAs) and prostacyclin analogues (PC) show better treatment results in female PAH patients, while phosphodiesterase-5 inhibitors (PD5-I) seem to exert a more beneficial effect on male patients. However, to date no clear consensus could be formed by the available literature, which is constituted mainly by retrospective studies. Females with PAH are more prone to develop PAH, while males experience poorer outcomes. Females PAH might benefit more from ERAs and PC, while males seem to have more beneficial effects from PD5-I administration. However, more research is warranted in order to assess the most effective treatment for PAH patients according to gender.