Analysis of acute naproxen administration on memory in young adults: A randomized, double-blind, placebo-controlled study.

PubMed

Wilson, Jack H; Criss, Amy H; Spangler, Sean A; Walukevich, Katherine; Hewett, Sandra

2017-10-01

Nonsteroidal anti-inflammatory drugs work by non-selectively inhibiting cyclooxygenase enzymes. Evidence indicates that metabolites of the cyclooxygenase pathway play a critical role in the process of learning and memory. We evaluated whether acute naproxen treatment impairs short-term working memory, episodic memory, or semantic memory in a young, healthy adult population. Participants received a single dose of placebo or naproxen (750 mg) in random order separated by 7-10 days. Two hours following administration, participants completed five memory tasks. The administration of acute high-dose naproxen had no effect on memory in healthy young adults.

Drug Abuse Control--Administrative Guidelines.

ERIC Educational Resources Information Center

Los Angeles City Schools, CA.

These guidelines were developed to assist administrators, teachers, and other staff members of the Los Angeles Public Schools in the formulation of an effective program designed to alleviate drug abuse. Staff responsibilities are spelled out. Specific attention is directed to the problems of drug abuse, drug possession and drug selling. The…

A systematic review of validated methods for identifying acute respiratory failure using administrative and claims data.

PubMed

Jones, Natalie; Schneider, Gary; Kachroo, Sumesh; Rotella, Philip; Avetisyan, Ruzan; Reynolds, Matthew W

2012-01-01

The Food and Drug Administration's (FDA) Mini-Sentinel pilot program initially aims to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest (HOIs) from administrative and claims data. This paper summarizes the process and findings of the algorithm review of acute respiratory failure (ARF). PubMed and Iowa Drug Information Service searches were conducted to identify citations applicable to the anaphylaxis HOI. Level 1 abstract reviews and Level 2 full-text reviews were conducted to find articles using administrative and claims data to identify ARF, including validation estimates of the coding algorithms. Our search revealed a deficiency of literature focusing on ARF algorithms and validation estimates. Only two studies provided codes for ARF, each using related yet different ICD-9 codes (i.e., ICD-9 codes 518.8, "other diseases of lung," and 518.81, "acute respiratory failure"). Neither study provided validation estimates. Research needs to be conducted on designing validation studies to test ARF algorithms and estimating their predictive power, sensitivity, and specificity. Copyright © 2012 John Wiley & Sons, Ltd.

78 FR 55728 - Society of Clinical Research Associates-Food and Drug Administration: Food and Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-11

...: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The Food and Drug Administration... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Society of Clinical Research Associates-Food and Drug Administration: Food and Drug Administration...

Drug-Induced Acute Pancreatitis: A Review

PubMed Central

Jones, Mark R.; Hall, Oliver Morgan; Kaye, Adam M.; Kaye, Alan David

2015-01-01

Background The majority of drug-induced pancreatitis cases are mild to moderate in severity, but severe and even fatal cases can occur. Management of drug-induced pancreatitis requires withdrawal of the offending agent and supportive care. Methods This review focuses on differential diagnosis, clinical presentation, drug-mediated effects, treatments, and mechanisms of pancreatitis, with an emphasis on drug-induced pancreatitis. Results Although only a minority of cases associated with acute pancreatitis are linked to drugs, clinical presentation and mechanisms of injury to the pancreas are not well understood by clinicians in terms of individual drug effects in the mediation or modulation of injury to the pancreas. In recent years, a large number of commonly prescribed medications has been linked to drug-induced pancreatitis pathogenesis. Although mechanisms are proposed, the exact cause of injury is either not well understood or controversial. Conclusion Future investigation into the mechanisms of pancreatitis and an appreciation by clinicians of the drugs commonly linked to the condition will help establish earlier diagnosis and quicker cessation of offending drugs in the treatment of drug-induced acute pancreatitis. PMID:25829880

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0142] Drug and Medical Device Forum on Food and Drug Administration Drug and Device Requirements and Supplier Controls; Public Educational Forum AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public...

Administration costs of intravenous biologic drugs for rheumatoid arthritis.

PubMed

Soini, Erkki J; Leussu, Miina; Hallinen, Taru

2013-01-01

Cost-effectiveness studies explicitly reporting infusion times, drug-specific administration costs for infusions or real-payer intravenous drug cost are few in number. Yet, administration costs for infusions are needed in the health economic evaluations assessing intravenously-administered drugs. To estimate the drug-specific administration and total cost of biologic intravenous rheumatoid arthritis (RA) drugs in the adult population and to compare the obtained costs with published cost estimates. Cost price data for the infusions and drugs were systematically collected from the 2011 Finnish price lists. All Finnish hospitals with available price lists were included. Drug administration and total costs (administration cost + drug price) per infusion were analysed separately from the public health care payer's perspective. Further adjustments for drug brand, dose, and hospital type were done using regression methods in order to improve the comparability between drugs. Annual expected drug administration and total costs were estimated. A literature search not limited to RA was performed to obtain the per infusion administration cost estimates used in publications. The published costs were converted to Finnish values using base-year purchasing power parities and indexing to the year 2011. Information from 19 (95%) health districts was obtained (107 analysable prices out of 176 observations). The average drug administration cost for infliximab, rituximab, abatacept, and tocilizumab infusion in RA were €355.91; €561.21; €334.00; and €293.96, respectively. The regression-adjusted (dose, hospital type; using semi-log ordinary least squares) mean administration costs for infliximab and rituximab infusions in RA were €289.12 (95% CI €222.61-375.48) and €542.28 (95% CI €307.23-957.09). The respective expected annual drug administration costs were €2312.96 for infliximab during the first year, €1879.28 for infliximab during the forthcoming years, and �

Acute recreational drug toxicity

PubMed Central

Liakoni, Evangelia; Yates, Christopher; Dines, Alison M.; Dargan, Paul I.; Heyerdahl, Fridtjof; Hovda, Knut Erik; Wood, David M.; Eyer, Florian; Liechti, Matthias E.

2018-01-01

Abstract The aim of the study was to compare self-reported and analytically confirmed substance use in cases of acute recreational drug toxicity. We performed a retrospective analysis of emergency department presentations of acute recreational drug toxicity over 2 years (October 2013 to September 2015) within the European Drug Emergencies Network Plus project. Among the 10,956 cases of acute recreational drug toxicity during the study period, 831 could be included. Between the self-reported substance use and the toxicological results, the highest agreement was found for heroin (86.1%) and cocaine (74.1%), whereas inhalants, poppers, and magic mushrooms were self-reported but not analytically detected. Cathinones and other new psychoactive substances (NPS) could be detected using additional analytical methods. Among cases with both immunoassay (IA) and confirmation with mass spectrometry (MS), the results were consistent for methadone (100%) and cocaine (95.5%) and less consistent for amphetamines (81.8%). In cases with a positive IA for amphetamines (n = 54), MS confirmed the presence of 3,4-methylenedioxymethamphetamine (MDMA), amphetamine, methamphetamine, and NPS in 37, 20, 10, and 6 cases, respectively, also revealing use of more than 1 substance in some cases. MS yielded positive results in 21 cases with a negative IA for amphetamines, including amphetamine, MDMA, methamphetamine, and NPS, in 14, 7, 2, and 2 cases, respectively. In conclusion, the highest agreement was found between self-reports and analytical findings for heroin and cocaine. The diagnosis of NPS use was mainly based on self-report. The IAs accurately identified methadone and cocaine, and MS had advantages for the detection of NPS and amphetamine derivatives. PMID:29384873

Preclinical Determinants of Drug Choice under Concurrent Schedules of Drug Self-Administration

PubMed Central

Banks, Matthew L.; Negus, S. Stevens

2012-01-01

Drug self-administration procedures have played a critical role in the experimental analysis of psychoactive compounds, such as cocaine, for over 50 years. While there are numerous permutations of this procedure, this paper will specifically focus on choice procedures using concurrent schedules of intravenous drug self-administration. The aims of this paper are to first highlight the evolution of drug choice procedures and then review the subsequent preclinical body of literature utilizing these choice procedures to understand the environmental, pharmacological, and biological determinants of the reinforcing stimulus effects of drugs. A main rationale for this paper is our proposition that choice schedules are underutilized in investigating the reinforcing effects of drugs in assays of drug self-administration. Moreover, we will conclude with potential future directions and unexplored scientific space for the use of drug choice procedures. PMID:23243420

[Drug-induced acute pancreatitis: about 10 cases].

PubMed

Maghrebi, Houcine; Rhaeim, Rami; Haddad, Anis; Makni, Amin; Mohamed, Jouini; Montasser, Kacem; Zoubeir, Ben Safta

2017-01-01

Drug-induced acute pancreatitis (AP) accounts for approximately 2% of acute pancreatitis. Its incidence is increasing, with more than 260 incriminated drugs. However, very few cases have been described in the literature due to accountability problem. We report our experience with 10 cases whose data were collected over a period of 7 years. Clinical presentation of AP was often equivocal. Ranson's score ranged from 0 to 5. We recorded 5 cases of edematous pancreatitis and 5 cases of necro-bleeding pancreatitis. These pancreatitis were often successfully treated without recurrence after discontinuation of the incriminated drug.

Risk of Acute Kidney Injury After Intravenous Contrast Media Administration.

PubMed

Hinson, Jeremiah S; Ehmann, Michael R; Fine, Derek M; Fishman, Elliot K; Toerper, Matthew F; Rothman, Richard E; Klein, Eili Y

2017-05-01

The study objective was to determine whether intravenous contrast administration for computed tomography (CT) is independently associated with increased risk for acute kidney injury and adverse clinical outcomes. This single-center retrospective cohort analysis was performed in a large, urban, academic emergency department with an average census of 62,179 visits per year; 17,934 ED visits for patients who underwent contrast-enhanced, unenhanced, or no CT during a 5-year period (2009 to 2014) were included. The intervention was CT scan with or without intravenous contrast administration. The primary outcome was incidence of acute kidney injury. Secondary outcomes included new chronic kidney disease, dialysis, and renal transplantation at 6 months. Logistic regression modeling and between-groups odds ratios with and without propensity-score matching were used to test for an independent association between contrast administration and primary and secondary outcomes. Treatment decisions, including administration of contrast and intravenous fluids, were examined. Rates of acute kidney injury were similar among all groups. Contrast administration was not associated with increased incidence of acute kidney injury (contrast-induced nephropathy criteria odds ratio=0.96, 95% confidence interval 0.85 to 1.08; and Acute Kidney Injury Network/Kidney Disease Improving Global Outcomes criteria odds ratio=1.00, 95% confidence interval 0.87 to 1.16). This was true in all subgroup analyses regardless of baseline renal function and whether comparisons were made directly or after propensity matching. Contrast administration was not associated with increased incidence of chronic kidney disease, dialysis, or renal transplant at 6 months. Clinicians were less likely to prescribe contrast to patients with decreased renal function and more likely to prescribe intravenous fluids if contrast was administered. In the largest well-controlled study of acute kidney injury following contrast

Acute Pancreatitis and Use of Pancreatitis-Associated Drugs: A 10-Year Population-Based Cohort Study.

PubMed

Bertilsson, Sara; Kalaitzakis, Evangelos

2015-10-01

To assess the use of acute pancreatitis (AP)-associated drugs in patients with AP, the relation between sales of these drugs and the incidence of AP, and the potential impact on AP severity and recurrence. All patients with incident AP between 2003 and 2012, in a well-defined area, were retrospectively identified. Data regarding AP etiology, severity, and recurrence and use of AP-associated drugs were extracted from medical records. Drugs were classified according to an evidence-based classification system. Annual drug sales data were obtained from the Swedish drug administration service. Overall, 1457 cases of incident AP were identified. Acute pancreatitis-associated drug users increased from 32% in 2003 to 51% in 2012, reflecting increasing user rates in the general population. The incidence of AP increased during the study period but was not related to AP-associated drug user rates (P > 0.05). Recurrent AP occurred in 23% but was unrelated to AP-associated drug use (P > 0.05). In logistic regression analysis, after adjustment for comorbidity, AP-associated drug use was not related to AP severity (P > 0.05). Use of AP-associated drugs is increasingly frequent in patients with AP. However, it does not have any major impact on the observed epidemiological changes in occurrence, severity, or recurrence of AP.

76 FR 25358 - 2011 Parenteral Drug Association/Food and Drug Administration Glass Quality Conference; Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] 2011 Parenteral Drug Association/Food and Drug Administration Glass Quality Conference; Public Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. SUMMARY: The Food...

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

PubMed

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 (SD(50)) in the CAM were measured and calculated for these drugs. The resultant ideal LD(50) 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 (r(2)=0.42 - 0.68, P<0.005-0.05) between the ideal LD(50) values obtained using the CAM model with LD(50) 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.

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

75 FR 29561 - Memorandum of Understanding Between the Food and Drug Administration and Drugs.Com

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0004] [FDA 225-09-0012] Memorandum of Understanding Between the Food and Drug Administration and Drugs.Com... Administration (FDA) is providing notice of a memorandum of understanding (MOU) between FDA and Drugs.Com. The...

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 SERVICES...

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

Evaluation of drug administration errors in a teaching hospital.

PubMed

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

2012-03-12

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. 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. 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. Medication administration errors are frequent. The identification of its determinants helps to undertake designed interventions.

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 Drug...

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 Drug...

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 Drug...

21 CFR 20.107 - Food and Drug Administration manuals.

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 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 Drug...

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 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 Drug...

Guide to drug porphyrogenicity prediction and drug prescription in the acute porphyrias

PubMed Central

Thunell, Stig; Pomp, Erik; Brun, Atle

2007-01-01

What is already known about this subject Many drug safety lists for acute porphyrias, largely based on anecdotal evidence, are put forward, but no methods or rationale for the risk estimates are given. Many unexplained discrepancies between the lists exist. What this study adds A standardized method for assessment of the risk that a certain drug may activate these diseases has been developed. It also allows risk assessments for drugs lacking porphyria related clinical experience. About one thousand therapeutic drugs have been classified with regard to porphyrogenicity by the proposed method, which is most valuable for the care of porphyria patients. Aims This paper addresses two common problems in the care of carriers of acute porphyria: the choice of safe drugs for pharmacotherapy and the strategy to apply when potentially unsafe drugs cannot be avoided. Methods and results A technique is presented for prediction of risk that a certain drug may activate the disease in a gene carrier for acute porphyria. It is based on a model explaining the clinical manifestations as a result of the acute overloading of a deficient enzyme within the hepatic heme biosynthetic chain. The capacity of the drug for induction of the rate-limiting enzyme in heme biosynthesis, e.g. housekeeping 5-aminolevulinate synthase (ALAS1), is assessed by critical appraisal of reports of the outcomes of clinical use of the drug, and by theoretical criteria. The assessment occurs within the frame of a flow-scheme employing variables of increasing specificity, i.e. endocrine properties of the drug, structure and metabolism pointing to affinity to cytochrome P450, hepatic load in therapeutic use, recognized affinity to major CYP species, capacity for CYP-induction or irreversible inhibition, and capacity to activate or modulate the transduction mechanisms of nuclear receptors affecting ALAS1-gene transcription. It is proposed that in the absence of a safer alternative, an urgently needed drug not

76 FR 6477 - Industry Exchange Workshop on Food and Drug Administration Drug and Device Requirements; Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Industry Exchange Workshop on Food and Drug Administration Drug and Device Requirements; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. SUMMARY: The Food and Drug...

Acute organic brain syndrome due to drug-induced eosinophilia.

PubMed

Ng, S C; Lee, M K; Teh, A

1989-11-01

A 72 year old man developed acute organic brain syndrome associated with marked eosinophilia following self medication with a variety of drugs. Investigations revealed no other known causes of eosinophilia. Withdrawal of drugs resulted in dramatic drop in eosinophil count paralleled by clinical resolution of neurological problems. To our knowledge drug-induced eosinophilia has not previously been associated with acute organic brain syndrome.

[New drug development by innovative drug administration--"change" in pharmaceutical field].

PubMed

Nagai, T

1997-11-01

New drug development can be made by providing products of higher "selectivity for the drug" for medical treatment. There are two ways for the approach to get higher "selectivity of drug": 1) discovery of new compounds with high selectivity of drug; 2) innovation of new drug administration, that is new formulation and/or method with high selectivity of drug by integration and harmonization of various hard/soft technologies. An extensive increase of biological information and advancement of surrounding science and technology may modify the situation as the latter overcomes the former in the 21 century. As the science and technology in the 21 century is said to be formed on "3H", that is, 1. hybrid; 2. hi-quality; 3. husbandry, the new drug development by innovative drug administration is exactly based on the science and technology of 3H. Its characteristic points are interdisciplinary/interfusion, international, of philosophy/ethics, and systems of hard/hard/heart. From these points of view, not only the advance of unit technology but also a revolution in thinking way should be "must" subjects. To organize this type of research well, a total research activity such as ROR (research on research) might take an important and efficient role. Here the key words are the "Optimization technology" and "Change in Pharmaceutical Fields." As some examples of new drug innovation, our trials on several topical mucosal adhesive dosage forms and parenteral administration of peptide drugs such as insulin and erythropoietin will be described.

Drug-related acute renal failure in hospitalised patients.

PubMed

Iavecchia, Lujan; Cereza García, Gloria; Sabaté Gallego, Mònica; Vidal Guitart, Xavier; Ramos Terrades, Natalia; de la Torre, Judith; Segarra Medrano, Alfons; Agustí Escasany, Antònia

2015-01-01

The information available on the incidence and the characteristics of patients with acute renal failure (ARF) related to drugs is scarce. To estimate the incidence of drug-related ARF in hospitalised patients and to compare their characteristics with those of patients with ARF due to other causes. We selected a prospective cohort of patients with ARF during hospital admission (July 2010-July 2011). Information on patients' demographics, medical antecedents, ARF risk factors, ARF severity according to the RIFLE classification and hospital drug administration was collected. We analysed the relationship of drugs with the ARF episodes using Spanish Pharmacovigilance System methods and algorithm. A total of 194 cases had an episode of hospital-acquired ARF. The median age of patients was 72 years [IQR 20]; 60% were men. The ARF incidence during hospitalization was 9.6 per 1,000 admissions. According to the RIFLE classification, a risk of kidney damage or kidney injury was present in 77.8% of cases. In 105 (54.1%) cases, ARF was drug-related; the drugs most frequently involved were diuretics, agents acting on the renin-angiotensin system, immunosuppressants, β-blocking agents, calcium channel blockers, contrast media and non-steroid anti-inflammatory drugs. Patients with drug-related ARF had more multi-morbidity, fewer ARF risk factors and lower mortality. Half of ARF episodes during hospitalisation were drug related. Patients with drug-related ARF had higher cardiovascular morbidity than those with ARF related to other causes, but they had a lower frequency of ARF risk factors and mortality. Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

The use-dependent, nicotinic antagonist BTMPS reduces the adverse consequences of morphine self-administration in rats in an abstinence model of drug seeking

PubMed Central

Hall, Brandon J.; Pearson, Laura S.; Terry, Alvin V.; Buccafusco, Jerry J.

2011-01-01

In this study, the use-dependent, nicotinic receptor antagonist bis (2, 2, 6, 6-tetramethyl-4-piperidinyl) sebacate (BTMPS) was evaluated for its ability to attenuate the adverse consequences associated with morphine in rats in all three phases of an abstinence model of drug seeking: self-administration, acute withdrawal, and delayed test of drug seeking. Rats were allowed to self-administer morphine (FR1 schedule) with an active response lever, on a 24hr basis inside operant chambers, for 14 days. Each rat was subsequently evaluated for stereotypical behaviors associated with spontaneous morphine withdrawal. Rats were then placed in standard housing cages for a six week period of protracted abstinence from morphine. After this period, each rat was placed back into its respective operant chamber for a 14 day assessment of unrewarded drug seeking responses. BTMPS was administered to the animals in all three clinically relevant phases in three separate sets of experiments. BTMPS treatment during the self-administration phase resulted in up to a 34% reduction of lever responses to morphine when compared to vehicle treated control animals, as well as a 32% reduction in the dose of morphine self-administered. When given during self-administration and acute withdrawal, BTMPS treatment decreased acute withdrawal symptoms (up to 64%) of morphine use and reduced (up to 45%) drug seeking responses after six weeks of protracted withdrawal compared to control animals. BTMPS treatment after six weeks of abstinence from morphine had no effect. These results offer insight into the role of central cholinergic receptors in the onset and maintenance of drug addiction. PMID:21651919

Acute organic brain syndrome due to drug-induced eosinophilia.

PubMed Central

Ng, S. C.; Lee, M. K.; Teh, A.

1989-01-01

A 72 year old man developed acute organic brain syndrome associated with marked eosinophilia following self medication with a variety of drugs. Investigations revealed no other known causes of eosinophilia. Withdrawal of drugs resulted in dramatic drop in eosinophil count paralleled by clinical resolution of neurological problems. To our knowledge drug-induced eosinophilia has not previously been associated with acute organic brain syndrome. PMID:2616421

PRESYNAPTIC DOPAMINE MODULATION BY STIMULANT SELF ADMINISTRATION

PubMed Central

España, Rodrigo A.; Jones, Sara R.

2013-01-01

The mesolimbic dopamine system is an essential participant in the initiation and modulation of various forms of goal-directed behavior, including drug reinforcement and addiction processes. Dopamine neurotransmission is increased by acute administration of all drugs of abuse, including the stimulants cocaine and amphetamine. Chronic exposure to these drugs via voluntary self-administration provides a model of stimulant abuse that is useful in evaluating potential behavioral and neurochemical adaptations that occur during addiction. This review describes commonly used methodologies to measure dopamine and baseline parameters of presynaptic dopamine regulation, including exocytotic release and reuptake through the dopamine transporter in the nucleus accumbens core, as well as dramatic adaptations in dopamine neurotransmission and drug sensitivity that occur with acute non-contingent and chronic, contingent self-administration of cocaine and amphetamine. PMID:23277050

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Food and Drug Administration Health Professional Organizations Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. The Food and Drug Administration (FDA) is announcing a...

Comparison of the effects of acute fluvoxamine and desipramine administration on melatonin and cortisol production in humans.

PubMed Central

Skene, D J; Bojkowski, C J; Arendt, J

1994-01-01

1. Acute administration of the specific serotonin uptake inhibitor, fluvoxamine (100 mg at 16.00 h), markedly increased nocturnal plasma melatonin concentrations, with high levels extending into the morning hours. 2. Acute administration of the noradrenaline uptake inhibitor, desipramine (DMI) (100 mg at 16.00 h), increased evening plasma melatonin concentrations. 3. Both drug treatments increased the duration of melatonin secretion, fluvoxamine significantly delaying the offset time and DMI significantly advancing the onset time. 4. The stimulatory effect of DMI on plasma melatonin was mirrored by increased urinary 6-sulphatoxymelatonin (aMT6s) excretion. 5. On the contrary, there was no correlation between plasma melatonin and urinary aMT6s concentrations following fluvoxamine treatment, suggesting that fluvoxamine may inhibit the metabolism of melatonin. 6. Treatment with DMI increased plasma cortisol concentrations in the evening and early morning, treatment with fluvoxamine increased plasma cortisol at 03.00 h, 10.00 h and 11.00 h. 7. The drug treatments affected different aspects of the nocturnal plasma melatonin profile suggesting that the amplitude of the melatonin rhythm may depend upon serotonin availability and/or melatonin metabolism whilst the onset of melatonin production depends upon noradrenaline availability. PMID:8186063

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

PubMed Central

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

2010-01-01

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. PMID:20530792

Increased Late Sodium Current Contributes to the Electrophysiological Effects of Chronic, but Not Acute, Dofetilide Administration.

PubMed

Qiu, Xiaoliang S; Chauveau, Samuel; Anyukhovsky, Evgeny P; Rahim, Tania; Jiang, Ya-Ping; Harleton, Erin; Feinmark, Steven J; Lin, Richard Z; Coronel, Ruben; Janse, Michiel J; Opthof, Tobias; Rosen, Tove S; Cohen, Ira S; Rosen, Michael R

2016-04-01

Drugs are screened for delayed rectifier potassium current (IKr) blockade to predict long QT syndrome prolongation and arrhythmogenesis. However, single-cell studies have shown that chronic (hours) exposure to some IKr blockers (eg, dofetilide) prolongs repolarization additionally by increasing late sodium current (INa-L) via inhibition of phosphoinositide 3-kinase. We hypothesized that chronic dofetilide administration to intact dogs prolongs repolarization by blocking IKr and increasing INa-L. We continuously infused dofetilide (6-9 μg/kg bolus+6-9 μg/kg per hour IV infusion) into anesthetized dogs for 7 hours, maintaining plasma levels within the therapeutic range. In separate experiments, myocardial biopsies were taken before and during 6-hour intravenous dofetide infusion, and the level of phospho-Akt was determined. Acute and chronic dofetilide effects on action potential duration (APD) were studied in canine left ventricular subendocardial slabs using microelectrode techniques. Dofetilide monotonically increased QTc and APD throughout 6.5-hour exposure. Dofetilide infusion during ≥210 minutes inhibited Akt phosphorylation. INa-L block with lidocaine shortened QTc and APD more at 6.5 hours than at 50 minutes (QTc) or 30 minutes (APD) dofetilide administration. In comparison, moxifloxacin, an IKr blocker with no effects on phosphoinositide 3-kinase and INa-L prolonged APD acutely but no additional prolongation occurred on chronic superfusion. Lidocaine shortened APD equally during acute and chronic moxifloxacin superfusion. Increased INa-L contributes to chronic dofetilide effects in vivo. These data emphasize the need to include time and INa-L in evaluating the phosphoinositide 3-kinase inhibition-derived proarrhythmic potential of drugs and provide a mechanism for benefit from lidocaine administration in clinical acquired long QT syndrome. © 2016 American Heart Association, Inc.

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.

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.

21 CFR 20.1 - Testimony by Food and Drug Administration employees.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Testimony by Food and Drug Administration employees. 20.1 Section 20.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... laws administered by the Food and Drug Administration, shall give any testimony before any tribunal...

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

Early lessons from schistosomiasis mass drug administration programs

PubMed Central

Secor, W. Evan

2015-01-01

Mass drug administration using praziquantel is the backbone of the current strategy for the control of schistosomiasis. As the theoretical plans have moved into practical application, certain challenges with this approach have surfaced, and it is likely that annual mass drug administration alone may not be sufficient to achieve program goals. However, mass drug administration is still the only available intervention that can be readily used in the wide variety of settings where schistosomiasis is endemic. The task then becomes how to improve this approach and identify what adjuncts to mass drug administration are effective, as programs move from morbidity control to elimination goals. Other aspects worthy of consideration include how best to employ new diagnostic tools to more easily identify where treatment is needed, and new formulations of praziquantel to extend the availability of treatment to all age groups. The aim of this review is to highlight both areas of challenge and of opportunity to improve the public health impact of schistosomiasis control programs. PMID:26937275

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

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

78 FR 6824 - Considerations Regarding Food and Drug Administration Review and Regulation of Drugs for the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-31

... Amyotrophic Lateral Sclerosis; Public Hearing AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public hearing; request for comments. SUMMARY: The Food and Drug Administration (FDA or the Agency) is... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0035...

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0124] 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...

[Innovative therapeutic strategies for intravesical drug administration].

PubMed

Moch, C; Salmon, D; Rome, P; Marginean, R; Pivot, C; Colombel, M; Pirot, F

2013-05-01

Perspectives for innovative pharmaceutical molecules and intravesical administration of pharmacological agents are presented in the present review carried out from a recent literature. This review of the literature was built by using the PubMed and ScienceDirect databases running 20keywords revealing 34publications between 1983 and 2012. The number of referenced articles on ScienceDirect has increased in recent years, highlighting the interest of scientists for intravesical drug administration and the relevance of innovating drug delivery systems. Different modalities of intravesical administration using physical (e.g., iontophoresis, electroporation) or chemical techniques (e.g., enzyme, solvent, nanoparticles, liposomes, hydrogels) based on novel formulation methods are reported. Finally, the development of biopharmaceuticals (e.g., bacillus Calmette-Guérin, interferon α) and gene therapies is also presented and analyzed in this review. The present review exhibits new development in the pipeline for emerging intravesical drug administration strategies. Knowledge of all these therapies allows practitioners to propose a specific and tailored treatment to each patient with limiting systemic side effects. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Individual Differences in Initial Sensitivity and Acute Tolerance Predict Patterns of Chronic Drug Tolerance to Nitrous-Oxide-Induced Hypothermia in Rats

PubMed Central

Ramsay, Douglas S.; Kaiyala, Karl J.; Leroux, Brian G.; Woods, Stephen C.

2006-01-01

Rationale: A preventive strategy for drug addiction would benefit from being able to identify vulnerable individuals. Understanding how an individual responds during an initial drug exposure may be useful for predicting how that individual will respond to repeated drug administrations. Objectives: This study investigated whether individual differences in initial drug sensitivity and acute tolerance can predict how chronic tolerance develops. Methods: During an initial 3-h administration of 60% nitrous oxide (N2O), male Long-Evans rats were screened for N2O’s hypothermic effect into subsets based on being initially insensitive (II), sensitive with acute tolerance (AT), or sensitive with no intrasessional recovery (NR). Animals in each individual difference category were randomly assigned to receive six 90-min exposures of either 60% N2O or placebo gas. Core temperature was measured telemetrically. Results: Rats that exhibited a comparable degree of hypothermia during an initial N2O exposure, but differed in acute tolerance development, developed different patterns of chronic tolerance. Specifically, the NR group did not become fully tolerant over repeated N2O exposures while the AT group developed an initial hyperthermia followed by a return of core temperature to control levels indicative of full tolerance development. By the second N2O exposure, the II group breathing N2O became hyperthermic relative to the placebo control group and this hyperthermia persisted throughout the multiple N2O exposures. Conclusions: Individual differences in initial drug sensitivity and acute tolerance development predict different patterns of chronic tolerance. The hypothesis is suggested that individual differences in opponent adaptive responses may mediate this relationship. PMID:15778887

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 management...

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 management...

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 management...

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 management...

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 management...

Co-administration of pentoxifylline and thiopental causes death by acute pulmonary oedema in rats

PubMed Central

Pereda, J; Gómez-Cambronero, L; Alberola, A; Fabregat, G; Cerdá, M; Escobar, J; Sabater, L; García-de-la-Asuneión, J; Viña, J; Sastre, J

2006-01-01

Background and purpose: Pentoxifylline exhibits rheological properties that improve microvascular flow and it is widely used in vascular perfusion disorders. It also exhibits marked anti-inflammatory properties by inhibiting tumour necrosis factor α production. Thiopental is one of the most widely used drugs for rapid induction of anaesthesia. During experimental studies on the treatment of acute pancreatitis, we observed that when pentoxifylline was administered after anaesthesia with thiopental, most of the rats exhibited dyspnea, signs of pulmonary oedema and died. The aim of the work described here was to investigate the cause of the unexpected toxic effect of the combined treatment with thiopental and pentoxifylline. Experimental approach: Pulmonary vascular permeability and arterial blood gases were measured, and a histological analysis was performed. The possible role of haemodynamic changes in the formation of pulmonary oedema was also assessed. Key results: Co-administration of pentoxifylline and thiopental increased pulmonary vascular permeability and markedly decreased arterial pO2, with one third of rats suffering from hypoxemia. This combined treatment caused death by acute pulmonary oedema in 27% of normal rats and aggravated the respiratory insufficiency associated with acute pancreatitis in which the mortality rate increased to 60%. This pulmonary oedema was not mediated by cardiac failure or by pulmonary hypertension. Conclusions and Implications: Co-administration of pharmacological doses of pentoxifylline and thiopental caused pulmonary oedema and death in rats. Consequently, pentoxifylline should not be administered when anaesthesia is induced with thiopental to avoid any possible risk of acute pulmonary oedema and death in humans. PMID:16953192

Dopamine D3 receptor antagonist SB-277011A inhibits methamphetamine self-administration and methamphetamine-induced reinstatement of drug-seeking in rats

PubMed Central

Higley, Amanda E.; Kiefer, Stephen W.; Li, Xia; Gaál, József; Xi, Zheng-Xiong; Gardner, Eliot L.

2013-01-01

We have previously reported that selective blockade of brain dopamine D3 receptors by SB-277011A significantly attenuates cocaine self-administration and cocaine-induced reinstatement of drug-seeking behavior. In the present study, we investigated whether SB-277011A similarly inhibits methamphetamine self-administration and methamphetamine-induced reinstatement to drug-seeking behavior. Male Long–Evans rats were allowed to intravenously self-administer methamphetamine (0.05 mg/kg/infusion) under fixed-ratio 2 (FR2) or progressive-ratio (PR) reinforcement conditions, and some rats were tested for methamphetamine-induced reinstatement of drug-seeking behavior after extinction of self-administration. The effects of SB-277011A on each of these methamphetamine-supported behaviors were then tested. Acute intraperitoneal (i.p.) administration of SB-277011A failed to alter methamphetamine self-administration under FR2 reinforcement, but significantly lowered the break-point for methamphetamine self-administration under PR reinforcement. SB-277011A also significantly inhibited methamphetamine-triggered reinstatement of extinguished drug-seeking behavior. Overall, these data show that blockade of dopamine D3 receptors by SB-277011A attenuates the rewarding and incentive motivational effects of methamphetamine in rats, supporting the development of selective dopamine D3 antagonists for the treatment of methamphetamine addiction. PMID:21466803

Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers.

PubMed

Martin-Santos, R; Crippa, J A; Batalla, A; Bhattacharyya, S; Atakan, Z; Borgwardt, S; Allen, P; Seal, M; Langohr, K; Farré, M; Zuardi, A W; McGuire, P K

2012-01-01

Animal and humans studies suggest that the two main constituents of cannabis sativa, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have quite different acute effects. However, to date the two compounds have largely been studied separately. To evaluate and compare the acute pharmacological effects of both THC and CBD in the same human volunteers. A randomised, double-blind, cross-over, placebo controlled trial was conducted in 16 healthy male subjects. Oral THC 10 mg or CBD 600 mg or placebo was administered in three consecutive sessions, at one-month interval. Physiological measures and symptom ratings were assessed before, and at 1, 2 and 3 hours post drug administration. The area under the curve (AUC) between baseline and 3 hours, and the maximum absolute change from baseline at 2 hours were analysed by one-way repeated measures analysis of variance, with drug condition (THC or CBD or placebo) as the factor. Relative to both placebo and CBD, administration of THC was associated with anxiety, dysphoria, positive psychotic symptoms, physical and mental sedation, subjective intoxication (AUC and effect at 2 hours: p < 0.01), an increase in heart rate (p < 0.05). There were no differences between CBD and placebo on any symptomatic, physiological variable. In healthy volunteers, THC has marked acute behavioural and physiological effects, whereas CBD has proven to be safe and well tolerated.

[Preparation and administration of cytotoxic drugs: prickly innovation].

PubMed

Mullot, H; Simon, L; Payen, C; Gentes, P

2005-06-01

The requirement for safe and optimal administration of cytotoxic drugs led us to test a new product manufactured by Codan. The transfer set (CONNECT SET) and the administration set (CYTO-AD-SET) were assessed successively by pharmacist assistance within a centralized unit for cytotoxic drug preparation and by the nursing staff in an ambulatory unit. Transfer sets can be handled in the centralized units without using needles, but with an increased sterilization load and production cost. Assessment of the administration sets demonstrated time saving for the nursing staff. These materials require significant expenditures, careful training, and a change in treatment routine, but provide important time savings for the nursing staff and considerable improvement in the safety of handling cytotoxic drugs.

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0196] 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...

Idiosyncratic drug-induced agranulocytosis or acute neutropenia.

PubMed

Andrès, Emmanuel; Maloisel, Frédéric

2008-01-01

Idiosyncratic drug-induced agranulocytosis or acute neutropenia is an adverse event resulting in a neutrophil count of under 0.5 x 10/l. Patients with such severe neutropenia are likely to experience life-threatening and sometimes fatal infections. Over the last 20 years, the incidence of idiosyncratic drug-induced agranulocytosis or acute neutropenia has remained stable at 2.4-15.4 cases per million, despite the emergence of new causative drugs: antibiotics (beta-lactam and cotrimoxazole), antiplatelet agents (ticlopidine), antithyroid drugs, sulfasalazine, neuroleptics (clozapine), antiepileptic agents (carbamazepine), nonsteroidal anti-inflammatory agents and dipyrone. Drug-induced agranulocytosis remains a serious adverse event due to the occurrence of severe sepsis with severe deep infections (such as pneumonia), septicemia and septic shock in around two thirds of patients. In this setting, old age (>65 years), septicemia or shock, metabolic disorders such as renal failure, and a neutrophil count under 0.1 x 10/l are poor prognostic factors. Nevertheless with appropriate management using preestablished procedures, with intravenous broad-spectrum antibiotic therapy and hematopoietic growth factors, the mortality rate is currently around 5%. Given the increased life expectancy and subsequent longer exposure to drugs, as well as the development of new agents, healthcare professionals should be aware of this adverse event and its management.

Acute and subchronic administration of anandamide or oleamide increases REM sleep in rats.

PubMed

Herrera-Solís, Andrea; Vásquez, Khalil Guzmán; Prospéro-García, Oscar

2010-03-01

Anandamide and oleamide, induce sleep when administered acutely, via the CB1 receptor. Their subchronic administration must be tested to demonstrate the absence of tolerance to this effect, and that the sudden withdrawal of these endocannabinoids (eCBs) does not affect sleep negatively. The sleep-waking cycle of rats was evaluated for 24h, under the effect of an acute or subchronic administration of eCBs, and during sudden eCBs withdrawal. AM251, a CB1 receptor antagonist (CB1Ra) was utilized to block eCBs effects. Our results indicated that both acute and subchronic administration of eCBs increase REMS. During eCBs withdrawal, rats lack the expression of an abstinence-like syndrome. AM251 was efficacious to prevent REMS increase caused by both acute and subchronic administration of these eCBs, suggesting that this effect is mediated by the CB1 receptor. Our data further support a role of the eCBs in REMS regulation. (c) 2009 Elsevier Inc. All rights reserved.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] 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...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] 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...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] 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...

[Pharmaceutical revision of hospital drug administration].

PubMed

Smith-Meyer, Ellen; Bjørneklett, Arvid; Swärd, Elisabeth; Refsum, Nina

2002-01-20

Quality audits of the implementation of drug administration procedures are carried out in order to determine objectively to what extent implementation conforms to procedures. Since September 1997, the pharmacy at Rikshospitalet University Hospital in Norway has performed quality audits of drug administration at the hospital, using interviews and surveys. Staff members in the audited unit and the auditing pharmacist agree on prospects for quality improvements and review possible action. A survey was carried out in the autumn of 2000 in order to determine staff opinion of the quality audits. On the basis of the observations made, improvements have been carried out at all levels of the organisation. The survey indicates that hospital staff members are satisfied with the quality audits performed by the pharmacy.

78 FR 36711 - Food and Drug Administration Safety and Innovation Act Title VII-Drug Supply Chain; Standards for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-19

...: Food and Drug Administration, HHS. ACTION: Notification of public meeting; request for comments. SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing a public meeting regarding FDA's... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I [Docket Nos...

Suspected drug-induced infiltrative lung disease culminating in acute respiratory failure in a dog treated with cytarabine and prednisone.

PubMed

Hart, Samantha K; Waddell, Lori

2016-11-01

To describe a case of suspected drug-induced infiltrative lung disease (ILD) and acute respiratory failure associated with the administration of cytarabine and prednisone in a dog requiring mechanical ventilation. A 4.5-year-old, female spayed Yorkshire Terrier presented to the ICU with acute onset of respiratory distress following a 24-hour cytarabine infusion. The patient was previously diagnosed with meningoencephalitis of unknown etiology (MUO), caudal occipital malformation, and syringohydromyelia, and was being treated with oral prednisone and levetiracetam, and cytarabine infusions. The patient developed tachypnea and dyspnea, and had diffuse crackles on auscultation of all lung fields, and hypoxemia 6 hours following completion of the fourth cytarabine infusion (300 mg/m 2 ). Thoracic radiographs revealed diffuse, bilateral infiltrates consistent with noncardiogenic pulmonary edema or acute respiratory distress syndrome. Respiratory distress and hypoxemia persisted despite oxygen supplementation and furosemide therapy and led to initiation of mechanical ventilation. Approximately 12 hours later, the dog became progressively hypoxemic with worsening pulmonary edema. The owners elected euthanasia. Postmortem examination revealed pulmonary edema and diffuse interstitial pneumonia. Histopathologic evaluation revealed pulmonary edema, severe acute neutrophilic and histiocytic pneumonia, and multifocal interstitial fibrosis. Bacterial culture yielded no growth. Drug-induced ILD is rarely reported in the veterinary literature, and has not previously been reported in dogs receiving cytarabine. As with administration of any medication, adverse events may occur. While ILD is unlikely to be commonly recognized, it may be considered in veterinary patients receiving chemotherapy that acutely become dyspneic. © Veterinary Emergency and Critical Care Society 2016.

75 FR 34464 - Memorandum of Understanding Between the Food and Drug Administration and Drugs.Com; Correction of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0004] FDA 225-09-0012 Memorandum of Understanding Between the Food and Drug Administration and Drugs.Com... date of the memorandum of understanding (MOU) between FDA and Drugs.Com that published in the Federal...

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

...] Society of Clinical Research Associates-Food and Drug Administration: Food and Drug Administration... an educational conference co-sponsored with the Society of Clinical Research Associates (SOCRA). The...: 510-287-2739; or Society of Clinical Research Associates (SOCRA), 530 West Butler Ave., Suite 109...

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. 874.5220 Section 874.5220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5220 Ear, nose...

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. 874.5220 Section 874.5220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5220 Ear, nose...

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ear, nose, and throat drug administration device. 874.5220 Section 874.5220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5220 Ear, nose...

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. 874.5220 Section 874.5220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5220 Ear, nose...

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

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ear, nose, and throat drug administration device. 874.5220 Section 874.5220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5220 Ear, nose...

Discrete-choice modelling of patient preferences for modes of drug administration.

PubMed

Tetteh, Ebenezer Kwabena; Morris, Steve; Titcheneker-Hooker, Nigel

2017-12-01

The administration of (biologically-derived) drugs for various disease conditions involves consumption of resources that constitutes a direct monetary cost to healthcare payers and providers. An often ignored cost relates to a mismatch between patients' preferences and the mode of drug administration. The "intangible" benefits of giving patients what they want in terms of the mode of drug delivery is seldom considered. This study aims to evaluate, in monetary terms, end-user preferences for the non-monetary attributes of different modes of drug administration using a discrete-choice experiment. It provides empirical support to the notion that there are significant benefits from developing patient-friendly approaches to drug delivery. The gross benefits per patient per unit administration is in the same order of magnitude as the savings in resource costs of administering drugs. The study argues that, as long as the underlying manufacturing science is capable, a patient-centred approach to producing drug delivery systems should be encouraged and pursued.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0790] Food and Drug Administration Decisions for Investigational Device Exemption Clinical Investigations; Draft Guidance for Industry and Food and Drug Administration Staff; Availability AGENCY: Food and Drug...

21 CFR 20.2 - Production of records by Food and Drug Administration employees.

Code of Federal Regulations, 2010 CFR

2010-04-01

... upon an officer or employee of the Food and Drug Administration commanding the production of any record... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Production of records by Food and Drug Administration employees. 20.2 Section 20.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

Adverse drug event monitoring at the Food and Drug Administration.

PubMed

Ahmad, Syed Rizwanuddin

2003-01-01

The Food and Drug Administration (FDA) is responsible not only for approving drugs but also for monitoring their safety after they reach the market. The complete adverse event profile of a drug is not known at the time of approval because of the small sample size, short duration, and limited generalizability of pre-approval clinical trials. This report describes the FDA's postmarketing surveillance system, to which many clinicians submit reports of adverse drug events encountered while treating their patients. Despite its limitations, the spontaneous reporting system is an extremely valuable mechanism by which hazards with drugs that were not observed or recognized at the time of approval are identified. Physicians are strongly encouraged to submit reports of adverse outcomes with suspect drugs to the FDA, and their reports make a difference. The FDA is strengthening its postmarketing surveillance with access to new data sources that have the potential to further improve the identification, quantification, and subsequent management of drug risk.

Adverse Drug Event Monitoring at the Food and Drug Administration

PubMed Central

Ahmad, Syed Rizwanuddin

2003-01-01

The Food and Drug Administration (FDA) is responsible not only for approving drugs but also for monitoring their safety after they reach the market. The complete adverse event profile of a drug is not known at the time of approval because of the small sample size, short duration, and limited generalizability of pre-approval clinical trials. This report describes the FDA's postmarketing surveillance system, to which many clinicians submit reports of adverse drug events encountered while treating their patients. Despite its limitations, the spontaneous reporting system is an extremely valuable mechanism by which hazards with drugs that were not observed or recognized at the time of approval are identified. Physicians are strongly encouraged to submit reports of adverse outcomes with suspect drugs to the FDA, and their reports make a difference. The FDA is strengthening its postmarketing surveillance with access to new data sources that have the potential to further improve the identification, quantification, and subsequent management of drug risk. PMID:12534765

Effects of acute and chronic methamphetamine administration on cynomolgus monkey hippocampus structure and cellular transcriptome.

PubMed

Choi, Mi Ran; Chun, Ji-Won; Kwak, Su Min; Bang, Sol Hee; Jin, Yeung-Bae; Lee, Youngjeon; Kim, Han-Na; Chang, Kyu-Tae; Chai, Young Gyu; Lee, Sang-Rae; Kim, Dai-Jin

2018-05-23

Methamphetamine (MA), a psychostimulant abused worldwide, gives rise to neurotoxicity in the hippocampus, resulting in cognitive impairments and hippocampal volume reduction. The cellular and molecular mechanisms associated with hippocampal impairments due to MA remain unknown. The aim of this study was to investigate the effects of MA on structural alterations and gene expressions in the hippocampus. We analyzed the pattern of volumetric changes in the hippocampus using magnetic resonance imaging (MRI) after acute and chronic administration of MA to cynomolgus macaques. In addition, we performed large-scale transcriptome profiling in the hippocampus using RNA-Seq technology. The hippocampus in response to acute and chronic MA exhibited a significant volumetric atrophy compared with the hippocampus of controls. The genes associated with cytoskeleton organization and phagocytosis were downregulated in the acute MA-treated group compared to the control group. On the other hand, genes associated with synaptic transmission, regulation of neuron differentiation and regulation of neurogenesis were downregulated in the chronic MA-treated group. We confirmed that expression patterns for ADM, BMP4, CHRD, PDYN, UBA1, profilin 2 (PFN2), ENO2 and NSE mRNAs were similar to the results from RNA-Seq based on quantitative RT-PCR. In particular, PFN2 mRNA and protein expression levels, which play important roles in actin cytoskeleton dynamics, were decreased by acute and chronic MA administration. These results not only aid the understanding of cellular and molecular mechanisms regulated by MA in the hippocampus but also suggest basic information aiding biomarker and novel drug development for treating hippocampal impairment caused by MA abuse. Copyright © 2017. Published by Elsevier Inc.

Pharmacokinetics of rectal drug administration, Part I. General considerations and clinical applications of centrally acting drugs.

PubMed

van Hoogdalem, E; de Boer, A G; Breimer, D D

1991-07-01

Generally, oral administration is the route of choice in the daily practice of pharmacotherapy. However, in some circumstances this is impractical or even impossible (during nausea and vomiting or convulsions, in uncooperative patients and before surgery). In these cases, the rectal route may represent a practical alternative and rectal administration is now well accepted for delivering, for example, anticonvulsants, non-narcotic and narcotic analgesics, theophylline, antiemetics and antibacterial agents, and for inducing anaesthesia in children. It may also represent an interesting alternative to intravenous or other injection routes of drug administration. The rate and extent of rectal drug absorption are often lower than with oral absorption, possibly an inherent factor owing to the relatively small surface area available for drug uptake. In addition, the composition of the rectal formulation (solid vs liquid, nature of the suppository base) appears to be an important factor in the absorption process by determining the pattern of drug release. This relation between formulation and drug uptake has been clearly demonstrated for drugs like diazepam, paracetamol (acetaminophen), indomethacin, methadone and diflunisal. Coadministration of absorption-promoting agents (surfactants, sodium salicylate, enamines) represents another approach towards manipulating rectal drug absorption, although this concept requires further research concerning both efficacy and safety. For a number of drugs the extent of rectal absorption has been reported to exceed oral values, which may reflect partial avoidance of hepatic first-pass metabolism after rectal delivery. This phenomenon has been reported for morphine, metoclopramide, ergotamine, lidocaine (lignocaine) and propranolol. Rectal drug delivery in a site- and rate-controlled manner using osmotic pumps or hydrogel formulations may provide opportunities for manipulating systemic drug concentrations and drug effects. The extent of

T-cell involvement in drug-induced acute generalized exanthematous pustulosis

PubMed Central

Britschgi, Markus; Steiner, Urs C.; Schmid, Simone; Depta, Jan P.H.; Senti, Gabriela; Bircher, Andreas; Burkhart, Christoph; Yawalkar, Nikhil; Pichler, Werner J.

2001-01-01

Acute generalized exanthematous pustulosis (AGEP) is an uncommon eruption most often provoked by drugs, by acute infections with enteroviruses, or by mercury. It is characterized by acute, extensive formation of nonfollicular sterile pustules on erythematous background, fever, and peripheral blood leukocytosis. We present clinical and immunological data on four patients with this disease, which is caused by different drugs. An involvement of T cells could be implied by positive skin patch tests and lymphocyte transformation tests. Immunohistochemistry revealed a massive cell infiltrate consisting of neutrophils in pustules and T cells in the dermis and epidermis. Expression of the potent neutrophil-attracting chemokine IL-8 was elevated in keratinocytes and infiltrating mononuclear cells. Drug-specific T cells were generated from the blood and skin of three patients, and phenotypic characterization showed a heterogeneous distribution of CD4/CD8 phenotype and of T-cell receptor Vβ-expression. Analysis of cytokine/chemokine profiles revealed that IL-8 is produced significantly more by drug-specific T cells from patients with AGEP compared with drug-specific T cells from patients that had non-AGEP exanthemas. In conclusion, our data demonstrate the involvement of drug-specific T cells in the pathomechanism of this rather rare and peculiar form of drug allergy. In addition, they indicate that even in some neutrophil-rich inflammatory responses specific T cells are engaged and might orchestrate the immune reaction. PMID:11390425

Psychosis associated with acute recreational drug toxicity: a European case series.

PubMed

Vallersnes, Odd Martin; Dines, Alison M; Wood, David M; Yates, Christopher; Heyerdahl, Fridtjof; Hovda, Knut Erik; Giraudon, Isabelle; Dargan, Paul I

2016-08-18

Psychosis can be associated with acute recreational drug and novel psychoactive substance (NPS) toxicity. However, there is limited data available on how common this is and which drugs are most frequently implicated. We describe a European case series of psychosis associated with acute recreational drug toxicity, and estimate the frequency of psychosis for different recreational drugs. The European Drug Emergencies Network (Euro-DEN) collects data on presentations to Emergency Departments (EDs) with acute recreational drug and NPS toxicity at 16 centres in ten countries. Euro-DEN data from October 2013 through September 2014 was retrospectively searched, and cases with psychosis were included. The proportion of cases with psychosis per drug was calculated in the searched Euro-DEN dataset. Psychosis was present in 348 (6.3 %) of 5529 cases. The median (interquartile range) age was 29 (24-38) years, 276 (79.3 %) were male and 114 (32.8 %) were admitted to psychiatric ward. The drugs most commonly reported were cannabis in 90 (25.9 %) cases, amphetamine in 87 (25.0 %) and cocaine in 56 (16.1 %). More than one drug was taken in 189 (54.3 %) cases. Psychosis was frequent in those ED presentations involving tryptamines (4/7; 57.1 %), methylenedioxypyrovalerone (MDPV) (6/22; 27.3 %), methylphenidate (6/26; 23.1 %), lysergic acid diethylamide (LSD) (18/86; 20.9 %), psilocybe mushrooms (3/16; 18.8 %), synthetic cannabinoid receptor agonists (4/26; 15.4 %) and amphetamine (87/593; 14.7 %), but less common in those involving mephedrone (14/245; 5.7 %), methylenedioxymethamphetamine (MDMA) (20/461; 4.3 %) and methedrone (3/92; 3.3 %). Amphetamine was the most frequent drug associated with psychosis when only one agent was reported, with psychosis occurring in 32.4 % of these presentations. The frequency of psychosis in acute recreational drug toxicity varies considerably between drugs, but is a major problem in amphetamine poisoning. In rapidly changing drug markets and

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 14, and 17 [Docket No. FDA-2010-N-0560] 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...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 14, and 17 [Docket No. FDA-2010-N-0560] 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...

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

Code of Federal Regulations, 2010 CFR

2010-04-01

... Administration records. 20.20 Section 20.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... the record will be so used, may be requested when: (1) The requested record is contained in a Privacy... Administration records. (a) The Food and Drug Administration will make the fullest possible disclosure of records...

78 FR 30317 - Science Board to the Food and Drug Administration; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-22

...] Science Board to the Food and Drug Administration; Notice of Meeting AGENCY: Food and Drug Administration... Food and Drug Administration (FDA). The meeting will be open to the public. Name of Committee: Science Board to the Food and Drug Administration (Science Board). General Function of the Committee: The...

78 FR 6332 - Science Board to the Food and Drug Administration; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-30

...] Science Board to the Food and Drug Administration; Notice of Meeting AGENCY: Food and Drug Administration... Food and Drug Administration (FDA). The meeting will be open to the public. Name of Committee: Science Board to the Food and Drug Administration (Science Board). General Function of the Committee: The...

77 FR 51031 - Science Board to the Food and Drug Administration; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-23

...] Science Board to the Food and Drug Administration; Notice of Meeting AGENCY: Food and Drug Administration... Food and Drug Administration (FDA). The meeting will be open to the public. Name of Committee: Science Board to the Food and Drug Administration (Science Board). General Function of the Committee: The...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No FDA-2012-N-0001] Science Board to the Food and Drug Administration; Notice of Meeting AGENCY: Food and Drug Administration... Food and Drug Administration (FDA). The meeting will be open to the public. Name of Committee: Science...

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. Copyright © 2015 by the American Society of Nephrology.

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0080... Food and Drug Administration (FDA) is announcing the availability of a draft guidance entitled ``FDA... that address nearly all aspects of the FDA approval and surveillance processes, including application...

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0080... and Drug Administration (FDA) is announcing the availability of a guidance entitled ``FDA Oversight of... nearly all aspects of the FDA approval and surveillance processes, including application submission...

[Enteral nutrition: drug administration via feeding tube].

PubMed

Behnken, I; Gaschott, T; Stein, J

2005-11-01

Enteral nutrition support via a feeding tube is a preferred and broadly applied way of artificial nutrition in patients who cannot take up orally an adequate amount of nutrients. These patients often need simultaneous drug therapy as well. Thus, there is a high risk of drug-nutrient interactions. Although enteral nutrition is commonly used there is a lack of awareness and knowledge about the appropriate handling and drug administration via the feeding tube. On the one hand, drug-nutrient interactions can lead to clogging of the tube, on the other hand, the change in bioavailability of the drug can have a direct effect on the therapeutic effort. To optimise safety and efficacy of drug therapy in patients with feeding tubes, some basic rules have been set up.

Effect of Antiepileptic Drugs for Acute and Chronic Seizures in Children with Encephalitis.

PubMed

Lin, Kuang-Lin; Lin, Jainn-Jim; Hsia, Shao-Hsuan; Chou, Min-Liang; Hung, Po-Cheng; Wang, Huei-Shyong

2015-01-01

Encephalitis presents with seizures in the acute phase and increases the risk of late unprovoked seizures and epilepsy. This study aimed to evaluate the effect of antiepileptic drugs in pediatric patients with acute seizures due to encephalitis and epilepsy. Cases of acute pediatric encephalitis between January 2000 and December 2010 were reviewed. Clinical data, including onset at age, seizure type, seizure frequency, effects of antiepileptic drugs, and prognosis were analyzed. During the study period, 1038 patients (450 girls, 588 boys) were enrolled. Among them, 44.6% (463) had seizures in the acute phase, 33% had status epilepticus, and 26% (251) developed postencephalitic epilepsy. At one year of follow-up, 205 of the 251 patients with postencephalitic epilepsy were receiving antiepileptic drugs while 18% were seizure free even after discontinuing the antiepileptic drugs. Among those with postencephalitic epilepsy, 67% had favorable outcomes and were using <2 anti-epileptic drugs while 15% had intractable seizures and were using ≥ 2 antiepileptic drugs. After benzodiazepines, intravenous phenobarbital was preferred over phenytoin as treatment of postencephalitic seizures in the acute phase. For refractory status epilepticus, high-dose topiramate combined with intravenous high-dose phenobarbital or high-dose lidocaine had less side effects. Children with encephalitis have a high rate of postencephalitic epilepsy. Phenobarbital and clonazepam are the most common drugs used, alone or in combination, for postencephalitic epilepsy.

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

Effects of acute buspirone administration on inhibitory control and sexual discounting in cocaine users.

PubMed

Strickland, Justin C; Bolin, B Levi; Romanelli, Michael R; Rush, Craig R; Stoops, William W

2017-01-01

Cocaine users display deficits in inhibitory control and make impulsive choices that may increase risky behavior. Buspirone is an anxiolytic that activates dopaminergic and serotonergic systems and improves impulsive choice (i.e., reduces sexual risk-taking intent) in cocaine users when administered chronically. We evaluated the effects of acutely administered buspirone on inhibitory control and impulsive choice. Eleven subjects with a recent history of cocaine use completed this within-subject, placebo-controlled study. Subjects performed two cued go/no-go and a sexual risk delay-discounting task following oral administration of buspirone (10 and 30 mg), triazolam (0.375 mg; positive control), and placebo (negative control). Physiological and psychomotor performance and subject-rated data were also collected. Buspirone failed to change inhibitory control or impulsive choice; however, slower reaction times were observed at the highest dose tested. Buspirone did not produce subject-rated drug effects but dose-dependently decreased diastolic blood pressure. Triazolam impaired psychomotor performance and increased ratings of positive subject-rated effects (e.g., Like Drug). These findings indicate that acutely administered buspirone has little impact on behavioral measures of inhibitory control and impulsive sexual decision-making. Considering previous findings with chronic dosing, these findings highlight that the behavioral effects of buspirone differ as a function of dosing conditions. Copyright © 2017 John Wiley & Sons, Ltd.

Acute epigastric and low back pain during amiodarone infusion; is it the drug or the vehicle to blame?

PubMed

Petrou, Emmanouil; Iakovou, Ioannis; Boutsikou, Maria; Girasis, Chrysafios; Mavrogeni, Sophie; Pavlides, Gregory

2014-01-01

Amiodarone is a Class III antiarrhythmic agent used for cardioversion and prevention of recurrences of atrial fibrillation. However, its use is limited due to its side-effects resulting from the drug's long-term administration. We have described acute epigastric pain following treatment with intravenous amiodarone for atrial fibrillation in a previous report. Hereby, we describe a second patient who suffered acute epigastric pain, as well as one who suffered acute low back pain. Intravenous amiodarone has been related to a series of minor and major adverse reactions, indicating other constituents of the intravenous solution as the possible cause, possibly polysorbate-80. A possible correlation between acute epigastric and low back pain after intravenous amiodarone loading is unproven; however it is of crucial importance for clinicians to be aware of this phenomenon, and especially since an acute epigastric pain is implicated in the differential diagnosis of cardiac ischemia. Copyright © 2014 Elsevier Inc. All rights reserved.

Cost effectiveness of drug-eluting stents in acute myocardial infarction patients in Germany: results from administrative data using a propensity score-matching approach.

PubMed

Bäumler, Michael; Stargardt, Tom; Schreyögg, Jonas; Busse, Reinhard

2012-07-01

The high number of patients with acute myocardial infarction (AMI) has facilitated greater research, resulting in the development of innovative medical devices. So far, results from economic evaluations that compared drug-eluting stents (DES) and bare-metal stents (BMS) have not shown clear evidence that one intervention is more cost effective than the other. The aim of this study was to measure the cost effectiveness of DES compared with BMS in routine care. We used administrative data from a large German sickness fund to compare the costs and effectiveness of DES and BMS in patients with AMI. Patients with hospital admission after AMI in 2004 and 2005 were followed up for 1 year after hospital discharge. The cost of treatment and survival after 365 days were compared for patients treated with DES and BMS. We adjusted for covariates defined according to the Ontario Acute Myocardial Infarction Mortality Prediction Rules using propensity score matching. After matching, we calculated incremental cost-effectiveness ratios (ICERs) by (i) using sample means based on bootstrapping procedures and (ii) estimating generalized linear mixed models for costs and survival. After propensity score matching, the sample included 719 patients treated with DES and 719 patients treated with BMS. A comparison of sample means resulted in average costs of € 12 714 and € 11 714 for DES and BMS, respectively, in 2005 German euros. Difference in 365-day survival was not statistically significant (700 patients with DES and 701 with BMS). The ICER of DES versus BMS was -€ 718 709 per life saved. Bootstrapping resulted in DES being dominated by BMS in 54.5% of replications and DES being a dominant strategy in 2.7% of replications. Results from regression models and sensitivity analyses confirm these results. Treatment with DES after admission with AMI is less cost effective than treatment with BMS. Our results are in line with other cost-effectiveness analyses that used administrative

Accuracy of manual entry of drug administration data into an anesthesia information management system.

PubMed

Avidan, Alexander; Dotan, Koren; Weissman, Charles; Cohen, Matan J; Levin, Phillip D

2014-11-01

Data on drug administration are entered manually into anesthesia information management systems (AIMS). This study examined whether these data are accurate regarding drug name, dose administered, and time of administration, and whether the stage of anesthesia influences data accuracy. Real-time observational data on drug administration during elective operations were compared with computerized information on drug administration entered by anesthesiologists. A trained observer (K.D.) performed the observations. Data were collected during 57 operations which included 596 separate occasions of drug administration by 22 anesthesiologists. No AIMS records were found for 90 (15.1%) occasions of drug administration (omissions), while there were 11 (1.8%) AIMS records where drug administration was not observed. The AIMS and observer data matched for drug name on 495 of 596 (83.1%) occasions, for dose on 439 of 495 (92.5%) occasions, and for time on 476 of 495 (96.2%) occasions. Amongst the 90 omitted records, 34 (37.8%) were for vasoactive drugs with 24 (27.7%) for small doses of hypnotics. Omissions occurred mostly during maintenance: 50 of 153 (24.6%), followed by induction: 30 of 325 (9.2%) and emergence: 10 of 57 (17.5%) (P < 0.001). Time and dose inaccuracies occurred mainly during induction, followed by maintenance and emergence; time inaccuracies were 7/325 (8.3%), 10/203 (4.9%), and 0/57 (0%), respectively (P = 0.07), and dose inaccuracies were 15/325 (4.6%), 3/203 (1.5%), and 1/57 (1.7%), respectively (P = 0.11). The range of accuracy varies when anesthesiologists manually enter drug administration data into an AIMS. Charting omissions represent the largest cause of inaccuracy, principally by omissions of records for vasopressors and small doses of hypnotic drugs. Manually entered drug administration data are not without errors. Accuracy of entering drug administration data remains the responsibility of the anesthesiologist.

Effect of Antiepileptic Drugs for Acute and Chronic Seizures in Children with Encephalitis

PubMed Central

Lin, Kuang-Lin; Lin, Jainn-Jim; Hsia, Shao-Hsuan; Chou, Min-Liang; Hung, Po-Cheng; Wang, Huei-Shyong

2015-01-01

Background Encephalitis presents with seizures in the acute phase and increases the risk of late unprovoked seizures and epilepsy. This study aimed to evaluate the effect of antiepileptic drugs in pediatric patients with acute seizures due to encephalitis and epilepsy. Patients and Methods Cases of acute pediatric encephalitis between January 2000 and December 2010 were reviewed. Clinical data, including onset at age, seizure type, seizure frequency, effects of antiepileptic drugs, and prognosis were analyzed. Results During the study period, 1038 patients (450 girls, 588 boys) were enrolled. Among them, 44.6% (463) had seizures in the acute phase, 33% had status epilepticus, and 26% (251) developed postencephalitic epilepsy. At one year of follow-up, 205 of the 251 patients with postencephalitic epilepsy were receiving antiepileptic drugs while 18% were seizure free even after discontinuing the antiepileptic drugs. Among those with postencephalitic epilepsy, 67% had favorable outcomes and were using <2 anti-epileptic drugs while 15% had intractable seizures and were using ≥ 2 antiepileptic drugs. After benzodiazepines, intravenous phenobarbital was preferred over phenytoin as treatment of postencephalitic seizures in the acute phase. For refractory status epilepticus, high-dose topiramate combined with intravenous high-dose phenobarbital or high-dose lidocaine had less side effects. Conclusions Children with encephalitis have a high rate of postencephalitic epilepsy. Phenobarbital and clonazepam are the most common drugs used, alone or in combination, for postencephalitic epilepsy. PMID:26444013

Hierarchical pulmonary target nanoparticles via inhaled administration for anticancer drug delivery.

PubMed

Chen, Rui; Xu, Liu; Fan, Qin; Li, Man; Wang, Jingjing; Wu, Li; Li, Weidong; Duan, Jinao; Chen, Zhipeng

2017-11-01

Inhalation administration, compared with intravenous administration, significantly enhances chemotherapeutic drug exposure to the lung tissue and may increase the therapeutic effect for pulmonary anticancer. However, further identification of cancer cells after lung deposition of inhaled drugs is necessary to avoid side effects on normal lung tissue and to maximize drug efficacy. Moreover, as the action site of the major drug was intracellular organelles, drug target to the specific organelle is the final key for accurate drug delivery. Here, we designed a novel multifunctional nanoparticles (MNPs) for pulmonary antitumor and the material was well-designed for hierarchical target involved lung tissue target, cancer cell target, and mitochondrial target. The biodistribution in vivo determined by UHPLC-MS/MS method was employed to verify the drug concentration overwhelmingly increasing in lung tissue through inhaled administration compared with intravenous administration. Cellular uptake assay using A549 cells proved the efficient receptor-mediated cell endocytosis. Confocal laser scanning microscopy observation showed the location of MNPs in cells was mitochondria. All results confirmed the intelligent material can progressively play hierarchical target functions, which could induce more cell apoptosis related to mitochondrial damage. It provides a smart and efficient nanocarrier platform for hierarchical targeting of pulmonary anticancer drug. So far, this kind of material for pulmonary mitochondrial-target has not been seen in other reports.

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... 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 Drug Administration operates two public reading rooms. The Freedom of Information Staff's Public Reading Room is...

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

Code of Federal Regulations, 2010 CFR

2010-04-01

... 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 Drug Administration operates two public reading rooms. The Freedom of Information Staff's Public Reading Room is...

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

Vildagliptin-induced acute lung injury: a case report.

PubMed

Ohara, Nobumasa; Kaneko, Masanori; Sato, Kazuhiro; Maruyama, Ryoko; Furukawa, Tomoyasu; Tanaka, Junta; Kaneko, Kenzo; Kamoi, Kyuzi

2016-08-12

Dipeptidyl peptidase-4 inhibitors are a class of oral hypoglycemic drugs and are used widely to treat type 2 diabetes mellitus in many countries. Adverse effects include nasopharyngitis, headache, elevated serum pancreatic enzymes, and gastrointestinal symptoms. In addition, a few cases of interstitial pneumonia associated with their use have been reported in the Japanese literature. Here we describe a patient who developed drug-induced acute lung injury shortly after the administration of the dipeptidyl peptidase-4 inhibitor vildagliptin. A 38-year-old Japanese woman with diabetes mellitus developed acute respiratory failure 1 day after administration of vildagliptin. Chest computed tomography revealed nonsegmental ground-glass opacities in her lungs. There was no evidence of bacterial pneumonia or any other cause of her respiratory manifestations. After discontinuation of vildagliptin, she recovered fully from her respiratory disorder. She received insulin therapy for her diabetes mellitus, and her subsequent clinical course has been uneventful. The period of drug exposure in previously reported cases of patients with drug-induced interstitial pneumonia caused by dipeptidyl peptidase-4 inhibitor varied from several days to over 6 months. In the present case, our patient developed interstitial pneumonia only 1 day after the administration of vildagliptin. The precise mechanism of her vildagliptin-induced lung injury remains uncertain, but physicians should consider that dipeptidyl peptidase-4 inhibitor-induced lung injury, although rare, may appear acutely, even within days after administration of this drug.

Acute Administration of Natural Honey Protects Isolated Heart in Normothermic Ischemia

PubMed Central

Gharekhani, Afshin; Najafi, Moslem; Ghavimi, Hamed

2012-01-01

This study intended to assess the efficacy of acute administration of natural honey on cardiac arrhythmias and infarct size when it is used during the normothermic ischemia in isolated rat heart. During 30 min of regional normothermic ischemia followed by 120 min of reperfusion, the isolated hearts were perfused by a modified drug free Krebs-Henseleit solution (control) or the solution containing 0.125, 0.25, 0.5 and 1% of freshly prepared natural honey (test groups), respectively. Cardiac arrhythmias were analyzed and determined through the recorded ECGs. The infarct size was measured using computerized planimetry package. At the ischemic phase, honey (0.25 and 0.5%) decreased the number and duration of ventricular tachycardia (VT), total number of ventricular ectopic beats (VEBs), duration and incidence of reversible ventricular fibrillation (VF) and total VF (p < 0.05 for all). During the reperfusion, concentrations of 0.125, 0.25 and 0.5% lowered the number of VT (p < 0.05), duration of reversible VF (p < 0.01) and total number of VEBs (p < 0.05). In addition, VT duration was reduced significantly with honey 0.125 and 0.25%. Moreover, the infarct size was 45.6 ± 3.4% in the control group, while the perfusion of honey (0.125, 0.25 and 0.5%) reduced it to 14.8 ± 5.1 (p < 0.001), 24.6 ± 7.3 (p < 0.01) and 31.4 ± 7.3% (p < 0.05), respectively. Regarding the results, it is concluded that the acute administration of natural honey in normothermic ischemia conditions can protect the rat heart as the reduction of infarct size and arrhythmias. Conceivably, the antioxidant and free radical scavenging activity, the reduction of necrotized tissue and the providence of rich energy source are more important mechanisms in cardioprotective effects of natural honey. PMID:24250562

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

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.

Systematic review of drug administration costs and implications for biopharmaceutical manufacturing.

PubMed

Tetteh, Ebenezer; Morris, Stephen

2013-10-01

The acquisition costs of biologic drugs are often considered to be relatively high compared with those of nonbiologics. However, the total costs of delivering these drugs also depend on the cost of administration. Ignoring drug administration costs may distort resource allocation decisions because these affect cost effectiveness. The objectives of this systematic review were to develop a framework of drug administration costs that considers both the costs of physical administration and the associated proximal costs; and, as a case example, to use this framework to evaluate administration costs for biologics within the UK National Health Service (NHS). We reviewed literature that reported estimates of administration costs for biologics within the UK NHS to identify how these costs were quantified and to examine how differences in dosage forms and regimens influenced administration costs. The literature reviewed were identified by searching the Centre for Review and Dissemination Databases (DARE, NHS EED and HTA); EMBASE (The Excerpta Medica Database); MEDLINE (using the OVID interface); Econlit (EBSCO); Tufts Medical Center Cost Effectiveness Analysis (CEA) Registry; and Google Scholar. We identified 4,344 potentially relevant studies, of which 43 studies were selected for this systematic review. We extracted estimates of the administration costs of biologics from these studies. We found evidence of variation in the way that administration costs were measured, and that this affected the magnitude of costs reported, which could then influence cost effectiveness. Our findings suggested that manufacturers of biologic medicines should pay attention to formulation issues and their impact on administration costs, because these affect the total costs of healthcare delivery and cost effectiveness.

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... HUMAN SERVICES GENERAL PUBLIC INFORMATION General Policy § 20.30 Food and Drug Administration Freedom of Information Staff. (a) The Office responsible for agency compliance with the Freedom of Information Act and...

27 CFR 17.136 - Compliance with Food and Drug Administration requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 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 ALCOHOL... Compliance with Food and Drug Administration requirements. A product is not a medicine, medicinal preparation...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-15

... drug supply chain. Specifically, FDA will be able to administratively detain drugs encountered during... integrity of the drug supply chain. Specifically, administrative detention is intended to protect the public... better protect the integrity of the drug supply chain. One of those new authorities is section 709, which...

Common errors of drug administration in infants: causes and avoidance.

PubMed

Anderson, B J; Ellis, J F

1999-01-01

Drug administration errors are common in infants. Although the infant population has a high exposure to drugs, there are few data concerning pharmacokinetics or pharmacodynamics, or the influence of paediatric diseases on these processes. Children remain therapeutic orphans. Formulations are often suitable only for adults; in addition, the lack of maturation of drug elimination processes, alteration of body composition and influence of size render the calculation of drug doses complex in infants. The commonest drug administration error in infants is one of dose, and the commonest hospital site for this error is the intensive care unit. Drug errors are a consequence of system error, and preventive strategies are possible through system analysis. The goal of a zero drug error rate should be aggressively sought, with systems in place that aim to eliminate the effects of inevitable human error. This involves review of the entire system from drug manufacture to drug administration. The nuclear industry, telecommunications and air traffic control services all practise error reduction policies with zero error as a clear goal, not by finding fault in the individual, but by identifying faults in the system and building into that system mechanisms for picking up faults before they occur. Such policies could be adapted to medicine using interventions both specific (the production of formulations which are for children only and clearly labelled, regular audit by pharmacists, legible prescriptions, standardised dose tables) and general (paediatric drug trials, education programmes, nonpunitive error reporting) to reduce the number of errors made in giving medication to infants.

76 FR 78933 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical Practice; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The...

76 FR 17138 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical Practice; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] 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...

[Local adverse reactions associated with parenteral administration of drugs].

PubMed

Bjånes, Tormod Karlsen

2011-03-04

Parenteral administration of drugs may cause adverse reactions which in severe cases outweigh the intended therapeutic effects. This paper outlines local adverse reactions associated with various routes of parenteral administration. Different measures for prevention and management of such reactions are presented.

21 CFR 20.110 - Data and information about Food and Drug Administration employees.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Data and information about Food and Drug Administration employees. 20.110 Section 20.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.110...

21 CFR 20.3 - Certification and authentication of 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 Certification and authentication of Food and Drug... authentication of Food and Drug Administration records. (a) Upon request, the Food and Drug Administration will... or for authentication of records shall be sent in writing to the Freedom of Information Staff (HFI-35...

76 FR 72953 - Science Board to the Food and Drug Administration; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No: FDA-2011-N-0002] Science Board to the Food and Drug Administration; Notice of Meeting AGENCY: Food and Drug Administration... pace with technical and scientific evolutions in the fields of regulatory science, on formulating an...

77 FR 40069 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0563... Labeled for Human Use; Enforcement Action Dates AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing its intention to take enforcement...

Transmitted drug resistance in patients with acute/recent HIV infection in Brazil.

PubMed

Ferreira, Ana Cristina G; Coelho, Lara E; Grinsztejn, Eduarda; Jesus, Carlos S de; Guimarães, Monick L; Veloso, Valdiléa G; Grinsztejn, Beatriz; Cardoso, Sandra W

The widespread use of antiretroviral therapy increased the transmission of antiretroviral resistant HIV strains. Antiretroviral therapy initiation during acute/recent HIV infection limits HIV reservoirs and improves immune response in HIV infected individuals. Transmitted drug resistance may jeopardize the early goals of early antiretroviral treatment among acute/recent HIV infected patients. Patients with acute/recent HIV infection who underwent resistance test before antiretroviral treatment initiation were included in this analysis. HIV-1 sequences were obtained using an in house protease/reverse transcriptase genotyping assay. Transmitted drug resistance was identified according to the Stanford HIV Database for Transmitted Drug Resistance Mutations, based on WHO 2009 surveillance list, and HIV-1 subtyping according to Rega HIV-1 subtyping tool. Comparison between patients with and without transmitted drug resistance was made using Kruskal-Wallis and Chi-square tests. Forty-three patients were included, 13 with acute HIV infection and 30 with recent HIV infection. The overall transmitted drug resistance prevalence was 16.3% (95% confidence interval [CI]: 8.1-30.0%). The highest prevalence of resistance (11.6%, 95% CI: 8.1-24.5) was against non-nucleoside reverse transcriptase inhibitors, and K103N was the most frequently identified mutation. The high prevalence of nonnucleoside reverse transcriptase inhibitors resistance indicates that efavirenz-based regimen without prior resistance testing is not ideal for acutely/recently HIV-infected individuals in our setting. In this context, the recent proposal of including integrase inhibitors as a first line regimen in Brazil could be an advantage for the treatment of newly HIV infected individuals. However, it also poses a new challenge, since integrase resistance test is not routinely performed for antiretroviral naive individuals. Further studies on transmitted drug resistance among acutely/recently HIV-infected are

Acute recreational drug and new psychoactive substance toxicity in Europe: 12 months data collection from the European Drug Emergencies Network (Euro-DEN).

PubMed

Dines, Alison M; Wood, David M; Yates, Christopher; Heyerdahl, Fridtjof; Hovda, Knut Erik; Giraudon, Isabelle; Sedefov, Roumen; Dargan, Paul I

2015-11-01

Despite the potential for recreational drugs and new psychoactive substances (NPSs) to cause significant morbidity and mortality, there is limited collection of systematic data on acute drug/NPS toxicity in Europe. To report data on acute drug/NPS toxicity collected by a network of sentinel centres across Europe with a specialist clinical and research interest in the acute toxicity of recreational drugs and NPS to address this knowledge gap. Sixteen sentinel centres in 10 European countries (Denmark, Estonia, France, Germany, Ireland, Norway, Poland, Spain, Switzerland and the UK) collected data on all acute drug toxicity presentations to their Emergency Rooms (ERs) for 12 months (October 2013-September 2014); information on the drug(s) involved in the presentations was on the basis of patient self-reporting. Data were collected on a total of 5529 presentations involving 8709 drugs (median (interquartile range [IQR]): 1 (1-2) drugs per presentation), a median of 0.3% of all ER attendances. Classical recreational drugs were most common (64.6%) followed by prescription drugs (26.5%) and NPS (5.6%). The 'top five' drugs recorded were heroin (1345 reports), cocaine (957), cannabis (904), GHB/GBL (711) and amphetamine (593). 69.5% of individuals went to hospital by ambulance (peak time between 19:00 and 02:00 at weekends); the median (IQR) age was 31 (24-39) years and 75.4% were male. Although serious clinical features were not seen in most presentations and 56.9% were medically discharged from the ER (median length of stay: 4.6 hours), a significant number (26.5%) was agitated, in 10.5% the GCS was 8 or less and 35 presented in cardiac arrest. There were 27 fatalities with opioids implicated in 13. The Euro-DEN dataset provides a unique insight into the drugs involved in and clinical pattern of toxicity/outcome of acute recreational drug toxicity presentations to hospitals around Europe. This is complimentary to other indicators of drug-related harm and helps to build

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

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

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.

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0590] 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...

21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Correlation of bioavailability with an acute pharmacological effect or clinical evidence. 320.28 Section 320.28 Food and Drugs FOOD AND DRUG ADMINISTRATION... Correlation of bioavailability with an acute pharmacological effect or clinical evidence. Correlation of in...

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

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0247] Food and Drug Administration Transparency Initiative: Draft Proposals for Public Comment to Increase...: Food and Drug Administration, HHS. [[Page 61367

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

Code of Federal Regulations, 2010 CFR

2010-04-01

... 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 Record...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-13

... INFORMATION CONTACT: Astrid Lopez-Goldberg, Center for Drug Evaluation and Research, Food and Drug... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0563] Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration and...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-12

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0247... Administration, HHS. ACTION: Notice; request for comments. SUMMARY: The Food and Drug Administration (FDA) is soliciting comments from interested persons on ways in which FDA can increase transparency between FDA and...

Acute citalopram administration may disrupt contextual information processing in healthy males.

PubMed

Almeida, S; Glahn, D C; Argyropoulos, S V; Frangou, S

2010-03-01

Selective serotonin reuptake inhibitors (SSRI) are the most commonly prescribed antidepressants. It has been suggested however that SSRI administration may affect response inhibition and contextual processing but the available evidence is minimal. Therefore, the purpose of this study was to identify the effect size of acute (within 24 hours) and chronic (28 days) administration of the highly selective SSRI, Citalopram, compared to placebo on response inhibition (measured by the Degraded Symbol Continuous Performance Task [DS-CPT]) and contextual processing (assessed using a Delayed Non-Matching to Sample Task [DNMS]) in healthy males (n=20) using a randomised double-blind design. We found no effect of Citalopram on participants' performance on the DS-CPT which suggests either that SSRIs do not affect response inhibition or that this measure is insensitive to any potential disinhibition effects of SSRI. Acute, but not chronic, Citalopram administration was associated with a measurable decrement in the DNMS suggestive of a negative impact of SSRI administration on contextual processing at least during treatment initiation. These findings provide a useful guide for designing future studies in clinical populations. 2009. Published by Elsevier SAS.

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] 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 (FDA) Office of Orphan Products Development...

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

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 Conflict of Interest... HUMAN SERVICES GENERAL STANDARDS OF CONDUCT AND CONFLICTS OF INTEREST General Provisions § 19.10 Food and Drug Administration Conflict of Interest Review Board. (a) The Commissioner shall establish a...

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.

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 HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.120 Records available in Food and Drug...

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 HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.120 Records available in Food and Drug...

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 HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.120 Records available in Food and Drug...

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

... of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0375...

78 FR 14557 - Guidance for Industry and Food and Drug Administration Staff: Investigational Device Exemption...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-D-0010] Guidance for Industry and Food and Drug Administration Staff: Investigational Device Exemption Guidance for Retinal Prostheses; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The...

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] 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...

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] 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...

Adverse Drug Reactions Related to Drug Administration in Hospitalized Patients.

PubMed

Gallelli, Luca; Siniscalchi, Antonio; Palleria, Caterina; Mumoli, Laura; Staltari, Orietta; Squillace, Aida; Maida, Francesca; Russo, Emilio; Gratteri, Santo; De Sarro, Giovambattista

2017-01-01

Drug treatment may be related to the development of adverse drug reactions (ADRs). In this paper, we evaluated the ADRs in patients admitted to Catanzaro Hospital. After we obtained the approval by local Ethical Committee, we performed a retrospective study on clinical records from March 01, 2013 to April 30, 2015. The association between drug and ADR or between drug and drug-drug-interactions (DDIs) was evaluated using the Naranjo's probability scale and Drug Interaction Probability Scale (DIPS), respectively. During the study period, we analyzed 2870 clinical records containing a total of 11,138 prescriptions, and we documented the development of 770 ADRs. The time of hospitalization was significantly higher (P<0.05) in women with ADRs (12.6 ± 1.2 days) with respect to men (11.8± 0.83 days). Using the Naranjo score, we documented a probable association in 78% of these reactions, while DIPS revealed that about 22% of ADRs were related to DDIs. Patients with ADRs received 3052 prescriptions on 11,138 (27.4%) having a mean of 6.1±0.29 drugs that was significantly higher (P<0.01) with respect to patients not experiencing ADRs (mean of 3.4±0.13 drugs). About 19% of ADRs were not diagnosed and were treated as new diseases. Our results indicate that drug administration induces the development of ADRs also during the hospitalization, particularly in elderly women. Moreover, we also documented that ADRs in some patients are under-diagnosed, therefore, it is important to motivate healthcare to report the ADRs in order to optimize the patients' safety. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

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. © The Author(s) 2014.

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

... for Premium Intraocular Lenses; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice. The Food and Drug Administration (FDA) is announcing the following public workshop entitled ``FDA... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001...

78 FR 54901 - Food and Drug Administration/American Academy of Ophthalmology Workshop on Developing Novel...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-06

... for Premium Intraocular Lenses; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The Food and Drug Administration (FDA) is announcing the following public... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001...

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…

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

... Dependence; Public Hearing; Extension of Comment Period AGENCY: Food and Drug Administration, HHS. ACTION: Notification of public hearing; Extension of comment period. SUMMARY: The Food and Drug Administration (FDA) is... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 15 [Docket No...

Identifying injection drug use and estimating population size of people who inject drugs using healthcare administrative datasets.

PubMed

Janjua, Naveed Zafar; Islam, Nazrul; Kuo, Margot; Yu, Amanda; Wong, Stanley; Butt, Zahid A; Gilbert, Mark; Buxton, Jane; Chapinal, Nuria; Samji, Hasina; Chong, Mei; Alvarez, Maria; Wong, Jason; Tyndall, Mark W; Krajden, Mel

2018-05-01

Large linked healthcare administrative datasets could be used to monitor programs providing prevention and treatment services to people who inject drugs (PWID). However, diagnostic codes in administrative datasets do not differentiate non-injection from injection drug use (IDU). We validated algorithms based on diagnostic codes and prescription records representing IDU in administrative datasets against interview-based IDU data. The British Columbia Hepatitis Testers Cohort (BC-HTC) includes ∼1.7 million individuals tested for HCV/HIV or reported HBV/HCV/HIV/tuberculosis cases in BC from 1990 to 2015, linked to administrative datasets including physician visit, hospitalization and prescription drug records. IDU, assessed through interviews as part of enhanced surveillance at the time of HIV or HCV/HBV diagnosis from a subset of cases included in the BC-HTC (n = 6559), was used as the gold standard. ICD-9/ICD-10 codes for IDU and injecting-related infections (IRI) were grouped with records of opioid substitution therapy (OST) into multiple IDU algorithms in administrative datasets. We assessed the performance of IDU algorithms through calculation of sensitivity, specificity, positive predictive, and negative predictive values. Sensitivity was highest (90-94%), and specificity was lowest (42-73%) for algorithms based either on IDU or IRI and drug misuse codes. Algorithms requiring both drug misuse and IRI had lower sensitivity (57-60%) and higher specificity (90-92%). An optimal sensitivity and specificity combination was found with two medical visits or a single hospitalization for injectable drugs with (83%/82%) and without OST (78%/83%), respectively. Based on algorithms that included two medical visits, a single hospitalization or OST records, there were 41,358 (1.2% of 11-65 years individuals in BC) recent PWID in BC based on health encounters during 3- year period (2013-2015). Algorithms for identifying PWID using diagnostic codes in linked administrative

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

... Administration--Partnering With Industry; Public Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. The Food and Drug Administration (FDA) is announcing a joint conference with... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001...

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

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] 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 Drug...

78 FR 21085 - Establishment of a Public Docket for Administrative Detention Under the Food and Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-09

... Administration Safety and Innovation Act AGENCY: Food and Drug Administration, HHS. ACTION: Establishment of... authority with respect to drugs under the Food and Drug Administration Safety and Innovation Act (FDASIA....regulations.gov . Submit written comments to the Division of Dockets Management (HFA- 305), Food and Drug...

Administrative Destruction of Certain Drugs Refused Admission to the United States. Final rule.

PubMed

2015-09-15

The Food and Drug Administration (FDA or Agency) is implementing its authority to destroy a drug valued at $2,500 or less (or such higher amount as the Secretary of the Treasury may set by regulation) that has been refused admission into the United States under the Federal Food, Drug, and Cosmetic Act (the FD&C Act), by issuing a rule that provides to the owner or consignee notice and an opportunity to appear and introduce testimony to the Agency prior to destruction. This regulation is authorized by amendments made to the FD&C Act by the Food and Drug Administration Safety and Innovation Act (FDASIA). Implementation of this authority will allow FDA to better protect the public health by providing an administrative process for the destruction of certain refused drugs, thus increasing the integrity of the drug supply chain.

Acute Morphine Administration Reduces Cell-Mediated Immunity and Induces Reactivation of Latent Herpes Simplex Virus Type 1 in BALB/c Mice

PubMed Central

Mojadadi, Shafi; Jamali, Abbas; Khansarinejad, Behzad; Soleimanjahi, Hoorieh; Bamdad, Taravat

2009-01-01

Acute morphine administration is known to alter the course of herpes simplex virus infection. In this study, the effect of acute morphine administration on the reactivation of latent herpes was investigated in a mouse model. Because of the important role of cytolytic T lymphocyte (CTL) activity in the inhibition of herpes simplex virus type 1 (HSV-1) reactivation, the effect of acute morphine administration on CTL responses was also evaluated. Furthermore, lymphocyte proliferation and IFN-γ production were evaluated for their roles in the induction of the CTL response. The findings showed that acute morphine administration significantly reduced CTL responses, lymphocyte proliferation, and IFN-γ production. Furthermore, acute morphine administration has been shown to reactivate latent HSV-1. Previous studies have shown that cellular immune responses have important roles in the inhibition of HSV reactivation. These findings suggest that suppression of a portion of the cellular immune response after acute morphine administration may constitute one part of the mechanism that induces HSV reactivation. PMID:19403060

21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

Code of Federal Regulations, 2010 CFR

2010-04-01

... pharmacological effect or clinical evidence. 320.28 Section 320.28 Food and Drugs FOOD AND DRUG ADMINISTRATION... Correlation of bioavailability with an acute pharmacological effect or clinical evidence. Correlation of in vivo bioavailability data with an acute pharmacological effect or clinical evidence of safety and...

76 FR 9027 - Draft Guidance for Industry and Food and Drug Administration Staff on Best Practices for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0057] Draft Guidance for Industry and Food and Drug Administration Staff on Best Practices for Conducting and...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

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

A single administration of cortisol acutely reduces preconscious attention for fear in anxious young men.

PubMed

Putman, Peter; Hermans, Erno J; Koppeschaar, Hans; van Schijndel, Alexandra; van Honk, Jack

2007-08-01

Chronically elevated HPA activity has often been associated with fear and anxiety, but there is evidence that single administrations of glucocorticoids may acutely reduce fear. Moreover, peri-traumatic cortisol elevation may protect against development of post-traumatic stress disorder. Hypervigilant processing of threat information plays a role in anxiety disorders and although relations with HPA functioning have been established, causality of these relations remains unclear. Presently, self-reported anxiety and response time patterns on a masked emotional Stroop task with fearful faces were measured in 20 healthy young men after double-blind, placebo-controlled oral administration of 40 mg cortisol. The masked fearful Stroop task measures vocal colornaming response latencies for pictures of neutral and fearful faces presented below the threshold for conscious perception. Results showed increased response times on trials for fearful compared to neutral faces after placebo, but this emotional Stroop effect was acutely abolished by cortisol administration. This effect was most pronounced in subjects with heightened anxiety levels. This is the first evidence showing that exogenous cortisol acutely reduces anxiety-driven selective attention to threat. These results extend earlier findings of acute fear reduction after glucocorticoid administration. This suggests interactions of HPA functioning and vigilant attention in the pathogenesis of anxiety disorders. Possible neuroendocrine mechanisms of action are discussed.

Role of mass drug administration in elimination of Plasmodium falciparum malaria: a consensus modelling study.

PubMed

Brady, Oliver J; Slater, Hannah C; Pemberton-Ross, Peter; Wenger, Edward; Maude, Richard J; Ghani, Azra C; Penny, Melissa A; Gerardin, Jaline; White, Lisa J; Chitnis, Nakul; Aguas, Ricardo; Hay, Simon I; Smith, David L; Stuckey, Erin M; Okiro, Emelda A; Smith, Thomas A; Okell, Lucy C

2017-07-01

Mass drug administration for elimination of Plasmodium falciparum malaria is recommended by WHO in some settings. We used consensus modelling to understand how to optimise the effects of mass drug administration in areas with low malaria transmission. We collaborated with researchers doing field trials to establish a standard intervention scenario and standard transmission setting, and we input these parameters into four previously published models. We then varied the number of rounds of mass drug administration, coverage, duration, timing, importation of infection, and pre-administration transmission levels. The outcome of interest was the percentage reduction in annual mean prevalence of P falciparum parasite rate as measured by PCR in the third year after the final round of mass drug administration. The models predicted differing magnitude of the effects of mass drug administration, but consensus answers were reached for several factors. Mass drug administration was predicted to reduce transmission over a longer timescale than accounted for by the prophylactic effect alone. Percentage reduction in transmission was predicted to be higher and last longer at lower baseline transmission levels. Reduction in transmission resulting from mass drug administration was predicted to be temporary, and in the absence of scale-up of other interventions, such as vector control, transmission would return to pre-administration levels. The proportion of the population treated in a year was a key determinant of simulated effectiveness, irrespective of whether people are treated through high coverage in a single round or new individuals are reached by implementation of several rounds. Mass drug administration was predicted to be more effective if continued over 2 years rather than 1 year, and if done at the time of year when transmission is lowest. Mass drug administration has the potential to reduce transmission for a limited time, but is not an effective replacement for existing

Effect of intravenous drug administration mode on drug distribution in a tumor slab: a finite Fourier transform analysis.

PubMed

Subramaniam, B; Claudius, J S

1990-03-08

Cancer therapy using chemotherapeutic drugs frequently involves injection of the drug into the body through some intravenous mode of administration, viz, continuous (drip) infusion or single/multiple bolus injection(s). An understanding of the effect of the various modes of administration upon tumor penetration of drug is essential to rational design of drug therapy. This paper investigates drug penetration into a model tumor of slab geometry (between two capillaries) in which the overall transport rate of drug is limited by intra-tumor transport characterized by an effective diffusion coefficient. Employing the method of Finite Fourier Transforms (FFT), analytical solutions have been obtained for transient drug distribution in both the plasma and the tumor following three modes of administration, viz, continuous infusion, single bolus injection and equally-spaced equal-dose multiple bolus injections, of a given amount of drug. The qualitative trends exhibited by the plasma drug distribution profiles are consistent with reported experimental studies. Two concepts, viz, the dimensionless decay constant and the plasma/tumor drug concentration trajectories, are found to be particularly useful in the rational design of drug therapy. The dimensionless decay constant provides a measure of the rate of drug decay in the plasma relative to the rate of drug diffusion into the tumor and is thus characteristic of the tumor/drug system. The magnitude of this parameter dictates the choice of drug administration mode for minimizing drug decay in the plasma while simultaneously maximizing drug transport into the tumor. The concentration trajectories provide a measure of the plasma drug concentration relative to the tumor drug concentration at various times following injection. When the tumor drug concentration exceeds the plasma drug concentration, the drug will begin to diffuse out of the tumor. Knowledge of the time at which this diffusion reversal occurs is especially useful

How are drugs approved? Part 1: the evolution of the Food and Drug Administration.

PubMed

Howland, Robert H

2008-01-01

The discovery, development, and marketing of drugs for clinical use is a process that is complex, arduous, expensive, highly regulated, often criticized, and sometimes controversial. In the United States, the Food and Drug Administration (FDA) is the governmental agency responsible for regulating the development and marketing of drugs, medical devices, biologics, foods, cosmetics, radiation-emitting electronic devices, and veterinary products, with the objective of ensuring their safety and efficacy. As part of a broad overview of the drug development process, this article will describe the historical evolution of the FDA. This will provide background for two subsequent articles in this series, which will describe the ethical foundations of clinical research and hethe stages of drug development.

Transparency and the Food and Drug Administration--a quantitative study.

PubMed

Lofstedt, Ragnar; Bouder, Frederic; Chakraborty, Sweta

2013-01-01

In Europe and North America, there is increasing political pressure being put on health regulatory agencies to become more transparent. To date, however, there has been little academic evaluation--let alone analysis--of these transparency initiatives from a risk communication perspective. This review examines whether the U.S. Food and Drug Administration's Adverse Event Reporting System quarterly signal postings, put in place after the passage of the Food and Drug Administration Amendments Act 2007, will assist patients and doctors in their decision-making processes, on the basis of results of a quantitative Internet survey of 433 physicians and 1,000 American adults. The results indicate that there is significant disagreement between physicians and the public about when medical safety issues should be communicated in the first place, with physicians opposed to early signal postings while the public in general is in favor. In addition the findings show that if the public were to find their drugs listed on the Adverse Event Reporting System signals web postings, more than a quarter would stop taking their medicine. Going forward, the Food and Drug Administration needs to work to a greater degree with social scientists in developing scientific-based communication strategies, rather than developing transparency initiatives on the basis of stakeholder consultations.

Oxidative metabolism of limbic structures after acute administration of diazepam, alprazolam and zolpidem.

PubMed

González-Pardo, Héctor; Conejo, Nélida M; Arias, Jorge L

2006-08-30

The effects of acute administration of two benzodiazepines and a non-benzodiazepine hypnotic on behavior and brain metabolism were evaluated in rats. After testing the behavioral action of the benzodiazepines on the open field and the elevated plus-maze, the effects of the three drugs on neuronal metabolism of particular limbic regions were measured using cytochrome c oxidase (CO) histochemistry. Diazepam (5 mg/kg i.p.) and alprazolam (0.5 mg/kg i.p.) induced clear anxiolytic effects and a decrease in locomotion, whereas zolpidem (2 mg/kg i.p.) caused an intense hypnotic effect. The anxiolytic effects of alprazolam were distinguishable from diazepam due to the pharmacological and clinical profile of this triazolobenzodiazepine. CO activity decreased significantly in almost all the limbic regions evaluated after zolpidem administration. However, significant prominent decreases in CO activity were found after diazepam treatment in the medial mammillary nucleus, anteroventral thalamus, cingulate cortex, dentate gyrus and basolateral amygdala. Alprazolam caused similar decreases in CO activity, with the exception of the prelimbic and cingulate cortices, where significant increases were detected. In agreement with previous studies using other functional mapping techniques, our results indicate that particular benzodiazepines and non-benzodiazepine hypnotics induce selective changes in brain oxidative metabolism.

75 FR 22819 - Considerations Regarding Food and Drug Administration Review and Regulation of Articles for the...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

... Diseases; Public Hearing AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public hearing; request for comment. SUMMARY: The Food and Drug Administration (FDA) is announcing a public hearing... with rare diseases, a recent public law (Agriculture, Rural Development, Food and Drug Administration...

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0635] Guidance for Industry and Food and Drug Administration Staff; Section 905(j) Reports: Demonstrating Substantial Equivalence for Tobacco Products; Availability AGENCY: Food and Drug Administration, HHS. ACTION...

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0395] Draft Guidance for Industry and Food and Drug Administration Staff; Recommendations for Premarket Notifications for Lamotrigine and Zonisamide Assays; Availability AGENCY: Food and Drug Administration, HHS...

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0514] Draft Guidance for Industry and Food and Drug Administration Staff; Procedures for Handling Section 522 Postmarket Surveillance Studies; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice...

Exposure Matching of Pediatric Anti-infective Drugs: Review of Drugs Submitted to the Food and Drug Administration for Pediatric Approval

PubMed Central

Zimmerman, Kanecia; Putera, Martin; Hornik, Christoph P.; Smith, P. Brian; Benjamin, Daniel K.; Mulugeta, Yeruk; Burckart, Gilbert J.; Cohen-Wolkowiez, Michael; Gonzalez, Daniel

2016-01-01

Purpose Over the last decade, few novel antibiotics have been approved by the Food and Drug Administration (FDA) for pediatric use. For most anti-infective agents, including antibiotics, extrapolation of efficacy from adults to children is possible if the disease and therapeutic exposures are similar between the 2 populations. This approach reduces the number of studies required in children, but relies heavily on exposure matching between children and adults. Failures in exposure matching can lead to delays in pediatric approvals of new anti-infective agents. We sought to determine the extent of exposure matching, defined by a comparison of area under the concentration-time curve, between children and adults, for anti-infective drug products submitted to the FDA for approval. Methods We reviewed anti-infective submissions to the FDA (2002–2014) for pediatric indication. We included drug products administered via oral, intravenous, or intramuscular administration routes, and those with AUC estimates for children in available FDA reports. Our main outcome of interest was the proportion of drugs with median (or mean) pediatric AUC within 20% of the median (or mean) reported adult value. Findings We identified 29 drug products that met inclusion criteria, 14 (48%) of which had mean (or median) AUCs of all submitted age groups within 20% of that in adults. Only route of administration and drug class were associated with pediatric AUC within 20% of adult AUC. Implications Future research is needed to define criteria for and predictors of successful exposure matching of anti-infectives between children and adults. PMID:27364807

Exposure Matching of Pediatric Anti-infective Drugs: Review of Drugs Submitted to the Food and Drug Administration for Pediatric Approval.

PubMed

Zimmerman, Kanecia; Putera, Martin; Hornik, Christoph P; Brian Smith, P; Benjamin, Daniel K; Mulugeta, Yeruk; Burckart, Gilbert J; Cohen-Wolkowiez, Michael; Gonzalez, Daniel

2016-09-01

Over the last decade, few new antibiotics have been approved by the Food and Drug Administration (FDA) for pediatric use. For most anti-infective agents, including antibiotics, extrapolation of efficacy from adults to children is possible if the disease and therapeutic exposures are similar between the 2 populations. This approach reduces the number of studies required in children, but relies heavily on exposure matching between children and adults. Failures in exposure matching can lead to delays in pediatric approvals of new anti-infective agents. We sought to determine the extent of exposure matching, defined by a comparison of area under the concentration-time curve, between children and adults, for anti-infective drug products submitted to the FDA for approval. We reviewed anti-infective submissions to the FDA (2002-2014) for pediatric indication. We included drug products administered via oral, intravenous, or intramuscular administration routes, and those with AUC estimates for children in available FDA reports. Our main outcome of interest was the proportion of drugs with median (or mean) pediatric AUC within 20% of the median (or mean) reported adult value. We identified 29 drug products that met inclusion criteria, 14 (48%) of which had mean (or median) AUCs of all submitted age groups within 20% of that in adults. Only route of administration and drug class were associated with pediatric AUC within 20% of adult AUC. Future research is needed to define criteria for and predictors of successful exposure matching of anti-infectives between children and adults. Published by Elsevier Inc.

78 FR 44574 - Third Annual Food and Drug Administration Health Professional Organizations Conference

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-24

... . Contact: Brenda Rose, Office of Special Health Issues, 10903 New Hampshire Ave., Silver Spring, MD 20993... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Third Annual Food and Drug Administration Health Professional Organizations Conference AGENCY: Food and...

77 FR 55845 - Science Board to the Food and Drug Administration: Request for Nominations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001... Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is requesting nominations to serve on the Science Board to FDA (Science Board). FDA seeks to include the views of women and men...

Thromboelastographic evidence of inhibition of fibrinolysis after ε-aminocaproic acid administration in a dog with suspected acute traumatic coagulopathy.

PubMed

Yoo, Seung H; Venn, Emilee; Sullivan, Lauren A; Olver, Christine S

2016-09-01

To describe the thromboelastographic changes in fibrinolysis with ε-aminocaproic acid treatment in a dog with suspected acute traumatic coagulopathy. A 9-year-old female spayed Airedale Terrier was presented with multiple injuries consistent with motor vehicle trauma. After surgical repair of a diaphragmatic hernia and minor laceration of the right cranial lung lobe, the dog continued to produce copious volumes of hemorrhagic fluid from the thoracic cavity despite multiple plasma transfusions, autotransfusions, and failure to locate a definitive source of bleeding during 2 separate surgeries. ε-Aminocaproic acid treatment was initiated and was associated with rapid clinical improvement and diminished fibrinolysis based on a modified plasma-based thromboelastogram. This report describes thromboelastographic evidence of inhibition of fibrinolysis after ε-aminocaproic acid administration in a dog with suspected acute traumatic coagulopathy. Thromboelastrography may be useful in monitoring therapy with antifibrinolytic drugs. © Veterinary Emergency and Critical Care Society 2016.

76 FR 30727 - Food and Drug Administration Food Safety Modernization Act: Focus on Inspections and Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0366] Food and Drug Administration Food Safety Modernization Act: Focus on Inspections and Compliance AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public meeting; request for comments. SUMMARY: The...

75 FR 48699 - Memorandum of Understanding Between United States Food and Drug Administration and the Centers...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0004] [FDA 225-10-0010] Memorandum of Understanding Between United States Food and Drug Administration and the Centers for Medicare and Medicaid Services AGENCY: Food and Drug Administration, HHS. ACTION...

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0847] Guidance for Industry and Food and Drug Administration Staff; Humanitarian Use Device (HUD) Designations... public comment ``Draft Guidance for Industry and Food and Drug Administration Staff on Humanitarian Use...

Estimating preferences for modes of drug administration: The case of US healthcare professionals.

PubMed

Tetteh, Ebenezer K; Morris, Steve; Titchener-Hooker, Nigel

2018-01-01

There are hidden drug administration costs that arise from a mismatch between end-user preferences and how manufacturers choose to formulate their drug products for delivery to patients. The corollary of this is: there are "intangible benefits" from considering end-user preferences in manufacturing patient-friendly medicines. It is important then to have some idea of what pharmaceutical manufacturers should consider in making patient-friendly medicines and of the magnitude of the indirect benefits from doing so. This study aimed to evaluate preferences of healthcare professionals in the US for the non-monetary attributes of different modes of drug administration. It uses these preference orderings to compute a monetary valuation of the indirect benefits from making patient-friendly medicines. A survey collected choice preferences of a sample of 210 healthcare professionals in the US for two unlabelled drug options. These drugs were identical except in the levels of attributes of drug administration. Using the choice data collected, statistical models were estimated to compute gross welfare benefits, measured by the expected compensating variation, from making drugs in a more patient-friendly manner. The monetary value of end-user benefits from developing patient-friendly drug delivery systems is: (1) as large as the annual acquisition costs per full treatment episode for some biologic drugs; and (2) likely to fall in the "high end" of the distribution of the direct monetary costs of drug administration. An examination of end-user preferences should help manufacturers make more effective and efficient use of limited resources for innovations in drug delivery system, or manufacturing research in general. Copyright © 2017 Elsevier Inc. All rights reserved.

Oral administration of levo-tetrahydropalmatine attenuates reinstatement of extinguished cocaine seeking by cocaine, stress or drug-associated cues in rats.

PubMed

Figueroa-Guzman, Yazmin; Mueller, Christopher; Vranjkovic, Oliver; Wisniewski, Samantha; Yang, Zheng; Li, Shi-Jiang; Bohr, Colin; Graf, Evan N; Baker, David A; Mantsch, John R

2011-07-01

Cocaine addiction is characterized by a persistently heightened susceptibility to drug relapse. For this reason, the identification of medications that prevent drug relapse is a critical goal of drug abuse research. Drug re-exposure, the onset of stressful life events, and exposure to cues previously associated with drug use have been identified as determinants of relapse in humans and have been found to reinstate extinguished cocaine seeking in rats. This study examined the effects of acute oral (gavage) administration of levo-tetrahydropalmatine (l-THP), a tetrahydroprotoberberine isoquinoline with a pharmacological profile that includes antagonism of D1, D2 and D3 dopamine receptors, on the reinstatement of extinguished cocaine seeking by a cocaine challenge (10mg/kg, ip), a stressor (uncontrollable electric footshock [EFS]) or response-contingent exposure to a stimulus (tone and light complex) previously associated with drug delivery in male Sprague-Dawley rats. Extinguished drug seeking was reinstated by ip cocaine, EFS, or response-contingent presentation of drug-associated cues in vehicle-pretreated rats following extinction of iv cocaine self-adminisration. Oral administration of either 3.0 or 10.0mg/kg l-THP 1h prior to reinstatement testing significantly attenuated reinstatement by each of the stimuli. Food-reinforced responding and baseline post-extinction responding were significantly attenuated at the 10.0, but not the 3.0mg/kg, l-THP dose, indicating that the effects of 3mg/kg l-THP on reinstatement were likely independent of non-specific motor impairment. These findings further suggest that l-THP may have utility for the treatment of cocaine addiction. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

A Challenge for Diagnosing Acute Liver Injury with Concomitant/Sequential Exposure to Multiple Drugs: Can Causality Assessment Scales Be Utilized to Identify the Offending Drug?

PubMed Central

Lim, Roxanne; Conner, Kim; Karnsakul, Wikrom

2014-01-01

Drug-induced hepatotoxicity most commonly manifests as an acute hepatitis syndrome and remains the leading cause of drug-induced death/mortality and the primary reason for withdrawal of drugs from the pharmaceutical market. We report a case of acute liver injury in a 12-year-old Hispanic boy, who received a series of five antibiotics (amoxicillin, ceftriaxone, vancomycin, ampicillin/sulbactam, and clindamycin) for cervical lymphadenitis/retropharyngeal cellulitis. Histopathology of the liver biopsy specimen revealed acute cholestatic hepatitis. All known causes of acute liver injury were appropriately excluded and (only) drug-induced liver injury was left as a cause of his cholestasis. Liver-specific causality assessment scales such as Council for the International Organization of Medical Sciences/Roussel Uclaf Causality Assessment Method scoring system (CIOMS/RUCAM), Maria and Victorino scale, and Digestive Disease Week-Japan were applied to seek the most likely offending drug. Although clindamycin is the most likely cause by clinical diagnosis, none of causality assessment scales aid in the diagnosis. PMID:25506455

77 FR 47652 - Second Annual Food and Drug Administration Health Professional Organizations Conference

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-09

... of Special Health Issues, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD... between health professional organizations and FDA staff. The Office of Special Health Issues serves as a... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001...

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

75 FR 74063 - Supplemental Funding Under the Food and Drug Administration's Convener of Active Medical Product...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0576] Supplemental Funding Under the Food and Drug Administration's Convener of Active Medical Product Surveillance Discussions (U13) RFA- FD-09-012; Request for Supplemental Application AGENCY: Food and Drug Administration...

FDA approves efavirenz. Food and Drug Administration.

PubMed

Highleyman, L

1998-10-01

The Food and Drug Administration (FDA) approved DuPont Pharma's new non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva, DMP-266). Efavirenz has shown promise in trials with over 2000 participants for up to 24 weeks, and early data suggests it may be as effective as protease inhibitors when used in a combination regimen. It is the first anti-HIV drug approved for once-daily dosing. Efavirenz is well tolerated, and the main side effects reported are dizziness, insomnia, abnormal dreams, and skin rash. Efavirenz has been approved for adults and children, but should not be used by pregnant women. Contact information is provided.

Does being drunk or high cause HIV sexual risk behavior? A systematic review of drug administration studies.

PubMed

Berry, Meredith S; Johnson, Matthew W

2018-01-01

HIV sexual risk behavior is broadly associated with substance use. Yet critical questions remain regarding the potential causal link between substance use (e.g., intoxication) and HIV sexual risk behavior. The present systematic review was designed to examine and synthesize the existing literature regarding the effects of substance administration on HIV sexual risk behavior. Randomized controlled experiments investigating substance administration and HIV sexual risk behavior (e.g., likelihood of condom use in a casual sex scenario) were included. Across five databases, 2750 titles/abstracts were examined and forty-three total peer reviewed published manuscripts qualified (few were multi-study manuscripts, and those details are outlined in the text). The majority of articles investigated the causal role of acute alcohol administration on HIV sexual risk behavior, although one article investigated the effects of acute THC administration, one the effects of acute cocaine administration, and two the effects of buspirone. The results of this review suggest a causal role in acute alcohol intoxication increasing HIV sexual risk decision-making. Although evidence is limited with other substances, cocaine administration also appears to increase sexual risk, while acute cannabis and buspirone maintenance may decrease sexual risk. In the case of alcohol intoxication, the pharmacological effects independently contribute to HIV sexual risk decision-making, and these effects are exacerbated by alcohol expectancies, increased arousal, and delay to condom availability. Comparisons across studies showed that cocaine led to greater self-reported sexual arousal than alcohol, potentially suggesting a different risk profile. HIV prevention measures should take these substance administration effects into account. Increasing the amount of freely and easily accessible condoms to the public may attenuate the influence of acute intoxication on HIV sexual risk decision-making. Copyright �

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

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0004] Memorandum of Understanding Between the Food and Drug Administration, United States Department of Health and... understanding (MOU) between the Food and Drug Administration, U.S. Department of Health and Human Services and...

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

Enhancing topical analgesic administration: review and prospect for transdermal and transbuccal drug delivery systems.

PubMed

Sanz, Roser; Calpena, Ana C; Mallandrich, Mireia; Clares, Beatriz

2015-01-01

Topical administration is an appealing method for drug delivery due to its non-invasiveness, self-controlled application, avoidance of first-pass metabolism in the liver and reduction of systemic side effects compared to other conventional routes such as oral and parenteral. However, topical administration must overcome the permeable barriers that skin and mucosa represent for the drug to achieve its desired therapeutic effect. Penetration of drugs through human skin is mainly impaired by the stratum corneum- the uppermost keratinized skin layer. In contrast, the stratified squamous epithelium (a nonkeratinized tissue) represents the major physical barrier for transbuccal drug administration in humans. Different technologies have been studied to enhance the bioavailability or local effects of drugs administered through skin and buccal mucosa. Those technologies involve the use of physical or chemical enhancers and new dosage forms such as vesicles, cyclodextrins, nanoparticles and other complex systems. Combinations of these technologies may further increase drug delivery in some cases. As analgesia is one of the main therapeutic effects sought through topical administration, this paper focuses on the review of drug delivery systems to improve the topical and transdermal/transbuccal drug delivery of substances with known analgesic action. A discussion of their possibilities and limitations is also included.

21 CFR 868.5115 - Device to relieve acute upper airway obstruction.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Device to relieve acute upper airway obstruction. 868.5115 Section 868.5115 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5115 Device to...

21 CFR 868.5115 - Device to relieve acute upper airway obstruction.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Device to relieve acute upper airway obstruction. 868.5115 Section 868.5115 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5115 Device to...

21 CFR 868.5115 - Device to relieve acute upper airway obstruction.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Device to relieve acute upper airway obstruction. 868.5115 Section 868.5115 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5115 Device to...

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.

Update on administration of anesthetics and psychoactive drugs for pain management in China.

PubMed

Gu, Weiping

2015-06-01

Anesthetics and psychoactive drugs could relieve diseases, if used properly. However, they can cause dependency, and their misuse or abuse could adversely affect people's health and social stability. For a long time, the Chinese government has been reinforcing the regulation on anesthetics and psychoactive drugs to ensure their legal and proper usage, and to prevent abuse. The state council issued 'the regulations on the administration of anesthetic drugs and psychotropic drugs' in 2005, based on which a legal system was established for administration of anesthetics and psychoactive drugs with the objectives of ensuring their legitimate medical utilization, and preventing illegal abuse. Copyright © 2015. Published by Elsevier B.V.

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

Code of Federal Regulations, 2010 CFR

2010-07-01

... 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 occasionally...

Antiretroviral drugs and acute pancreatitis in HIV/AIDS patients: is there any association? A literature review

PubMed Central

Oliveira, Natalia Mejias; Ferreira, Felipe Augusto Yamauti; Yonamine, Raquel Yumi; Chehter, Ethel Zimberg

2014-01-01

ABSTRACT In HIV-seropositive individuals, the incidence of acute pancreatitis may achieve 40% per year, higher than the 2% found in the general population. Since 1996, when combined antiretroviral therapy, known as HAART (highly active antiretroviral therapy), was introduced, a broad spectrum of harmful factors to the pancreas, such as opportunistic infections and drugs used for chemoprophylaxis, dropped considerably. Nucleotide analogues and metabolic abnormalities, hepatic steatosis and lactic acidosis have emerged as new conditions that can affect the pancreas. To evaluate the role of antiretroviral drugs to treat HIV/AIDS in a scenario of high incidence of acute pancreatitis in this population, a systematic review was performed, including original articles, case reports and case series studies, whose targets were HIV-seropositive patients that developed acute pancreatitis after exposure to any antiretroviral drugs. This association was confirmed after exclusion of other possible etiologies and/or a recurrent episode of acute pancreatitis after re-exposure to the suspected drug. Zidovudine, efavirenz, and protease inhibitors are thought to lead to acute pancreatitis secondary to hyperlipidemia. Nucleotide reverse transcriptase inhibitors, despite being powerful inhibitors of viral replication, induce a wide spectrum of side effects, including myelotoxicity and acute pancreatitis. Didanosine, zalcitabine and stavudine have been reported as causes of acute and chronic pancreatitis. They pose a high risk with cumulative doses. Didanosine with hydroxyurea, alcohol or pentamidine are additional risk factors, leading to lethal pancreatitis, which is not a frequent event. In addition, other drugs used for prophylaxis of AIDS-related opportunistic diseases, such as sulfamethoxazole-trimethoprim and pentamidine, can produce necrotizing pancreatitis. Despite comorbidities that can lead to pancreatic involvement in the HIV/AIDS population, antiretroviral drug

Acute hypersensitivity reactions associated with administration of crotalidae polyvalent immune Fab antivenom.

PubMed

Cannon, Robert; Ruha, Anne-Michelle; Kashani, John

2008-04-01

Acute hypersensitivity reactions are well known to occur with the administration of the Antivenin (Crotalidae) Polyvalent (Wyeth Laboratories, Marietta, PA). Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV, Protherics, Inc., Brentwood, TN) was introduced in 2001, and early studies reported a hypersensitivity reaction rate up to 19%. We describe the incidence of acute hypersensitivity reactions to FabAV in patients bitten by rattlesnakes. This was a nonconcurrent observational cohort study, with data obtained by chart review of all patients admitted to our service for rattlesnake bites from July 2000 to June 2004. The study was conducted at an urban Level I trauma center and urban children's hospital. All patients treated with FabAV were included. Those who received no antivenom or who were treated with Antivenin (Crotalidae) Polyvalent were excluded. The main outcome variable was whether an acute hypersensitivity reaction developed. Ninety-three patients were included in the review (72 male and 21 female patients). The mean age was 34.5 years (range 16 months to 91 years), and the mean dose of antivenom was 12 vials (range 4 to 32 vials). The incidence of acute hypersensitivity reactions was 5 of 93, or 5.4%. Four patients developed a mild reaction that was easily treated and were able to finish the full course of antivenom. Only 1 patient developed a reaction that prevented further antivenom administration. FabAV appears to be associated with a lower incidence of acute hypersensitivity than initially reported. Most reactions are mild and easily treated and do not preclude further dosing of antivenom.

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... Act Record Systems § 21.20 Procedures for notice of Food and Drug Administration Privacy Act Record... of each year a notice concerning each Privacy Act Record System as defined in § 21.3(c) that is not...

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... Act Record Systems § 21.20 Procedures for notice of Food and Drug Administration Privacy Act Record... of each year a notice concerning each Privacy Act Record System as defined in § 21.3(c) that is not...

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... Act Record Systems § 21.20 Procedures for notice of Food and Drug Administration Privacy Act Record... of each year a notice concerning each Privacy Act Record System as defined in § 21.3(c) that is not...

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... Act Record Systems § 21.20 Procedures for notice of Food and Drug Administration Privacy Act Record... of each year a notice concerning each Privacy Act Record System as defined in § 21.3(c) that is not...

Operational and Clinical Strategies to Address Drug Cost Containment in the Acute Care Setting.

PubMed

McConnell, Karen J; Guzman, Oscar E; Pherwani, Nisha; Spencer, Dustin D; Van Cura, Jennifer D; Shea, Katherine M

2017-01-01

To provide clinical and operational strategies to generate drug cost savings in the hospital setting. A search of the PubMed database was performed with no time limit through July 2016. All original prospective and retrospective studies, peer-reviewed guidelines, consensus statements, review articles, and accompanying references were evaluated for inclusion. Only articles published in the English language were included. Investigators reviewed 937 abstracts. The review of the literature showed that acute care hospitals are under increasing financial pressures, and the pharmacy is often responsible for opportunities to manage drug costs. The literature also indicated that cost-containment strategies in the acute care setting range from pharmacy-directed activities to initiatives requiring interdisciplinary collaboration and strategic planning. Hospital pharmacies should consider establishing an interdisciplinary team that is responsible for systematically reviewing drug cost implications and leading any initiatives that are deemed necessary. Acute care settings can use various operational and clinical strategies to lower their expenditures on high-cost drugs. Operational strategies include various activities that pharmacy staff implement related to contracting, purchasing, and inventory management. Clinical strategies utilize clinical pharmacists working with interdisciplinary teams to develop and maintain a formulary, implement established-use criteria for select drugs, use dose optimization, and implement other clinical tactics aimed at cost containment. After initiatives are implemented, assessing the outcomes of the initiatives is important to determine how successful they were at lowering costs safely and effectively. Acute care hospitals can use various operational and clinical strategies to lower overall drug costs. A systematic stepwise approach is recommended to ensure relevant drugs are regularly reviewed and addressed as needed. © 2016 Pharmacotherapy

Sex-specific respiratory effects of acute and chronic caffeine administration in newborn rats.

PubMed

Kouchi, Hayet; Uppari, NagaPraveena; Joseph, Vincent; Bairam, Aida

2017-06-01

Caffeine is widely used for the treatment of apnea of prematurity (AoP) but whether this effect varies with sex is unknown. To shed some light on this question, we present a summary of data obtained on the effects of caffeine on the respiratory chemoreflexes and apnea frequency in 1- and 12-days old male and female rats. Caffeine was either administered as a single acute injection (10mg/kg, i.p.) or for 10 consecutive days (7.5mg/kg/day between 3 and 12days of life by gavage, simulating its clinical use). Acute caffeine had little effects on breathing in 1-day old male and female rats. In 12-days old female rats caffeine reduced the response to hypercapnia (not hypoxia) compared to males. During the steady state of hypoxia females had a lower frequency of apneas than males, and acute injection of caffeine decreased the frequency of apnea, suppressing the differences between males and females. In 12-days old rats chronic administration of caffeine stimulated basal breathing and decreased the frequency of apnea similarly in males and females. In response to hypoxia, chronic caffeine administration also masked the difference in respiratory frequency between males and females observed in control rats. Female rats had lower frequency of apnea than males with or without caffeine treatment. These observations indicate that sex influences the respiratory responses to caffeine and this effect seems to depend on the modality of administration (acute vs chronic) and environmental oxygen (normoxia vs hypoxia). Copyright © 2017 Elsevier B.V. All rights reserved.

Knowledge Transfer and Dissemination of Advanced Practice Nursing Information and Research to Acute-Care Administrators.

PubMed

Carter, Nancy; Dobbins, Maureen; Peachey, Gladys; Hoxby, Heather; Ireland, Sandra; Akhtar-Danesh, Noori; DiCenso, Alba

2014-03-01

The objective of this study was to ascertain the information needs and knowledge-dissemination preferences of acute-care administrators with respect to advanced practice nursing (APN). Supportive leadership is imperative for the success of APN roles and administrators need up-to-date research evidence and information, but it is unclear what the information needs of administrators are and how they prefer to receive the information. A survey tool was developed from the literature and from the findings of a qualitative study with acute-care leaders. Of 107 surveys distributed to nursing administrators in 2 teaching hospitals, 79 (73.8%) were returned. Just over half of respondents reported wanting APN information related to model of care and patient and systems outcomes of APN care; the majority expressed a preference for electronic transmission of the information. Researchers need multiple strategies for distributing context-specific APN evidence and information to nursing administrators. Copyright© by Ingram School of Nursing, McGill University.

Assessment of knowledge of pediatric nurses related with drug administration and preparation.

PubMed

Bülbül, Ali; Kunt, Ayşe; Selalmaz, Melek; Sözeri, Şehrinaz; Uslu, Sinan; Nuhoğlu, Asiye

2014-12-01

Aim of this study is to determine the levels of knowledge related with drug administration and drug administration errors of nurses who care for pediatric patients. The study data were obtained from the nurses who were working in the departments of pediatrics in two education and research hospitals in the province of İstanbul and who accepted to participate in the study. The questionnaire form of the study was established by the investigators in accordance with the experiences and literature information. A total of 31 questions related with drug preparation, calculation and administration together with the general working properties of the individual were filled out by face to face interview. The data were evaluated using percent and chi-square tests. The study was initiated after ethics committee approval was obtained from Şişli Hamidiye Etfal Education and Research Hospital (365/2013). The study was conducted with 98 nurses who accepted the questionnaire. The education levels of the participants were as follows: undergraduate (48%), high school (32.7%), associate degree (12.2%), master's degree (6.1%) and postgraduate (1%). It was found that 88.8% of the participants worked in a patient-centered fashion and 11.2% worked in a work-centered fashion. The frequency of interruption/distraction during preparation of treatment was found to be 92.9%. It was found that the frequency of checking by two people during preparation or administration of high risk drugs was 64.3% and the conditions under which drugs should be kept were found to known correctly with a rate of 76.5%. It was found that undergraduate healthcare workers were more successful in converting units (p= 0.000). It was found that powder weight of drugs was considered with a rate of 85.7% in calculation. Conclusively, it was found that nurses who worked in pediatric wards did not receive a standard education in terms of drug administration and preparation. It was found that undergraduate nurses were more

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0167] 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...

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.

How Often Are Drugs Made Available Under the Food and Drug Administration's Expanded Access Process Approved?

PubMed

McKee, Amy E; Markon, André O; Chan-Tack, Kirk M; Lurie, Peter

2017-10-01

In this review of individual patient expanded-access requests to the Center for Drug Evaluation and Research for the period Fiscal Year 2010 to Fiscal Year 2014, we evaluated the number of applications received and the number allowed to proceed. We also evaluated whether drugs and certain biologics obtained under expanded access went on to be approved by the Food and Drug Administration. Finally, we considered concerns that adverse events occurring during expanded access might place sponsors at risk for legal liability. Overall, 98% of individual patient expanded-access requests were allowed to proceed. During the study period, among drugs without a previous approval for any indication or dosage form, 24% of unique drugs (ie, multiple applications for access to the same drug were considered to relate to 1 unique drug), and 20% of expanded-access applications received marketing approval by 1 year after initial submission; 43% and 33%, respectively, were approved by 5 years after initial submission. A search of 3 legal databases and a database of news articles did not appear to identify any product liability cases arising from the use of a product in expanded access. Our analyses seek to give physicians and patients a realistic perspective on the likelihood of a drug's approval as well as certain information regarding the product liability risks for commercial sponsors when providing expanded access to investigational drugs. The US Food and Drug Administration (FDA)'s expanded-access program maintains a careful balance between authorizing patient access to potentially beneficial drugs and protecting them from drugs that may have unknown risks. At the same time, the agency wishes to maintain the integrity of the clinical trials process, ultimately the best way to get safe and effective drugs to patients. © 2017, The American College of Clinical Pharmacology.

Innovative nanocompounds for cutaneous administration of classical antifungal drugs: a systematic review.

PubMed

Santos, Rafael Silva; Loureiro, Kahynna; Rezende, Polyana; Nalone, Luciana; Barbosa, Raquel de Melo; Santini, Antonello; Santos, Ana Cláudia; da Silva, Classius F; Souto, Eliana Barbosa; de Souza, Damião Pergentino; Amaral, Ricardo Guimarães; Severino, Patrícia

2018-06-01

Nanomedicine manipulates materials at atomic, molecular, and supramolecular scale, with at least one dimension within the nanometer range, for biomedical applications. The resulting nanoparticles have been consistently shown beneficial effects for antifungal drugs delivery, overcoming the problems of low bioavailability and high toxicity of these drugs. Due to their unique features, namely the small mean particle size, nanoparticles contribute to the enhanced drug absorption and uptake by the target cells, potentiating the therapeutic drug effect. The topical route is desirable due to the adverse effects arising from oral administration. This review provides a comprehensive analysis of the use of nano compounds for the current treatment of topical fungal infections. A special emphasis is given to the employment of lipid nanoparticles, due to their recognized efficacy, versatility and biocompatibility, attracting the major attention as novel topical nanocompounds used for the administration of antifungal drugs.

76 FR 77542 - Draft Guidance for Industry and Food and Drug Administration Staff on Humanitarian Use Device...

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2011-12-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0847] Draft Guidance for Industry and Food and Drug Administration Staff on Humanitarian Use Device Designations; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

76 FR 51993 - Draft Guidance for Industry and Food and Drug Administration Staff on In Vitro Companion...

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2011-08-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0215] Draft Guidance for Industry and Food and Drug Administration Staff on In Vitro Companion Diagnostic Devices; Extension of Comment Period AGENCY: Food and Drug Administration, HHS. ACTION: Notice; extension...

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0469] Draft Guidance for Industry and Food and Drug Administration Staff: Applying Human Factors and Usability Engineering To Optimize Medical Device Design; Availability AGENCY: Food and Drug Administration, HHS. ACTION...

78 FR 14305 - Draft Guidance for Industry and Food and Drug Administration Staff; Types of Communication During...

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2013-03-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-0147] Draft Guidance for Industry and Food and Drug Administration Staff; Types of Communication During the Review of Medical Device Submissions; Availability AGENCY: Food and Drug Administration, HHS. ACTION...

77 FR 41413 - Draft Guidance for Industry and Food and Drug Administration Staff; Medical Devices: The Pre...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0530... Program and Meetings With FDA Staff; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the draft...

76 FR 36133 - Draft Guidances for Industry and Food and Drug Administration Staff: Classification of Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0429] Draft Guidances for Industry and Food and Drug Administration Staff: Classification of Products as Drugs... Action'' in the Definition of Device Under Section 201(h) of the Federal Food, Drug, and Cosmetic Act...

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

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Drug Enforcement Administration... ENVIRONMENTAL POLICY ACT Pt. 61, App. B Appendix B to Part 61—Drug Enforcement Administration Procedures.... This part applies to all organizational elements of the Drug Enforcement Administration [DEA]. 2...

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

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2011-10-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0529] Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small Business; Extension of Comment Period AGENCY: Food and Drug Administration, HHS. ACTION: Notice; extension of comment...

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

Code of Federal Regulations, 2010 CFR

2010-04-01

... Specific Categories of Records § 20.108 Agreements between the Food and Drug Administration and other... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Agreements between the Food and Drug Administration and other departments, agencies, and organizations. 20.108 Section 20.108 Food and Drugs FOOD AND...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1056] 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...

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0140] Draft Guidance for Industry on Notification to Food and Drug Administration of Issues That May Result in a Prescription Drug Shortage; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice...

Food and Drug Administration Regulation of in Vitro Diagnostic Devices

PubMed Central

Mansfield, Elizabeth; O’Leary, Timothy J.; Gutman, Steven I.

2005-01-01

The Food and Drug Administration regulates the sale and distribution of laboratory devices under a statutory and regulatory framework that is unfamiliar to most clinical laboratory scientists. In this article we briefly describe the criteria that are used to classify and review in vitro diagnostic devices. We discuss the similarities and differences between devices that are not subject to premarket review, and those that are required to undergo either a premarket application or premarket notification [510(k)] pathway. We then discuss the methods that the Food and Drug Administration uses to assess the performance of in vitro diagnostic devices in the marketplace as a component of the total life cycle approach to medical device regulation. PMID:15681468

Effects of acute administration of nicotine, amphetamine, diazepam, morphine, and ethanol on risky decision-making in rats

PubMed Central

Mitchell, Marci R.; Vokes, Colin M.; Blankenship, Amy L.; Simon, Nicholas W.

2011-01-01

Rationale Most individuals can accurately assess the risks and rewards associated with choice alternatives and decide accordingly; however, drug users often display maladaptive decision-making, such that choices are biased toward excessively risky options. Objective The purpose of this study was to investigate the effects of a range of drugs of abuse on risky decision-making. Methods Male Long–Evans rats were trained in the Risky Decision-Making Task, in which they chose between two levers, one which produced a small, “safe” food reward and the other which produced a large, “risky” food reward. The large reward was accompanied by the risk of a mild footshock, the probability of which increased over the course of each test session (0%, 25%, 50%, 75%, and 100%). Results Nicotine (0.6 mg/kg) and amphetamine (1.5 mg/kg) caused a significant decrease in choice of the large risky reward (decreased risk taking). Diazepam (1.0 mg/kg) caused a significant increase in choice of the large risky reward (increased risk taking), whereas morphine (3.0 mg/kg) caused only a trend toward increased choice of the large risky reward. Ethanol had no effect on choice behavior. Conclusions These results show that acute administration of drugs of abuse can modulate risk taking in a drug-specific manner, either increasing or decreasing preference for highly rewarding, but risky, options. PMID:21638222

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2002-D-0094; (formerly Docket No. 02D-0049)] Guidance for the Public, Food and Drug Administration (FDA) Advisory... Food and Drug Administration (FDA) is announcing the availability of a guidance for the public, FDA...

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...

Drug distribution in man: a positron emission tomography study after oral administration of the labelled neuroprotective drug vinpocetine.

PubMed

Gulyás, Balázs; Halldin, Christer; Sóvágó, Judit; Sandell, Johan; Cselényi, Zsolt; Vas, Adám; Kiss, Béla; Kárpáti, Egon; Farde, Lars

2002-08-01

Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [(11)C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [(11)C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [(11)C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and pharmacokinetics of orally

21 CFR 868.5115 - Device to relieve acute upper airway obstruction.

Code of Federal Regulations, 2014 CFR

2014-04-01

... the event of choking on a foreign body, can be applied to the abdomen and pushed upward to generate... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Device to relieve acute upper airway obstruction. 868.5115 Section 868.5115 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 868.5115 - Device to relieve acute upper airway obstruction.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Device to relieve acute upper airway obstruction. 868.5115 Section 868.5115 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... the event of choking on a foreign body, can be applied to the abdomen and pushed upward to generate...

75 FR 21000 - Draft Guidance for the Public, Food and Drug Administration Advisory Committee Members, and Food...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-22

...] (formerly Docket No. 02D-0049) Draft Guidance for the Public, Food and Drug Administration Advisory Committee Members, and Food and Drug Administration Staff: Public Availability of Advisory Committee Members... and Drug Administration Amendments Act of 2007, Public Law No. 110-85), and section 701 (21 U.S.C. 371...

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

...] Draft Guidance for Industry and Food and Drug Administration Staff; Providing Information About... Guidance for Industry and Food and Drug Administration Staff: Providing Information About Pediatric Uses of...ComplianceRegulatoryInformation/default.htm . To receive ``Draft Guidance for Industry and Food and Drug...

77 FR 21982 - Cardiovascular and Renal Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-12

...] Cardiovascular and Renal Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS...: Cardiovascular and Renal Drugs Advisory Committee. General Function of the Committee: To provide advice and...., to reduce the risk of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS...

A rare cause of acute coronary syndrome: Kounis syndrome.

PubMed

Almeida, João; Ferreira, Sara; Malheiro, Joana; Fonseca, Paulo; Caeiro, Daniel; Dias, Adelaide; Ribeiro, José; Gama, Vasco

2016-12-01

Kounis syndrome is an acute coronary syndrome in the context of a hypersensitivity reaction. The main pathophysiological mechanism appears to be coronary vasospasm. We report the case of a patient with a history of allergy to quinolones, who was given ciprofloxacin before an elective surgical procedure and during drug administration developed symptoms and electrocardiographic changes suggestive of ST-segment elevation acute coronary syndrome. The drug was suspended and coronary angiography excluded epicardial coronary disease. Two hours after withdrawal of the drug the symptoms and ST elevation had resolved completely. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Age-Dependent Effects of Acute Alcohol Administration in the Hippocampal Phosphoproteome.

PubMed

Contreras, Ana; Morales, Lidia; Tebourbi, Ali; Miguéns, Miguel; Olmo, Nuria Del; Pérez-García, Carmen

2017-12-18

Alcohol consumption during adolescence is deleterious to the developing brain and leads to persistent deficits in adulthood. Several results provide strong evidence for ethanol-associated alterations in glutamatergic signaling and impaired synaptic plasticity in the hippocampus. Protein phosphorylation is a well-known and well-documented mechanism in memory processes, but information on phosphoprotein alterations in hippocampus after ethanol exposure is limited. This study focuses on age-related changes in the hippocampal phosphoproteome after acute alcohol administration. We have compared the phosphoprotein expression in the hippocampus of adult and adolescent Wistar rats treated with a single dose of ethanol (5 g/kg i.p.), using a proteomic approach including phosphoprotein enrichment by immobilized metal affinity chromatography (IMAC). Our proteomic analysis revealed that 13 proteins were differentially affected by age, ethanol administration, or both. Most of these proteins are involved in neuroprotection and are expressed less in young rats treated with ethanol. We conclude that acute alcohol induces important changes in the expression of phosphoproteins in the hippocampus that could increase the risk of neurodegenerative disorders, especially when the alcohol exposure begins in adolescence.

Effect of 'chronic' versus 'acute' ketamine administration and its 'withdrawal' effect on behavioural alterations in mice: implications for experimental psychosis.

PubMed

Chatterjee, Manavi; Ganguly, Surajit; Srivastava, Mukesh; Palit, Gautam

2011-01-01

Lack of appropriate animal models simulating core behavioural aspects of human psychosis is a major limitation in schizophrenia research. The use of drugs, that is believed to act through N-methyl d-aspartate receptor, has been demonstrated to mimic relatively broader range of behavioural symptoms in putative animal models. Our goal in this study has been to further evaluate one such drug, ketamine in mice and characterize some selective behavioural phenotypes associated with the drug dosage, treatment period and withdrawal effects to extend the understanding of this model. Our results indicate that acute treatment of ketamine (100 mg/kg, i.p.) induced hyperlocomotory response and reduced the 'transfer-latency time' in passive avoidance test but did not have any effect in the forced swim test (negative symptoms). In contrast, chronic administration of ketamine not only produced significant 'hyperactivity' response but also enhanced the immobility period in animals during the forced swim test and reduced the latency period in the passive avoidance test. Further, these behavioural alterations persisted at least for 10 days after the withdrawal of ketamine treatment. These observations were substantiated by using standard typical and atypical antipsychotic drugs, haloperidol (0.25 mg/kg, i.p.), clozapine (10 mg/kg, i.p.) and risperidone (0.025 mg/kg, i.p.). Therefore, the present study suggests that the chronic treatment with ketamine has the potential of exhibiting changes in broader range of behavioural domains than the acute treatment. Hence, animals chronically treated with ketamine might serve as a useful tool to study the underlying pathogenic mechanisms associated with some symptoms in schizophrenia and other psychiatric disorders. Copyright © 2010 Elsevier B.V. All rights reserved.

Opioid analgesic administration in patients with suspected drug use.

PubMed

Kreling, Maria Clara Giorio Dutra; Mattos-Pimenta, Cibele Andrucioli de

2017-01-01

To identify the prevalence of patients suspected of drug use according to the nursing professionals' judgement, and compare the behavior of these professionals in opioid administration when there is or there is no suspicion that patient is a drug user. A cross-sectional study with 507 patients and 199 nursing professionals responsible for administering drugs to these patients. The Chi-Square test, Fisher's Exact and a significance level of 5% were used for the analyzes. The prevalence of suspected patients was 6.7%. The prevalence ratio of administration of opioid analgesics 'if necessary' is twice higher among patients suspected of drug use compared to patients not suspected of drug use (p = 0.037). The prevalence of patients suspected of drug use was similar to that of studies performed in emergency departments. Patients suspected of drug use receive more opioids than patients not suspected of drug use. Identificar a prevalência de pacientes com suspeita de uso de drogas conforme opinião de profissionais de enfermagem e comparar a conduta desses profissionais na administração de opioides quando há ou não suspeita de que o paciente seja usuário de drogas. Estudo transversal com 507 pacientes e 199 profissionais de enfermagem responsáveis pela administração de medicamentos a esses pacientes. Para as análises foram utilizados os testes de Qui-Quadrado, Exato de Fisher e um nível de significância de 5%. A prevalência de pacientes suspeitos foi 6,7%. A razão de prevalência de administração de analgésicos opioides "se necessário" é duas vezes maior entre os pacientes suspeitos em relação aos não suspeitos (p=0,037). A prevalência de suspeitos foi semelhante à de estudos realizados em departamentos de emergência. Os suspeitos de serem usuários de drogas recebem mais opioides do que os não suspeitos.

Acute effects of intravenous cocaine administration on serum concentrations of ghrelin, amylin, glucagon-like peptide-1, insulin, leptin and peptide YY and relationships with cardiorespiratory and subjective responses.

PubMed

Bouhlal, Sofia; Ellefsen, Kayla N; Sheskier, Mikela B; Singley, Erick; Pirard, Sandrine; Gorelick, David A; Huestis, Marilyn A; Leggio, Lorenzo

2017-11-01

Food intake and use of drugs of abuse like cocaine share common central and peripheral physiological pathways. Appetitive hormones play a major role in regulating food intake; however, little is known about the effects of acute cocaine administration on the blood concentrations of these hormones in cocaine users. We evaluated serum concentrations of six appetitive hormones: ghrelin (total and acyl-ghrelin), amylin, glucagon-like peptide-1 (GLP-1), insulin, leptin and peptide YY (PYY), as well as acute cardiorespiratory and subjective responses of 8 experienced cocaine users who received 25mg intravenous (IV) cocaine. Serum concentrations of GLP-1 (p=0.014) and PYY (p=0.036) were significantly decreased one hour following IV cocaine administration; there was a trend towards a decrease for insulin (p=0.055) and amylin (p=0.063) concentrations, while no significant IV cocaine effect was observed for ghrelin (total or acyl-ghrelin) or leptin concentrations (p's≫>0.5). We also observed associations between hormone concentrations acutely affected by IV cocaine (GLP-1, PYY, insulin, amylin) and some cocaine-related cardiorespiratory and subjective responses (e.g., increased heart and respiratory rates; feeling high and anxious). These findings show a significant effect of acute IV cocaine administration on some appetitive hormones and suggest potential associations between these hormones and cocaine-related cardiorespiratory and subjective responses. Additional research is needed to further investigate the potential mechanisms underlining these associations. Published by Elsevier B.V.

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,...

Elimination and eradication of neglected tropical diseases with mass drug administrations: a survey of experts.

PubMed

Keenan, Jeremy D; Hotez, Peter J; Amza, Abdou; Stoller, Nicole E; Gaynor, Bruce D; Porco, Travis C; Lietman, Thomas M

2013-01-01

Lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths, and trachoma are the five most prevalent neglected tropical diseases in the world, and each is frequently treated with mass drug administrations. We performed a survey of neglected tropical diseases experts to elicit their opinions on the role of mass drug administrations for the elimination of these infections. We sent an online survey to corresponding authors who had published an article about a neglected tropical disease from 2007 to 2011. Of 825 unique authors who were invited to complete the survey, 365 (44.2%) responded, including 234 (28.4%) who answered questions regarding one of the five most prevalent neglected tropical diseases. Respondents had varying opinions about the goals of programmatic activities for their chosen neglected tropical disease, with elimination or eradication identified as the most important goal by 87% of lymphatic filariasis respondents, 66% of onchocerciasis respondents, 55% of trachoma respondents, 24% of schistosomiasis respondents, and 21% of soil-transmitted helminth respondents. Mass drug administrations, other non-medication health measures, and education were generally thought to be more important for elimination than vector control, development of a new tool, or the presence of a secular trend. Drug resistance was thought to be a major limitation of mass drug administrations for all five neglected tropical diseases. Over half of respondents for lymphatic filariasis and trachoma thought that repeated mass drug administrations could eliminate infection within ten years of the initiation of mass treatments. Respondents for lymphatic filariasis, onchocerciasis, and trachoma were more enthusiastic about the prospects of elimination and eradication than were respondents for schistosomiasis or soil-transmitted helminths. Mass drug administrations were generally believed to be among the most important factors for the success of elimination efforts

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

... http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/GuidancesInformationSheetsand...] (formerly 1999D-4396) Guidance for Clinical Investigators, Industry, and Food and Drug Administration Staff: Financial Disclosure by Clinical Investigators; Availability AGENCY: Food and Drug Administration, HHS...

GABAergic modulation of human social interaction in a prisoner’s dilemma model via acute administration of alprazolam

PubMed Central

Lane, Scott D.; Gowin, Joshua L.

2010-01-01

Recent work in neuroeconomics has utilized 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 (PD) model following acute administration of the 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 PD 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. PMID:19667972

Preclinical drug evaluation for combination therapy in acute stroke using systematic review, meta-analysis, and subsequent experimental testing

PubMed Central

O'Collins, Victoria E; Macleod, Malcolm R; Cox, Susan F; Van Raay, Leena; Aleksoska, Elena; Donnan, Geoffrey A; Howells, David W

2011-01-01

There is some evidence that in animal models of acute ischaemic stroke, combinations of neuroprotective agents might be more efficacious than the same agents administered alone. Hence, we developed pragmatic, empirical criteria based on therapeutic target, cost, availability, efficacy, administration, and safety to select drugs for testing in combination in animal models of acute stroke. Magnesium sulphate, melatonin, and minocycline were chosen from a library of neuroprotective agents, and were tested in a more ‘realistic' model favoured by the STAIR (Stroke Therapy Academic Industry Roundtable). Outcome was assessed with infarct volume, neurologic score, and two newly developed scales measuring general health and physiologic homeostasis. Owing to the failure to achieve neuroprotection in aged, hypertensive animals with drug delivery at 3 hours, the bar was lowered in successive experiments to determine whether neuroprotection could be achieved under conditions more conducive to recovery. Testing in younger animals showed more favourable homeostasis and general health scores than did testing in older animals, but infarct volume and neurologic scores did not differ with age, and treatment efficacy was again not shown. Testing with shorter occlusions resulted in smaller infarct volumes; nevertheless, treatment efficacy was still not observed. It was concluded that this combination, in these stroke models, was not effective. PMID:20978519

75 FR 31450 - Memorandum of Understanding by and Between the United States Food and Drug Administration and the...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-03

... Administration and the International Anesthesia Research Society for the Safety of Key Inhaled and Intravenous Drugs in Pediatrics Public-Private Partnership AGENCY: Food and Drug Administration, HHS. ACTION: Notice... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0004...

78 FR 28228 - Guidance for Industry and Food and Drug Administration Staff on Best Practices for Conducting and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0057] Guidance for Industry and Food and Drug Administration Staff on Best Practices for Conducting and Reporting Pharmacoepidemiologic Safety Studies Using Electronic Healthcare Data; Availability AGENCY: Food and Drug Administration...

Reduced fear-recognition sensitivity following acute buprenorphine administration in healthy volunteers.

PubMed

Ipser, Jonathan C; Terburg, David; Syal, Supriya; Phillips, Nicole; Solms, Mark; Panksepp, Jaak; Malcolm-Smith, Susan; Thomas, Kevin; Stein, Dan J; van Honk, Jack

2013-01-01

In rodents, the endogenous opioid system has been implicated in emotion regulation, and in the reduction of fear in particular. In humans, while there is evidence that the opioid antagonist naloxone acutely enhances the acquisition of conditioned fear, there are no corresponding data on the effect of opioid agonists in moderating responses to fear. We investigated whether a single 0.2mg administration of the mu-opioid agonist buprenorphine would decrease fear sensitivity with an emotion-recognition paradigm. Healthy human subjects participated in a randomized placebo-controlled within-subject design, in which they performed a dynamic emotion recognition task 120min after administration of buprenorphine and placebo. In the recognition task, basic emotional expressions were morphed between their full expression and neutral in 2% steps, and presented as dynamic video-clips with final frames of different emotional intensity for each trial, which allows for a fine-grained measurement of emotion sensitivity. Additionally, visual analog scales were used to investigate acute effects of buprenorphine on mood. Compared to placebo, buprenorphine resulted in a significant reduction in the sensitivity for recognizing fearful facial expressions exclusively. Our data demonstrate, for the first time in humans, that acute up-regulation of the opioid system reduces fear recognition sensitivity. Moreover, the absence of an effect of buprenorphine on mood provides evidence of a direct influence of opioids upon the core fear system in the human brain. Copyright © 2012 Elsevier Ltd. All rights reserved.

Administration of human recombinant activated protein C is not associated with pancreatic parenchymal haemorrhage in L-arginine-induced experimental acute pancreatitis.

PubMed

Jamdar, Saurabh; Babu, Benoy I; Nirmalan, Mahesh; Jeziorska, Maria; McMahon, Raymond F T; Siriwardena, Ajith K

2013-11-10

Microvascular thrombosis is a critical event in severe acute pancreatitis. Human recombinant activated protein C (Xigris®, Eli Lilly, Indianapolis, IN, USA) modulates the interplay between pro-inflammatory and pro-coagulant pathways and maintains microvascular patency. However, the anticoagulant properties of Xigris® may precipitate bleeding from the inflamed pancreas. This study tests the hypothesis that Xigris® can ameliorate experimental acute pancreatitis without causing pancreatic haemorrhage. Sprague Dawley rats were allocated as follows: Group 1: control (n=7); Group 2: acute pancreatitis (n=6); Group 3: administration of Xigris® 500 µg/kg body weight before induction of acute pancreatitis (n=6); and Group 4: Administration of Xigris® 500 µg/kg body weight 30 minutes after induction of acute pancreatitis (n=6). Acute pancreatitis was induced by intraperitoneal administration of L-arginine 300 mg/100 g body weight. Animals were sacrificed at 48 hours and biochemical, haematological, and histological markers of pancreatic haemorrhage and inflammation assessed. Median lipase in animals with acute pancreatitis was 10 U/mL (range: 7-16 U/mL) compared to 5.5 (range: 3-8 U/mL) in controls (P=0.028). Lipase was also elevated in animals given Xigris® both before (12 U/mL, range: 8-22 U/mL; P=0.031 vs. control group) and after (46 U/mL, range: 9-71 U/mL; P=0.015 vs. control group) induction of acute pancreatitis). Haemoglobin levels were similar among all groups (P=0.323). There was no histological evidence of pancreatic haemorrhage in animals treated with Xigris®. Pre-treatment with Xigris® was associated with a significant reduction in pancreatic injury. This effect was absent when Xigris® was administered after induction of acute pancreatitis. Xigris® did not lead to pancreatic haemorrhage in experimental acute pancreatitis. Administration of Xigris® prior to induction of acute pancreatitis was associated with amelioration of injury. This effect was

77 FR 70166 - Provisions of the Food and Drug Administration Safety and Innovation Act Related to Medical Gases...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-23

...; Establishment of a Public Docket AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is establishing a public docket for information pertaining to FDA's... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1090...

Effects of escitalopram and imipramine on cocaine reinforcement and drug-seeking behaviors in a rat model of depression.

PubMed

Jastrzębska, Joanna; Frankowska, Małgorzata; Suder, Agata; Wydra, Karolina; Nowak, Ewa; Filip, Małgorzata; Przegaliński, Edmund

2017-10-15

Depression and substance cocaine abuse are disorders with a high frequency of comorbidity. In the present study, we combined bilateral olfactory bulbectomy (OBX), an animal model of depression, with intravenous cocaine self-administration and extinction/reinstatement in rats to investigate the effects of two antidepressant drugs, escitalopram (ESC) and imipramine (IMI), with the goal of determining whether these drugs altered cocaine-induced reinforcement and seeking behaviors. Acute administration of IMI (2.5-30mg/kg) reduced the cocaine reinforcement in OBX and SHAM rats. Moreover, IMI effectively reduced the cocaine-seeking behavior after the drug acute or repeated administration during extinction training in OBX rats and SHAM-operated controls. By contrast, acutely administered ESC (2.5-20mg/kg) did not alter cocaine reinforcement in OBX rats or SHAM-operated controls. The lack of ESC effects was also demonstrated during reinstatement tests to study drug-seeking behavior after ESC repeated daily treatment during extinction trials. However, acute treatment with ESC dose-dependently decreased the cocaine-seeking behavior and relapse triggered by cocaine priming or drug-associated conditioned cues in both OBX and SHAM rats. These results indicate the cocaine anti-reinforcement and anti-seeking efficacy of the two antidepressant drugs studied here. However, the mechanisms for the IMI and ESC activity should be clarified in further studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Acute behavioral effects of co-administration of mephedrone and MDMA in mice.

PubMed

Budzynska, Barbara; Michalak, Agnieszka; Frankowska, Małgorzata; Kaszubska, Katarzyna; Biała, Grażyna

2017-04-01

Abuse of more than one psychoactive drug is becoming a global problem. Our experiments were designed to examine the effects of a concomitant administration of 3,4-methylenedioxy-methamphetamine (MDMA) and mephedrone on depression- and anxiety-like behaviors and cognitive processes in Swiss mice. In order to investigate the drug interactions the forced swimming test (FST) - an animal model of depression, the passive avoidance (PA) test - a memory and learning paradigm, as well as the elevated plus maze (EPM) test - test for anxiety level were used. The results revealed that a concomitant administration of non-effective doses of mephedrone (1mg/kg) and MDMA (1mg/kg) exerted marked antidepressive effects in the FST. Also a co-administration of mephedrone (2.5mg/kg) and MDMA (1mg/kg) displayed a pro-cognitive action in the PA paradigm. Furthermore, even though mephedrone and MDMA can, in general, exert some anxiogenic effects in mice, the concomitant administration of nonactive doses of both drugs (0.05 and 0.1mg/kg, respectively) in the EPM test, did not show any synergistic effect in our study. The effects of mephedrone and MDMA combination on mammalian organisms were attempted to be evaluated in our study and the results are described in the present report. These results may help explain the reasons for and consequences of a concomitant administration of psychoactive substances with regards to the central nervous system, while being possibly useful in the treatment of polydrug intoxication. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Presentations to an urban emergency department in Bern, Switzerland associated with acute recreational drug toxicity.

PubMed

Liakoni, Evangelia; Müller, Sabine; Stoller, Adrian; Ricklin, Meret; Liechti, Matthias E; Exadaktylos, Aristomenis K

2017-03-07

Although the recreational use of psychoactive substances is common there is only limited systematic collection of data on acute drug toxicity or hospital presentations. Currently, data from Switzerland are only available from the University Hospital of Basel. The present study aimed to describe the presentations due to recreational drug use at an emergency department in Bern, Switzerland during a 4 year period. Retrospective analysis of cases presenting from May 2012 to April 2016 at the emergency department of the University Hospital of Bern, Switzerland, with symptoms/signs consistent with acute toxicity of recreational drug use. The cases were retrieved using a comprehensive full-text search algorithm of the electronic health records. Isolated ethanol intoxications were excluded. During the study period, 503 of the 157,328 emergency department attendances were directly related to acute toxicity of substances used recreationally. The mean patient age was 33 years (range 16-74), 68% were male. Alcohol co-ingestion was reported in 54% of the cases, and use of more than one recreational drug in 37% of the cases. Most presentations were related to cocaine (29%), cannabis (26%), heroin (20%) and benzodiazepines/sedatives (18%). Urine drug screening immunoassay was available in 277 cases (55%). The most frequently detected substances were cannabis (29%), cocaine (22%), benzodiazepines (21%) and opioids excluding methadone (20%). There were only two intoxications with novel psychoactive substances (NPSs): One with methylone and one with 2,5-dimethoxy-4(n)-propylphenethylamine (2C-P). The majority of patients (58%) displayed impaired consciousness (Glasgow Coma Scale (GCS) <15) upon presentation and/or pre-hospital; 21% were unconscious (GCS <8). Other frequent symptoms were agitation (36%), tachycardia (29%), and anxiety (24%). Severe complications included two fatalities, three acute myocardial infarctions, two intracranial haemorrhages, as well as psychosis and

The effects of nicotine dependence and acute abstinence on the processing of drug and non-drug rewards.

PubMed

Lawn, W; Freeman, T P; Hindocha, C; Mokrysz, C; Das, R K; Morgan, C J A; Curran, H V

2015-07-01

Drug addiction may be characterised by a hypersensitivity to drug rewards and a hyposensitivity to non-drug rewards. This imbalance may become further polarised during acute abstinence. (i) Examine the differences between dependent and occasional smokers in choices for, motivation for and self-reported wanting and liking of cigarette and non-drug rewards. (ii) Examine the effects of 12-h nicotine abstinence on these metrics. Dependent (n = 20) and occasional, non-dependent smokers (n = 20) were tested after ad libitum smoking and ≥12-h of nicotine abstinence. A novel task was developed (Drug, Reward and Motivation-Choice (DReaM-Choice)) in which different rewards (cigarettes, music and chocolate) could be won. In each trial, participants chose between two rewards and then could earn the chosen reward via repeated button-pressing. Participants subsequently 'consumed' and rated subjective liking of the rewards they had won. Compared with occasional smokers, dependent smokers made more choices for (p < 0.001), pressed more for (p = 0.046) and reported more wanting (p = 0.007) and liking (p < 0.001) of cigarettes, and also made fewer choices for chocolate (p = 0.005). There were no differences between the groups on button-pressing for chocolate or music. However, the balance between drug and non-drug reward processing was different between the groups across all metrics. Twelve-hour nicotine abstinence led to more cigarette choices (p < 0.001) and fewer music choices (p = 0.042) in both groups. Nicotine dependence was associated with a hypersensitivity to cigarette rewards, but we found little evidence indicating a hyposensitivity to non-drug rewards. Our findings question the moderating influence of dependence on how acute nicotine abstinence affects reward processing.

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0247] Food and Drug Administration Transparency Initiative: Exploratory Program To Increase Access to the... responsible for a broad range of compliance and enforcement activities. Increasing the transparency of these...

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

Serotonin antagonists fail to alter MDMA self-administration in rats.

PubMed

Schenk, Susan; Foote, Jason; Aronsen, Dane; Bukholt, Natasha; Highgate, Quenten; Van de Wetering, Ross; Webster, Jeremy

2016-09-01

Acute exposure to ±3,4-methylenedioxymethamphetamine (MDMA) preferentially increases release of serotonin (5-HT), and a role of 5-HT in many of the behavioral effects of acute exposure to MDMA has been demonstrated. A role of 5-HT in MDMA self-administration in rats has not, however, been adequately determined. Therefore, the present study measured the effect of pharmacological manipulation of some 5-HT receptor subtypes on self-administration of MDMA. Rats received extensive experience with self-administered MDMA prior to tests with 5-HT ligands. Doses of the 5-HT1A antagonist, WAY 100635 (0.1-1.0mg/kg), 5-HT1B antagonist, GR 127935 (1.0-3.0mg/kg), and the 5-HT2A antagonist, ketanserin (1.0-3.0mg/kg) that have previously been shown to decrease self-administration of other psychostimulants and that decreased MDMA-produced hyperactivity in the present study did not alter MDMA self-administration. Experimenter-administered injections of MDMA (10.0mg/kg, ip) reinstated extinguished drug-taking behavior, but this also was not decreased by any of the antagonists. In contrast, both WAY 100635 and ketanserin, but not GR 127935, decreased cocaine-produced drug seeking in rats that had been trained to self-administered cocaine. The 5-HT1A agonist, 8-OH-DPAT (0.1-1.0mg/kg), but not the 5-HT1B/1A agonist, RU 24969 (0.3-3.0mg/kg), decreased drug-seeking produced by the reintroduction of a light stimulus that had been paired with self-administered MDMA infusions. These findings suggest a limited role of activation of 5-HT1A, 5-HT1B or 5-HT2 receptor mechanisms in MDMA self-administration or in MDMA-produced drug-seeking following extinction. The data suggest, however, that 5-HT1A agonists inhibit cue-induced drug-seeking following extinction of MDMA self-administration and might, therefore, be useful adjuncts to therapies to limit relapse to MDMA use. Copyright © 2016 Elsevier Inc. All rights reserved.

A systematic review of validated methods to capture acute bronchospasm using administrative or claims data.

PubMed

Sharifi, Mona; Krishanswami, Shanthi; McPheeters, Melissa L

2013-12-30

To identify and assess billing, procedural, or diagnosis code, or pharmacy claim-based algorithms used to identify acute bronchospasm in administrative and claims databases. We searched the MEDLINE database from 1991 to September 2012 using controlled vocabulary and key terms related to bronchospasm, wheeze and acute asthma. We also searched the reference lists of included studies. Two investigators independently assessed the full text of studies against pre-determined inclusion criteria. Two reviewers independently extracted data regarding participant and algorithm characteristics. Our searches identified 677 citations of which 38 met our inclusion criteria. In these 38 studies, the most commonly used ICD-9 code was 493.x. Only 3 studies reported any validation methods for the identification of bronchospasm, wheeze or acute asthma in administrative and claims databases; all were among pediatric populations and only 2 offered any validation statistics. Some of the outcome definitions utilized were heterogeneous and included other disease based diagnoses, such as bronchiolitis and pneumonia, which are typically of an infectious etiology. One study offered the validation of algorithms utilizing Emergency Department triage chief complaint codes to diagnose acute asthma exacerbations with ICD-9 786.07 (wheezing) revealing the highest sensitivity (56%), specificity (97%), PPV (93.5%) and NPV (76%). There is a paucity of studies reporting rigorous methods to validate algorithms for the identification of bronchospasm in administrative data. The scant validated data available are limited in their generalizability to broad-based populations. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multimodal system designed to reduce errors in recording and administration of drugs in anaesthesia: prospective randomised clinical evaluation.

PubMed

Merry, Alan F; Webster, Craig S; Hannam, Jacqueline; Mitchell, Simon J; Henderson, Robert; Reid, Papaarangi; Edwards, Kylie-Ellen; Jardim, Anisoara; Pak, Nick; Cooper, Jeremy; Hopley, Lara; Frampton, Chris; Short, Timothy G

2011-09-22

To clinically evaluate a new patented multimodal system (SAFERSleep) designed to reduce errors in the recording and administration of drugs in anaesthesia. Prospective randomised open label clinical trial. Five designated operating theatres in a major tertiary referral hospital. Eighty nine consenting anaesthetists managing 1075 cases in which there were 10,764 drug administrations. Use of the new system (which includes customised drug trays and purpose designed drug trolley drawers to promote a well organised anaesthetic workspace and aseptic technique; pre-filled syringes for commonly used anaesthetic drugs; large legible colour coded drug labels; a barcode reader linked to a computer, speakers, and touch screen to provide automatic auditory and visual verification of selected drugs immediately before each administration; automatic compilation of an anaesthetic record; an on-screen and audible warning if an antibiotic has not been administered within 15 minutes of the start of anaesthesia; and certain procedural rules-notably, scanning the label before each drug administration) versus conventional practice in drug administration with a manually compiled anaesthetic record. Primary: composite of errors in the recording and administration of intravenous drugs detected by direct observation and by detailed reconciliation of the contents of used drug vials against recorded administrations; and lapses in responding to an intermittent visual stimulus (vigilance latency task). Secondary: outcomes in patients; analyses of anaesthetists' tasks and assessments of workload; evaluation of the legibility of anaesthetic records; evaluation of compliance with the procedural rules of the new system; and questionnaire based ratings of the respective systems by participants. The overall mean rate of drug errors per 100 administrations was 9.1 (95% confidence interval 6.9 to 11.4) with the new system (one in 11 administrations) and 11.6 (9.3 to 13.9) with conventional methods (one

Increased Excitability of Lateral Habenula Neurons in Adolescent Rats following Cocaine Self-Administration

PubMed Central

Ishikawa, Masago; Otaka, Mami; Huang, Yanhua H.; Schlüter, Oliver M.

2015-01-01

Background: The lateral habenula is a brain region that has been critically implicated in modulating negative emotional states and responses to aversive stimuli. Exposure to addictive drugs such as cocaine negatively impacts affective states, an effect persisting longer than acute drug effects. However, the mechanisms of this effect are poorly understood. We hypothesized that drugs of abuse, such as cocaine, may contribute to drug-induced negative affective states by altering the firing properties of lateral habenula neurons, thus changing the signaling patterns from the lateral habenula to downstream circuits. Methods: Using whole-cell current-clamp recording of acutely prepared brain slices of rats after various periods of withdrawal from cocaine self-administration, we characterized an important heterogeneous subregion of the lateral habenula based on membrane properties. Results: We found two major relevant neuronal subtypes: burst firing neurons and regular spiking neurons. We also found that lateral habenula regular spiking neurons had higher membrane excitability for at least 7 days following cocaine self-administration, likely due to a greater membrane resistance. Both the increase in lateral habenula excitability and membrane resistance returned to baseline when tested after a more prolonged period of 45 days of withdrawal. Conclusion: This is the first study to look at intrinsic lateral habenula neuron properties following cocaine exposure beyond acute drug effects. These results may help to explain how cocaine and other drugs negatively impact affect states. PMID:25548105

Comparing errors in ED computer-assisted vs conventional pediatric drug dosing and administration.

PubMed

Yamamoto, Loren; Kanemori, Joan

2010-06-01

Compared to fixed-dose single-vial drug administration in adults, pediatric drug dosing and administration requires a series of calculations, all of which are potentially error prone. The purpose of this study is to compare error rates and task completion times for common pediatric medication scenarios using computer program assistance vs conventional methods. Two versions of a 4-part paper-based test were developed. Each part consisted of a set of medication administration and/or dosing tasks. Emergency department and pediatric intensive care unit nurse volunteers completed these tasks using both methods (sequence assigned to start with a conventional or a computer-assisted approach). Completion times, errors, and the reason for the error were recorded. Thirty-eight nurses completed the study. Summing the completion of all 4 parts, the mean conventional total time was 1243 seconds vs the mean computer program total time of 879 seconds (P < .001). The conventional manual method had a mean of 1.8 errors vs the computer program with a mean of 0.7 errors (P < .001). Of the 97 total errors, 36 were due to misreading the drug concentration on the label, 34 were due to calculation errors, and 8 were due to misplaced decimals. Of the 36 label interpretation errors, 18 (50%) occurred with digoxin or insulin. Computerized assistance reduced errors and the time required for drug administration calculations. A pattern of errors emerged, noting that reading/interpreting certain drug labels were more error prone. Optimizing the layout of drug labels could reduce the error rate for error-prone labels. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Radiopharmaceutical regulation and Food and Drug Administration policy.

PubMed

Rotman, M; Laven, D; Levine, G

1996-04-01

The regulatory policy of the Food and Drug Administration (FDA) on radiopharmaceuticals flows from a rigid, traditional, drug-like interpretation of the FDC Act on the licensing of radiopharmaceuticals. This contributes to significant delays in the drug-approval process for radiopharmaceuticals, which are very costly to the nuclear medicine community and the American public. It seems that radiopharmaceuticals would be better characterized as molecular devices. Good generic rule-making principles include: use of a risk/benefit/cost analysis; intent based on sound science; performance standards prepared by outside experts; a definite need shown by the regulatory agency; to live with the consequences of any erroneous cost estimates; and design individual credential requirements so that additional training results in enhanced professional responsibility. When these common elements are applied to current FDA policy, it seems that the agency is out of sync with the stated goals for revitalizing federal regulatory policies as deemed necessary by the Clinton administration. Recent FDA rulings on positron-emission tomography, Patient Package inserts, and on medical device service accentuate the degree of such asynchronization. Radiopharmaceutical review and licensing flexibility could be dramatically improved by excluding radiopharmaceuticals from the drug category and reviewing them as separate entities. This new category would take into account their excellent record of safety and their lack of pharmacological action. Additionally, their evaluation of efficacy should be based on their ability to provide useful scintiphotos, data, or responses of the physiological system it portends to image, quantitate, or describe. To accomplish the goal of transforming the FDA's rigid, prescriptive policy into a streamlined flexible performance-based policy, the Council on Radionuclides and Radiopharmaceuticals proposal has been presented. In addition, it is suggested that the United

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0149] (Formerly 2007D-0309) Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Electrocardiograph Electrodes; Availability AGENCY: Food and Drug...

Evaluating the administration costs of biologic drugs: development of a cost algorithm.

PubMed

Tetteh, Ebenezer K; Morris, Stephen

2014-12-01

Biologic drugs, as with all other medical technologies, are subject to a number of regulatory, marketing, reimbursement (financing) and other demand-restricting hurdles applied by healthcare payers. One example is the routine use of cost-effectiveness analyses or health technology assessments to determine which medical technologies offer value-for-money. The manner in which these assessments are conducted suggests that, holding all else equal, the economic value of biologic drugs may be determined by how much is spent on administering these drugs or trade-offs between drug acquisition and administration costs. Yet, on the supply-side, it seems very little attention is given to how manufacturing and formulation choices affect healthcare delivery costs. This paper evaluates variations in the administration costs of biologic drugs, taking care to ensure consistent inclusion of all relevant cost resources. From this, it develops a regression-based algorithm with which manufacturers could possibly predict, during process development, how their manufacturing and formulation choices may impact on the healthcare delivery costs of their products.

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

Code of Federal Regulations, 2010 CFR

2010-07-01

... Enforcement Administration Senior Executive Service. 0.157 Section 0.157 Judicial Administration DEPARTMENT OF... Administrative Matters § 0.157 Federal Bureau of Investigation—Drug Enforcement Administration Senior Executive Service. (a) Pursuant to 5 U.S.C. 3151, there is established a personnel system for senior personnel...

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 Docket FDA-2008-N-0041; Formerly 2008N-0004] Guidance for Industry on Acute Bacterial Otitis Media... entitled ``Acute Bacterial Otitis Media: Developing Drugs for Treatment.'' This guidance addresses FDA's... an indication for the treatment of acute bacterial otitis media (ABOM). This guidance finalizes the...

21 CFR 20.110 - Data and information about Food and Drug Administration employees.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Data and information about Food and Drug... Data and information about Food and Drug Administration employees. (a) The name, title, grade, position... are available for public disclosure. The home address and home telephone number of any such employee...

21 CFR 20.110 - Data and information about Food and Drug Administration employees.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Data and information about Food and Drug... Data and information about Food and Drug Administration employees. (a) The name, title, grade, position... are available for public disclosure. The home address and home telephone number of any such employee...

21 CFR 20.110 - Data and information about Food and Drug Administration employees.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Data and information about Food and Drug... Data and information about Food and Drug Administration employees. (a) The name, title, grade, position... are available for public disclosure. The home address and home telephone number of any such employee...

76 FR 50741 - 2011 Parenteral Drug Association/Food and Drug Administration Joint Public Conference; Quality...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-16

... Compliance in Today's Regulatory Enforcement Environment AGENCY: Food and Drug Administration, HHS. ACTION... Regulatory Enforcement Environment.'' The conference will span 2\\1/2\\ days and cover current issues affecting... facilitate the development and continuous improvement of safe and effective medical products. The conference...

Obstetric Neuraxial Drug Administration Errors: A Quantitative and Qualitative Analytical Review.

PubMed

Patel, Santosh; Loveridge, Robert

2015-12-01

Drug administration errors in obstetric neuraxial anesthesia can have devastating consequences. Although fully recognizing that they represent "only the tip of the iceberg," published case reports/series of these errors were reviewed in detail with the aim of estimating the frequency and the nature of these errors. We identified case reports and case series from MEDLINE and performed a quantitative analysis of the involved drugs, error setting, source of error, the observed complications, and any therapeutic interventions. We subsequently performed a qualitative analysis of the human factors involved and proposed modifications to practice. Twenty-nine cases were identified. Various drugs were given in error, but no direct effects on the course of labor, mode of delivery, or neonatal outcome were reported. Four maternal deaths from the accidental intrathecal administration of tranexamic acid were reported, all occurring after delivery of the fetus. A range of hemodynamic and neurologic signs and symptoms were noted, but the most commonly reported complication was the failure of the intended neuraxial anesthetic technique. Several human factors were present; most common factors were drug storage issues and similar drug appearance. Four practice recommendations were identified as being likely to have prevented the errors. The reported errors exposed latent conditions within health care systems. We suggest that the implementation of the following processes may decrease the risk of these types of drug errors: (1) Careful reading of the label on any drug ampule or syringe before the drug is drawn up or injected; (2) labeling all syringes; (3) checking labels with a second person or a device (such as a barcode reader linked to a computer) before the drug is drawn up or administered; and (4) use of non-Luer lock connectors on all epidural/spinal/combined spinal-epidural devices. Further study is required to determine whether routine use of these processes will reduce drug

Drug Enforcement Administration

MedlinePlus

... Cannabis Plant Counterfeit Prescription Pills Containing Fentanyls: A Global Threat Public Drug Disposal: Search for an Authorized Drug Disposal Location RESOURCE CENTER Controlled Substances Act DEA Museum and Visitors Center Doing Business with DEA Drug Disposal Employee Assistance Program For ...

75 FR 6209 - Guidance for Industry and Food and Drug Administration; Guidance for the Use of Bayesian...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2006-D-0410] (formerly Docket No. 2006D-0191) Guidance for Industry and Food and Drug Administration; Guidance for the Use of Bayesian Statistics in Medical Device Clinical Trials; Availability AGENCY: Food and Drug...

Drug administration adjustments for elderly patients with dysphagia: A case report.

PubMed

Mastroianni, Patrícia de Carvalho; Forgerini, Marcela

2018-01-01

An elderly patient, aged 76 years, diagnosed with dysphagia, depression, hypothyroidism, Alzheimer's disease and mild cognitive deficit, was identified with sertraline and levothyroxine- drug-related problems. Medication Therapy Management (MTM) was used to adjust therapy to the patient's needs by macerating sertraline tablets and solubilizing them in 10-30 mL of orange juice. The patient was advised to take levothyroxine after fasting. Six months later, pharmaceutical follow-up identified an increase in the Mini-Mental State Exam score from 22 to 26 and a decrease in the Clinical Dementia Rating (CDR) scale score from 1.0 to 0.5 in conjunction with mood and physical improvements, as well as a significant decrease in aggressiveness and agitation. Cognitive deficit may be a result of poor drug administration procedures, leading to drug ineffectiveness. Optimizing levothyroxine and sertraline administration, based on knowledge of their physicochemical properties, improves their clinical effectiveness, including the cognition of patients with Alzheimer's disease and dysphagia.

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

Code of Federal Regulations, 2010 CFR

2010-07-01

... 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 and...

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 and...

Examination of Acute Sensitivity to Morphine and Morphine Self-Administration Following Physical and Environmental Stressors in Fischer-344 and Lewis Female Rats

DTIC Science & Technology

1997-01-16

Administration Following Physical and Environmental Stressors in Fischer-344 and Lewis Female Rats" Name of Candidate: Kelly Brown Doctor...Title ofDissertation: Examination ofAcute Sensitivity to Morphine and Morphine Self- Administration Following Physical and Environmental Stressors in...to tolerance, toxicity, or addiction liability. IV Examination ofAcute Sensitivity to Morphine and Morphine Self-Administration Following Physical and

Establishment of a drug-induced rhabdomyolysis mouse model by co-administration of ciprofloxacin and atorvastatin.

PubMed

Matsubara, Akiko; Oda, Shingo; Akai, Sho; Tsuneyama, Koichi; Yokoi, Tsuyoshi

2018-07-01

Rhabdomyolysis is one of the serious side effects of ciprofloxacin (CPFX), a widely used antibacterial drug; and occasionally, acute kidney injury (AKI) occurs. Often, rhabdomyolysis has occurred in patients taking CPFX co-administered with statins. The purpose of this study is to establish a mouse model of drug-induced rhabdomyolysis by co-administration of CPFX and atorvastatin (ATV) and to clarify the mechanisms of its pathogenesis. C57BL/6J mice treated with L-buthionine-(S,R)-sulfoximine (BSO), a glutathione synthesis inhibitor, were orally administered with CPFX and ATV for 4 days. Plasma levels of creatinine phosphokinase (CPK) and aspartate aminotransferase (AST) were significantly increased in the CPFX and ATV-co-administered group. Histopathological examination of skeletal muscle observed degeneration in gastrocnemius muscle and an increased number of the satellite cells. Expressions of skeletal muscle-specific microRNA and mRNA in plasma and skeletal muscle, respectively, were significantly increased. The area under the curve (AUC) of plasma CPFX was significantly increased in the CPFX and ATV-co-administered group. Furthermore, cytoplasmic vacuolization and a positively myoglobin-stained region in kidney tissue and high content of myoglobin in urine were observed. These results indicated that AKI was induced by myoglobin that leaked from skeletal muscle. The established mouse model in the present study would be useful for predicting potential rhabdomyolysis risks in preclinical drug development. Copyright © 2018 Elsevier B.V. All rights reserved.

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. Copyright

Numerical Comparison of Nasal Aerosol Administration Systems for Efficient Nose-to-Brain Drug Delivery.

PubMed

Dong, Jingliang; Shang, Yidan; Inthavong, Kiao; Chan, Hak-Kim; Tu, Jiyuan

2017-12-29

Nose-to-brain drug administration along the olfactory and trigeminal nerve pathways offers an alternative route for the treatment of central nervous system (CNS) disorders. The characterization of particle deposition remains difficult to achieve in experiments. Alternative numerical approach is applied to identify suitable aerosol particle size with maximized inhaled doses. This study numerically compared the drug delivery efficiency in a realistic human nasal cavity between two aerosol drug administration systems targeting the olfactory region: the aerosol mask system and the breath-powered bi-directional system. Steady inhalation and exhalation flow rates were applied to both delivery systems. The discrete phase particle tracking method was employed to capture the aerosol drug transport and deposition behaviours in the nasal cavity. Both overall and regional deposition characteristics were analysed in detail. The results demonstrated the breath-powered drug delivery approach can produce superior olfactory deposition with peaking olfactory deposition fractions for diffusive 1 nm particles and inertial 10 μm. While for particles in the range of 10 nm to 2 μm, no significant olfactory deposition can be found, indicating the therapeutic agents should avoid this size range when targeting the olfactory deposition. The breath-powered bi-directional aerosol delivery approach shows better drug delivery performance globally and locally, and improved drug administration doses can be achieved in targeted olfactory region.

Acute spinal cord injury changes the disposition of some, but not all drugs given intravenously.

PubMed

García-López, P; Martínez-Cruz, A; Guízar-Sahagún, G; Castañeda-Hernández, G

2007-09-01

Experimental laboratory investigations in paraplegic rats. In order to understand why acute spinal cord injury (SCI) changes the disposition of some, but not all drugs given intravenously (i.v.), pharmacokinetic parameters of drugs with different pharmacological properties were evaluated to determine the influence of SCI on physiological processes such as distribution, metabolism and excretion. Mexico City, Mexico. Rats were subjected to severe SCI (contusion) at T-9 level; pharmacokinetic studies of phenacetin, naproxen or gentamicin were performed 24 h after. These drugs were not chosen as markers because of their therapeutic properties, but because of their pharmacokinetic characteristics. Additional studies including plasma proteins, liver and renal function tests, and micro-vascular hepatic blood flow, were also performed at the same time after injury. Acute SCI significantly reduced distribution of drugs with intermediate and low binding to plasma proteins (phenacetin 30% and gentamicin 10%, respectively), but distribution did not change when naproxen - a drug highly bound to plasma proteins (99%) - was used, in absence of changes in plasma proteins. Metabolism was significantly altered only for a drug with liver blood flow - limited clearance (phenacetin) and not for a drug with liver capacity-limited clearance (naproxen). The liver function test did not change, whereas the hepatic micro-vascular blood flow significantly decreased after SCI. Renal excretion, evaluated by gentamicin clearance, was significantly reduced as a consequence of SCI, without significant changes in serum creatinine. Changes in drug disposition associated to acute SCI are complex and generalization is not possible. They are highly dependent on each drug properties as well as on the altered physiological processes. Results motivate the quest for strategies to improve disposition of selective i.v. drugs during spinal shock, in an effort to avoid therapeutic failure.

Errors in preparation and administration of parenteral drugs in neonatology: evaluation and corrective actions.

PubMed

Hasni, Nesrine; Ben Hamida, Emira; Ben Jeddou, Khouloud; Ben Hamida, Sarra; Ayadi, Imene; Ouahchi, Zeineb; Marrakchi, Zahra

2016-12-01

The medication iatrogenic risk is quite unevaluated in neonatology Objective: Assessment of errors that occurred during the preparation and administration of injectable medicines in a neonatal unit in order to implement corrective actions to reduce the occurrence of these errors. A prospective, observational study was performed in a neonatal unit over a period of one month. The practice of preparing and administering injectable medications were identified through a standardized data collection form. These practices were compared with summaries of the characteristics of each product (RCP) and the bibliography. One hundred preparations were observed of 13 different drugs. 85 errors during preparations and administration steps were detected. These errors were divided into preparation errors in 59% of cases such as changing the dilution protocol (32%), the use of bad solvent (11%) and administration errors in 41% of cases as errors timing of administration (18%) or omission of administration (9%). This study showed a high rate of errors during stages of preparation and administration of injectable drugs. In order to optimize the care of newborns and reduce the risk of medication errors, corrective actions have been implemented through the establishment of a quality assurance system which consisted of the development of injectable drugs preparation procedures, the introduction of a labeling system and staff training.

Recommended drug use after acute myocardial infarction by migration status and education level.

PubMed

Dzayee, Dashti Ali Mustafa; Moradi, Tahereh; Beiki, Omid; Alfredsson, Lars; Ljung, Rickard

2015-04-01

The purpose of this study is to investigate the association between migration status and education level and the use of recommended drugs after first acute myocardial infarction (MI). A nationwide cohort study performed in Sweden from January 1, 2006 to August 1, 2008. The cohort consisted of 49,037 incident cases of first acute MI. In total, 37,570 individuals survived 180 days after MI, of whom 4782 (12.7%) were foreign-born. We used logistic regression to estimate the odds ratio (OR) with 95% confidence interval (CI) of the association between migration status and education level and prescribed drugs after MI. One third of the patients who were not on any recommended cardiovascular drugs before MI continued to be without recommended cardiovascular drugs after MI. Among those with no cardiovascular drugs before MI, we found no difference in recommended drug use after MI by migration status (OR 1.00, 95% CI 0.89-1.12). Among those with some but not all recommended cardiovascular drugs before MI, foreign-born cases had a slightly non-significant lower use of recommended drugs (OR 0.92, 95% CI 0.83-1.03). Foreign-born patients with low education had a slightly lower use of recommended drug compared to Sweden-born. Women with low education had a lower use of drugs after MI (Sweden born, OR 0.85; 95% CI 0.74-0.96 and foreign born OR 0.51; 95% CI 0.34-0.77). There is no apparent difference between foreign-born and Sweden-born in recommended drug use after MI. However, our study reveals an inequity in secondary prevention therapy after myocardial infarction by education level.

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

Routines and rituals: a grounded theory of the pain management of drug users in acute care settings.

PubMed

McCreaddie, May; Lyons, Imogen; Watt, Debbie; Ewing, Elspeth; Croft, Jeanette; Smith, Marion; Tocher, Jennifer

2010-10-01

This study reviewed the perceptions and strategies of drug users and nurses with regard to pain management in acute care settings. Drug users present unique challenges in acute care settings with pain management noted to be at best suboptimal, at worst non-existent. Little is known about why and specifically how therapeutic effectiveness is compromised. Qualitative: constructivist grounded theory. A constructivist grounded theory approach incorporating a constant comparative method of data collection and analysis was applied. The data corpus comprised interviews with drug users (n = 11) and five focus groups (n = 22) of nurses and recovering drug users. Moral relativism as the core category both represents the phenomenon and explains the basic social process. Nurses and drug users struggle with moral relativism when addressing the issue of pain management in the acute care setting. Drug users lay claim to expectations of compassionate care and moralise via narration. Paradoxically, nurses report that the caring ideal and mutuality of caring are diminished. Drug users' individual sensitivities, anxieties and felt stigma in conjunction with opioid-induced hyperalgesia complicate the processes. Nurses' and hospitals' organisational routines challenge drug user rituals and vice versa leading both protagonists to become disaffected. Consequently, key clinical issues such as preventing withdrawal and managing pain are left unaddressed and therapeutic effectiveness is compromised. This study provides a robust account of nurses' and drug users' struggle with pain management in the acute care setting. Quick technological fixes such as urine screens, checklists or the transient effects of (cognitive-based) education (or training) are not the answer. This study highlights the need for nurses to engage meaningfully with this perceptibly 'difficult' group of patients. The key aspects likely to contribute to problematic interactions with this patient cohort are outlined so that

Development of an opioid self-administration assay to study drug seeking in zebrafish.

PubMed

Bossé, Gabriel D; Peterson, Randall T

2017-09-29

The zebrafish (Danio rerio) has become an excellent tool to study mental health disorders, due to its physiological and genetic similarity to humans, ease of genetic manipulation, and feasibility of small molecule screening. Zebrafish have been shown to exhibit characteristics of addiction to drugs of abuse in non-contingent assays, including conditioned place preference, but contingent assays have been limited to a single assay for alcohol consumption. Using inexpensive electronic, mechanical, and optical components, we developed an automated opioid self-administration assay for zebrafish, enabling us to measure drug seeking and gain insight into the underlying biological pathways. Zebrafish trained in the assay for five days exhibited robust self-administration, which was dependent on the function of the μ-opioid receptor. In addition, a progressive ratio protocol was used to test conditioned animals for motivation. Furthermore, conditioned fish continued to seek the drug despite an adverse consequence and showed signs of stress and anxiety upon withdrawal of the drug. Finally, we validated our assay by confirming that self-administration in zebrafish is dependent on several of the same molecular pathways as in other animal models. Given the ease and throughput of this assay, it will enable identification of important biological pathways regulating drug seeking and could lead to the development of new therapeutic molecules to treat addiction. Copyright © 2017 Elsevier B.V. All rights reserved.

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0147] Draft Guidance for Industry and Food and Drug Administration Staff; Demonstrating the Substantial Equivalence of a New Tobacco Product: Responses to Frequently Asked Questions; Availability AGENCY: Food and...

Demystifying the U.S. Food and Drug Administration: I. Understanding agency structure and function.

PubMed

Levi, Benjamin; Lisiecki, Jeffrey; Rubin, Peter; D'Amico, Richard A; Hume, Keith M; Seward, Bill; Cederna, Paul S

2014-06-01

The U.S. Food and Drug Administration is the government agency responsible for oversight of the safety and efficacy of pharmaceuticals and devices, including biologics and devices that combine biologics with other materials. Within the U.S. Food and Drug Administration, the Center for Biologics Evaluation and Research is specifically responsible for the evaluation and approval of biological products. This department of the U.S. Food and Drug Administration has a series of mechanisms in place to aid researchers in the process of developing new biologics. This article outlines the study phases involved in developing new biologics and how the Center for Biologics Evaluation and Research and investigators can work together to facilitate this process. It also discusses issues specific to biologics that have been encountered in the past and that investigators should consider when developing and obtaining approval for new biologics. The equivalent center within the U.S. Food and Drug Administration for approving medical devices is the Center for Devices and Radiological Health. The equivalent process of development and approval of medical devices is similarly discussed. Finally, essential contacts for investigators within the Center for Biologics Evaluation and Research and the Center for Devices and Radiological Health are provided.

Acute administration of THC impairs spatial but not associative memory function in zebrafish.

PubMed

Ruhl, Tim; Prinz, Nicole; Oellers, Nadine; Seidel, Nathan Ian; Jonas, Annika; Albayram, Onder; Bilkei-Gorzo, Andras; von der Emde, Gerhard

2014-10-01

The present study examined the effect of acute administration of endocannabinoid receptor CB1 ligand ∆-9-tetrahydrocannabinol (THC) on intracellular signalling in the brain and retrieval from two different memory systems in the zebrafish (Danio rerio). First, fish were treated with THC and changes in the phosphorylation level of mitogen-activated protein (MAP) kinases Akt and Erk in the brain were determined 1 h after drug treatment. Next, animals of a second group learned in a two-alternative choice paradigm to discriminate between two colours, whereas a third group solved a spatial cognition task in an open-field maze by use of an ego-allocentric strategy. After memory acquisition and consolidation, animals were pharmacologically treated using the treatment regime as in the first group and then tested again for memory retrieval. We found an enhanced Erk but not Akt phosphorylation suggesting that THC treatment specifically activated Erk signalling in the zebrafish telencephalon. While CB1 agonist THC did not affect behavioural performance of animals in the colour discrimination paradigm, spatial memory was significantly impaired. The effect of THC on spatial learning is probably specific, since neither motor activity nor anxiety-related behaviour was influenced by the drug treatment. That indicates a striking influence of the endocannabinoid system (ECS) on spatial cognition in zebrafish. The results are very coincident with reports on mammals, demonstrating that the ECS is functional highly conserved during vertebrate evolution. We further conclude that the zebrafish provides a promising model organism for ongoing research on the ECS.

Heparin in acute ischemic stroke revisited.

PubMed

Chamorro, A

2008-10-01

The evidence gathered in clinical trials of low molecular weight heparins (LMWHs) or with unfractionated heparin (UH) given subcutaneously at low or medium doses to patients with acute stroke cannot be extrapolated to the insufficiently tested effects of intravenous, weight-adjusted UH. Recent small studies have provided encouraging results but are potentially confounded and deserve confirmation in larger randomized controlled trials. In accordance with the current understanding of the biology of acute ischemic stroke and the pharmacology of UH, the new randomized controlled trials on heparin should give appropriate credit to the importance of a short therapeutic window, adequate dose adjustment of the drug, intravenous administration, and close monitoring of biological effects. UH is an orphan drug and only an academic driven trial would be able to face such an enterprise. Meanwhile, recommendations against the value of "early" anticoagulation with full dose of weight adjusted UH in the setting of acute ischemic stroke are not based on direct evidence but on extrapolations.

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 explicitly...

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 explicitly...

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 explicitly...

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 explicitly...

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 explicitly...

Comparison of oncology drug approval between Health Canada and the US Food and Drug Administration.

PubMed

Ezeife, Doreen A; Truong, Tony H; Heng, Daniel Y C; Bourque, Sylvie; Welch, Stephen A; Tang, Patricia A

2015-05-15

The drug approval timeline is a lengthy process that often varies between countries. The objective of this study was to delineate the Canadian drug approval timeline for oncology drugs and to compare the time to drug approval between Health Canada (HC) and the US Food and Drug Administration (FDA). In total, 54 antineoplastic drugs that were approved by the FDA between 1989 and 2012 were reviewed. For each drug, the following milestones were determined: the dates of submission and approval for both the FDA and HC and the dates of availability on provincial drug formularies in Canadian provinces and territories. The time intervals between the aforementioned milestones were calculated. Of 54 FDA-approved drugs, 49 drugs were approved by HC at the time of the current study. The median time from submission to approval was 9 months (interquartile range [IQR], 6-14.5 months) for the FDA and 12 months (IQR, 10-21.1 months) for HC (P < .0006). The time from HC approval to the placement of a drug on a provincial drug formulary was a median of 16.7 months (IQR, 5.9-27.2 months), and there was no interprovincial variability among the 5 Canadian provinces that were analyzed (P = .5). The time from HC submission to HC approval takes 3 months longer than the same time interval for the FDA. To the authors' knowledge, this is the first documentation of the time required to bring an oncology drug from HC submission to placement on a provincial drug formulary. © 2015 American Cancer Society.

Factors affecting registered nurses' use of medication administration technology in acute care settings: A systematic review.

PubMed

San, Tay Hui; Lin, Serena Koh Siew; Fai, Chan Moon

Information technology to aid reduction in medication errors has been encouraged over the years and one of them is the medication administration technology. It consists of the electronic Medication Administration Record, Bar-Code Medication Administration system and Automated Medication Dispensing system. Studies had examined the effectiveness and impact of this technology to reduce medication error. However, user's acceptance towards this technology has often been neglected. To date, no systematic review has been undertaken to examine the possible factors that affect nurses' use of this technology in the acute care settings. The objective of this systematic review was to explore and determine the factors that affect nurses' use of medication administration technology in the acute care settings. All quantitative studies published in English which examined factors affecting nurses' use of the medication administration technology were considered.Primary focus was on registered nurses with experience of operating medication administration technology in the acute care settings. Other healthcare personnel were excluded.This review considered studies that evaluated factors affecting nurses' use of the medication administration technology.The outcome measures of interest were the factors that affect nurses' use of the medication administration technology in the acute care settings. The search was conducted across published and unpublished databases. A search was conducted in JBI Library of Systematic Reviews, The Cochrane Library, CINAHL, MEDLINE, Scopus, ScienceDirect, Wiley InterScience, SpringerLink, PsycINFO (ovid), Web of science, ProQuest Dissertations and Theses, and MedNar. Papers selected for retrieval were assessed by two independent reviewers for methodological validity prior to inclusion in the review, using the standardised critical appraisal instruments developed by the Joanna Briggs Institute. Quantitative data were extracted from papers included in the

Safe handling of antineoplastic drugs.

PubMed

Harrison, B R

1994-07-01

Managers should be aware of the hazardous properties of antineoplastic drugs and of the procedures and equipment commonly recommended to provide a safe working environment for employees, patients, and visitors. Compliance with the many published guidelines should help ensure passage of the inevitable Occupational Safety and Health Administration (OSHA) or Joint Commission inspection. Acute and chronic toxicities of the antineoplastic drugs, the potential for exposure in the workplace, and the basic guidelines for safe handling of these agents are reviewed.

Performance of schizophrenic patients in the Stroop Color Word Test and electrodermal responsiveness after acute administration of cannabidiol (CBD).

PubMed

Hallak, Jaime E C; Machado-de-Sousa, João Paulo; Crippa, José Alexandre S; Sanches, Rafael Faria; Trzesniak, Clarissa; Chaves, Cristiano; Bernardo, Sandra Aparecida; Regalo, Simone Cecílio; Zuardi, Antonio Waldo

2010-03-01

The last decade has seen increasing evidence of dysfunctions in the endogenous cannabinoid system in schizophrenia and of its relationship with the typical cognitive impairment of the disorder. Studies in animal models, healthy volunteers, and psychotic patients clearly suggest an antipsychotic-like effect of cannabidiol. This study investigated the effects of cannabidiol on selective attention in 28 schizophrenic patients using the Stroop Color Word Test and on these patients' electrodermal responsiveness to auditive stimuli. The subjects attended two experimental sessions, the first one without the administration of drugs. In the second session the subjects were divided into three groups that received either a single dose of cannabidiol 300 mg or cannabidiol 600 mg or placebo. The three groups did not differ significantly with respect to electrodermal measures in the two experimental sessions. When the first and second sessions were compared improved performance was found in all three groups, with patients who received placebo and cannabidiol 300 mg performing better than those who received cannabidiol 600 mg. The single, acute administration of cannabidiol seems to have no beneficial effects on the performance of schizophrenic patients in the Stroop Color Word Test, although the hypothesis that chronic administration may lead to improvement cannot be disregarded.

Inside the black box: current policies and concerns with the United States Food and Drug Administration's highest drug safety warning system.

PubMed

Halloran, Kylene; Barash, Paul G

2010-06-01

To evaluate the United States Food and Drug Administration use of the black-box warning system to promote drug safety and to examine the droperidol black-box warning as a case study. Scientific studies report that there is no basis to issue a black-box warning for perioperative administration of droperidol for postoperative nausea and vomiting on the basis of the potential of adverse cardiac events (prolongation of the QT interval and/or development of torsades de pointes). Rather than relying on well conducted clinical investigations, the Food and Drug Administration subjectively issued a black-box warning to droperidol, which effectively removed droperidol from clinical practice for the indication of postoperative nausea and vomiting. Newer data suggest that the incidence of prolongation of the QT interval and the occurrence of torsades de pointes is similar to more expensive alternative medications used to treat postoperative nausea and vomiting.

[The curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning].

PubMed

Liu, Jing; Wang, Qiu-ying; Wang, Bei; Xuan, Xiao-qiang; Chen, Qiong; Xu, Dong-wei; Cheng, Ning

2011-02-01

To assess the curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning. In present study 220 SD rats were divided into control group (10 rats), carbonyl nickel group (10 rats), 20 mg/kg methylprednisolone group (40 rats), 100 mg/kg DDC group (40 rats), 10 µmol/kg sodium selenite group (40 rats), 0.25 ml shenfuhuiyangtang group (40 rats) and 20 mg/kg methylprednisolone with 100 mg/kg DDC group (40 rats). All rats except for control group inhaled passively 250 mg/m(3) carbonyl nickel for 30 minutes. At 4h and 30h after exposure, the drugs were given intraperitoneally to the rats. On the 3rd and 7th days after exposure, the liver samples were taken from 10 rats each group. The DNA damage of liver cells was detected using comet assay, the ultrastructure changes in liver cells were examined under an electronmicroscope. Compared to carbonyl nickel group, the tail lengths of liver cells in 5 groups administrated at 4 h or 30 h and tested on the 3rd or 7th day after exposure decreased significantly (P < 0.05). Compared to the control group, the tail lengths of liver cells in sodium selenite and shenfuhuiyangtang groups administrated at 4h after exposure or sodium selenite, shenfuhuiyangtang and methylprednisolone with DDC groups administrated at 30h after exposure increased significantly (P < 0.05 or P < 0.01), when tested on the 3rd day after exposure. Except from methylprednisolone sub-group administrated at 4h and tested on the 7th day after exposure, the tail lengths of liver cells in other groups administrated at 4 h or 30 h and tested on the 7th day after exposure increased significantly (P < 0.05). Compared to carbonyl nickel group, the Olive moment of liver cells in 5 groups administrated at 4 h or 30 h tested on the 3rd or 7th day after exposure decreased significantly (P < 0.05 or P < 0.01). Compared to the control group, the Olive moment of liver cells in following groups (selenite and shenfuhuiyangtang groups

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0004] [FDA 225-10-0007] Memorandum of Understanding Between the Food and Drug Administration, United States...) is providing notice of a memorandum of understanding (MOU) between the FDA, U.S. Department of Health...

Naltrexone modulates dopamine release following chronic, but not acute amphetamine administration: a translational study

PubMed Central

Jayaram-Lindström, N; Guterstam, J; Häggkvist, J; Ericson, M; Malmlöf, T; Schilström, B; Halldin, C; Cervenka, S; Saijo, T; Nordström, A-L; Franck, J

2017-01-01

The opioid antagonist naltrexone has been shown to attenuate the subjective effects of amphetamine. However, the mechanisms behind this modulatory effect are currently unknown. We hypothesized that naltrexone would diminish the striatal dopamine release induced by amphetamine, which is considered an important mechanism behind many of its stimulant properties. We used positron emission tomography and the dopamine D2-receptor radioligand [11C]raclopride in healthy subjects to study the dopaminergic effects of an amphetamine injection after pretreatment with naltrexone or placebo. In a rat model, we used microdialysis to study the modulatory effects of naltrexone on dopamine levels after acute and chronic amphetamine exposure. In healthy humans, naltrexone attenuated the subjective effects of amphetamine, confirming our previous results. Amphetamine produced a significant reduction in striatal radioligand binding, indicating increased levels of endogenous dopamine. However, there was no statistically significant effect of naltrexone on dopamine release. The same pattern was observed in rats, where an acute injection of amphetamine caused a significant rise in striatal dopamine levels, with no effect of naltrexone pretreatment. However, in a chronic model, naltrexone significantly attenuated the dopamine release caused by reinstatement of amphetamine. Collectively, these data suggest that the opioid system becomes engaged during the more chronic phase of drug use, evidenced by the modulatory effect of naltrexone on dopamine release following chronic amphetamine administration. The importance of opioid-dopamine interactions in the reinforcing and addictive effects of amphetamine is highlighted by the present findings and may help to facilitate medication development in the field of stimulant dependence. PMID:28440810

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... preceded by oral communication or by a visit from an authorized representative of the local Food and Drug Administration district office, with formal, written confirmation from the Commissioner or his designee afterward..., the recall strategy, and other appropriate instructions for conducting the recall. (c) Upon receipt of...

Intratracheal Milrinone Bolus Administration During Acute Right Ventricular Dysfunction After Cardiopulmonary Bypass.

PubMed

Gebhard, Caroline Eva; Desjardins, Georges; Gebhard, Cathérine; Gavra, Paul; Denault, André Y

2017-04-01

To evaluate intratracheal milrinone (tMil) administration for rapid treatment of right ventricular (RV) dysfunction as a novel route after cardiopulmonary bypass. Retrospective analysis. Single-center study. The study comprised 7 patients undergoing cardiac surgery who exhibited acute RV dysfunction after cardiopulmonary bypass. After difficult weaning caused by cardiopulmonary bypass-induced acute RV dysfunction, milrinone was administered as a 5-mg bolus inside the endotracheal tube. RV function improvement, as indicated by decreasing pulmonary artery pressure and changes of RV waveforms, was observed in all 7 patients. Adverse effects of tMil included dynamic RV outflow tract obstruction (2 patients) and a decrease in systemic mean arterial pressure (1 patient). tMil may be an effective, rapid, and easily applicable therapeutic alternative to inhaled milrinone for the treatment of acute RV failure during cardiac surgery. However, sufficiently powered clinical trials are needed to confirm these findings. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute and sub-chronic toxicity of four cytostatic drugs in zebrafish.

PubMed

Kovács, Róbert; Bakos, Katalin; Urbányi, Béla; Kövesi, Judit; Gazsi, Gyöngyi; Csepeli, Andrea; Appl, Ádám János; Bencsik, Dóra; Csenki, Zsolt; Horváth, Ákos

2016-08-01

The acute and sub-chronic effects of four cytostatic drugs-5-fluorouracil (5-FU), cisplatin (CisPt), etoposide (ET) and imatinib mesylate (IM)-on zebrafish (Danio rerio) were investigated. Acute tests were carried out in a static system in accordance with the OECD guideline 203 for adult fish and the draft guideline for fish embryos (FET test) in order to find the LC50 values of the four cytostatic drugs. Early-life stage toxicity test on zebrafish was conducted according the OECD guideline 210 using the cytostatic drugs 5-FU and IM in a semistatic system with the objective of investigating the sub-chronic effects of the cytostatic drugs on fish. In adult fish, the cytostatic drugs 5-FU and ET did not pass the limit test, thus, are considered non-toxic. In case of cisplatin, LC50 was calculated at 64.5 mg L(-1), whereas in case of IM, LC50 was at 70.8 mg L(-1). In the FET test, LC50 of 5-FU at 72-h post fertilization (hpf) was 2441.6 mg L(-1). In case of CisPt, LC50 was 349.9 mg L(-1) at 48 hpf and it progressively decreased to 81.3 mg L(-1) at 120 hpf. In addition, CisPt caused a significant delay in the hatch of larvae. In case of ET, LC50 values were not calculable as they were higher than 300 mg L(-1) at which concentration the substance crystallized in the solution. LC50 values of IM were 48 hpf; 158.3 mg L(-1) , 72 hpf; 141.6 mg L(-1), 96 hpf; 118.0 mg L(-1), and 120 hpf; 65.9 mg L(-1). In the Early-life Stage Test with 5-FU, embryonic deformities were not detected during the tests. Regarding mortalities, the 10 mg L(-1) concentration can be considered as LOEC, as statistically significant difference in mortalities was detected in this group alone. Concerning dry body weight and standard length, 1 mg L(-1) is the LOEC. In case of IM, the highest tested concentration (10 mg L(-1)) can be considered LOEC for mortalities, however, the treatment did not have an effect on the other investigated parameters (dry and wet weight, standard length). All four cytostatic

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. Copyright © 2015 Elsevier Inc. All rights reserved.

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. Copyright © 2015. Published by Elsevier Ltd.

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0281] Draft Guidance for Industry and Food and Drug Administration Staff; ```Harmful and Potentially Harmful... Food, Drug, and Cosmetic Act.'' This draft guidance provides written guidance to industry and FDA staff...

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

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false The Food and Drug Administration's (FDA's... (CONTINUED) FOOD ADDITIVES Premarket Notifications § 170.105 The Food and Drug Administration's (FDA's... data or other information available to FDA, including data not submitted by the manufacturer or...

Alteration of glucose metabolism in liver by acute administration of cannabis.

PubMed

Sanz, P; Rodríguez-Vicente, C; Repetto, M

1985-01-01

In previous research on the effects of cannabis on cellular functions the authors observed an increase in glucose metabolism in the postmitochondrial fraction of the liver of rats submitted to chronic administration of cannabis extracts. Continuing this research on rats submitted to acute cannabis intoxication a single dose of cannabis extract (600 mg/kg) in olive oil is administered to male adult rats and the animals are killed within a 36-hour period. The analyses show that energetic and detoxifying metabolism of glucose is increased, as indicated by the increase of F-1, 6-di P-aldolase and uridin-diphosphoglucose-dehydrogenase activities, which parallels the observed decrease of glycogen levels. Maximum effect appears between 8 and 16 hours after administration.

Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain.

PubMed

Inage, Kazuhide; Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

2016-08-01

Retrospective study. To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p<0.001). Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent the transition of acute low back pain to chronic low back pain.

Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain

PubMed Central

Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

2016-01-01

Study Design Retrospective study. Purpose To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Overview of Literature Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Methods Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. Results No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p<0.001). Conclusions Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent

Oral drug self-administration: an overview of laboratory animal studies.

PubMed

Meisch, R A

2001-06-01

Many abused drugs can be established as orally delivered reinforcers for rhesus monkeys and other animals. Benzodiazepines, barbiturates, opioids, psychomotor stimulants, dissociative anesthetics, and ethanol can come to serve as reinforcers when taken by mouth. The principal problems in establishing drugs as reinforcers by the oral route of administration are (1) aversive taste, (2) delay in onset of central nervous system effects, and (3) consumption of low volumes of drug solution. Strategies have been devised to successfully overcome these problems, and orally delivered drugs can be established as effective reinforcers. Reinforcing actions are demonstrated by consumption of greater volumes of drug solution than volumes of the water vehicle, and supporting evidence for reinforcing effects consists of the maintenance of behavior under intermittent schedules of reinforcement and the generation of orderly dose-response functions. This article presents an overview of studies of behavior reinforced by oral drug reinforcement. Factors that control oral drug intake include dose, schedule of reinforcement, food restriction, and alternative reinforcers. Many drugs, administered by the experimenter, can alter oral drug reinforcement. Relative reinforcing effects can be assessed by choice procedures and by persistence of behavior across increases in schedule size. In general, reinforcing effects increase directly with dose. Rhesus monkeys prefer combinations of reinforcing drugs to the component drugs. The taste of drug solutions may act as a conditioned reinforcer and a discriminative stimulus. Consequences of drug intake include tolerance and physiological dependence. Findings with orally self-administered drugs are similar to many findings with other positive reinforcers, including intravenously self-administered drugs.

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

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

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

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

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

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

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

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…

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

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

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

Robust model predictive control for optimal continuous drug administration.

PubMed

Sopasakis, Pantelis; Patrinos, Panagiotis; Sarimveis, Haralambos

2014-10-01

In this paper the model predictive control (MPC) technology is used for tackling the optimal drug administration problem. The important advantage of MPC compared to other control technologies is that it explicitly takes into account the constraints of the system. In particular, for drug treatments of living organisms, MPC can guarantee satisfaction of the minimum toxic concentration (MTC) constraints. A whole-body physiologically-based pharmacokinetic (PBPK) model serves as the dynamic prediction model of the system after it is formulated as a discrete-time state-space model. Only plasma measurements are assumed to be measured on-line. The rest of the states (drug concentrations in other organs and tissues) are estimated in real time by designing an artificial observer. The complete system (observer and MPC controller) is able to drive the drug concentration to the desired levels at the organs of interest, while satisfying the imposed constraints, even in the presence of modelling errors, disturbances and noise. A case study on a PBPK model with 7 compartments, constraints on 5 tissues and a variable drug concentration set-point illustrates the efficiency of the methodology in drug dosing control applications. The proposed methodology is also tested in an uncertain setting and proves successful in presence of modelling errors and inaccurate measurements. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1083] Draft Guidance for Industry and Food and Drug Administration Staff; Civil Money Penalties for Tobacco... guidance for industry entitled ``Civil Money Penalties for Tobacco Retailers: Responses to Frequently Asked...

78 FR 72900 - Guidance for Industry and Food and Drug Administration Staff; Civil Money Penalties for Tobacco...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1083] Guidance for Industry and Food and Drug Administration Staff; Civil Money Penalties for Tobacco Retailers... the guidance entitled ``Civil Money Penalties for Tobacco Retailers: Responses to Frequently Asked...

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

... on the sources of L. monocytogenes contamination, the effects of individual manufacturing and/or... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1182] Draft Joint Food and Drug Administration/Health Canada Quantitative Assessment of the Risk of...

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

... method comparison section and the sample selection inclusion and exclusion criteria section. The... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0428] Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

76 FR 48870 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-09

... selection inclusion and exclusion criteria section. The revisions define and differentiate the required... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0428] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document...

Pharmacogenomic biomarker information in drug labels approved by the United States food and drug administration: prevalence of related drug use.

PubMed

Frueh, Felix W; Amur, Shashi; Mummaneni, Padmaja; Epstein, Robert S; Aubert, Ronald E; DeLuca, Teresa M; Verbrugge, Robert R; Burckart, Gilbert J; Lesko, Lawrence J

2008-08-01

To review the labels of United States Food and Drug Administration (FDA)-approved drugs to identify those that contain pharmacogenomic biomarker information, and to collect prevalence information on the use of those drugs for which pharmacogenomic information is included in the drug labeling. Retrospective analysis. The Physicians' Desk Reference Web site, Drugs@FDA Web site, and manufacturers' Web sites were used to identify drug labels containing pharmacogenomic information, and the prescription claims database of a large pharmacy benefits manager (insuring > 55 million individuals in the United States) was used to obtain drug utilization data. Pharmacogenomic biomarkers were defined, FDA-approved drug labels containing this information were identified, and utilization of these drugs was determined. Of 1200 drug labels reviewed for the years 1945-2005, 121 drug labels contained pharmacogenomic information based on a key word search and follow-up screening. Of those, 69 labels referred to human genomic biomarkers, and 52 referred to microbial genomic biomarkers. Of the labels referring to human biomarkers, 43 (62%) pertained to polymorphisms in cytochrome P450 (CYP) enzyme metabolism, with CYP2D6 being most common. Of 36.1 million patients whose prescriptions were processed by a large pharmacy benefits manager in 2006, about 8.8 million (24.3%) received one or more drugs with human genomic biomarker information in the drug label. Nearly one fourth of all outpatients received one or more drugs that have pharmacogenomic information in the label for that drug. The incorporation and appropriate use of pharmacogenomic information in drug labels should be tested for its ability to improve drug use and safety in the United States.

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

... Administration, HHS. ACTION: Notice. The Food and Drug Administration's (FDA) Office of Orphan Products... educate the rare disease community on the FDA regulatory processes. This educational meeting will consist...

Acute And Subchronic Toxicity Studies Of SNEDDS (Self Nanoemulsifying Drug Delivery Systems) From Ethyl Acetate Extract Of Bay Leaf (Eugenia polyantha W.) with Virgin Coconut Oil As Oil Phase

NASA Astrophysics Data System (ADS)

Prihapsara, F.; Alamsyah, R. I.; Widiyani, T.; Artanti, A. N.

2018-03-01

Bay leaf (Eugenia polyantha) is widely used as an alternative therapy for diabetic and hypercholesterol. However, the administration of the extract has a low oral bioavailability, therefore it is prepared by Self Nanoemulsifying Drug Delivery Systems (SNEDDS) ethyl acetate extract of bay leaf. Therefore, acute and subchronic toxicity test is required. The toxicity test performed was an experimental study, including acute and subchronic toxicity tests. Animal experiments were used using Wistar strain rats. Acute toxicity test using 5 groups (n=5) consisted of 1 control group and 4 groups of SNEDDS dose with 48 mg/kgBW 240 mg/kg, 1200 mg/kg, and 6000 mg/kg, while for subchronic toxicity test with 1 group control and 3 groups of doses of SNEDDS with dose group variation 91.75 mg/kgBW, 183.5 mg/kg, and 367 mg/kg. Duration of observation at acute toxicity test for 14 days while for subcronic toxicity test for 28 days with continuous SNEDDS dosage. The results of the acute toxicity test showed toxic symptoms and obtained median lethal dose (LD50) values from SNEDDS from ethyl acetate extract of bay leaf 1409.30 mg/kgBW belonging to slightly toxic category. Subchronic toxicity studies show that the test drug has minor damage in liver and kidneys and moderate damage in pancreas.

Acute systemic rapamycin induces neurobehavioral alterations in rats.

PubMed

Hadamitzky, Martin; Herring, Arne; Keyvani, Kathy; Doenlen, Raphael; Krügel, Ute; Bösche, Katharina; Orlowski, Kathrin; Engler, Harald; Schedlowski, Manfred

2014-10-15

Rapamycin is a drug with antiproliferative and immunosuppressive properties, widely used for prevention of acute graft rejection and cancer therapy. It specifically inhibits the activity of the mammalian target of rapamycin (mTOR), a protein kinase known to play an important role in cell growth, proliferation and antibody production. Clinical observations show that patients undergoing therapy with immunosuppressive drugs frequently suffer from affective disorders such as anxiety or depression. However, whether these symptoms are attributed to the action of the distinct compounds remains rather elusive. The present study investigated in rats neurobehavioral consequences of acute rapamycin treatment. Systemic administration of a single low dose rapamycin (3mg/kg) led to enhanced neuronal activity in the amygdala analyzed by intracerebral electroencephalography and FOS protein expression 90min after drug injection. Moreover, behavioral investigations revealed a rapamycin-induced increase in anxiety-related behaviors in the elevated plus-maze and in the open-field. The behavioral alterations correlated to enhanced amygdaloid expression of KLK8 and FKBP51, proteins that have been implicated in the development of anxiety and depression. Together, these results demonstrate that acute blockade of mTOR signaling by acute rapamycin administration not only causes changes in neuronal activity, but also leads to elevated protein expression in protein kinase pathways others than mTOR, contributing to the development of anxiety-like behavior. Given the pivotal role of the amygdala in mood regulation, associative learning, and modulation of cognitive functions, our findings raise the question whether therapy with rapamycin may induce alterations in patients neuropsychological functioning. Copyright © 2014 Elsevier B.V. All rights reserved.

Towards a Computable Data Corpus of Temporal Correlations between Drug Administration and Lab Value Changes

PubMed Central

Newe, Axel; Wimmer, Stefan; Neubert, Antje; Becker, Linda; Prokosch, Hans-Ulrich; Ganslandt, Thomas

2015-01-01

Background The analysis of electronic health records for an automated detection of adverse drug reactions is an approach to solve the problems that arise from traditional methods like spontaneous reporting or manual chart review. Algorithms addressing this task should be modeled on the criteria for a standardized case causality assessment defined by the World Health Organization. One of these criteria is the temporal relationship between drug intake and the occurrence of a reaction or a laboratory test abnormality. Appropriate data that would allow for developing or validating related algorithms is not publicly available, though. Methods In order to provide such data, retrospective routine data of drug administrations and temporally corresponding laboratory observations from a university clinic were extracted, transformed and evaluated by experts in terms of a reasonable time relationship between drug administration and lab value alteration. Result The result is a data corpus of 400 episodes of normalized laboratory parameter values in temporal context with drug administrations. Each episode has been manually classified whether it contains data that might indicate a temporal correlation between the drug administration and the change of the lab value course, whether such a change is not observable or whether a decision between those two options is not possible due to the data. In addition, each episode has been assigned a concordance value which indicates how difficult it is to assess. This is the first open data corpus of a computable ground truth of temporal correlations between drug administration and lab value alterations. Discussion The main purpose of this data corpus is the provision of data for further research and the provision of a ground truth which allows for comparing the outcome of other assessments of this data with the outcome of assessments made by human experts. It can serve as a contribution towards systematic, computerized ADR detection in

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0431] Guidance for Food and Drug Administration Staff and Tobacco Retailers on Civil Money Penalties and No... entitled ``Civil Money Penalties and No- Tobacco-Sale Orders for Tobacco Retailers.'' This guidance...

75 FR 53316 - Draft Guidance for Food and Drug Administration Staff and Tobacco Retailers on Civil Money...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0431] Draft Guidance for Food and Drug Administration Staff and Tobacco Retailers on Civil Money Penalties and... guidance entitled ``Civil Money Penalties and No-Tobacco-Sale Orders for Tobacco Retailers.'' This guidance...

Quit Intentions Moderate Subjective and Physiological Responses to Acute Nicotine Replacement Therapy Administration in Dependent Smokers.

PubMed

Schlagintweit, Hera E; Campbell, Niamh K; Barrett, Sean P

2017-08-01

This study assessed the impact of expectancy and administration components of acute nicotine inhaler use on craving, heart rate, and smoking behavior in smokers with varying intentions to quit. 47 dependent smokers that differed in self-reported intention to quit (no intention to quit during the next month N = 26 vs. intention to initiate a quit attempt within 2 weeks N = 21) were randomly administered a 4 mg nicotine or nicotine-free inhaler across two sessions. Instructions regarding the inhaler's nicotine content (expect nicotine vs. expect nicotine-free; nicotine expectancy) and flavor (mint vs. citrus) varied across sessions. Craving and heart rate were assessed before and after inhaler administration (two-second inhalations every 10 seconds over 20 minutes). Next, participants were offered an opportunity to self-administer puffs of their preferred tobacco brand during an hour-long progressive ratio task. Across participants, nicotine expectancy independently reduced withdrawal related craving (p = .018), but no comparable effects of nicotine administration were evident. In quitting motivated smokers, nicotine expectancy and administration interacted to reduce intention to smoke (p = .040), while nicotine expectancy (p = .047) and administration (p = .025) independently reduced intention to smoke in quitting unmotivated smokers. Blunted heart rate reactivity to nicotine administration was observed in quitting motivated relative to unmotivated smokers (p = .042); however, neither expectancy nor administration impacted smoking behavior in either group (p values > .25). Findings indicate that participant quitting intentions moderate acute nicotine replacement therapy responses. In quitting motivated smokers, a combination of pharmacological and psychological factors may be necessary for nicotine replacement therapy to impact craving. Findings from this study demonstrate that motivations to quit smoking moderate subjective and physiological responses to acute

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. © The Author(s) 2016.

Current practice of methylprednisolone administration for acute spinal cord injury in Germany: a national survey.

PubMed

Druschel, Claudia; Schaser, Klaus-Dieter; Schwab, Jan M

2013-05-15

Written mail-out survey. To determine current practice in high-dose methylprednisolone succinate (MPSS) administration for treatment of acute spinal cord injury (SCI) in Germany. Reanalysis of the National Acute Spinal Cord Injury Studies (NASCIS) resulted in criticism of the use of high-dose MPSS for treatment of acute SCI. Subsequently, SCI treatment guidelines were revised leading to a reduction in MPSS use across North America. The impact of these revisions on SCI treatment in Germany is not known. A questionnaire was sent to all trauma, orthopedic and neurosurgical departments of German university centers, affiliated teaching hospitals, and specialized SCI care centers. Survey included 6 questions about the administration of MPSS after acute SCI. Three hundred seventy-two respondents completed the survey (response rate: 51% overall, 76% university hospitals, 85% specialized SCI care centers). Overall, 55% of departments that treat SCI prescribe MPSS. Among them, 73% are "frequent" users administering MPSS to more than 50% of their patients. Ten percent prescribe according to NASCIS I, 43% NASCIS II, 33% NASCIS III, and 13% "generic protocols." As justification for MPSS treatment, "effectiveness" ranked before "common practice" and "medicolegal reasons." "Specialized" SCI care centers differ in that (1) MPSS is administered less frequently, (2) NASCIS I doses are not used, and (3) during the past several years, practice patterns are more likely to have shifted away from the treatment of SCI with MPSS. About one-half of the institutions continue to prescribe MPSS in the setting of acute SCI. A need for further education in almost one-fourth of German departments treating acute SCI is demonstrated through responses indicating use of the outdated NASCIS I protocol, a "legal need" or "unchanged MPSS application during the last years." "Specialized" SCI centers are more likely to change their practice in accordance with evolving literature. 3.

New strategies for the treatment of acute venous thromboembolism.

PubMed

Prandoni, Paolo; Lensing, Anthonie W A; Pesavento, Raffaele

2006-11-01

In recent years, new opportunities have emerged that have the potential to change rapidly the therapeutic scenario of patients with acute venous thromboembolism (VTE). Selected patients with deep vein thrombosis (DVT) can be treated effectively and safely at home with fixed doses of low molecular weight heparins. The prompt administration of compression elastic stockings in addition to anticoagulant drugs in patients with acute DVT has the potential to halve the rate of late postthrombotic sequelae. The long-term use of low molecular weight heparins is likely to be more effective than oral anticoagulants for the secondary prevention of VTE in patients with advanced malignancy. Patients with pulmonary embolism and right ventricular dysfunction might benefit from the early administration of thrombolytic drugs in combination with heparin to a greater extent than from heparin alone. Despite an impressive amount of clinical information on the proper duration of oral anticoagulants in patients with unprovoked VTE, the optimal long-term treatment of these patients remains undefined. Finally, new categories of drugs are emerging that have the potential to replace conventional anticoagulants in the near future. They include compounds that inhibit factor Xa or thrombin.

Acute and chronic toxicity of six anticancer drugs on rotifers and crustaceans.

PubMed

Parrella, Alfredo; Lavorgna, Margherita; Criscuolo, Emma; Russo, Chiara; Fiumano, Vittorio; Isidori, Marina

2014-11-01

The growing use of cytostatic drugs is gaining relevance as an environmental concern. Environmental and distribution studies are increasing due to the development of accurate analytical methods, whereas ecotoxicological studies are still lacking. The aim of the present study was to investigate the acute and chronic toxicity of six cytostatics (5-fluorouracil, capecitabine, cisplatin, doxorubicin, etoposide, and imatinib) belonging to five classes of Anatomical Therapeutic Classification (ATC) on primary consumers of the aquatic chain (Daphnia magna, Ceriodaphnia dubia, Brachionus calyciflorus, and Thamnocephalus platyurus). Acute ecotoxicological effects occurred at concentrations in the order of mgL(-)(1), higher than those predicted in the environment, and the most acutely toxic drugs among those tested were cisplatin and doxorubicin for most aquatic organisms. For chronic toxicity, cisplatin and 5-fluorouracil showed the highest toxic potential in all test organisms, inducing 50% reproduction inhibition in crustaceans at concentrations on the order of μgL(-)(1). Rotifers were less susceptible to these pharmaceuticals. On the basis of chronic results, the low effective concentrations suggest a potential environmental risk of cytostatics. Thus, this study could be an important starting point for establishing the real environmental impact of these substances. Copyright © 2014 Elsevier Ltd. All rights reserved.

Acute cognitive impact of antiseizure drugs in naive rodents and corneal-kindled mice.

PubMed

Barker-Haliski, Melissa L; Vanegas, Fabiola; Mau, Matthew J; Underwood, Tristan K; White, H Steve

2016-09-01

Some antiseizure drugs (ASDs) are associated with cognitive liability in patients with epilepsy, thus ASDs without this risk would be preferred. Little comparative pharmacology exists with ASDs in preclinical models of cognition. Few pharmacologic studies exist on the acute effects in rodents with chronic seizures. Predicting risk for cognitive impact with preclinical models may supply valuable ASD differentiation data. ASDs (phenytoin [PHT]; carbamazepine [CBZ]; valproic acid [VPA]; lamotrigine [LTG]; phenobarbital [PB]; tiagabine [TGB]; retigabine [RTG]; topiramate [TPM]; and levetiracetam [LEV]) were administered equivalent to maximal electroshock median effective dose ([ED50]; mice, rats), or median dose necessary to elicit minimal motor impairment (median toxic dose [TD50]; rats). Cognition models with naive adult rodents were novel object/place recognition (NOPR) task with CF-1 mice, and Morris water maze (MWM) with Sprague-Dawley rats. Selected ASDs were also administered to rats prior to testing in an open field. The effect of chronic seizures and ASD administration on cognitive performance in NOPR was also determined with corneal-kindled mice. Mice that did not achieve kindling criterion (partially kindled) were included to examine the effect of electrical stimulation on cognitive performance. Sham-kindled and age-matched mice were also tested. No ASD (ED50) affected latency to locate the MWM platform; TD50 of PB, RTG, TPM, and VPA reduced this latency. In naive mice, CBZ and VPA (ED50) reduced time with the novel object. Of interest, no ASD (ED50) affected performance of fully kindled mice in NOPR, whereas CBZ and LEV improved cognitive performance of partially kindled mice. Standardized approaches to the preclinical evaluation of an ASD's potential cognitive impact are needed to inform drug development. This study demonstrated acute, dose- and model-dependent effects of therapeutically relevant doses of ASDs on cognitive performance of naive mice and

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

...: Ovarian Adnexal Mass Assessment Score Test System; Availability AGENCY: Food and Drug Administration, HHS... assessment score test system into class II (special controls) under section 513(f)(2) of the Federal Food... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0028...

Proteomic study of acute respiratory distress syndrome: current knowledge and implications for drug development

PubMed Central

Levitt, Joseph E.; Rogers, Angela J.

2017-01-01

The acute respiratory distress syndrome (ARDS) is a common cause of acute respiratory failure, and is associated with substantial mortality and morbidity. Dozens of clinical trials targeting ARDS have failed, with no drug specifically targeting lung injury in widespread clinical use. Thus, the need for drug development in ARDS is great. Targeted proteomic studies in ARDS have identified many key pathways in the disease, including inflammation, epithelial injury, endothelial injury or activation, and disordered coagulation and repair. Recent studies reveal the potential for proteomic changes to identify novel subphenotypes of ARDS patients who may be most likely to respond to therapy and could thus be targeted for enrollment in clinical trials. Nontargeted studies of proteomics in ARDS are just beginning and have the potential to identify novel drug targets and key pathways in the disease. Proteomics will play an important role in phenotyping of patients and developing novel therapies for ARDS in the future. PMID:27031735

Fighting fire with fire: mass antimalarial drug administrations in an era of antimalarial resistance.

PubMed

von Seidlein, Lorenz; Dondorp, Arjen

2015-06-01

The emergence and spread of antimalarial resistance has been a major liability for malaria control. The spread of chloroquine-resistant Plasmodium falciparum strains had catastrophic consequences for people in malaria-endemic regions, particularly in sub-Saharan Africa. The recent emergence of artemisinin-resistant P. falciparum strains is of highest concern. Current efforts to contain artemisinin resistance have yet to show success. In the absence of more promising plans, it has been suggested to eliminate falciparum malaria from foci of artemisinin resistance using a multipronged approach, including mass drug administrations. The use of mass drug administrations is controversial as it increases drug pressure. Based on current knowledge it is difficult to conceptualize how targeted malaria elimination could contribute to artemisinin resistance, provided a full treatment course is ensured.

Drug-Induced Acute Myocardial Infarction: Identifying ‘Prime Suspects’ from Electronic Healthcare Records-Based Surveillance System

PubMed Central

Coloma, Preciosa M.; Schuemie, Martijn J.; Trifirò, Gianluca; Furlong, Laura; van Mulligen, Erik; Bauer-Mehren, Anna; Avillach, Paul; Kors, Jan; Sanz, Ferran; Mestres, Jordi; Oliveira, José Luis; Boyer, Scott; Helgee, Ernst Ahlberg; Molokhia, Mariam; Matthews, Justin; Prieto-Merino, David; Gini, Rosa; Herings, Ron; Mazzaglia, Giampiero; Picelli, Gino; Scotti, Lorenza; Pedersen, Lars; van der Lei, Johan; Sturkenboom, Miriam

2013-01-01

Background Drug-related adverse events remain an important cause of morbidity and mortality and impose huge burden on healthcare costs. Routinely collected electronic healthcare data give a good snapshot of how drugs are being used in ‘real-world’ settings. Objective To describe a strategy that identifies potentially drug-induced acute myocardial infarction (AMI) from a large international healthcare data network. Methods Post-marketing safety surveillance was conducted in seven population-based healthcare databases in three countries (Denmark, Italy, and the Netherlands) using anonymised demographic, clinical, and prescription/dispensing data representing 21,171,291 individuals with 154,474,063 person-years of follow-up in the period 1996–2010. Primary care physicians’ medical records and administrative claims containing reimbursements for filled prescriptions, laboratory tests, and hospitalisations were evaluated using a three-tier triage system of detection, filtering, and substantiation that generated a list of drugs potentially associated with AMI. Outcome of interest was statistically significant increased risk of AMI during drug exposure that has not been previously described in current literature and is biologically plausible. Results Overall, 163 drugs were identified to be associated with increased risk of AMI during preliminary screening. Of these, 124 drugs were eliminated after adjustment for possible bias and confounding. With subsequent application of criteria for novelty and biological plausibility, association with AMI remained for nine drugs (‘prime suspects’): azithromycin; erythromycin; roxithromycin; metoclopramide; cisapride; domperidone; betamethasone; fluconazole; and megestrol acetate. Limitations Although global health status, co-morbidities, and time-invariant factors were adjusted for, residual confounding cannot be ruled out. Conclusion A strategy to identify potentially drug-induced AMI from electronic healthcare data has

Distribution of trans-resveratrol and its metabolites after acute or sustained administration in mouse heart, brain, and liver.

PubMed

Menet, Marie-Claude; Baron, Stephanie; Taghi, Meryam; Diestra, Remi; Dargère, Delphine; Laprévote, Olivier; Nivet-Antoine, Valérie; Beaudeux, Jean-Louis; Bédarida, Tatiana; Cottart, Charles-Henry

2017-08-01

Trans-resveratrol is widely studied for its potentially beneficial effects on numerous disorders. It is rapidly metabolized and its metabolites can exhibit biological activity. The present study aimed to investigate whether acute or sustained trans-resveratrol administration impacted on the distribution of trans-resveratrol and its metabolites in brain, heart, and liver. We used ultra-HPLC quadrupole-TOF (UHPLC-Q-TOF) in a full-scan mode to identify and assess large numbers of resveratrol metabolites. For acute intake, mice were overfed with a single dose of trans-resveratrol (150 mg/kg) and organs were collected after 30 and 60 min. For sustained intake, trans-resveratrol was given in the chow (0.04% w/w corresponding to 40 mg/kg/day), and plasma and the organs were collected after 3 months of this resveratrol diet. We found that trans-resveratrol-3-O-glucuronide and resveratrol-3-sulfate were the main metabolites found after acute intake, and free trans-resveratrol (in the brain and heart) and dihydroresveratrol derivatives were found after sustained administration CONCLUSIONS: Our results show notable differences between acute and sustained administration of trans-resveratrol and distribution of trans-resveratrol and its metabolites in mouse heart, brain, and liver. The results suggest a strategy for development of galenic forms of resveratrol. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0465] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document... guidance document will serve as the special control for rTMS systems. Section 513(f)(2) of the Federal Food...

A drug's life: the pathway to drug approval.

PubMed

Keng, Michael K; Wenzell, Candice M; Sekeres, Mikkael A

2013-10-01

In the United States, drugs and medical devices are regulated by the US Food and Drug Administration (FDA). A drug must undergo rigorous testing prior to marketing to and medical use by the general public. The FDA grants marketing approval for drug products based on a comprehensive review of safety and efficacy data. This review article explains the history behind the establishment of the FDA and examines the historical legislation and approval processes for drugs, specifically in the fields of medical oncology and hematology. The agents imatinib (Gleevec, Novartis) and decitabine (Dacogen, Eisai) are used to illustrate both the current FDA regulatory process-specifically the orphan drug designation and accelerated approval process-and why decitabine failed to gain an indication for acute myeloid leukemia. The purpose and construct of the Oncologic Drugs Advisory Committee are also discussed, along with examples of 2 renal cell cancer drugs-axitinib (Inlyta, Pfizer) and tivozanib-that used progression-free survival as an endpoint. Regulatory approval of oncology drugs is the cornerstone of the development of new treatment agents and modalities, which lead to improvements in the standard of cancer care. The future landscape of drug development and regulatory approval will be influenced by the new breakthrough therapy designation, and choice of drug will be guided by genomic insights.

Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Xiaobing; Graduate School of Peking Union Medical College, Dongcheng District, Beijing, 100730; Ma, Ben

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 resultsmore » 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.« less

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.

Effect of acute and chronic administration of caffeine on pain-like behaviors in rats with partial sciatic nerve injury.

PubMed

Wu, Wei-Ping; Hao, Jing-Xia; Fredholm, Bertil B; Wiesenfeld-Hallin, Zsuzsanna; Xu, Xiao-Jun

2006-07-10

Caffeine, used in many pain medications as an adjuvant analgesic, is an adenosine A1 and A2A receptor antagonist. Here we examined the effects of acute or chronic caffeine administration in rats after partial sciatic nerve injury. The hindpaw response to mechanical or cold stimulation was assessed following photochemically induced sciatic nerve injury which leads to hypersensitivity to these stimuli. Caffeine was administered i.p. acutely or in the drinking water chronically. The mechanical and cold hypersensitivity of sciatic nerve-injured rats was dose-dependently alleviated by acute systemic administration of caffeine (10-80 mg/kg). The effect of caffeine was, however, associated with side effects including locomotor stimulation or depression. Chronic oral administration (average daily doses 27.5 mg/kg/day or 61.5 mg/kg/day for 2 weeks) of caffeine starting at the time of nerve injury did not significantly affect the development of pain-like behaviors. Thus, acute, but not long term, caffeine intake reduced neuropathic pain state in nerve-injured rats, but only at very high doses. The potential hyperalgesic effect of chronic A1 adenosine receptor blockade may have been compensated for by an antinociceptive effect of caffeine through antagonism of A2A receptors and tolerance development.

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

...] Guidance for Industry and Food and Drug Administration Staff; User Fees for 513(g) Requests for Information... Administration (FDA) is announcing the availability of the guidance entitled ``Guidance for Industry and Food and... ``Guidance for Industry and Food and Drug Administration Staff; User Fees for 513(g) Requests for Information...

Alpha3beta4 nicotinic acetylcholine receptors in the medial habenula modulate the mesolimbic dopaminergic response to acute nicotine in vivo

PubMed Central

McCallum, Sarah E.; Cowe, Matthew A.; Lewis, Samuel W.; Glick, Stanley D.

2012-01-01

Habenulo-interpeduncular nicotinic receptors, particularly those containing α3, β4 and α5 subunits, have recently been implicated in the reinforcing effects of nicotine. Our laboratory has shown that injection of α3β4 nicotinic receptor antagonists into the medial habenula (MHb) decreases self-administration of multiple abused drugs, including nicotine (Glick et al., 2006; 2008; 2011). However, it is unclear whether blockade of MHb nicotinic receptors has a direct effect on mesolimbic dopamine. Here, we performed in vivo microdialysis in female rats. Microdialysis probes were implanted into the nucleus accumbens (NAcc) and α3β4 nicotinic receptor antagonists (18-methoxycoronaridine; 18-MC or α-conotoxin AuIB; AuIB), were injected into the ipsilateral MHb, just prior to systemic nicotine (0.4 mg/kg, s.c.). Dialysate samples were collected before and after drug administration and levels of extracellular dopamine and its metabolites were measured using HPLC. Acute nicotine administration increased levels of extracellular dopamine and its metabolites in the NAcc. Pre-treatment with intra-habenular AuIB or 18-MC prevented nicotine-induced increases in accumbal dopamine. Neither drug had an effect on nicotine-induced increases in dopamine metabolites, suggesting that α3β4 receptors do not play a role in dopamine metabolism. The effect of intra-habenular blockade of α3β4 receptors on NAcc dopamine was selective for acute nicotine: neither AuIB nor 18-MC prevented increases in NAcc dopamine stimulated by acute d-amphetamine or morphine. These results suggest the mesolimbic response to acute nicotine, but not to acute administration of other drugs of abuse, is directly modulated by α3β4 nicotinic receptors in the MHb, and emphasize a critical role for habenular nicotinic receptors in nicotine’s reinforcing effects. PMID:22561751

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

... Assistance, Center for Devices and Radiological Health (CDRH), Food and Drug Administration, 10903 New... CDRH: Anastacia Bilek, Center for Devices and Radiological Health, Food and Drug Administration, 10903... PMA Supplements for Manufacturing Method or Process Changes, Guidance for Industry and CDRH,'' that...

Multidrug-resistant malaria and the impact of mass drug administration.

PubMed

Zuber, Janie Anne; Takala-Harrison, Shannon

2018-01-01

Based on the emergence and spread throughout the Greater Mekong Subregion (GMS) of multiple artemisinin-resistant lineages, the prevalence of multidrug resistance leading to high rates of artemisinin-based combination treatment failure in parts of the GMS, and the declining malaria burden in the region, the World Health Organization has recommended complete elimination of falciparum malaria from the GMS. Mass drug administration (MDA) is being piloted as one elimination intervention to be employed as part of this effort. However, concerns remain as to whether MDA might exacerbate the already prevalent problem of multidrug resistance in the region. In this review, we briefly discuss challenges of MDA, the use of MDA in the context of multidrug-resistant malaria, and the potential of different drug combinations and drug-based elimination strategies for mitigating the emergence and spread of resistance.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-28

...] Proyecto Informar: Food and Drug Administration Hispanic Outreach Initiative (U01) AGENCY: Food and Drug... initiatives that will communicate risk and emergency public health information to millions of Spanish-speaking... (The Alliance). The purpose of this agreement is to support initiatives that will communicate risk and...

Best practice strategies to safeguard drug prescribing and drug administration: an anthology of expert views and opinions.

PubMed

Seidling, Hanna M; Stützle, Marion; Hoppe-Tichy, Torsten; Allenet, Benoît; Bedouch, Pierrick; Bonnabry, Pascal; Coleman, Jamie J; Fernandez-Llimos, Fernando; Lovis, Christian; Rei, Maria Jose; Störzinger, Dominic; Taylor, Lenka A; Pontefract, Sarah K; van den Bemt, Patricia M L A; van der Sijs, Heleen; Haefeli, Walter E

2016-04-01

While evidence on implementation of medication safety strategies is increasing, reasons for selecting and relinquishing distinct strategies and details on implementation are typically not shared in published literature. We aimed to collect and structure expert information resulting from implementing medication safety strategies to provide advice for decision-makers. Medication safety experts with clinical expertise from thirteen hospitals throughout twelve European and North American countries shared their experience in workshop meetings, on-site-visits and remote structured interviews. We performed an expert-based, in-depth assessment of implementation of best-practice strategies to improve drug prescribing and drug administration. Workflow, variability and recommended medication safety strategies in drug prescribing and drug administration processes. According to the experts, institutions chose strategies that targeted process steps known to be particularly error-prone in the respective setting. Often, the selection was channeled by local constraints such as the e-health equipment and critically modulated by national context factors. In our study, the experts favored electronic prescribing with clinical decision support and medication reconciliation as most promising interventions. They agreed that self-assessment and introduction of medication safety boards were crucial to satisfy the setting-specific differences and foster successful implementation. While general evidence for implementation of strategies to improve medication safety exists, successful selection and adaptation of a distinct strategy requires a thorough knowledge of the institute-specific constraints and an ongoing monitoring and adjustment of the implemented measures.

Acquired drug resistance conferred by a KRAS gene mutation following the administration of cetuximab: a case report

PubMed Central

2013-01-01

Background Although a number of studies have reported acquired drug resistance due to administration of epidermal growth factor receptor antibody inhibitors, the underlying causes of this phenomenon remain unclear. Case presentation Here we report a case of a 75-year-old man with liver metastasis at 3 years after a successful transverse colectomy to treat KRAS wild-type colorectal cancer. While initial administration of epidermal growth factor receptor inhibitors proved effective, continued use of the same treatment resulted in new peritoneal seeding. An acquired KRAS mutation was found in a resected tissue specimen from one such area. This mutation, possibly caused by administration of epidermal growth factor receptor inhibitors, appears to have conferred drug resistance. Conclusion The present findings suggest that administration of epidermal growth factor receptor inhibitors results in an acquired KRAS mutation that confers drug resistance. PMID:24304820

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

FDA publishes conflict of interest rules for clinical trials. Food and Drug Administration.

PubMed

James, J S

1998-03-06

The Food and Drug Administration (FDA) published new rules defining conflict of interests between drug companies and medical researchers and clinicians. Certain financial arrangements will need to be disclosed, although the FDA estimates that only one to ten percent of pharmaceutical companies will need to submit disclosures for one or more of their investigators. The purpose of the new rule is to prevent bias in safety and efficacy studies of drugs and medical devices. The full rule is published in the Federal Register.

Acute versus chronic administration of phosphodiesterase inhibitors on allergen-induced pulmonary cell influx in sensitized guinea-pigs.

PubMed Central

Banner, K H; Page, C P

1995-01-01

1. The aims of this study were to determine which phosphodiesterase (PDE) isoenzymes are involved in the control of eosinophil accumulation in the airways of ovalbumin (OVA)-immunized guinea-pigs by the use of isoenzyme selective inhibitors and to compare the effects of acute versus chronic administration of PDE isozyme inhibitors on pulmonary cell influx in ovalbumin-immunized guinea-pigs. 2. Guinea-pigs were sensitized and subsequently challenged with aerosolized OVA. Twenty four hours later bronchoalveolar lavage (BAL) was performed to permit assessment of inflammatory cell accumulation. A significant increase in the number of eosinophils was observed in the lavage fluid from OVA-immunized (13.6 +/- 1.4 x 10(4) ml-1 in acute experiments and 10.1 +/- 1.4 x 10(4) ml-1 in chronic experiments) animals compared with sham-treated controls (5.6 +/- 0.6 x 10(4) ml-1 in acute experiments and 5.1 +/- 0.6 x 10(4) ml-1 in chronic experiments). There was no difference in neutrophil, mononuclear cell or total cell numbers between the two groups. 3. Acute administration of a high dose of selective and non-selective PDE inhibitors by the i.p. route had no significant effect on eosinophil accumulation in the airways. 4. Chronic administration of a low dose (3 mg kg-1, i.p., twice daily for 7 days) of the type IV PDE inhibitor, RO 20-1724, and the PDE III/IV inhibitor, zardaverine, produced a significant inhibition of eosinophil accumulation (46% and 59% respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7536098

Food and Drug Administration: Helping pharmacists ensure that patients receive high-quality medicines.

PubMed

Kremzner, Mary

2016-01-01

Ensuring that the drugs patients take are safe and effective is critical to the Food and Drug Administration (FDA) mission and a major reason for testing an active pharmaceutical ingredient or currently marketed drug product. To address gaps in the assessment of drug quality, FDA's Center for Drug Evaluation and Research (CDER) has created the Office of Pharmaceutical Quality (OPQ). This newly formed "super-office" within CDER launched a concerted new strategy that enhances the surveillance of drug manufacturing and will bring a comprehensive approach to quality oversight. With OPQ and these new performance measures in place, FDA can sharpen its focus on issues critical to quality and can identify and respond to manufacturing issues before they become major systemic problems. Published by Elsevier Inc.

Lack of effect of acute repaglinide administration on postprandial lipaemia in patients with type 2 diabetes mellitus.

PubMed

Tentolouris, N; Kolia, M; Tselepis, A D; Perea, D; Kitsou, E; Kyriaki, D; Tambaki, A P; Karabina, S P; Sala, C; Fragoulopoulos, E; Katsilambros, N

2003-09-01

The effect of acute repaglinide administration (2 mg) on postprandial glycaemia and lipaemia has been examined in 20 subjects with type 2 diabetes mellitus. Each subject received in the morning, after a 12 to 14 h fast, a standard mixed meal (total energy 783 kcal), preceded by one tablet of 2 mg repaglinide or placebo. Chylomicrons and chylomicron-deficient plasma were prepared by ultracentrifugation. Triglyceride levels in CM fraction (CM-triglycerides) in total plasma as well as in CM-deficient plasma (non-CM-triglycerides) were determined. A significant reduction in postprandial glycaemia was observed after repaglinide administration compared to placebo ( p < 0.001). Plasma concentrations of total triglycerides, CM-triglycerides, non-CM-triglycerides, free fatty acids and the other plasma lipids measured, were not significantly different between the two phases of the study. It is concluded that, in contrast to sulphonylureas, acute repaglinide administration does not improve postprandial lipaemia in patients with type 2 diabetes.

Drugs' development in acute heart failure: what went wrong?

PubMed

Teneggi, Vincenzo; Sivakumar, Nithy; Chen, Deborah; Matter, Alex

2018-05-08

Acute heart failure (AHF) is a major burden disease, with a complex physiopathology, unsatisfactory diagnosis, treatment and a very poor prognosis. In the last two decades, a number of drugs have progressed from preclinical to early and late clinical development, but only a few of them have been approved and added to a stagnant pharmacological armamentarium. We have reviewed the data published on drugs developed for AHF since early 2000s, trying to recognise factors that have worked for a successful approval or for the stoppage of the program, in an attempt to delineate future trajectories for AHF drug development. Our review has identified limitations at both preclinical and clinical levels. At the preclinical level, the major shortcoming is represented by animal models looking at short-term endpoints which do not recapitulate the complexity of the human disease. At the clinical level, the main weakness is given by the disconnect between short-term endpoints assessed in the early stage of drug development, and medium-long-term endpoints requested in Phase 3 for regulatory approval. This is further amplified by the lack of validation and standardisation of short- and long-term endpoints; absence of predictive biomarkers; conduct of studies on heterogeneous populations; and use of different eligibility criteria, time of assessments, drug schedules and background therapies. Key goals remain a better understanding of AHF and the construction of a successful drug development program. A reasonable way to move forward resides in a strong collaboration between main stakeholders of therapeutic innovation: scientific community, industry and regulatory agencies.

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.

76 FR 74791 - Memorandum of Understanding Between the Food and Drug Administration and the U.S. Department of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0005] Memorandum of Understanding Between the Food and Drug Administration and the U.S. Department of Agriculture's... memorandum of understanding (MOU) with the U.S. Department of Agriculture's (USDA) Agricultural and Marketing...

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... Categories of Records § 20.105 Testing and research conducted by or with funds provided by the Food and Drug Administration. (a) Any list that may be prepared by the Food and Drug Administration of testing and research...

21 CFR 20.105 - Testing and research conducted by or with funds provided by the Food and Drug Administration.