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Sample records for acting antitussive drugs

  1. Centrally acting non-narcotic antitussives prevent hyperactivity in mice: Involvement of GIRK channels.

    PubMed

    Soeda, Fumio; Fujieda, Yoshiko; Kinoshita, Mizue; Shirasaki, Tetsuya; Takahama, Kazuo

    2016-05-01

    We have previously reported that centrally acting non-narcotic antitussives inhibited G protein-coupled inwardly rectifying potassium (GIRK) channel-activated currents, and that the antitussives had multiple pharmacological actions on various models of intractable brain diseases in rodents. In this study, the question of whether these antitussives inhibit drug-induced hyperactivity in mice was investigated. Antitussives, such as cloperastine and tipepidine, at cough suppressant doses, inhibited an increase in ambulation of mice neonatally treated with 6-hydroxydopamine. In addition, all antitussives studied inhibited an increase in methamphetamine-induced hyperactivity in mice. Methylphenidate, which is used for treatment of ADHD, inhibited 6-hydroxydopamine-lesion-induced, but not methamphetamine-induced, hyperactivity in mice. By the rota-rod test, the drugs had little effect on motor coordination of the hyperactive mice. Significant correlation was found between the ameliorating effects of antitussives on methamphetamine-induced hyperactivity and their inhibitory actions on GIRK channel currents (coefficient factor, 0.998). Furthermore, tertiapin, a GIRK channel blocker, prevented an increase in methamphetamine-induced hyperactivity of mice. These results demonstrated that antitussive drugs (cloperastine, tipepidine and caramiphen) possessing inhibitory action on GIRK channels inhibit drug-induced hyperactivity in mice, suggesting that such antitussives may potentially be therapeutic for patients with ADHD. PMID:26892760

  2. Antidepressant-like effect of centrally acting non-narcotic antitussive caramiphen in a forced swimming test.

    PubMed

    Kawaura, Kazuaki; Miki, Risa; Shima, Eriko; Honda, Sokichi; Soeda, Fumio; Shirasaki, Tetsuya; Takahama, Kazuo

    2010-09-13

    Recently, we reported that a centrally acting non-narcotic antitussive (cough suppressant drug), tipepidine produces an antidepressant-like effect in the forced swimming test in rats. Because pharmacological properties of tipepidine apparently differ from those of typical antidepressants developed to date, we speculated that caramiphen, another centrally acting antitussive, has an antidepressant-like effect. That effect of caramiphen was studied in rats using the forced swimming test. Caramiphen at 20 and 40mg/kg i.p. significantly reduced immobility. At 40mg/kg i.p., it increased climbing behavior. Even at 40mg/kg, this drug had no effect on locomotor activity. Results suggest that a centrally acting antitussive possessing inhibition of GIRK channels has an antidepressant-like effect. PMID:20621160

  3. Anaphylaxis caused by tipepidine hibenzate, a central antitussive drug

    PubMed Central

    Mochizuki, Eisuke; Shirai, Toshihiro; Noguchi, Rie; Mitsui, Chihiro; Taniguchi, Masami; Suda, Takafumi

    2015-01-01

    Tipepidine hibenzate, a central antitussive drug, is widely used in the management of cough and is generally safe and well tolerated. We present here a case of anaphylaxis caused by this drug. When the patient had caught a cold over the previous 10 years, she had received medications, including tipepidine hibenzate, from her family doctor. However, this time, she developed dyspnea, skin eruption, and anaphylactic shock after taking a Chinese herbal medicine and this drug. After her conditions improved due to adequate treatment, she was referred to our hospital to confirm the causative drug. Double-blind placebo-controlled oral challenge tests were performed after obtaining informed consent. Oral challenge with one-third tablet dose of tipepidine hibenzate caused a positive reaction. Urinary leukotriene E4 rose during the challenge with tipepidine hibenzate, but not with control. Clinicians should keep in mind that common antitussive drug use can cause anaphylactic reactions in very rare cases and can be harmful. PMID:25802739

  4. Anaphylaxis caused by tipepidine hibenzate, a central antitussive drug.

    PubMed

    Mochizuki, Eisuke; Shirai, Toshihiro; Noguchi, Rie; Mitsui, Chihiro; Taniguchi, Masami; Suda, Takafumi

    2015-03-01

    Tipepidine hibenzate, a central antitussive drug, is widely used in the management of cough and is generally safe and well tolerated. We present here a case of anaphylaxis caused by this drug. When the patient had caught a cold over the previous 10 years, she had received medications, including tipepidine hibenzate, from her family doctor. However, this time, she developed dyspnea, skin eruption, and anaphylactic shock after taking a Chinese herbal medicine and this drug. After her conditions improved due to adequate treatment, she was referred to our hospital to confirm the causative drug. Double-blind placebo-controlled oral challenge tests were performed after obtaining informed consent. Oral challenge with one-third tablet dose of tipepidine hibenzate caused a positive reaction. Urinary leukotriene E4 rose during the challenge with tipepidine hibenzate, but not with control. Clinicians should keep in mind that common antitussive drug use can cause anaphylactic reactions in very rare cases and can be harmful. PMID:25802739

  5. A common antitussive drug, clobutinol, precipitates the long QT syndrome 2.

    PubMed

    Bellocq, Chloé; Wilders, Ronald; Schott, Jean-Jacques; Louérat-Oriou, Bénédicte; Boisseau, Pierre; Le Marec, Hervé; Escande, Denis; Baró, Isabelle

    2004-11-01

    QT prolongation, a classic risk factor for arrhythmias, can result from a mutation in one of the genes governing cardiac repolarization and also can result from the intake of a medication acting as blocker of the cardiac K(+) channel human ether-a-go-go-related gene (HERG). Here, we identified the arrhythmogenic potential of a nonopioid antitussive drug, clobutinol. The deleterious effects of clobutinol were suspected when a young boy, with a diagnosis of congenital long QT syndrome, experienced arrhythmias while being treated with this drug. Using the patch-clamp technique, we showed that clobutinol dose-dependently inhibited the HERG K(+) current with a half-maximum block concentration of 2.9 microM. In the proband, we identified a novel A561P HERG mutation. Two others long QT mutations (A561V and A561T) had been reported previously at the same position. None of the three mutants led to a sizeable current in heterologous expression system. When coexpressed with wild-type (WT) HERG channels, the three Ala561 mutants reduced the trafficking of WT and mutant heteromeric channels, resulting in decreased K(+) current amplitude (dominant-negative effects). In addition, A561P but not A561V and A561T mutants induced a approximately -11 mV shift of the current activation curve and accelerated deactivation, thereby partially counteracting the dominant-negative effects. A561P mutation and clobutinol effects on the human ventricular action potential characteristics were simulated using the Priebe-Beuckelmann model. Our work shows that clobutinol has limited effects on WT action potential but should be classified as a "drug to be avoided by congenital long QT patients" rather than as a "drug with risk of torsades de pointes". PMID:15280442

  6. Effects of common antitussive drugs on the hERG potassium channel current.

    PubMed

    Deisemann, Heike; Ahrens, Nadine; Schlobohm, Irene; Kirchhoff, Christian; Netzer, Rainer; Möller, Clemens

    2008-12-01

    A common over-the-counter (OTC) non-opioid antitussive drug, clobutinol, was recently withdrawn from the market due to its potential to induce cardiac arrhythmias by a blockade of the potassium channel coded by the human ether-à-go-go-related gene (hERG). In this study, we investigated the effects of a number of antitussive compounds on the hERG ion channel current using patch-clamp electrophysiology, and compared the effects to that of clobutinol. The compounds clobutinol, pentoxyverine, dextromethorphan, and codeine inhibited the outward current in hERG transfected cells with half-maximal inhibition concentrations (IC50) of 1.9 microM, 3.0 microM, 5.1 microM, and 97 microM, respectively. For theobromine, no significant effect on the hERG current at a concentration up to 100 microM was detected. Safety margins between the effects of the drugs on the hERG ion channel current and their calculated maximal free therapeutic plasma concentration were calculated. These results were compared to assess potential risks of the compounds to induce torsade de pointes-type arrhythmias. PMID:19034038

  7. Effects of the antitussive drug cloperastine on ventricular repolarization in halothane-anesthetized guinea pigs.

    PubMed

    Takahara, Akira; Fujiwara, Kaori; Ohtsuki, Atsushi; Oka, Takayuki; Namekata, Iyuki; Tanaka, Hikaru

    2012-01-01

    Cloperastine is an antitussive drug, which can be received as an over-the-counter cold medicine. The chemical structure of cloperastine is quite similar to that of the antihistamine drug diphenhydramine, which is reported to inhibit hERG K⁺ channels and clinically induce long QT syndrome after overdose. To analyze its proarrhythmic potential, we compared effects of cloperastine and diphenhydramine on the hERG K⁺ channels expressed in HEK293 cells. We further assessed their effects on the halothane-anesthetized guinea-pig heart under the monitoring of monophasic action potential (MAP) of the ventricle. Cloperastine inhibited the hERG K⁺ currents in a concentration-dependent manner with an IC₅₀ value of 0.027 μM, whose potency was 100 times greater than that of diphenhydramine (IC₅₀; 2.7 μM). In the anesthetized guinea pigs, cloperastine at a therapeutic dose of 1 mg/kg prolonged the QT interval and MAP duration without affecting PR interval or QRS width. Diphenhydramine at a therapeutic dose of 10 mg/kg prolonged the QT interval and MAP duration together with increase in PR interval and QRS width. The present results suggest that cloperastine may be categorized as a QT-prolonging drug that possibly induces arrhythmia at overdoses like diphenhydramine does. PMID:23047467

  8. Codeine: A Relook at the Old Antitussive.

    PubMed

    Vora, Agam; Nadkar, Milind Y

    2015-04-01

    Cough is the most frequent complaint of patients seeking medical attention in general and hospital practice. Cough is controlled by treating the cause, however, when no cause can be found, symptomatic relief of cough must be considered. Treatment of dry cough resulting from increased sensitivity of the cough reflex remains a challenge in some subjects. Codeine in combination with other medicines has been a mainstay for the effective short-term symptomatic relief of dry or nonproductive cough in clinical practice. This article focuses on the current status of codeine as an antitussive formulation in the treatment of dry cough. Codeine is one of the centrally acting narcotic opioids approved for use as an antitussive, a prodrug that is bioactivated by CYP2D6 into morphine in the liver. The opioid effects of codeine are related to plasma morphine concentrations. Codeine is one of the most frequently used antitussive in clinical practice and has been widely regarded as the standard cough suppressant against which newer drugs are being evaluated. Codeine has an advantage as an antitussive because of its multifaceted effect as an analgesic and sedative along with cough suppression. However, codeine may have efficacy to suppress cough in humans only in specific situations. Caution is also needed to limit its use only when and as long as it is clinically necessary, particularly in children. PMID:26591180

  9. RSD931, a novel anti-tussive agent acting on airway sensory nerves

    PubMed Central

    Adcock, J J; Douglas, G J; Garabette, M; Gascoigne, M; Beatch, G; Walker, M; Page, C P

    2003-01-01

    The anti-tussive effects, of the local anaesthetic, lidocaine and carcainium chloride (RSD931) have been investigated in guinea-pigs and rabbits. Pre-treatment of guinea-pigs with aerosols of lidocaine or RSD931 at 0.1, 1.0 and 10 mg ml−1 reduced the number of citric acid-induced coughs by 9.3, 32.6 and 40.9% (P>0.05) for lidocaine and by 25.3% (P>0.05), 40.4% (P>0.05) and 97.6% (P<0.01) for RSD931, respectively and increased the latency to onset of cough at 10.0 mg ml−1 only. In addition, RSD931 at 10 mg ml−1 reduced citric acid-evoked cough responses in rabbits (with prior exposure to ozone at 3 p.p.m. for 1 h) from 22.1±5.1 to 2.7±0.9 coughs (P<0.01). Acute pre-treatment of guinea-pigs with aerosols of lidocaine or RSD931 at 10.0 and 30.0 mg ml−1 reduced the number of capsaicin-evoked coughs by 42.2 and 10.3% (P>0.05) (lidocaine) and by 25% (P>0.05) and 76.9% (P<0.01) (RSD931), respectively. Lidocaine had little effect on the latency of cough onset at either 10.0 or 30.0 mg ml−1, however, RSD at 30.0 mg ml−1 significantly (P<0.05) prolonged the latency of cough onset. RSD931 (10.0 mg ml−1) significantly (P<0.05–<0.01) reduced the spontaneous and histamine-evoked discharges in Aδ-fibres originating from airway, rapidly adapting stretch receptors (RARs) without affecting histamine-evoked bronchoconstriction. Lidocaine at 10.0 mg ml−1 also significantly (P<0.05) inhibited the spontaneous and histamine-induced discharges of RARs without affecting histamine-evoked bronchoconstriction. Aerosols of RSD931 (10.0 mg ml−1) caused a transient, but significant (P<0.05), activation of pulmonary C-fibre endings 2.5 min after administration started. RSD931 had no significant (P>0.05) effects on discharges in bronchial C-fibres originating from bronchial C-fibre endings, capsaicin-evoked discharges of either pulmonary or bronchial C-fibre endings or on capsaicin-evoked bronchoconstriction. In contrast, lidocaine (10.0 mg ml−1) significantly (P<0

  10. Antitussive activity of Withania somnifera and opioid receptors.

    PubMed

    Nosálová, Gabriela; Sivová, Veronika; Ray, Bimalendu; Fraňová, Soňa; Ondrejka, Igor; Flešková, Dana

    2015-01-01

    Arabinogalactan is a polysaccharide isolated from the roots of the medicinal plant Withania somnifera L. It contains 65% arabinose and 18% galactose. The aim of the present study was to evaluate the antitussive activity of arabinogalactan in conscious, healthy adult guinea pigs and the role of the opioid pathway in the antitussive action. A polysaccharide extract was given orally in a dose of 50 mg/kg. Cough was induced by an aerosol of citric acid in a concentration 0.3 mol/L, generated by a jet nebulizer into a plethysmographic chamber. The intensity of cough response was defined as the number of cough efforts counted during a 3-min exposure to the aerosol. The major finding was that arabinogalactan clearly suppressed the cough reflex; the suppression was comparable with that of codeine that was taken as a reference drug. The involvement of the opioid system was tested with the use of a blood-brain barrier penetrable, naloxone hydrochloride, and non-penetrable, naloxone methiodide, to distinguish between the central and peripheral mu-opioid receptor pathways. Both opioid antagonists acted to reverse the arabinogalactan-induced cough suppression; the reversion was total over time with the latter antagonist. We failed to confirm the presence of a bronchodilating effect of the polysaccharide, which could be involved in its antitussive action. We conclude that the polysaccharide arabinogalactan from Withania somnifera has a distinct antitussive activity consisting of cough suppression and that this action involves the mu-opioid receptor pathways. PMID:25252908

  11. Antitussives and substance abuse

    PubMed Central

    Burns, Jarrett M; Boyer, Edward W

    2013-01-01

    Abuse of antitussive preparations is a continuing problem in the United States and throughout the world. Illicit, exploratory, or recreational use of dextromethorphan and codeine/promethazine cough syrups is widely described. This review describes the pharmacology, clinical effects, and management of toxicity from commonly abused antitussive formulations. PMID:24648790

  12. Antitussives and substance abuse.

    PubMed

    Burns, Jarrett M; Boyer, Edward W

    2013-01-01

    Abuse of antitussive preparations is a continuing problem in the United States and throughout the world. Illicit, exploratory, or recreational use of dextromethorphan and codeine/promethazine cough syrups is widely described. This review describes the pharmacology, clinical effects, and management of toxicity from commonly abused antitussive formulations. PMID:24648790

  13. Antitussive properties of levodropropizine.

    PubMed

    Malandrino, S; Melillo, G; Bestetti, A; Borsa, M; Giuliani, P; Tonon, G C

    1988-08-01

    The antitussive activity of levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526), was evaluated in anaesthetized guinea-pigs and rabbits and in unanaesthetized guinea-pigs. Levodropropizine was shown to have good antitussive activity. Intravenously, it was 1/10 to 1/20 as active as codeine and comparable to dropropizine, from which it is derived, on mechanically and electrically induced coughing in rabbits and guinea-pigs. After oral administration to the guinea-pig the antitussive activity of levodropropizine was comparable with those of both dropropizine and codeine against coughing induced by irritant aerosols. PMID:3196407

  14. Important drugs for cough in advanced cancer.

    PubMed

    Homsi, J; Walsh, D; Nelson, K A

    2001-11-01

    Cough is a defense mechanism that prevents the entry of noxious materials into the respiratory system and clears foreign materials and excess secretions from the lungs and respiratory tract. In advanced cancer, it is a common symptom that interferes with the patient's daily activity and quality of life. Empiric treatment with antitussive agents is often needed. Two classes of antitussive drugs are available: (1) centrally acting: (a) opioids and (b) non-opioids; (2) peripherally acting: (a) directly and (b) indirectly. Antitussive availability varies widely around the world. Many antitussives, such as benzonatate, codeine, hydrocodone, and dextromethorphan, were extensively studied in the acute and chronic cough settings and showed relatively high efficacy and safety profiles. Benzonatate, clobutinol, dihydrocodeine, hydrocodone, and levodropropizine were the only antitussives specifically studied in cancer and advanced cancer cough. They all have shown to be effective and safe in recommended daily dose for cough. In advanced cancer the patient's current medications, previous antitussive use, the availability of routes of administration, any history of drug abuse, the presence of other symptoms and other factors, all have a role in the selection of antitussives for prescription. A good knowledge of the pharmacokinetics, dosage, efficacy, and side effects of the available antitussives provides for better management. PMID:11762966

  15. [Comparative study of two antitussive drugs in the treatment of acute dry cough of infectious origin (prospective, randomized, single blind study)].

    PubMed

    Pujet, J C; Keddad, K; Sévenier, F; Jolivet-Landreau, I

    2002-01-01

    The objective was to compare, during a 5-day therapy, the efficacy and tolerability of an antihistaminic antitussive syrup, oxomemazine, combining a small quantity of guaifenesine (T), with a centrally acting antitussive, clobutinol (S), in adult patients aged from 18 to 70 years and presenting with a dry cough of infectious origin. This study was performed by 22 general practitioners and 130 ambulatory patients were enrolled. The primary criterion of this multicenter, randomized, single blind study was to compare the evolution of cough intensity using a Visual Analog Squale (VAS) graduated from 0 to 10 cm. Nine secondary criteria including tolerability were also assessed. With regard to cough intensity, the treatments were not equivalent. A greater reduction was observed with T (-5.2 +/- 2.3 versus -4.3 +/- 2.3). This result was confirmed by a further reduction in cough intensity at days: 2 (p = 0.04), 4 (p = 0.05), and 5 (p = 0.02). The frequency of cough disappearance before the end of the study was significantly greater for T than for S: 46% versus 29% (p = 0.05). The time before disappearance of the cough was 4.0 + 1.1 days for both medicines. Induction of sleep and the frequency of nocturnal wakening were significantly better for T from day 4 (p = 0.02). The drowsiness induced by T meant that diurnal quality of life was better with S on days 1 (p = 0.002) and 2 (p = 0.01). Tolerability was similar for both medicines. In conclusion, as a symptomatic treatment of dry cough, T is efficient and well tolerated. Moreover, we have observed a tendency towards superior efficacy of T than S. T is therefore a useful alternative in the therapeutic armamentarium available to the general practitioner. PMID:12611200

  16. Spectrophotometric determination of some anti-tussive and anti-spasmodic drugs through ion-pair complex formation with thiocyanate and cobalt(II) or molybdenum(V)

    NASA Astrophysics Data System (ADS)

    El-Shiekh, Ragaa; Zahran, Faten; El-Fetouh Gouda, Ayman Abou

    2007-04-01

    Two rapid, simple and sensitive extractive specrophotometric methods has been developed for the determination of anti-tussive drugs, e.g., dextromethorphan hydrobromide (DEX) and pipazethate hydrochloride (PiCl) and anti-spasmodic drugs, e.g., drotaverine hydrochloride (DvCl) and trimebutine maleate (TM) in bulk and in their pharmaceutical formulations. The proposed methods depend upon the reaction of cobalt(II)-thiocyanate (method A) and molybdenum(V)-thiocyanate ions (method B) with the cited drugs to form stable ion-pair complexes which extractable with an n-butnol-dichloromethane solvent mixture (3.5:6.5) and methylene chloride for methods A and B, respectively. The blue and orange red color complexes are determined either colorimetrically at λmax 625 nm (using method A) and 467 or 470 nm for (DEX and PiCl) or (DvCl and TM), respectively (using method B). The concentration range is 20-400 and 2.5-50 μg mL -1 for methods A and B, respectively. The proposed method was successfully applied for the determination of the studied drugs in pure and in pharmaceutical formulations applying the standard additions technique and the results obtained in good agreement well with those obtained by the official method.

  17. Spectrophotometric determination of some anti-tussive and anti-spasmodic drugs through ion-pair complex formation with thiocyanate and cobalt(II) or molybdenum(V).

    PubMed

    El-Shiekh, Ragaa; Zahran, Faten; El-Fetouh Gouda, Ayman Abou

    2007-04-01

    Two rapid, simple and sensitive extractive specrophotometric methods has been developed for the determination of anti-tussive drugs, e.g., dextromethorphan hydrobromide (DEX) and pipazethate hydrochloride (PiCl) and anti-spasmodic drugs, e.g., drotaverine hydrochloride (DvCl) and trimebutine maleate (TM) in bulk and in their pharmaceutical formulations. The proposed methods depend upon the reaction of cobalt(II)-thiocyanate (method A) and molybdenum(V)-thiocyanate ions (method B) with the cited drugs to form stable ion-pair complexes which extractable with an n-butnol-dichloromethane solvent mixture (3.5:6.5) and methylene chloride for methods A and B, respectively. The blue and orange red color complexes are determined either colorimetrically at lambdamax 625 nm (using method A) and 467 or 470 nm for (DEX and PiCl) or (DvCl and TM), respectively (using method B). The concentration range is 20-400 and 2.5-50 microg mL-1 for methods A and B, respectively. The proposed method was successfully applied for the determination of the studied drugs in pure and in pharmaceutical formulations applying the standard additions technique and the results obtained in good agreement well with those obtained by the official method. PMID:17142094

  18. Potential transducers based man-tailored biomimetic sensors for selective recognition of dextromethorphan as an antitussive drug.

    PubMed

    El-Naby, Eman H; Kamel, Ayman H

    2015-09-01

    A biomimetic potentiometric sensor for specific recognition of dextromethorphan (DXM), a drug classified according to the Drug Enforcement Administration (DEA) as a "drug of concern", is designed and characterized. A molecularly imprinted polymer (MIP), with special molecular recognition properties of DXM, was prepared by thermal polymerization in which DXM acted as template molecule, methacrylic acid (MAA) and acrylonitrile (AN) acted as functional monomers in the presence of ethylene glycol dimethacrylate (EGDMA) as crosslinker. The sensors showed a high selectivity and a sensitive response to the template in aqueous system. Electrochemical evaluation of these sensors revealed near-Nernstian response with slopes of 49.6±0.5 and 53.4±0.5 mV decade(-1) with a detection limit of 1.9×10(-6), and 1.0×10(-6) mol L(-1) DXM with MIP/MAA and MIP/AN membrane based sensors, respectively. Significantly improved accuracy, precision, response time, stability, selectivity and sensitivity were offered by these simple and cost-effective potentiometric sensors compared with other standard techniques. The method has the requisite accuracy, sensitivity and precision to assay DXM in pharmaceutical products. PMID:26046285

  19. 21 CFR 341.14 - Antitussive active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Antitussive active ingredients. 341.14 Section 341.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients §...

  20. [Toxicological characteristics of the antitussive preparation glaucine].

    PubMed

    Mironova, M I; Arzamastsev, E V; Bortnikova, V V; Krepkova, L V

    1983-01-01

    A toxicological study was made of the antitussive drug glaucinee hydrochloride, an alkaloid of the isoquinoline series (4,5,7,8-tetramethoxyaporphine hydrochloride) isolated from Glaucinum flavum Crantz. of the Papaveraceae family. Upon a single intraperitoneal injection to different laboratory animals the LD50 was found to be equal to 150--180 mg/kg whereas upon intragastric administration, to 510--620 mg/kg. Under the conditions of chronic experiments (intragastric administration to rats in doses of 5, 25 adn 75 mg/kg daily for 3 months) glaucin hydrochloride did not affect the general status of the animals, hematological characteristics, functions of the liver, cardiovascular and excretory systems, and the morphological indicators of the internal organs as shown by electron microscopy. The drug does not possess any allergizing, mutagenic, embryotoxic or teratogenic properties. The data obtained attest to the possibilities of a wide clinical application of glaucin hydrochloride as an antitussive drug. PMID:6617832

  1. Currently available antitussives.

    PubMed

    Dicpinigaitis, Peter V

    2009-04-01

    Cough is among the most common complaints for which patients seek medical attention. Acute cough, usually due to a viral upper respiratory tract infection, generates a huge expenditure on prescription and over-the-counter cough and cold preparations worldwide. Most of these agents, however, have not been shown to be more effective than placebo in adequately performed clinical trials. The goal of management in chronic cough is treatment of its underlying cause. However, certain situations will necessitate cough suppressant therapy for symptomatic relief. Unfortunately, currently available antitussives, such as the opioids, are not consistently effective, or achieve therapeutic effect at the expense of unpleasant or intolerable side effects. Safer and more effective cough suppressants are desperately needed. Potential novel antitussives will need to be evaluated in properly formulated clinical trials, measuring relevant subjective and objective end points in appropriate subject populations. PMID:18771744

  2. 21 CFR 341.14 - Antitussive active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... and 21 CFR 1308.15(c). (i) Codeine. (ii) Codeine phosphate. (iii) Codeine sulfate. (3...) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR OVER-THE... established for each ingredient in § 341.74(d): (a) Oral antitussives. (1) Chlophedianol hydrochloride....

  3. 21 CFR 341.14 - Antitussive active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... and 21 CFR 1308.15(c). (i) Codeine. (ii) Codeine phosphate. (iii) Codeine sulfate. (3...) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR OVER-THE... established for each ingredient in § 341.74(d): (a) Oral antitussives. (1) Chlophedianol hydrochloride....

  4. 21 CFR 341.14 - Antitussive active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... and 21 CFR 1308.15(c). (i) Codeine. (ii) Codeine phosphate. (iii) Codeine sulfate. (3...) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR OVER-THE... established for each ingredient in § 341.74(d): (a) Oral antitussives. (1) Chlophedianol hydrochloride....

  5. 21 CFR 341.14 - Antitussive active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and 21 CFR 1308.15(c). (i) Codeine. (ii) Codeine phosphate. (iii) Codeine sulfate. (3...) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR OVER-THE... established for each ingredient in § 341.74(d): (a) Oral antitussives. (1) Chlophedianol hydrochloride....

  6. A comparative randomized double-blind clinical trial of isoaminile citrate and chlophedianol hydrochloride as antitussive agents.

    PubMed

    Diwan, J; Dhand, R; Jindal, S K; Malik, S K; Sharma, P L

    1982-08-01

    The efficacy and safety of a new centrally acting antitussive agent, isoaminile citrate, was compared with that of chlophedianol hydrochloride in a double-blind, randomized interpatient study. A total of 66 patients participated, two and four patients were lost to follow-up with isoaminile and chlophedianol, respectively. In the experimentally induced cough in 12 normal human subjects, isoaminile (40 mg) was as effective as chlophedianol (20 mg), but its duration of action was somewhat longer. One subject developed allergic skin rash with chlophedianol and was withdrawn from the study. In 60 patients with cough associated with chest diseases, isoaminile (40 mg, 3 x daily) was as effective as chlophedianol (20 mg, 3 x daily) in suppressing cough as judged from the 3-h and 24-h cough counts. The increase in PEFR at day 7 of treatment was somewhat more marked with chlophedianol as compared with isoaminile. None of the drugs interfered with the expectoration process. The side effects observed were few, mild in nature, and did not require a decrease in dose or withdrawal of treatment in any of the patients. Isoaminile citrate was concluded to be an effective and relatively safe antitussive agent. Isoaminile citrate, alpha(isopropyl)-alpha-(beta-dimethylaminoproyl) phenylacetonitrile citrate, is a centrally acting antitussive agent. In animal experiments this drug was as efficacious as codeine but was devoid of any respiratory depressant effect [Krause 1958, Kuroda et al. 1971]. This controlled double-randomized interpatient study was designed to test the comparative efficacy and safety of isoaminile and chlophedianol, another centrally acting antitussive, in humans. PMID:6749701

  7. Evaluation of antitussive agents in man.

    PubMed

    Parvez, L; Vaidya, M; Sakhardande, A; Subburaj, S; Rajagopalan, T G

    1996-01-01

    Methodology to evaluate the efficacy of antitussive drugs rely largely on subjective methods and cough counts. There are few studies in cough due to natural disease especially using objective techniques. This paper presents data from a series of randomized, double blind, placebo controlled clinical trials in cough due to both chronic bronchopulmonary disease and acute upper respiratory tract infections. In these studies, cough was quantified using a standardized and validated computerized system for the acquisition and multidimensional analysis of the cough sound. Key objective parameters like cough counts, intensity, latency and total effort expended were studied. Guaiphenesin and bromhexine showed significant expectorant effects in patients with productive cough due to chronic bronchopulmonary disease. Differences were observed in speed of action, and objective and subjective measures, that probably indicate differences in drug action. More recently, three studies evaluated the antitussive drug dextromethorphan in non-productive cough due to uncomplicated upper respiratory tract infections. Reproducible cough suppressant effects were demonstrated after a single 30 mg dose using objective measures of cough counts, latency and total effort. These results establish the sensitivity and robustness of the cough quantitation methodology in the objective evaluation of cough treatments. PMID:9232667

  8. Erdosteine: antitussive and anti-inflammatory effects.

    PubMed

    Dal Negro, Roberto W

    2008-01-01

    Erdosteine is a multifactorial drug currently used in COPD for its rheologic activity on bronchial secretions and its positive effects on bacterial adhesiveness. Erdosteine produces an active metabolite (Met 1) which was shown to produce antioxidant effects during the respiratory burst of human PMNs, due to the presence of an SH group. The substantial antitussive effects of erdosteine were first documented in clinical trials even though mucolytic agents are regarded as not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Actually, a mucolytic drug could exert antitussive effects if it also affects mucus consistency and enhances ciliary function. In the last decade, data from several studies on animal models pointed to the possible antitussive and anti-inflammatory properties of erdosteine and an indirect anti-inflammatory mechanism of action was suggested. Recently, data from some controlled versus placebo studies documented the antioxidant properties of erdosteine in humans and in current smokers with COPD. The mechanism of action was described as related to erdosteine's ability to inhibit some inflammatory mediators and some pro-inflammatory cytokines that are specifically involved in oxidative stress. As oxidative stress is also presumed to impair beta-adrenoceptor function and contribute to airway obstruction, specific controlled studies recently investigated the effect of antioxidant intervention on short-term airway response to salbutamol in nonreversible COPD, according to a double-blind design versus placebo and NAC. Only erdosteine consistently restored a significant short-term reversibility in COPD subjects, previously unresponsive to beta(2) adrenergics. This peculiar activity of erdosteine (to our knowledge never previously assessed) proved related to the ROS scavenging activity (which actually proved equal to that of N), and its significant inhibiting effect on

  9. Evaluation of antitussive potential of Jussiaea suffruticosa linn. extract in albino mice.

    PubMed

    Murugesan, T; Ghosh, L; Mukherjee, P K; Pal, M; Saha, B P

    2000-11-01

    The antitussive activity of a methanol extract of Jussiaea suffruticosa Linn. (MEJS) (family Onagraceae) leaves has been evaluated for its potential on a cough induced by sulphur dioxide (SO(2)) gas model in mice. The extract (MEJS) showed significant antitussive activity in a dose dependent manner. The antitussive potential of MEJS was comparable to that of codeine phosphate (10 mg/kg), a standard drug. The extract (MEJS) at a dose level of 200 and 400 mg/kg, p.o. showed appreciable inhibition on the cough reflex by 48.52% and 59.8% respectively during 120 min of the experiment. PMID:11054846

  10. Antitussive effect of nociceptin/orphanin FQ in experimental cough models.

    PubMed

    McLeod, Robbie L; Bolser, Donald C; Jia, Yanlin; Parra, Leonard E; Mutter, Jennifer C; Wang, Xin; Tulshian, Deen B; Egan, Robert W; Hey, John A

    2002-01-01

    Cough is an important defensive pulmonary reflex that removes irritants, fluids or foreign materials from the airways. However, often cough is non-productive and requires suppression. Opioid mu receptor agonists, such as codeine are commonly used as antitussive agents and are among the most widely administered drugs in the world. Codeine suppresses the responsiveness of one or more components of the central reflex pathway for cough and is an efficacious antitussive drug for cough due to diverse aetiologies. However, opioids produce side effects that include sedation, addiction potential and constipation. Therefore, novel cough suppressant therapies should maintain or improve upon the antitussive efficacy profile of opioids. Moreover, these novel therapies should have a safety profile significantly better than current antitussive therapies. Presently, we discuss preclinical findings showing that activation of the 'opioid-like' receptor (NOP(1)) inhibits cough in the guinea pig and cat. PMID:12099766

  11. Antitussive effects of levodropropizine in the dog.

    PubMed

    Munt, P L; Clavenna, G; Algate, D R; Leach, R M

    1994-02-01

    The antitussive activity of levodropropizine (S(-)3-(4-phenyl-piperazine-1-yl)-propane-1,2-diol, DF 526, CAS 99291-25-5) was evaluated after oral administration to the conscious dog. Levodropropizine had a good antitussive activity, comparable with, but having a longer duration of action than dropropizine, the racemate from which it is derived. The antitussive activity of levodropropizine in the dog was approximately 1/20 of that of codeine phosphate. PMID:8147948

  12. Levocloperastine in the treatment of chronic nonproductive cough: comparative efficacy versus standard antitussive agents.

    PubMed

    Aliprandi, P; Castelli, C; Bernorio, S; Dell'Abate, E; Carrara, M

    2004-01-01

    The medical and social impact of cough is substantial. Current antitussive agents at effective doses have adverse events such as drowsiness, nausea and constipation that limit their use. There is also recent evidence that standard antitussive agents, such as codeine, may not reduce cough during upper respiratory infections. Therefore, there is a need for more effective and better-tolerated agents. The efficacy of levocloperastine, a novel antitussive, which acts both centrally on the cough center and on peripheral receptors in the tracheobronchial tree in treating chronic cough, was compared with that of other standard antitussive agents (codeine, levodropropizine and DL-cloperastine) in six open clinical trials. The studies enrolled patients of all ages with cough associated with various respiratory disorders including bronchitis, asthma, pneumonia and chronic obstructive pulmonary disease. Levocloperastine significantly improved cough symptoms (intensity and frequency of cough) in all trials, and improvements were observed after the first day of treatment. In children, levocloperastine reduced nighttime awakenings and irritability, and in adults it was effective in treating cough induced by angiotensin-converting enzyme inhibitors. When compared with other antitussive agents, levocloperastine had improved or comparable efficacy, with a more rapid onset of action. Importantly, no evidence of central adverse events was recorded with levocloperastine, whereas drowsiness was reported by a significant number of patients receiving codeine. Levocloperastine is an effective antitussive agent for the treatment of cough in patients of all ages. It has a more rapid onset of action than standard agents with an improved tolerability profile. PMID:15553659

  13. Antitussive activity of iodo-resiniferatoxin in guinea pigs

    PubMed Central

    Trevisani, M; Milan, A; Gatti, R; Zanasi, A; Harrison, S; Fontana, G; Morice, A; Geppetti, P

    2004-01-01

    Background: Iodo-resiniferatoxin (I-RTX) has recently been described as an ultra potent antagonist of the transient receptor potential vanilloid-1 (TRPV1). Methods: The ability of I-RTX to inhibit cough induced by inhalation of two putative TRPV1 stimulants (capsaicin and citric acid) was tested in non-anaesthetised guinea pigs. Results: Pretreatment with I-RTX either intraperitoneally (0.03–0.3 µmol/kg) or by aerosol (0.1–3 µM) reduced the number of coughs produced by inhalation of citric acid (0.25 M) and capsaicin (30 µM) in a dose dependent manner. Capsazepine (CPZ) also reduced citric acid and capsaicin induced cough, but the activity of I-RTX was 10–100 times more potent than CPZ in all the experimental conditions tested. Conclusions: I-RTX is a novel and potent antitussive drug which inhibits cough mediated by agents possibly acting via TRPV1 activation. PMID:15333853

  14. Antitussive activity and respiratory system effects of levodropropizine in man.

    PubMed

    Bossi, R; Braga, P C; Centanni, S; Legnani, D; Moavero, N E; Allegra, L

    1988-08-01

    Antitussive activity of the new antitussive drug, levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526), was evaluated in healthy volunteers by the classical method of citric acid-induced coughing. Levodropropizine dose-dependently reduced cough frequency. Maximal inhibition was observed at 6 h after administration. Cough intensity was also reduced, as shown by the analysis of cough noise. Levodropropizine, at the dosage of 60 mg t.i.d., had no adverse effects on respiratory function nor on airway clearance mechanisms: in fact, it did not affect spirometric parameters. Levodropropizine had no effects on the rheological properties of mucus nor on ciliary activity of airway epithelium. PMID:3196411

  15. Current and future centrally acting antitussives☆

    PubMed Central

    Bolser, Donald C.

    2011-01-01

    The purpose of this review is to highlight some important issues regarding current centrally acting antitussive drugs as well as discuss the implications of these matters on the development of future cough suppressants. Drugs that act in the central nervous system to inhibit cough are termed centrally acting and this designation is based exclusively on evidence obtained from animal models. This classification can include drugs that act both at peripheral and central sites following systemic administration. These drugs are intended to reduce the frequency and/or intensity of coughing resulting from disorders of any etiology. There are a number of central cough suppressants identified by their efficacy in animal models and the most prominent of these are codeine and dextromethorphan. Although the exact neural elements on which these drugs act are currently unknown, they are thought to inhibit a functionally identified component of the central system for cough known as the gating mechanism. The efficacy of codeine and dextromethorphan in humans has recently been questioned. These drugs are less effective on cough induced by upper airway disorders than in pathological conditions involving the lower airways in humans. The reasons for this difference in antitussive sensitivity are not clear. We propose that sensory afferents from different regions of the airways actuate coughing in humans by antitussive sensitive and insensitive control elements in the central nervous system. This hypothesis is consistent with results from an animal model in which laryngeal and tracheobronchial cough had different sensitivities to codeine. Other factors that may be very important in the action of central antitussive drugs in humans include the role of sensations produced by a tussigenic stimulus as well as plasticity of central pathways in response to airway inflammation. Resolution of these issues in the human will be a challenging process, but one which will lay the foundation for the

  16. The Prescription Drug Marketing Act of 1987.

    PubMed

    Greenberg, R B

    1988-10-01

    The Prescription Drug Marketing Act of 1987 is described, and its implications for hospitals and other health-care entities are discussed. The act, which became effective on July 21, 1988, is intended to reduce public health risks from adulterated, misbranded, and counterfeit drug products that enter the marketplace through drug diversion. The law provides that prescription drug products manufactured in the United States and exported can no longer be reimported, except by the product's manufacturer. It also establishes restrictions on sales of prescription drug products and samples. Samples of prescription drug products may be distributed only if a licensed prescriber requests them. Other distribution channels for samples specified in the law are permissible, provided records are maintained. Under the law, wholesale distributors must be licensed by the state and meet uniform standards. Penalties for violations of the law are also identified. According to FDA's advisory guidelines on the statute, the law will permit hospitals to return drug products, provided the return is made to the manufacturer or wholesaler and provided written notice is secured that the goods were received (for manufacturers) or the goods were destroyed or returned to the manufacturer (for wholesalers). The final chapter on drug diversion must await issuance of final FDA regulations. PMID:3228083

  17. Antitussive effect of naringin on experimentally induced cough in Guinea pigs.

    PubMed

    Gao, Sen; Li, Peibo; Yang, Hongliang; Fang, Siqi; Su, Weiwei

    2011-01-01

    The mechanism of action of naringin has been investigated in different models of experimentally induced cough in guinea pigs. In contrast to codeine phosphate (6 mg/kg, intravenous administration [i. v.]), naringin (15, 30, and 60 mg/kg, i. v.) had no central antitussive effect on cough elicited by electrical stimulation of the superior laryngeal nerve. Naringin (0.5, 1.0, and 2.0 µmol) could not prevent the cough reflex induced by stimulation of the trachea after intracerebroventricular injection (i. c. v.), while codeine phosphate (0.5 µmol) was highly effective. Further characterizing the peripheral mechanism of naringin, we found that its effect (50 mg/kg, i. v.) was not affected by the depletion of sensory neuropeptides, whereas levodropropizine (10 mg/kg, i. v.) lost its capacity to prevent cough in the capsaicin-desensitized guinea pig. Furthermore, pretreatment with glibenclamide (10 mg/kg, intraperitoneal [i. p.]) significantly reduced the antitussive effect of pinacidil (5 mg/kg, subcutaneous [s. c.]), but could not antagonize the antitussive effect of naringin (30 mg/kg, s. c.). Our present results suggest that naringin is not a central antitussive drug. And naringin does not exert its peripheral antitussive effect through either the sensory neuropeptides system or the modulation of ATP-sensitive K (+) channels. PMID:20645246

  18. 75 FR 12555 - Prescription Drug User Fee Act; Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-16

    ... HUMAN SERVICES Food and Drug Administration Prescription Drug User Fee Act; Public Meeting AGENCY: Food... Administration (FDA) is announcing a public meeting on the Prescription Drug User Fee Act (PDUFA). The... FDA to continue collecting user fees for the prescription drug program. The Federal Food, Drug,...

  19. Antitussive Effects of Memantine in Guinea Pigs

    PubMed Central

    Smith, Jaclyn A.; Hilton, Emma C. Y.; Saulsberry, Loren

    2012-01-01

    Background: The treatment of cough is a significant clinical unmet need because there is little evidence that current therapies are effective. Based on evidence supporting a role for N-methyl d-aspartate receptors (NMDARs) in cough, we hypothesized that memantine, a low-affinity, uncompetitive NMDAR channel blocker in routine use for the treatment of Alzheimer disease, could be an effective, well-tolerated, antitussive therapy. The aim of this study was to establish preclinical evidence that memantine has antitussive effects. Methods: We studied the influence of memantine on experimentally induced coughing in response to citric acid and bradykinin inhalation in guinea pigs. We also compared the potency and efficacy of memantine as an antitussive to other NMDAR antagonists, dextromethorphan and ketamine, and to the γ-aminobutyric acid class B receptor agonist baclofen. Results: Compared with control subjects, 10 mg/kg memantine significantly reduced the cumulative number of coughs evoked by both citric acid (median, 24.0 [interquartile range (IQR), 13.0-25.5] vs 1.5 [IQR, 0.3-10.3] coughs; P = .012) and bradykinin aerosols (median, 16.0 [IQR, 9.5-18.5] vs 0.0 [IQR, 0-0.75] coughs; P = .002). Memantine 10 mg/kg produced a similar reduction in the cumulative number of coughs to baclofen 3 mg/kg and demonstrated comparatively greater cough suppression than 30 mg/kg dextromethorphan or 30 mg/kg ketamine. This dose of memantine produced no sedative or respiratory depressive effects. Conclusions: This study illustrates that memantine has marked antitussive effects in guinea pigs, most likely mediated through NMDAR channel blockade. Memantine, therefore, has the potential to be a safe, effective, and well-tolerated antitussive agent. PMID:22016492

  20. Comprehensive evidence-based review on European antitussives.

    PubMed

    Morice, Alyn; Kardos, Peter

    2016-01-01

    Acute cough caused by viral respiratory tract infections is probably the most common illness to afflict mankind. Despite the widespread but ineffective prescribing of antibiotics, there is no specific therapy. Home remedies and over-the-counter medicines are the mainstay for treatment of this short-lived but debilitating condition where cough is a major troublesome symptom. Across Europe, there are large variations in the recommendations made by healthcare professionals for the treatment of acute cough. This has arisen through custom and practice based on the evidence of historical studies performed to standards well short of what would be considered legitimate today. Acute cough is particularly difficult to study in a controlled setting because of the high rate of spontaneous remission and a large placebo effect. Here we detail the validated modern methodology used to assess the efficacy of antitussives and review the drugs commonly used in Europe against these standards. PMID:27547407

  1. Comprehensive evidence-based review on European antitussives

    PubMed Central

    Morice, Alyn; Kardos, Peter

    2016-01-01

    Acute cough caused by viral respiratory tract infections is probably the most common illness to afflict mankind. Despite the widespread but ineffective prescribing of antibiotics, there is no specific therapy. Home remedies and over-the-counter medicines are the mainstay for treatment of this short-lived but debilitating condition where cough is a major troublesome symptom. Across Europe, there are large variations in the recommendations made by healthcare professionals for the treatment of acute cough. This has arisen through custom and practice based on the evidence of historical studies performed to standards well short of what would be considered legitimate today. Acute cough is particularly difficult to study in a controlled setting because of the high rate of spontaneous remission and a large placebo effect. Here we detail the validated modern methodology used to assess the efficacy of antitussives and review the drugs commonly used in Europe against these standards. PMID:27547407

  2. The Orphan Drug Act: Restoring the Mission to Rare Diseases.

    PubMed

    Daniel, Michael G; Pawlik, Timothy M; Fader, Amanda N; Esnaola, Nestor F; Makary, Martin A

    2016-04-01

    The Orphan Drug Act has fostered drug development for patients with rare cancers and other diseases; however, current data suggest that companies are gaming the system to use the law for mainstream drugs. We identify a pattern of pharmaceutical companies submitting drugs to the Food and Drug Administration (FDA) as orphan drugs but once approved, the drugs are used broadly off-label with the lucrative orphan drug protections and exclusivity benefits. Since the law was passed, the proportion of new FDA-approved drugs that were submitted as orphan drugs has increased with a peak last year of 41% of all FDA-approved drugs approved as orphan drugs. On the basis of the current data, we suggest that patients with rare cancers and other diseases may suffer due to dilution of the incentives and benefits. We propose reform to increase submission scrutiny, decrease benefits based on off-label use, and increase price transparency. PMID:26580246

  3. Drug-Resistant Malaria: The Era of ACT

    PubMed Central

    Lin, Jessica T.; Juliano, Jonathan J.

    2010-01-01

    As drug-resistant falciparum malaria has continued to evolve and spread worldwide, artemisinin-based combination therapies (ACT) have become the centerpiece of global malaria control over the past decade. This review discusses how advances in antimalarial drug resistance monitoring and rational use of the array of ACTs now available can maximize the impact of this highly efficacious therapy, even as resistance to artemisinins is emerging in Southeast Asia. PMID:21308525

  4. 21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT... Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. (a)...

  5. 21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT... Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act. (a) The...

  6. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT... Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a)...

  7. 21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT... Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act. (a) The...

  8. 21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT... Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. (a)...

  9. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT... Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a)...

  10. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT... Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a)...

  11. 21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT... Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. (a)...

  12. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT... Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a)...

  13. Multitarget drugs of plants origin acting on Alzheimer's disease.

    PubMed

    Russo, P; Frustaci, A; Del Bufalo, A; Fini, M; Cesario, A

    2013-01-01

    The etiopathology of Alzheimer's disease (AD) is extremely complex and heterogeneous, often associated with comorbidities. As a result it may be unlikely that AD may be mitigated by drug acting on a single specific target. The current tendency in drug design and discovery in AD is the rational design or "serendipitous" discovery of new drug entities challenging multiple targets. Since two of the presently approved drugs for AD are based on natural products (galantamine and the physostigmine-derivative rivastigmine), many plants are now under investigation as a potential source of new drugs. Multifunctional drugs often have their origin in natural sources. This review is limited to plant chemicals having different targets with actual (galantamine) or promising (drugs from Crocus sativus, Ginkgo biloba, Salvia species, and Huperzia serrata) clinical evidence in people with dementia or AD. PMID:23410167

  14. Review of the 2015 Drug Supply Chain Security Act.

    PubMed

    Brechtelsbauer, Erich D; Pennell, Benjamin; Durham, Mary; Hertig, John B; Weber, Robert J

    2016-06-01

    The integrity of the pharmaceutical supply chain is threatened by medication counterfeiting, importation of unapproved and substandard drugs, and grey markets - all of which have the potential to distribute drug products with the potential for serious harm. On November 27, 2013, President Obama signed into law Title II of the Drug Quality and Security Act, now known as the Drug Supply Chain Security Act (DSCSA). Over the next 10 years, the DSCSA will require the pharmaceutical supply chain to implement medication tracking and tracing; serialization, verification, and detection of suspicious products; and strict guidelines for wholesaler licensing and reporting. This article reviews the important aspects of the DSCSA and outlines the role of health-system pharmacy leaders in ensuring compliance to the DSCSA. By verifying that medication supplies are free from adulteration and tampering, the DSCSA serves as a foundational law to ensure quality in providing patient-centered pharmacy services. PMID:27354753

  15. Clinical trials with the new antitussive levodropropizine in adult bronchitic patients.

    PubMed

    Allegra, L; Bossi, R

    1988-08-01

    The results of 6 clinical trials involving a total of 174 patients are reported. Levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526) was compared in double-blind manner with placebo, morclofone and cloperastine. The antitussive activity and therapeutic efficacy of the drug were shown to be greater than those of placebo and morclofone and similar to those of cloperastine. Levodropropizine was effective in about 80% of patients; in responders, cough frequency was reduced by an average of 33-51%. Levodropropizine was generally well tolerated and mild side-effects were reported for only 3% of patients. PMID:3058135

  16. 19 CFR 147.23 - Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Food, Drug, and Cosmetic Act. 147.23 Section 147.23 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) TRADE FAIRS Requirements of Other Laws § 147.23 Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act. (a)...

  17. 19 CFR 147.23 - Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Food, Drug, and Cosmetic Act. 147.23 Section 147.23 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) TRADE FAIRS Requirements of Other Laws § 147.23 Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act. (a)...

  18. 19 CFR 147.23 - Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Food, Drug, and Cosmetic Act. 147.23 Section 147.23 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) TRADE FAIRS Requirements of Other Laws § 147.23 Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act. (a)...

  19. 19 CFR 147.23 - Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Food, Drug, and Cosmetic Act. 147.23 Section 147.23 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) TRADE FAIRS Requirements of Other Laws § 147.23 Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act. (a)...

  20. Drug Interactions of Direct-Acting Oral Anticoagulants.

    PubMed

    Fitzgerald, John Leonard; Howes, Laurence Guy

    2016-09-01

    In recent years, new direct-acting oral anticoagulants (DOACs) have been introduced into clinical practice that specifically inhibit either factor Ia or Xa. These drugs have, to a large extent, replaced warfarin for the treatment of venous thrombosis, pulmonary embolism, and non-valvular atrial fibrillation. They have potential advantages over warfarin in providing more stable anticoagulation and the lack of a need for regular venesection to monitor activity. They also have the promise of less drug and food interactions. All of these drugs are substrates for the permeability glycoprotein (P-gp) excretion system, and several are metabolised, in part, by cytochrome P450 (CYP) 3A4. This current article assesses the interactions that do or may occur with the DOACs, particularly with respect to the P-gp and CYP3A4 systems. PMID:27435452

  1. 77 FR 72356 - Animal Drug User Fee Act; Public Meeting; Request for Comments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-05

    ... HUMAN SERVICES Food and Drug Administration Animal Drug User Fee Act; Public Meeting; Request for... Food and Drug Administration (FDA) is announcing the following meeting: Animal Drug User Fee Act. The topic to be discussed is proposed recommendations for the reauthorization of the Animal Drug User...

  2. 21 CFR 862.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 862.9 Section 862.9 Food and Drugs FOOD AND DRUG... Federal Food, Drug, and Cosmetic Act (the act). The exemption from the requirement of...

  3. 21 CFR 880.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 880.9 Section 880.9 Food and Drugs FOOD AND DRUG... Food, Drug, and Cosmetic Act (the act). The exemption from the requirement of premarket...

  4. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE RECORDS AND REPORTS OF LISTED CHEMICALS AND CERTAIN MACHINES § 1310.11 Reinstatement of exemption for...

  5. 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

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I Food and Drug Administration Safety and Innovation Act Title VII--Drug Supply Chain; Standards for Admission of Imported Drugs, Registration of...: Food and Drug Administration, HHS. ACTION: Notification of public meeting; request for...

  6. 78 FR 15019 - Food and Drug Administration Prescription Drug User Fee Act V Benefit-Risk Plan; Request for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-08

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

  7. Evaluation of antitussive activity of formulations with herbal extracts in sulphur dioxide (SO2) induced cough model in mice.

    PubMed

    Gupta, Y K; Katyal, Jatinder; Kumar, Gajendra; Mehla, Jogender; Katiyar, C K; Sharma, Naveen; Yadav, Satpal

    2009-01-01

    Cough is the most common symptom of respiratory diseases. When cough becomes serious, opioids are effective, but they have side effects like sedation, constipation, some addiction liability and also compromise the respiratory function. Therefore, there is need to have effective anti-tussive agent which do not have respiratory suppressant activity. The present study was carried out to evaluate anti-tussive activity of combination of herbal drugs as formulations in sulphur dioxide (SO2)-induced cough model in mice. Albino mice of either sex, weighing 25-30 g were divided into eight groups, (n = 6). Group 1 served as normal control, group 2 mice were given distilled water, group 3 was positive control and received codeine sulphate (10 mg/kg, p.o.) and group 4, 5, 6, 7 received coded 1 formulations 1, 2, 3 and 4 respectively at a dose of 0.3 ml/mice, orally, while group VIII was the vehicle control. Thirty minutes later, the mice were exposed to sulphur dioxide again for 45 sec. The mice were then placed in an observation chamber for counting of cough bouts, by two independent observers, for five minutes. All the formulations used showed significant antitussive activity in sulphur dioxide induced cough model. Thus, these formulations can prove to be useful for alleviating cough. PMID:19810578

  8. 71 FR 66448 - Prescription Drug Marketing Act Pedigree Requirements under 21 CFR Part 203 Compliance Policy...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2006-11-15

    ... 92N-0297), 1988N-0258 (Formerly 88N- 0258), 2006D-0226] Prescription Drug Marketing Act Pedigree... Marketing Act Pedigree Requirements Questions and Answers; Notice of Availability AGENCY: Food and Drug... ``Prescription Drug Marketing Act--Pedigree Requirements under 21 CFR Part 203'' (PDMA CPG). This CPG...

  9. On the sites of antitussive action of dl-glaucine phosphate.

    PubMed

    Kasé, Y; Matsumoto, Y; Takahama, K; Miyata, T; Hitoshi, T; Hirotsu, I; Okano, Y

    1983-01-01

    The sites of antitussive action of dl-1,2,9,10-tetramethoxy-6a,alpha-aporphine phosphate (dl-glaucine phosphate, DL-832) were studied. It was assumed from the following results that DL-832 acts on the cough center per se. a) When DL-832 was given by the routes leading to the brain stem such as the vertebral artery and the cerebello-medullary cistern, far smaller doses were sufficient to obtain the same effect as that by i.v. administration. b) DL-832 showed neither effect on the afferent pathway for cough reflex nor influence on pulmonary stretch receptors. c) It exhibited practically no influence on the efferent pathways for cough reflex, that is, that for innervating respiratory muscle movement as well as that for controlling bronchial muscle tone. d) Decerebration exerted no influence on the antitussive effect. e) DL-832 definitely depressed the potentials of both the recurrent and internal intercostal nerves evoked by the superior laryngeal nerve stimulation. f) In deafferentated and decerebrate cats, DL-832 rather increased the spontaneous discharges of the phrenic nerve, whereas codeine decreased them. PMID:6684930

  10. 78 FR 78366 - Draft Generic Drug User Fee Act Information Technology Plan; Availability for Comment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-26

    ... HUMAN SERVICES Food and Drug Administration Draft Generic Drug User Fee Act Information Technology Plan; Availability for Comment AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug... Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51,...

  11. Provisions of Anti-Drug Abuse Amendments Act of 1988 Relating to Drug Law Enforcement. Information Memorandum 89-1.

    ERIC Educational Resources Information Center

    Matthias, Mary

    This document describes major provisions of the Anti-Drug Abuse Amendments Act of 1988, a federal law relating to enforcement of controlled substances laws which authorizes over two billion dollars for anti-drug activities. Provisions of the Act relating primarily to drug abuse education, prevention or treatment and regulation of the manufacture,…

  12. 21 CFR 870.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 870.9 Section 870.9 Food and Drugs FOOD AND DRUG... Cosmetic Act (the act). The exemption from the requirement of premarket notification (section 510(k) of...

  13. 21 CFR 884.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 884.9 Section 884.9 Food and Drugs FOOD AND DRUG..., and Cosmetic Act (the act). The exemption from the requirement of premarket notification (section...

  14. 21 CFR 890.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 890.9 Section 890.9 Food and Drugs FOOD AND DRUG... Cosmetic Act (the act). The exemption from the requirement of premarket notification (section 510(k) of...

  15. 21 CFR 868.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 868.9 Section 868.9 Food and Drugs FOOD AND DRUG... Cosmetic Act (the act). The exemption from the requirement of premarket notification (section 510(k) of...

  16. 21 CFR 878.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 878.9 Section 878.9 Food and Drugs FOOD AND DRUG..., and Cosmetic Act (the act). The exemption from the requirement of premarket notification (section...

  17. 21 CFR 876.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 876.9 Section 876.9 Food and Drugs FOOD AND DRUG..., and Cosmetic Act (the act). The exemption from the requirement of premarket notification (section...

  18. Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs

    PubMed Central

    Guarnieri, Michael; Tyler, Betty M.; DeTolla, Louis; Zhao, Ming; Kobrin, Barry

    2014-01-01

    Background: Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents. Objective: Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Methods: Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. Results: Drug levels are below the level of detection (0.5 ng/mL plasma) within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant. Discussion: The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Conclusion: Drug implants can retain significant and unintended reservoirs of drugs. PMID:24459402

  19. Drug-Free Schools and Communities Act of 1986, Part 2, Handbook (Anti-Drug Abuse Act of 1988, Part B).

    ERIC Educational Resources Information Center

    Hawaii State Dept. of Education, Honolulu. Office of Instructional Services.

    The purpose of the Drug-Free Schools and Communities Act of 1988, Part B, is to establish, implement, and improve programs of drug abuse prevention, early intervention, rehabilitation referral, and education programs in elementary and secondary schools. The act also aims to support innovative, community-based programs of coordinated services for…

  20. Antitussive activity of ethanolic extract of Curcuma aromatica rhizomes on sulfur dioxide induced cough in mice

    PubMed Central

    Marina, G.D.; Kekuda, T.R Prashith; Sudarshan, S.J

    2008-01-01

    Ethanolic extract of rhizomes of Curcuma aromatica (Zingiberaceae) was investigated for its antitussive effect on Sulfur dioxide induced cough model in mice. The extract exhibited significant antitussive activity in a dose dependant manner. The activity was compared with the prototype antitussive agent codeine phosphate. The ethanolic extract at the dose of lOOmg. 200mg and 400mg/kg body weight, po, showed 68%, 74% and 79% of inhibition of cough with respect to control group. PMID:22557276

  1. 76 FR 79195 - Animal Drug User Fee Act; Reopening of the Comment Period

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-21

    ... September 20, 2011 (76 FR 58279). In that notice, FDA requested comments on the Animal Drug User Fee Act... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Animal Drug User Fee Act; Reopening of the Comment...

  2. Pharmacological studies on dl-glaucine phosphate as an antitussive.

    PubMed

    Kasé, Y; Kawaguchi, M; Takahama, K; Miyata, T; Hirotsu, I; Hitoshi, T; Okano, Y

    1983-01-01

    Antitussive effect, toxicity and other related pharmacological properties of dl-1,2,9,10-tetramethoxy-6a,alpha-aporphine phosphate (dl-glaucine phosphate, DL-832) were studied in comparison with those of codeine. Acute toxicity of DL-832 in mice was 2/5 to 7/10 of that of codeine for any routes of i.v., i.p., s.c. and p.o. The antitussive effect as tested by "coughing dog and cat" methods and Domenjoz's method in cats was 1/5 to 4/5 that of codeine, according to the routes administered. Safety margin in antitussive effect was similar to or less than that of codeine. Differing from codeine, levallorphan exerted no influence on the antitussive effect of DL-832. In vitro, DL-832 exerted moderate relaxant actions on normal tone and on contractions induced by histamine and acetylcholine of tracheal muscle. In vivo, it showed a moderate relaxant effect on histamine-induced bronchial constriction. The decrease in the volume of respiratory tract fluid caused by DL-832 was smaller than that by codeine. DL-832 slightly reduced the transportation rate of intratracheal foreign body, although to much lesser extent as compared to codeine. On respiration, blood pressure and heart rate, DL-832 showed depressant effects and moreover it caused changes in ECG. However, all of these effects were similar to and a little weaker than those observed with codeine. DL-832 prolonged hexobarbital sleeping time significantly. Neither analgesic nor anticonvulsant effect was observed. When given in larger doses, DL-832 inhibited intestinal transportation in vivo, although this effect was much weaker than that of codeine. DL-832 showed slight local anesthetic effect. PMID:6354197

  3. Novel antitussive effect of suplatast tosilate in guinea pigs.

    PubMed

    Zhou, Jian-Rong; Syono, Ryo-ichi; Fukumi, Syu-ichi; Kimoto, Kenji; Shirasaki, Tetsuya; Soeda, Fumio; Takahama, Kazuo

    2015-01-01

    We studied the antitussive effects of suplatast, a Th2 cytokine inhibitor, and compared them with the effects of codeine using an experimental cough model in guinea pigs. Suplatast and codeine dose-dependently inhibited cough caused by mechanical stimulation of the larynx, but they did not inhibit cough caused by mechanical stimulation of the bifurcation of the trachea. In guinea pigs with bronchitis, suplatast had an antitussive effect on cough caused by stimulation of the larynx, whereas codeine did not inhibit such cough. In SO2-exposed guinea pigs, suplatast tended to inhibit cough caused by mechanical stimulation of the tracheal bifurcation. Further, suplatast inhibited citric acid-induced cough augmented by pretreatment with an angiotensin-converting enzyme inhibitor, whereas codeine did not inhibit such cough. Suplatast also inhibited bradykinin-induced discharges of airway vagal afferent nerves and significantly inhibited 4-aminopyridine-induced discharges of airway vagal afferent nerves. These findings indicate that the antitussive effects of suplatast are mediated by a novel mechanism involving the peripheral nervous system. PMID:25592147

  4. Antitussive, expectorant activity of Marsilea minuta L., an Indian vegetable

    PubMed Central

    Chakraborty, Raja; De, Biplab; Devanna, N.; Sen, Saikat

    2013-01-01

    Marsilea minuta L., an aquatic or sub-aquatic fern used as a vegetable, has wide applications in traditional/folk medicine in India and Bangladesh. In our study, we evaluated the antitussive, expectorant activity of M. minuta crude extracts. The antitussive activity of M. minuta methanol, ethyl acetate, and petroleum ether extracts was evaluated using ammonia and sulfur dioxide induced mice coughing. The expectorant activity was evaluated by the volume of phenol red in mice's tracheas. Extracts significantly increased mice's cough latent period and inhibited the frequency of cough induced by ammonia and sulfur dioxide, and improved tracheal phenol red output in expectorant evaluation. Methanol extract produced the highest activity in all tested models. Methanol extract at 500 mg/kg showed 59.5% and 55.8% inhibition in the number of coughing induced by ammonium liquor and SO2, respectively, while it showed 89.3% increase in phenol red secretion at the same dose, which showed superior activity compared to other extracts. The present study provided evidence for M. minuta to be used as an antitussive and expectorant in Indian folk medicine. PMID:23662283

  5. 75 FR 69093 - Prescription Drug User Fee Act; Reopening of the Comment Period

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-10

    ...The Food and Drug Administration (FDA) is reopening until October 31, 2011, the comment period for the notice of public meeting that published in the Federal Register of March 16, 2010 (75 FR 12555). In the notice, FDA announced a public meeting to solicit input on the reauthorization of the Prescription Drug User Fee Act (PDUFA) program. The Federal Food, Drug, and Cosmetic Act (the FD&C Act)......

  6. 21 CFR 886.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 886.9 Section 886.9 Food and Drugs FOOD AND DRUG... Provisions § 886.9 Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic...

  7. 21 CFR 872.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 872.9 Section 872.9 Food and Drugs FOOD AND DRUG... Provisions § 872.9 Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic...

  8. 21 CFR 882.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 882.9 Section 882.9 Food and Drugs FOOD AND DRUG... Provisions § 882.9 Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic...

  9. 21 CFR 888.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 888.9 Section 888.9 Food and Drugs FOOD AND DRUG... Provisions § 888.9 Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic...

  10. 19 CFR 147.23 - Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act. 147.23 Section 147.23 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) TRADE FAIRS Requirements of Other Laws § 147.23 Compliance with...

  11. 77 FR 72359 - Animal Generic Drug User Fee Act; Public Meeting; Request for Comments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-05

    ... HUMAN SERVICES Food and Drug Administration Animal Generic Drug User Fee Act; Public Meeting; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION: Notice of meeting; request for comments. The Food and Drug Administration (FDA) is announcing the following meeting: Animal Generic...

  12. 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

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Procedures for notice of Food and Drug 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...

  13. 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

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Procedures for notice of Food and Drug 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...

  14. 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

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Procedures for notice of Food and Drug 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...

  15. 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

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Procedures for notice of Food and Drug 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...

  16. Analgesic and Antineuropathic Drugs Acting Through Central Cholinergic Mechanisms

    PubMed Central

    Bartolini, Alessandro; Cesare Mannelli, Lorenzo Di; Ghelardini, Carla

    2011-01-01

    The role of muscarinic and nicotinic cholinergic receptors in analgesia and neuropathic pain relief is relatively unknown. This review describes how such drugs induce analgesia or alleviate neuropathic pain by acting on the central cholinergic system. Several pharmacological strategies are discussed which increase synthesis and release of acetylcholine (ACh) from cholinergic neurons. The effects of their acute and chronic administration are described. The pharmacological strategies which facilitate the physiological functions of the cholinergic system without altering the normal modulation of cholinergic signals are highlighted. It is proposed that full agonists of muscarinic or nicotinic receptors should be avoided. Their activation is too intense and un-physiological because neuronal signals are distorted when these receptors are constantly activated. Good results can be achieved by using agents that are able to a) increase ACh synthesis, b) partially inhibit cholinesterase activity c) selectively block the autoreceptor or heteroreceptor feedback mechanisms. Activation of M1 subtype muscarinic receptors induces analgesia. Chronic stimulation of nicotinic (N1) receptors has neuronal protective effects. Recent experimental results indicate a relationship between repeated cholinergic stimulation and neurotrophic activation of the glial derived neurotrophic factor (GDNF) family. At least 9 patents covering novel chemicals for cholinergic system modulation and pain control are discussed. PMID:21585331

  17. Drug Abuse Resistance Education Act of 1990. House of Representatives, 101st Congress, 2d Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House Committee on Education and Labor.

    This document is a congressional report on the Drug Abuse Resistance Education Act of 1990, House of Representatives (H.R.) 5064 which requires the Secretary of Education to reserve $15 million from the appropriations made for the Drug Free Schools and Communities Act for grants to consortia of local educational agencies and other agencies to…

  18. 71 FR 34249 - Prescription Drug Marketing Act Pedigree Requirements; Effective Date and Compliance Policy Guide...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2006-06-14

    ...), 1988N-0258 (Formerly 88N- 0258), 2006D-0226] Prescription Drug Marketing Act Pedigree Requirements... provisions of the final regulation published in the Federal Register of ] December 3, 1999 (64 FR 67720). The... of a new compliance policy guide (CPG) 160.900 entitled ``Prescription Drug Marketing Act...

  19. 21 CFR 341.74 - Labeling of antitussive drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... of the signal words (“extremely flammable,” “flammable,” “combustible”) as described in 16 CFR 1500.3... suitable ointment vehicle and that does not contain a flammability signal word as described in 16 CFR 1500... vehicle and that contains a flammability signal word as described in 16 CFR 1500.3(b)(10). “When...

  20. 21 CFR 341.74 - Labeling of antitussive drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... of the signal words (“extremely flammable,” “flammable,” “combustible”) as described in 16 CFR 1500.3... suitable ointment vehicle and that does not contain a flammability signal word as described in 16 CFR 1500... vehicle and that contains a flammability signal word as described in 16 CFR 1500.3(b)(10). “When...

  1. 21 CFR 341.74 - Labeling of antitussive drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... of the signal words (“extremely flammable,” “flammable,” “combustible”) as described in 16 CFR 1500.3... suitable ointment vehicle and that does not contain a flammability signal word as described in 16 CFR 1500... vehicle and that contains a flammability signal word as described in 16 CFR 1500.3(b)(10). “When...

  2. 21 CFR 341.74 - Labeling of antitussive drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... of the signal words (“extremely flammable,” “flammable,” “combustible”) as described in 16 CFR 1500.3... suitable ointment vehicle and that does not contain a flammability signal word as described in 16 CFR 1500... vehicle and that contains a flammability signal word as described in 16 CFR 1500.3(b)(10). “When...

  3. 21 CFR 341.74 - Labeling of antitussive drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... of the signal words (“extremely flammable,” “flammable,” “combustible”) as described in 16 CFR 1500.3... suitable ointment vehicle and that does not contain a flammability signal word as described in 16 CFR 1500... vehicle and that contains a flammability signal word as described in 16 CFR 1500.3(b)(10). “When...

  4. 21 CFR 874.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 874.9 Section 874.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT...

  5. 21 CFR 874.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 874.9 Section 874.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT...

  6. 21 CFR 872.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 872.9 Section 872.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES General Provisions § 872.9 Limitations...

  7. 21 CFR 890.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 890.9 Section 890.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES General Provisions § 890.9...

  8. 21 CFR 888.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 888.9 Section 888.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES General Provisions § 888.9 Limitations...

  9. 21 CFR 862.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 862.9 Section 862.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES...

  10. 21 CFR 870.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 870.9 Section 870.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES General Provisions § 870.9 Limitations...

  11. 21 CFR 886.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 886.9 Section 886.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES General Provisions § 886.9 Limitations...

  12. 21 CFR 884.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 884.9 Section 884.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES General Provisions §...

  13. 21 CFR 876.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 876.9 Section 876.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES General Provisions §...

  14. 21 CFR 880.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 880.9 Section 880.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL HOSPITAL AND PERSONAL USE DEVICES General Provisions §...

  15. 21 CFR 882.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 882.9 Section 882.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES General Provisions § 882.9 Limitations...

  16. 21 CFR 868.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 868.9 Section 868.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES General Provisions § 868.9 Limitations...

  17. 21 CFR 878.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 878.9 Section 878.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES General Provisions §...

  18. 21 CFR 884.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 884.9 Section 884.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES General Provisions §...

  19. 21 CFR 888.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 888.9 Section 888.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES General Provisions § 888.9 Limitations...

  20. 21 CFR 880.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 880.9 Section 880.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL HOSPITAL AND PERSONAL USE DEVICES General Provisions §...

  1. 21 CFR 862.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 862.9 Section 862.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES...

  2. 21 CFR 890.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 890.9 Section 890.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES General Provisions § 890.9...

  3. 21 CFR 868.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 868.9 Section 868.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES General Provisions § 868.9 Limitations...

  4. 21 CFR 872.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 872.9 Section 872.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES General Provisions § 872.9 Limitations...

  5. 21 CFR 886.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 886.9 Section 886.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES General Provisions § 886.9 Limitations...

  6. 21 CFR 882.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 882.9 Section 882.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES General Provisions § 882.9 Limitations...

  7. 21 CFR 870.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 870.9 Section 870.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES General Provisions § 870.9 Limitations...

  8. 21 CFR 864.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 864.9 Section 864.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES General Provisions §...

  9. 21 CFR 876.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 876.9 Section 876.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES General Provisions §...

  10. 21 CFR 874.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 874.9 Section 874.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES General Provisions §...

  11. 21 CFR 878.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 878.9 Section 878.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC...

  12. 21 CFR 864.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 864.9 Section 864.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND...

  13. 21 CFR 864.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 864.9 Section 864.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND...

  14. 21 CFR 892.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 892.9 Section 892.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES...

  15. 21 CFR 892.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 892.9 Section 892.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES...

  16. 21 CFR 892.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 892.9 Section 892.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES...

  17. 21 CFR 866.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 866.9 Section 866.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND...

  18. 21 CFR 866.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 866.9 Section 866.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND...

  19. 21 CFR 866.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 866.9 Section 866.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND...

  20. 21 CFR 866.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 866.9 Section 866.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND...

  1. 21 CFR 866.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 866.9 Section 866.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND...

  2. Antitussive profile of the NOP agonist Ro-64-6198 in the guinea pig.

    PubMed

    McLeod, Robbie L; Jia, Yanlin; Fernandez, Xiomara; Parra, Leonard E; Wang, Xin; Tulshian, Deen B; Kiselgof, Eugenia J; Tan, Zheng; Fawzi, Ahmad B; Smith-Torhan, April; Zhang, Hongtao; Hey, John A

    2004-07-01

    We have previously shown that N/OFQ, the endogenous peptide ligand for the 'opioid-like' NOP receptor, inhibits cough in guinea pigs and cats. In the present study we sought to continue our characterization of the cough-suppressant effects of NOP stimulation by profiling the pulmonary and antitussive effects of a novel non-peptide NOP agonist, Ro-64-6198, in guinea pigs. In receptor-binding assays, we confirmed that Ro-64-6198 selectively binds to NOP receptors over other opioid receptors. The Ki values for Ro-64-6198 at NOP, MOP, KOP and DOP receptors was 0.3, 36, 214 and 3,787 nmol/l, respectively. In GTPgammaS-binding assays, Ro-64-6198 displayed >900-fold functional selectivity at NOP relative to MOP receptors. We evaluated the effects of Ro-64-6198 (3 and 10 micromol/l) in isolated guinea pig nodose ganglia cells on the increases in intracellular Ca2+ concentration evoked by capsaicin stimulation (1 x 10(-8)-1 x 10(-6) mol/l). Similar to previously reported data with N/OFQ, Ro-64-6198 (3 and 10 micromol/l) significantly attenuated Ca2+ responses in nodose ganglia cells produced by exposure to capsaicin. The effect of Ro-64-6198 (3 micromol/l) on capsaicin-induced intracellular Ca2+ responses was blocked by the NOP antagonist, J113397 (3 micromol/l). In guinea pig in vivo studies, aerosolized capsaicin (10-300 micromol/l) produced a dose-dependent increase in cough number. Ro-64-6198 given i.p. significantly inhibited cough due to capsaicin (300 micromol/l) exposure. In a duration study we found that the maximum antitussive effect (42 +/- 8% inhibition) of Ro-64-6198 (3 mg/kg) was observed at 1 h after i.p. administration. Also at 1 h after administration, Ro-64-6198 (0.003-3.0 mg/kg, i.p.) produced a dose-dependent inhibition of cough. The antitussive effect of Ro-64-6198 (3 mg/kg, i.p.) was blocked by J113397 (12 mg/kg, i.p.) but not by the classical opioid antagonist naltrexone (10 mg/kg, i.p.). Although the antitussive action of Ro-64-6198 may be mediated

  3. 76 FR 41434 - Removal of Certain Requirements Related to the Prescription Drug Marketing Act; Opportunity for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-14

    .... drug supply chain. Among other things, the PDMA, in section 503(e)(1)(A) of the FD&C Act (21 U.S.C. 353... or control number(s) in the pedigree as well. FDA continues to believe that drug supply chain... our drug supply chain and the action proposed in this document should not be interpreted to mean...

  4. 76 FR 79195 - Animal Generic Drug User Fee Act; Reopening of the Comment Period

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-21

    ... of September 20, 2011 (76 FR 58277). In that notice, FDA requested comments on the Animal Generic... HUMAN SERVICES Food and Drug Administration Animal Generic Drug User Fee Act; Reopening of the Comment Period AGENCY: Food and Drug Administration, HHS. ACTION: Notice; reopening of the comment...

  5. 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

    ... reportable food that is the subject of a summary posting and that are part of a chain of establishments with... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Food Safety Modernization Act: Focus on Inspections and Compliance AGENCY: Food and Drug Administration, HHS. ACTION: Notice of...

  6. 21 CFR 341.70 - Labeling of OTC drug products containing ingredients that are used for treating concurrent...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .../cough suppressant” or “antihistamine/antitussive (cough suppressant).” The indications shall be combined... name of the drug, if any, and identifies the product as a “cough suppressant/oral anesthetic” or “antitussive (cough suppressant)/oral anesthetic.” The indications shall be combined from § 341.74(b) and...

  7. 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

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Procedures for notice of Food and Drug 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...

  8. Intranasal delivery of systemic-acting drugs: small-molecules and biomacromolecules.

    PubMed

    Fortuna, Ana; Alves, Gilberto; Serralheiro, Ana; Sousa, Joana; Falcão, Amílcar

    2014-09-01

    As a non-invasive route, intranasal administration offers patient comfort and compliance which are hurdled in parenteral drug therapy. In addition, the current recognition that the high permeability and vascularization of nasal mucosa coupled to the avoidance of the first-pass elimination and/or gastrointestinal decomposition ensure higher systemic drug absorption than oral route has contributed to the growing interest for intranasal delivery of drugs that require considerable systemic exposure to exert their therapeutic actions (systemic-acting drugs). Nevertheless, several features may hamper drug absorption through the nasal mucosa, particularly the drug molecular weight and intrinsic permeability, and, therefore, several strategies have been employed to improve it, propelling a constant challenge during nasal drug (formulation) development. This review will firstly provide an anatomical, histological and mechanistic overview of drug systemic absorption after nasal administration and the relevant aspects of the therapeutic interest and limitations of the intranasal systemic delivery. The current studies regarding the nasal application of systemic-acting small drugs (analgesic drugs, cardiovascular drugs and antiviral drugs) and biomacromolecular drugs (peptide/protein drugs and vaccines) will also be outlined, addressing drug pharmacokinetics and pharmacodynamic improvements. PMID:24681294

  9. Sleep-wake mechanisms and drug discovery: sleep EEG as a tool for the development of CNS-acting drugs

    PubMed Central

    Staner, Luc

    2002-01-01

    Sleep laboratory investigations constitute a unique noninvasive tool to analyze brain functioning, Polysomnographic recordings, even in the very early phase of development in humans, are mandatory in a developmental plan of a new sleep-acting compound. Sleep is also an interesting tool for the development of other drugs acting on the central nervous system (CNS), Indeed, changes in sleep electroencephalographic (EEG) characteristics are a very sensitive indication of the objective central effects of psychoactive drugs, and these changes are specific to the way the drug acts on the brain neurotransmitter systems. Moreover, new compounds can be compared with reference drugs in terms of the sleep EEG profile they induce. For instance, cognitive enhancers involving cholinergic mechanism have been consistently demonstrated to increase rapid eye movement (REM) sleep pressure, and studying drug-induced slow wave sleep (SWS) alteration is a particularly useful tool for the development of CNS compounds acting at the 5-HT2A/C receptor, such as most atypical antipsychotics and some antidepressant drugs. The sleep EEG profile of antidepressants, and particularly their effects on REM sleep, are specific to their ability to enhance noradrenergic or serotonergic transmission, it is suggested that the effects of noradrenergic versus serotonergic reuptake inhibition could be disentangled using specific monoamine depletion tests and by studying drug effects on sleep microsiructure. PMID:22034388

  10. Antitussive Activity of the Water-Extracted Carbohydrate Polymer from Terminalia chebula on Citric Acid-Induced Cough

    PubMed Central

    Chatterjee, Udipta Ranjan; Majee, Sujay Kumar; Ray, Bimalendu

    2013-01-01

    Terminalia chebula, a medicinal plant, is widely used in the management of various diseases. As the water extract of its dried ripe fruit is a frequently used preparation, we decided to look for bioactive polysaccharide in this extract. We demonstrate that the obtained polysaccharide fraction, CP, contained a highly branched arabinogalactan protein having a (1 → 3)-, (1 → 6)- and (1 → 3, 6)-linked β-D-Galp together with (1 → 5)- and (1 → 3)-linked α-L-Araf and nonreducing end units of α-L-Araf. This polymer possesses strong antitussive property. Our results showed that the number of citric acid-induced cough efforts decreased significantly after the oral application of polysaccharide fraction in a dose of 50 mg kg−1 body weight. Its antitussive efficacy was higher than cough suppressive effect of standard drug codeine. Therefore, traditional aqueous extraction method provides a major polysaccharide, which induces a pharmacological effect: this could represent an attractive approach in phytotherapeutic managements. PMID:23878602

  11. Exercise acts as a drug; the pharmacological benefits of exercise

    PubMed Central

    Vina, J; Sanchis-Gomar, F; Martinez-Bello, V; Gomez-Cabrera, MC

    2012-01-01

    The beneficial effects of regular exercise for the promotion of health and cure of diseases have been clearly shown. In this review, we would like to postulate the idea that exercise can be considered as a drug. Exercise causes a myriad of beneficial effects for health, including the promotion of health and lifespan, and these are reviewed in the first section of this paper. Then we deal with the dosing of exercise. As with many drugs, dosing is extremely important to get the beneficial effects of exercise. To this end, the organism adapts to exercise. We review the molecular signalling pathways involved in these adaptations because understanding them is of great importance to be able to prescribe exercise in an appropriate manner. Special attention must be paid to the psychological effects of exercise. These are so powerful that we would like to propose that exercise may be considered as a psychoactive drug. In moderate doses, it causes very pronounced relaxing effects on the majority of the population, but some persons may even become addicted to exercise. Finally, there may be some contraindications to exercise that arise when people are severely ill, and these are described in the final section of the review. Our general conclusion is that exercise is so effective that it should be considered as a drug, but that more attention should be paid to the dosing and to individual variations between patients. PMID:22486393

  12. 75 FR 70011 - Guidance for Industry, Mammography Quality Standards Act Inspectors, and Food and Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ...The Food and Drug Administration (FDA) is announcing the availability of the guidance entitled ``The Mammography Quality Standards Act Final Regulations: Modifications and Additions to Policy Guidance Help System 13.'' This document is intended to assist mammography facilities and their personnel in meeting the requirements of the Mammography Quality Standards Act (MQSA)...

  13. 76 FR 58277 - Animal Generic Drug User Fee Act; Public Meeting; Request for Comments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-20

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Animal Generic Drug User Fee Act; Public Meeting; Request... meeting participants better understand the history and evolution of AGDUFA, and its current status....

  14. 78 FR 78367 - Draft Prescription Drug User Fee Act V Information Technology Plan; Availability for Comment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-26

    ...The Food and Drug Administration (FDA) is announcing the availability for public comment of the draft information technology (IT) plan entitled ``PDUFA V Information Technology Plan.'' This plan is intended to provide FDA's approach for enhancing business processes, data quality and consistency, supporting technologies, and IT operations as described in the Prescription Drug User Fee Act......

  15. 76 FR 58020 - Prescription Drug User Fee Act IV Information Technology Plan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-19

    ... HUMAN SERVICES Food and Drug Administration Prescription Drug User Fee Act IV Information Technology... Administration (FDA) is announcing the availability of an updated information technology (IT) plan entitled ``PDUFA IV Information Technology Plan'' (updated plan) to achieve the objectives defined in...

  16. A comparative study of the antitussive activity of levodropropizine and dropropizine in the citric acid-induced cough model in normal subjects.

    PubMed

    Fumagalli, G; Cordaro, C I; Vanasia, M; Balzarotti, C; Camusso, L; Caiazzo, G; Maghini, L; Mazzocchi, M; Zennaro, M

    1992-01-01

    Levodropropizine is the levo-rotatory (S)-enantiomer of dropropizine, a racemic non-opiate antitussive agent which has been used clinically for many years. Compared with the racemic drug, levodropropizine exhibits in animal models similar antitussive activity but considerably lower central nervous system (CNS) depressant effects. It is also less likely to cause sedation in treated patients. Since the comparative antitussive potency of the two drugs in clinical experimental models has not been evaluated, the authors performed a randomized, double blind, cross over investigation in which the effects of single oral doses (60 and 90 mg) of levodropropizine and dropropizine were assessed by using the citric acid-induced cough model in eight normal volunteers. Stimulation tests involved inhalation of individual cumulative doses of citric acid (6.3 to 53.3 mg) which at pre-study assessment had been found to induce reproducibly at least ten coughs over a 30 sec period. Each subject was studied by repeating the citric acid stimulation test four times (0 h, 1 h, 2 h and 6 h) on each of five different days separated by intervals of at least three days. In the absence of drug administration (control session), cough response to citric inhalation was remarkably reproducible throughout the 6 h period of observation. A marked and statistically significant reduction in cough response (to about one third--one sixth of the pre-drug values) was observed 1 h after intake for both compounds. At subsequent testing 2 h and 6 h after dosing, cough response was still depressed and did not differ significantly from that observed at 1 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1295724

  17. Assessment of antitussive effects by citric acid threshold.

    PubMed

    Rees, P J; Clark, T J

    1983-01-01

    The cough threshold to citric acid inhalation was measured in eight subjects by single inhalations of increasing concentrations of citric acid until a cough was consistently produced. The cough threshold was measured before and after 60 mg glaucine, 60 mg codeine and matched placebo on three separate days a week apart. Base-line cough threshold in each subject was consistent from week to week. Codeine increased the threshold by more than one citric acid concentration in three subjects. Placebo and glaucine did not produce a threshold change of more than one citric acid concentration. We conclude that the citric acid threshold is a simple measure of antitussive activity. No such activity was found with glaucine. PMID:6344901

  18. Hepatitis C Virus Direct-Acting Antiviral Drug Interactions and Use in Renal and Hepatic Impairment.

    PubMed

    Hill, Lucas

    2015-01-01

    Direct-acting antiviral (DAA) drugs exhibit considerable variability in mechanisms of metabolism and the extent to which they are substrates, inhibitors, or inducers of cytochrome P450 enzymes or P-glycoprotein and other drug transporters. Thus, potential drug-drug interactions with other commonly used therapies also vary, as do the effects of renal and hepatic impairment on DAA drug exposure. Drug-drug interaction profiles and use in cases of renal or hepatic impairment are reviewed for the DAAs simeprevir; sofosbuvir; ledipasvir; the fixed-dose combination regimen of paritaprevir, ritonavir, and ombitasvir plus dasabuvir; and the investigational drugs daclatasvir and asunaprevir. This article summarizes a presentation by Lucas Hill, PharmD, at the IAS-USA continuing education program held in Chicago, Illinois, in October 2014. PMID:26200709

  19. Efficacy and tolerability of glaucine as an antitussive agent.

    PubMed

    Gastpar, H; Criscuolo, D; Dieterich, H A

    1984-01-01

    One hundred and thirty out-patients, affected by acute and chronic cough caused by upper respiratory tract inflammation, took part in two clinical studies aimed at evaluating the efficacy and tolerability of glaucine , a new antitussive agent. The first study involved 90 patients in a double-blind comparative trial of glaucine and codeine: both treatments were administered as a syrup at a dosage of 30 mg 3-times daily for 7 days. The cough suppressant effect of the two treatments was checked by the physician and the patient using a 4-point scale (from absent to severe), and by the patient using a visual analogue scale. Mean scores of the physician's evaluation decreased from 3.0 to 1.10 after codeine and from 3.0 to 0.47 after glaucine (p less than 0.001 between treatments). Mean values of the patients' visual analogue scales decreased from 83 mm to 17 mm after codeine, and from 85 mm to 7 mm after glaucine (p less than 0.001 between treatments). Constipation and nausea were reported by 9 patients on codeine and by no patient on glaucine (p less than 0.01). One patient on codeine was withdrawn from the study after 3 days because of vomiting, constipation and nausea. The second study was an open trial in 40 patients who received glaucine capsules at a dosage of 30 mg 3-times daily for 28 days. The antitussive effect of the treatment was evaluated on the basis of the same criteria as in the first study. The mean score of the physician's evaluation decreased from 3.0 to 0.15 (p less than 0.001); the mean value of the patients' visual analogue scales decreased from 93 mm to 1 mm (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6373156

  20. Drugs acting on calcium channels: potential treatment for ischaemic stroke.

    PubMed Central

    Alps, B J

    1992-01-01

    Calcium subserves a ubiquitous role in the organisation of cell function. Ca2+ channels which control influx may be modified in disease states. Animal models of cerebral ischaemia do present some problems when investigating potential therapies involving Ca2+ channels. However, it is important not to be too rigid in searching for models which exactly mimic the human disease state, when even the best experimental approaches fall short of such an ideal. There are differences between different classes of calcium entry blocking drugs with regard to their activity on Ca2+ channels and transmembrane Ca2+ movement. Some calcium antagonists may also affect ion channels other than Ca2+, and this potential is exemplified by the novel ion channel modulator RS-87476, which affords experimental neurocytoprotection. Limitation of intracellular Na+ influx during ischaemia-induced depolarization may be useful. PMID:1327050

  1. Extracted polysaccharide from Nyctanthes arbor-tristis leaves: chemical and antitussive properties.

    PubMed

    Ghosh, Kanika; Nosalova, Gabriela; Ray, Sayani; Sivova, Veronika; Nosal, Slavomir; Ray, Bimalendu

    2015-04-01

    The prevalence of cough is reflected in antitussives being one of the most widely used therapies in the world; however no new class of drugs has been introduced into the market for many years. Water decoction of the leaves of Nyctanthes arbor-tristis L. is used in Indian Ayurvedic system to alleviate a wide range of diseases including cough. Herein, we have isolated a carbohydrate polymer (CP) containing fraction from its leaves by aqueous extraction method. CP is a branched polysaccharide containing, amongst others, 1,3-/1,3,6-linked galactopyranosyl, 1,5-/1,3,5-linked arabinofuranosyl and 1,2-/1,2,4-linked rhamnopyranosyl residues. Oral administration of CP fraction in doses of 25 and 50 mg kg(-1) body weight significantly inhibited the number of citric acid-induced cough efforts in guinea pigs in a dose dependent manner. Remarkably, CP did not altered specific airway resistance of animals significantly. Consequently, aqueous extraction method provided a molecular entity, which exhibited the cough suppressive activity: this could symbolize an attractive approach in phytotherapeutic treatment. PMID:25600986

  2. [Evaluation of the safety of antitussive agents during respiratory rehabilitation. A clinical study of L-dropropizine].

    PubMed

    Bejor, M; Arrigo, A

    1990-06-30

    This study proves that L-dropropizine, a new peripheral antitussive drug, does not hinder the positive and useful effect of cough. This is particularly the case of physiokinesis in chronic obstructive lung disease patients. To quantify results, the respiratory voluntary muscles have been examined by surface electromyography and the peak expiratory flow has been registered by a computer-assisted device. By analysing the curves obtained relating the intensity of muscle contraction to expiratory flow, i.e. the muscle work exerted, no difference has been found after L-dropropizine and placebo. Statistical analysis evidenced increase in maximal peak expiratory flow and decrease in muscle work with both therapies. Both were significant (Student's test for paired data: p less than 0.01) in attaining functional improvement. Levodropropizine does not seem to impair the efficacy of cough elicited as part of respiratory clearance mechanisms. PMID:2147884

  3. Antitussive activity of sigma-1 receptor agonists in the guinea-pig

    PubMed Central

    Brown, Claire; Fezoui, Malika; Selig, William M; Schwartz, Carl E; Ellis, James L

    2003-01-01

    Current antitussive medications have limited efficacy and often contain the opiate-like agent dextromethorphan (DEX). The mechanism whereby DEX inhibits cough is ill defined. DEX displays affinity at both NMDA and sigma receptors, suggesting that the antitussive activity may involve central or peripheral activity at either of these receptors. This study examined and compared the antitussive activity of DEX and various putative sigma receptor agonists in the guinea-pig citric-acid cough model. Intraperitoneal (i.p.) administration of DEX (30 mg kg−1) and the sigma-1 agonists SKF-10,047 (1–5 mg kg−1), Pre-084 (5 mg kg−1), and carbetapentane (1–5 mg kg−1) inhibited citric-acid-induced cough in guinea-pigs. Intraperitoneal administration of a sigma-1 antagonist, BD 1047 (1–5 mg kg−1), reversed the inhibition of cough elicited by SKF-10,047. In addition, two structurally dissimilar sigma agonists SKF-10,047 (1 mg ml−1) and Pre-084 (1 mg ml−1) inhibited cough when administered by aerosol. Aerosolized BD 1047 (1 mg ml−1, 30 min) prevented the antitussive action of SKF-10,047 (5 mg kg−1) or DEX (30 mg kg−1) given by i.p. administration and, likewise, i.p. administration of BD 1047 (5 mg kg−1) prevented the antitussive action of SKF-10,047 given by aerosol (1 mg ml−1). These results therefore support the argument that antitussive effects of DEX may be mediated via sigma receptors, since both systemic and aerosol administration of sigma-1 receptor agonists inhibit citric-acid-induced cough in guinea-pigs. While significant systemic exposure is possible with aerosol administration, the very low doses administered (estimated <0.3 mg kg−1) suggest that there may be a peripheral component to the antitussive effect. PMID:14691051

  4. Industry invites regulation: the passage of the Pure Food and Drug Act of 1906.

    PubMed Central

    Barkan, I D

    1985-01-01

    Ending its 27-year stranglehold on proposals for federal pure food and drug legislation, Congress passed the Pure Food and Drug Act and its companion bill, the Meat Inspection Act, on June 30, 1906. An unprecedented convergence of consumer, scientific, and industrial support in 1906 prompted such action; most industries even planned for it, hoping regulation would restore the competitiveness of their products on weak foreign and domestic markets. The ways in which these interests converged, and the reasons therefore, suggest a change in their relationships to each other and with the federal government as America headed into the twentieth century. Images p21-a p21-b PMID:3881052

  5. The Controlled Substances Act: how a "big tent" reform became a punitive drug law.

    PubMed

    Courtwright, David T

    2004-10-01

    The 1970 Controlled Substances Act was part of an omnibus reform package designed to rationalize, and in some respects to liberalize, American drug policy. While the legislation provided additional resources for law enforcement and a systematic means for regulating the use of most psychoactive drugs, it also did away with mandatory minimum sentences and provided more support for treatment and research. Over the next three decades, and in response to public alarm about drug abuse, the US Congress continuously amended the law to produce a more punitive system of drug control. The amendments, which gave the Drug Enforcement Administration greater control over scheduling and maintenance and which substantially increased penalties for illicit trafficking, transformed the law into the legal foundation of America's "drug war," as the stricter criminal approach came to be known. By the 1980s, the flexibility and innovative spirit of the original Controlled Substances Act (and that of Nixon-era drug strategy generally) had largely disappeared from American drug policy. PMID:15380284

  6. Antitussive, expectorant and analgesic effects of the ethanol seed extract of Picralima nitida (Stapf) Th. & H. Durand.

    PubMed

    Dapaah, Gabriel; Koffuor, George Asumeng; Mante, Priscilla Kolibea; Ben, Inemesit Okon

    2016-01-01

    Picralima nitida is used traditionally for management of cough. This study, therefore, investigated the antitussive, expectorant, and analgesic properties of the ethanolic seed extract of Picralima nitida (PNE), and ascertained its safety for use. Presence of secondary metabolites, and safety of PNE (10-2000 mg/kg) were evaluated by preliminary phytochemical screening, and by Irwin's test respectively. Percentage reduction in cough count, percentage increase in latency of cough, and percentage protection offered by PNE were established by the citric acid-induced cough, acetylcholine- and Histamine-induced bronchoconstriction models. Dunkin-Hartley guinea pigs were treated with 100-500 mg/kg PNE or reference drugs, dihydrocodiene, atropine, mepyramine. Expectorant property of PNE (100-1000 mg/kg) was determined using the tracheal phenol red secretion; with ammonium chloride as a reference medication. Percentage maximal possible analgesic effect in the tail immersion test and the total nociceptive score in acetic acid-induced abdominal writhes, after treatment of BALB/c mice with PNE (100-500 mg/kg), diclofenac, and morphine were also estimated. Phytochemical screening revealed the presence of tannins, alkaloids, glycosides, saponins, steroids, terpenoids and anthraquinones. PNEdid not cause any extract-related physical, pharmacological and CNS toxicities or mortality; sedation was observed at doses 1000-2000 mg/kg. It showed significant dose-dependent reduction in cough count, and increased cough latency. PNE (1000 mg/kg) enhanced tracheal phenol red secretion. PNE (100-500 mg/kg) significantly and dose dependently increased tail withdrawal latencies, and nociceptive score. PNE has antitussive, expectorant, and analgesic properties, with an LD50>2000 mg/kg. PMID:27168749

  7. Antitussive, expectorant and analgesic effects of the ethanol seed extract of Picralima nitida (Stapf) Th. & H. Durand

    PubMed Central

    Dapaah, Gabriel; Koffuor, George Asumeng; Mante, Priscilla Kolibea; Ben, Inemesit Okon

    2016-01-01

    Picralima nitida is used traditionally for management of cough. This study, therefore, investigated the antitussive, expectorant, and analgesic properties of the ethanolic seed extract of Picralima nitida (PNE), and ascertained its safety for use. Presence of secondary metabolites, and safety of PNE (10-2000 mg/kg) were evaluated by preliminary phytochemical screening, and by Irwin's test respectively. Percentage reduction in cough count, percentage increase in latency of cough, and percentage protection offered by PNE were established by the citric acid-induced cough, acetylcholine- and Histamine-induced bronchoconstriction models. Dunkin-Hartley guinea pigs were treated with 100-500 mg/kg PNE or reference drugs, dihydrocodiene, atropine, mepyramine. Expectorant property of PNE (100-1000 mg/kg) was determined using the tracheal phenol red secretion; with ammonium chloride as a reference medication. Percentage maximal possible analgesic effect in the tail immersion test and the total nociceptive score in acetic acid-induced abdominal writhes, after treatment of BALB/c mice with PNE (100-500 mg/kg), diclofenac, and morphine were also estimated. Phytochemical screening revealed the presence of tannins, alkaloids, glycosides, saponins, steroids, terpenoids and anthraquinones. PNEdid not cause any extract-related physical, pharmacological and CNS toxicities or mortality; sedation was observed at doses 1000-2000 mg/kg. It showed significant dose-dependent reduction in cough count, and increased cough latency. PNE (1000 mg/kg) enhanced tracheal phenol red secretion. PNE (100–500 mg/kg) significantly and dose dependently increased tail withdrawal latencies, and nociceptive score. PNE has antitussive, expectorant, and analgesic properties, with an LD50>2000 mg/kg. PMID:27168749

  8. Prevalence of Malaria Parasitemia and Purchase of Artemisinin-Based Combination Therapies (ACTs) among Drug Shop Clients in Two Regions in Tanzania with ACT Subsidies

    PubMed Central

    Briggs, Melissa A.; Kalolella, Admirabilis; Bruxvoort, Katia; Wiegand, Ryan; Lopez, Gerard; Festo, Charles; Lyaruu, Pierre; Kenani, Mitya; Abdulla, Salim; Goodman, Catherine; Kachur, S. Patrick

    2014-01-01

    Background Throughout Africa, many people seek care for malaria in private-sector drug shops where diagnostic testing is often unavailable. Recently, subsidized artemisinin-based combination therapies (ACTs), a first-line medication for uncomplicated malaria, were made available in these drug shops in Tanzania. This study assessed the prevalence of malaria among and purchase of ACTs by drug shop clients in the setting of a national ACT subsidy program and sub-national drug shop accreditation program. Method and Findings A cross-sectional survey of drug shop clients was performed in two regions in Tanzania, one with a government drug shop accreditation program and one without, from March-May, 2012. Drug shops were randomly sampled from non-urban districts. Shop attendants were interviewed about their education, training, and accreditation status. Clients were interviewed about their symptoms and medication purchases, then underwent a limited physical examination and laboratory testing for malaria. Malaria prevalence and predictors of ACT purchase were assessed using univariate analysis and multiple logistic regression. Amongst 777 clients from 73 drug shops, the prevalence of laboratory-confirmed malaria was 12% (95% CI: 6–18%). Less than a third of clients with malaria had purchased ACTs, and less than a quarter of clients who purchased ACTs tested positive for malaria. Clients were more likely to have purchased ACTs if the participant was <5 years old (aOR: 6.6; 95% CI: 3.9–11.0) or the shop attendant had >5 years, experience (aOR: 2.8; 95% CI: 1.2–6.3). Having malaria was only a predictor of ACT purchase in the region with a drug shop accreditation program (aOR: 3.4; 95% CI: 1.5–7.4). Conclusion Malaria is common amongst persons presenting to drug shops with a complaint of fever. The low proportion of persons with malaria purchasing ACTs, and the high proportion of ACTs going to persons without malaria demonstrates a need to better target who receives

  9. Effect of the antitussive glaucine on bronchomotor tone in man.

    PubMed Central

    Constant, O; Slavin, B; Lehane, J R; Jordan, C; Jones, J G

    1983-01-01

    In view of the observation that the antitussive agent glaucine prevents histamine-induced bronchoconstriction in guinea pigs we investigated this agent for a possible peripheral action in man, using a new method for measuring changes in bronchomotor tone. The forced airflow oscillation method was used to determine respiratory resistance (Rrs) over a range of lung volumes (VL) in seven healthy supine subjects. Computer analysis of the hyperbolic relationship between Rrs and VL was used to determine the asymptotic resistance and yield estimates of lower airways conductance (Glaw). Specific lower airways conductance (sGlaw) was expressed as the slope of the linear plot of Glaw against VL and is a sensitive index of bronchomotor tone. After baseline measurements of sGlaw subjects received placebo or 60 mg glaucine orally according to a double-blind crossover protocol. Histamine, 500 micrograms, was inhaled 45 minutes later. Measurements of sGlaw were repeated every 10 minutes for two hours. Although there was a trend towards bronchodilatation after glaucine administration (sGlaw = 130% of baseline) there was no significant difference from the effect of placebo (sGlaw = 89% of baseline). After inhalation of histamine sGlaw fell to 26% of baseline after both glaucine and placebo (p less than 0.01). In a further study three subjects received glaucine and placebo according to an identical protocol except that the histamine was omitted. Again the increase in sGlaw failed to achieve significance. Glaucine does not affect the bronchoconstrictor response to histamine in man and there is no convincing evidence of an effect on resting bronchomotor tone. PMID:6612639

  10. Effect of the antitussive glaucine on bronchomotor tone in man.

    PubMed

    Constant, O; Slavin, B; Lehane, J R; Jordan, C; Jones, J G

    1983-07-01

    In view of the observation that the antitussive agent glaucine prevents histamine-induced bronchoconstriction in guinea pigs we investigated this agent for a possible peripheral action in man, using a new method for measuring changes in bronchomotor tone. The forced airflow oscillation method was used to determine respiratory resistance (Rrs) over a range of lung volumes (VL) in seven healthy supine subjects. Computer analysis of the hyperbolic relationship between Rrs and VL was used to determine the asymptotic resistance and yield estimates of lower airways conductance (Glaw). Specific lower airways conductance (sGlaw) was expressed as the slope of the linear plot of Glaw against VL and is a sensitive index of bronchomotor tone. After baseline measurements of sGlaw subjects received placebo or 60 mg glaucine orally according to a double-blind crossover protocol. Histamine, 500 micrograms, was inhaled 45 minutes later. Measurements of sGlaw were repeated every 10 minutes for two hours. Although there was a trend towards bronchodilatation after glaucine administration (sGlaw = 130% of baseline) there was no significant difference from the effect of placebo (sGlaw = 89% of baseline). After inhalation of histamine sGlaw fell to 26% of baseline after both glaucine and placebo (p less than 0.01). In a further study three subjects received glaucine and placebo according to an identical protocol except that the histamine was omitted. Again the increase in sGlaw failed to achieve significance. Glaucine does not affect the bronchoconstrictor response to histamine in man and there is no convincing evidence of an effect on resting bronchomotor tone. PMID:6612639

  11. 28 CFR 0.177 - Applications for orders under the Comprehensive Drug Abuse Prevention and Control Act.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Comprehensive Drug Abuse Prevention and Control Act. 0.177 Section 0.177 Judicial Administration DEPARTMENT OF... the Comprehensive Drug Abuse Prevention and Control Act. Notwithstanding the delegation of functions... authorized to exercise the authority vested in the Attorney General by section 514 of the Comprehensive...

  12. 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...

  13. 40 CFR 2.308 - Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... information obtained under the Federal Food, Drug and Cosmetic Act. 2.308 Section 2.308 Protection of... § 2.308 Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic... Cosmetic Act, as amended, 21 U.S.C. 301 et seq. (2) Petition means a petition for the issuance of...

  14. 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...

  15. 40 CFR 2.308 - Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... information obtained under the Federal Food, Drug and Cosmetic Act. 2.308 Section 2.308 Protection of... § 2.308 Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic... Cosmetic Act, as amended, 21 U.S.C. 301 et seq. (2) Petition means a petition for the issuance of...

  16. 40 CFR 2.308 - Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... information obtained under the Federal Food, Drug and Cosmetic Act. 2.308 Section 2.308 Protection of... § 2.308 Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic... Cosmetic Act, as amended, 21 U.S.C. 301 et seq. (2) Petition means a petition for the issuance of...

  17. 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...

  18. 40 CFR 2.308 - Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... information obtained under the Federal Food, Drug and Cosmetic Act. 2.308 Section 2.308 Protection of... § 2.308 Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic... Cosmetic Act, as amended, 21 U.S.C. 301 et seq. (2) Petition means a petition for the issuance of...

  19. 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...

  20. 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...

  1. 40 CFR 2.308 - Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... information obtained under the Federal Food, Drug and Cosmetic Act. 2.308 Section 2.308 Protection of... § 2.308 Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic... Cosmetic Act, as amended, 21 U.S.C. 301 et seq. (2) Petition means a petition for the issuance of...

  2. 77 FR 28620 - Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-15

    ... (59 FR 11308). This 15th report, covering 2010-2011, the period since the previous report, is to be... COMMISSION Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication AGENCY... Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication. DATES: July 3, 2012: Deadline...

  3. 75 FR 24967 - Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-06

    ... in the Federal Register of March 10, 1994 (59 FR 11308). This 14th report, covering the period since... COMMISSION Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication AGENCY.... 332-352, Andean ] Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop...

  4. Antitussive Efficacy and Safety Profile of Ethyl Acetate Fraction of Terminalia chebula

    PubMed Central

    Wahab, Abdul; Ayub, Khurshed; Sherkheli, M. Azhar; Khan, Rafeeq Alam; Raza, Mohsin

    2013-01-01

    Antitussive effects of ethyl acetate fraction of Terminalia chebula on sulphur dioxide (SO2) gas induced cough have been examined in mice. Safety profile of Terminalia chebula was established by determining LD50 and acute neurotoxicity. The result showed that extract of Terminalia chebula dose dependently suppressed SO2 gas induced cough in mice. Terminalia chebula, after i.p. administration at dose level 500 mg/kg, offered maximum cough suppressive effects; that is, number of coughs at 60 min was 12 ± 1.52 (mean ± SEM) as compared to codeine 10 mg/kg; i.p., dextromethorphan 10 mg/kg; i.p., and saline, having frequency of cough 10.375 ± 0.866, 12.428 ± 0.81, and 46 ± 2.61, respectively. LD50 value of Terminalia chebula was approximately 1265 mg/kg, respectively. No sign of neural impairment was observed at antitussive doses of extract. Antitussive effect of Terminalia chebula was partly reversed with treatment by naloxone (3 mg/kg; s.c.) while rimcazole (3 mg/kg; s.c.) did not antagonize its cough suppression activity. This may suggest that opioid receptors partially contribute in antitussive action of Terminalia chebula. Along with this, the possibility of presence of single or multiple mechanisms activated by several different pharmacological actions (mainly anti-inflammatory, antioxidant, spasmolytic, antibacterial, and antiphlegmatic) could not be eliminated. PMID:24024039

  5. Clinical aspects of blood pressure crisis due to withdrawal of centrally acting antihypertensive drugs

    PubMed Central

    Hansson, L.

    1983-01-01

    1 Sudden cessation of antihypertensive therapy, in particular centrally acting drugs such as clonidine, may cause a withdrawal syndrome characterised by a rapid increase in blood pressure, headaches, tremor, restlessness and nausea. 2 The withdrawal syndrome is associated with a marked increase in sympathetic activity, as indicated by the increased levels of urinary and plasma catecholamines. 3 The clonidine withdrawal syndrome is reproducible. 4 The crisis can be managed acutely either by reinstituting the drug which has been withdrawn or by giving α- and β-adrenoceptor blocking drugs, either separately or in the form of labetalol. 5 The withdrawal syndrome can now be reproduced in animal models, but in spite of extensive studies, the exact underlying mechanism remains to be elucidated.

  6. Identifying mechanism-of-action targets for drugs and probes

    PubMed Central

    Gregori-Puigjané, Elisabet; Setola, Vincent; Hert, Jérôme; Crews, Brenda A.; Irwin, John J.; Lounkine, Eugen; Marnett, Lawrence; Roth, Bryan L.; Shoichet, Brian K.

    2012-01-01

    Notwithstanding their key roles in therapy and as biological probes, 7% of approved drugs are purported to have no known primary target, and up to 18% lack a well-defined mechanism of action. Using a chemoinformatics approach, we sought to “de-orphanize” drugs that lack primary targets. Surprisingly, targets could be easily predicted for many: Whereas these targets were not known to us nor to the common databases, most could be confirmed by literature search, leaving only 13 Food and Drug Administration—approved drugs with unknown targets; the number of drugs without molecular targets likely is far fewer than reported. The number of worldwide drugs without reasonable molecular targets similarly dropped, from 352 (25%) to 44 (4%). Nevertheless, there remained at least seven drugs for which reasonable mechanism-of-action targets were unknown but could be predicted, including the antitussives clemastine, cloperastine, and nepinalone; the antiemetic benzquinamide; the muscle relaxant cyclobenzaprine; the analgesic nefopam; and the immunomodulator lobenzarit. For each, predicted targets were confirmed experimentally, with affinities within their physiological concentration ranges. Turning this question on its head, we next asked which drugs were specific enough to act as chemical probes. Over 100 drugs met the standard criteria for probes, and 40 did so by more stringent criteria. A chemical information approach to drug-target association can guide therapeutic development and reveal applications to probe biology, a focus of much current interest. PMID:22711801

  7. Identifying mechanism-of-action targets for drugs and probes.

    PubMed

    Gregori-Puigjané, Elisabet; Setola, Vincent; Hert, Jérôme; Crews, Brenda A; Irwin, John J; Lounkine, Eugen; Marnett, Lawrence; Roth, Bryan L; Shoichet, Brian K

    2012-07-10

    Notwithstanding their key roles in therapy and as biological probes, 7% of approved drugs are purported to have no known primary target, and up to 18% lack a well-defined mechanism of action. Using a chemoinformatics approach, we sought to "de-orphanize" drugs that lack primary targets. Surprisingly, targets could be easily predicted for many: Whereas these targets were not known to us nor to the common databases, most could be confirmed by literature search, leaving only 13 Food and Drug Administration-approved drugs with unknown targets; the number of drugs without molecular targets likely is far fewer than reported. The number of worldwide drugs without reasonable molecular targets similarly dropped, from 352 (25%) to 44 (4%). Nevertheless, there remained at least seven drugs for which reasonable mechanism-of-action targets were unknown but could be predicted, including the antitussives clemastine, cloperastine, and nepinalone; the antiemetic benzquinamide; the muscle relaxant cyclobenzaprine; the analgesic nefopam; and the immunomodulator lobenzarit. For each, predicted targets were confirmed experimentally, with affinities within their physiological concentration ranges. Turning this question on its head, we next asked which drugs were specific enough to act as chemical probes. Over 100 drugs met the standard criteria for probes, and 40 did so by more stringent criteria. A chemical information approach to drug-target association can guide therapeutic development and reveal applications to probe biology, a focus of much current interest. PMID:22711801

  8. Antitussive effects of GABAB agonists in the cat and guinea-pig.

    PubMed Central

    Bolser, D. C.; Aziz, S. M.; DeGennaro, F. C.; Kreutner, W.; Egan, R. W.; Siegel, M. I.; Chapman, R. W.

    1993-01-01

    1. GABAB agonists inhibit neuronal processes which are important in the pathogenesis of airway disease, such as bronchospasm. Cough is a prominent symptom of pulmonary disease, but the effects of GABAB agonists on this airway reflex are unknown. Experiments were conducted to determine the antitussive effect of GABAB receptor agonists in comparison to the known antitussive agents, codeine and dextromethorphan. 2. Unanaesthetized guinea-pigs were exposed to aerosols of 0.3 mM capsaicin to elicit coughing, which was detected with a microphone and counted. Cough also was produced in anaesthetized cats by mechanical stimulation of the intrathoracic trachea and was recorded from electromyograms of respiratory muscle activity. 3. In guinea-pigs, the GABAB agonists baclofen and 3-aminopropyl-phosphinic acid (3-APPi) produced dose-dependent inhibition of capsaicin-induced cough when administered by subcutaneous or inhaled routes. The potencies of baclofen and 3-APPi compared favourably with codeine and dextromethorphan. 4. The GABAB antagonist, CGP 35348 (0.3- 30 mg kg-1, s.c.) inhibited the antitussive effect of baclofen (3.0 mg kg-1, s.c.). However, CGP 35348 (10 mg kg-1, s.c.) had no effect on the antitussive activity of codeine (30 mg kg-1, s.c.). The antitussive effect of baclofen was not influenced by the GABAA antagonist, bicuculline (3 mg kg-1, s.c.) or naloxone (0.3 mg kg-1, s.c.). 5. In the cat, baclofen (0.3-3.0 mg kg-1, i.v.) decreased mechanically-induced cough in a dose-dependent manner. In this model, baclofen (ED50 = 0.63 mg kg-1) was less potent than either codeine or dextromethorphan.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8220912

  9. Venetoclax (ABT-199) Might Act as a Perpetrator in Pharmacokinetic Drug–Drug Interactions

    PubMed Central

    Weiss, Johanna; Gajek, Thomas; Köhler, Bruno Christian; Haefeli, Walter Emil

    2016-01-01

    Venetoclax (ABT-199) represents a specific B-cell lymphoma 2 (Bcl-2) inhibitor that is currently under development for the treatment of lymphoid malignancies. So far, there is no published information on its interaction potential with important drug metabolizing enzymes and drug transporters, or its efficacy in multidrug resistant (MDR) cells. We therefore scrutinized its drug–drug interaction potential in vitro. Inhibition of cytochrome P450 enzymes (CYPs) was quantified by commercial kits. Inhibition of drug transporters (P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP), and organic anion transporting polypeptides (OATPs)) was evaluated by the use of fluorescent probe substrates. Induction of drug transporters and drug metabolizing enzymes was quantified by real-time RT-PCR. The efficacy of venetoclax in MDR cells lines was evaluated with proliferation assays. Venetoclax moderately inhibited P-gp, BCRP, OATP1B1, OATP1B3, CYP3A4, and CYP2C19, whereas CYP2B6 activity was increased. Venetoclax induced the mRNA expression of CYP1A1, CYP1A2, UGT1A3, and UGT1A9. In contrast, expression of ABCB1 was suppressed, which might revert tumor resistance towards antineoplastic P-gp substrates. P-gp over-expression led to reduced antiproliferative effects of venetoclax. Effective concentrations for inhibition and induction lay in the range of maximum plasma concentrations of venetoclax, indicating that it might act as a perpetrator drug in pharmacokinetic drug–drug interactions. PMID:26927160

  10. Safety of long acting muscarinic antagonists: are all these drugs always and equally safe?

    PubMed

    Melani, Andrea S; Sestini, Piersante

    2016-05-01

    Inhaled bronchodilators - such as long-acting muscarinic receptor antagonists (LAMAs) - are central to the pharmacological management of symptomatic chronic obstructive pulmonary disease. LAMAs are considered to be safe drugs at recommended dosages. In the present issue of the Journal safety of umeclidinium, a recently marketed LAMA, at twice the recommended dosage, has been evaluated with good results in a Japanese, COPD population. However, because muscarinic receptors are expressed not only in the lungs but also at the level of heart, digestive and urinary apparatus, the potential exists for LAMAs to cause adverse events related to stimulation of receptors in these organs. Head-to-head and post-marketing vigilance studies are required to determine the profile risk of these drugs, ultimately, and whether differences exist between currently available LAMAs. PMID:26789695

  11. The effects of centrally acting drugs on the EEG correlates of meditation.

    PubMed

    Sim, M K; Tsoi, W F

    1992-09-01

    The present study investigated the effects of three centrally acting drugs on the significant increase in the intermediate alpha frequency of the electroencephalogram (EEG) that accompanied meditation in a male volunteer. When compared to the EEG recorded before each of the three drugs was administered, naloxone tended to enhance the increase in the power of the intermediate alpha EEG (9.4-10.4 Hz), while diazepam tended to spread the increase to the slow (7.4-9.4 Hz) alpha EEG, and flumazenil was without much effect on the overall EEG pattern. However, these EEG changes when compared to similar changes obtained with saline administration were not significantly different from the latter. Thus, it is unlikely that the EEG correlates of meditation are causally related to the rise or fall of endogenous opioid peptides or benzodiazepinelike substances in the brain. PMID:1515478

  12. Can a Bug in the Gut Act Like a Drug in the Brain?

    PubMed

    Howland, Robert H

    2015-10-01

    Microorganisms inhabiting the gut exist in a symbiotic relationship with our bodies, performing many essential metabolic tasks for human physiology. The gut-brain axis is a bidirectional communication system integrating neural, hormonal, and immunological signaling between the gut and brain. There is strong experimental evidence from animal studies that the intestinal microbiome has an important role in the control of brain development, function, and behavior. A small number of clinical studies, mainly in healthy individuals, using probiotic formulations as an experimental probe suggest that gut bugs may indeed act like a drug and affect the brain, but much more work is needed. PMID:26489100

  13. 77 FR 31039 - Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-24

    ... Commission's notice published in the Federal Register on May 15, 2012 (77 FR 28620) contained an error that... COMMISSION Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication AGENCY... under investigation No. 332-352, Andean Trade Preference Act: Impact on the U.S. Economy and on...

  14. 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

    ...The Food and Drug Administration (FDA) is establishing a public docket for information pertaining to FDA's implementation of the provisions of the Food and Drug Administration Safety and Innovation Act (FDASIA) related to medical gases. This action is intended to ensure that information submitted to FDA on the implementation of the medical gas provisions of FDASIA is available to all......

  15. Expectorant and Antitussive Effect of Hedera helix and Rhizoma coptidis Extracts Mixture

    PubMed Central

    Song, Kee Jae; Shin, Young-June; Lee, Kang Ro; Lee, Eun Jung; Suh, Yun Suk

    2015-01-01

    Purpose This study aims to investigate the additive effect of the Hedera helix (HH) and Rhizoma coptidis (RC) extracts mixture on antitussive and expectorant activities in animals. Materials and Methods The expectorant assay was performed with phenol red secretion in mice trachea. Mice or guinea pigs were randomly divided into groups of 8 each, including negative and positive control groups. After gastric administration of the test extracts in mice, 2.5% phenol red solution (0.2 mL) was intraperitoneally injected. Trachea was dissected and optical density of tracheal secretion was measured. After gastric administration of the test extracts in guinea pigs, the antitussive activities were assessed using a citric acid-induced cough measurement. Results The extracts of HH and RC significantly increased tracheal secretion and inhibited cough. The mixture of HH and RC extracts in a 1:1 concentration at a dose of 200 mg/kg showed a more potent effect on phenol red secretion (25.25±3.14) and cough inhibition (61.25±5.36) than the individual use of each extracts [phenol red secretion; HH 13.39±4.22 (p=0.000), RC 20.78±2.50 (p=0.010), cough inhibition; HH 9.89±4.14 (p=0.010), RC 30.25±7.69 (p=0.000)]. A 3:1 ratio mixture of HH to RC demonstrated an optimal expectorant effect (p<0.001), and this mixture showed expectorant and antitussive effects in a dose-dependent manner. Conclusion This study provides evidence for antitussive and expectorant effect of a 3:1 mixture of HH and RC, which may be a useful therapeutic option for respiratory diseases. PMID:25837191

  16. TREX1 acts in degrading damaged DNA from drug-treated tumor cells

    PubMed Central

    Wang, Chuan-Jen; Lam, Wing; Bussom, Scott; Chang, Hua-Mei; Cheng, Yung-Chi

    2009-01-01

    The major mammalian exonuclease TREX1 has been proposed to play a role in DNA repair and drug resistance. However, no cellular evidence substantiates this claim. Recent reports indicate TREX1’s involvement in autoimmunity. To further understand its role, we studied TREX1 expression and functionality in anticancer drug-treated tumor cells. We report that the expression and localization of TREX1 are cell-type dependent. Camptothecin and other DNA damaging agents induced both TREX1 protein and its mRNA in a dose- and time-dependent manner. Using a TREX1-inducible cell line, we performed clonogenic assays and found no change in sensitivity of the cells to the agents upon TREX1 induction, suggesting that TREX1 may not play a role in DNA repair or drug sensitivity. Nevertheless, TREX1 serves as a key enzyme in the degradation of DNA from dying cells leading to less cellular DNA. Ubiquitously expressed in normal tissues, TREX1 may act in degrading DNA in all cell types undergoing a dying process before phagocytosis occurs. PMID:19617005

  17. CYTOLOGY OF CANDIDA ALBICANS AS INFLUENCED BY DRUGS ACTING ON THE CYTOPLASMIC MEMBRANE

    PubMed Central

    Gale, Glen R.

    1963-01-01

    Gale, Glen R. (Veterans Administration Hospital, Durham, N.C.) Cytology of Candida albicans as influenced by drugs acting on the cytoplasmic membrane. J. Bacteriol. 86:151–157. 1963.—An electron microscopic comparison was made of the cytological responses of Candida albicans to benzalkonium chloride, amphotericin B, and filipin, all of which are thought to exert their primary pharmacological actions on the cytoplasmic membrane of susceptible microorganisms. After 5 to 15 min of exposure to benzalkonium chloride, most of the cytoplasm became less dense, and intact nuclei, mitochondria, or intracytoplasmic membranes were not observed. The remaining dense cytoplasm contained numerous small holes. The polyene antifungal agents, amphotericin B and filipin, caused a reduction in cytoplasmic density, but had no observable effect on nuclei or mitochondria. The intervals before onset of changes induced by the polyene agents correlated with the known time-dependent binding of these drugs by cells, and the decreased electron scattering induced by all three agents was compatible with their known abilities to cause a loss of integrity of the cytoplasmic membrane with resultant leakage of cytoplasmic components. No consistent morphological effect of any of these drugs on the cytoplasmic membrane could be shown. Images PMID:14054376

  18. Safety monitoring of drugs granted exclusivity under the Best Pharmaceuticals for Children Act: what the FDA has learned.

    PubMed

    Mathis, L L; Iyasu, S

    2007-08-01

    The Best Pharmaceuticals for Children Act (BPCA) was signed into law on 4 January 2002, shortly after the pediatric exclusivity provision of the Food and Drug Administration (FDA) Modernization Act expired on 1 January 2002. This Act provides six months of marketing exclusivity for a drug when a pharmaceutical company studies that drug for use in the pediatric population as requested by the FDA. Section 17 of the BPCA specifically requires that the FDA review all adverse events reported for drugs that receive pediatric exclusivity. In most of the cases, no unexpected adverse events were reported in the pediatric population; however, in some cases, this focused safety review provided information important to the safety of medication use in children. PMID:17632537

  19. The antitussive effect of dextromethorphan in relation to CYP2D6 activity

    PubMed Central

    Abdul Manap, R; Wright, C E; Gregory, A; Rostami-Hodjegan, A; Meller, S T; Kelm, G R; Lennard, M S; Tucker, G T; Morice, A H

    1999-01-01

    Aims To test the hypothesis that inhibition of cytochrome P450 2D6 (CYP2D6) by quinidine increases the antitussive effect of dextromethorphan (DEX) in an induced cough model. Methods Twenty-two healthy extensive metaboliser phenotypes for CYP2D6 were studied according to a double-blind, randomised cross-over design after administration of: (1) Placebo antitussive preceded at 1 h by placebo inhibitor; (2) 30 mg oral DEX preceded at 1 h by placebo inhibitor (DEX30); (3) 60 mg oral DEX preceded at 1 h by placebo inhibitor (DEX60); (4) 30 mg oral DEX preceded at 1 h by 50 mg oral quinidine sulphate (QDEX30). Cough frequency following inhalation of 10% citric acid was measured at baseline and at intervals up to 12 h. Plasma concentrations of DEX and its metabolites were measured up to 96 h by h.p.l.c. Results Inhibition of CYP2D6 by quinidine caused a significant increase in the mean ratio of DEX to dextrorphan (DEX:DOR) plasma AUC(96) (0.04 vs 1.81, P < 0.001). The mean (±s.d.) decrements in cough frequency below baseline over 12 h (AUEC) were: 8% (11), 17% (14.5), 25% (16.2) and 25% (16.9) for placebo, DEX30, DEX60 and QDEX30 treatments, respectively. Statistically significant differences in antitussive effect were detected for the contrasts between DEX60/placebo (P < 0.001; 95% CI of difference +80, +327) and QDEX30/placebo (P < 0.001, +88, +336), but not for DEX30/placebo, DEX30/DEX60 or DEX30/QDEX30 (P = 0.071, −7, +241; P = 0.254, −37, +211; P = 0.187, −29, +219, respectively). Conclusions A significant antitussive effect was demonstrated after 60 mg dextromethorphan and 30 mg dextromethorphan preceded by 50 mg quinidine using an induced cough model. However, although the study was powered to detect a 10% difference in cough response, the observed differences for other contrasts were less than 10%, such that it was possible only to imply a dose effect (30 vs 60 mg) in the antitussive activity of DEX and enhancement of this effect by CYP2D6 inhibition. PMID

  20. 21 CFR 314.151 - Withdrawal of approval of an abbreviated new drug application under section 505(j)(5) of the act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Withdrawal of approval of an abbreviated new drug application under section 505(j)(5) of the act. 314.151 Section 314.151 Food and Drugs FOOD AND DRUG... APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.151...

  1. 21 CFR 314.151 - Withdrawal of approval of an abbreviated new drug application under section 505(j)(5) of the act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Withdrawal of approval of an abbreviated new drug application under section 505(j)(5) of the act. 314.151 Section 314.151 Food and Drugs FOOD AND DRUG... APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.151...

  2. Dual-drug delivery of curcumin and platinum drugs in polymeric micelles enhances the synergistic effects: a double act for the treatment of multidrug-resistant cancer.

    PubMed

    Scarano, Wei; de Souza, Paul; Stenzel, Martina H

    2015-01-01

    Combinational chemotherapy is often used to prevent drug induced resistance in cancer. The aim of this work is to test whether the co-delivery of drugs within one nanoparticle can result in increased synergistic effects of both drugs. Therefore, a micelle system with two different compartments, one for the drug curcumin and one for the conjugation of platinum drugs was designed. A triblock copolymer, based on the biodegradable polycaprolactone PCL, a PEG based shell and an amine bearing polymer as the interphase for the conjugation of platinum drugs was prepared by combination of ring-opening polymerization and RAFT polymerization. Curcumin was incorporated into the self-assembled onion-type micelle by physical encapsulation into the PCL core with an entrapment capacity of 6 wt%. The platinum(iv) drug oxoplatin was reacted with succinic anhydride to yield Pt(NH3)2Cl2[(COOH)2], which acted as the drug and as a crosslinker for the stabilisation of micelles. The size of the dual drug micelles was measured to be 38 nm by DLS, which was confirmed by TEM. The toxicity of the dual drug delivery system was tested against the A2780 human ovarian cancer cell line and compared with the IC50 value of micelles that deliver either curcumin or the platinum drug alone. The results were analysed using the CalcuSyn software. While curcumin and the platinum drug together without a carrier already showed synergy with a combination index ranging from 0.4 to 0.8, the combined delivery in one nanoparticle did enhance the synergistic effects resulting in a combination index of approximately 0.2-0.35. For comparison, a mixture of two nanoparticles, one with curcumin and the other with the platinum drug, was tested revealing a less noticeable synergistic effect compared to the co-delivery of both drugs in one drug carrier. PMID:26214199

  3. The Affordable Care Act, health care reform, prescription drug formularies and utilization management tools.

    PubMed

    Ung, Brian L; Mullins, C Daniel

    2015-01-01

    The U.S. Patient Protection and Affordable Care Act (hence, Affordable Care Act, or ACA) was signed into law on March 23, 2010. Goals of the ACA include decreasing the number of uninsured people, controlling cost and spending on health care, increasing the quality of care provided, and increasing insurance coverage benefits. This manuscript focuses on how the ACA affects pharmacy benefit managers and consumers when they have prescriptions dispensed. PBMs use formularies and utilization control tools to steer drug usage toward cost-effective and efficacious agents. A logic model was developed to explain the effects of the new legislation. The model draws from peer-reviewed and gray literature commentary about current and future U.S. healthcare reform. Outcomes were identified as desired and undesired effects, and expected unintended consequences. The ACA extends health insurance benefits to almost 32 million people and provides financial assistance to those up to 400% of the poverty level. Increased access to care leads to a similar increase in overall health care demand and usage. This short-term increase is projected to decrease downstream spending on disease treatment and stunt the continued growth of health care costs, but may unintentionally exacerbate the current primary care physician shortage. The ACA eliminates limitations on insurance and increases the scope of benefits. Online health care insurance exchanges give patients a central location with multiple insurance options. Problems with prescription drug affordability and control utilization tools used by PBMs were not addressed by the ACA. Improving communication within the U.S. healthcare system either by innovative health care delivery models or increased usage of health information technology will help alleviate problems of health care spending and affordability. PMID:25217142

  4. Triple-acting Lytic Enzyme Treatment of Drug-Resistant and Intracellular Staphylococcus aureus

    PubMed Central

    Becker, Stephen C.; Roach, Dwayne R.; Chauhan, Vinita S.; Shen, Yang; Foster-Frey, Juli; Powell, Anne M.; Bauchan, Gary; Lease, Richard A.; Mohammadi, Homan; Harty, William J.; Simmons, Chad; Schmelcher, Mathias; Camp, Mary; Dong, Shengli; Baker, John R.; Sheen, Tamsin R.; Doran, Kelly S.; Pritchard, David G.; Almeida, Raul A.; Nelson, Daniel C.; Marriott, Ian; Lee, Jean C.; Donovan, David M.

    2016-01-01

    Multi-drug resistant bacteria are a persistent problem in modern health care, food safety and animal health. There is a need for new antimicrobials to replace over used conventional antibiotics. Here we describe engineered triple-acting staphylolytic peptidoglycan hydrolases wherein three unique antimicrobial activities from two parental proteins are combined into a single fusion protein. This effectively reduces the incidence of resistant strain development. The fusion protein reduced colonization by Staphylococcus aureus in a rat nasal colonization model, surpassing the efficacy of either parental protein. Modification of a triple-acting lytic construct with a protein transduction domain significantly enhanced both biofilm eradication and the ability to kill intracellular S. aureus as demonstrated in cultured mammary epithelial cells and in a mouse model of staphylococcal mastitis. Interestingly, the protein transduction domain was not necessary for reducing the intracellular pathogens in cultured osteoblasts or in two mouse models of osteomyelitis, highlighting the vagaries of exactly how protein transduction domains facilitate protein uptake. Bacterial cell wall degrading enzyme antimicrobials can be engineered to enhance their value as potent therapeutics. PMID:27121552

  5. Triple-acting Lytic Enzyme Treatment of Drug-Resistant and Intracellular Staphylococcus aureus.

    PubMed

    Becker, Stephen C; Roach, Dwayne R; Chauhan, Vinita S; Shen, Yang; Foster-Frey, Juli; Powell, Anne M; Bauchan, Gary; Lease, Richard A; Mohammadi, Homan; Harty, William J; Simmons, Chad; Schmelcher, Mathias; Camp, Mary; Dong, Shengli; Baker, John R; Sheen, Tamsin R; Doran, Kelly S; Pritchard, David G; Almeida, Raul A; Nelson, Daniel C; Marriott, Ian; Lee, Jean C; Donovan, David M

    2016-01-01

    Multi-drug resistant bacteria are a persistent problem in modern health care, food safety and animal health. There is a need for new antimicrobials to replace over used conventional antibiotics. Here we describe engineered triple-acting staphylolytic peptidoglycan hydrolases wherein three unique antimicrobial activities from two parental proteins are combined into a single fusion protein. This effectively reduces the incidence of resistant strain development. The fusion protein reduced colonization by Staphylococcus aureus in a rat nasal colonization model, surpassing the efficacy of either parental protein. Modification of a triple-acting lytic construct with a protein transduction domain significantly enhanced both biofilm eradication and the ability to kill intracellular S. aureus as demonstrated in cultured mammary epithelial cells and in a mouse model of staphylococcal mastitis. Interestingly, the protein transduction domain was not necessary for reducing the intracellular pathogens in cultured osteoblasts or in two mouse models of osteomyelitis, highlighting the vagaries of exactly how protein transduction domains facilitate protein uptake. Bacterial cell wall degrading enzyme antimicrobials can be engineered to enhance their value as potent therapeutics. PMID:27121552

  6. Drug Interactions with the Direct-Acting Antiviral Combination of Ombitasvir and Paritaprevir-Ritonavir.

    PubMed

    Badri, Prajakta S; Dutta, Sandeep; Wang, Haoyu; Podsadecki, Thomas J; Polepally, Akshanth R; Khatri, Amit; Zha, Jiuhong; Chiu, Yi-Lin; Awni, Walid M; Menon, Rajeev M

    2016-01-01

    The two direct-acting antiviral (2D) regimen of ombitasvir and paritaprevir (administered with low-dose ritonavir) is being developed for treatment of genotype subtype 1b and genotypes 2 and 4 chronic hepatitis C virus (HCV) infection. Drug-drug interactions were evaluated in healthy volunteers to develop dosing recommendations for HCV-infected subjects. Mechanism-based interactions were evaluated for ketoconazole, pravastatin, rosuvastatin, digoxin, warfarin, and omeprazole. Interactions were also evaluated for duloxetine, escitalopram, methadone, and buprenorphine-naloxone. Ratios of geometric means with 90% confidence intervals for the maximum plasma concentration and the area under the plasma concentration-time curve were estimated to assess the magnitude of the interactions. For most medications, coadministration with the 2D regimen resulted in a <50% change in exposures. Ketoconazole, digoxin, pravastatin, and rosuvastatin exposures increased by up to 105%, 58%, 76%, and 161%, respectively, and omeprazole exposures decreased by approximately 50%. Clinically meaningful changes in ombitasvir, paritaprevir, or ritonavir exposures were not observed. In summary, all 11 medications evaluated can be coadministered with the 2D regimen, with most medications requiring no dose adjustment. Ketoconazole, digoxin, pravastatin, and rosuvastatin require lower doses, and omeprazole may require a higher dose. No dose adjustment is required for the 2D regimen. PMID:26459906

  7. What is the prognosis for new centrally-acting anti-obesity drugs?

    PubMed

    Heal, David J; Gosden, Jane; Smith, Sharon L

    2012-07-01

    Obesity is a global problem that is predominantly caused by the increasing adoption of a low-cost, Westernised diet that is rich in fat and sugar and a more sedentary lifestyle. The costs of this epidemic are substantial increases in Type 2 diabetes, cardiovascular disease and some types of cancer that are certain to place a huge burden on individuals, healthcare providers and society. In this review, we provide an overview of the chequered history of pharmacotherapy for the treatment of obesity and an analysis of the regulatory and commercial challenges for developing new centrally-acting drugs in this metabolic indication. The efficacy and safety of the drug candidates that are currently at the pre-registration phase, i.e., lorcaserin, Qnexa and Contrave, are critically assessed. The main focus, however, is to provide a comprehensive review of the wide range of novel CNS compounds that are in the discovery phase or early clinical development. The profiles of various clinical candidates in animal models of obesity predict that several new CNS approaches in the clinic have the potential to deliver greater weight-loss than existing agents. This article is part of a Special Issue entitled 'Central Control of Food Intake'. PMID:22313529

  8. Drug Interactions with the Direct-Acting Antiviral Combination of Ombitasvir and Paritaprevir-Ritonavir

    PubMed Central

    Dutta, Sandeep; Wang, Haoyu; Podsadecki, Thomas J.; Polepally, Akshanth R.; Khatri, Amit; Zha, Jiuhong; Chiu, Yi-Lin; Awni, Walid M.; Menon, Rajeev M.

    2015-01-01

    The two direct-acting antiviral (2D) regimen of ombitasvir and paritaprevir (administered with low-dose ritonavir) is being developed for treatment of genotype subtype 1b and genotypes 2 and 4 chronic hepatitis C virus (HCV) infection. Drug-drug interactions were evaluated in healthy volunteers to develop dosing recommendations for HCV-infected subjects. Mechanism-based interactions were evaluated for ketoconazole, pravastatin, rosuvastatin, digoxin, warfarin, and omeprazole. Interactions were also evaluated for duloxetine, escitalopram, methadone, and buprenorphine-naloxone. Ratios of geometric means with 90% confidence intervals for the maximum plasma concentration and the area under the plasma concentration-time curve were estimated to assess the magnitude of the interactions. For most medications, coadministration with the 2D regimen resulted in a <50% change in exposures. Ketoconazole, digoxin, pravastatin, and rosuvastatin exposures increased by up to 105%, 58%, 76%, and 161%, respectively, and omeprazole exposures decreased by approximately 50%. Clinically meaningful changes in ombitasvir, paritaprevir, or ritonavir exposures were not observed. In summary, all 11 medications evaluated can be coadministered with the 2D regimen, with most medications requiring no dose adjustment. Ketoconazole, digoxin, pravastatin, and rosuvastatin require lower doses, and omeprazole may require a higher dose. No dose adjustment is required for the 2D regimen. PMID:26459906

  9. Design and synthesis of HIV-1 protease inhibitors for a long-acting injectable drug application.

    PubMed

    Kesteleyn, Bart; Amssoms, Katie; Schepens, Wim; Hache, Geerwin; Verschueren, Wim; Van De Vreken, Wim; Rombauts, Klara; Meurs, Greet; Sterkens, Patrick; Stoops, Bart; Baert, Lieven; Austin, Nigel; Wegner, Jörg; Masungi, Chantal; Dierynck, Inge; Lundgren, Stina; Jönsson, Daniel; Parkes, Kevin; Kalayanov, Genadiy; Wallberg, Hans; Rosenquist, Asa; Samuelsson, Bertil; Van Emelen, Kristof; Thuring, Jan Willem

    2013-01-01

    The design and synthesis of novel HIV-1 protease inhibitors (PIs) (1-22), which display high potency against HIV-1 wild-type and multi-PI-resistant HIV-mutant clinical isolates, is described. Lead optimization was initiated from compound 1, a Phe-Phe hydroxyethylene peptidomimetic PI, and was directed towards the discovery of new PIs suitable for a long-acting (LA) injectable drug application. Introducing a heterocyclic 6-methoxy-3-pyridinyl or a 6-(dimethylamino)-3-pyridinyl moiety (R(3)) at the para-position of the P1' benzyl fragment generated compounds with antiviral potency in the low single digit nanomolar range. Halogenation or alkylation of the metabolic hot spots on the various aromatic rings resulted in PIs with high stability against degradation in human liver microsomes and low plasma clearance in rats. Replacing the chromanolamine moiety (R(1)) in the P2 protease binding site by a cyclopentanolamine or a cyclohexanolamine derivative provided a series of high clearance PIs (16-22) with EC(50)s on wild-type HIV-1 in the range of 0.8-1.8 nM. PIs 18 and 22, formulated as nanosuspensions, showed gradual but sustained and complete release from the injection site over two months in rats, and were therefore identified as interesting candidates for a LA injectable drug application for treating HIV/AIDS. PMID:23177258

  10. The effect of thyroid hormones on the action of some centrally acting drugs.

    PubMed

    Coville, P F; Telford, J M

    1970-12-01

    1. The effect of administration of thyroxine or thyroidectomy on the pharmacological action of (+)-amphetamine, caffeine, hexobarbitone and morphine was determined in rats or mice.2. Locomotor activity induced by (+)-amphetamine or caffeine was increased by hyperthyroidism and decreased by hypothyroidism.3. The LD50s of (+)-amphetamine and caffeine in hyperthyroid rats were 1/30 and 2/5 that of control rats. With each drug, the LD50 regression lines in hyperthyroid and control rats were not parallel, suggesting that hyperthyroidism modifies the mechanism of the toxic effects. Hypothyroidism reduced toxicity to (+)-amphetamine.4. Hexobarbitone sleeping time was prolonged in hyperthyroid male rats, but was shortened in hyperthyroid female rats. In control rats, sleeping time was approximately four times as long in females as it was in males. Ethinyloestradiol treatment and castration also prolonged sleeping time in male rats. No further prolongation was produced by combined administration of thyroxine and ethinyloestradiol, but thyroxine further prolonged the sleeping time of castrated rats indicating that its mode of action in producing these changes is not mediated via sex hormones.5. In contrast to rats, a sex difference in the duration of action of hexobarbitone was not found in mice. Thyroxine prolonged sleeping time equally in each sex.6. Analgesia induced by morphine in mice was unaffected by hyperthyroidism. No increase in sedative or ;Straub tail' activity could be detected, but toxicity was increased when higher doses of morphine were used.7. The mechanism by which thyroid hormones produce these changes in sensitivity to centrally acting drugs is discussed. It is suggested that the effects of thyroxine vary according to whether the mode of action of the drug or its metabolism is modified. PMID:5531341

  11. The effects of drugs on cough.

    PubMed

    Irwin, R S; Curley, F J; Pratter, M R

    1987-01-01

    The pharmacologic treatment of cough can be divided into two main categories: therapy with controls, prevents or eliminates cough (i.e., antitussive) and therapy that makes cough more effective (i.e., pro-tussive). Definitive antitussive therapy depends on determining the aetiology or operant pathophysiologic mechanism and then initiating specific treatment; it can be almost uniformly successful. Non-specific antitussive therapy is directed at the symptom; it is indicated when definitive therapy cannot be given. For pathologic cough in man, predominantly studied in patients with chronic bronchitis, the following non-specific antitussive drugs have been shown to be effective: aerosolized ipratropium bromide, all narcotics of the phenanthrene alkaloid group (e.g., morphine and codeine), and the non-narcotics, dextromethorphan, glaucine, diphenhydramine, caramiphen, viminol and diviminol. Although studies have shown that hypertonic saline aerosol can improve cough clearance, there are no data, to date, that have convincingly demonstrated this agent or any other pro-tussive drug to be clinically useful. PMID:3322860

  12. 77 FR 58848 - Prescription Drug User Fee Act V Patient-Focused Drug Development; Consultation Meetings; Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-24

    ...The Food and Drug Administration (FDA) is issuing this notice to request that patient stakeholders notify FDA of their intention to participate in periodic consultation meetings on process issues related to FDA's patient-focused drug development initiative. This initiative is being conducted to fulfill FDA performance commitments made as part of the fifth authorization of the Prescription Drug......

  13. Pharmacological study of the antitussive and respiratory-analeptic properties of N-(2'-ethylpyrrolidino)diphenylacetamide hydrochloride (F 1459).

    PubMed

    Tarayre, J P; Vilain, P; Lauressergues, H; Cauquil, J; Bru, M; Caillol, V; Pouget, G; Jougla, A M; Go, M

    1983-01-01

    The antitussive and respiratory stimulant properties of N-(2'-ethylpyrrolidino)diphenylacetamide hydrochloride (F 1459) in animals are reported. In the mechanical stimulation of the trachea in guinea pigs and after intraperitoneal administration of the product, F 1459 showed a better antitussive action as compared to oxeladin, zipeprol, codeine and clobutinol. Low intraduodenal doses of F 1459 also reduced in cats the cough induced by the electrical stimulation of the superior laryngeal nerve. In anesthetized dogs whose respiratory functions had been depressed by morphine, F 1459 significantly increased the volume inspired per minute, an effect not due to any uncoupling effect on oxidative phosphorylation. F 1459 has local anesthetic and broncholytic properties that may play a role in the mechanism of its antitussive action. Contrarily to codeine, the test compound did not induce a decrease in the intestinal transit. PMID:6684929

  14. Differential profile and treatment development of drug-addicted patients depending on violent behaviours and/or criminal acts.

    PubMed

    López-Goñi, José J; Fernández-Montalvo, Javier; Arteaga, Alfonso; Cacho, Raúl

    2015-01-01

    This study explored the prevalence of violent and/or criminal behaviors in drug-addicted patients. A sample of 252 drug-addicted patients who sought treatment was assessed. Information was collected on violent behaviors, criminal acts, socio-demographic factors, consumption factors, psychopathological factors, and personality variables. The sample was divided into 4 groups according to the presence of violence and/or criminal behaviors. There were significant differences between the groups on some variables. In general, patients associated with both violence and criminal behaviors showed a greater severity in drug consumption and maladjustment variables, as well as a higher rate of treatment dropout and re-entry. PMID:25774971

  15. In vitro bioequivalence approach for a locally acting gastrointestinal drug: lanthanum carbonate.

    PubMed

    Yang, Yongsheng; Shah, Rakhi B; Yu, Lawrence X; Khan, Mansoor A

    2013-02-01

    A conventional human pharmacokinetic (PK) in vivo study is often considered as the "gold standard" to determine bioequivalence (BE) of drug products. However, this BE approach is not always applicable to the products not intended to be delivered into the systemic circulation. For locally acting gastrointestinal (GI) products, well designed in vitro approaches might be more practical in that they are able not only to qualitatively predict the presence of the active substance at the site of action but also to specifically assess the performance of the active substance. For example, lanthanum carbonate chewable tablet, a locally acting GI phosphate binder when orally administrated, can release free lanthanum ions in the acid environment of the upper GI tract. The lanthanum ions directly reach the site of action to bind with dietary phosphate released from food to form highly insoluble lanthanum-phosphate complexes. This prevents the absorption of phosphate consequently reducing the serum phosphate. Thus, using a conventional PK approach to demonstrate BE is meaningless since plasma levels are not relevant for local efficacy in the GI tract. Additionally the bioavailability of lanthanum carbonate is less than 0.002%, and therefore, the PK approach is not feasible. Therefore, an alternative assessment method is required. This paper presents an in vitro approach that can be used in lieu of PK or clinical studies to determine the BE of lanthanum carbonate chewable tablets. It is hoped that this information can be used to finalize an in vitro guidance for BE studies of lanthanum carbonate chewable tablets as well as to assist with "in vivo" biowaiver decision making. The scientific information might be useful to the pharmaceutical industry for the purpose of planning and designing future BE studies. PMID:23249191

  16. 28 CFR 0.177 - Applications for orders under the Comprehensive Drug Abuse Prevention and Control Act.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Applications for orders under the Comprehensive Drug Abuse Prevention and Control Act. 0.177 Section 0.177 Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE Assigning Responsibility Concerning Applications for Orders Compelling Testimony or...

  17. Federal Strategy for Prevention of Drug Abuse and Drug Trafficking, 1982. Prepared for the President Pursuant to the Drug Abuse Office and Treatment Act of 1972.

    ERIC Educational Resources Information Center

    Office of Policy Development, Washington, DC.

    This document describes the Federal response to drug abuse and drug trafficking. The actions of President Reagan, in Executive Order 12368, establishing an official advisor on drug abuse policy matters, and the priorities, issues, and objectives (international cooperation, drug law enforcement, education and prevention, detoxification and…

  18. Ex vivo activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of Plasmodium falciparum

    PubMed Central

    2012-01-01

    Background The aim of the present work was to assess i) ex vivo activity of pyronaridine (PND) and piperaquine (PPQ), as new components of artemisinin-based combination therapy (ACT), to define susceptibility baseline, ii) their activities compared to other partner drugs, namely monodesethylamodiaquine (MDAQ), lumefantrine (LMF), mefloquine (MQ), artesunate (AS) and dihydroartemisinin (DHA) against 181 Plasmodium falciparum isolates from African countries, India and Thailand, and iii) in vitro cross-resistance with other quinoline drugs, chloroquine (CQ) or quinine (QN). Methods The susceptibility of the 181 P. falciparum isolates to the nine anti-malarial drugs was assessed using the standard 42-hours 3H-hypoxanthine uptake inhibition method. Results The IC50 values for PND ranged from 0.55 to 80.0 nM (geometric mean = 19.9 nM) and from 11.8 to 217.3 nM for PPQ (geometric mean = 66.8 nM). A significant positive correlation was shown between responses to PPQ and PND responses (rho = 0.46) and between PPQ and MDAQ (rho = 0.30). No significant correlation was shown between PPQ IC50 and responses to other anti-malarial drugs. A significant positive correlation was shown between responses to PND and MDAQ (rho = 0.37), PND and LMF (rho = 0.28), PND and QN (rho = 0.24), PND and AS (rho = 0.19), PND and DHA (rho = 0.18) and PND and CQ (rho = 0.16). All these coefficients of correlation are too low to suggest cross-resistance between PPQ or PND and the other drugs. Conclusions In this study, the excellent anti-malarial activity of PPQ and PND was confirmed. The absence of cross-resistance with quinolines and artemisinin derivatives is consistent with the efficacy of the combinations of PPQ and DHA or PND and AS in areas where parasites are resistant to conventional anti-malarial drugs. PMID:22333675

  19. Comparison of the effects of two opioid antitussives, vadocaine hydrochloride, clobutinol and lidocaine on lung mechanics in guinea-pigs.

    PubMed

    Salonen, R O

    1988-04-01

    Intravenous administration of opioids, e.g. morphine and codeine, causes bronchoconstriction in animals and susceptible patients such as asthmatics. Therefore, the effects of two opioid antitussives (codeine and dextromethorphan), two non-opioid antitussives (vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl) propionanilide hydrochloride, OR K-242-HCl; INN: vadocaine) and clobutinol), and lidocaine on basal lung mechanics and methacholine (MeCh, 6 micrograms/kg i.v.)-induced airway obstruction were investigated in anaesthetized guinea-pigs. Intravenous administration of codeine (10-20 mg/kg) produced a dual response in the airways; initial bronchoconstriction was followed by attenuation of the MeCh-response. Dextromethorphan (10 and 15 mg/kg) caused bronchoconstriction only. Both the opioids affected dynamic lung compliance (CDyn) more than lung resistance (RL). At doses between 1 and 20 mg/kg i.v., vadocaine, clobutinol, and lidocaine had no obvious effect on the airways. Dextromethorphan and vadocaine, both at doses of 10 and 15 mg/kg, and clobutinol (15 and 20 mg/kg) caused irreversible bradycardia and hypotension, whereas codeine (5-20 mg/kg) increased blood pressure, and to a lesser extent heart rate. These results suggest that intravenous administration of an opioid antitussive influences the small peripheral airways more than the large airways, whether the opioid has euphoric analgesic properties or not. In contrast to this, non-opioid antitussives such as vadocaine and clobutinol are without effect. At large doses, all antitussives influence the cardiovascular system considerably. PMID:3395396

  20. The ethics of postmarketing observational studies of drug safety under section 505(o)(3) of the Food, Drug, and Cosmetic Act.

    PubMed

    Evans, Barbara J

    2012-01-01

    In 2007, Congress granted the Food and Drug Administration (FDA) new powers to order pharmaceutical companies to conduct drug safety studies and clinical trials in the postmarketing period after drugs are approved The methodologies include observational studies that examine patients' insurance claims data and clinical records to infer whether drugs are safe in actual clinical practice. Such studies offer a valuable tool for improving drug safety, but they raise ethical and privacy concerns because they would entail widespread use of patients' health information in commercial research by drug manufacturers. This is the first article to explore the ethics of these section 505(0)(3) observational studies, so named after the section of the Food, Drug, and Cosmetic Act that authorizes them. Data access problems threaten to make the FDA's section 505(0)(3) study requirements unenforceable. Under existing federal privacy regulations, it appears highly unlikely that pharmaceutical companies will have reliable access to crucial data resources, such as insurance claims data and healthcare records, to use in these studies. State privacy laws present another potential barrier to data access. If pharmaceutical companies do manage to gain access to the needed data, this will raise serious privacy concerns because section 505(0)(3) observational studies do not appear to be covered by any of the major federal regulations that afford ethical and privacy protections to persons whose data are used in research. If the FDA's program of section 505(o)(3) observational studies fails because of the above problems, this failure will have a number of bad consequences: the public will be exposed to avoidable drug safety risks; taxpayers may be forced to bear the costs of having the FDA conduct drug safety investigations that would have been funded by drug manufacturers if data had been available; and, perhaps most troubling, the FDA may be forced to order postmarketing clinical trials to

  1. Do cyclodextrins bound to dextran microspheres act as sustained delivery systems of drugs?

    PubMed

    Constantin, Marieta; Bucatariu, Sanda; Harabagiu, Valeria; Ascenzi, Paolo; Fundueanu, Gheorghe

    2014-07-20

    The use of cyclodextrins (CDs) for controlled delivery of drugs is largely presented in the literature. However, the question of whether CDs themselves linked to a polymeric network are able to sustain the release of drugs still persists. Here, CD immobilization within dextran microspheres is reported, and CD-dextran complexes were packed in a glass column and then, the retention time of different drugs and drug model compounds was determined by liquid chromatography. The release profiles of drugs and of drug model compounds (indole, 3-nitrophenol, p-hydroxybenzoic acid, diclofenac), characterized by different values of the retention time (high, moderate or low), were investigated. The release rates were quite high even for drugs that exhibit very high retention time (high association equilibrium constant). Moreover, the volume of the release fluid strongly influences the rate of drug release. As a whole, "the sink conditions" must be continuously maintained, since at each drug concentration in the release medium, equilibrium occurs between the free and the CD-bound drug. PMID:24726631

  2. Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; policies, requirements, and administrative procedures; delay of effective date. Final rule; delay of effective date.

    PubMed

    2004-02-23

    The Food and Drug Administration (FDA) is further delaying, until December 1, 2006, the effective date of certain requirements of a final rule published in the Federal Register of December 3, 1999 (64 FR 67720). In the Federal Register of May 3, 2000 (65 FR 25639), the agency delayed until October 1, 2001, the effective date of certain requirements in the final rule relating to wholesale distribution of prescription drugs by distributors that are not authorized distributors of record, and distribution of blood derivatives by entities that meet the definition of a "health care entity" in the final rule. The agency further delayed the effective date of these requirements in three subsequent Federal Register notices. Most recently, in the Federal Register of January 31, 2003 (68 FR 4912), FDA delayed the effective date until April 1, 2004. This action further delays the effective date of these requirements until December 1, 2006. The final rule implements the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA), and the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). The agency is taking this action to address concerns about the requirements in the final rule raised by affected parties. As explained in the SUPPLEMENTARY INFORMATION section, FDA is working with stakeholders through its counterfeit drug initiative to facilitate widespread, voluntary adoption of track and trace technologies that will generate a de facto electronic pedigree, including prior transaction history back to the original manufacturer, as a routine course of business. If this technology is widely adopted, it is expected to help fulfill the pedigree requirements of the PDMA and obviate or resolve many of the concerns that have been raised with respect to the final rule by ensuring that an electronic pedigree travels with a drug product at all times. Therefore, it is necessary to delay the effective date of Sec

  3. Modeling the Overproduction of Ribosomes when Antibacterial Drugs Act on Cells.

    PubMed

    Maitra, Arijit; Dill, Ken A

    2016-02-01

    Bacteria that are subjected to ribosome-inhibiting antibiotic drugs show an interesting behavior: Although the drug slows down cell growth, it also paradoxically increases the cell's concentration of ribosomes. We combine our earlier nonlinear model of the energy-biomass balance in undrugged Escherichia coli cells with Michaelis-Menten binding of drugs that inactivate ribosomes. Predictions are in good agreement with experiments on ribosomal concentrations and synthesis rates versus drug concentrations and growth rates. The model indicates that the added drug drives the cell to overproduce ribosomes, keeping roughly constant the level of ribosomes producing ribosomal proteins, an important quantity for cell growth. The model also predicts that ribosomal production rates should increase and then decrease with added drug. This model gives insights into the driving forces in cells and suggests new experiments. PMID:26840738

  4. Potential for Drug-Drug Interactions between Antiretrovirals and HCV Direct Acting Antivirals in a Large Cohort of HIV/HCV Coinfected Patients

    PubMed Central

    Poizot-Martin, Isabelle; Naqvi, Alissa; Obry-Roguet, Véronique; Valantin, Marc-Antoine; Cuzin, Lise; Billaud, Eric; Cheret, Antoine; Rey, David; Jacomet, Christine; Duvivier, Claudine; Pugliese, Pascal; Pradat, Pierre; Cotte, Laurent

    2015-01-01

    Objectives Development of direct acting antivirals (DAA) offers new benefits for patients with chronic hepatitis C. The combination of these drugs with antiretroviral treatment (cART) is a real challenge in HIV/HCV coinfected patients. The aim of this study was to describe potential drug-drug interactions between DAAs and antiretroviral drugs in a cohort of HIV/HCV coinfected patients. Methods Cross-sectional study of all HIV/HCV coinfected patients attending at least one visit in 2012 in the multicenter French Dat’AIDS cohort. A simulation of drug-drug interactions between antiretroviral treatment and DAAs available in 2015 was performed. Results Of 16,634 HIV-infected patients, 2,511 had detectable anti-HCV antibodies, of whom 1,196 had a detectable HCV-RNA and were not receiving HCV treatment at the time of analysis. 97.1% of these patients were receiving cART and 81.2% had a plasma HIV RNA <50 copies/mL. cART included combinations of nucleoside reverse transcriptase inhibitors with a boosted protease inhibitor in 43.6%, a non-nucleoside reverse transcriptase inhibitor in 17.3%, an integrase inhibitor in 15.4% and various combinations or antiretroviral drugs in 23.7% of patients. A previous treatment against HCV had been administered in 64.4% of patients. Contraindicated associations/potential interactions were expected between cART and respectively sofosbuvir (0.2%/0%), sofosbuvir/ledipasvir (0.2%/67.6%), daclatasvir (0%/49.4%), ombitasvir/boosted paritaprevir (with or without dasabuvir) (34.4%/52.2%) and simeprevir (78.8%/0%). Conclusions Significant potential drug-drug interactions are expected between cART and the currently available DAAs in the majority of HIV/HCV coinfected patients. Sofosbuvir/ledipasvir and sofosbuvir/daclatasvir with or without ribavirin appeared the most suitable combinations in our population. A close collaboration between hepatologists and HIV/AIDS specialists appears necessary for the management of HCV treatment concomitantly to c

  5. EthA, a Common Activator of Thiocarbamide-Containing Drugs Acting on Different Mycobacterial Targets▿

    PubMed Central

    Dover, Lynn G.; Alahari, Anuradha; Gratraud, Paul; Gomes, Jessica M.; Bhowruth, Veemal; Reynolds, Robert C.; Besra, Gurdyal S.; Kremer, Laurent

    2007-01-01

    Many of the current antimycobacterial agents require some form of cellular activation unmasking reactive groups, which in turn will bind to their specific targets. Therefore, understanding the mechanisms of activation of current antimycobacterials not only helps to decipher mechanisms of drug resistance but may also facilitate the development of alternative activation strategies or of analogues that do not require such processes. Herein, through the use of genetically defined strains of Mycobacterium bovis BCG we provide evidence that EthA, previously shown to activate ethionamide, also converts isoxyl (ISO) and thiacetazone (TAC) into reactive species. These results were further supported by the development of an in vitro assay using purified recombinant EthA, which allowed direct assessment of the metabolism of ISO. Interestingly, biochemical analysis of [14C]acetate-labeled cultures suggested that all of these EthA-activated drugs inhibit mycolic acid biosynthesis via different mechanisms through binding to specific targets. This report is also the first description of the molecular mechanism of action of TAC, a thiosemicarbazone antimicrobial agent that is still used in the treatment of tuberculosis as a second-line drug in many developing countries. Altogether, the results suggest that EthA is a common activator of thiocarbamide-containing drugs. The broad specificity of EthA can now be used to improve the activation process of these drugs, which may help overcome the toxicity problems associated with clinical thiocarbamide use. PMID:17220416

  6. The Regulation of Medical Computer Software as a “Device” under the Food, Drug, and Cosmetic Act

    PubMed Central

    Brannigan, Vincent

    1986-01-01

    Recent developments in computer software have raised the possibility that federal regulators may claim to control medical computer software as a “device” under the Food, Drug and Cosmetic Act. The purpose of this paper is to analyze the FDCA to determine whether computer software is included in the statutory scheme, examine constitutional arguments relating to computer software, and discuss regulatory principles that should be taken into account when deciding appropriate regulation. This paper is limited to computer program output used by humans in deciding appropriate medical therapy for a patient.

  7. Direct-acting antiviral drugs for the treatment of chronic hepatitis C virus infection: Interferon free is now.

    PubMed

    Florian, J; Mishra, P; Arya, V; Harrington, P; Connelly, S; Reynolds, K S; Sinha, V

    2015-10-01

    Chronic hepatitis C (CHC) is a global, serious, and life-threatening disease. Virologic response at 12 weeks post-treatment (SVR12) signifies a durable virologic response and is currently the primary efficacy endpoint used in registrational trials. This change led to more rapid clinical development and earlier approvals of highly effective and well-tolerated therapies, facilitating access to those in need. Hepatitis C virus (HCV) infection is a therapeutic area where mathematical modeling has proven helpful in understanding the drug mechanism and characterizing viral kinetics to inform therapy decisions. The availability of direct-acting antivirals (DAAs) provides various treatment options for HIV/HCV coinfected patients, but the complexity of predicting and managing drug-drug interactions presents a unique challenge. Real-world experience or noninterventional studies can provide insight regarding the safety and use of therapeutics that may not be readily available from traditional clinical trials. This article provides a brief overview of the development of promising drugs for the treatment of CHC. PMID:26179495

  8. 75 FR 996 - Medicare Prescription Drug, Improvement, and Modernization Act of 2003 Section 1013: Request for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-07

    ... Modernization Act of 2003 Section 1013: Request for Nominations--The Effective Health Care Stakeholder Group... nominations for the Effective Health Care Stakeholder Group. SUMMARY: The DHHS Agency for Healthcare Research... members of the Stakeholder Group to support the work of the Effective Health Care Program,...

  9. 76 FR 58279 - Animal Drug User Fee Act; Public Meeting; Request for Comments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-20

    ... Parks, Food and Drug Administration, Center for Veterinary Medicine, 7519 Standish Pl., Rockville, MD... Administration, Center for Veterinary Medicine, 7519 Standish Pl., Rockville, MD 20855, 240-276-9724, FAX: 240... seating is limited. FDA may limit the number of participants from each organization based on...

  10. 78 FR 57320 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules on Foreign Supplier...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-18

    ...The Food and Drug Administration (FDA or we) is announcing two public meetings to discuss two proposed rules aimed at strengthening assurances that imported food meets the same safety standards as food produced domestically. The Foreign Supplier Verification Programs (FSVP) proposal establishes requirements for importers to verify that their foreign suppliers are implementing the modern,......

  11. Double Jeopardy: An Assessment of the Felony Drug Provision of the Welfare Reform Act.

    ERIC Educational Resources Information Center

    Adams, Rukaiyah; Onek, David; Riker, Alissa

    In 1996 the Aid to Families with Dependent Children program was replaced with a federal block grant program called Temporary Assistance for Needy Families (TANF), which imposed time limits and work requirements on welfare recipients. The welfare legislation placed a lifetime ban on TANF and food stamp benefits for convicted drug felons, although…

  12. 75 FR 32483 - Prescription Drug User Fee Act; Meetings on Reauthorization; Request for Notification of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-08

    ... reauthorization (75 FR 12555, March 16, 2010). This meeting and written comments submitted to the docket have...; Request for Notification of Stakeholder Intention to Participate AGENCY: Food and Drug Administration, HHS...) is issuing this notice to request that public stakeholders--including patient and consumer...

  13. Triple-acting antimicrobial treatment for drug-resistant and intracellular Staphylococcus aureus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multi-drug resistant bacteria are a persistent problem in modern health care, food safety and animal health. There is a need for new antimicrobials to replace over-used conventional antibiotics. Staphylococcus aureus (S. aureus) is a notorious pathogen for both animal and human health with multi-d...

  14. Triple-acting antimicrobial treatment for drug-resistant and intracellular Staphylococcus aureus.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multi-drug resistant bacteria are a persistent problem in modern health care, food safety and animal health. There is a need for new antimicrobials to replace over-used conventional antibiotics. Staphylococcus aureus (S. aureus) is a notorious pathogen for both animal and human health with multi-d...

  15. Triple-acting Peptidoglycan hydrolase treatment for drug-resistant and intracellular Staphylococcus aureus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multi-drug resistant bacteria are a persistent problem in modern health care, food safety and animal health. There is a need for new antimicrobials to replace over-used conventional antibiotics. Staphylococcus aureus (S. aureus) is a notorious pathogen for both animal and human health with multi-d...

  16. COPD - control drugs

    MedlinePlus

    Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - control drugs; ...

  17. Time to act: a call for comprehensive responses to HIV in people who use drugs

    PubMed Central

    Beyrer, Chris; Malinowska-Sempruch, Kasia; Kamarulzaman, Adeeba; Kazatchkine, Michel; Sidibe, Michel; Strathdee, Steffanie A

    2013-01-01

    The published work on HIV in people who use drugs shows that the global burden of HIV infection in this group can be reduced. Concerted action by governments, multilateral organisations, health systems, and individuals could lead to enormous benefits for families, communities, and societies. We review the evidence and identify synergies between biomedical science, public health, and human rights. Cost-effective interventions, including needle and syringe exchange programmes, opioid substitution therapy, and expanded access to HIV treatment and care, are supported on public health and human rights grounds; however, only around 10% of people who use drugs worldwide are being reached, and far too many are imprisoned for minor offences or detained without trial. To change this situation will take commitment, advocacy, and political courage to advance the action agenda. Failure to do so will exacerbate the spread of HIV infection, undermine treatment programmes, and continue to expand prison populations with patients in need of care. PMID:20650515

  18. Levetiracetam might act as an efficacious drug to attenuate cognitive deficits of Alzheimer's disease.

    PubMed

    Xiao, Rong

    2016-01-01

    Levetiracetam is a homologue of piracetam with an a-ethyl side-chain substitution and it is a Food and Drug Administration (FDA) approved antiepileptic drug. Recently, several studies have found that levetiracetam was able to reduce seizure frequency in epileptic seizures patients without affecting their cognitive functions. In the present review, the effects of levetiracetam on cognitive improvement were summarized in epileptic seizures patients with or without Alzheimer's disease (AD), high-grade glioma (HGG) patients and amnestic mild cognitive impairment (aMCI) patients. In addition, levetiracetam was observed to improve the cognitive deficits in normal aged animals and the transgenic animal models with AD, suggesting that levetiracetam may be a better choice for the prevention or treatment of AD. PMID:26268327

  19. Assessment of antitussive efficacy of dextromethorphan in smoking related cough: objective vs. subjective measures

    PubMed Central

    Ramsay, James; Wright, Caroline; Thompson, Rachel; Hull, David; Morice, Alyn H

    2008-01-01

    AIMS Using an established model of smokers cough we measured the antitussive effects of dextromethorphan compared with placebo. METHODS The study was a randomized, double-blind placebo controlled, crossover comparison of 22 mg 0.8 ml−1 dextromethorphan delivered pregastrically with matched placebo. Objective and subjective measurements of cough were recorded. Subjective measures included a daily diary record of cough symptoms and the Leicester quality of life questionnaire. Cough frequency was recorded using a manual cough counter. The objective measure of cough reflex sensitivity was the citric acid, dose–response cough challenge. RESULTS Dextromethorphan was significantly associated with an increase in the concentration of citric acid eliciting an average of two coughs/inhalation (C2) when compared with placebo, 1 h post dose by 0.49 mM (95% CI 0.05, 0.45, geometric mean 3.09) compared with placebo 0.24 mM (geometric mean 1.74) P < 0.05 and at 2 h 0.57 mM (95% CI 0.01, 0.43, geometric mean 3.75) compared with placebo 0.34 mM (geometric mean 2.19) P < 0.05). There was a highly significant improvement in the subjective data when compared with baseline. However, there was no significant difference between placebo and active treatment. No correlation was seen between cough sensitivity to citric acid and recorded cough counts or symptoms. When both subjective and objective data were compared with screening data there was evidence of a marked ‘placebo’ effect. CONCLUSIONS The objective measure of cough sensitivity demonstrates dextromethorphan effectively diminishes the cough reflex sensitivity. However, subjective measures do not support this. Other studies support these findings, which may represent a profound sensitivity of the cough reflex to higher influences. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Dextromethorphan is widely used as a cough suppressant in over the counter medications. Its efficacy in altering cough reflex sensitivity has been shown in

  20. Diffusion of subsidized ACTs in accredited drug shops in Tanzania: determinants of stocking and characteristics of early and late adopters

    PubMed Central

    2013-01-01

    Background Many households in sub-Saharan Africa utilize the private sector as a primary source of treatment for malaria episodes. Expanding access to effective treatment in private drug shops may help reduce incidence of severe disease and mortality. This research leveraged a longitudinal survey of stocking of subsidized artemisinin combination therapies (ACTs), an effective anti-malarial, in Accredited Drug Dispensing Outlets (ADDOs) in two regions of Tanzania. This provided a unique opportunity to explore shop and market level determinants of product diffusion in a developing country retail market. Methods 356 ADDOs in the Rukwa and Mtwara regions of Tanzania were surveyed at seven points between Feb 2011 and May 2012. Shop level audits were used to measure the availability of subsidized ACTs at each shop. Data on market and shop level factors were collected during the survey and also extracted from GIS layers. Regression and network based methodologies were used. Shops classified as early and late adopters, following Rogers’ model of product diffusion, were compared. The Bass model of product diffusion was applied to determine whether shops stocked ACTs out of a need to imitate market competitors or a desire to satisfy customer needs. Results Following the introduction of a subsidy for ACTs, stocking increased from 12% to nearly 80% over the seven survey rounds. Stocking was influenced by higher numbers of proximal shops and clinics, larger customer traffic and the presence of a licensed pharmacist. Early adopters were characterized by a larger percentage of customers seeking care for malaria, a larger catchment and sourcing from specific wholesalers/suppliers. The Bass model of product diffusion indicated that shops were adopting products in response to competitor behavior, rather than customer demand. Conclusions Decisions to stock new pharmaceutical products in Tanzanian ADDOs are influenced by a combination of factors related to both market competition

  1. Establishing a list of qualifying pathogens under the Food and Drug Administration Safety and Innovation Act. Final rule.

    PubMed

    2014-06-01

    The Food and Drug Administration (FDA or Agency) is issuing a regulation to establish a list of "qualifying pathogens'' that have the potential to pose a serious threat to public health. This final rule implements a provision of the Generating Antibiotic Incentives Now (GAIN) title of the Food and Drug Administration Safety and Innovation Act (FDASIA). GAIN is intended to encourage development of new antibacterial and antifungal drugs for the treatment of serious or life-threatening infections, and provides incentives such as eligibility for designation as a fast-track product and an additional 5 years of exclusivity to be added to certain exclusivity periods. Based on analyses conducted both in the proposed rule and in response to comments to the proposed rule, FDA has determined that the following pathogens comprise the list of ``qualifying pathogens:'' Acinetobacter species, Aspergillus species, Burkholderia cepacia complex, Campylobacter species, Candida species, Clostridium difficile, Coccidioides species, Cryptococcus species, Enterobacteriaceae (e.g., Klebsiella pneumoniae), Enterococcus species, Helicobacter pylori, Mycobacterium tuberculosis complex, Neisseria gonorrhoeae, N. meningitidis, Non-tuberculous mycobacteria species, Pseudomonas species, Staphylococcus aureus, Streptococcus agalactiae, S. pneumoniae, S. pyogenes, and Vibrio cholerae. The preamble to the proposed rule described the factors the Agency considered and the methodology used to develop the list of qualifying pathogens. As described in the preamble of this final rule, FDA applied those factors and that methodology to additional pathogens suggested via comments on the proposed rule. PMID:24908687

  2. The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol.

    PubMed

    Plevkova, J; Kollarik, M; Poliacek, I; Brozmanova, M; Surdenikova, L; Tatar, M; Mori, N; Canning, B J

    2013-07-15

    The cold-sensitive cation channel TRPM8 is a target for menthol, which is used routinely as a cough suppressant and as an additive to tobacco and food products. Given that cold temperatures and menthol activate neurons through gating of TRPM8, it is unclear how menthol actively suppresses cough. In this study we describe the antitussive effects of (-)-menthol in conscious and anesthetized guinea pigs. In anesthetized guinea pigs, cough evoked by citric acid applied topically to the tracheal mucosa was suppressed by menthol only when it was selectively administered as vapors to the upper airways. Menthol applied topically to the tracheal mucosa prior to and during citric acid application or administered continuously as vapors or as an aerosol to the lower airways was without effect on cough. These actions of upper airway menthol treatment were mimicked by cold air delivered to the upper airways but not by (+)-menthol, the inactive isomer of menthol, or by the TRPM8/TRPA1 agonist icilin administered directly to the trachea. Subsequent molecular analyses confirmed the expression of TRPM8 in a subset of nasal trigeminal afferent neurons that do not coincidently express TRPA1 or TRPV1. We conclude that menthol suppresses cough evoked in the lower airways primarily through a reflex initiated from the nose. PMID:23640596

  3. Drug-Drug Interaction of Omeprazole With the HCV Direct-Acting Antiviral Agents Paritaprevir/Ritonavir and Ombitasvir With and Without Dasabuvir.

    PubMed

    Polepally, Akshanth R; Dutta, Sandeep; Hu, Beibei; Podsadecki, Thomas J; Awni, Walid M; Menon, Rajeev M

    2016-07-01

    Paritaprevir (administered with low-dose ritonavir), ombitasvir, and dasabuvir are direct-acting antiviral agents administered as combination regimens for the treatment of chronic hepatitis C virus infection. Drug-drug interactions between 2D (ombitasvir/paritaprevir/ritonavir) or 3D (ombitasvir/paritaprevir/ritonavir and dasabuvir) regimens and omeprazole, a CYP2C19 substrate and acid-reducing agent, were evaluated in 24 healthy volunteers. Subjects received omeprazole (40 mg once daily) on day 1 and days 20-24 and the 2D or 3D regimen (ombitasvir/paritaprevir/ritonavir 25/150/100 mg once daily ± dasabuvir 250 mg twice daily) on days 6-24. Compared with omeprazole alone, coadministration with the 2D or 3D regimen decreased omeprazole geometric mean Cmax and AUCt values by 40% to 50%. Ombitasvir, dasabuvir, and ritonavir mean exposures showed <10% change, and paritaprevir mean exposures showed <20% change when the 2D or 3D regimen was administered with omeprazole compared with administration without omeprazole. Although no a priori dose adjustment is needed, a higher omeprazole dose should be considered if clinically indicated when coadministered with the 2D or 3D regimen. No dose adjustment is required for the 2D or 3D regimen when administered with omeprazole, other acid-reducing agents, or CYP2C19 inhibitors. PMID:27310328

  4. Antischizophrenic drugs of the diphenylbutylpiperidine type act as calcium channel antagonists.

    PubMed Central

    Gould, R J; Murphy, K M; Reynolds, I J; Snyder, S H

    1983-01-01

    Antischizophrenic neuroleptic drugs of the diphenylbutylpiperidine class, which includes pimozide, fluspirilene, penfluridol, and clopimozide, inhibit [3H]nitrendipine binding with IC50 values of 13-30 nM. This inhibition involves receptors for the verapamil/prenylamine class of calcium channel antagonists. These diphenylbutylpiperidines also inhibit potassium-induced calcium-dependent contractions of rat vas deferens at concentrations of 40-350 nM. Other phenothiazine and butyrophenone neuroleptics lack such potent calcium-antagonist actions. Diphenylbutylpiperidines also differ from other neuroleptics in their ability to relieve negative symptoms of schizophrenia, such as emotional withdrawal, as well as the positive symptoms which respond to all neuroleptics. We suggest that these unique antischizophrenic actions are related to a blockade by diphenylbutylpiperidines of voltage-operated calcium channels. PMID:6136040

  5. Uliginosin B, a Possible New Analgesic Drug, Acts by Modulating the Adenosinergic System

    PubMed Central

    Stolz, Eveline Dischkaln; da Costa, Paola Fontoura; Medeiros, Liciane Fernandes; Souza, Andressa; Battastini, Ana Maria Oliveira; von Poser, Gilsane Lino; Bonan, Carla; Torres, Iraci L. S.; Rates, Stela Maris Kuze

    2016-01-01

    Uliginosin B (ULI) is a natural acylphloroglucinol that has been proposed as a new molecular scaffold for developing analgesic and antidepressant drugs. Its effects seem to be due to its ability to increase monoamines in the synaptic cleft by inhibiting their neuronal uptake without binding to their respective transporters, but its exact mode of action is still unknown. Considering the importance of the purinergic system to pain transmission and its modulation by monoamines availability, the aim of this study was to investigate the involvement of adenosinergic signaling in antinociceptive effect of uliginosin B. The selective adenosine A1 receptor antagonist DPCPX and the selective A2A antagonist ZM 241385 prevented the effect of ULI in the hot-plate test in mice. Pretreatment with inhibitors of adenosine reuptake (dipyridamole) or adenosine deaminase (EHNA) did not affect the ULI effect. On the other hand, its effect was completely prevented by an inhibitor of ecto-5′-nucleotidase (AMPCP). This finding was confirmed ex vivo, whereby ULI treatment increased AMP and ATP hydrolysis in spinal cord and cerebral cortex synaptosomes, respectively. Altogether, these data indicate that activation of A1 and A2A receptors and the modulation of ecto-5′-nucleotidase activity contribute to the antinociceptive effect of ULI. PMID:27087824

  6. [Rational estimation of drug dosage through pharmacometric modeling: The case of a long-acting depot antipsychotic].

    PubMed

    Simon, N; Azorin, J-M

    2015-04-01

    Drug manufacturer seeking authorization to bring a newly medicinal compound to the market (Market Authorization Application) have to undertake various studies, each of them providing a specific report. It is however essential to know how to pool results in order to understand the behavior of the drug in all the situations likely to be encountered in clinical practice. The exploitation of these data is now carried out through pharmacometric analyzes which aim at quantifying the exposure and the response of a drug over time. These methods (named "population approach") are based on non-linear mixed effects model and therefore, on the identification of a mathematical model. A first step is to model the variations in concentrations over time by integrating the physio-pathological characteristics of the patients. At this stage, the Bayesian analysis is essential to identify and select the factors of interindividual variability. This pharmacokinetic (PK) modeling allows us to obtain the prescribed dose for each patient, but also their exposure. The second step consists in defining the relationship between exposure and effect: pharmacodynamic (PD) modeling. In psychiatry, the response can be the receptors' occupancy rate or the evolution of a clinical score (BPRS, PANSS…) over time. The final PK-PD model defines the target exposure, that is to say, the concentration values required to achieve maximum effect on the score studied without risking over-exposure. Ultimately, a Monte Carlo simulation will be conducted which will test the expected response for different doses and will facilitate a rational choice in dosage. Assessing the process behind the transition from an oral to a long-acting injectable form of an active ingredient such as aripiprazole can be done by following the same protocol. A 10- to 30-mg per day therapeutic range has thus been identified. The model incorporates all the identified factors of variability of aripiprazole (drug interactions and genetic

  7. Within-drug benefit-risk evaluation of olanzapine long-acting injection at one and two years of treatment.

    PubMed

    Detke, Holland C; Lauriello, John; Landry, John; McDonnell, David P

    2014-12-01

    We sought to evaluate the within-drug benefit-risk of olanzapine long-acting injection (LAI) using both quantitative and qualitative methods. Subjects included 1192 adult patients with schizophrenia or schizoaffective disorder who participated in clinical trials with the opportunity for at least two years of continuous treatment with olanzapine LAI (45-405 mg every two to four weeks). Using the Benefit Risk Action Team (BRAT) framework, we evaluated frequency versus duration of benefits and risks commonly observed with atypical antipsychotics. We then used the Transparent Uniform Risk/Benefit Overview (TURBO) method, which weighs the drug's two most medically serious and/or frequent adverse events versus its primary benefit (effectiveness) and an ancillary benefit. The most frequent events among all patients were remaining free of relapse (91.4% for an average of 306 days at one year, 88.4% for 546 days at two years) and symptomatic remission (81.7% for an average of 239 days at one year, 84.1% for 438 days at two years). One- and two-year incidence of ≥7% weight gain was 33.3% and 41.7%. Incidences for sexual dysfunction, hyperprolactinemia, and post-injection delirium/sedation syndrome (PDSS) were <2%. TURBO ratings unanimously selected PDSS and weight gain as key risks and resulted in an average score in the acceptable benefit-risk balance range. PMID:24996038

  8. Hepatitis C virus cures after direct acting antiviral-related drug-induced liver injury: Case report.

    PubMed

    Hasin, Yaakov; Shteingart, Shimon; Dahari, Harel; Gafanovich, Inna; Floru, Sharon; Braun, Marius; Shlomai, Amir; Verstandig, Anthony; Dery, Ilana; Uprichard, Susan L; Cotler, Scott J; Lurie, Yoav

    2016-07-18

    The United States Food and Drug Administration recently warned that the direct acting antiviral (DAA) combination hepatitis C virus (HCV) treatment of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin (PODr + R) can cause severe liver injury in patients with advanced liver disease. Drug induced liver injury was observed in a small number of patients with decompensated cirrhosis treated with other DAAs, but has not been reported in patients with compensated cirrhosis. We report a case of a 74-year-old woman with chronic HCV and Child-Pugh class A cirrhosis (compensated cirrhosis) treated with PODr + R. The patient presented on day 14 of PODr + R therapy with jaundice and new-onset ascites. Her total bilirubin level increased to 23 mg/dL and international normalized ratio rose to 1.65, while aminotransferase levels remained relatively stable. Hepatitis C treatment was discontinued on day 24 and she gradually recovered. Follow-up testing showed that she achieved a sustained virologic response. In conclusion, hepatic decompensation developed within two weeks of starting treatment with PODr + R in a patient with Child-Pugh class A cirrhosis and was characterized by jaundice and ascites with stable aminotransferase levels. Careful monitoring is warranted in patients with HCV-related cirrhosis treated with PODr + R. PMID:27458506

  9. Hepatitis C virus cures after direct acting antiviral-related drug-induced liver injury: Case report

    PubMed Central

    Hasin, Yaakov; Shteingart, Shimon; Dahari, Harel; Gafanovich, Inna; Floru, Sharon; Braun, Marius; Shlomai, Amir; Verstandig, Anthony; Dery, Ilana; Uprichard, Susan L; Cotler, Scott J; Lurie, Yoav

    2016-01-01

    The United States Food and Drug Administration recently warned that the direct acting antiviral (DAA) combination hepatitis C virus (HCV) treatment of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin (PODr + R) can cause severe liver injury in patients with advanced liver disease. Drug induced liver injury was observed in a small number of patients with decompensated cirrhosis treated with other DAAs, but has not been reported in patients with compensated cirrhosis. We report a case of a 74-year-old woman with chronic HCV and Child-Pugh class A cirrhosis (compensated cirrhosis) treated with PODr + R. The patient presented on day 14 of PODr + R therapy with jaundice and new-onset ascites. Her total bilirubin level increased to 23 mg/dL and international normalized ratio rose to 1.65, while aminotransferase levels remained relatively stable. Hepatitis C treatment was discontinued on day 24 and she gradually recovered. Follow-up testing showed that she achieved a sustained virologic response. In conclusion, hepatic decompensation developed within two weeks of starting treatment with PODr + R in a patient with Child-Pugh class A cirrhosis and was characterized by jaundice and ascites with stable aminotransferase levels. Careful monitoring is warranted in patients with HCV-related cirrhosis treated with PODr + R. PMID:27458506

  10. Cardiovascular effects of withdrawal of some centrally acting antihypertensive drugs in the rat

    PubMed Central

    Thoolen, M. J. M. C.; Timmermans, P. B. M. W. M.; Van Zwieten, P. A.

    1983-01-01

    1 We have studied on the cardiovascular effects appearing after termination of 12 day continuous infusions with clonidine (500 μg/kg/day), guanfacine (10 mg/kg/day), azepexole (B-HT 933, 10 and 60 mg/kg/day) and α-methyldopa (200 mg/kg/day) in conscious spontaneously hypertensive rats. 2 The infusions of the four drugs reduced the mean arterial pressure to approximately the same extent. 3 Following withdrawal of clonidine, a marked overshoot of heart rate and a period of blood pressure lability appeared, together with an elevation of the plasma noradrenaline concentration. 4 The severities of the withdrawal responses after cessation of infusion with clonidine and azepexole were comparable, whereas those observed after guanfacine and α-methyldopa were of an insignificant degree. 5 Precipitation of the discontinuation symptoms by i.p. injection of yohimbine (3 and 10 mg/kg) at day 12 of the infusions resulted in equally severe responses in clonidine- and guanfacine-treated animals, whereas those observed in α-methyldopa treated rats were absent or much less severe. 6 Morphine and oxymetazoline suppress the appearance of blood pressure upswings after clonidine withdrawal when applied intracerebroventricularly (10 and 30 μg/kg, respectively). The withdrawal tachycardia is abolished by i.p. injection of 30 μg oxymetazoline/kg, but not by morphine (up to 10 mg/kg). 7 These results indicate, that cessation of prolonged α2-adrenoceptor stimulation by imidazolines or azepexole leads to a cardiovascular withdrawal syndrome. Central as well as peripheral factors play a role in this phenomenon.

  11. Developments on drug discovery and on new therapeutics: highly diluted tinctures act as biological response modifiers

    PubMed Central

    2011-01-01

    Background In the search for new therapies novel drugs and medications are being discovered, developed and tested in laboratories. Highly diluted substances are intended to enhance immune system responses resulting in reduced frequency of various diseases, and often present no risk of serious side-effects due to its low toxicity. Over the past years our research group has been investigating the action of highly diluted substances and tinctures on cells from the immune system. Methods We have developed and tested several highly diluted tinctures and here we describe the biological activity of M1, M2, and M8 both in vitro in immune cells from mice and human, and in vivo in mice. Cytotoxicity, cytokines released and NF-κB activation were determined after in vitro treatment. Cell viability, oxidative response, lipid peroxidation, bone marrow and lymph node cells immunophenotyping were accessed after mice in vivo treatment. Results None of the highly diluted tinctures tested were cytotoxic to macrophages or K562. Lipopolysaccharide (LPS)-stimulated macrophages treated with all highly diluted tinctures decreased tumour necrosis factor alpha (TNF-α) release and M1, and M8 decreased IFN-γ production. M1 has decreased NF-κB activity on TNF-α stimulated reporter cell line. In vivo treatment lead to a decrease in reactive oxygen species (ROS), nitric oxide (NO) production was increased by M1, and M8, and lipid peroxidation was induced by M1, and M2. All compounds enhanced the innate immunity, but M1 also augmented acquired immunity and M2 diminished B lymphocytes, responsible to acquired immunity. Conclusions Based on the results presented here, these highly diluted tinctures were shown to modulate immune responses. Even though further investigation is needed there is an indication that these highly diluted tinctures could be used as therapeutic interventions in disorders where the immune system is compromised. PMID:22029602

  12. The redox-active drug metronidazole and thiol-depleting garlic compounds act synergistically in the protist parasite Spironucleus vortens.

    PubMed

    Williams, C F; Vacca, A R; Dunham, L; Lloyd, D; Coogan, M P; Evans, G; Graz, M; Cable, J

    2016-01-01

    Spironucleus vortens is a protozoan parasite associated with significant mortalities in the freshwater angelfish, Pterophyllum scalare. Control of this parasite is especially problematic due to restrictions on the use of the drug of choice, metronidazole (MTZ), on fish farms. Use of garlic (Allium sativum) is undergoing a renaissance following experimental validations of its antimicrobial efficiency. Ajoene ((E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide), is a stable transformation product of allicin, the primary biologically active component of garlic. In the current study, an ajoene oil crude extract had a minimum inhibitory concentration (MIC) of 40μg/ml against S. vortens. GC-MS and NMR spectroscopy revealed this ajoene extract contained a mixture of the (E) and (Z)-ajoene isomers along with diallyl disulphide (DADS) and diallyl trisulphide (DATS). The only component of the ajoene crude oil found to substantially inhibit S. vortens growth by optical density monitoring (Bioscreen C Reader) was (Z)-ajoene (MIC 16μg/ml). Ajoene oil acted in synergy with MTZ in vitro, reducing the individual MIC of this drug (4μg/ml) by 16-fold, and that of ajoene oil by 200-fold with a fractional inhibitory concentration (FIC) index of 0.263. This synergistic interaction was confirmed in vivo. S. vortens-infected Pterophyllum scalare angelfish dosed orally with 0.5% (v/w) MTZ combined with 0.05% (v/w) ajoene displayed a significant reduction in faecal trophozoite count, whilst those fed on 0.5% MTZ flakes (half the recommended oral dose) alone did not. This study demonstrates for the first time the synergistic interaction between the synthetic drug MTZ and natural ajoene oil both in vitro and in vivo. Future work should evaluate the potential synergy of ajoene and MTZ against MTZ-resistant bacteria and protists. PMID:26968264

  13. Central antitussive activity of the NK1 and NK2 tachykinin receptor antagonists, CP-99,994 and SR 48968, in the guinea-pig and cat

    PubMed Central

    Bolser, Donald C; DeGennaro, Frances C; O'Reilly, Sandra; McLeod, Robbie L; Hey, John A

    1997-01-01

    The purpose of this study was to investigate the antitussive activity and sites of action of the NK1 and NK2 tachykinin receptor antagonists, CP-99,994, SR 48968, and the racemate of SR 48968, SR 48212A in the cat and guinea-pig. Guinea-pigs were dosed subcutaneously (s.c.) with CP-99,994, SR 48212A or SR 48968 one hour before exposure to aerosols of capsaicin (0.3 mM) to elicit coughing. Coughs were detected with a microphone and counted. Intracerebroventricular (i.c.v.) cannulae were placed in the lateral cerebral ventricles of anaesthetized guinea-pigs. Approximately one week later, the animals were dosed with CP-99,994 or SR 48212A (i.c.v.) and exposed to aerosols of capsaicin (0.3 mM) to elicit coughing. Cough was produced in anaesthetized cats by mechanical stimulation of the intrathoracic trachea and was monitored from electromyograms of respiratory muscle activity. Cannulae were placed for intravenous (i.v.) or, in separate groups of animals, intravertebral arterial (i.a.) administration of CP-99,994, SR 48212A or SR 48968. Dose-response relationships for i.v. and i.a. administration of each drug were generated to determine a ratio of i.v. ED50 to i.a. ED50, known as the effective dose ratio (EDR). The EDR will be 20 or greater for a centrally active drug and less than 20 for a peripherally active drug. In the guinea-pig, CP-99,994 (0.1–30 mg kg−1, s.c.), SR 48212A (1.0–30 mg kg−1, s.c.), and SR 48968 (0.3–3.0 mg kg−1, s.c.) inhibited capsaicin-induced cough in a dose-dependent manner. Capsaicin-induced cough was also inhibited by i.c.v. administration of CP-99,994 (10 and 100 μg) or SR 48212A (100 μg). In the cat, both CP-99,994 (0.0001–0.3 mg kg−1, i.a., n=5; 0.003–3.0 mg kg−1, i.v., n=5) and SR 48212A (0.003–1.0 mg kg−1, i.a., n=5; 0.01–3.0 mg kg−1, i.v., n=5) inhibited mechanically induced cough by either the i.v. or i.a. routes in a dose-dependent manner. SR 48968 (0.001–0.3

  14. Reducing Prescriptions of Long-Acting Benzodiazepine Drugs in Denmark: A Descriptive Analysis of Nationwide Prescriptions during a 10-Year Period.

    PubMed

    Eriksen, Sophie Isabel; Bjerrum, Lars

    2015-06-01

    Prolonged consumption of benzodiazepine drugs (BZD) and benzodiazepine receptor agonists (zolpidem, zaleplon, zopiclone; altogether Z drugs) is related to potential physiological and psychological dependence along with other adverse effects. This study aimed to analyse the prescribing of long-acting BZD (half-life >10 hr), compared to short-acting BZD in Denmark during a 10-year period. Descriptive analysis of total sales data from the Danish Register of Medicinal Product Statistics, to individuals in the primary healthcare sector, of all BZD and Z drugs in the period of 2003-2013. Prescription data derive from all community and hospital pharmacies in Denmark. The prescribing of long-acting BZD was reduced from 25.8 defined daily doses (DDD)/1000 inhabitants/day in 2003 to 8.8 DDD/1000 inhabitants/day in 2013, a relative reduction of 66%. The prescribing of short-acting BZD was reduced from 26.1 DDD/1000 inhabitants/day in 2003 to 16.4 DDD/1000 inhabitants/day in 2013, a relative reduction of 37%. Prescription data in this study did not include information about indications for initiating treatments. In addition, due to compliance problems, some of the prescribed drugs may not have been consumed according to the prescription. The observed reduction in BZD use was correlated to the introduction of new national guidelines on prescription of addictive drugs, but this study was not designed to detect a causal relationship. The prescribing of long-acting BZD decreased considerably more than the prescribing of short-acting BZD in the 10-year period. PMID:25382355

  15. The effect of administering long-acting oxytetracycline and tilmicosin either by dart gun or by hand on injection site lesions and drug residues in beef cattle.

    PubMed Central

    Van Donkersgoed, J; VanderKop, M; Salisbury, C; Sears, L; Holowath, J

    1999-01-01

    Forty yearling cattle were injected intramuscularly with long-acting oxytetracycline and subcutaneously with tilmicosin by dart gun or by hand in a chute 28 days prior to slaughter. The drugs caused injection site lesions and antibiotic residues in the neck and thigh that varied by technique, dose, and site. PMID:12001341

  16. A comparison of complex sleep behaviors with two short-acting Z-hypnosedative drugs in nonpsychotic patients

    PubMed Central

    Chen, Li-Fen; Lin, Ching-En; Chou, Yu-Ching; Mao, Wei-Chung; Chen, Yi-Chyan; Tzeng, Nian-Sheng

    2013-01-01

    Objective Complex sleep behaviors (CSBs) are classified as “parasomnias” in the International Classifcation of Sleep Disorders, Second Edition (ICSD-2). To realize the potential danger after taking two short-acting Z-hypnosedative drugs, we estimated the incidence of CSBs in nonpsychotic patients in Taiwan. Methods Subjects (N = 1,220) using zolpidem or zopiclone were enrolled from the psychiatric outpatient clinics of a medical center in Taiwan over a 16-month period in 2006–2007. Subjects with zolpidem (N = 1,132) and subjects with zopiclone (N = 88) were analyzed. All subjects completed a questionnaire that included demographic data and complex sleep behaviors after taking hypnotics. Results Among zolpidem and zopiclone users, 3.28% of patients reported incidents of somnambulism or amnesic sleep-related behavior problems. The incidence of CSBs with zolpidem and zopiclone were 3.27%, and 3.41%, respectively, which was signifcantly lower than other studies in Taiwan. Conclusion These results serve as a reminder for clinicians to make inquiries regarding any unusual performance of parasomnic activities when prescribing zolpidem or zopiclone. PMID:23976857

  17. 21 CFR 511.1 - New animal drugs for investigational use exempt from section 512(a) of the act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... CFR 103.2. Conditional authorization may be granted in advance of identification of the name(s) and... drugs. (b) New animal drugs for clinical investigation in animals. A shipment or other delivery of a new animal drug or an animal feed containing a new animal drug intended for clinical investigational use...

  18. Decreased prevalence of Plasmodium falciparum resistance markers to amodiaquine despite its wide scale use as ACT partner drug in Zanzibar

    PubMed Central

    2012-01-01

    Background Zanzibar has recently undergone a rapid decline in Plasmodium falciparum transmission following combined malaria control interventions with artemisinin-based combination therapy (ACT) and integrated vector control. Artesunate-amodiaquine (ASAQ) was implemented as first-line treatment for uncomplicated P. falciparum malaria in Zanzibar in 2003. Resistance to amodiaquine has been associated with the single nucleotide polymorphism (SNP) alleles pfcrt 76T, pfmdr1 86Y, 184Y and 1246Y. An accumulation of these SNP alleles in the parasite population over time might threaten ASAQ efficacy. The aim of this study was to assess whether prolonged use of ASAQ as first-line anti-malarial treatment selects for P. falciparum SNPs associated with resistance to the ACT partner drug amodiaquine. Methods The individual as well as the combined SNP allele prevalence were compared in pre-treatment blood samples from patients with uncomplicated P. falciparum malaria enrolled in clinical trials conducted just prior to the introduction of ASAQ in 2002–2003 (n = 208) and seven years after wide scale use of ASAQ in 2010 (n = 122). Results There was a statistically significant decrease of pfcrt 76T (96–63%), pfmdr1 86Y (75–52%), 184Y (83–72%), 1246Y (28–16%) and the most common haplotypes pfcrt/pfmdr1 TYYD (46–26%) and TYYY (17–8%), while an increase of pfcrt/pfmdr1 KNFD (0.4–14%) and KNYD (1–12%). Conclusions This is the first observation of a decreased prevalence of pfcrt 76T, pfmdr1 86Y, 184Y and 1246Y in an African setting after several years of extensive ASAQ use as first-line treatment for uncomplicated malaria. This may support sustained efficacy of ASAQ on Zanzibar, although it was unexpected considering that all these SNPs have previously been associated with amodiaquine resistance. The underlying factors of these results are unclear. Genetic dilution by imported P. falciparum parasites from mainland Tanzania, a de-selection by artesunate per se

  19. Long-acting antipsychotic drugs for the treatment of schizophrenia: use in daily practice from naturalistic observations

    PubMed Central

    2012-01-01

    Background Current guidelines suggest specific criteria for oral or long-acting injectable antipsychotic drugs (LAIs). This review aims to describe the demographic and clinical characteristics of the ideal profile of the patient with schizophrenia treated with LAIs, through the analysis of nonrandomized studies. Methods A systematic review of nonrandomized studies in English was performed attempting to analyze the factors related to the choice and use of LAIs in daily practice. The contents were outlined using the Cochrane methods for nonrandomized studies and the variables included demographic as well as clinical characteristics. The available literature did not allow any statistical analysis that could be used to identify the ideal profile of patients with schizophrenia to be treated with LAIs. Results Eighty publications were selected and reviewed. Prevalence of LAI use ranged from 4.8% to 66%. The only demographic characteristics that were consistently assessed through retrieved studies were age (38.5 years in the 1970’s, 35.8 years in the 1980’s, 39.3 years in the 1990’s, to 39.5 years in the 2000’s) and gender (male > female). Efficacy was assessed through the use of various symptom scales and other indirect measurements; safety was assessed through extrapyramidal symptoms and the use of anticholinergic drugs, but these data were inconsistent and impossible to pool. Efficacy and safety results reported in the different studies yielded a good therapeutic profile with a maximum of 74% decrease in hospital admissions and the prevalence of extrapyramidal symptoms with LAIs consistently increased at 6, 12, 18, and 24 months (35.4%, 37.1%, 36.9%, and 41.3%, respectively). Conclusions This analysis of the available literature strongly suggests that further observational studies on patients with schizophrenia treated with LAIs are needed to systematically assess their demographic and clinical characteristics and the relationships between them

  20. 21 CFR 511.1 - New animal drugs for investigational use exempt from section 512(a) of the act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... CFR 103.2. Conditional authorization may be granted in advance of identification of the name(s) and... 21 Food and Drugs 6 2011-04-01 2011-04-01 false New animal drugs for investigational use exempt..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW...

  1. Similar in vitro drug release as a surrogate of therapeutic equivalence of locally acting gastrointestinal products--what is the right in vitro method?

    PubMed

    Klein, S

    2015-08-01

    There is--apart from clinical trials--an ongoing discussion on how to demonstrate therapeutic equivalence for locally applied and locally acting products in the gastrointestinal tract. Possibly, among other alternatives, in vitro drug release models could be considered surrogates of drug release and availability at the site of action. However, to date the conditions in which in vitro models provide valid surrogates of in vivo release and availability at the site of action would have to be defined. To demonstrate the potential applicability of in vitro test methods for screening therapeutic equivalence of locally applied and locally acting gastrointestinal products and also to get an idea of which would be the right dosage form for an individual patient a series of in vitro studies was performed comparing a variety of in vitro release methods ranging from pharmacopoeial methods to "patient-specific" release methods in examining drug release of four mesalazine tablet formulations intended for local drug delivery in the gastrointestinal tract. Results from this study indicated that pharmacopoeial quality control methods are hardly applicable to predict the therapeutic equivalence of such products. Moreover, comparison of the results obtained with the different in vitro methods reveal that a prediction of the therapeutic equivalence for locally acting products in the gastrointestinal tract is unlikely based on release profiles obtained in a single drug release experiment. However, results from the study also indicated that a set of individualized biorelevant in vitro test scenarios might be very useful for both demonstrating therapeutic equivalence and selecting the appropriate drug product for a particular patient. PMID:26380523

  2. Re-re-treatment of hepatitis C virus: Eight patients who relapsed twice after direct-acting-antiviral drugs

    PubMed Central

    Hartman, Joshua; Bichoupan, Kian; Patel, Neal; Chekuri, Sweta; Harty, Alyson; Dieterich, Douglas; Perumalswami, Ponni; Branch, Andrea D

    2015-01-01

    AIM: To determine risk factors associated with hepatitis C virus (HCV) treatment failure after direct acting antivirals in patients with complex treatment histories. METHODS: All HCV mono-infected patients who received treatment at our institution were queried. Analysis was restricted to patients who previously failed treatment with boceprevir (BOC) or telaprevir (TVR) and started simeprevir (SMV) and sofosbuvir (SOF) ± ribavirin (RBV) between December 2013 and June 2014. Patients with human immunodeficiency virus (HIV)/HCV co-infection or patients who received a liver transplant in the past were excluded. Viral loads were recorded while on treatment and after treatment. Data collection continued until December, 31st 2014 when data analysis was initiated. Patients missing virologic outcomes data were not included in the analysis. Analysis of 35 patients who had virologic outcome data available resulted in eight patients who were viral load negative at the end of treatment with SMF/SOF but later relapsed. Data related to patient demographics, HCV infection, and treatment history was collected in order to identify risk factors shared among patients who failed treatment with SMF/SOF. RESULTS: Eight patients who were treated with the first generation HCV protease inhibitors BOC or TVR in combination with pegylated-interferon (PEG) and RBV who failed this triple therapy were subsequently re-treated with an off-label all-oral regimen of SMV and SOF for 12 wk, with RBV in seven cases. Treatment was initiated before the Food and Drug Administration approved a 24-wk SMV/SOF regimen for patients with liver cirrhosis. All eight patients had an end of treatment response, but later relapsed. Eight (100%) patients were male. Mean age was 56 (range, 49-64). Eight (100%) patients had previously failed PEG/RBV dual therapy at least once in addition to prior failure with triple therapy. Total number of times treated ranged from 3-6 (mean 3.8). Eight (100%) patients were male had

  3. Combating Drugs in America: Putting the Drug Strategy into Action. Hearing on Examining the Administration's Drug Strategy and How It Relates to the Violent Crime Control and Law Enforcement Act (Public Law 103-322) before the Committee on the Judiciary. United States Senate, One Hundred Third Congress, Second Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Senate Committee on the Judiciary.

    Following the passage of the Violent Crime Control and Law Enforcement Act, a Senate hearing was held to examine whether the prescriptions set forth in the Act could function and how they could be implemented as part of the U.S. government's drug strategy. This transcript of the hearing contains statements (in order) by: Senators Joseph R. Biden…

  4. Asthma - control drugs

    MedlinePlus

    Asthma - inhaled corticosteroids; Asthma - long-acting beta-agonists; Asthma - leukotriene modifiers; Asthma - cromolyn; Bronchial asthma-control drugs; Wheezing - control drugs; Reactive airway disease - control drugs

  5. 76 FR 64354 - Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-18

    ...'' that appeared in the Federal Register of August 1, 2011 (76 FR 45818). In that document, FDA announced.... Background In the Federal Register of August 1, 2011 (76 FR 45818), FDA published a notice with a 78-day... HUMAN SERVICES Food and Drug Administration Burden of Food and Drug Administration Food...

  6. 78 FR 47712 - Food and Drug Administration Modernization Act of 1997: Modifications to the List of Recognized...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-06

    ... of February 25, 1998 (63 FR 9561), FDA announced the availability of a guidance entitled... meter. 13-59 Systems and software engineering--Systems and ISO/IEC 15026-4 First edition software... HUMAN SERVICES Food and Drug Administration (formerly 2004N-0226) Food and Drug...

  7. The striatal balancing act in drug addiction: distinct roles of direct and indirect pathway medium spiny neurons.

    PubMed

    Lobo, Mary Kay; Nestler, Eric J

    2011-01-01

    The striatum plays a key role in mediating the acute and chronic effects of addictive drugs, with drugs of abuse causing long-lasting molecular and cellular alterations in both dorsal striatum and nucleus accumbens (ventral striatum). Despite the wealth of research on the biological actions of abused drugs in striatum, until recently, the distinct roles of the striatum's two major subtypes of medium spiny neurons (MSNs) in drug addiction remained elusive. Recent advances in cell-type-specific technologies, including fluorescent reporter mice, transgenic, or knockout mice, and viral-mediated gene transfer, have advanced the field toward a more comprehensive understanding of the two MSN subtypes in the long-term actions of drugs of abuse. Here we review progress in defining the distinct molecular and functional contributions of the two MSN subtypes in mediating addiction. PMID:21811439

  8. The Striatal Balancing Act in Drug Addiction: Distinct Roles of Direct and Indirect Pathway Medium Spiny Neurons

    PubMed Central

    Lobo, Mary Kay; Nestler, Eric J.

    2011-01-01

    The striatum plays a key role in mediating the acute and chronic effects of addictive drugs, with drugs of abuse causing long-lasting molecular and cellular alterations in both dorsal striatum and nucleus accumbens (ventral striatum). Despite the wealth of research on the biological actions of abused drugs in striatum, until recently, the distinct roles of the striatum’s two major subtypes of medium spiny neurons (MSNs) in drug addiction remained elusive. Recent advances in cell-type-specific technologies, including fluorescent reporter mice, transgenic, or knockout mice, and viral-mediated gene transfer, have advanced the field toward a more comprehensive understanding of the two MSN subtypes in the long-term actions of drugs of abuse. Here we review progress in defining the distinct molecular and functional contributions of the two MSN subtypes in mediating addiction. PMID:21811439

  9. Evaluation of Drug-Drug Interactions between Direct-Acting Anti-Hepatitis C Virus Combination Regimens and the HIV-1 Antiretroviral Agents Raltegravir, Tenofovir, Emtricitabine, Efavirenz, and Rilpivirine.

    PubMed

    Khatri, Amit; Dutta, Sandeep; Dunbar, Martin; Podsadecki, Thomas; Trinh, Roger; Awni, Walid; Menon, Rajeev

    2016-05-01

    The three direct-acting antiviral agent (3D) regimen is a novel combination of direct-acting antiviral agents (DAAs) that has proven effective for the treatment of hepatitis C virus (HCV) infection. Given the potential for coadministration in patients with human immunodeficiency virus infection, possible drug interactions with antiretroviral drugs must be carefully considered. Four phase 1, multiple-dose pharmacokinetic studies were conducted in healthy volunteers (n = 66). The 3D regimen of 150/100 mg daily paritaprevir/ritonavir, 25 mg daily ombitasvir, and 400 mg twice-daily dasabuvir was administered alone or in combination with 200 mg daily of emtricitabine and 300 mg daily of tenofovir disoproxil fumarate (tenofovir DF), 25 mg daily of rilpivirine, or 400 mg of raltegravir twice daily. A 2-DAA regimen of 150/100 mg daily paritaprevir/ritonavir and 400 mg of dasabuvir twice daily was also studied in combination with efavirenz/emtricitabine/tenofovir DF at 600/200/300 mg daily, respectively (Atripla; Bristol-Myers Squibb). Pharmacokinetic parameters were determined from plasma drug concentrations. No clinically significant drug interactions were observed (≤32% change in exposure) between the 3D regimen and that of emtricitabine plus tenofovir DF. Raltegravir exposure was increased up to 134% when the drug was coadministered with the 3D regimen. Although coadministration with rilpivirine was well tolerated in healthy volunteers, observed elevations in rilpivirine exposures may increase the potential for adverse drug reactions. Concomitant use of the 2-DAA regimen and efavirenz/emtricitabine/tenofovir DF was discontinued owing to poor tolerability and adverse events. No dose adjustment is required during coadministration of raltegravir, tenofovir DF, or emtricitabine with the 3D regimen. Rilpivirine is not recommended and efavirenz is contraindicated for coadministration with the 3D regimen. PMID:26953200

  10. Implementation of the Comprehensive Methamphetamine Control Act of 1996; regulation of pseudoephedrine, phenylpropanolamine, and combination ephedrine drug products and reports of certain transactions to nonregulated persons. Final rule.

    PubMed

    2002-03-28

    DEA is amending its regulations to implement the requirements of the Comprehensive Methamphetamine Control Act of 1996 (MCA) with respect to the regulation of pseudoephedrine, phenylpropanolamine, and combination ephedrine drug products as List I chemicals, and the reporting of certain transactions involving pseudoephedrine, phenylpropanolamine, and combination ephedrine drug products. The MCA removed the previous exemption from regulation as List I chemicals which had applied to pseudoephedrine, phenylpropanolamine, and combination ephedrine drug products. This action makes persons who distribute the products subject to the registration requirement. Also, distributions, importations, and exportations of the products became subject to the existing chemical controls relating to regulated transactions, except in certain circumstances specified in the MCA. The MCA also requires that reports be submitted for certain distributions involving pseudoephedrine, phenylpropanolamine, and ephedrine (including drug products containing those chemicals) by Postal Service or private or commercial carrier to nonregulated persons. This final rule amends the regulations to make them consistent with the language of the MCA and to establish specific procedures to be followed to satisfy the new reporting requirement. DEA has, where possible, taken action to limit the public impact of these new requirements while remaining consistent with the intent of the MCA to attack the diversion of regulated drug products to the clandestine manufacture of methamphetamine. PMID:11922057

  11. Pharmacological control of the hormonally modulated immune response. II. Blockade of antibody production by a combination of drugs acting on neuroendocrine functions. Its prevention by gonadotropins and corticotrophin.

    PubMed Central

    Pierpaoli, W; Maestroni, G J

    1978-01-01

    Injection of a combination of three drugs, 5-hydroxytryptophan, the alpha-blocker phentolamine and the neuroleptic drug haloperidol into mice before or together with sheep red blood cells (SRBC) induces a complete and long-lasting inhibition of antibody production to SRBC and leads to specific unresponsiveness. The mice unresponsive to SRBC respond normally to another antigen. Treatment with a combination of luteotropic (LH), follicle stimulating (FSH) and corticotropic hormone (ACTH) before administration of drugs and antigen prevents the immune blockade. Injection of SRBC induces an early elevation of LH in blood. This effect is prevented by previous administration of the three drugs in combination. The hormonal response to a second injection of the same antigen of mice previously made 'unresponsive' is different from that of immunized animals. The suppression of these hormonal changes which follow antigen injection by drugs acting on neuroendocrine regulation and cell membrane adrenergic receptors represents a step forward in efforts aimed at a pharmacological control of acquired immunity. PMID:205502

  12. Identification of Known Drugs that Act as Inhibitors of NF-κB Signaling and their Mechanism of Action

    PubMed Central

    Miller, Susanne C.; Huang, Ruili; Sakamuru, Srilatha; Shukla, Sunita J.; Attene-Ramos, Matias S.; Shinn, Paul; Van Leer, Danielle; Leister, William; Austin, Christopher P.; Xia, Menghang

    2010-01-01

    Nuclear factor-kappa B (NF-κB) is a transcription factor that plays a critical role across many cellular processes including embryonic and neuronal development, cell proliferation, apoptosis, immune responses to infection, and inflammation. Dysregulation of NF-κB signaling is associated with inflammatory diseases and certain cancers. Constitutive activation of NF-κB signaling has been found in some types of tumors including breast, colon, prostate, skin and lymphoid, hence therapeutic blockade of NF-κB signaling in cancer cells provides an attractive strategy for the development of anticancer drugs. To identify small molecule inhibitors of NF-κB signaling, we screened approximately 2,800 clinically approved drugs and bioactive compounds from the NIH Chemical Genomics Center Pharmaceutical Collection (NPC) in a NF-κB mediated β-lactamase reporter gene assay. Each compound was tested at fifteen different concentrations in a quantitative high throughput screening format. We identified nineteen drugs that inhibited NF-κB signaling, with potencies as low as 20 nM. Many of these drugs, including emetine, fluorosalan, sunitinib malate, bithionol, narasin, tribromsalan, and lestaurtinib, inhibited NF-κB signaling via inhibition of IκBα phosphorylation. Others, such as ectinascidin 743, chromomycin A3 and bortezomib utilized other mechanisms. Furthermore, many of these drugs induced caspase 3/7 activity and had an inhibitory effect on cervical cancer cell growth. Our results indicate that many currently approved pharmaceuticals have previously unappreciated effects on NF-κB signaling, which may contribute to anticancer therapeutic effects. Comprehensive profiling of approved drugs provides insight into their molecular mechanisms, thus providing a basis for drug repurposing. PMID:20067776

  13. Dopamine-related drugs act presynaptically to potentiate GABA(A) receptor currents in VTA dopamine neurons.

    PubMed

    Michaeli, Avner; Yaka, Rami

    2011-01-01

    Electrical activity of ventral tegmental area (VTA) dopamine (DA) neurons is immediately inhibited following in vivo administration of cocaine and other DA-related drugs. While various forms of synaptic modulation were demonstrated in the VTA following exposure to DA-related drugs, comprehensive understanding of their ability to inhibit the activity of DA neurons, however, is still lacking. In this study, using whole-cell patch-clamp recordings from rat brain slices, a novel form of synaptic modulation induced by DA-related drugs was isolated. DA exposure was shown to cause potentiation of γ-amino-butyric acid (GABA) receptor type A (GABA(A)R)-mediated evoked inhibitory postsynaptic currents (eIPSCs), recorded from VTA DA neurons, under conditions of potassium channels blockade. The potentiation of these eIPSCs lasted for more than twenty minutes, could be mimicked by activation of D2-like but not D1-like DA receptors, and was accompanied by an increase in the frequency of GABA(A)R-mediated spontaneous miniature inhibitory postsynaptic currents (mIPSCs). Furthermore, exposure to inhibitors of DA transporter (DAT) led to potentiation of GABA(A) currents in a manner similar to the DA-mediated potentiation. Finally, a prolonged presence of l-NAME, an inhibitor of nitric-oxide (NO) signaling was found to conceal the potentiation of GABA(A) currents induced by the DA-related drugs. Taken together, this study demonstrates a new modulatory form of VTA GABA(A) neurotransmission mediated by DA-related drugs. These results also suggest better understanding of the initial inhibitory action of DA-related drugs on the activity of DA neurons in the VTA. PMID:21527263

  14. Drugs targeting the mitochondrial pore act as citotoxic and cytostatic agents in temozolomide-resistant glioma cells

    PubMed Central

    Lena, Annalisa; Rechichi, Mariarosa; Salvetti, Alessandra; Bartoli, Barbara; Vecchio, Donatella; Scarcelli, Vittoria; Amoroso, Rosina; Benvenuti, Lucia; Gagliardi, Rolando; Gremigni, Vittorio; Rossi, Leonardo

    2009-01-01

    Background High grade gliomas are one of the most difficult cancers to treat and despite surgery, radiotherapy and temozolomide-based chemotherapy, the prognosis of glioma patients is poor. Resistance to temozolomide is the major barrier to effective therapy. Alternative therapeutic approaches have been shown to be ineffective for the treatment of genetically unselected glioma patients. Thus, novel therapies are needed. Mitochondria-directed chemotherapy is an emerging tool to combat cancer, and inner mitochondrial permeability transition (MPT) represents a target for the development of cytotoxic drugs. A number of agents are able to induce MPT and some of them target MPT-pore (MPTP) components that are selectively up-regulated in cancer, making these agents putative cancer cell-specific drugs. Objective The aim of this paper is to report a comprehensive analysis of the effects produced by selected MPT-inducing drugs (Betulinic Acid, Lonidamine, CD437) in a temozolomide-resistant glioblastoma cell line (ADF cells). Methods EGFRvIII expression has been assayed by RT-PCR. EGFR amplification and PTEN deletion have been assayed by differential-PCR. Drugs effect on cell viability has been tested by crystal violet assay. MPT has been tested by JC1 staining. Drug cytostatic effect has been tested by mitotic index analysis. Drug cytotoxic effect has been tested by calcein AM staining. Apoptosis has been assayed by Hoechst incorporation and Annexine V binding assay. Authophagy has been tested by acridine orange staining. Results We performed a molecular and genetic characterization of ADF cells and demonstrated that this line does not express the EGFRvIII and does not show EGFR amplification. ADF cells do not show PTEN mutation but differential PCR data indicate a hemizygous deletion of PTEN gene. We analyzed the response of ADF cells to Betulinic Acid, Lonidamine, and CD437. Our data demonstrate that MPT-inducing agents produce concentration-dependent cytostatic and

  15. Lipid-Core Nanocapsules Act as a Drug Shuttle Through the Blood Brain Barrier and Reduce Glioblastoma After Intravenous or Oral Administration.

    PubMed

    Rodrigues, Stephen F; Fiel, Luana A; Shimada, Ana L; Pereira, Natalia R; Guterres, Silvia S; Pohlmann, Adriana R; Farsky, Sandra H

    2016-05-01

    Lipid-core nanocapsules (LNC) are formed by an organogel surrounded by poly(epsilon-caprolactone) and stabilized by polysorbate 80. LNCs increase the concentration of drugs in the brain after oral or intravenous administration. We proposed to determine whether the drug is released from the LNC to cross the blood brain barrier (BBB) or the drug-loaded LNCs can cross the BBB to release the drug. We synthesized a Rhodamine B-polymer conjugate to prepare a fluorescent-labeled LNC formulation, and intravital microscopy was used to determine the ability of the LNCs to cross the brain barrier using different administration routes in C57BI/6 mice. A glioblastoma model was used to determine the impact of the LNC as a shuttle for treatment. After pial vessel exposure, intense fluorescence was detected inside the vessels 10 min after intravenous or 20 min after intraperitoneal injections of fluorescent-labeled LNC. The fluorescence was observed in the perivascular tissue after 30 and 60 min, respectively. Increased tissue fluorescence was detected 240 min after oral administration. The integrity of the barrier was determined during the experiments. Normal leukocyte and platelet adhesion to the vessel wall indicated that Rhodamine B-labeled LNC did not cause pial vessel alterations. After intravenous or oral administration, Rhodamine B-labeled LNC-containing co-encapsulated indomethacin and indomethacin ethyl ester exhibited similar behavior in pial vessels, being more efficient in the treatment of mice with glioblastoma than indomethacin in solution. Therefore, we demonstrated that LNCs act as drug shuttles through the BBB, delivering drugs in brain tissue with high efficiency and reducing glioblastoma after intravenous or oral administration. PMID:27305820

  16. Low Frequency of Drug-Resistant Variants Selected by Long-Acting Rilpivirine in Macaques Infected with Simian Immunodeficiency Virus Containing HIV-1 Reverse Transcriptase

    PubMed Central

    Melody, Kevin; McBeth, Sarah; Kline, Christopher; Kashuba, Angela D. M.; Mellors, John W.

    2015-01-01

    Preexposure prophylaxis (PrEP) using antiretroviral drugs is effective in reducing the risk of human immunodeficiency virus type 1 (HIV-1) infection, but adherence to the PrEP regimen is needed. To improve adherence, a long-acting injectable formulation of the nonnucleoside reverse transcriptase (RT) inhibitor rilpivirine (RPV LA) has been developed. However, there are concerns that PrEP may select for drug-resistant mutations during preexisting or breakthrough infections, which could promote the spread of drug resistance and limit options for antiretroviral therapy. To address this concern, we administered RPV LA to macaques infected with simian immunodeficiency virus containing HIV-1 RT (RT-SHIV). Peak plasma RPV levels were equivalent to those reported in human trials and waned over time after dosing. RPV LA resulted in a 2-log decrease in plasma viremia, and the therapeutic effect was maintained for 15 weeks, until plasma drug concentrations dropped below 25 ng/ml. RT mutations E138G and E138Q were detected in single clones from plasma virus in separate animals only at one time point, and no resistance mutations were detected in viral RNA isolated from tissues. Wild-type and E138Q RT-SHIV displayed similar RPV susceptibilities in vitro, whereas E138G conferred 2-fold resistance to RPV. Overall, selection of RPV-resistant variants was rare in an RT-SHIV macaque model despite prolonged exposure to slowly decreasing RPV concentrations following injection of RPV LA. PMID:26438501

  17. Low Frequency of Drug-Resistant Variants Selected by Long-Acting Rilpivirine in Macaques Infected with Simian Immunodeficiency Virus Containing HIV-1 Reverse Transcriptase.

    PubMed

    Melody, Kevin; McBeth, Sarah; Kline, Christopher; Kashuba, Angela D M; Mellors, John W; Ambrose, Zandrea

    2015-12-01

    Preexposure prophylaxis (PrEP) using antiretroviral drugs is effective in reducing the risk of human immunodeficiency virus type 1 (HIV-1) infection, but adherence to the PrEP regimen is needed. To improve adherence, a long-acting injectable formulation of the nonnucleoside reverse transcriptase (RT) inhibitor rilpivirine (RPV LA) has been developed. However, there are concerns that PrEP may select for drug-resistant mutations during preexisting or breakthrough infections, which could promote the spread of drug resistance and limit options for antiretroviral therapy. To address this concern, we administered RPV LA to macaques infected with simian immunodeficiency virus containing HIV-1 RT (RT-SHIV). Peak plasma RPV levels were equivalent to those reported in human trials and waned over time after dosing. RPV LA resulted in a 2-log decrease in plasma viremia, and the therapeutic effect was maintained for 15 weeks, until plasma drug concentrations dropped below 25 ng/ml. RT mutations E138G and E138Q were detected in single clones from plasma virus in separate animals only at one time point, and no resistance mutations were detected in viral RNA isolated from tissues. Wild-type and E138Q RT-SHIV displayed similar RPV susceptibilities in vitro, whereas E138G conferred 2-fold resistance to RPV. Overall, selection of RPV-resistant variants was rare in an RT-SHIV macaque model despite prolonged exposure to slowly decreasing RPV concentrations following injection of RPV LA. PMID:26438501

  18. 78 FR 17611 - Provisions of the Food and Drug Administration Safety and Innovation Act Related to Medical Gases...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-22

    ... these new sections. On November 23, 2012 (77 FR 70166), FDA issued a Federal Register notice... FR 74852), FDA issued a notice of availability announcing publication of a draft guidance for... Administration Safety and Innovation Act Related to Medical Gases; Request for Comments Regarding...

  19. Controlled drugs.

    PubMed

    2016-05-18

    Essential facts Controlled drugs are defined and governed by the Misuse of Drugs Act 1971 and associated regulations. Examples of controlled drugs include morphine, pethidine and methadone. Since 2012, appropriately qualified nurses and midwives can prescribe controlled drugs for medical conditions within their competence. There are some exceptions when treating addiction. PMID:27191427

  20. 77 FR 15765 - Food and Drug Administration Modernization Act of 1997: Modifications to the List of Recognized...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-16

    ...The Food and Drug Administration (FDA) is announcing a publication containing modifications the Agency is making to the list of standards FDA recognizes for use in premarket reviews (FDA recognized consensus standards). This publication, entitled ``Modifications to the List of Recognized Standards, Recognition List Number: 028'' (Recognition List Number: 028), will assist manufacturers who......

  1. 78 FR 32390 - Food and Drug Administration Safety and Innovation Act (FDASIA): Request for Comments on the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-30

    ...): Request for Comments on the Development of a Risk-Based Regulatory Framework and Strategy for Health Information Technology AGENCY: Office of the National Coordinator for Health Information Technology...: The Food and Drug Administration (FDA), Office of the National Coordinator for Health...

  2. Preemptive antiretroviral therapy modifications for the management of potential clinically significant drug interactions with direct acting hepatitis C therapies.

    PubMed

    Stambough, Megan; Roman, Martha; Blair, Donald C; Sidman, Eric F; Miller, Christopher D

    2016-03-01

    We report a case series of HIV/HCV co-infected patients who underwent preemptive antiretroviral therapy modifications to manage clinically significant drug interactions with HCV therapy. Among the 15 patients reviewed, all changed to a raltegravir-based regimen and none experienced a loss of virologic suppression or increase in HIV-RNA. PMID:25824150

  3. 78 FR 52202 - Request for Comments on the Food and Drug Administration Safety and Innovation Act Section 907...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-22

    ... Management (HFA- 305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. All..., 10903 New Hampshire Ave., Bldg. 32, Rm. 2320, Silver Spring, MD 20903, ] 301-796-9441, FDASIASECTION907... subgroups in summaries of product safety and effectiveness and in labeling; on the inclusion of such...

  4. In Vivo Evaluation of the Antiasthmatic, Antitussive, and Expectorant Activities and Chemical Components of Three Elaeagnus Leaves.

    PubMed

    Ge, Yuebin; Zhang, Fei; Qin, Qin; Shang, Yingying; Wan, Dingrong

    2015-01-01

    The leaf of Elaeagnus lanceolata and Elaeagnus henryi as well as Elaeagnus pungens has been documented as an effective herb for the treatment of asthma and chronic bronchitis in traditional clinical medicine. This study was aimed at evaluating the antiasthmatic, antitussive, and expectorant activities of the water extracts from the three plants in vivo and analyzing their chemical components by HPLC-DAD. At the medium and high doses, the water extracts of three Elaeagnus leaves significantly prolonged the preconvulsive time (P < 0.01) in guinea pigs, lengthened the latent period of cough (P < 0.01) and decreased the cough frequency caused by aqueous ammonia in mice (P < 0.01), and enhanced tracheal phenol red output in mice (P < 0.01). There were no significant differences in the pharmacological actions between the three Elaeagnus leaves. Moreover, there was more similarity on overlap peaks in the range of retention time from 10 to 40 min by HPLC and many peaks that belonged to flavonoids compounds. It suggested that the main constituents of the three Elaeagnus leaves were flavonoid for the pharmacological activities. These effects were the important evidence for the traditional use of E. henryi leaf and E. lanceolata leaf as well as E. pungens to treat asthma and chronic bronchitis. PMID:26576193

  5. Suhuang antitussive capsule at lower doses attenuates airway hyperresponsiveness, inflammation, and remodeling in a murine model of chronic asthma

    PubMed Central

    Zhang, Chao; Zhang, Lan-Hong; Wu, Yin-Fang; Lai, Tian-Wen; Wang, Hai-Sheng; Xiao, Hui; Che, Luan-Qing; Ying, Song-Min; Li, Wen; Chen, Zhi-Hua; Shen, Hua-Hao

    2016-01-01

    Suhuang antitussive capsule (Suhuang), a traditional Chinese medication, is found effective in treating chronic cough and cough variant asthma (CVA). This study aimed to determine the possible effects and underlying mechanisms of Suhuang on chronic ovalbumin (OVA)-induced airway hyperresponsiveness (AHR), inflammation, and remodeling in mice. Mice were randomly assigned to six experimental groups: control, OVA model with or without Suhuang (low dose: 3.5 g/kg, middle dose: 7.0 g/kg, high dose: 14.0 g/kg), or dexamethasone (2.5 mg/kg). AHR, inflammatory cells, cytokines in bronchoalveolar lavage fluid (BALF), lung pathology, mucus production, and airway remodeling were examined. We found Suhuang treated at lower doses effectively inhibited OVA-induced AHR, airway inflammation, mucus production and collagen deposition around the airway. High dose of Suhuang reduced most of the inflammatory hallmarks while exerted inconsiderable effects on the number of macrophages in BALF and AHR. At all doses, Suhuang significantly reduced the levels of interlukin (IL) -13 and transforming growth factor (TGF)-β1, but had little effects on IL-4, IL-5, IL-17A and interferon (IFN)-γ. Thus, Suhuang administration alleviates the pathological changes of chronic asthma likely through inhibition of IL-13 and TGF-β1. Suhuang might be a promising therapy for patients with allergic asthma in the future. PMID:26861679

  6. Suhuang antitussive capsule at lower doses attenuates airway hyperresponsiveness, inflammation, and remodeling in a murine model of chronic asthma.

    PubMed

    Zhang, Chao; Zhang, Lan-Hong; Wu, Yin-Fang; Lai, Tian-Wen; Wang, Hai-Sheng; Xiao, Hui; Che, Luan-Qing; Ying, Song-Min; Li, Wen; Chen, Zhi-Hua; Shen, Hua-Hao

    2016-01-01

    Suhuang antitussive capsule (Suhuang), a traditional Chinese medication, is found effective in treating chronic cough and cough variant asthma (CVA). This study aimed to determine the possible effects and underlying mechanisms of Suhuang on chronic ovalbumin (OVA)-induced airway hyperresponsiveness (AHR), inflammation, and remodeling in mice. Mice were randomly assigned to six experimental groups: control, OVA model with or without Suhuang (low dose: 3.5 g/kg, middle dose: 7.0 g/kg, high dose: 14.0 g/kg), or dexamethasone (2.5 mg/kg). AHR, inflammatory cells, cytokines in bronchoalveolar lavage fluid (BALF), lung pathology, mucus production, and airway remodeling were examined. We found Suhuang treated at lower doses effectively inhibited OVA-induced AHR, airway inflammation, mucus production and collagen deposition around the airway. High dose of Suhuang reduced most of the inflammatory hallmarks while exerted inconsiderable effects on the number of macrophages in BALF and AHR. At all doses, Suhuang significantly reduced the levels of interlukin (IL) -13 and transforming growth factor (TGF)-β1, but had little effects on IL-4, IL-5, IL-17A and interferon (IFN)-γ. Thus, Suhuang administration alleviates the pathological changes of chronic asthma likely through inhibition of IL-13 and TGF-β1. Suhuang might be a promising therapy for patients with allergic asthma in the future. PMID:26861679

  7. In Vivo Evaluation of the Antiasthmatic, Antitussive, and Expectorant Activities and Chemical Components of Three Elaeagnus Leaves

    PubMed Central

    Ge, Yuebin; Zhang, Fei; Qin, Qin; Shang, Yingying; Wan, Dingrong

    2015-01-01

    The leaf of Elaeagnus lanceolata and Elaeagnus henryi as well as Elaeagnus pungens has been documented as an effective herb for the treatment of asthma and chronic bronchitis in traditional clinical medicine. This study was aimed at evaluating the antiasthmatic, antitussive, and expectorant activities of the water extracts from the three plants in vivo and analyzing their chemical components by HPLC-DAD. At the medium and high doses, the water extracts of three Elaeagnus leaves significantly prolonged the preconvulsive time (P < 0.01) in guinea pigs, lengthened the latent period of cough (P < 0.01) and decreased the cough frequency caused by aqueous ammonia in mice (P < 0.01), and enhanced tracheal phenol red output in mice (P < 0.01). There were no significant differences in the pharmacological actions between the three Elaeagnus leaves. Moreover, there was more similarity on overlap peaks in the range of retention time from 10 to 40 min by HPLC and many peaks that belonged to flavonoids compounds. It suggested that the main constituents of the three Elaeagnus leaves were flavonoid for the pharmacological activities. These effects were the important evidence for the traditional use of E. henryi leaf and E. lanceolata leaf as well as E. pungens to treat asthma and chronic bronchitis. PMID:26576193

  8. Sulfa and trimethoprim-like drugs - antimetabolites acting as carbonic anhydrase, dihydropteroate synthase and dihydrofolate reductase inhibitors.

    PubMed

    Capasso, Clemente; Supuran, Claudiu T

    2014-06-01

    Recent advances in microbial genomics, synthetic organic chemistry and X-ray crystallography provided opportunities to identify novel antibacterial targets for the development of new classes of antibiotics and to design more potent antimicrobial compounds derived from existing antibiotics in clinical use for decades. The antimetabolites, sulfa drugs and trimethoprim (TMP)-like agents, are inhibitors of three families of enzymes. One family belongs to the carbonic anhydrases, which catalyze a simple but physiologically relevant reaction in all life kingdoms, carbon dioxide hydration to bicarbonate and protons. The other two enzyme families are involved in the synthesis of tetrahydrofolate (THF), i.e. dihydropteroate synthase (DHPS) and dihydrofolate reductase. The antibacterial agents belonging to the THF and DHPS inhibitors were developed decades ago and present significant bacterial resistance problems. However, the molecular mechanisms of drug resistance both to sulfa drugs and TMP-like inhibitors were understood in detail only recently, when several X-ray crystal structures of such enzymes in complex with their inhibitors were reported. Here, we revue the state of the art in the field of antibacterials based on inhibitors of these three enzyme families. PMID:23627736

  9. Analysis of U.S. Food and Drug Administration food allergen recalls after implementation of the food allergen labeling and consumer protection act.

    PubMed

    Gendel, Steven M; Zhu, Jianmei

    2013-11-01

    To avoid potentially life-threatening reactions, food allergic consumers rely on information on food labels to help them avoid exposure to a food or ingredient that could trigger a reaction. To help consumers in the United States obtain the information that they need, the Food Allergen Labeling and Consumer Protection Act of 2004 defined a major food allergen as being one of eight foods or food groups and any ingredient that contains protein from one of these foods or food groups. A food that contains an undeclared major food allergen is misbranded under the U.S. Food, Drug, and Cosmetic Act and is subject to recall. Food allergen labeling problems are the most common cause of recalls for U.S. Food and Drug Administration (FDA)-regulated food products. To help understand why food allergen recalls continue to occur at a high rate, information on each food allergen recall that occurred in fiscal years 2007 through 2012 was obtained from the FDA recall database. This information was analyzed to identify the food, allergen, root cause, and mode of discovery for each food allergen recall. Bakery products were the most frequently recalled food type, and milk was the most frequently undeclared major food allergen. Use of the wrong package or label was the most frequent problem leading to food allergen recalls. These data are the first reported that indicate the importance of label and package controls as public health measures. PMID:24215698

  10. Suppression of postoperative pain by the combination of a nonsteroidal anti-inflammatory drug, flurbiprofen, and a long-acting local anesthetic, etidocaine.

    PubMed

    Dionne, R A; Wirdzek, P R; Fox, P C; Dubner, R

    1984-04-01

    The analgesic efficacy of the combination of a nonsteroidal anti-inflammatory drug, flurbiprofen, and a long-acting local anesthetic, etidocaine, was evaluated for the suppression of acute postoperative pain. Subjects having two impacted third molars removed at two appointments received either the experimental combination or standard treatment in a randomized, crossover design. The experimental treatment consisted of 100 mg flurbiprofen 30 minutes before surgery, 1.5% etidocaine with 1:200,000 epinephrine five minutes before surgery, and 100 mg flurbiprofen three hours after surgery. Standard treatment consisted of 10 mg oxycodone plus 650 mg acetaminophen 30 minutes before surgery, 2% lidocaine with 1:100,000 epinephrine five minutes before surgery, and a second dose of the oxycodone-acetaminophen combination three hours after surgery. Pain intensity was rated hourly from one to seven hours after surgery, using a variety of ordinal and analog scales. The flurbiprofen-etidocaine combination resulted in significantly less postoperative pain than the oxycodone plus acetaminophen-lidocaine combination on all four analgesic scales used and was preferred by the majority of the patients. This study shows that pretreatment with a nonsteroidal anti-inflammatory drug, flurbiprofen, in combination with a long-acting local analgesic, etidocaine, suppresses pain to a greater extent than a potent opiate mild/analgesic combination and lidocaine without an increase in side-effect liability. PMID:6586802

  11. Non-opioid antitussives and methadone differentially influence hippocampal long-term potentiation in freely moving rats.

    PubMed

    Krug, M; Matthies, R; Wagner, M; Brödemann, R

    1993-02-16

    Long-term potentiation (LTP) of monosynaptically evoked field potentials (MEFP) in the dentate gyrus of freely moving rats following tetanization of the perforant pathway was investigated after peripheral application of substances which have been shown to influence NMDA receptor-mediated effects (dextromethorphan, methadone) as well as structurally related substances with similar antitussive effects (codeine, normethadone). The noncompetitive NMDA receptor antagonist MK 801 was also tested for comparison. Whereas under control conditions the field e.p.s.p. (excitatory postsynaptic potential) and the population spike of the MEFP were largely uninfluenced by these substances, different effects were seen after the induction of LTP. MK 801 (0.2 mg/kg i.p.) suppressed the induction of LTP of both the field e.p.s.p. and the population spike. Dextromethorphan (40 mg/kg i.p.) also prevented the potentiation of the field e.p.s.p. and the population spike, thus resembling MK 801 in its effect. Codeine (20 mg/kg i.p.), the levorotatory structural analogue of dextromethorphan had no effect. Methadone and normethadone did not influence the potentiation of the field e.p.s.p. or interfere with the induction of potentiation of the population spike but depressed its maintenance. The results obtained with MK 801 confirm those reported by others. Comparison of the effects of dextromethorphan with those of MK 801, suggests that there is a direct interaction with the NMDA receptor-ionophore complex. The effects of methadone and normethadone appear not to be linked to an interaction with opioid receptors, since naloxone did not influence the suppression of LTP caused by methadone. The possibility of interference with the NMDA receptor-ionophore complex is discussed. PMID:8449228

  12. Export of pharmaceuticals and medical devices under the federal Food, Drug & Cosmetic Act: FDA's striking change in interpretation post-Shelhigh.

    PubMed

    Basile, Edward M; Tolomeo, Deborah; Gluck, Elizabeth

    2009-01-01

    With no communication to industry except court filings in United States v. Undetermined Quantities of Boxes of Articles of Device (Shelhigh) and a draft guidance document, the Food and Drug Administration (FDA) has articulated new policies regarding export of pharmaceutical products and medical devices. FDA's departure from its historic interpretation of the export provisions of the Federal Food, Drug, and Cosmetic Act (FDCA) significantly limits the ability of manufacturers to export misbranded drugs and medical devices that FDA deems "adulterated," contrary to the plain language and legislative intent of the FDCA. To further exacerbate the issue, FDA has begun to implement these policies without the notice-and-comment rulemaking required by the Administrative Procedures Act (APA), but rather through an enforcement proceeding brought in the United States District Court for the District of New Jersey. In a letter opinion, the District Court prevented the export of Current Good Manufacturing Practices (CGMP) --adulterated medical devices that complied with FDCA Section 801(e)(1), at least as historically interpreted by FDA. The purpose of this article is to review the history of FDA's export policies for pharmaceuticals and medical devices, particularly those aspects of the export policies that are affected by FDA's recent change in position. Three changes in FDA's interpretation of the export provisions of the FDCA will be addressed: 1) unapproved devices that a manufacturer reasonably believes are eligible for Section 510(k) clearance may no longer be exported under Section 801(e) and now must be exported under Section 802, in substantial compliance with Current CGMP; 2) adulterated devices and misbranded drugs can only be exported if the foreign purchaser's specifications cause the product to be adulterated; and 3) an article may not be exported if a like article has ever been sold or offered for sale in domestic commerce. FDA's new interpretations of FDCA

  13. Disorder in Milk Proteins: α-Lactalbumin. Part B. A Multifunctional Whey Protein Acting as an Oligomeric Molten Globular "Oil Container" in the Anti-Tumorigenic Drugs, Liprotides.

    PubMed

    Uversky, Vladimir N; Permyakov, Serge E; Breydo, Leonid; Redwan, Elrashdy M; Almehdar, Hussein A; Permyakov, Eugene A

    2016-07-15

    This is a second part of the three-part article from a series of reviews on the abundance and roles of intrinsic disorder in milk proteins. We continue to describe α-lactalbumin, a small globular Ca2+-binding protein, which besides being one of the two components of lactose synthase that catalyzes the final step of the lactose biosynthesis in the lactating mammary gland, possesses a multitude of other functions. In fact, recent studies indicated that some partially folded forms of this protein possess noticeable bactericidal activity and other forms might be related to induction of the apoptosis of tumor cells. In its anti-tumorigenic function, oligomeric α-lactalbumin serves as a founding member of a new family of anticancer drugs termed liprotides (for lipids and partially denatured proteins), where an oligomeric molten globular protein acts as an "oil container" or cargo for the delivery of oleic acid to the cell membranes. PMID:26916155

  14. Fatty Acid Amide Hydrolase-Dependent Generation of Antinociceptive Drug Metabolites Acting on TRPV1 in the Brain

    PubMed Central

    Blomgren, Anders; Simonsen, Charlotte; Daulhac, Laurence; Libert, Frédéric; Chapuy, Eric; Etienne, Monique; Högestätt, Edward D.; Zygmunt, Peter M.; Eschalier, Alain

    2013-01-01

    The discovery that paracetamol is metabolized to the potent TRPV1 activator N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (AM404) and that this metabolite contributes to paracetamol’s antinociceptive effect in rodents via activation of TRPV1 in the central nervous system (CNS) has provided a potential strategy for developing novel analgesics. Here we validated this strategy by examining the metabolism and antinociceptive activity of the de-acetylated paracetamol metabolite 4-aminophenol and 4-hydroxy-3-methoxybenzylamine (HMBA), both of which may undergo a fatty acid amide hydrolase (FAAH)-dependent biotransformation to potent TRPV1 activators in the brain. Systemic administration of 4-aminophenol and HMBA led to a dose-dependent formation of AM404 plus N-(4-hydroxyphenyl)-9Z-octadecenamide (HPODA) and arvanil plus olvanil in the mouse brain, respectively. The order of potency of these lipid metabolites as TRPV1 activators was arvanil = olvanil>>AM404> HPODA. Both 4-aminophenol and HMBA displayed antinociceptive activity in various rodent pain tests. The formation of AM404, arvanil and olvanil, but not HPODA, and the antinociceptive effects of 4-aminophenol and HMBA were substantially reduced or disappeared in FAAH null mice. The activity of 4-aminophenol in the mouse formalin, von Frey and tail immersion tests was also lost in TRPV1 null mice. Intracerebroventricular injection of the TRPV1 blocker capsazepine eliminated the antinociceptive effects of 4-aminophenol and HMBA in the mouse formalin test. In the rat, pharmacological inhibition of FAAH, TRPV1, cannabinoid CB1 receptors and spinal 5-HT3 or 5-HT1A receptors, and chemical deletion of bulbospinal serotonergic pathways prevented the antinociceptive action of 4-aminophenol. Thus, the pharmacological profile of 4-aminophenol was identical to that previously reported for paracetamol, supporting our suggestion that this drug metabolite contributes to paracetamol’s analgesic activity via activation

  15. The success of the citizen suit: protecting consumers from inaccurate food labeling by amending the Federal Food, Drug, and Cosmetic Act.

    PubMed

    Springer, James

    2013-01-01

    The Federal Food, Drug, and Cosmetic Act ("FDCA"), amended in 1990 by the Nutrition Education and Labeling Act ("NLEA"), established a national framework for the administration and promulgation of uniform food labeling standards. Specifically, the NLEA created affirmative obligations for the food--requiring detailed disclosure of food content and strict adherence to regulations governing the use of health and nutritional claims on food packaging. To accomplish these goals, Congress tasked the Food and Drug Administration ("FDA") with the sole responsibility of the enforcement of these new requirements. Under the statutory framework of the FDCA, the United States Supreme Court ("Court") has held that there is no private right of action, of which extended to the enforcement of NLEA standards. This interpretation has left individuals with no federal outlet for relief in the enforcement of federal food labeling standards. Adherence to this interpretation is especially concerning when the FDA currently faces exponential growth in administrative responsibilities while simultaneously experiencing employment reduction, a $206 million "Sequester," and a recent government-wide shutdown. As a result, the American people are left to depend on an Agency that is struggling with drastic resource reduction while being accountable for ever increasing enforcement responsibilities. To ensure consumer protection, this Article argues that Congress should amend the FDCA to include a citizen suit provision in order to provide individuals with a right of private action for the enforcement of NLEA standards. Borrowing from the successes realized under similar citizen suit provisions found in environmental legislation, this Article argues that a citizen suit provision is amendable to the FDCA and would relieve fiscal pressures, strengthen the current enforcement framework of the FDCA, encourage more robust enforcement by the FDA and states, and ensure uniform interpretation of NLEA

  16. [Evolution of oral drug forms of metoprolol: advantages of long acting modified release forms with modified release].

    PubMed

    Leonova, M V; Maneshina, O A; Belousov, Iu B

    2010-01-01

    Review oral modified release drug forms of beta-adrenoblocker metoprolol which is used in arterial hypertension and ischemic heart disease is presented. Metoprolol has salts such as tartrate which is used for production of immediate release (IR) and sustained release (SR) forms and succinate used for production of controlled release form (CR/XL). Metoprolol SR has monolith matrix type, metoprolol CR/XL-system of multiple pellets. Effect of metoprolol tartrate (IR) on mortality was demonstrated in a number of studies in patients with arterial hypertension (AH) (MAPHY), myocardial infarction (SMT, GMT, MIAMI), dilated cardiomyopathy and heart failure (MDC). Studies of efficacy of metoprolol SR are scarce. Antihypertensive efficacy of metoprolol SR in patients with AH did not exceed that of a metoprolol IR or CR/XL. First retrospective analysis of efficacy of metoprolol tartrate and succinate (CR/XL) in patients after myocardial infarction allowed to obtain comparable results of 34% mortality lowering. In a prospective study in patients with chronic heart failure (COMET) metoprolol tartrate IR was not superior to carvedilol when mortality lowering was concerned. At the same time administration of controlled release metoprolol (CR/XL) in 2 large clinical trials (RESOLVD, MERITAHF) was advantageous in patients with chronic heart failure relative to lowering of mortality and rate of hospitalizations. A novel controlled release form of metoprolol has been created as a tartrate salt on the basis of pellet technology (CD/ERT) and its bioequivalence to metoprolol CR/XL has been proved. PMID:21591398

  17. Concurrent Oral Antipsychotic Drug Use Among Schizophrenia Patients Initiated on Long-Acting Injectable Antipsychotics Post-Hospital Discharge.

    PubMed

    Doshi, Jalpa A; Pettit, Amy R; Stoddard, Jeffrey J; Zummo, Jacqueline; Marcus, Steven C

    2015-08-01

    Pharmacological treatment is central to effective management of schizophrenia. Prescribing clinicians have an increasing array of options from which to choose, and oral antipsychotic polypharmacy is common in routine clinical practice. Practice guidelines recommend long-acting injectable (LAI) formulations, typically viewed as monotherapeutic alternatives, for patients with established nonadherence. Yet there are limited data on the prevalence and nature of concurrent oral antipsychotic prescriptions in patients receiving LAIs. Our observational, claims-based study examined the frequency and duration of concurrent oral prescriptions in 340 Medicaid patients receiving LAI therapy. Specifically, we examined patients with a recent history of nonadherence and hospitalization for schizophrenia and included both first-generation antipsychotic depot medications (fluphenazine decanoate, haloperidol decanoate) and more recently available second-generation injectables (LAI risperidone, paliperidone palmitate). Of all patients initiated on LAIs, 75.9% had a concurrent oral antipsychotic prescription in the 6 months post-hospital discharge. Patients receiving concurrent prescriptions were frequently prescribed an oral formulation of their LAI agent, but many first-generation LAI users received a concurrent second-generation oral medication. The lowest rate of concurrent prescribing (58.8%) was found with paliperidone palmitate, whereas the highest rate was with LAI risperidone (88.9%). Overlap in oral and LAI prescriptions typically occurred for a substantial period of time (ie, >30 days) and for a notable percentage of the days covered by LAIs (often 50% or more). Our findings highlight the need to further examine such prescribing patterns, to probe the reasons for them, and to clarify the optimal roles of different antipsychotic treatments in clinical practice. PMID:26075492

  18. HCV Drug Resistance Challenges in Japan: The Role of Pre-Existing Variants and Emerging Resistant Strains in Direct Acting Antiviral Therapy

    PubMed Central

    Chayama, Kazuaki; Hayes, C. Nelson

    2015-01-01

    Sustained virological response (SVR) rates have increased dramatically following the approval of direct acting antiviral (DAA) therapies. While individual DAAs have a low barrier to resistance, most patients can be successfully treated using DAA combination therapy. However, DAAs are vulnerable to drug resistance, and resistance-associated variants (RAVs) may occur naturally prior to DAA therapy or may emerge following drug exposure. While most RAVs are quickly lost in the absence of DAAs, compensatory mutations may reinforce fitness. However, the presence of RAVs does not necessarily preclude successful treatment. Although developments in hepatitis C virus (HCV) therapy in Asia have largely paralleled those in the United States, Japan’s July 2014 approval of asunaprevir plus daclatasvir combination therapy as the first all-oral interferon-free therapy was not repeated in the United States. Instead, two different combination therapies were approved: sofosbuvir/ledipasvir and paritaprevir/ritonavir/ombitasvir/dasabuvir. This divergence in treatment approaches may lead to differences in resistance challenges faced by Japan and the US. However, the recent approval of sofosbuvir plus ledipasvir in Japan and the recent submissions of petitions for approval of paritaprevir/ritonavir plus ombitasvir suggest a trend towards a new consensus on emerging DAA regimens. PMID:26473914

  19. HCV Drug Resistance Challenges in Japan: The Role of Pre-Existing Variants and Emerging Resistant Strains in Direct Acting Antiviral Therapy.

    PubMed

    Chayama, Kazuaki; Hayes, C Nelson

    2015-10-01

    Sustained virological response (SVR) rates have increased dramatically following the approval of direct acting antiviral (DAA) therapies. While individual DAAs have a low barrier to resistance, most patients can be successfully treated using DAA combination therapy. However, DAAs are vulnerable to drug resistance, and resistance-associated variants (RAVs) may occur naturally prior to DAA therapy or may emerge following drug exposure. While most RAVs are quickly lost in the absence of DAAs, compensatory mutations may reinforce fitness. However, the presence of RAVs does not necessarily preclude successful treatment. Although developments in hepatitis C virus (HCV) therapy in Asia have largely paralleled those in the United States, Japan's July 2014 approval of asunaprevir plus daclatasvir combination therapy as the first all-oral interferon-free therapy was not repeated in the United States. Instead, two different combination therapies were approved: sofosbuvir/ledipasvir and paritaprevir/ritonavir/ombitasvir/dasabuvir. This divergence in treatment approaches may lead to differences in resistance challenges faced by Japan and the US. However, the recent approval of sofosbuvir plus ledipasvir in Japan and the recent submissions of petitions for approval of paritaprevir/ritonavir plus ombitasvir suggest a trend towards a new consensus on emerging DAA regimens. PMID:26473914

  20. Direct-acting antiviral drug approvals for treatment of chronic hepatitis C virus infection: Scientific and regulatory approaches to clinical trial designs.

    PubMed

    Mishra, Poonam; Murray, Jeffrey; Birnkrant, Debra

    2015-10-01

    Therapeutic options for treatment of chronic hepatitis C have improved substantially since the approval of direct-acting antiviral agents (DAAs). Several interferon (IFN)-free or IFN- and ribavirin (RBV)-free treatment regimens with shorter durations and improved efficacy and safety profiles are now available. The U.S. Food and Drug Administration (FDA) used several scientific approaches and regulatory mechanisms, such as (1) use of a "validated" surrogate (sustained virological response) for a primary endpoint, (2) shortening the time point for measuring the surrogate by 12 weeks, (3) use of historical controls when clinically appropriate, and (4) use of modeling when scientifically sound to extend treatment indications to subpopulations not fully evaluated in clinical trials, which had an impact on DAA development and subsequent approvals. This article intends to provide increased transparency about the FDA's scientific approaches and regulatory processes that supported drug development and marketing approval of DAAs for treatment of hepatitis C, a serious, life-threatening infection. PMID:25953139

  1. [On the Differential Diagnosis of Intractable Psychogenic Chronic Cough: Neuropathic Larynx Irritable - Gabapentin's Antitussive Action].

    PubMed

    Bonnet, U; Ossowski, A; Schubert, M; Gall, H; Steinkamp, I; Richter, L E; Khalil-Boutros, Y; Nefedev, A; Kuhlmann, R

    2015-10-01

    We present the case of a 76 year old female inpatient who suffered from a chronic intractable cough which arose simultaneously to a severe major depression and was secondary to an exorbitant psychological distress. Chronic cough had never been experienced before and was initially considered to have a mere psychogenic origin since a comprehensive and guideline-based diagnostic screening did not reveal any underlying somatic cause. However, several factors cast doubt on the solitary psychic genesis of the chronic cough: i) occurrence immediately after a penetrant cold, ii) embedding in other complaints of laryngeal hyperreagibility (larynx irritable), such as persistent globus pharyngeus sensation, throat clearing and episodic dysphonia, iii) first occurrence on old life, iv) erupting from sleep as well, v) persistence despite remission of the major depression, and v) no sustaining benefit from specific psychotherapy and speech therapy. Therefore, diagnostics were extended to apparative tools for objective evaluation of swallowing by using fiberoptic videoendoscopic (FEES) and videofluoroscopic (VFS) techniques, which revealed signs of laryngeal neuropathy but without evidence of penetration or aspiration. A co-existing small goiter and an impaired glucose tolerance along with a putative intracellular vitamin B12 or folate deficiency (as indirectly derived from an apparent hyperhomocysteinemia) were assumed to be responsible for the neuropathy and underwent specific treatments. The impaired glucose tolerance and putative vitamin deficit were compatible with a distal symmetric sensorimotoric, even subclinical polyneuropathy of the lower extremities. The larynx irritable improved under gabapentin being confirmed by drug removals several times, and finally calmed down almost completely under gabapentin, which was in line with the scant literature of this topic. Re-examination of the larynx per FEES nine months later showed no deficits any more under the well

  2. Deeming Tobacco Products To Be Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act; Restrictions on the Sale and Distribution of Tobacco Products and Required Warning Statements for Tobacco Products. Final rule.

    PubMed

    2016-05-10

    The Food and Drug Administration (FDA) is issuing this final rule to deem products meeting the statutory definition of "tobacco product,'' except accessories of the newly deemed tobacco products, to be subject to the Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act). The Tobacco Control Act provides FDA authority to regulate cigarettes, cigarette tobacco, roll-your-own tobacco, smokeless tobacco, and any other tobacco products that the Agency by regulation deems to be subject to the law. With this final rule, FDA is extending the Agency's "tobacco product'' authorities in the FD&C Act to all other categories of products that meet the statutory definition of "tobacco product" in the FD&C Act, except accessories of such newly deemed tobacco products. This final rule also prohibits the sale of "covered tobacco products" to individuals under the age of 18 and requires the display of health warnings on cigarette tobacco, roll-your own tobacco, and covered tobacco product packages and in advertisements. FDA is taking this action to reduce the death and disease from tobacco products. In accordance with the Tobacco Control Act, we consider and intend the extension of our authorities over tobacco products and the various requirements and prohibitions established by this rule to be severable. PMID:27192730

  3. Hepatitis C virus treatment for prevention among people who inject drugs: Modeling treatment scale-up in the age of direct-acting antivirals

    PubMed Central

    Martin, Natasha K; Vickerman, Peter; Grebely, Jason; Hellard, Margaret; Hutchinson, Sharon J; Lima, Viviane D; Foster, Graham R; Dillon, John F; Goldberg, David J; Dore, Gregory J; Hickman, Matthew

    2013-01-01

    Substantial reductions in hepatitis C virus (HCV) prevalence among people who inject drugs (PWID) cannot be achieved by harm reduction interventions such as needle exchange and opiate substitution therapy (OST) alone. Current HCV treatment is arduous and uptake is low, but new highly effective and tolerable interferon-free direct-acting antiviral (DAA) treatments could facilitate increased uptake. We projected the potential impact of DAA treatments on PWID HCV prevalence in three settings. A dynamic HCV transmission model was parameterized to three chronic HCV prevalence settings: Edinburgh, UK (25%); Melbourne, Australia (50%); and Vancouver, Canada (65%). Using realistic scenarios of future DAAs (90% sustained viral response, 12 weeks duration, available 2015), we projected the treatment rates required to reduce chronic HCV prevalence by half or three-quarters within 15 years. Current HCV treatment rates may have a minimal impact on prevalence in Melbourne and Vancouver (<2% relative reductions) but could reduce prevalence by 26% in 15 years in Edinburgh. Prevalence could halve within 15 years with treatment scale-up to 15, 40, or 76 per 1,000 PWID annually in Edinburgh, Melbourne, or Vancouver, respectively (2-, 13-, and 15-fold increases, respectively). Scale-up to 22, 54, or 98 per 1,000 PWID annually could reduce prevalence by three-quarters within 15 years. Less impact occurs with delayed scale-up, higher baseline prevalence, or shorter average injecting duration. Results are insensitive to risk heterogeneity or restricting treatment to PWID on OST. At existing HCV drug costs, halving chronic prevalence would require annual treatment budgets of US $3.2 million in Edinburgh and approximately $50 million in Melbourne and Vancouver. Conclusion: Interferon-free DAAs could enable increased HCV treatment uptake among PWID, which could have a major preventative impact. However, treatment costs may limit scale-up, and should be addressed. (Hepatology 2013;58:1598

  4. Evolution of the National All Schedules Prescription Electronic Reporting Act (NASPER): a public law for balancing treatment of pain and drug abuse and diversion.

    PubMed

    Manchikanti, Laxmaiah; Whitfield, Ed; Pallone, Frank

    2005-10-01

    In the United States, physicians are faced with two opposing dilemmas in the treatment of pain - the potential for drug abuse and diversion, and the possible undertreatment of pain. While controlled prescription drugs such as narcotic analgesics, anxiolytics, antidepressants, stimulants, and sedative-hypnotics, play a legitimate role in managing chronic pain and other conditions, the illicit use of prescribed medicines is increasing at epidemic proportions. Diversion and abuse of prescription drugs is costly in terms of addiction, overdose, death, and related criminal activities, but chronic pain carries significant economic, social, and health impact as well. The American Society of Interventional Pain Physicians (ASIPP), as the introducing organization, was joined by several physician and nurse practitioner organizations in support of the National All Schedules Prescription Electronic Reporting (NASPER) Act of 2005, legislation that not only will give physicians an information tool to aid in prescribing controlled substances but also will help identify illicit use and abuse. NASPER is the law that provides for the establishment of a controlled substances monitoring program in each state. The concept for NASPER originated with ASIPP and was modeled after the highly successful Kentucky All Schedules Prescription Electronic Reporting Program (KASPER). Legislation was introduced in the United States House of Representatives during three different Congresses, the 107th, 108th, and 109th, by Reps. Edward Whitfield (R-KY) and Frank Pallone (D-NJ). It was first introduced in the United States Senate in the 107th Congress by Sen. Tim Hutchinson (R-AK), and in the 108th and 109th by Sens. Jeff Sessions (R-AL) and Dick Durbin (D-IL), with multiple cosponsors in both chambers. NASPER passed the House on July 27, 2005, by voice vote and passed the Senate by unanimous consent on July 29, 2005. President George W. Bush signed NASPER on August 11, 2005, and it became Public Law

  5. BRAF V600E mutation in early-stage multiple myeloma: good response to broad acting drugs and no relation to prognosis

    PubMed Central

    Rustad, E H; Dai, H Y; Hov, H; Coward, E; Beisvag, V; Myklebost, O; Hovig, E; Nakken, S; Vodák, D; Meza-Zepeda, L A; Sandvik, A K; Wader, K F; Misund, K; Sundan, A; Aarset, H; Waage, A

    2015-01-01

    In this study, we analyzed the prevalence and clone size of BRAF V600E mutation in 209 patients with multiple myeloma and related the results to clinical phenotype, response and survival. Biopsies were screened for BRAF V600E by allele-specific real-time PCR (AS-PCR). Positive results were confirmed by immunohistochemistry, Sanger sequencing and, in three patients from whom we had stored purified myeloma cells, whole-exome sequencing. Eleven patients (5.3%) were BRAF V600E mutation positive by AS-PCR and at least one other method. The fraction of mutated cells varied from 4 to 100%. BRAF V600E-positive patients had no characteristic clinical phenotype except for significantly higher levels of serum creatinine (125 versus 86 μmol/l) Seven of eleven patients responded with at least very good partial response to alkylators, immunomodulatory agents or proteasome inhibitors. Progression-free and overall survival were similar in patients with and without the mutation. By this integrated approach, we found that patients with BRAF V600E mutation responded very well to broad acting drugs and there was no relation to prognosis in early-stage myeloma. In particular, a large mutated cell fraction did not correlate with aggressive disease. PMID:25794135

  6. Drug Supply Chain Security Act

    THOMAS, 113th Congress

    Sen. Bennet, Michael F. [D-CO

    2013-05-15

    05/15/2013 Read twice and referred to the Committee on Health, Education, Labor, and Pensions. (All Actions) Notes: For further action, see H.R.3204, which became Public Law 113-54 on 11/27/2013. Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  7. Central mechanisms II: pharmacology of brainstem pathways.

    PubMed

    Bolser, D C

    2009-01-01

    Following systemic administration, centrally acting antitussive drugs are generally assumed to act in the brainstem to inhibit cough. However, recent work in humans has raised the possibility of suprapontine sites of action for cough suppressants. For drugs that may act in the brainstem, the specific locations, types of neurones affected, and receptor specificities of the compounds represent important issues regarding their cough-suppressant actions. Two medullary areas that have received the most attention regarding the actions of antitussive drugs are the nucleus of the tractus solitarius (NTS) and the caudal ventrolateral respiratory column. Studies that have implicated these two medullary areas have employed both microinjection and in vitro recording methods to control the location of action of the antitussive drugs. Other brainstem regions contain neurones that participate in the production of cough and could represent potential sites of action of antitussive drugs. These regions include the raphe nuclei, pontine nuclei, and rostral ventrolateral medulla. Specific receptor subtypes have been associated with the suppression of cough at central sites, including 5-HT1A, opioid (mu, kappa, and delta), GABA-B, tachykinin neurokinin-1 (NK-1) and neurokinin-2, non-opioid (NOP-1), cannabinoid, dopaminergic, and sigma receptors. Aside from tachykinin NK-1 receptors in the NTS, relatively little is known regarding the receptor specificity of putative antitussive drugs in particular brainstem regions. Our understanding of the mechanisms of action of antitussive drugs would be significantly advanced by further work in this area. PMID:18825342

  8. Microtubule-acting drugs lead to the nonpolarized delivery of the influenza hemagglutinin to the cell surface of polarized Madin-Darby canine kidney cells.

    PubMed

    Rindler, M J; Ivanov, I E; Sabatini, D D

    1987-02-01

    The synchronized directed transfer of the envelope glycoproteins of the influenza and vesicular stomatitis viruses from the Golgi apparatus to the apical and basolateral surfaces, respectively, of polarized Madin-Darby canine kidney (MDCK) cells can be achieved using temperature-sensitive mutant viruses and appropriate temperature shift protocols (Rindler, M. J., I. E. Ivanov, H. Plesken, and D. D. Sabatini, 1985, J. Cell Biol., 100:136-151). The microtubule-depolymerizing agents colchicine and nocodazole, as well as the microtubule assembly-promoting drug taxol, were found to interfere with the normal polarized delivery and exclusive segregation of hemagglutinin (HA) to the apical surface but not with the delivery and initial accumulation of G on the basolateral surface. Immunofluorescence analysis of permeabilized monolayers of influenza-infected MDCK cells treated with the microtubule-acting drugs demonstrated the presence of substantial amounts of HA protein on both the apical and basolateral surfaces. Moreover, in cells infected with the wild-type influenza virus, particles budded from both surfaces. Viral counts in electron micrographs showed that approximately 40% of the released viral particles accumulated in the intercellular spaces or were trapped between the cell and monolayer and the collagen support as compared to less than 1% on the basolateral surface of untreated infected cells. The effect of the microtubule inhibitors was not a result of a rapid redistribution of glycoprotein molecules initially delivered to the apical surface since a redistribution was not observed when the inhibitors were added to the cells after the HA was permitted to reach the apical surface at the permissive temperature and the synthesis of new HA was inhibited with cycloheximide. The altered segregation of the HA protein that occurs may result from the dispersal of the Golgi apparatus induced by the inhibitors or from the disruption of putative microtubules containing tracks

  9. Tumour-associated macrophages act as a slow-release reservoir of nano-therapeutic Pt(IV) pro-drug

    PubMed Central

    Miller, Miles A.; Zheng, Yao-Rong; Gadde, Suresh; Pfirschke, Christina; Zope, Harshal; Engblom, Camilla; Kohler, Rainer H.; Iwamoto, Yoshiko; Yang, Katherine S.; Askevold, Bjorn; Kolishetti, Nagesh; Pittet, Mikael; Lippard, Stephen J.; Farokhzad, Omid C.; Weissleder, Ralph

    2015-01-01

    Therapeutic nanoparticles (TNPs) aim to deliver drugs more safely and effectively to cancers, yet clinical results have been unpredictable owing to limited in vivo understanding. Here we use single-cell imaging of intratumoral TNP pharmacokinetics and pharmacodynamics to better comprehend their heterogeneous behaviour. Model TNPs comprising a fluorescent platinum(IV) pro-drug and a clinically tested polymer platform (PLGA-b-PEG) promote long drug circulation and alter accumulation by directing cellular uptake toward tumour-associated macrophages (TAMs). Simultaneous imaging of TNP vehicle, its drug payload and single-cell DNA damage response reveals that TAMs serve as a local drug depot that accumulates significant vehicle from which DNA-damaging Pt payload gradually releases to neighbouring tumour cells. Correspondingly, TAM depletion reduces intratumoral TNP accumulation and efficacy. Thus, nanotherapeutics co-opt TAMs for drug delivery, which has implications for TNP design and for selecting patients into trials. PMID:26503691

  10. Are Interferon-Free Direct-Acting Antivirals for the Treatment of HCV Enough to Control the Epidemic among People Who Inject Drugs?

    PubMed Central

    Lima, Viviane D.; Rozada, Ignacio; Grebely, Jason; Hull, Mark; Lourenco, Lillian; Nosyk, Bohdan; Krajden, Mel; Yoshida, Eric; Wood, Evan; Montaner, Julio S. G.

    2015-01-01

    Background Widely access to interferon-free direct-acting antiviral regimens (IFN-free DAA) is poised to dramatically change the impact of the HCV epidemic among people who inject drugs (PWID). We evaluated the long-term effect of increasing HCV testing, treatment and engagement into harm-reduction activities, focused on active PWID, on the HCV epidemic in British Columbia (BC), Canada. Methods We built a compartmental model of HCV disease transmission stratified by disease progression, transmission risk, and fibrosis level. We explored the effect of: (1) Increasing treatment rates from 8 to 20, 40 and 80 per 1000 infected PWID/year; (2) Increasing treatment eligibility based on fibrosis level; (3) Maximizing the effect of testing by performing it immediately upon ending the acute phase; (4) Increasing access to harm-reduction activities to reduce the risk of re-infection; (5) Different HCV antiviral regimens on the Control Reproduction Number Rc. We assessed the impact of these interventions on incidence, prevalence and mortality from 2016 to 2030. Results Of all HCV antiviral regimens, only IFN-free DAAs offered a high chance of disease elimination (i.e. Rc < 1), but it would be necessary to substantially increase the current low testing and treatment rates. Assuming a treatment rate of 80 per 1000 infected PWID per year, coupled with a high testing rate, the incidence rate, at the end of 2030, could decrease from 92.9 per 1000 susceptible PWID per year (Status Quo) to 82.8 (by treating only PWID with fibrosis level F2 and higher) or to 65.5 (by treating PWID regardless of fibrosis level). If PWID also had access to increased harm-reduction activities, the incidence rate further decreased to 53.1 per 1000 susceptible PWID per year. We also obtained significant decreases in prevalence and mortality at the end of 2030. Conclusions The combination of increased access to HCV testing, highly efficacious antiviral treatment and harm-reduction programs can substantially

  11. Hearings on the Reauthorization of Title 3(b) of the Anti-Drug Abuse Act of 1988: Drug Abuse Education and Prevention Programs for Runaway and Homeless Youth and Youth Gangs. Hearings before the Subcommittee on Human Resources of the Committee on Education and Labor. House of Representatives, One Hundred Second Congress, First Session (Washington, D.C., July 18, 1991; Downey, California, August 2, 1991).

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House Committee on Education and Labor.

    This document contains witness testimonies from two Congressional hearings examining the reauthorization of Title 3(b) of the Anti-Drug Abuse Act of 1988 relating to the drug abuse education and prevention for runaway and homeless youth and youth gangs. Opening statements are included from Representatives Martinez and Fawell. Witnesses providing…

  12. Solution structure of the ActD–5′-CCGTT3GTGG-3′ complex: drug interaction with tandem G·T mismatches and hairpin loop backbone

    PubMed Central

    Chin, Ko-Hsin; Chen, Fu-Ming; Chou, Shan-Ho

    2003-01-01

    Binding of actinomycin D (ActD) to the seemingly single-stranded DNA (ssDNA) oligomer 5′-CCGTT3 GTGG-3′ has been studied in solution using high-resolution nuclear magnetic resonance (NMR) techniques. A strong binding constant (8 × 106 M–1) and high quality NMR spectra have allowed us to determine the initial DNA structure using distance geometry as well as the final ActD–5′-CCGTT3 GTGG-3′ complex structure using constrained molecular dynamics calculations. The DNA oligomer 5′-CCGTT3GTGG-3′ in the complex forms a hairpin structure with tandem G·T mismatches at the stem region next to a loop of three stacked thymine bases pointing toward the major groove. Bipartite T2O–GH1 and T2O–G2NH2 hydrogen bonds were detected for the G·T mismatches that further stabilize this unusual DNA hairpin. The phenoxazone chromophore of ActD intercalates nicely between the tandem G·T mismatches in essentially one major orientation. Additional hydrophobic interactions between the ActD quinoid amino acid residues with the loop T5–T6–T7 backbone protons were also observed. The hydrophobic G–phenoxazone–G interaction in the ActD–5′-CCGTT3GTGG-3′ complex is more robust than that of the classical ActD– 5′-CCGCT3GCGG-3′ complex, consistent with the roughly 2-fold stronger binding of ActD to the 5′-CCGTT3GTGG-3′ sequence than to its 5′-CCG CT3GCGG-3′ counterpart. Stabilization by ActD of a hairpin containing non-canonical stem base pairs further strengthens the notion that ActD or other related compounds may serve as a sequence- specific ssDNA-binding agent that inhibits human immunodeficiency virus (HIV) and other retroviruses replicating through ssDNA intermediates. PMID:12736312

  13. 21 CFR 1230.2 - Scope of the act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Scope of the act. 1230.2 Section 1230.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS... CAUSTIC POISON ACT General Provisions § 1230.2 Scope of the act. The provisions of the act apply to...

  14. 21 CFR 1210.2 - Scope of act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Scope of act. 1210.2 Section 1210.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER... MILK ACT General Provisions § 1210.2 Scope of act. The provisions of the act apply to all milk...

  15. From Bench-Top to Bedside: A Prospective In Vitro Antibiotic Combination Testing (iACT) Service to Guide the Selection of Rationally Optimized Antimicrobial Combinations against Extensively Drug Resistant (XDR) Gram Negative Bacteria (GNB)

    PubMed Central

    Lim, Tze-Peng; Teo, Jocelyn Qi-Min; Lee, Winnie; Kurup, Asok; Koh, Tse-Hsien; Tan, Thuan-Tong; Kwa, Andrea L.

    2016-01-01

    Introduction Combination therapy is increasingly utilized against extensively-drug resistant (XDR) Gram negative bacteria (GNB). However, choosing a combination can be problematic as effective combinations are often strain-specific. An in vitro antibiotic combination testing (iACT) service, aimed to guide the selection of individualized and rationally optimized combination regimens within 48 hours, was developed. We described the role and feasibility of the iACT service in guiding individualized antibiotic combination selection in patients with XDR-GNB infections. Methods A retrospective case review was performed in two Singapore hospitals from April 2009–June 2014. All patients with XDR-GNB and antibiotic regimen guided by iACT for clinical management were included. The feasibility and role of the prospective iACT service was evaluated. The following patient outcomes were described: (i) 30-day in-hospital all-cause and infection-related mortality, (ii) clinical response, and (iii) microbiological eradication in patients with bloodstream infections. Results From 2009–2014, the iACT service was requested by Infectious Disease physicians for 39 cases (20 P. aeruginosa, 13 A. baumannii and 6 K. pneumoniae). Bloodstream infection was the predominant infection (36%), followed by pneumonia (31%). All iACT recommendations were provided within 48h from request for the service. Prior to iACT-guided therapy, most cases were prescribed combination antibiotics empirically (90%). Changes in the empiric antibiotic regimens were recommended in 21 (54%) cases; in 14 (36%) cases, changes were recommended as the empiric regimens were found to be non-bactericidal in vitro. In 7 (18%) cases, the number of antibiotics used in combination empirically was reduced by the iACT service. Overall, low 30-day infection-related mortality (15%) and high clinical response (82%) were observed. Microbiological eradication was observed in 79% of all bloodstream infections. Conclusions The iACT

  16. Phenylbutazone, a New Long-Acting Agent that can Improve the Peptide Pharmacokinetic Based on Serum Albumin as a Drug Carrier.

    PubMed

    Zhou, Jie; Li, Xue; Zhu, Xiaoyun; Sun, Jian; Qiu, Qianqian; Huang, Wenlong; Qian, Hai

    2016-06-01

    As a NPY-2 receptor agonist, PYY24-36- Leu31 is reported to suppress appetite and has a potential in obesity treatment, but its short half-life limits the clinical application. The use of chemical modification to improve interactions with human serum albumin (HSA) is an effective strategy for prolonging the half-lives of peptide analogues. So based on the characteristics that phenylbutazone has a good combination with HSA, we selected a proper linker to link with PYY24-36 -Leu31 to create long-acting and highly biologically active PYY24-36 -Leu31 conjugates, and successfully find a novel, long-acting PYY24-36 -Leu31 conjugate 8 that, when dosed every other day in diet induce obese (DIO) mice for 2 weeks, results in a significant reduction in food intake and body weight and improvement in blood parameter and hepatic steatosis. PMID:26808199

  17. Expression of Mycobacterium tuberculosis NLPC/p60 family protein Rv0024 induce biofilm formation and resistance against cell wall acting anti-tuberculosis drugs in Mycobacterium smegmatis.

    PubMed

    Padhi, Avinash; Naik, Sumanta Kumar; Sengupta, Srabasti; Ganguli, Geetanjali; Sonawane, Avinash

    2016-04-01

    Bacterial species are capable of living as biofilm and/or planktonic forms. Role of biofilms in the pathogenesis of several human pathogens is well established. However, in case of Mycobacterium tuberculosis (Mtb) infection the role of biofilms and the genetic requirements for biofilm formation remains largely unknown. We herein report that ectopic expression of Mtb Rv0024, encoding a putative peptidoglycan amidase, in non-pathogenic Mycobacterium smegmatis(Msm) strain (MsmRv0024) confer at least 10-fold increase in resistance against two prominent anti-tuberculosis drugs isoniazid and pyrazinamide. We further report that the development of resistance was due to significant increase in biofilm formation by Rv0024. Transmission electron microscopy revealed differences in cell surface architecture of MsmRv0024 when compared with Msm wild-type (WT) and vector control Msm pSMT3 (pSMT3) strains and this aggregation pattern was due to increased cell wall hydrophobicity, as determined by Bacterial adhesion to hydrocarbons assay (BATH). Confocal microscopy study showed increased adherence of MsmRv0024 bacteria to lung epithelial cells as compared to pSMT3 strain. However, infection studies showed no differences in host cell invasion and intracellular survival in mouse macrophages. We envision that Rv0024 may play a critical role in initial infection process, adherence to host cells and drug resistance. Thus, Rv0024 may be considered as a potential drug target for the treatment of tuberculosis. PMID:26706821

  18. In-Silico docking of HIV-1 integrase inhibitors reveals a novel drug type acting on an enzyme/DNA reaction intermediate

    PubMed Central

    Savarino, Andrea

    2007-01-01

    Background HIV-1 integrase (IN) is an emerging drug target, as IN strand transfer inhibitors (INSTIs) are proving potent antiretroviral agents in clinical trials. One credible theory sees INSTIs as docking at the cellular (acceptor) DNA-binding site after IN forms a transitional complex with viral (donor) DNA. However, mapping of the DNA and INSTI binding sites within the IN catalytic core domain (CCD) has been uncertain. Methods Structural superimpositions were conducted using the SWISS PDB and Cn3D free software. Docking simulations of INSTIs were run by a widely validated genetic algorithm (GOLD). Results Structural superimpositions suggested that a two-metal model for HIV-1 IN CCD in complex with small molecule, 1-(5-chloroindol-3-yl)-3-(tetrazoyl)-1,3-propandione-ene (5CITEP) could be used as a surrogate for an IN/viral DNA complex, because it allowed replication of contacts documented biochemically in viral DNA/IN complexes or displayed by a crystal structure of the IN-related enzyme Tn5 transposase in complex with transposable DNA. Docking simulations showed that the fitness of different compounds for the catalytic cavity of the IN/5CITEP complex significantly (P < 0.01) correlated with their 50% inhibitory concentrations (IC50s) in strand transfer assays in vitro. The amino acids involved in inhibitor binding matched those involved in drug resistance. Both metal binding and occupation of the putative viral DNA binding site by 5CITEP appeared to be important for optimal drug/ligand interactions. The docking site of INSTIs appeared to overlap with a putative acceptor DNA binding region adjacent to but distinct from the putative donor DNA binding site, and homologous to the nucleic acid binding site of RNAse H. Of note, some INSTIs such as 4,5-dihydroxypyrimidine carboxamides/N-Alkyl-5-hydroxypyrimidinone carboxamides, a highly promising drug class including raltegravir/MK-0518 (now in clinical trials), displayed interactions with IN reminiscent of those

  19. Pituitary apoplexy causing spontaneous remission of acromegaly following long-acting octreotide therapy: a rare drug side effect or just a coincidence

    PubMed Central

    Kumar, Sunil; Sharma, Shruti

    2016-01-01

    Pituitary apoplexy is characterized by abrupt onset of haemorrhage or non-haemorrhagic infarction of a pituitary adenoma. The clinical features include acute onset severe headache, visual field defects, meningeal irritation, ophthalmoplegia and hypopituitarism. The pituitary apoplexy may be clinically silent in ∼25% of patients. We report a case of acromegaly due to pituitary macroadenoma. The patient was started on long-acting octreotide therapy. On 3-month follow-up, the patient showed clinical and biochemical remission and the magnetic resonance imaging (MRI) of the brain showed subclinical haemorrhage and resolution of tumour. The octreotide therapy was stopped. On 6-month follow-up, the patient was still in remission and the MRI of brain revealed non-enhancing mixed intensities haemorrhagic and cystic areas of the pituitary gland. In our patient, whether spontaneous remission of acromegaly due to subclinical pituitary haemorrhage was coincidental or due to long-acting octreotide therapy is still a dilemma. We report this case because of rarity and clinical importance of this unusual occurrence. PMID:27123308

  20. Utility of small-animal positron emission tomographic imaging of rats for preclinical development of drugs acting on the serotonin transporter.

    PubMed

    Saijo, Takeaki; Maeda, Jun; Okauchi, Takashi; Maeda, Jun-Ichi; Morio, Yasunori; Kuwahara, Yasuhiro; Suzuki, Masayuki; Goto, Nobuharu; Suzuki, Kazutoshi; Higuchi, Makoto; Suhara, Tetsuya

    2009-09-01

    Visualization of neurotransmission components in living small animals using positron emission tomography (PET) has the potential of contributing to the preclinical development of neuroactive drugs, although it is yet to be examined whether quantitative animal PET data on candidate compounds can be extrapolated to humans. Here, we investigated the comparability of the occupancies of serotonin transporter (5-HTT) by therapeutic agents in rat PET studies with our predetermined data from ex- vivo animal experiments and clinical PET scans. Rats were treated with varying doses of fluvoxamine and a newly developed compound, (2S)-1-[4-(3,4-dichlorophenyl) piperidin-1-yl]-3-[2-(5-methyl-1,3,4-oxadiazol-2-yl)benzo[b]furan-4-yloxy]propan-2-ol monohydrochloride (Wf-516), and underwent PET scans with [11C]3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile ([11C]DASB), a selective radioligand for in-vivo quantification of 5-HTT. PET images indicated a reduction of [11C]DASB binding to 5-HTT as a function of the doses and/or plasma concentrations of fluvoxamine and Wf-516. The doses of these drugs at half-maximal effect (15.2 mg/kg and 3.1 mg/kg, respectively), determined that using binding potentials for [11C]DASB, were comparable to those estimated by our previous ex-vivo measurements in rats (4.5 mg/kg and 1.1 mg/kg, respectively), as there was only a 3-fold difference between these results. Moreover, the plasma concentration of fluvoxamine needed for 50% occupancy of central 5-HTT (6.1 ng/ml) was almost equivalent to the value determined in human PET studies (4.6 ng/ml). These findings support the view that the conjunctive use of small-animal PET and [11C]DASB facilitates a quantitative comparison of in-development drugs targeting 5-HTT with established inhibitors and a predictive estimation of their plasma concentrations exerting therapeutic effects in humans. PMID:19236731

  1. Review: Effect of drugs on human cough reflex sensitivity to inhaled capsaicin

    PubMed Central

    2012-01-01

    Capsaicin, the pungent extract of red peppers, has been used in clinical research for almost three decades. Capsaicin has gained favor as the provocative agent of choice to measure cough reflex sensitivity, as it induces cough in a safe, reproducible, and dose-dependent manner. One of the major uses of capsaicin cough challenge testing has been to evaluate the effect of a pharmacological intervention on the human cough reflex. The current review summarizes the published experience with capsaicin inhalation challenge in the evaluation of drug effects on cough reflex sensitivity. A notable contrast evident between studies demonstrating a drug effect (inhibition of cough reflex sensitivity) and those that do not, is the predominance of healthy volunteers as subjects in the latter. This observation suggests that subjects with pathological cough, rather than normal volunteers, comprise the optimal group in which to evaluate the effect of potential antitussive agents on human cough reflex sensitivity. PMID:23146824

  2. US Food and Drug Administration's Risk Evaluation and Mitigation Strategy for extended-release and long-acting opioids: pros and cons, and a European perspective.

    PubMed

    Mercadante, Sebastiano; Craig, David; Giarratano, Antonello

    2012-12-24

    Prescriptions for opioid analgesics to manage moderate-to-severe chronic non-cancer pain have increased markedly over the last decade. An unintentional consequence of greater prescription opioid utilization has been the parallel increase in misuse, abuse and overdose, which are serious risks associated with all opioid analgesics. In response to disturbing rises in prescription opioid abuse, the US Food and Drug Administration (FDA) has proposed the implementation of aggressive Risk Evaluation and Mitigation Strategies (REMS). While REMS could dramatically change the development, release, marketing and prescription of extended-release opioids, questions remain on how these programmes may influence prescribing practices, patient safety and ultimately patient access to these agents. The extent of the availability and misuse of prescription opioids in Europe is difficult to assess from the data currently available, due in large part to the considerable differences in prescribing patterns and regulations between countries. Balancing the availability of prescription opioids for those patients who have pain, while discouraging illicit use, is a complex challenge and requires effective efforts on many levels, particularly in Europe where policies are quite different between countries. PMID:23116252

  3. Differences between magnetoencephalographic (MEG) spectral profiles of drugs acting on GABA at synaptic and extrasynaptic sites: a study in healthy volunteers.

    PubMed

    Nutt, David; Wilson, Sue; Lingford-Hughes, Anne; Myers, Jim; Papadopoulos, Andreas; Muthukumaraswamy, Suresh

    2015-01-01

    A range of medications target different aspects of the GABA system; understanding their effects is important to inform further drug development. Effects on the waking EEG comparing these mechanisms have not been reported; in this study we compare the effects on resting MEG spectra of the benzodiazepine receptor agonist zolpidem, the delta sub-unit selective agonist gaboxadol (also known as THIP) and the GABA reuptake inhibitor tiagabine. These were two randomised, single-blind, placebo-controlled, crossover studies in healthy volunteers, one using zolpidem 10 mg, gaboxadol 15 mg and placebo, and the other tiagabine 15 mg and placebo. Whole head MEG recordings and individual MEG spectra were divided into frequency bands. Baseline spectra were subtracted from each post-intervention spectra and then differences between intervention and placebo compared. After zolpidem there were significant increases in beta frequencies and reduction in alpha frequency power; after gaboxadol and tiagabine there were significant increases in power at all frequencies up to beta. Enhancement of tonic inhibition via extrasynaptic receptors by gaboxadol gives rise to a very different MEG signature from the synaptic action of zolpidem. Tiagabine theoretically can affect both types of receptor; from these MEG results it is likely that the latter is the more prominent effect here. PMID:25195191

  4. The Potential Impact of a Hepatitis C Vaccine for People Who Inject Drugs: Is a Vaccine Needed in the Age of Direct-Acting Antivirals?

    PubMed Central

    Stone, Jack; Martin, Natasha K.; Hickman, Matthew; Hellard, Margaret; Scott, Nick; McBryde, Emma; Drummer, Heidi; Vickerman, Peter

    2016-01-01

    Background and Aims The advent of highly effective hepatitis C (HCV) treatments has questioned the need for a vaccine to control HCV amongst people who inject drugs (PWID). However, high treatment costs and ongoing reinfection risk suggest it could still play a role. We compared the impact of HCV vaccination amongst PWID against providing HCV treatment. Methods Dynamic HCV vaccination and treatment models among PWID were used to determine the vaccination and treatment rates required to reduce chronic HCV prevalence or incidence in the UK over 20 or 40 years. Projections considered a low (50% protection for 5 years), moderate (70% protection for 10 years) or high (90% protection for 20 years) efficacy vaccine. Sensitivities to various parameters were examined. Results To halve chronic HCV prevalence over 40 years, the low, moderate and high efficacy vaccines required annual vaccination rates (coverage after 20 years) of 162 (72%), 77 (56%) and 44 (38%) per 1000 PWID, respectively. These vaccination rates were 16, 7.6 and 4.4 times greater than corresponding treatment rates. To halve prevalence over 20 years nearly doubled these vaccination rates (moderate and high efficacy vaccines only) and the vaccination-to-treatment ratio increased by 20%. For all scenarios considered, required annual vaccination rates and vaccination-to-treatment ratios were at least a third lower to reduce incidence than prevalence. Baseline HCV prevalence had little effect on the vaccine’s impact on prevalence or incidence, but substantially affected the vaccination-to-treatment ratios. Behavioural risk heterogeneity only had an effect if we assumed no transitions between high and low risk states and vaccinations were targeted or if PWID were high risk for their first year. Conclusions Achievable coverage levels of a low efficacy prophylactic HCV vaccine could greatly reduce HCV transmission amongst PWID. Current high treatment costs ensure vaccination could still be an important

  5. Balancing Acts

    MedlinePlus

    ... Current Issue Past Issues Special Section: Focus on Communication Balancing Acts Past Issues / Fall 2008 Table of ... from the National Institute on Deafness and Other Communication Disorders (NIDCD). It involves simulated trips down the ...

  6. Acting Atoms.

    ERIC Educational Resources Information Center

    Farin, Susan Archie

    1997-01-01

    Describes a fun game in which students act as electrons, protons, and neutrons. This activity is designed to help students develop a concrete understanding of the abstract concept of atomic structure. (DKM)

  7. ACT Test

    MedlinePlus

    ... this page helpful? Also known as: ACT; Activated Coagulation Time Formal name: Activated Clotting Time Related tests: ... in the blood called platelets and proteins called coagulation factors are activated in a sequence of steps ...

  8. Child Labor Act of 1990. Hearing before the Subcommittee on Labor and Subcommittee on Children, Family, Drugs and Alcoholism of the Committee on Labor and Human Resources. United States Senate, One Hundred First Congress, Second Session on S. 2548 To Amend the Fair Labor Standards Act of 1938 To Increase Penalities for Employers Who Violate the Child Labor Provisions of Such Act.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Senate Committee on Labor and Human Resources.

    On May 8, 1990, testimony concerning the Child Labor Act of 1990 was heard at a joint hearing of two U.S. Senate subcommittees. Opening statements by Senators Metzenbaum and Jeffords concerned: (1) the increase in child labor law violations since 1983; (2) the lack of increase in penalty fines since that time; (3) child death and injury during…

  9. 78 FR 72897 - Draft Guidance for Industry on Interim Product Reporting for Human Drug Compounding Outsourcing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-04

    ... Human Drug Compounding Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic... of the Federal Food, Drug, and Cosmetic Act.'' The draft guidance addresses new provisions in the Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Drug Quality and Security Act...

  10. Physician Dispensing of Drugs. Hearing before the Subcommittee on Health and the Environment of the Committee on Energy and Commerce. House of Representatives, One Hundredth Congress, First Session on H.R. 2093, a Bill To Amend the Federal Food, Drug, and Cosmetic Act To Limit the Dispensing of Certain Drugs by Practitioners.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House Committee on Energy and Commerce.

    The text of a Congressional hearing considering limitations on the dispensing of drugs by physicians for profit is presented in this document. It focuses in particular on H.R. 2093, a bill introduced by Representative Ron Wyden which would generally prohibit physicians and other practitioners from directly profiting from the sale of drugs which…

  11. Cancer drug discovery by repurposing: teaching new tricks to old dogs.

    PubMed

    Gupta, Subash C; Sung, Bokyung; Prasad, Sahdeo; Webb, Lauren J; Aggarwal, Bharat B

    2013-09-01

    Progressively increasing failure rates, high cost, poor bioavailability, poor safety, limited efficacy, and a lengthy design and testing process associated with cancer drug development have necessitated alternative approaches to drug discovery. Exploring established non-cancer drugs for anticancer activity provides an opportunity rapidly to advance therapeutic strategies into clinical trials. The impetus for development of cancer therapeutics from non-cancer drugs stems from the fact that different diseases share common molecular pathways and targets in the cell. Common molecular origins of diverse diseases have been discovered through advancements in genomics, proteomics, and informatics technologies, as well as through the development of analytical tools that allow researchers simultaneously to screen large numbers of existing drugs against a particular disease target. Thus, drugs originally identified as antitussive, sedative, analgesic, antipyretic, antiarthritic, anesthetic, antidiabetic, muscle relaxant, immunosuppressant, antibiotic, antiepileptic, cardioprotective, antihypertensive, erectile function enhancing, or angina relieving are being repurposed for cancer. This review describes the repurposing of these drugs for cancer treatment. PMID:23928289

  12. Dangerous Synthetic Drug Control Act of 2016

    THOMAS, 112th Congress

    Rep. Katko, John [R-NY-24

    2016-09-06

    09/15/2016 Referred to the Subcommittee on Crime, Terrorism, Homeland Security, and Investigations. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  13. Unmuzzle the Drug Czar Act of 2014

    THOMAS, 113th Congress

    Rep. Cohen, Steve [D-TN-9

    2014-02-11

    03/20/2014 Referred to the Subcommittee on Crime, Terrorism, Homeland Security, and Investigations. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  14. Medicare Prescription Drug Integrity Act of 2013

    THOMAS, 113th Congress

    Rep. Pallone, Frank, Jr. [D-NJ-6

    2013-08-01

    09/13/2013 Referred to the Subcommittee on Crime, Terrorism, Homeland Security, and Investigations. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  15. Counterfeit Drug Penalty Enhancement Act of 2012

    THOMAS, 112th Congress

    Rep. Meehan, Patrick [R-PA-7

    2011-12-14

    06/19/2012 Received in the Senate and Read twice and referred to the Committee on the Judiciary. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  16. Prescription Drug Labeling Promotion Act of 2012

    THOMAS, 112th Congress

    Rep. Markey, Edward J. [D-MA-7

    2012-02-24

    02/24/2012 Referred to the House Committee on Energy and Commerce. (All Actions) Notes: For further action, see S.3187, which became Public Law 112-144 on 7/9/2012. Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  17. Synthetic Drug Control Act of 2011

    THOMAS, 112th Congress

    Rep. Dent, Charles W. [R-PA-15

    2011-03-30

    12/08/2011 Received in the Senate and Read twice and referred to the Committee on the Judiciary. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  18. Transnational Drug Trafficking Act of 2013

    THOMAS, 113th Congress

    Rep. Marino, Tom [R-PA-10

    2013-05-22

    06/14/2013 Referred to the Subcommittee on Crime, Terrorism, Homeland Security, and Investigations. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  19. Major Drug Trafficking Prosecution Act of 2013

    THOMAS, 113th Congress

    Rep. Waters, Maxine [D-CA-43

    2013-09-12

    10/15/2013 Referred to the Subcommittee on Crime, Terrorism, Homeland Security, and Investigations. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  20. 75 FR 22599 - Draft Guidance for Industry and Food and Drug Administration Staff; Food and Drug Administration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-29

    ... Under the Federal Food, Drug, and Cosmetic Act AGENCY: Food and Drug Administration, HHS. ACTION: Notice...) Requests for Information Under the Federal Food, Drug, and Cosmetic Act.'' This draft guidance is not final...) Requests for Information Under the Federal Food, Drug, and Cosmetic Act'' to the Division of...

  1. Federal Strategy for Drug Abuse and Drug Traffic Prevention 1974.

    ERIC Educational Resources Information Center

    Strategy Council on Drug Abuse, Washington, DC.

    The Drug Abuse Office and Treatment Act of 1972 directed the development and promulgation of a comprehensive, coordinated long-term Federal strategy for all drug abuse prevention and drug traffic control functions conducted, sponsored, or supported by the Federal Government. This second annual report of the Strategy Council builds on the…

  2. 78 FR 72838 - Bulk Drug Substances That May Be Used To Compound Drug Products in Accordance With Section 503B...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-04

    ... Compound Drug Products in Accordance With Section 503B of the Federal Food, Drug, and Cosmetic Act... to develop a list of bulk drug substances (bulk drugs) that may be used to compound drug products in... facility does not compound using a bulk drug substance unless: (1) The bulk drug substance appears on...

  3. Adverse ocular reactions to drugs.

    PubMed Central

    Spiteri, M. A.; James, D. G.

    1983-01-01

    Drugs acting on various parts of the body may also affect the eye insidiously. Increased awareness of such drug toxicity by the prescribing doctor should encourage him to consider effects on the cornea, lens, retina, optic nerve and elsewhere when checking the patient's progress. The following review concerns adverse ocular effects of systemic drug administration. PMID:6356101

  4. Club Drugs

    MedlinePlus

    ... Rohypnol, ketamine, as well as MDMA (ecstasy) and methamphetamine ( Drug Facts: Club Drugs , National Institute on Drug ... Club Drugs , National Institute on Drug Abuse, 2010). Methamphetamine is a powerfully addictive stimulant associated with serious ...

  5. 76 FR 20686 - Draft Guidance for Industry on Safety Labeling Changes; Implementation of the Federal Food, Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-13

    ...; Implementation of the Federal Food, Drug, and Cosmetic Act; Availability AGENCY: Food and Drug Administration...) of the Federal Food, Drug, and Cosmetic Act.'' The Food and Drug Administration Amendments Act of 2007 (FDAAA) added new provisions to the Federal Food, Drug, and Cosmetic Act (the FD&C...

  6. Erosive and cariogenicity potential of pediatric drugs: study of physicochemical parameters

    PubMed Central

    2013-01-01

    Background Pediatric medications may possess a high erosive potential to dental tissues due to the existence of acid components in their formulations. The purpose was to determine the erosive and cariogenic potential of pediatric oral liquid medications through the analysis of their physicochemical properties in vitro. Methods A total of 59 substances were selected from the drug reference list of the National Health Surveillance Agency (ANVISA), which belong to 11 therapeutic classes, as follows: analgesics, non-steroidal anti-inflammatory, corticosteroids, antihistamines, antitussives, bronchodilators, antibacterials, antiparasitics, antiemetics, anticonvulsants and antipsychotics. Measurement of pH was performed by potentiometry, using a digital pH meter. For the Total Titratable Acidity (TTA) chemical assay, a 0.1 N NaOH standard solution was used, which was titrated until drug pH was neutralized. The Total Soluble Solids Contents (TSSC) quantification was carried out by refractometry using Brix scale and the analysis of Total Sugar Content was performed according to Fehling’s method. In addition, it was analyzed the information contained in the drug inserts with regard to the presence of sucrose and type of acid and sweetener added to the formulations. Results All drug classes showed acidic pH, and the lowest mean was found for antipsychotics (2.61 ± 0.08). There was a large variation in the TTA (0.1% - 1.18%) and SST (10.44% - 57.08%) values. High total sugar contents were identified in the antitussives (53.25%) and anticonvulsants (51.75%). As described in the drug inserts, sucrose was added in 47.5% of the formulations, as well as citric acid (39.0%), sodium saccharin (36.4%) and sorbitol (34.8%). Conclusion The drugs analyzed herein showed physicochemical characteristics indicative of a cariogenic and erosive potential on dental tissues. Competent bodies’ strategies should be implemented in order to broaden the knowledge of health professionals

  7. 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

    ... Food, Drug, and Cosmetic Act; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice... Pediatric Uses of Medical Devices Under Section 515A of the Federal Food, Drug, and Cosmetic Act.'' FDA is... information required under the Federal Food, Drug, and Cosmetic Act (the FD&C Act). This draft guidance is...

  8. Projecting future drug expenditures--1994.

    PubMed

    Santell, J P

    1994-01-15

    The use of information on inflation, generic competition, market introduction of new drug entities, institution-specific drug-use patterns, and federal legislation to project drug expenditures is discussed. Inflation of pharmaceutical prices has been decreasing over the past few years. Increases in the producer price index for drugs and pharmaceuticals diminished from 6.9% in 1991 to 4.3% in the first half of 1993; the specter of government regulation may be one reason. Pharmacy group purchasing organizations (GPOs) predicted that in 1994 expenditures would increase an average of 2.1% for contracted drug items and 8.3% for noncontracted items. Expenditures for biotechnology drugs in January through July 1993 increased 16% over the same period in 1992; such agents are now hospital pharmacies' third most costly drug category, at 10% of total expenditures. Future price competition by generic drug products can be predicted from information on patent or market-exclusivity expiration. To predict the market release of new drug products, new-drug applications filed with FDA can be monitored. The most important component in projecting drug expenditures is a specific institution's pattern of use of high-cost drugs. Mechanisms that can be used to monitor changes in therapeutic strategies and drug-use protocols include drug cost indexes, assessment of drug-use patterns by outside companies, and computerized models for specific high-cost drugs. Drug expenditures can be affected by legislative changes such as the Medicaid rebate provisions of the Omnibus Budget Reconciliation Act of 1990 and the Medicare outpatient drug benefit in the proposed American Health Security Act. The accuracy of projections of drug expenditures can be improved by examining inflation, generic competition, the introduction of new drug entities, institution-specific drug-use patterns, and legislative issues. Pharmacy managers need better methods for estimating institution-specific use of high-cost drugs

  9. 78 FR 72899 - Draft Guidance for Industry on Registration for Human Drug Compounding Outsourcing Facilities...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-04

    ... Compounding Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act..., and Cosmetic Act.'' The draft guidance addresses new provisions in the Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Drug Quality and Security Act (DQSA). The draft guidance...

  10. 75 FR 45636 - Animal Generic Drug User Fee Rates and Payment Procedures for Fiscal Year 2011

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-03

    ... HUMAN SERVICES Food and Drug Administration Animal Generic Drug User Fee Rates and Payment Procedures... generic new animal drug user fees. The Federal Food, Drug, and Cosmetic Act (the act), as amended by the Animal Generic Drug User Fee Act of 2008 (AGDUFA), authorizes FDA to collect user fees for...

  11. 77 FR 45629 - Animal Generic Drug User Fee Rates and Payment Procedures for Fiscal Year 2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-01

    ... HUMAN SERVICES Food and Drug Administration Animal Generic Drug User Fee Rates and Payment Procedures... generic new animal drug user fees. The Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Animal Generic Drug User Fee Act of 2008 (AGDUFA), authorizes FDA to collect user fees for...

  12. Act resilient.

    PubMed

    Joseph, Genie; Bice-Stephens, Wynona

    2014-01-01

    Attendees have reported changing from being fearful to serene, from listless to energized, from disengaged to connected, and becoming markedly less anxious in a few weeks. Anecdotally, self-reported stress levels have been reduced by over 50% after just one class. Attendees learn not to be afraid of their feelings by working with emotions in a playful manner. When a person can act angry, but separate himself from his personal story, the emotional energy exists in a separate form that is not attached to specific events, and can be more easily dealt with and neutralized. Attendees are taught to "take out the emotional trash" through expressive comedy. They become less intimated by their own emotional intensity and triggers as they learn how even metaphorical buckets of anger, shame, guilt and hurt can be emotionally emptied. The added benefit is that this is accomplished without the disclosure of personal information of the requirement to reexperience past pain which can trigger its own cascade of stress. PMID:24706248

  13. Drug allergies

    MedlinePlus

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The ...

  14. Drug allergies

    MedlinePlus

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... Adverse reactions to drugs are common. (adverse means unwanted or unexpected.) Almost any drug can cause an adverse reaction. Reactions range from irritating ...

  15. Drug Safety

    MedlinePlus

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  16. Club Drugs

    MedlinePlus

    ... uses. Other uses of these drugs are abuse. Club drugs are also sometimes used as "date rape" drugs, to make someone unable to say no to or fight back against sexual assault. Abusing these drugs can ...

  17. 21 CFR 316.36 - Insufficient quantities of orphan drugs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Insufficient quantities of orphan drugs. 316.36... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.36 Insufficient quantities of orphan drugs. (a) Under section 527 of the act, whenever the Director has reason to believe...

  18. Drug-drug interactions between clopidogrel and novel cardiovascular drugs.

    PubMed

    Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J

    2015-10-15

    The combination of aspirin and the thienopyridine clopidogrel is a cornerstone in the prevention of atherothrombotic events. These two agents act in concert to ameliorate the prothrombotic processes stimulated by plaque rupture and vessel injury complicating cardiovascular disease. Guidelines recommend the use of clopidogrel in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention, and the drug remains the most utilized P2Y12 receptor inhibitor despite the fact that newer antiplatelet agents are now available. In recent years, numerous studies have shown inconsistency in the efficacy of clopidogrel to prevent atherothrombotic events. Studies of platelet function testing have shown variability in the response to clopidogrel. One of the major reason for this phenomenon lies in the interaction between clopidogrel and other drugs that may affect clopidogrel absorption, metabolism, and ultimately its antiplatelet action. Importantly, these drug-drug interactions have prognostic implications, since patients with high on-treatment platelet reactivity associated with reduced clopidogrel metabolism have an increased risk of ischemia. Previous systematic reviews have focused on drug-drug interactions between clopidogrel and specific pharmacologic classes, such as proton pump inhibitors, calcium channel blockers, and statins. However, more recent pieces of scientific evidence show that clopidogrel may also interact with newer drugs that are now available for the treatment of cardiovascular patients. Accordingly, the aim of this review is to highlight and discuss recent data on drug-drug interactions between clopidogrel and third-generation proton pump inhibitors, pantoprazole and lansoprazole, statins, pitavastatin, and antianginal drug, ranolazine. PMID:26341013

  19. Drug companies, UNAIDS make drugs available.

    PubMed

    1998-01-01

    The United Nations AIDS (UNAIDS) initiative is working with several drug companies and four countries on a pilot program to build a health infrastructure that provides affordable drugs to insure that combination therapies are used appropriately. The countries involved in the program are Uganda, Chile, Vietnam and Cote d'Ivoire, and the drug companies are Glaxo Wellcome, Hoffmann-La Roche, and Virco NV. Each country agreed to form national HIV/AIDS drug advisory boards, and non-profit companies will act as clearinghouses. Financing will come from the pharmaceutical companies, local health ministries, and a $1 million grant from UNAIDS. The program will be evaluated in terms of improvements to overall health care delivery, number of people treated, the impact on emergency care, and the rate of illness and death. PMID:11364863

  20. Drugs, drugs--who has the drugs?

    PubMed

    Blair, James

    2012-01-01

    Drug diversion, although on the increase, is not the only problem involving drugs that hospital security officials should be concerned with. Growing drug shortages, offshore production, counterfeiting, and weaknesses in the drug supply chain in case of a world-wide pandemic, are even greater causes for concern, the author claims. PMID:22423518

  1. Cough management: a practical approach

    PubMed Central

    2011-01-01

    Cough is one of the most common symptoms for which patients seek medical attention from primary care physicians and pulmonologists. Cough is an important defensive reflex that enhances the clearance of secretions and particles from the airways and protects the lower airways from the aspiration of foreign materials. Therapeutic suppression of cough may be either disease-specific or symptom related. The potential benefits of an early treatment of cough could include the prevention of the vicious cycle of cough. There has been a long tradition in acute cough, which is frequently due to upper respiratory tract infections, to use symptom-related anti-tussives. Suppression of cough (during chronic cough) may be achieved by disease-specific therapies, but in many patients it is often necessary to use symptomatic anti-tussives, too. According to the current guidelines of the American College of Chest Physician on "Cough Suppressants and Pharmacologic Protussive Therapy" and additional clinical trials on the most frequent anti-tussive drugs, it should be possible to diagnose and treat cough successfully in a majority of cases. Among drugs used for the symptomatic treatment of cough, peripherally acting anti-tussives such as levodropropizine and moguisteine show the highest level of benefit and should be recommended especially in children. By improving our understanding of the specific effects of these anti-tussive agents, the therapeutic use of these drugs may be refined. The present review provides a summary of the most clinically relevant anti-tussive drugs in addition to their potential mechanism of action. PMID:21985340

  2. Cough management: a practical approach.

    PubMed

    De Blasio, Francesco; Virchow, Johann C; Polverino, Mario; Zanasi, Alessandro; Behrakis, Panagiotis K; Kilinç, Gunsely; Balsamo, Rossella; De Danieli, Gianluca; Lanata, Luigi

    2011-01-01

    Cough is one of the most common symptoms for which patients seek medical attention from primary care physicians and pulmonologists. Cough is an important defensive reflex that enhances the clearance of secretions and particles from the airways and protects the lower airways from the aspiration of foreign materials. Therapeutic suppression of cough may be either disease-specific or symptom related. The potential benefits of an early treatment of cough could include the prevention of the vicious cycle of cough. There has been a long tradition in acute cough, which is frequently due to upper respiratory tract infections, to use symptom-related anti-tussives. Suppression of cough (during chronic cough) may be achieved by disease-specific therapies, but in many patients it is often necessary to use symptomatic anti-tussives, too. According to the current guidelines of the American College of Chest Physician on "Cough Suppressants and Pharmacologic Protussive Therapy" and additional clinical trials on the most frequent anti-tussive drugs, it should be possible to diagnose and treat cough successfully in a majority of cases. Among drugs used for the symptomatic treatment of cough, peripherally acting anti-tussives such as levodropropizine and moguisteine show the highest level of benefit and should be recommended especially in children. By improving our understanding of the specific effects of these anti-tussive agents, the therapeutic use of these drugs may be refined. The present review provides a summary of the most clinically relevant anti-tussive drugs in addition to their potential mechanism of action. PMID:21985340

  3. Less discontinuation of ADHD drug use since the availability of long-acting ADHD medication in children, adolescents and adults under the age of 45 years in the Netherlands

    PubMed Central

    Souverein, Patrick C.; Swaab, Hanna; van Engeland, Herman; Egberts, Toine C. G.; Heerdink, Eibert R.

    2010-01-01

    Treatment options for ADHD in the Netherlands have increased with the introduction of the extended-release formulations of methylphenidate (MPH ER, Concerta®) in 2003 and atomoxetine (ATX, Strattera®) in 2005, but data on the effect on drug usage patterns are scarce. The objective of the present study was to describe changes in the patterns of ADHD medication use and determinants thereof among children, adolescents and adults (<45 years) starting ADHD medication since the introduction of MPH ER and ATX. Data were obtained from Dutch community pharmacies as collected by the Foundation for Pharmaceutical Statistics, covering 97% of all dispenses for prescription medicines to outpatients in the Netherlands. Usage patterns (continuation, discontinuation, switching and addition) of ADHD drugs were evaluated at 3, 6 and 12 months after initiation for three separate time cohorts (patients starting ADHD medication in Jan-Dec 2002, Jan 2003–June 2004, respectively July 2004–Dec 2005). It was found that between 2002 and 2006, most ADHD drug users were initiated on methylphenidate IR. Discontinuation of any ADHD drug treatment decreased over time partly in favour of switching and addition. Discontinuation at 3 months decreased from around 33% to around 25%, at 6 months from less than 50% to almost 35%, and at 12 months from just fewer than 60% to less than 45%. Discontinuation was higher among females and in adults >18 years. After the introduction of MPH ER and ATX (time cohort III), 16.5% of the incident ADHD drug users switched their medication and almost 9% added an ADHD drug to the prior ADHD drug. In conclusion, discontinuation of incident ADHD drug use is high after 3, 6 and 12 months. During the study period, the incidence of discontinuation decreased because of the availability of extended-release methylphenidate and atomoxetine. PMID:21258431

  4. Drug Facts

    MedlinePlus Videos and Cool Tools

    ... Weed, Pot) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Other Drugs of Abuse What ... About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs You can call 1-800- ...

  5. Drug Reactions

    MedlinePlus

    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as gingko and blood thinners ...

  6. Drug Resistance

    MedlinePlus

    HIV Treatment Drug Resistance (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  7. Serious drug interactions.

    PubMed

    Aronson, J

    1993-10-01

    Of the many varieties of drug interactions, which occur when the disposition or actions of one drug are changed by another, only a few are serious or potentially fatal. A representative outline of some of these illustrates the problem. Precipitant drugs are those which produce the interaction, and object drugs are those whose effects are changed. The interactions which are usually significant are those which alter the metabolism, involve renal excretion, or change the effects of the object drug, especially when the object drug has a low therapeutic index (cardiovascular drugs, anticoagulants, drugs acting on the brain, hypoglycemic drugs, hormones, and cytotoxic drugs). Warfarin toxicity, for example, is produced by aspirin, phenylbutazone, and azapropazone. The dosage requirements of warfarin are reduced by chloramphenicol, ciprofloxacin and other quinolones, erythromycin and some of the other macrolides, metronidazole and other imidazoles, tetracyclines, amiodarone, cimetidine (but not ranitidine), and fibrates. Potassium-depleting drugs can potentiate the action of digoxin, and the elimination of digoxin can be reduced by amiodarone, propafenone, quinidine, and verapamil. Combined oral contraceptives can lose effectiveness through the interaction of carbamazepine, griseofulvin, phenytoin, or rifampicin, which increase estrogen metabolism. In addition, broad-spectrum antibiotics such as ampicillin or tetracyclines also reduce contraceptive effectiveness by altering gut absorption. Even a single drink of an alcoholic beverage may be dangerous to people taking antidepressants, antihistamines, antipsychotic drugs, benzodiazepines, or lithium. Antihistamines suffer inhibited metabolism in the liver if taken in conjunction with the antifungal imidazoles and some of the macrolide antibiotics. Cardiotoxicity of antihistamines is also enhanced by drugs with similar cardiotoxic effects. Lithium potentiation is enhanced by the new serotonin-reuptake inhibitors, and lithium

  8. Does Drug Testing Deter Drug Court Participants from Using Drugs or Alcohol?

    ERIC Educational Resources Information Center

    Kleinpeter, Christine B.; Brocato, Jo; Koob, Jeffrey J.

    2010-01-01

    This study evaluates 3 drug-testing strategies implemented in 5 different jurisdictions with drug courts in Orange County, California. The purpose of the study was to determine whether the sweat patch acts as a deterrent and under what conditions it can be used to improve outcomes. Results indicated that although the use of the sweat patch did not…

  9. 75 FR 160 - Paperwork Reduction Act; 30-Day Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-04

    ... From the Federal Register Online via the Government Publishing Office OFFICE OF NATIONAL DRUG CONTROL POLICY Paperwork Reduction Act; 30-Day Notice AGENCY: Office of National Drug Control Policy. The Office of National Drug Control Policy (ONDCP) proposes the collection of information concerning...

  10. Canadian drug regulatory framework.

    PubMed

    Kelly, L; Lazzaro, M; Petersen, C

    2007-03-01

    The role of regulatory drug submission evaluators in Canada is to critically assess both the data submitted and the sponsor's interpretation of the data in order to reach an evidence-, and context-based recommendation as to the potential benefits and potential harms (i.e., risks) associated with taking the drug under the proposed conditions of use. The purpose of this document is to outline the regulatory framework in which this assessment occurs, including: defining what "authorization to market a drug in Canada" means, in terms of the role of the sponsor, the responsibility of Health Canada in applying the Food and Drugs Act prior to and after marketing authorization, and the distinction between regulatory authorization versus physician authorization; highlighting organizational, process and legal factors within Health Canada related to authorization of clinical trials and authorization to market a drug; considerations during the review process, such as regulatory and scientific issues related to the drug, patient populations and trial designs; application of international guidelines, and decisions from other jurisdictions; regulatory realities regarding drug authorization, including the requirement for wording in the Product Monograph to accurately reflect the information currently available on the safe and effective use of a drug, and that hypothesis-confirming studies are essential to regulatory endorsement; current issues related to the review of therapies for dementia, such as assessing preventative treatments, and therapies that have symptomatic versus disease-modifying effects, statistical issues regarding missing data, and trial design issues. PMID:17469674

  11. Interoception and Drug Addiction

    PubMed Central

    Paulus, Martin P.; Stewart, Jennifer L.

    2013-01-01

    The role of interoception and its neural basis with relevance to drug addiction is reviewed. Interoception consists of the receiving, processing, and integrating body-relevant signals with external stimuli to affect ongoing motivated behavior. The insular cortex is the central nervous system hub to process and integrate these signals. Interoception is an important component of several addiction relevant constructs including arousal, attention, stress, reward, and conditioning. Imaging studies with drug-addicted individuals show that the insular cortex is hypo-active during cognitive control processes but hyperactive during cue reactivity and drug-specific, reward-related processes. It is proposed that interoception contributes to drug addiction by incorporating an “embodied” experience of drug uses together with the individual’s predicted versus actual internal state to modulate approach or avoidance behavior, i.e. whether to take or not to take drugs. This opens the possibility of two types of interventions. First, one may be able to modulate the embodied experience by enhancing insula reactivity where necessary, e.g. when engaging in drug seeking behavior, or attenuating insula when exposed to drug-relevant cues. Second, one may be able to reduce the urge to act by increasing the frontal control network, i.e. inhibiting the urge to use by employing cognitive training. PMID:23855999

  12. Interoception and drug addiction.

    PubMed

    Paulus, Martin P; Stewart, Jennifer L

    2014-01-01

    The role of interoception and its neural basis with relevance to drug addiction is reviewed. Interoception consists of the receiving, processing, and integrating body-relevant signals with external stimuli to affect ongoing motivated behavior. The insular cortex is the central nervous system hub to process and integrate these signals. Interoception is an important component of several addiction relevant constructs including arousal, attention, stress, reward, and conditioning. Imaging studies with drug-addicted individuals show that the insular cortex is hypo-active during cognitive control processes but hyperactive during cue reactivity and drug-specific, reward-related processes. It is proposed that interoception contributes to drug addiction by incorporating an "embodied" experience of drug uses together with the individual's predicted versus actual internal state to modulate approach or avoidance behavior, i.e. whether to take or not to take drugs. This opens the possibility of two types of interventions. First, one may be able to modulate the embodied experience by enhancing insula reactivity where necessary, e.g. when engaging in drug seeking behavior, or attenuating insula when exposed to drug-relevant cues. Second, one may be able to reduce the urge to act by increasing the frontal control network, i.e. inhibiting the urge to use by employing cognitive training. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. PMID:23855999

  13. 21 CFR 201.100 - Prescription drugs for human use.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Prescription drugs for human use. 201.100 Section 201.100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... for human use. A drug subject to the requirements of section 503(b)(1) of the act shall be exempt...

  14. 21 CFR 201.100 - Prescription drugs for human use.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Prescription drugs for human use. 201.100 Section 201.100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... for human use. A drug subject to the requirements of section 503(b)(1) of the act shall be exempt...

  15. 76 FR 76738 - Generic Drug User Fee; Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-08

    ... HUMAN SERVICES Food and Drug Administration Generic Drug User Fee; Public Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public meeting; request for comments. The Food and Drug Administration... Drug User Fee Act (GDUFA), which will authorize FDA to collect fees and use them for the process...

  16. 21 CFR 332.30 - Labeling of antiflatulent drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... commerce of unapproved new drugs in violation of section 505(a) of the act. (1) (Select one of the... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of antiflatulent drug products. 332.30 Section 332.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  17. ADATSA Treatment Outcomes: Employment and Cost Avoidance: An Eighteen Month Follow-Up Study of Indigent Persons Served by Washington State's Alcoholism and Drug Addiction Treatment and Support Act. Report No. 4-19.

    ERIC Educational Resources Information Center

    Longhi, Dario; And Others

    This report provides a cost-benefit analysis of a program that provides publicly-funded treatment and support for persons who are addicted to alcohol or other drugs and who are judged to be indigent, unemployable, and incapacitated due to their addiction. The study focused on two client outcomes: (1) determine employment outcomes during an 18…

  18. Current good manufacturing practice for positron emission tomography drugs.

    PubMed

    2009-12-10

    The Food and Drug Administration (FDA) is issuing regulations on current good manufacturing practice (CGMP) for positron emission tomography (PET) drugs. The regulations are intended to ensure that PET drugs meet the requirements of the Federal Food, Drug, and Cosmetic Act (the act) regarding safety, identity, strength, quality, and purity. In this final rule, we are establishing CGMP regulations for approved PET drugs. For investigational and research PET drugs, the final rule states that the requirement to follow CGMP may be met by complying with these regulations or by producing PET drugs in accordance with the United States Pharmacopeia (USP) general chapter on compounding PET radiopharmaceuticals. We are establishing these CGMP requirements for PET drugs under the provisions of the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). Elsewhere in this issue of the Federal Register, we are announcing the availability of a guidance entitled "PET Drugs--Current Good Manufacturing Practice (CGMP)." PMID:20169678

  19. 76 FR 45811 - Animal Drug User Fee Rates and Payment Procedures for Fiscal Year 2012

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-01

    ...The Food and Drug Administration (FDA) is announcing the rates and payment procedures for fiscal year (FY) 2012 animal drug user fees. The Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Animal Drug User Fee Act of 2003 (ADUFA) and the Animal Drug User Fee Amendments of 2008 (ADUFA II), authorizes FDA to collect user fees for certain animal drug applications and......

  20. Parent Drug Education: A Participatory Action Research Study into Effective Communication about Drugs between Parents and Unrelated Young People

    ERIC Educational Resources Information Center

    Mallick, Jane

    2007-01-01

    Parent drug education is considered a key aspect of drug prevention. Effective communication acts as protective factor for drug misuse in young people. This study is a Participatory Action Research study of "Drugsbridge", a drug education programme that has an emphasis on facilitating intergenerational communication about drugs between parents and…

  1. 78 FR 46958 - Animal Generic Drug User Fee Rates and Payment Procedures for Fiscal Year 2014

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-02

    ...,'' from the upper right-hand corner of your completed Animal Generic Drug User Fee Cover Sheet. Also write... HUMAN SERVICES Food and Drug Administration Animal Generic Drug User Fee Rates and Payment Procedures... generic new animal drug user fees. The Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended...

  2. Drug Abuse

    MedlinePlus

    ... as drugged driving, violence, stress, and child abuse. Drug abuse can lead to homelessness, crime, and missed work or problems with keeping a job. It harms unborn babies and destroys families. There are different types of treatment for drug abuse. But the best is to prevent drug ...

  3. Drug-facilitated sexual assault ('date rape').

    PubMed

    Schwartz, R H; Milteer, R; LeBeau, M A

    2000-06-01

    In the past few years, drug-facilitated sexual assaults have received widespread media coverage. In addition to alcohol, the most frequently used date-rape drug, flunitrazepam (Rohypnol), a fast-acting benzodiazepine, and gamma-hydroxybutyrate (GHB) and its congeners are among the most popular drugs used for this purpose. The latter drug is easily procured at some gymnasiums, popular bars, discos, and rave clubs, as well as over the Internet. Perpetrators choose these drugs because they act rapidly, produce disinhibition and relaxation of voluntary muscles, and cause the victim to have lasting anterograde amnesia for events that occur under the influence of the drug. Alcoholic beverages potentiate the drug effects. We review several date-rape drugs, provide information on laboratory testing for them, and offer guidelines for preventing drug-facilitated sexual assault. PMID:10881768

  4. [Pharmacokinetic interactions of telaprevir with other drugs].

    PubMed

    Berenguer Berenguer, Juan; González-García, Juan

    2013-07-01

    Telaprevir is a new direct-acting antiviral drug for the treatment of hepatitis C virus (HCV) infection and is both a substrate and an inhibitor of cytochrome P450 (CYP450) isoenzymes. With the introduction of this new drug, assessment of drug-drug interactions has become a key factor in the evaluation of patients under treatment for HCV infection. During the treatment of this infection, many patients require other drugs to mitigate the adverse effects of anti-HCV drugs and to control other comorbidities. Moreover, most patients coinfected with HIV and HCV require antiretroviral therapy during treatment for HCV. Physicians should therefore be familiar with the pharmacokinetic properties of direct-acting antivirals for HCV treatment and their potential drug-drug interactions. The present article reviews the available information to date on the interactions of telaprevir with other drugs and provides recommendations for daily clinical practice. PMID:24063902

  5. Drug diversion

    PubMed Central

    Wood, Danielle

    2015-01-01

    SUMMARY Prescription drug diversion has significant health, legal and social implications. Deaths from misuse of prescription drugs account for a significant proportion of overdose deaths. The drugs most commonly involved are analgesics, particularly opioids, and psychoactive drugs, particularly benzodiazepines. Diverted drugs are most often sourced from a family member or friend, but are also sourced from overseas pharmacies or laboratories, or bought from drug dealers. Drug diversion can be mitigated by good prescribing practices. Systems for monitoring the prescribing and dispensing of medicines are being instituted across Australia. PMID:26648654

  6. 78 FR 35117 - Orphan Drug Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-12

    ..., 2011 (76 FR 64868), FDA issued a proposed rule to amend the Orphan Drug Regulations (part 316 (21 CFR... orphan drug program. As described in the proposed rule (76 FR 64868), FDA believes these revisions will... serve the intent of the Orphan Drug Act, as explained in the proposed rule (76 FR 64868 at 64869...

  7. 21 CFR 1210.28 - Permits waiving clause 4, section 2 of the Federal Import Milk Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Import Milk Act. 1210.28 Section 1210.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... DRUG ADMINISTRATION REGULATIONS UNDER THE FEDERAL IMPORT MILK ACT Permit Control § 1210.28 Permits waiving clause 4, section 2 of the Federal Import Milk Act. The Secretary, in his discretion, will...

  8. 21 CFR 1210.27 - Permits waiving clauses 2 and 5, section 2 of the Federal Import Milk Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Federal Import Milk Act. 1210.27 Section 1210.27 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... FOOD AND DRUG ADMINISTRATION REGULATIONS UNDER THE FEDERAL IMPORT MILK ACT Permit Control § 1210.27 Permits waiving clauses 2 and 5, section 2 of the Federal Import Milk Act. A permit to ship or...

  9. Child Labor Amendments of 1991. Joint Hearing on S.600 To Amend the Fair Labor Standards Act of 1938 To Improve Enforcement of the Child Labor Provisions of Such Act, and for Other Purposes, before the Subcommittee on Labor and Subcommittee on Children, Family, Drugs and Alcoholism of the Committee on Labor and Human Resources. United States Senate, One Hundred Second Congress, First Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Senate Committee on Labor and Human Resources.

    A joint hearing was held to consider S. 600, a U.S. Senate bill designed to help educate the public about federal child labor laws and strengthen enforcement of child labor laws through an amendment to the Fair Labor Standards Act of 1938. Senator Howard M. Metzenbaum presided. The hearings were called because of sporadic enforcement of inadequate…

  10. Medicare prescription drug discount cards.

    PubMed

    Bryant, Natasha

    2004-01-01

    With the passage of the Medicare Prescription Drug Improvement and Modernization Act of 2003 came the creation of a Part D drug benefit through Medicare. Until that benefit is implemented, Medicare has established a drug discount card program to help your clients save money on their outpatient prescription drug expenses. In this brief, we discuss the Medicare-approved discount cards--who is eligible, how they work, how your clients can best make important decisions about them, and what help is out there for people with low incomes. PMID:15224690

  11. Long-acting hormonal contraception.

    PubMed

    Benagiano, Giuseppe; Gabelnick, Henry; Brosens, Ivo

    2015-11-01

    Today, a new category of fertility-regulating agents has been created: long-acting, reversible hormonal contraceptives; they minimize compliance, while maximize effectiveness. They comprise subdermal implants and intrauterine devices. Other long-acting agents exist, such as Depo Provera and Noristerat. Use of Depo Provera and Noristerat carries great effectiveness, good clinical safety and usefulness in developing countries. They cause no significant increase in breast cancer risk, but they may carry an increased risk of HIV. Subcutaneous delivery systems have two common features: prolongation of effect is obtained by a drug reservoir and for most of their duration of action they provide a continuous, sustained release of the active hormone. Finally, the intrauterine system Mirena represents both a very effective contraceptive and a specific treatment for menorrhagia. PMID:26626534

  12. 77 FR 20826 - Guidance for Industry and Food and Drug Administration Staff; Food and Drug Administration and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-06

    ..., 2010 (75 FR 22599), FDA announced the availability of the draft guidance. Comments on the draft... the Federal Food, Drug, and Cosmetic Act; Availability AGENCY: Food and Drug Administration, HHS... Procedures for Section 513(g) Requests for Information under the Federal Food, Drug, and Cosmetic Act.''...

  13. 21 CFR 1210.27 - Permits waiving clauses 2 and 5, section 2 of the Federal Import Milk Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Permits waiving clauses 2 and 5, section 2 of the Federal Import Milk Act. 1210.27 Section 1210.27 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION REGULATIONS...

  14. 21 CFR 1210.28 - Permits waiving clause 4, section 2 of the Federal Import Milk Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Permits waiving clause 4, section 2 of the Federal Import Milk Act. 1210.28 Section 1210.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION REGULATIONS UNDER...

  15. Pediatric drug development: formulation considerations.

    PubMed

    Ali, Areeg Anwer; Charoo, Naseem Ahmad; Abdallah, Daud Baraka

    2014-10-01

    Absence of safe, effective and appropriate treatment is one of the main causes of high mortality and morbidity rates among the pediatric group. This review provides an overview of pharmacokinetic differences between pediatric and adult population and their implications in pharmaceutical development. Different pediatric dosage forms, their merits and demerits are discussed. Food and Drug Administration Act of 1997 and the Best Pharmaceuticals for Children Act 2002 added 6 months patent extension and exclusivity incentives to pharmaceutical companies for evaluation of medicinal products in children. Prescription Drug User Fee Act and Food and Drug Administration Amendments Act of 2007 made it mandatory for pharmaceutical companies to perform pediatric clinical studies on new drug products. Drug development program should include additional clinical bridge studies to evaluate differences in pharmacokinetics and pharmacodynamics of drugs in adult and child populations. Additionally, pharmaceutical development should consider ease of administration, palatability, appropriate excipients, stability and therapeutic equivalency of pediatric dosage forms. Pediatric population is diverse with individual preferences and demand for custom made dosage formulations. Practically it is not feasible to have different pharmaceutical dosage forms for each group. Hence, an appropriate dosage form that can be administered across pediatric population is warranted. PMID:24483293

  16. Drugged Driving

    MedlinePlus

    ... Infographics » Drugged Driving Drugged Driving Email Facebook Twitter Text Description of Infographic Top Right Figure : In 2009, ... crash than those who don't smoke. Bottom Text: Develop Social Strategies Offer to be a designated ...

  17. Drug Control

    ERIC Educational Resources Information Center

    Leviton, Harvey S.

    1975-01-01

    This article attempts to assemble pertinent information about the drug problem, particularily marihuana. It also focuses on the need for an educational program for drug control with the public schools as the main arena. (Author/HMV)

  18. Generic Drugs

    MedlinePlus

    ... drugs. There are a few other differences— like color, shape, size, or taste—but they do not ... different . Brand-name drugs are often advertised by color and shape. Remember the ads for the “purple ...

  19. Drug Debacle.

    PubMed

    Sorrel, Amy Lynn

    2016-01-01

    Medicaid's Vendor Drug Program is under examination by the Texas Legislature. TMA's Physicians Medicaid Congress is seizing the opportunity to call for an administrative overhaul of a drug benefit physicians describe as unnecessarily complicated and confusing. PMID:27441421

  20. 78 FR 66806 - Privacy Act of 1974

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-06

    ... security number, physical address, phone number, email address), health-related information (e.g., vital... drug abuse, alcoholism or alcohol abuse, sickle cell anemia or infection with the human... Act) and guidelines issued by OMB (65 FR 77677), December 12, 2000. Approved: October 9, 2013. Jose...

  1. The Employee Polygraph Protection Act of 1988.

    ERIC Educational Resources Information Center

    Duffy, Patrick J.

    1989-01-01

    Aspects of the new Employee Polygraph Protection Act are discussed, including exemptions, prohibited devices, limitations, exceptions, injury and access requirements, reasonable suspicion, drug industry investigations, procedural requirements, disclosure, basis for discharge, enforcement and remedies, and preemption and existing state laws. (MSE)

  2. Drug Survey.

    ERIC Educational Resources Information Center

    Gill, Wanda E.; And Others

    Results of a survey of student perceptions of drugs and drug use that was conducted at Bowie State College are presented. Studies that have been conducted on college students' use of alcohol, marijuana, and cocaine in the last five years are reviewed, along with additional studies relating to the general population and the following drugs:…

  3. Glutamatergic transmission in drug reward: implications for drug addiction

    PubMed Central

    D'Souza, Manoranjan S.

    2015-01-01

    Individuals addicted to drugs of abuse such as alcohol, nicotine, cocaine, and heroin are a significant burden on healthcare systems all over the world. The positive reinforcing (rewarding) effects of the above mentioned drugs play a major role in the initiation and maintenance of the drug-taking habit. Thus, understanding the neurochemical mechanisms underlying the reinforcing effects of drugs of abuse is critical to reducing the burden of drug addiction in society. Over the last two decades, there has been an increasing focus on the role of the excitatory neurotransmitter glutamate in drug addiction. In this review, pharmacological and genetic evidence supporting the role of glutamate in mediating the rewarding effects of the above described drugs of abuse will be discussed. Further, the review will discuss the role of glutamate transmission in two complex heterogeneous brain regions, namely the nucleus accumbens (NAcc) and the ventral tegmental area (VTA), which mediate the rewarding effects of drugs of abuse. In addition, several medications approved by the Food and Drug Administration that act by blocking glutamate transmission will be discussed in the context of drug reward. Finally, this review will discuss future studies needed to address currently unanswered gaps in knowledge, which will further elucidate the role of glutamate in the rewarding effects of drugs of abuse. PMID:26594139

  4. Glutamatergic transmission in drug reward: implications for drug addiction.

    PubMed

    D'Souza, Manoranjan S

    2015-01-01

    Individuals addicted to drugs of abuse such as alcohol, nicotine, cocaine, and heroin are a significant burden on healthcare systems all over the world. The positive reinforcing (rewarding) effects of the above mentioned drugs play a major role in the initiation and maintenance of the drug-taking habit. Thus, understanding the neurochemical mechanisms underlying the reinforcing effects of drugs of abuse is critical to reducing the burden of drug addiction in society. Over the last two decades, there has been an increasing focus on the role of the excitatory neurotransmitter glutamate in drug addiction. In this review, pharmacological and genetic evidence supporting the role of glutamate in mediating the rewarding effects of the above described drugs of abuse will be discussed. Further, the review will discuss the role of glutamate transmission in two complex heterogeneous brain regions, namely the nucleus accumbens (NAcc) and the ventral tegmental area (VTA), which mediate the rewarding effects of drugs of abuse. In addition, several medications approved by the Food and Drug Administration that act by blocking glutamate transmission will be discussed in the context of drug reward. Finally, this review will discuss future studies needed to address currently unanswered gaps in knowledge, which will further elucidate the role of glutamate in the rewarding effects of drugs of abuse. PMID:26594139

  5. ACTS data center

    NASA Technical Reports Server (NTRS)

    Syed, Ali; Vogel, Wolfhard J.

    1993-01-01

    Viewgraphs on ACTS Data Center status report are included. Topics covered include: ACTS Data Center Functions; data flow overview; PPD flow; RAW data flow; data compression; PPD distribution; RAW Data Archival; PPD Audit; and data analysis.

  6. ACTS data center

    NASA Astrophysics Data System (ADS)

    Syed, Ali; Vogel, Wolfhard J.

    1993-08-01

    Viewgraphs on ACTS Data Center status report are included. Topics covered include: ACTS Data Center Functions; data flow overview; PPD flow; RAW data flow; data compression; PPD distribution; RAW Data Archival; PPD Audit; and data analysis.

  7. Recovery Act Milestones

    SciTech Connect

    Rogers, Matt

    2009-01-01

    Every 100 days, the Department of Energy is held accountable for a progress report on the American Recovery and Reinvestment Act. Update at 200 days, hosted by Matt Rogers, Senior Advisor to Secretary Steven Chu for Recovery Act Implementation.

  8. Recovery Act Milestones

    ScienceCinema

    Rogers, Matt

    2013-05-29

    Every 100 days, the Department of Energy is held accountable for a progress report on the American Recovery and Reinvestment Act. Update at 200 days, hosted by Matt Rogers, Senior Advisor to Secretary Steven Chu for Recovery Act Implementation.

  9. Drug Interactions

    PubMed Central

    Tong Logan, Angela; Silverman, Andrew

    2012-01-01

    One of the most clinically significant complications related to the use of pharmacotherapy is the potential for drug-drug or drug-disease interactions. The gastrointestinal system plays a large role in the pharmacokinetic profile of most medications, and many medications utilized in gastroenterology have clinically significant drug interactions. This review will discuss the impact of alterations of intestinal pH, interactions mediated by phase I hepatic metabolism enzymes and P-glycoprotein, the impact of liver disease on drug metabolism, and interactions seen with commonly utilized gastrointestinal medications. PMID:22933873

  10. Forgetting ACT UP

    ERIC Educational Resources Information Center

    Juhasz, Alexandra

    2012-01-01

    When ACT UP is remembered as the pinnacle of postmodern activism, other forms and forums of activism that were taking place during that time--practices that were linked, related, just modern, in dialogue or even opposition to ACT UP's "confrontational activism"--are forgotten. In its time, ACT UP was embedded in New York City, and a larger world,…

  11. 76 FR 45814 - Animal Generic Drug User Fee Rates and Payment Procedures for Fiscal Year 2012

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-01

    ...The Food and Drug Administration (FDA) is announcing the rates and payment procedures for fiscal year (FY) 2012 generic new animal drug user fees. The Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Animal Generic Drug User Fee Act of 2008 (AGDUFA), authorizes FDA to collect user fees for certain abbreviated applications for generic new animal drugs, on certain generic......

  12. 24 CFR 960.205 - Drug use by applicants: Obtaining information from drug treatment facility.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... required by 42 CFR 2.31; and (iii) Authorizes the PHA to receive such information from the drug abuse... Service Act, 42 U.S.C. 290dd-2, and implementing regulations at 42 CFR part 2, with respect to... drug (as defined in § 5.100 of this title). (2) The PHA's request to the drug abuse treatment...

  13. 24 CFR 960.205 - Drug use by applicants: Obtaining information from drug treatment facility.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... required by 42 CFR 2.31; and (iii) Authorizes the PHA to receive such information from the drug abuse... Service Act, 42 U.S.C. 290dd-2, and implementing regulations at 42 CFR part 2, with respect to... drug (as defined in § 5.100 of this title). (2) The PHA's request to the drug abuse treatment...

  14. 24 CFR 960.205 - Drug use by applicants: Obtaining information from drug treatment facility.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... required by 42 CFR 2.31; and (iii) Authorizes the PHA to receive such information from the drug abuse... Service Act, 42 U.S.C. 290dd-2, and implementing regulations at 42 CFR part 2, with respect to... drug (as defined in § 5.100 of this title). (2) The PHA's request to the drug abuse treatment...

  15. 24 CFR 960.205 - Drug use by applicants: Obtaining information from drug treatment facility.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... required by 42 CFR 2.31; and (iii) Authorizes the PHA to receive such information from the drug abuse... Service Act, 42 U.S.C. 290dd-2, and implementing regulations at 42 CFR part 2, with respect to... drug (as defined in § 5.100 of this title). (2) The PHA's request to the drug abuse treatment...

  16. Drugs and Crime: The Relationship of Drug Use and Concomitant Criminal Behavior. Research Issues 17.

    ERIC Educational Resources Information Center

    Austin, Gregory A., Ed.; Lettieri, Dan J., Ed.

    This volume of abstracts of major research and theoretical studies dealing with the relationship between drug use, criminal behavior and the law is concerned with criminal acts other than the possession of, or trafficking in, illicit drugs. Included are 107 selected studies categorized into seven major topic areas: Reviews and Theories, Drug Use…

  17. Projecting future drug expenditures--1996.

    PubMed

    Santell, J P

    1996-01-15

    The use of information on inflation, pharmacoeconomics, generic competition, new drug entities, site-specific drug-use patterns, legislation, and the changing health care environment in the projection of drug expenditures is discussed. Drug price inflation has declined from 6.9% in 1991 to 2.1% for part of 1995. Much of the decline is attributable to deep discounts given by manufacturers to managed care institutions. Some marketing specialists are predicting that drug manufacturers will begin to scale back discounts. Pharmaceutical industry analysts project that overall price increase for pharmaceuticals in the next 12-24 months will average 2.8% (range, 0-6%). Pharmacists need to be able to understand and critically evaluate pharmacoeconomic research, particularly studies conducted by the pharmaceutical industry. Savings due to increases in generic product selection may be offset to some degree by extensions of patent expiration dates under the General Agreement on Tariffs and Trade (GATT). Drug budget projections should include a complete review of new drugs and biotechnology agents pending FDA approval, drugs pending approval for new indications, and common unlabeled uses of expensive existing agents. Various methods are available for tracking drug-use patterns in specific practice settings. When resources are limited, pharmacy managers may elect to target only high-cost drugs; a proactive approach, such as projecting costs and developing guidelines for costly agents before their market release and before consideration by the pharmacy and therapeutics committee, is advantageous. Relevant legislative activities in 1995 included reform proposals for Medicare, Medicaid, and FDA; the Federal Acquisition Streamlining Act; and GATT. Disease management and other approaches to pharmacy benefits have increased opportunities for cooperative arrangements between drug companies and health care providers that may have major effects on drug marketing and pricing. Combining

  18. Drug Testing. ERIC Digest Series Number EA35 (Revised).

    ERIC Educational Resources Information Center

    Klauke, Amy; Hadderman, Margaret

    Despite privacy concerns, school administrators are feeling pressure to adopt urgent measures to keep drugs and alcohol from further endangering our youth's well-being and undermining staff performance. This urgency is reinforced by a national anti-drug campaign and Congressional passage of the Drug-Free Workplace Act (1988) and the Drug-Free…

  19. 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

    ... Administrative Detention Under the Food and Drug Administration Safety and Innovation Act AGENCY: Food and Drug... Administration Safety and Innovation Act (FDASIA). This document is intended to solicit input from all relevant..., and Cosmetic Act (the FD&C Act) (21 U.S.C. 334(g)) to provide FDA administrative detention...

  20. 16 CFR 1500.81 - Exemptions for food, drugs, cosmetics, and fuels.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Exemptions for food, drugs, cosmetics, and... § 1500.81 Exemptions for food, drugs, cosmetics, and fuels. (a) Food, drugs, and cosmetics. Substances subject to the Federal Food, Drug, and Cosmetic Act are exempted by section 2(f)(2) of the act; but...

  1. 16 CFR 1500.81 - Exemptions for food, drugs, cosmetics, and fuels.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Exemptions for food, drugs, cosmetics, and... § 1500.81 Exemptions for food, drugs, cosmetics, and fuels. (a) Food, drugs, and cosmetics. Substances subject to the Federal Food, Drug, and Cosmetic Act are exempted by section 2(f)(2) of the act; but...

  2. 16 CFR 1500.81 - Exemptions for food, drugs, cosmetics, and fuels.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Exemptions for food, drugs, cosmetics, and... § 1500.81 Exemptions for food, drugs, cosmetics, and fuels. (a) Food, drugs, and cosmetics. Substances subject to the Federal Food, Drug, and Cosmetic Act are exempted by section 2(f)(2) of the act; but...

  3. 16 CFR 1500.81 - Exemptions for food, drugs, cosmetics, and fuels.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Exemptions for food, drugs, cosmetics, and... § 1500.81 Exemptions for food, drugs, cosmetics, and fuels. (a) Food, drugs, and cosmetics. Substances subject to the Federal Food, Drug, and Cosmetic Act are exempted by section 2(f)(2) of the act; but...

  4. 16 CFR 1500.81 - Exemptions for food, drugs, cosmetics, and fuels.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Exemptions for food, drugs, cosmetics, and... § 1500.81 Exemptions for food, drugs, cosmetics, and fuels. (a) Food, drugs, and cosmetics. Substances subject to the Federal Food, Drug, and Cosmetic Act are exempted by section 2(f)(2) of the act; but...

  5. 21 CFR 16.24 - Regulatory hearing required by the act or a regulation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Regulatory hearing required by the act or a regulation. 16.24 Section 16.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL REGULATORY HEARING BEFORE THE FOOD AND DRUG ADMINISTRATION Initiation of Proceedings §...

  6. Drug Research

    NASA Technical Reports Server (NTRS)

    1989-01-01

    NBOD2, a program developed at Goddard Space Flight Center to solve equations of motion coupled N-body systems is used by E.I. DuPont de Nemours & Co. to model potential drugs as a series of elements. The program analyses the vibrational and static motions of independent components in drugs. Information generated from this process is used to design specific drugs to interact with enzymes in designated ways.

  7. Drug dependence

    MedlinePlus

    ... men References American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders . 5th ed. Arlington, VA: American Psychiatric Publishing. 2013. Kowalchuk A, Reed BC. Drug abuse. In: ...

  8. Drug abuse

    MedlinePlus

    ... abuse References American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders . 5th ed. Arlington, VA: American Psychiatric Publishing. 2013. Weiss RD. Drugs of abuse. In: Goldman ...

  9. Frequency of Natural Resistance within NS5a Replication Complex Domain in Hepatitis C Genotypes 1a, 1b: Possible Implication of Subtype-Specific Resistance Selection in Multiple Direct Acting Antivirals Drugs Combination Treatment.

    PubMed

    Bagaglio, Sabrina; Andolina, Andrea; Merli, Marco; Uberti-Foppa, Caterina; Morsica, Giulia

    2016-01-01

    Different HCV subtypes may naturally harbor different resistance selection to anti-NS5a inhibitors. 2761 sequences retrieved from the Los Alamos HCV database were analyzed in the NS5a domain 1, the target of NS5a inhibitors. The NS5a resistance-associated polymorphisms (RAPs) were more frequently detected in HCV G1b compared to G1a. The prevalence of polymorphisms associated with cross-resistance to compounds in clinical use (daclatasvir, DCV, ledipasvir, LDV, ombitasvir, and OMV) or scheduled to come into clinical use in the near future (IDX719, elbasvir, and ELV) was higher in G1b compared to G1a (37/1552 (2.4%) in 1b sequences and 15/1209 (1.2%) in 1a isolates, p = 0.040). Interestingly, on the basis of the genotype-specific resistance pattern, 95 (6.1%) G1b sequences had L31M RAP to DCV/IDX719, while 6 sequences of G1a (0.5%) harbored L31M RAP, conferring resistance to DCV/LDV/IDX719/ELV (p < 0.0001). Finally, 28 (2.3%) G1a and none of G1b isolates harbored M28V RAP to OMV (p < 0.0001). In conclusion, the pattern of subtype-specific resistance selection in the naturally occurring strains may guide the treatment option in association with direct acting antivirals (DAAs) targeting different regions, particularly in patients that are difficult to cure, such as those with advanced liver disease or individuals who have failed previous DAAs. PMID:27023593

  10. Frequency of Natural Resistance within NS5a Replication Complex Domain in Hepatitis C Genotypes 1a, 1b: Possible Implication of Subtype-Specific Resistance Selection in Multiple Direct Acting Antivirals Drugs Combination Treatment

    PubMed Central

    Bagaglio, Sabrina; Andolina, Andrea; Merli, Marco; Uberti-Foppa, Caterina; Morsica, Giulia

    2016-01-01

    Different HCV subtypes may naturally harbor different resistance selection to anti-NS5a inhibitors. 2761 sequences retrieved from the Los Alamos HCV database were analyzed in the NS5a domain 1, the target of NS5a inhibitors. The NS5a resistance-associated polymorphisms (RAPs) were more frequently detected in HCV G1b compared to G1a. The prevalence of polymorphisms associated with cross-resistance to compounds in clinical use (daclatasvir, DCV, ledipasvir, LDV, ombitasvir, and OMV) or scheduled to come into clinical use in the near future (IDX719, elbasvir, and ELV) was higher in G1b compared to G1a (37/1552 (2.4%) in 1b sequences and 15/1209 (1.2%) in 1a isolates, p = 0.040). Interestingly, on the basis of the genotype-specific resistance pattern, 95 (6.1%) G1b sequences had L31M RAP to DCV/IDX719, while 6 sequences of G1a (0.5%) harbored L31M RAP, conferring resistance to DCV/LDV/IDX719/ELV (p < 0.0001). Finally, 28 (2.3%) G1a and none of G1b isolates harbored M28V RAP to OMV (p < 0.0001). In conclusion, the pattern of subtype-specific resistance selection in the naturally occurring strains may guide the treatment option in association with direct acting antivirals (DAAs) targeting different regions, particularly in patients that are difficult to cure, such as those with advanced liver disease or individuals who have failed previous DAAs. PMID:27023593

  11. 7 CFR 29.41 - The Appropriations Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false The Appropriations Act. 29.41 Section 29.41 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards... Development, Food and Drug Administration, and Related Agencies Appropriations Act for 2002 (Pub. L. 107-76)....

  12. [Resistance to the antimalarial drugs].

    PubMed

    Venanzi, E; López-Vélez, R

    2016-09-01

    Malaria is one of the most widespread infectious diseases around the world with 214 million cases and 438,000 deaths in 2015. In the early twentieth century it was described for the first time the resistance to quinine and, since then, drug resistance to antimalarial drugs has spread up to represent a global challenge in the fight and control of malaria. Understanding the mechanisms, geography and monitoring tools that we can act against resistance to antimalarial drugs is critical to prevent its expansion. PMID:27608319

  13. Act II of the Sunshine Act.

    PubMed

    Pham-Kanter, Genevieve

    2014-11-01

    To coincide with the introduction in the United States of the Sunshine Act, Genevieve Pham-Kanter discusses what we need to look for to fight hidden bias and deliberate or unconscious corruption. Please see later in the article for the Editors' Summary. PMID:25369363

  14. [Drug dependence and psychotropic drugs].

    PubMed

    Giraud, M J; Lemonnier, E; Bigot, T

    1994-11-01

    Although the utility of psychotropic drugs has been well demonstrated, caution must still be exercised in their use. Among their potential risks, drug dependency must be kept in mind. This risk is well accepted with regard to benzodiazepines, and it appeared useful to study the potential risk for antidepressants, neuroleptics and thymoregulatory agents. Whatever the drug, the predominant factor appears to be psychological dependency. Prevention of drug dependency is most often achieved by informing the patient, limiting the length of use of the drug, making regular reevaluation of symptoms and of drug indication, and frequently be establishing a "treatment contract". The importance of the patient-physician relationship in the prescription of such treatment must be underlined. PMID:7984941

  15. Antineoplastic Drugs

    NASA Astrophysics Data System (ADS)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

    The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

  16. Drug Reactions

    MedlinePlus

    ... using any of these products. Some types of food may also cause adverse drug reactions. For example, grapefruit and grapefruit juice, as well as alcohol and caffeine, may affect how drugs work. Every time your doctor ... interactions with any foods or beverages. What about medicines I've used ...

  17. Drug Education.

    ERIC Educational Resources Information Center

    Sardana, Raj K.

    This autoinstructional lesson deals with the study of such drugs as marijuana and LSD, with emphasis on drug abuse. It is suggested that it can be used in science classes at the middle level of school. No prerequisites are suggested. The teacher's guide lists the behavioral objectives, the equipment needed to complete the experience and suggests…

  18. High-affinity dextromethorphan binding sites in guinea pig brain. II. Competition experiments.

    PubMed

    Craviso, G L; Musacchio, J M

    1983-05-01

    Binding of dextromethorphan (DM) to guinea pig brain is stereoselective, since levomethorphan is 20 times weaker than DM in competing for DM sites. In general, opiate agonists and antagonists as well as their corresponding dextrorotatory isomers are weak competitors for tritiated dextromethorphan ([3H]DM) binding sites and display IC50 values in the micromolar range. In contrast, several non-narcotic, centrally acting antitussives are inhibitory in the nanomolar range (IC50 values for caramiphen, carbetapentane, dimethoxanate, and pipazethate are 25 nM, 9 nM, 41 nM, and 190 nM, respectively). Other antitussives, such as levopropoxyphene, chlophedianol, and fominoben, have poor affinity for DM sites whereas the antitussive noscapine enhances DM binding by increasing the affinity of DM for its central binding sites. Additional competition studies indicate that there is no correlation of DM binding with any of the known or putative neurotransmitters in the central nervous system. DM binding is also not related to tricyclic antidepressant binding sites or biogenic amine uptake sites. However, certain phenothiazine neuroleptics and typical and atypical antidepressants inhibit binding with IC50 values in the nanomolar range. Moreover, the anticonvulsant drug diphenylhydantoin enhances DM binding in a manner similar to that of noscapine. Preliminary experiments utilizing acid extracts of brain have not demonstrated the presence of an endogenous ligand for DM sites. The binding characteristics of DM sites studied in rat and mouse brain indicate that the relative potencies of several antitussives to inhibit specific DM binding vary according to species. High-affinity, saturable, and stereoselective [3H]DM binding sites are present in liver homogenates, but several differences have been found for these peripheral binding sites and those described for brain. Although the nature of central DM binding sites is not known, the potent interaction of several classes of centrally

  19. Narcotic Drug and Marihuana Controls.

    ERIC Educational Resources Information Center

    Miller, Donald E.

    As a background paper for the National Association of Student Personnel Administrators Drug Education Conference held in November, 1966, this paper focuses first on narcotic control in general, and second, on the reasons for insisting on marijuana control. Brief descriptions are given of the currently existing narcotics acts at federal and state…

  20. Pharmacosomes: An Emerging Novel Vesicular Drug Delivery System for Poorly Soluble Synthetic and Herbal Drugs

    PubMed Central

    2013-01-01

    In the arena of solubility enhancement, several problems are encountered. A novel approach based on lipid drug delivery system has evolved, pharmacosomes. Pharmacosomes are colloidal, nanometric size micelles, vesicles or may be in the form of hexagonal assembly of colloidal drug dispersions attached covalently to the phospholipid. They act as befitting carrier for delivery of drugs quite precisely owing to their unique properties like small size, amphiphilicity, active drug loading, high entrapment efficiency, and stability. They help in controlled release of drug at the site of action as well as in reduction in cost of therapy, drug leakage and toxicity, increased bioavailability of poorly soluble drugs, and restorative effects. There has been advancement in the scope of this delivery system for a number of drugs used for inflammation, heart diseases, cancer, and protein delivery along with a large number of herbal drugs. Hence, pharmacosomes open new challenges and opportunities for improved novel vesicular drug delivery system. PMID:24106615

  1. 78 FR 41803 - Establishment of a Public Docket for Comment on the Report Prepared Under the Food and Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-11

    ... Prepared Under the Food and Drug Administration Safety and Innovation Act Section 1138 AGENCY: Food and... the report mandated under the Food and Drug Administration Safety and Innovation Act (FDASIA)...

  2. ACT and College Success

    ERIC Educational Resources Information Center

    Bleyaert, Barbara

    2010-01-01

    What is the relationship between ACT scores and success in college? For decades, admissions policies in colleges and universities across the country have required applicants to submit scores from a college entrance exam, most typically the ACT (American College Testing) or SAT (Scholastic Aptitude Test). This requirement suggests that high school…

  3. [Club drugs].

    PubMed

    Guerreiro, Diogo Frasquilho; Carmo, Ana Lisa; da Silva, Joaquim Alves; Navarro, Rita; Góis, Carlos

    2011-01-01

    Club drugs are the following substances: Methylenedioxymethamphetamine (MDMA); Methamphetamine; Lysergic Acid Diethylamide (LSD); Ketamine; Gamma-hydroxybutyrate (GHB) and Flunitrazepam. These substances are mainly used by adolescents and young adults, mostly in recreational settings like dance clubs and rave parties. These drugs have diverse psychotropic effects, are associated with several degrees of toxicity, dependence and long term adverse effects. Some have been used for several decades, while others are relatively recent substances of abuse. They have distinct pharmacodynamic and pharmacokinetic properties, are not easy to detect and, many times, the use of club drugs is under diagnosed. Although the use of these drugs is increasingly common, few health professionals feel comfortable with the diagnosis and treatment. The authors performed a systematic literature review, with the goal of synthesising the existing knowledge about club drugs, namely epidemiology, mechanism of action, detection, adverse reactions and treatment. The purpose of this article is creating in Portuguese language a knowledge data base on club drugs, that health professionals of various specialties can use as a reference when dealing with individual with this kind of drug abuse. PMID:22525626

  4. Prolonged cataleptogenic effects of potentized homoeopathic drugs.

    PubMed

    Sukul, N C; Bala, S K; Bhattacharyya, B

    1986-01-01

    The four homoeopathic drugs, Gelsemium, Cannabis Indica, Graphites and Agaricus Muscarius, administered orally in 30th and 200th potencies on white rats, enhanced restraint-induced catalepsy in a similar manner to the two standard drugs pilocarpine and haloperidol (IP injection at 5 mg/kg). All the drugs tested differed from each other in the duration of cataleptogenic effect, which was more prolonged with Cannabis, Graphites and Agaricus than with Gelsemium and the two non-homoeopathic drugs used. The 200th potency of any homoeopathic drug tested acted longer than its 30th potency. PMID:3088660

  5. Street Drugs and Pregnancy

    MedlinePlus

    ... drugs that are abused How can street drugs harm your pregnancy? Using street drugs can cause problems ... drugs that are abused How can street drugs harm your pregnancy? Using street drugs can cause problems ...

  6. Hazardous Drugs

    MedlinePlus

    ... OF LABOR Occupational Safety and Health Administration 200 Constitution Ave., NW, Washington, DC 20210 800-321-6742 (OSHA) TTY www.OSHA.gov FEDERAL GOVERNMENT White House Affordable Care Act Disaster Recovery ...

  7. Drug models of schizophrenia.

    PubMed

    Steeds, Hannah; Carhart-Harris, Robin L; Stone, James M

    2015-02-01

    Schizophrenia is a complex mental health disorder with positive, negative and cognitive symptom domains. Approximately one third of patients are resistant to currently available medication. New therapeutic targets and a better understanding of the basic biological processes that drive pathogenesis are needed in order to develop therapies that will improve quality of life for these patients. Several drugs that act on neurotransmitter systems in the brain have been suggested to model aspects of schizophrenia in animals and in man. In this paper, we selectively review findings from dopaminergic, glutamatergic, serotonergic, cannabinoid, GABA, cholinergic and kappa opioid pharmacological drug models to evaluate their similarity to schizophrenia. Understanding the interactions between these different neurotransmitter systems and their relationship with symptoms will be an important step towards building a coherent hypothesis for the pathogenesis of schizophrenia. PMID:25653831

  8. Drug models of schizophrenia

    PubMed Central

    Steeds, Hannah; Carhart-Harris, Robin L.

    2015-01-01

    Schizophrenia is a complex mental health disorder with positive, negative and cognitive symptom domains. Approximately one third of patients are resistant to currently available medication. New therapeutic targets and a better understanding of the basic biological processes that drive pathogenesis are needed in order to develop therapies that will improve quality of life for these patients. Several drugs that act on neurotransmitter systems in the brain have been suggested to model aspects of schizophrenia in animals and in man. In this paper, we selectively review findings from dopaminergic, glutamatergic, serotonergic, cannabinoid, GABA, cholinergic and kappa opioid pharmacological drug models to evaluate their similarity to schizophrenia. Understanding the interactions between these different neurotransmitter systems and their relationship with symptoms will be an important step towards building a coherent hypothesis for the pathogenesis of schizophrenia. PMID:25653831

  9. Pharmacogenetics of analgesic drugs

    PubMed Central

    Russo, Giovanna; Gubbay, Anthony; Branford, Ruth; Sato, Hiroe

    2013-01-01

    Summary points • Individual variability in pain perception and differences in the efficacy of analgesic drugs are complex phenomena and are partly genetically predetermined. • Analgesics act in various ways on the peripheral and central pain pathways and are regarded as one of the most valuable but equally dangerous groups of medications. • While pharmacokinetic properties of drugs, metabolism in particular, have been scrutinised by genotype–phenotype correlation studies, the clinical significance of inherited variants in genes governing pharmacodynamics of analgesics remains largely unexplored (apart from the µ-opioid receptor). • Lack of replication of the findings from one study to another makes meaningful personalised analgesic regime still a distant future. • This narrative review will focus on findings related to pharmacogenetics of commonly used analgesic medications and highlight authors’ views on future clinical implications of pharmacogenetics in the context of pharmacological treatment of chronic pain. PMID:26516523

  10. Club Drugs

    MedlinePlus

    Skip to main content En español Researchers Medical & Health Professionals Patients & ... Cold Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine Other Drugs ...

  11. Prescription Drugs

    MedlinePlus

    ... body, especially in brain areas involved in the perception of pain and pleasure. Prescription stimulants , such as ... of drug that causes changes in your mood, perceptions, and behavior can affect judgment and willingness to ...

  12. Antiretroviral drugs.

    PubMed

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one. PMID:20471318

  13. Drug Interactions

    MedlinePlus

    ... not be taken at the same time as antacids. WHAT CAUSES THE MOST INTERACTIONS WITH HIV MEDICATIONS? ... azole” Some antibiotics (names end in “mycin”) The antacid cimetidine (Tagamet) Some drugs that prevent convulsions, including ...

  14. Drugged Driving

    MedlinePlus

    ... Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine ... distance, and decrease coordination. Drivers who have used cocaine or methamphetamine can be aggressive and reckless when ...

  15. Drug allergy

    PubMed Central

    Warrington, Richard

    2012-01-01

    Allergic drug reactions occur when a drug, usually a low molecular weight molecule, has the ability to stimulate an immune response. This can be done in one of two ways. The first is by binding covalently to a self-protein, to produce a haptenated molecule that can be processed and presented to the adaptive immune system to induce an immune response. Sometimes the drug itself cannot do this but a reactive breakdown product of the drug is able to bind covalently to the requisite self-protein or peptide. The second way in which drugs can stimulate an immune response is by binding non-covalently to antigen presenting or antigen recognition molecules such as the major histocompatibility complex (MHC) or the T cell receptor. This is known as the p-I or pharmacological interaction hypothesis. The drug binding in this situation is reversible and stimulation of the response may occur on first exposure, not requiring previous sensitization. There is probably a dependence on the presence of certain MHC alleles and T cell receptor structures for this type of reaction to occur. PMID:22922763

  16. Drugs induced pulmonary arterial hypertension.

    PubMed

    Seferian, Andrei; Chaumais, Marie-Camille; Savale, Laurent; Günther, Sven; Tubert-Bitter, Pascale; Humbert, Marc; Montani, David

    2013-09-01

    Pulmonary arterial hypertension (PAH) is a rare disorder characterized by progressive obliteration of the pulmonary microvasculature, resulting in elevated pulmonary vascular resistance and premature death. According to the current classification, PAH can be associated with exposure to certain drugs or toxins, particularly appetite suppressant drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary arterial smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used but are also considered as possible risk factors for PAH. Dasatinib, a dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, in part reversible after its withdrawal. Recently several studies raised the potential endothelial dysfunction that could be induced by interferon, and few cases of PAH have been reported with interferon therapy. Other possible risk factors for PAH include: nasal decongestants, like phenylpropanolamine, dietary supplement - L-Tryptophan, selective serotonin reuptake inhibitors, pergolide and other drugs that could act on 5HT2B receptors. Interestingly, PAH remains a rare complication of these drugs, suggesting possible individual susceptibility and further studies are needed to identify patients at risk of drugs induced PAH. PMID:23972547

  17. 78 FR 3900 - Generic Drug User Fee-Active Pharmaceutical Ingredient and Finished Dosage Form Facility Fee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-17

    ...The Food and Drug Administration (FDA) is announcing the rate for the generic drug active pharmaceutical ingredient (API) and finished dosage form (FDF) facilities user fees for fiscal year (FY) 2013. The Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Generic Drug User Fee Amendments of 2012 (GDUFA), enacted the Food and Drug Administration Safety and Innovation Act, as......

  18. 75 FR 32952 - Draft Guidance for Industry and Food and Drug Administration Staff; “‘Harmful and Potentially...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-10

    ... the Federal Food, Drug, and Cosmetic Act''; Availability AGENCY: Food and Drug Administration, HHS... Products as Used in Section 904(e) of the Federal Food, Drug, and Cosmetic Act.'' This draft guidance... Cosmetic Act.'' This draft guidance, when finalized, will discuss the meaning of the term ``harmful...

  19. 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

    ... surveillance processes, including application submission, review, compliance with good manufacturing practices... Act directed FDA to establish appropriate approval procedures and current good manufacturing practices.../DevelopmentApprovalProcess/Manufacturing/ucm085783.htm . Recognizing that many PET drug producers...

  20. Assertive Community Treatment (ACT)

    MedlinePlus

    ... community treatment? Assertive community treatment (ACT) is a model of psychiatric care that can be very effective ... it the most. Similar to the “treatment team” model of an inpatient psychiatric unit, which includes nurses, ...

  1. The ACTS propagation program

    NASA Technical Reports Server (NTRS)

    Chakraborty, Dayamoy; Davarian, Faramaz

    1991-01-01

    The purpose of the Advanced Communications Technology Satellite (ACTS) is to demonstrate the feasibility of the Ka-band (20 and 30 GHz) spectrum for satellite communications, as well as to help maintain U.S. leadership in satellite communications. ACTS incorporates such innovative schemes as time division multiple access (TDMA), microwave and baseband switching, onboard regeneration, and adaptive application of coding during rain-fade conditions. The success or failure of the ACTS experiment will depend on how accurately the rain-fade statistics and fade dynamics can be predicted in order to derive an appropriate algorithm that will combat weather vagaries, specifically for links with small terminals, such as very small aperture terminals (VSAT's) where the power margin is a premium. This article describes the planning process and hardware development program that will comply with the recommendations of the ACTS propagation study groups.

  2. ACTS mobile SATCOM experiments

    NASA Technical Reports Server (NTRS)

    Abbe, Brian S.; Frye, Robert E.; Jedrey, Thomas C.

    1993-01-01

    Over the last decade, the demand for reliable mobile satellite communications (satcom) for voice, data, and video applications has increased dramatically. As consumer demand grows, the current spectrum allocation at L-band could become saturated. For this reason, NASA and the Jet Propulsion Laboratory are developing the Advanced Communications Technology Satellites (ACTS) mobile terminal (AMT) and are evaluating the feasibility of K/Ka-band (20/30 GHz) mobile satcom to meet these growing needs. U.S. industry and government, acting as co-partners, will evaluate K/Ka-band mobile satcom and develop new technologies by conducting a series of applications-oriented experiments. The ACTS and the AMT testbed will be used to conduct these mobile satcom experiments. The goals of the ACTS Mobile Experiments Program and the individual experiment configurations and objectives are further presented.

  3. 77 FR 10753 - Draft Guidance for Industry: Food and Drug Administration Records Access Authority Under the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-23

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry: Food and Drug Administration Records Access Authority Under the Federal Food, Drug, and Cosmetic Act; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

  4. 21 CFR 1306.07 - Administering or dispensing of narcotic drugs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Administering or dispensing of narcotic drugs. 1306.07 Section 1306.07 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE... qualifications, security, records, and unsupervised use of the drugs pursuant to the Act. (b) Nothing in...

  5. The ACTS propagation program

    NASA Technical Reports Server (NTRS)

    Chakraborty, D.; Davarian, Faramaz

    1992-01-01

    The success or failure of the ACTS experiment will depend on how accurately the rain-fade statistics and fade dynamics can be predicted in order to derive an appropriate algorithm that will combat weather vagaries, specifically for links with small terminals, such as very small aperture terminals (VSAT's) where the power margin is a premium. The planning process and hardware development program that will comply with the recommendations of the ACTS propagation study groups are described.

  6. Drug misuse.

    PubMed

    Waller, T

    1992-12-01

    1. Assessment by history and examination should include: a history of all drugs taken during each day for the previous 7 days (including alcohol), length of drug use and route (including the sharing of needles or syringes), the possibility of pregnancy if female, previous psychiatric history and treatment of drug misuse, social factors (including employment, family, friends, involvement in prostitution, legal problems), medical problems, including evidence of hepatitis, injection abscesses and other infections, suicide attempts, and weight loss. 2. Notification to the Chief Medical Officer of the Drug Branch of the Home Office is a legal obligation. 3. Investigations include: liver function tests (LFTs), hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis C antibody, full blood count (FBC), and urine for drug screening. Consider HIV testing if at risk but it is usually better arranged at a later stage. 4. Prescribing may be considered for a variety of drugs but objectives will differ according to drug type and individual. 5. In the case of opioid users, prescribing may be useful to stabilize their lives and to promote attendance for professional help. It may reduce high risk behaviour for contracting and spreading HIV. 6. If medication is given to opioid users, methadone mixture 1 mg/ml given once a day is the prescription of choice. Dispensing should be on a daily basis and the blue prescription form FP10 (MDA) allows the chemist to dispense daily for up to 14 days. A maximum ceiling of 100 mg methadone/day should not be exceeded. The initial dose will depend on the amount of opioid consumed in the previous week.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1345155

  7. Centrally acting agents and visceral sensitivity.

    PubMed

    Fioramonti, J; Bueno, L

    2002-07-01

    The evidence relating to the site and mechanism of action of "centrally acting" agents which may affect visceral sensitivity is reviewed. Antidepressant drugs such as amitriptyline as well as the newer selective serotonin reuptake inhibitors are thought to act at the level of the CNS. Opiates, including morphine as well as compounds such as trimebutine or fedotozine designed for therapeutic use in irritable bowel syndrome, are effective in reducing visceral nociception. Cytokines in the CNS are known to be involved in the modulation of pain and there is also evidence to suggest that centrally acting cytokines may play a role in the production of visceral hypersensitivity. Consequently, they may provide an interesting target for future research. PMID:12077076

  8. Drugs@FDA: FDA Approved Drug Products

    MedlinePlus

    ... Cosmetics Tobacco Products Drugs@FDA: FDA Approved Drug Products FDA Home Drug Databases Drugs@FDA - FAQ | Instructions | ... 6332) Contact FDA For Government For Press Combination Products Advisory Committees Science & Research Regulatory Information Safety Emergency ...

  9. The clinical pharmacology of antihypertensive drugs.

    PubMed

    Lowenthal, D T; Saris, S D; Haratz, A; Packer, J; Porter, R S; Conry, K

    1984-12-01

    Antihypertensive drugs act centrally (methyldopa, clonidine, guanabenz), peripherally (prazosin, guanadrel, guanethedine, hydralazine, minoxidil), centrally and peripherally (beta-adrenergic blocking drugs) and systemically [angiotensin converting enzyme (ACE) inhibitors and diuretics]. Centrally-acting antihypertensives decrease blood pressure by diminishing sympathetic outflow from the vasomotor centre. Peripherally-acting antihypertensives act by depleting or inhibiting the release of catecholamines from the peripheral nerve ending or altering the response at alpha 1- and alpha 2-receptor sites. Beta-adrenergic blocking drugs act through a variety of mechanisms by either decreasing cardiac output, decreasing renin release, inhibiting prejunctional release of norepinephrine or through central mechanisms. Diuretics act as indirect vasodilators by depleting salt and water not only within the intravascular compartment but within the intramural portion of the arteriole, thereby diminishing its responsiveness to catecholamine and angiotensin II stimulation. ACE inhibitors such as captopril and enalapril act by inhibiting the conversion of angiotensin I to angiotensin II thereby decreasing the vasoconstrictor effect of angiotensin II and the aldosterone production secondary to angiotensin II stimulation. The main differences between captopril and enalapril is that enalapril does not possess the potentially toxic sulphydryl group and can be given twice-daily. Both drugs may show accumulation in patients with impaired renal function. PMID:6152830

  10. Medicaid Program; Covered Outpatient Drugs. Final rule with comment period.

    PubMed

    2016-02-01

    This final rule implements provisions of the Patient Protection and Affordable Care Act of 2010, as amended by the Health Care and Education Reconciliation Act of 2010 (collectively referred to as the Affordable Care Act) pertaining to Medicaid reimbursement for covered outpatient drugs (CODs). This final rule also revises other requirements related to CODs, including key aspects of their Medicaid coverage and payment and the Medicaid drug rebate program. PMID:26859897

  11. The CEO's second act.

    PubMed

    Nadler, David A

    2007-01-01

    When a CEO leaves because of performance problems, the company typically recruits someone thought to be better equipped to fix what the departing executive couldn't--or wouldn't. The board places its confidence in the new person because of the present dilemma's similarity to some previous challenge that he or she dealt with successfully. But familiar problems are inevitably succeeded by less familiar ones, for which the specially selected CEO is not quite so qualified. More often than not, the experiences, skills, and temperament that yielded triumph in Act I turn out to be unequal to Act II's difficulties. In fact, the approaches that worked so brilliantly in Act I may be the very opposite of what is needed in Act II. The CEO has four choices: refuse to change, in which case he or she will be replaced; realize that the next act requires new skills and learn them; downsize or circumscribe his or her role to compensate for deficiencies; or line up a successor who is qualified to fill a role to which the incumbent's skills and interests are no longer suited. Hewlett-Packard's Carly Fiorina exemplifies the first alternative; Merrill Lynch's Stanley O'Neal the second; Google's Sergey Brin and Larry Page the third; and Quest Diagnostics' Ken Freeman the fourth. All but the first option are reasonable responses to the challenges presented in the second acts of most CEOs' tenures. And all but the first require a power of observation, a propensity for introspection, and a strain of humility that are rare in the ranks of the very people who need those qualities most. There are four essential steps executives can take to discern that they have entered new territory and to respond accordingly: recognition that their leadership style and approach are no longer working; acceptance of others' advice on why performance is faltering; analysis and understanding of the nature of the Act II shift; and, finally, decision and action. PMID:17286076

  12. Drug Allergy.

    PubMed

    Waheed, Abdul; Hill, Tiffany; Dhawan, Nidhi

    2016-09-01

    An adverse drug reaction relates to an undesired response to administration of a drug. Type A reactions are common and are predictable to administration, dose response, or interaction with other medications. Type B reactions are uncommon with occurrences that are not predictable. Appropriate diagnosis, classification, and entry into the chart are important to avoid future problems. The diagnosis is made with careful history, physical examination, and possibly allergy testing. It is recommended that help from allergy immunology specialists should be sought where necessary and that routine prescription of Epi pen should be given to patients with multiple allergy syndromes. PMID:27545730

  13. [Ureter drugs].

    PubMed

    Raynal, G; Bellan, J; Saint, F; Tillou, X; Petit, J

    2008-03-01

    Many improvements have been made recently in the field of the ureteral smooth muscle pharmacology. After a brief summary on physiological basis, we review what is known about effects on ureter of different drugs class. In a second part, we review clinical applications for renal colic analgesia, calculi expulsive medical therapy, ESWL adjuvant treatment and preoperative treatment before retrograde access. There are now sufficient data on NSAID and alpha-blockers. beta-agonists, especially for beta3 selective ones, and topical drugs before retrograde access are interesting and should be further evaluated. PMID:18472067

  14. Drug watch.

    PubMed

    Whitson, S

    1999-01-01

    Recent developments on new anti-HIV agents and drugs for opportunistic infections are highlighted. Information is provided on the infusion inhibitor T-20; DuPont's second generation non-nukes, DPC 961 and DPC 963; Papirine (PEN203) for the human papilloma virus; Sporanox for treating fungal infections; and the antiretroviral protein, lysozyme. In addition, information is given on a plant found in the Bolivian rainforest that may contain compounds to prevent HIV infection by blocking the enzyme, integrase. Other promising new drugs addressed at the 6th Conference on Retroviruses and Opportunistic Infections are listed in a table. Contact information for US clinical trials is provided. PMID:11366758

  15. Food and Drug Administration Safety and Innovation Act

    THOMAS, 112th Congress

    Sen. Harkin, Tom [D-IA

    2012-05-07

    05/07/2012 Placed on Senate Legislative Calendar under General Orders. Calendar No. 389. (All Actions) Notes: For further action, see S.3187, which became Public Law 112-144 on 7/9/2012. Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  16. Food and Drug Administration Reform Act of 2012

    THOMAS, 112th Congress

    Rep. Upton, Fred [R-MI-6

    2012-05-09

    06/04/2012 Received in the Senate. Read twice. Placed on Senate Legislative Calendar under General Orders. Calendar No. 420. (All Actions) Notes: For further action, see S.3187, which became Public Law 112-144 on 7/9/2012. Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  17. Prescription Drug and Health Improvement Act of 2011

    THOMAS, 112th Congress

    Sen. Franken, Al [D-MN

    2011-01-25

    01/25/2011 Read twice and referred to the Committee on Finance. (text of measure as introduced: CR S151-152) (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  18. Protecting Our Youth from Dangerous Synthetic Drugs Act of 2013

    THOMAS, 113th Congress

    Sen. Feinstein, Dianne [D-CA

    2013-07-18

    05/14/2014 Committee on United States Senate Caucus on International Narcotics Control. Hearings held. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  19. Prescription Drug Abuse Prevention and Treatment Act of 2013

    THOMAS, 113th Congress

    Rep. Rahall, Nick J., II [D-WV-3

    2013-02-13

    04/08/2013 Referred to the Subcommittee on Crime, Terrorism, Homeland Security, And Investigations. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  20. Saving Kids From Dangerous Drugs Act of 2013

    THOMAS, 113th Congress

    Sen. Feinstein, Dianne [D-CA

    2013-11-12

    11/12/2013 Read twice and referred to the Committee on the Judiciary. (text of measure as introduced: CR S7962) (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  1. Increasing the Safety of Prescription Drug Use Act of 2013

    THOMAS, 113th Congress

    Sen. Udall, Tom [D-NM

    2013-11-06

    05/14/2014 Committee on United States Senate Caucus on International Narcotics Control. Hearings held. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  2. 76 FR 56201 - Prescription Drug User Fee Act; Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-12

    ... reauthorization process with a public meeting held on April 12, 2010 (75 FR 12555, March 16, 2010). The meeting... published by notice in the Federal Register of August 1, 2011 (76 FR 45831). This amount includes the... published in the Federal Register of August 1, 2011 (76 FR 45831). \\3\\ Of this amount, $652,709,000 will...

  3. FEHBP Prescription Drug Integrity, Transparency, and Cost Savings Act

    THOMAS, 112th Congress

    Rep. Lynch, Stephen F. [D-MA-9

    2011-03-09

    03/18/2011 Referred to the Subcommittee on Federal Workforce, U.S. Postal Service, and Labor Policy. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  4. Drug Trafficking Safe Harbor Elimination Act of 2011

    THOMAS, 112th Congress

    Rep. Smith, Lamar [R-TX-21

    2011-01-18

    12/14/2011 Received in the Senate and Read twice and referred to the Committee on the Judiciary. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  5. Servicemembers and Veterans Prescription Drug Safety Act of 2013

    THOMAS, 113th Congress

    Rep. Cartwright, Matt [D-PA-17

    2013-12-12

    01/27/2014 Referred to the Subcommittee on Crime, Terrorism, Homeland Security, and Investigations. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  6. Pipotiazine palmitate, a long acting drug, indeed: a case report.

    PubMed

    Hyrman, V

    1985-04-01

    A case is presented, in which the extrapyramidal side effects of depot pipotiazine lasted well over 6 months, and possibly the therapeutic effect for almost 12 months following the last injection. The case report illustrates the need for flexible individualized dosage schedules, similar to other neuroleptics. PMID:2859922

  7. Ensuring Patient Access and Effective Drug Enforcement Act of 2014

    THOMAS, 113th Congress

    Rep. Marino, Tom [R-PA-10

    2014-05-21

    07/30/2014 Received in the Senate and Read twice and referred to the Committee on Health, Education, Labor, and Pensions. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  8. Generic Drug and Biosimilar User Fee Act of 2012

    THOMAS, 112th Congress

    Rep. Murphy, Tim [R-PA-18

    2012-02-08

    02/10/2012 Referred to the Subcommittee on Health. (All Actions) Notes: For further action, see S.3187, which became Public Law 112-144 on 7/9/2012. Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  9. Saving Kids From Dangerous Drugs Act of 2011

    THOMAS, 112th Congress

    Sen. Feinstein, Dianne [D-CA

    2011-03-08

    03/08/2011 Read twice and referred to the Committee on the Judiciary. (text of measure as introduced: CR S1411) (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  10. Medicare Prescription Drug Savings and Choice Act of 2011

    THOMAS, 112th Congress

    Sen. Durbin, Richard [D-IL

    2011-03-10

    03/10/2011 Read twice and referred to the Committee on Finance. (text of measure as introduced: CR S1561-1563) (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  11. Medicare Prescription Drug Savings and Choice Act of 2013

    THOMAS, 113th Congress

    Sen. Durbin, Richard [D-IL

    2013-02-28

    02/28/2013 Read twice and referred to the Committee on Finance. (text of measure as introduced: CR S1016-1017) (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  12. Drug- and non-drug-associated QT interval prolongation

    PubMed Central

    van Noord, Charlotte; Eijgelsheim, Mark; Stricker, Bruno H Ch

    2010-01-01

    Sudden cardiac death is among the most common causes of cardiovascular death in developed countries. The majority of sudden cardiac deaths are caused by acute ventricular arrhythmia following repolarization disturbances. An important risk factor for repolarization disturbances is use of QT prolonging drugs, probably partly explained by gene–drug interactions. In this review, we will summarize QT interval physiology, known risk factors for QT prolongation, including drugs and the contribution of pharmacogenetics. The long QT syndrome can be congenital or acquired. The congenital long QT syndrome is caused by mutations in ion channel subunits or regulatory protein coding genes and is a rare monogenic disorder with a mendelian pattern of inheritance. Apart from that, several common genetic variants that are associated with QT interval duration have been identified. Acquired QT prolongation is more prevalent than the congenital form. Several risk factors have been identified with use of QT prolonging drugs as the most frequent cause. Most drugs that prolong the QT interval act by blocking hERG-encoded potassium channels, although some drugs mainly modify sodium channels. Both pharmacodynamic as well as pharmacokinetic mechanisms may be responsible for QT prolongation. Pharmacokinetic interactions often involve drugs that are metabolized by cytochrome P450 enzymes. Pharmacodynamic gene–drug interactions are due to genetic variants that potentiate the QT prolonging effect of drugs. QT prolongation, often due to use of QT prolonging drugs, is a major public health issue. Recently, common genetic variants associated with QT prolongation have been identified. Few pharmacogenetic studies have been performed to establish the genetic background of acquired QT prolongation but additional studies in this newly developing field are warranted. PMID:20642543

  13. 20 CFR 638.511 - Drug use and abuse.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Drug use and abuse. 638.511 Section 638.511... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.511 Drug use and abuse. The Job... and education programs related to drug and alcohol use and abuse....

  14. 20 CFR 638.511 - Drug use and abuse.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Drug use and abuse. 638.511 Section 638.511... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.511 Drug use and abuse. The Job... and education programs related to drug and alcohol use and abuse....

  15. 20 CFR 638.511 - Drug use and abuse.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Drug use and abuse. 638.511 Section 638.511... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.511 Drug use and abuse. The Job... and education programs related to drug and alcohol use and abuse....

  16. 75 FR 73984 - Amendments to General Regulations of the Food and Drug Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ...'' (62 FR 62466, November 21, 1997). This guidance document may be accessed at http://www.fda.gov... Act was enacted on June 22, 2009, amending the Federal Food, Drug, and Cosmetic Act (the FD&C Act) and... 1 Cosmetics, Drugs, Exports, Food labeling, Imports, Labeling, Reporting and...

  17. The ACTS multibeam antenna

    NASA Astrophysics Data System (ADS)

    Regier, Frank A.

    1992-06-01

    The Advanced Communications Technology Satellite (ACTS) to be launched in 1993 is briefly introduced. Its multibeam antenna, consisting of electrically similar 30 GHz receive and 20 GHz transmit offset Cassegrain systems, both utilizing orthogonal polarizations, is described. Dual polarization is achieved by using one feed assembly for each polarization in conjunction with nested front and back subreflectors, the gridded front subreflector acting as a window for one polarization and a reflector for the other. The antennas produce spot beams with approximately 0.3 degree beamwidth and gains of approximately 50 dbi. High surface accuracy and high edge taper produce low sidelobe levels and high cross-polarization isolation. A brief description is given of several Ka-band components fabricated for ACTS. These include multiflare antenna feedhorns, beam-forming networks utilizing latching ferrite waveguide switches, a 30 GHz HEMT low-noise amplifier and a 20 GHz TWT power amplifier.

  18. The ACTS multibeam antenna

    NASA Technical Reports Server (NTRS)

    Regier, Frank A.

    1992-01-01

    The Advanced Communications Technology Satellite (ACTS) to be launched in 1993 is briefly introduced. Its multibeam antenna, consisting of electrically similar 30 GHz receive and 20 GHz transmit offset Cassegrain systems, both utilizing orthogonal polarizations, is described. Dual polarization is achieved by using one feed assembly for each polarization in conjunction with nested front and back subreflectors, the gridded front subreflector acting as a window for one polarization and a reflector for the other. The antennas produce spot beams with approximately 0.3 degree beamwidth and gains of approximately 50 dbi. High surface accuracy and high edge taper produce low sidelobe levels and high cross-polarization isolation. A brief description is given of several Ka-band components fabricated for ACTS. These include multiflare antenna feedhorns, beam-forming networks utilizing latching ferrite waveguide switches, a 30 GHz HEMT low-noise amplifier and a 20 GHz TWT power amplifier.

  19. 75 FR 68802 - Report on the Performance of Drug and Biologics Firms in Conducting Postmarketing Requirements...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-09

    ...Under the Food and Drug Administration Modernization Act of 1997 (Modernization Act), the Food and Drug Administration (FDA) is required to report annually in the Federal Register on the status of postmarketing requirements and commitments required of, or agreed upon by, holders of approved drug and biological products. This notice is the Agency's report on the status of the studies and......

  20. Drug Resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Drug resistance refers to both intrinsic and acquired abilities of cells or organisms to become insensitive or refractory to chemotherapeutic intervention. The advent of antibiotics is considered one of the most important medicinal developments in human history, which has led to significantly reduce...