DOCSLIB.ORG

Non-Steroidal Anti-Inflammatory Drugs and Prostaglandin Effects On

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Non-Steroidal Anti-Inflammatory Drugs and Prostaglandin Effects On Gut 1995; 36: 657-663 657 Non-steroidal anti-inflammatory drugs and prostaglandin effects on pepsinogen secretion by dispersed human peptic cells Gut: first published as 10.1136/gut.36.5.657 on 1 May 1995. Downloaded from A I Lanas, J Nerin, F Esteva, R Saiinz Abstract It is widely accepted that non-steroidal anti- The effects of aspirin and ibuprofen on inflammatory drug (NSAID) use is associated pepsinogen secretion were studied in with a high prevalence of gastroduodenal isolated human peptic cells prepared from injury.1 It is also recognised that the presence endoscopically obtained biopsy specimens of acid and pepsin enhances the potential after collagenase digestion, mechanical damaging effect of these drugsl 2 and, there- disruption, and percoli gradient centrifu- fore, anti-secretory therapy is commonly gation. Pharmacological concentrations prescribed to treat or prevent damage induced of aspirin and ibuprofen (10-8-10-4 M), by NSAIDs.3 The pathogenic mechanisms of potentiated histamine (10-6-10-4 M) and NSAID induced gastroduodenal damage forskolin (10-5 M) stimulated pepsinogen remains unclear,l 2 although different mech- secretion without affecting basal secre- anisms, most of them related to prostaglandin tion, acetylcholine (10-6 M) stimulated inhibition, have been proposed.2 4 pepsinogen secretion or cell vitality. Aspirin and other non-salicylate NSAIDs Augmentation of secretagogue stimulated have been reported to increase or potentiate pepsinogen secretion was dependent on histamine stimulated acid secretion in vivo5 6 extracellular calcium because potentia- and in vitro in different animal models,7-11 tion was abolished by calcium depletion of suggesting that enhanced gastric acid secretion the medium. Cimetidine inhibited the could play a part in the pathogenesis ofNSAID potentiation effect on histamine but not induced gastroduodenal mucosal damage. The http://gut.bmj.com/ on forskolin stimulated pepsinogen secre- mechanisms of NSAID stimulated acid secre- tion, thus suggesting that this augmenta- tion have been extensively explored by Levine tion was independent of histamine H2 et al 7-9 in an in vitro rabbit parietal cell model, receptors. Of interest, potentiation was suggesting that NSAID induced acid secretion also independent of endogenous prosta- is regulated by the presence of calcium and the glandin inhibition because exogenous inhibition of prostaglandins. addition of prostaglandin E2 and D2 Although available information provides on September 28, 2021 by guest. Protected copyright. increased both basal and acetylcholine sufficient evidence that intramucosal activa- stimulated pepsinogen secretion in a tion of acid proteases, mainly pepsinogens, dose dependent way, but they did not plays an important part in peptic diseases of modify histamine or histamine plus the upper gastrointestinal tract,'2 there are aspirin or ibuprofen stimulated pepsino- almost no data on the potential effects of gen secretion. In conclusion, aspirin NSAIDs on pepsinogen secretion by the and ibuprofen potentiate secretagogue stomach. In this study we have examined in Service of stimulated pepsinogen secretion by vitro the effects of two widely and more com- Gastroenterology, dispersed human peptic celis and this monly used NSAIDs (aspirin and ibuprofen) Universitario, might be an additional mechanism of on pepsinogen secretion by dispersed human Zaragoza, Spain non-steroidal anti-inflammatory drug peptic cells obtained from endoscopic biopsy A I Lanas J Nerin (NSAID) induced gastric injury.M This specimens. F Esteva potentiation effect is regulated by calcium, R Sainz independent of endogenous prostaglandin Correspondence to: inhibition and seems to act on pepsinogen Methods Dr A I Lanas, Servicio de secretion at a post-receptor site. Aparato Digestivo, Hospital. Clinico Universitario, 50009 (GutGul93657631995; 36: 657-663) Chemicals Zaragoza, Spain. Chemicals were obtained from the following Accepted for publication Keywords: non-steroidal anti-inflammatory drugs, sources: bovine serum albumin (fraction V), 16 August 1994 pepsinogen, prostaglandins. acetylcholine, histamine, cimetidine, aspirin, ibuprofen, forskolin, HEPES, percoll, crys- Effects ofaspirin and ibuprofen on basalpepsinogen secretionfrom dispersed human peptic cells talline porcine pepsinogen, soybean trypsin inhibitor, ethylene glycol tetraacetic acid Agent Number 10-4 M 10-6 M 10-8 M (EGTA), and glucose from Sigma Chemical Aspirin 6 -0.05 (0.56)% +0-66 (0.72)% +0 68 (0 70)% (St Louis, MO). Collagenase (type IV) from Ibuprofen 6 +0-14 (0 20)% +0.01 (0 25)% -0 55 (0.27)% Worthington Biochemical (Freeholdd, NJ); Pepsinogen released into the medium was expressed as percentage (%) of the total pepsinogen bovine haemoglobin from Gibco Diagnostics initially present in cells and secretory responses to stimuli were calculated in the output per unit and and D2 time with basal output subtracted. Basal secretion in these experiments was 5.79 (0.58)% of (Madison, WI), prostaglandin E2 total/30 min. Data expressed as mean (SEM). from Calbiochem (La Jolla, CA). 658 Lanas, Nein, Esteva, Sdinz 69 patients undergoing upper gastrointestinal a HIS endoscopy (45 men and 15 women). The 0E 4.0F HIS 104 + NSAID HIS + ASA mean (SEM) age of this population was 39.11 (0 3.5%,-,W F ii (1-59) (18-61). In 20 of these patients the 1- * HIS+ IBU endoscopy was normal, 18 had an active Gut: first published as 10.1136/gut.36.5.657 on 1 May 1995. Downloaded from Qto 3.0 i duodenal ulcer, 14 a healed duodenal ulcer, i nine a hiatal hernia, six oesophagitis, five 0 2.5 duodenitis, five antritis, and two a gastric 1 ulcer. Most of them (55 of 69) were or had 0 2.0 ez recently been receiving H2 receptor antago- 0 nists, and the rest were receiving antacids or 1.5 were free of any treatment. Helicobacter pylori c status in the corpus of the stomach was not 1.0 CD determined, but it was in the antrum (CLO C test) in 43 of 69 patients (positive in 40). The 0.5 ._ study was approved by the Institutional Review c Board and written informed consent was -44-8 -4 -6 -4- -4 -6 obtained from all patients. Molar concentration Figure 1: Effects ofdifferent concentrations ofboth aspirin (ASA) and ibuprofen (IBU) on two different concentrations of histamine (HIS) stimulated pepsinogen secretion from Cell isolation dispersed human peptic cells. Basal secretion in these experiments was 4-86 (0.57) % of The method used to isolate peptic cells had total/30 min. n=4-7. *p<0 05 with respect to histamine stimulated secretion, tp<0 05 with respect to basal secretion. been previously described elsewhere.'3 In brief, eight to 10 endoscopically obtained gastric biopsy specimens (jumbo forceps) from Unless otherwise stated, the standard Ringer the oxintic area were transported in Ringer's solution contained 82.2 mM NaCl, 4.0 mM solution that had been gassed with 95% 02 KCl, 1.8 mM CaCl2, 0.8 mM MgCl2, 0.8 and 5°/O CO2. The specimens then received NaSO4, 17.8 mM NaHCO3, 0-8 mM a 20 minute digestion in 0.1% collagenase NaH2PO4, 11.5 mM glucose, and 0-2% bovine solution with 0.2% trypsin inhibitor in a serum albumin. The medium was equilibrated shaking water bath at 370C. This initial colla- with 95% 02-5% C02 and pH was adjusted to genase solution was discarded and replaced 7-25. Call low medium contained 0.1 mM and digestion continued for 45 more minutes. CaCl2 and no MgCl2, and Ca free medium The cells and glands were collected by contained no CaCl2 or MgCl2. centrifugation, resuspended in Ringer's solu- http://gut.bmj.com/ tion without calcium and magnesium, and subjected to repetitive pipetting for several Biopsy specimens minutes. The cells were filtered through 100 Gastric biopsy specimens were obtained from ,um Teflon mesh and resuspended in Ringer's solution containing calcium and magnesium. The cells were then taken up in 1 ml of U Ca' Ringer's solution and layered onto 2 ml 50/O on September 28, 2021 by guest. Protected copyright. D (v/v) percoll containing isotonic HEPES Ca' free medium buffered Ringer's solution, which contained 82.2 mM NaCl, 4 mM KC1, 1.8 mM CaCl2, 0.8 mM MgCl2, 19.4 mM HEPES, 11.5 mM 6 * glucose, and 02% bovine serum albumin. The cells were then centrifuged at 14 000 g for 20 E minutes at 4°C (Eppendorf Centrifuge, Model 0 5412). After this centrifugation the bottom of InCo CoCD, the gradient containing mainly red blood cells cc was discarded, and the remaining cells were 4 washed and layered again onto a 2 ml 33% 0 CCo (v/v) containing isotonic HEPES buffered Ringer's solution. After another centrifugation 3 at 14000 g for 10 minutes, the top of the .._J, 0 gradient containing mainly the parietal cells 0cJ was discarded and a clearly different layer a) 2 at the bottom contained the chief cells. The isolated chief cells were greater than 90/o ._ pure by microscopy (haematoxylin and eosin 0.a) .7n0 staining procedure and periodic acid schiff CL reaction), and >90%/O viable by trypan blue exclusion and >89% by flow cytometry (Epics o Elite, Coulter, Hialeah Fl, USA) using the FK FK + ASA FK + fluorochromes, rhodamine 123 and propidium Figure 2: Effects ofboth aspirin (ASA) (10-6 M) and ibuprofen (IBU) (i0-4 M) on iodide to measure live and dead cells respec- forskolin (FK) (10-5 M) stimulated pepsinogen secretion from dispersed human peptic tively.'4 15 The pepsinogen content of this cells. Removal ofextracellular calcium from the medium suppressed the potentiation effect of was 100 times than the both drugs on forskolin stimulated pepsinogen secretion. Basal secretion in these experiments layer higher pepsinogen was 3.40 (0.29) % oftotalJ30 min. n= 4-5. *p< 0. 05 with respect to forskolin. obtained from the top layer containing mainly Non-steroidal anti-inflammatoty drugs and prostaglandin effects on pepsinogen secretion by dispersed human peptic cells 659 * Ringer's solution and counted (haemato- * cytometer).
Load more

Recommended publications
  • OBE022, an Oral and Selective Prostaglandin F2α Receptor Antagonist As an Effective and Safe Modality for the Treatment of Pret
    Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2018/05/18/jpet.118.247668.DC1 1521-0103/366/2/349–364$35.00 https://doi.org/10.1124/jpet.118.247668 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 366:349–364, August 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics OBE022, an Oral and Selective Prostaglandin F2a Receptor Antagonist as an Effective and Safe Modality for the Treatment of Preterm Labor s Oliver Pohl, André Chollet, Sung Hye Kim, Lucia Riaposova, François Spézia, Frédéric Gervais, Philippe Guillaume, Philippe Lluel, Murielle Méen, Frédérique Lemaux, Vasso Terzidou, Phillip R. Bennett, and Jean-Pierre Gotteland ObsEva SA, Plan-les-Ouates, Geneva, Switzerland (O.P., A.C., J.-P.G.); Imperial College London, Parturition Research Group, Institute of Reproductive and Developmental Biology,HammersmithHospitalCampus,EastActon,London,UnitedKingdom(S.H.K.,L.R., V.T., P.R.B.); Citoxlab, Evreux, France (F.S., F.G.); Porsolt Research Laboratory, Le Genest-Saint-Isle, France (P.G.); Urosphere SAS, Toulouse, France (P.L., M.M.); BioTrial, Rennes, France (F.L.); and André Chollet Consulting, Tannay, Switzerland (A.C.) Downloaded from Received February 26, 2018; accepted May 15, 2018 ABSTRACT Preterm birth is the major challenge in obstetrics, affecting aggregation. In in vitro studies, OBE002 inhibited sponta- ∼ 10% of pregnancies. Pan-prostaglandin synthesis inhibitors neous, oxytocin- and PGF2a-induced human myometrial jpet.aspetjournals.org [nonsteroidal anti-inflammatory drugs (NSAIDs)] prevent preterm contractions alone and was more effective in combination labor and prolong pregnancy but raise concerns about fetal renal with atosiban or nifedipine.
    [Show full text]
  • Success of Prostaglandin E2 in Structure–Function Is a Challenge for Structure-Based Therapeutics
    COMMENTARY Success of prostaglandin E2 in structure–function is a challenge for structure-based therapeutics Charles N. Serhan*† and Bruce Levy*‡ *Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine and ‡Critical Care and Pulmonary Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115 rostaglandin (PG) E2 is almost ubiquitous in humans and evokes potent diverse actions. Utility is the price of its perfec- Ption. PGE is a founding member of the 2 PGs, a class of mediators that belongs to the still growing family of bioactive au- tacoids known as the eicosanoids (1–3). The main classes include enzymatically generated products such as thrombox- anes, leukotrienes, lipoxins, and EETs, as well as others that are produced via nonenzymatic mechanisms, e.g., isopros- tanes and cyclopentaeone PGs that are increasing in number and appreciation (4, 5). PGE2 regulates key responses in the major human systems including re- productive, gastrointestinal, neuroendo- crine, and immune (Fig. 1). Formed by conversion of arachidonic acid via cyclo- oxygenase (COX) and specific synthases, Fig. 1. Diverse actions of PGE2 and selective targeted biosynthesis in inflammation. (Inset) Eicosanoid family major enzymatic classes of cyclooxygenases and lipoxygenase pathways (see text for details). PGE2 stereospecifically exerts potent (nano- to micromolar range) tissue- and cell type-selective actions (1–6). The importance of PGs in inflammation was from protecting gastrointestinal mucosa electrophoresis that this lipid-soluble brought into view by the discovery of J. to regulating smooth muscle and fever, activity behaved as an acid. Vane and colleagues (7) that nonsteroi- set a steep challenge for designer drug Bergstro¨m’s main research was in bile dal antiinflammatory drugs (NSAIDs) hunters to achieve, namely selectivity acids and steroids.
    [Show full text]
  • Effect of Hydrochloric Acid and Prostaglandins on Pepsinogen Synthesis and Secretion in Canine Gastric Chief Cell Monolayer Cultures
    Gut: first published as 10.1136/gut.30.6.774 on 1 June 1989. Downloaded from Gut, 1989, 30, 774-781 Effect of hydrochloric acid and prostaglandins on pepsinogen synthesis and secretion in canine gastric chief cell monolayer cultures J DEFIZE AND RICHARD H HUNT From the Intestinal Disease Research Unit, McMaster University, Hamilton, Ontario, Canada SUMMARY The actions ofhydrochloric acid, natural PGEI, PGE2 and a synthetic commercial PGE1 preparation, Enisoprost (Searle) on pepsinogen synthesis and secretion were studied in canine chief cell monolayer cultures. Hydrochloric acid, applied directly to the apical surface of chief cells using culture plate inserts (Millipore) had no effect on secretion, nor did it affect the action of any secretagogue in the basolateral medium. All prostaglandins tested showed significant stimulation of pepsinogen secretion. Basal secretion of pepsinogen after 90 min was 9.4 (1.3)% to total initial monolayer content. At 10`6 M, PGE1 stimulated secretion was 2641 (3.8)%; PGE2 27.9 (4)% and Enisoprost 28.8 (4.2)% of initial pepsinogen content. Stimulations by all tested prostaglandins were additive with carbachol (10-4 M) and CCK (10-9 M), but not with VIP (10-6 M), dbcAMP (10-3M) or forskolin (10` M) responses. All three prostaglandins stimulated pepsinogen synthesis as measured by 14C labelled amino acid incorporation into pepsinogen. Time course experiments were similar to those for forskolin and showed shorter time delays between stimulus and increased synthesis rate than carbachol but longer than dbcAMP. Stimulated pepsinogen secretion was inhibited by high in the medium. The inhibition abolished simultaneous pepsin concentrations (>800 Fg/ml) http://gut.bmj.com/ carbachol induced stimulation of synthesis but prostaglandin or forskolin stimulation only after two hours.
    [Show full text]
  • Effect of Latanoprost Or 8-Iso Prostaglandin E2 Alone and in Combination on Intraocular Pressure in Glaucomatous Monkey Eyes
    LABORATORY SCIENCES Effect of Latanoprost or 8-iso Prostaglandin E2 Alone and in Combination on Intraocular Pressure in Glaucomatous Monkey Eyes Rong-Fang Wang, MD; Steven M. Podos, MD; Janet B. Serle, MD; Thomas W. Mittag, PhD; F. Ventosa, MD; Bernard Becker, MD Objective: To evaluate the possible additivity of the ef- duction of IOP of 4.0 ± 0.6 mm Hg was produced when fects of latanoprost and 8-iso prostaglandin E2 (8-iso PGE2) 8-iso PGE2 was added to latanoprost and of 3.0 ± 0.7 on intraocular pressure (IOP) in monkey eyes with laser- mm Hg was produced when latanoprost was added to 8-iso induced glaucoma. PGE2 on day 13 before the morning dosing. Combina- tion therapy with both agents caused maximum IOP re- Methods: The IOP was measured hourly for 6 hours be- ductions from baseline of 11.3 ± 3.0 mm Hg (33%) (P,.05) ginning at 9:30 AM on day 1 (baseline day), days 6 and 7 (latanoprost with 8-iso PGE2 added) and of 9.8 ± 1.3 , (single-agent therapy), and days 13 and 14 (combination mm Hg (31%) (P .01) (8-iso PGE2 with latanoprost added) therapy with both agents). Following 1 day of baseline mea- on day 14. surement, 4 monkeys with unilateral glaucoma received monotherapy twice daily with either 1 drop of 0.005% la- Conclusion: Latanoprost and 8-iso PGE2 have an addi- tanoprost, or 0.1% 8-iso PGE2, 25 µL, at 9:30 AM and 3:30 tive effect on IOP in glaucomatous monkey eyes.
    [Show full text]
  • Effects of Prostaglandin F2α (Pgf2α) on Cell-Death Pathways in the Bovine Corpus Luteum
    Jonczyk et al. BMC Veterinary Research (2019) 15:416 https://doi.org/10.1186/s12917-019-2167-3 RESEARCH ARTICLE Open Access Effects of prostaglandin F2α (PGF2α) on cell- death pathways in the bovine corpus luteum (CL) Agnieszka Walentyna Jonczyk, Katarzyna Karolina Piotrowska-Tomala* and Dariusz Jan Skarzynski Abstract Background: Prostaglandin F2α (PGF2α) may differentially affect viability of luteal cells by inducing either proliferation or cell death (via apoptosis or necroptosis). The diverse effects of PGF2α may depend on its local vs. systemic actions. In our study, we determined changes in expression of genes related to: (i) apoptosis: caspase (CASP) 3, CASP8, BCL2 associated X (BAX), B-cell lymphoma 2 (BCL2) and (ii) necroptosis: receptor-interacting protein kinase (RIPK) 1, RIPK3, cylindromatosis (CYLD), and mixed lineage kinase domain-like (MLKL) in the early and mid-stage corpus luteum (CL) that accompany local (intra-CL) vs. systemic (i.m.) analogue of PGF2α (aPGF2α) actions. Cows at day 4 (n = 24) or day 10 (n = 24) of the estrous cycle were treated by injections as follows: (1) systemic saline, (2) systemic aPGF2α (25 mg; Dinoprost), (3) local saline, (4) local aPGF2α (2.5 mg; Dinoprost). After 4 h, CLs were collected by ovariectomy. Expression levels of mRNA and protein were investigated by RT-q PCR, Western blotting and immunohistochemistry, respectively. Results: We found that local and systemic administration of aPGF2α in the early-stage CL resulted in decreased expression of CASP3 (P < 0.01), but CASP8 mRNA expression was up-regulated (P < 0.05). However, the expression of CASP3 was up-regulated after local aPGF2α treatment in the middle-stage CL, whereas systemic aPGF2α administration increased both CASP3 and CASP8 expression (P < 0.01).
    [Show full text]
  • Misoprostol Induces Relaxation of Human Corpus Cavernosum Smooth Muscle: Comparison to Prostaglandin E1
    International Journal of Impotence Research (2000) 12, 107±110 ß 2000 Macmillan Publishers Ltd All rights reserved 0955-9930/00 $15.00 www.nature.com/ijir Misoprostol induces relaxation of human corpus cavernosum smooth muscle: comparison to prostaglandin E1 RB Moreland1, NN Kim1, A Nehra2, BG Parulkar3 and A Traish1,4* 1Department of Urology, Boston University School of Medicine, Boston, MA 02118, USA; 2Department of Urology, Mayo Clinic and Foundation, Rochester, MN 55905, USA; 3Department of Urology, University of Massachusetts Medical Center, Worcester, MA 01604, USA; and 4Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA Prostaglandin E1 (PGE1) relaxes trabecular smooth muscle by interacting with speci®c G-protein coupled receptors on human corpus cavernosum smooth muscle and increasing intracellular synthesis of cAMP. Misoprostol (CytotecTM), is an oral prostaglandin E analogue. The purpose of this study was to compare the functional activity of misoprostol with PGE1 in human corpus cavernosum and cultured human corpus cavernosum smooth muscle cells. Misoprostol, misoprostol free acid or PGE1 induced dose-dependent relaxations in strips of human corpus cavernosum. At concentrations greater than 1076 M, tissue recontraction was observed with all three agents. This was abrogated by pretreatment with the thromboxane A2 receptor antagonist SQ29,548. From these observations, we conclude that misoprostol is activated by human corpus cavernosum in situ and relaxes phenylephrine-precontrated tissue
    [Show full text]
  • Adverse Periocular Reactions to Five Types of Prostaglandin Analogs
    Eye (2012) 26, 1465–1472 & 2012 Macmillan Publishers Limited All rights reserved 0950-222X/12 www.nature.com/eye 1 1 1 1 Adverse periocular K Inoue , M Shiokawa , R Higa , M Sugahara , CLINICAL STUDY T Soga1, M Wakakura1 and G Tomita2 reactions to five types of prostaglandin analogs Abstract Purpose We investigated the appearance explained to patients before PG frequency of eyelid pigmentation and administration. eyelash bristles after the use of five types of Eye (2012) 26, 1465–1472; doi:10.1038/eye.2012.195; prostaglandin (PG) analogs. published online 5 October 2012 Methods This study included 250 eyes from 250 patients diagnosed with primary open- Keywords: prostaglandin analogs; adverse angle glaucoma or ocular hypertension who reactions; eyelid pigmentation; eyelash bristles; were treated with either latanoprost, patient’s subjective evaluation; physician’s travoprost, tafluprost, bimatoprost, or subjective evaluation isopropyl unoprostone for 43 months in only one eye. Photographs of both eyes were obtained, and the images were assessed by Introduction three ophthalmologists who were masked to treatment type. The existence of eyelid Prostaglandin (PG) analogs are the primary pigmentation and eyelash bristles was treatment for glaucoma because of their judged, and images of the left and right eyes powerful intraocular pressure (IOP) decreasing were compared. Subjective symptoms effect, few systematic adverse reactions, and regarding the existence of eyelid convenience of once a day administration (other pigmentation and eyelash bristles were than isopropyl unoprostone (unoprostone)).1 Five types of PG analogs (latanoprost, investigated through a questionnaire. 1Inouye Eye Hospital, Tokyo, Results There was no significant difference travoprost, tafluprost, bimatoprost, and Japan between the five types of medications with unoprostone) are currently available in Japan.
    [Show full text]
  • Tafluprost: the First Preservative-Free Prostaglandin to Treat Open-Angle Glaucoma and Ocular Hypertension
    See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/232647942 Tafluprost: The First Preservative-Free Prostaglandin to Treat Open-Angle Glaucoma and Ocular Hypertension Article in Annals of Pharmacotherapy · October 2012 DOI: 10.1345/aph.1R229 · Source: PubMed CITATIONS READS 13 154 2 authors, including: Michael Neville Wingate University School of Pharmacy 11 PUBLICATIONS 87 CITATIONS SEE PROFILE All content following this page was uploaded by Michael Neville on 21 November 2014. The user has requested enhancement of the downloaded file. ARTICLES New Drug Approvals Tafluprost: The First Preservative-Free Prostaglandin to Treat Open-Angle Glaucoma and Ocular Hypertension Cory Swymer and Michael W Neville afluprost 0.0015% ophthalmic solu- tion (Zioptan) was approved by the T OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical trial data, Food and Drug Administration on Febru- efficacy data, and adverse effect incidence of tafluprost. ary 10, 2012, for the treatment of elevated DATA SOURCES: A literature search was completed using PubMed, Web of intraocular pressure (IOP) in patients with Science, and Google Scholar. Tafluprost was the primary search term. Articles open-angle glaucoma, in addition to ocular published between January 2008 and April 2012 were included in this review. hypertension.1 Although it has been used Additional limits placed on the searches were “human” and “English.” Citations in in other countries since 2008, tafluprost is which tafluprost appeared in the title were 36, 29, and more than 300 in PubMed, Web of Science, and Google Scholar, respectively. the first preservative-free prostaglandin STUDY SELECTION AND DATA EXTRACTION: Three clinical trials were included in analogue commercially available in the this review.
    [Show full text]
  • Travatan, INN-Travoprost
    SCIENTIFIC DISCUSSION This module reflects the initial scientific discussion for the approval of Travatan. This scientific discussion has been updated until 1 November 2003. For information on changes after this date please refer to module 8B. 1. Introduction Travoprost is a prostaglandin analogue intended for use to reduce intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. The product is presented in a concentration of 40 µg/ml of preserved eye drops (0.004%). The dose is one drop of Travoprost Eye Drops in the conjunctival sac of the affected eye(s) once daily. Travoprost Eye Drops contains travoprost (AL- 6221), a prostaglandin analogue, in a sterile ophthalmic solution formulation and it is a selective, full agonist for the FP prostanoid receptor. FP receptor agonists are reported to reduce IOP by increasing uveoscleral outflow. Rationale for the product Glaucoma is the leading cause of irreversible blindness in the world. It is a frequent disease and it has been estimated that 66.8 million have glaucoma, 6.7 million of whom are bilaterally blind. Open angle glaucoma is the most common type, mainly primary but also, in some cases, open angle glaucoma is secondary to the exfoliation syndrome or other primary ocular diseases. Glaucoma is an optic neuropathy that leads to loss of optic-nerve tissue with an excavation of the ophthalmoscopically visible optic nerve head and consequently, to a progressive loss of vision. The elevated IOP is the main risk factor for its development and reduction of IOP has been demonstrated to protect against further damage to the optic nerve, even in patients with IOP that is statistically "normal" (so called normal tension glaucoma).
    [Show full text]
  • Summary of Product Characteristics
    SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT [Invented name] 0.3 mg/mL + 5 mg/mL eye drops, solution 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One mL of solution contains 0.3 mg of bimatoprost and 5 mg of timolol (as 6.8 mg of timolol maleate). Excipient with known effect One mL of solution contains 0.95 mg phosphates. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Eye drops, solution Clear, colorless, aqueous solution, practically free from particles pH: 6.8-7.8 Osmolality: 290 mOsm/Kg ± 10 % (261-319 mOsm/Kg) 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Reduction of intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to topical beta-blockers or prostaglandin analogues. 4.2 Posology and method of administration Posology Recommended dose in adults (including older people) The recommended dose is one drop of [Invented name] in the affected eye(s) once daily, administered either in the morning or in the evening. It should be administered at the same time each day. Existing literature data for preservative-containing bimatoprost/timolol 0.3 mg/mL + 5 mg/mL eye drops, solution suggest that evening dosing may be more effective in IOP lowering than morning dosing. However, consideration should be given to the likelihood of compliance when considering either morning or evening dosing (see section 5.1). If one dose is missed, treatment should continue with the next dose as planned. The dose should not exceed one drop in the affected eye(s) daily.
    [Show full text]
  • Bimatoprost 0.03%/Timolol 0.5% Preservative-Free Ophthalmic
    BJO Online First, published on March 25, 2014 as 10.1136/bjophthalmol-2013-304064 Clinical science Br J Ophthalmol: first published as 10.1136/bjophthalmol-2013-304064 on 25 March 2014. Downloaded from Bimatoprost 0.03%/timolol 0.5% preservative-free ophthalmic solution versus bimatoprost 0.03%/timolol 0.5% ophthalmic solution (Ganfort) for glaucoma or ocular hypertension: a 12-week randomised controlled trial Ivan Goldberg,1 Rafael Gil Pina,2 Aitor Lanzagorta-Aresti,3 Rhett M Schiffman,4 Charlie Liu,4 Marina Bejanian4 ▸ Additional material is ABSTRACT As topical medications are normally dispensed published online only. To view Aim To compare the efficacy and safety of single-dose from multiuse bottles, preservative (typically ben- please visit the journal online (http://dx.doi.org/10.1136/ bimatoprost 0.03%/timolol 0.5% preservative-free (PF) zalkonium chloride, BAK) is employed to maintain bjophthalmol-2013-304064). ophthalmic solution with bimatoprost 0.03%/timolol sterility. Although many patients use preservative- 0.5% ophthalmic solution in patients with open-angle containing medications without adverse effects,10 11 1Department of Ophthalmology, University of glaucoma or ocular hypertension. some become sensitive to ophthalmic preserva- 12 13 Sydney, Sydney Eye Hospital, Methods In this multicentre, randomised, parallel- tives. A single-dose, preservative-free (PF) oph- Sydney, Australia group study, patients were randomised to bimatoprost/ thalmic fixed combination would benefit this patient 2 Clinica Oftalmologica Rafael timolol
    [Show full text]
  • Carbamylcholine on Oxygen Uptake by Isolated Mammalian Parietal Cells
    The Interaction of Histamine with Gastrin and Carbamylcholine on Oxygen Uptake by Isolated Mammalian Parietal Cells ANDREW H. SOLL, Veterans Administration Wadsworth Hospital Cen ter, Los Angeles, California 90073, and the University of California at Los Angeles School of Medicine, Los Angeles, California 90024 A B ST RA CT Using oxygen uptake as an index of the histamine plus carbamylcholine produced maximal physiological response of isolated parietal cells, the responses that were greater than the maximal response interactions between histamine and gastrin and be- to histamine alone further supports the hypothesis that tween histamine and carbamylcholine and the effects of these agents each have direct actions on parietal cells. atropine and metiamide on these interactions have These observations are not consistent with the been studied. Parietal cells were isolated from canine hypothesis that histamine is the sole mediator for the fundic mucosa by sequential exposure of separated effects of other secretagogues. Furthermore, the inhibi- mucosa to collagenase and EDTA. In previous studies torv effects of atropine and metiamide on the specific carbamylcholine, isobutyl methyl xanthine, gastrin, cholinergic and histaminic components of the interac- and histamine have each been shown to increase tions that occur between secretagogues provide a oxygen uptake by these cells. Isobutyl methyl xanthine possible explanation for the apparent lack of specificity greatly enhanced the histamine effect. Carbamyl- of these agents on in vivo acid secretion. choline was inhibited by atropine but not by metiamide, histamine was inhibited by metiamide but not by atropine, and gastrin was inhibited by neither, INTRODUCTION suggesting that each of these agents has a direct action Histamine, gastrin, and cholinergic agents each stimu- on the parietal cell.
    [Show full text]