DOCSLIB.ORG

The Effect of Moxonidine on Plasma Lipid Profile and on LDL Subclass

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Effect of Moxonidine on Plasma Lipid Profile and on LDL Subclass Journal of Human Hypertension (1999) 13, 781–785 1999 Stockton Press. All rights reserved 0950-9240/99 $15.00 http://www.stockton-press.co.uk/jhh ORIGINAL ARTICLE The effect of moxonidine on plasma lipid profile and on LDL subclass distribution MS Elisaf, C Petris, E Bairaktari, S-A Karabina, C Tzallas, A Tselepis and KC Siamopoulos Department of Internal Medicine, University of Ioannina Medical School, Greece Moxonidine is a new antihypertensive agent whose cant decrease in both systolic and diastolic blood ,mechanism of action appears to involve specific stimu- pressure (from 147 ؎ 10 to 131 ؎ 11 mm Hg, P Ͻ 0.001 ,lation of imidazoline receptors resulting in an inhibition and from 98 ؎ 4.5 to 86 ؎ 5 mm Hg, P Ͻ 0.001 of the activity of the central and peripheral sympathetic respectively). No significant change in plasma lipid pro- nervous system. The drug seems to behave neutrally file was observed after moxonidine administration. with respect to plasma lipid parameters. However, there Additionally, no change in the susceptibility of LDL sub- are no data on the effects of moxonidine on the low- classes to copper-induced oxidative modification was density lipoprotein (LDL) subclass pattern or on the LDL noticed. Finally, drug therapy was not followed by any oxidation susceptibility, both of which are known to play change in either LDL phenotype or in mass and compo- a prominent role in the pathogenesis of atherosclerosis. sition of the three LDL subfractions. We conclude, that Thus, we undertook the present study to examine the unlike other antihypertensive drugs, such as beta-block- influence of moxonidine on the LDL subspecies profile ers which may predispose to expression of a relatively and their susceptibility to copper-induced oxidative atherogenic lipoprotein subclass pattern, moxonidine modification in 20 hypertensive patients (11 men, 9 does not affect either plasma lipid parameters or lipo- women) aged 38–61 years. Moxonidine administered at protein composition. a dose of 0.4 mg daily for 8 weeks produced a signifi- Keywords: moxonidine; plasma lipid profile; LDL oxidation susceptibility; LDL subclass pattern; sympathetic nervous system Introduction pheral vascular resistance. Moreover, the reduced sympathetic drive results in lower concentrations of It is well known that some antihypertensive agents, catecholamines and renin.10,11 Randomised com- especially diuretics in high dosage and beta-block- parative studies have shown that the efficacy of ers, have unfavourable effects on plasma lipids, moxonidine as monotherapy is similar to that of including elevation of triglycerides and total choles- other antihypertensive drugs.12 In clinical studies terol and reduction of high-density lipoprotein chol- moxonidine has been found to behave neutrally 1–4 esterol (HDL-C). Additionally, it has been shown with respect to plasma lipid parameters.12–14 How- that beta-blocker use may predispose to expression ever, there are no data on the effects of moxonidine of a relatively atherogenic lipoprotein subclass pro- on the LDL subclass pattern or on the LDL oxidation file, as it is associated with a predominance of susceptibility, both of which are known to play a smaller, denser, low-density lipoprotein (LDL) par- 5,6 prominent role in the pathogenesis of atheroscler- ticles and less HDL mass. Since an overview of all osis. Thus, we undertook the present study to exam- hypertension trials has shown that antihypertensive ine the influence of moxonidine on the LDL sub- treatment does lead to a less than expected species profile and their susceptibility to copper- reduction in coronary heart disease (CHD) event induced oxidative modification in patients with 7,8 rates, it is tempting to suggest that the adverse idiopathic hypertension. effects of the study drugs on lipid metabolism may have offset the potential benefit of blood pressure Materials and methods (BP) reduction. The selective imidazoline-I1-recep- tor agonists, a recently introduced class of antihy- Twenty patients (11 male, 9 female) aged 38–61 pertensive agents, offers an innovative therapeutic years with mild/moderate arterial hypertension approach to the treatment of hypertension.9 Moxoni- were studied. No patient had clinical or biochemical dine, the first drug of this class, stimulates imidazo- evidence of diabetes mellitus, thyroid, hepatic, or line I receptors in the medulla, thereby reducing renal disease. Additionally, none of them was taking central sympathetic drive and attenuating peri- any lipid lowering drugs or any other medication known to affect lipid metabolism, including hor- monal therapy. Individuals known to ingest more Correspondence: Dr Moses S Elisaf, Associate Professor of Medi- cine, Department of Internal Medicine, University of Ioannina, than two alcoholic drinks or to take vitamin sup- Medical School, GR 451 10 Ioannina, Greece plements were excluded from the study. To avoid Received 10 January 1999; accepted 25 February 1999 any possible effects of diet on the susceptibility of Effect of moxonidine on LDL subclass distribution MS Elisaf et al 782 the LDL subfractions to oxidation, all subjects were dation is divided into three consecutive phases, lag advised to avoid altering their dietary habits phase, propagation phase and decomposition phase. throughout the study. The lag time, the maximal rate of conjugated dienes After a wash-out period of at least 4 weeks for the formation, and the total amount of dienes formed patients on antihypertensive drugs, moxonidine was were calculated as previously described.16 The rela- given at a dose of 0.4 mg/day for 8 weeks. Before tive electrophoretic mobility (REM) of the oxidised and after treatment BP was measured by a calibrated subfractions was determined by agarose gel electro- sphygmomanometer as triplicate measurements phoresis on agarose gels [Lipo + Lp(a), Sebia]. after the patients had been sitting for 5 min. In addition to BP measurements, pulse rate was Analytical methods recorded and venous blood was obtained after a 14 h overnight fast for the determination of plasma Total plasma cholesterol and triglyceride levels lipid parameters. were measured by enzymatic colorimetric assays Subfractionation of LDL with density gradient using an RA 1000 analyser (Technicon Instruments, ultracentrifugation was performed and the suscepti- NY, USA). HDL-cholesterol levels were also deter- bility of LDL subclasses to copper-induced oxidative mined by the same method after precipitation of modification was tested. apoB-containing lipoproteins with magnesium-dex- tran sulphate. LDL-cholesterol levels were calcu- lated using the Friedewald formula.17 Plasma lipo- Subfractionation of low-density lipoprotein protein (a) [Lp(a)] levels were measured in duplicate Venous blood samples were collected from over- using a monoclonal anti-Lp(a) antibody technique night fasting donors in tubes containing 0.001% by the enzyme immunoassay Macra Lp(a) (Terumo Na2EDTA. Immediately after collection of plasma, Medical Corporation Diagnostic Division, Elkton, 1.3 mM EDTA and 50 ␮g/ml of gentamicin were MD, USA). The lower limit of detectability was added and plasma was stored at 4°C in order to pre- 0.8 mg/dL. Plasma apoAl and apoB were measured vent metal cation catalysed lipoprotein oxidation by immunonephelometry with the aid of a Beckman and microbial growth. Within 24 h from its collec- array analyser (Beckman Instruments, CA, USA). tion, plasma was submitted to density gradient ultra- The cholesterol, phospholipid and triglyceride con- centrifugation in a Beckman ultracentrifuge at tent of each lipoprotein subfraction was determined 40 000 rpm, 14°C for 24 h, using a Beckman SW41 enzymatically using the BioMerieux kits. The pro- Ti rotor as previously described.15 Construction of a tein content of the gradient fractions and lipoprotein discontinuous density gradient at ambient tempera- subfractions was determined by the BCA method. ture was initiated by pumping 3 ml of plasma into Lipoprotein mass in each subfraction was calculated the bottom of the tube. The density of the plasma as the sum of the concentrations of the individual was raised to 1.10 g/ml by dissolution of 0.42 g KBr. components (cholesterol, triglyceride, phospholipid The plasma was then successively overlayered by and protein) and allowed the determination of the four solutions of decreasing density (2 ml of d = percent chemical composition.16 1.065 g/ml, 3 ml of d = 1.035 g/ml, 3 ml of d = 1.019 g/ml and 1.0 ml of d = 1.006 g/ml). After ultra- Statistical analysis centrifugation, 30 fractions of 400 ␮l were collected by successive aspiration with a precision pipette Data were expressed as mean ± s.d., except for Lp(a), from the meniscus downwards. All fractions were which was expressed in terms of median and range. analysed for their protein content. Subsequently, Statistical analysis was performed using paired or equal volumes of specific gradient fractions corre- unpaired Student’s t-test or Wilcoxon signed-rank sponding to d = 1.030–1.034 g/ml, d = 1.034– test. A P value of less than 0.05 was considered to 1.041 g/ml and d = 1.041–1.048 g/ml were pooled to be significant. constitute the LDL1, LDL2 and LDL3 subfractions, respectively. Results Moxonidine produced a significant decrease in both Oxidation of low-density lipoprotein subfractions systolic and diastolic BP (from 147 ± 10 to 131 ± 11 Before oxidation, LDL subfractions were dialysed to mm Hg, P Ͻ 0.001, and from 98 ± 4.5 to 86 ± 5 remove EDTA against two changes of a 200-fold vol- mm Hg, P Ͻ 0.001, respectively) while no significant ume of 10 mM phosphate buffered saline solution change in heart rate was noticed. As shown in Table (PBS), pH 7.4 for 24 h at 4°C in the dark. From the 1, drug administration was not followed by any dialysed LDL subfractions, a volume of 1 ml con- significant change in plasma lipid parameters. taining 100 ␮g protein/ml PBS was oxidised in the presence of CuSO ,5␮M final concentration.
Load more

Recommended publications
  • Inline-Supplementary-Material-1.Pdf
    Appendix 1: STOPP/START criteria version 2 applied to the TRUST dataset Physiological system Criteria Criteria included Number (%) (The relevant () criteria for each participant were applied to the dataset and recorded in of Microsoft Office Excel ® (2013)) criteria included out of total criteria STOPP criteria Indication of medication A1. Any drug prescribed without an evidence-based clinical indication. X 1/3 (33.3) A2. Any drug prescribed beyond the recommended duration, where treatment duration is X well defined. A3. Any duplicate drug class prescription e.g. two concurrent NSAIDs, SSRIs, loop diuretics, ACE inhibitors, anticoagulants (optimisation of monotherapy within a single drug class should be observed prior to considering a new agent). Cardiovascular system B1. Digoxin for heart failure with preserved systolic ventricular function (no clear evidence X 7/13 (53.8) of benefit). B2. Verapamil or diltiazem with NYHA Class III or IV heart failure (may worsen heart failure). B3. Beta-blocker in combination with verapamil or diltiazem (risk of heart block). B4. Beta blocker with symptomatic bradycardia (< 50/min), type II heart block or complete heart block (risk of profound hypotension, asystole). B5. Amiodarone as first-line antiarrhythmic therapy in supraventricular tachyarrhythmias X (higher risk of side-effects than beta-blockers, digoxin, verapamil or diltiazem). B6. Loop diuretic as first-line treatment for hypertension (safer, more effective alternatives available). B7. Loop diuretic for dependent ankle oedema without clinical, biochemical evidence or radiological evidence of heart failure, liver failure, nephrotic syndrome or renal failure (leg elevation and /or compression hosiery usually more appropriate). B8. Thiazide diuretic with current significant hypokalaemia (i.e.
    [Show full text]
  • Imidazoline Antihypertensive Drugs: Selective I1-Imidazoline Receptors Activation K
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by FarFar - Repository of the Faculty of Pharmacy, University of Belgrade REVIEW Imidazoline Antihypertensive Drugs: Selective I1-Imidazoline Receptors Activation K. Nikolic & D. Agbaba Faculty of Pharmacy, Institute of Pharmaceutical Chemistry, University of Belgrade, Vojvode Stepe, Belgrade, Serbia Keywords SUMMARY α2-Adrenergic receptors; Centrally acting antihypertensives; Clonidine; Hypertension; Involvement of imidazoline receptors (IR) in the regulation of vasomotor tone as well as in Imidazoline receptors; Rilmenidine. the mechanism of action of some centrally acting antihypertensives has received tremen- dous attention. To date, pharmacological studies have allowed the characterization of three Correspondence main imidazoline receptor classes, the I1-imidazoline receptor which is involved in central K. Nikolic, Faculty of Pharmacy, Institute of inhibition of sympathetic tone to lower blood pressure, the I2-imidazoline receptor which Pharmaceutical Chemistry, University of is an allosteric binding site of monoamine oxidase B (MAO-B), and the I3-imidazoline re- Belgrade, Vojvode Stepe 450, 11000 Belgrade, ceptor which regulates insulin secretion from pancreatic β-cells. All three imidazoline re- Serbia. ceptors represent important targets for cardiovascular research. The hypotensive effect of + Tel: 381-63-84-30-677; clonidine-like centrally acting antihypertensives was attributed both to α2-adrenergic re- + Fax: 381-11-3974-349; ceptors and nonadrenergic I1-imidazoline receptors, whereas their sedative action involves E-mail: [email protected] activation of only α2-adrenergic receptors located in the locus coeruleus. Since more selec- tive I1-imidazoline receptors ligands reduced incidence of typical side effects of other cen- trally acting antihypertensives, there is significant interest in developing new agents with higher selectivity and affinity for I1-imidazoline receptors.
    [Show full text]
  • Low Dose of Moxonidine Within the Rostral Ventrolateral Medulla Improves the Baroreflex Sensitivity Control of Sympathetic Activity in Hypertensive Rat
    npg Acta Pharmacologica Sinica (2009) 30: 1594–1600 © 2009 CPS and SIMM All rights reserved 1671-4083/09 $32.00 www.nature.com/aps Original Article Low dose of moxonidine within the rostral ventrolateral medulla improves the baroreflex sensitivity control of sympathetic activity in hypertensive rat Jia-ling WANG1, 2, #, Long WANG3, #, Zhao-tang WU4, #, Wen-jun YUAN1, Ding-feng SU4, Xin NI1, Jian-jun YAN5,*, Wei-zhong WANG1,* Department of 1Physiology and 4Pharmacology, Second Military Medical University, Shanghai 200433, China; 2Department of Emergency, Changhai Hospital, Shanghai 200433, China; 3Shanghai Research Center for Biomodel Organism, Shanghai 200433, China; 5The First Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai 200433, China Aim: To determine the effects of the centrally antihypertensive drug moxonidine injected into the rostral ventrolateral medulla (RVLM) on baroreflex function in spontaneously hypertensive rats (SHR). Methods: Baroreflex sensitivity control of renal sympathetic nerve activity (RSNA) and barosensitivity of the RVLM presympathetic neu- rons were determined following application of different doses of moxonidine within the RVLM. Results: Three doses (0.05, 0.5, and 5 nmol in 50 nL) of moxonidine injected bilaterally into the RVLM dose-dependently reduced the baseline blood pressure (BP) and RSNA in SHR. At the highest dose (5 nmol) of moxonidine injection, the maximum gain (1.24%±0.04%/mmHg) of baroreflex control of RSNA was significantly decreased. However, the lower doses (0.05 and 0.5 nmol) of moxonidine injection into the RVLM significantly enhanced the baroreflex gain (2.34%±0.08% and 2.01%±0.07%/mmHg). The moxoni- dine-induced enhancement in baroreflex function was completely prevented by the imidazoline receptor antagonist efaroxan but not by the α2-adrenoceptor antagonist yohimbine.
    [Show full text]
  • What to Do When You Find Your Patient Is Non-Adherent to Antihypertensive Therapy ?
    What to do when you find your patient is non-adherent to antihypertensive therapy ? Indranil Dasgupta Consultant in nephrology and hypertension Heartlands Hospital Birmingham Honorary Reader, University of Birmingham Conflict of interest • Received – Research grants: Medtronic and Daiichi Sankyo – Speaker fees: Sanofi, MSD, Pfeizer, GSK, Mitshubishi pharma, Otsuka, Agenda • Case studies • Size of the problem • Cost to the NHS • Detection • Factors responsible • Measures to improve adherence • Further research Case study 1 Case study 1 • 57 year old lady, FH of hypertension, BMI 38 • Mean BP in clinic: 171/92 mmHg • Mean daytime ABP: 147/84 mmHg • Current medications: – Amlodipine 10 mg once daily – Bisoprolol 2.5 mg once daily – Doxazosin MR 8 mg once daily – Furosemide 40 mg once daily – Indapamide 2.5 mg once daily – Losartan 100 mg once daily • Urine sent for antihypertenive drug assay Urine antihypertensive drug assay • She was advised to take amlodipine 5mg only and given life style advice especially to lose weight Case study 2 • 55 year old lady, teacher – Deputy Head of English • Recent clinic BP 175/104, 177/75, 222/114 • Known white coat effect, BMI 41 • Medication: – Losartan 100 mg once daily – Felodipine 20 mg once daily – Doxazosin 8 mg twice daily – Furosemide 60 mg once daily – Bisoprolol 7.5 mg once daily • Urine AHT assay requested She wouldn’t accept the result but since then her BP control has improved! Case study 3 • 41 year old man, engineer Rolls Royce • Referred a year ago for drop in GFR 64 to 23 • Losartan 150mg,
    [Show full text]
  • Monteplase/Nadolol 1345 Moxisylyte Is Given As the Hydrochloride but the Dose May Be Tion Half-Life Is 2 to 3 Hours and Is Prolonged in Renal Pharmacopoeias
    Monteplase/Nadolol 1345 Moxisylyte is given as the hydrochloride but the dose may be tion half-life is 2 to 3 hours and is prolonged in renal Pharmacopoeias. In Eur. (see p.vii), Jpn, and US. expressed in terms of the base. Moxisylyte hydrochloride impairment. Moxonidine is about 7% bound to plasma Ph. Eur. 6.2 (Nadolol). A white or almost white crystalline 45.2 mg is equivalent to about 40 mg of moxisylyte. proteins. It is distributed into breast milk. powder. Slightly soluble in water; freely soluble in alcohol; prac- In the management of peripheral vascular disease, the usual tically insoluble in acetone. oral dose is the equivalent of 40 mg of moxisylyte four times dai- USP 31 (Nadolol). A white or off-white, practically odourless, ly increased if necessary to 80 mg four times daily. It should be Uses and Administration crystalline powder. Soluble in water at pH 2; slightly soluble in withdrawn if there is no response in 2 weeks. Moxonidine is a centrally acting antihypertensive water at pH 7 to 10; freely soluble in alcohol and in methyl alco- Moxisylyte has been used locally in the eye to reverse the my- structurally related to clonidine (p.1247). It appears to hol; insoluble in acetone, in ether, in petroleum spirit, in trichlo- driasis caused by phenylephrine and other sympathomimetics. It act through stimulation of central imidazoline recep- roethane, and in benzene; slightly soluble in chloroform, in dichloromethane, and in isopropyl alcohol. has also been used orally in benign prostatic hyperplasia, al- tors to reduce sympathetic tone, and also has alpha - though such use has been associated with hepatotoxicity; the 2 doses used in prostatic hyperplasia were generally higher than adrenoceptor agonist activity.
    [Show full text]
  • Update on Rilmenidine: Clinical Benefits
    AJH 2001; 14:322S–324S Update on Rilmenidine: Clinical Benefits John L. Reid Rilmenidine is an imidazoline derivative that appears to consistent with a reduction in long-term cardiovascular lower blood pressure (BP) by an interaction with imida- risk, as would recently described actions on the heart zoline (I1) receptors in the brainstem (and kidneys). Ril- (reducing left ventricular hypertrophy) and the kidney menidine is as effective in monotherapy as all other first- (reducing microalbuminuria). Although no data are yet Downloaded from https://academic.oup.com/ajh/article/14/S7/322S/137317 by guest on 28 September 2021 line classes of drugs, including diuretics, ␤-blockers, available from prospective long-term outcome studies, angiotensin converting enzyme (ACE) inhibitors, and cal- rilmenidine could represent an important new develop- cium antagonists. It is well tolerated and can be taken in ment in antihypertensive therapy and the prevention of combination for greater efficacy. Sedation and dry mouth cardiovascular disease. Am J Hypertens 2001;14:322S–324S are not prominent side effects and withdrawal hyperten- © 2001 American Journal of Hypertension, Ltd. sion is not seen when treatment is stopped abruptly. Recently, in addition to a reduction in BP, this agent Key Words: Blood pressure, rilmenidine, imidazoline, insu- has been shown to improve glucose tolerance, lipid risk lin resistance, metabolic syndrome, microalbuminuria, ventricu- factors, and insulin sensitivity. These changes would be lar hypertrophy, end-organ damage. n spite of major developments during the past 50 included in the treatment choice of several key outcome years, there is still no single ideal antihypertensive trials (Veterans Administration [VA] trials and European I drug.
    [Show full text]
  • Interaction of the Sympathetic Nervous System with Other Pressor Systems in Antihypertensive Therapy
    Journal of Clinical and Basic Cardiology An Independent International Scientific Journal Journal of Clinical and Basic Cardiology 2001; 4 (3), 185-192 Interaction of the Sympathetic Nervous System with other Pressor Systems in Antihypertensive Therapy Wenzel RR, Baumgart D, Bruck H, Erbel R, Heemann U Mitchell A, Philipp Th, Schaefers RF Homepage: www.kup.at/jcbc Online Data Base Search for Authors and Keywords Indexed in Chemical Abstracts EMBASE/Excerpta Medica Krause & Pachernegg GmbH · VERLAG für MEDIZIN und WIRTSCHAFT · A-3003 Gablitz/Austria FOCUS ON SYMPATHETIC TONE Interaction of SNS J Clin Basic Cardiol 2001; 4: 185 Interaction of the Sympathetic Nervous System with Other Pressor Systems in Antihypertensive Therapy R. R. Wenzel1, H. Bruck1, A. Mitchell1, R. F. Schaefers1, D. Baumgart2, R. Erbel2, U. Heemann1, Th. Philipp1 Regulation of blood pressure homeostasis and cardiac function is importantly regulated by the sympathetic nervous system (SNS) and other pressor systems including the renin-angiotensin system (RAS) and the vascular endothelium. Increases in SNS activity increase mortality in patients with hypertension, coronary artery disease and congestive heart failure. This review summarizes some of the interactions between the main pressor systems, ie, the SNS, the RAS and the vascular endothelium including the endothelin-system. Different classes of cardiovascular drugs interfere differently with the SNS and the other pressor systems. Beta-blockers, ACE-inhibitors and diuretics have no major effect on central SNS activity. Pure vasodilators including nitrates, alpha-blockers and DHP-calcium channel blockers increase SNS activity. In contrast, central sympatholytic drugs including moxonidine re- duce SNS activity. The effects of angiotensin-II receptor antagonist on SNS activity in humans are not clear, experimental data are discussed in this review.
    [Show full text]
  • Estonian Statistics on Medicines 2016 1/41
    Estonian Statistics on Medicines 2016 ATC code ATC group / Active substance (rout of admin.) Quantity sold Unit DDD Unit DDD/1000/ day A ALIMENTARY TRACT AND METABOLISM 167,8985 A01 STOMATOLOGICAL PREPARATIONS 0,0738 A01A STOMATOLOGICAL PREPARATIONS 0,0738 A01AB Antiinfectives and antiseptics for local oral treatment 0,0738 A01AB09 Miconazole (O) 7088 g 0,2 g 0,0738 A01AB12 Hexetidine (O) 1951200 ml A01AB81 Neomycin+ Benzocaine (dental) 30200 pieces A01AB82 Demeclocycline+ Triamcinolone (dental) 680 g A01AC Corticosteroids for local oral treatment A01AC81 Dexamethasone+ Thymol (dental) 3094 ml A01AD Other agents for local oral treatment A01AD80 Lidocaine+ Cetylpyridinium chloride (gingival) 227150 g A01AD81 Lidocaine+ Cetrimide (O) 30900 g A01AD82 Choline salicylate (O) 864720 pieces A01AD83 Lidocaine+ Chamomille extract (O) 370080 g A01AD90 Lidocaine+ Paraformaldehyde (dental) 405 g A02 DRUGS FOR ACID RELATED DISORDERS 47,1312 A02A ANTACIDS 1,0133 Combinations and complexes of aluminium, calcium and A02AD 1,0133 magnesium compounds A02AD81 Aluminium hydroxide+ Magnesium hydroxide (O) 811120 pieces 10 pieces 0,1689 A02AD81 Aluminium hydroxide+ Magnesium hydroxide (O) 3101974 ml 50 ml 0,1292 A02AD83 Calcium carbonate+ Magnesium carbonate (O) 3434232 pieces 10 pieces 0,7152 DRUGS FOR PEPTIC ULCER AND GASTRO- A02B 46,1179 OESOPHAGEAL REFLUX DISEASE (GORD) A02BA H2-receptor antagonists 2,3855 A02BA02 Ranitidine (O) 340327,5 g 0,3 g 2,3624 A02BA02 Ranitidine (P) 3318,25 g 0,3 g 0,0230 A02BC Proton pump inhibitors 43,7324 A02BC01 Omeprazole
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,080,578 B2 Liggett Et Al
    USO08080578B2 (12) United States Patent (10) Patent No.: US 8,080,578 B2 Liggett et al. (45) Date of Patent: *Dec. 20, 2011 (54) METHODS FOR TREATMENT WITH 5,998.458. A 12/1999 Bristow ........................ 514,392 BUCNDOLOL BASED ON GENETIC 6,004,744. A 12/1999 Goelet et al. ...... 435/5 6,013,431 A 1/2000 Söderlund et al. 435/5 TARGETING 6,156,503 A 12/2000 Drazen et al. ..... ... 435/6 6,221,851 B1 4/2001 Feldman ... 51446 (75) Inventors: Stephen B. Liggett, Clarksville, MD 6,316,188 B1 1 1/2001 Yan et al. .......................... 435/6 6,365,618 B1 4/2002 Swartz ... 514,411 (US); Michael Bristow, Englewood, CO 6,498,009 B1 12/2002 Liggett ............................. 435/6 (US) 6,566,101 B1 5/2003 Shuber et al. 435,912 6,586,183 B2 7/2003 Drysdale et al. .................. 435/6 (73) Assignee: The Regents of the University of 6,784, 177 B2 8/2004 Cohn et al. 514,248 Colorado, a body corporate, Denver, 6,797.472 B1 9/2004 Liggett ......... ... 435/6 6,821,724 B1 1 1/2004 Mittman et al. ... 435/6 CO (US) 6,861.217 B1 3/2005 Liggett ......... ... 435/6 7,041,810 B2 5/2006 Small et al. ... ... 435/6 (*) Notice: Subject to any disclaimer, the term of this 7, 195,873 B2 3/2007 Fligheddu et al. ... 435/6 patent is extended or adjusted under 35 7,211,386 B2 5/2007 Small et al. ....... ... 435/6 7,229,756 B1 6/2007 Small et al.
    [Show full text]
  • Marrakesh Agreement Establishing the World Trade Organization
    No. 31874 Multilateral Marrakesh Agreement establishing the World Trade Organ ization (with final act, annexes and protocol). Concluded at Marrakesh on 15 April 1994 Authentic texts: English, French and Spanish. Registered by the Director-General of the World Trade Organization, acting on behalf of the Parties, on 1 June 1995. Multilat ral Accord de Marrakech instituant l©Organisation mondiale du commerce (avec acte final, annexes et protocole). Conclu Marrakech le 15 avril 1994 Textes authentiques : anglais, français et espagnol. Enregistré par le Directeur général de l'Organisation mondiale du com merce, agissant au nom des Parties, le 1er juin 1995. Vol. 1867, 1-31874 4_________United Nations — Treaty Series • Nations Unies — Recueil des Traités 1995 Table of contents Table des matières Indice [Volume 1867] FINAL ACT EMBODYING THE RESULTS OF THE URUGUAY ROUND OF MULTILATERAL TRADE NEGOTIATIONS ACTE FINAL REPRENANT LES RESULTATS DES NEGOCIATIONS COMMERCIALES MULTILATERALES DU CYCLE D©URUGUAY ACTA FINAL EN QUE SE INCORPOR N LOS RESULTADOS DE LA RONDA URUGUAY DE NEGOCIACIONES COMERCIALES MULTILATERALES SIGNATURES - SIGNATURES - FIRMAS MINISTERIAL DECISIONS, DECLARATIONS AND UNDERSTANDING DECISIONS, DECLARATIONS ET MEMORANDUM D©ACCORD MINISTERIELS DECISIONES, DECLARACIONES Y ENTEND MIENTO MINISTERIALES MARRAKESH AGREEMENT ESTABLISHING THE WORLD TRADE ORGANIZATION ACCORD DE MARRAKECH INSTITUANT L©ORGANISATION MONDIALE DU COMMERCE ACUERDO DE MARRAKECH POR EL QUE SE ESTABLECE LA ORGANIZACI N MUND1AL DEL COMERCIO ANNEX 1 ANNEXE 1 ANEXO 1 ANNEX
    [Show full text]
  • Package Leaflet: Information for the User /.../ 0.2 Mg Film-Coated Tablets Moxonidine Read All of This Leaflet Carefully Before
    Package leaflet: Information for the user /.../ 0.2 mg film-coated tablets Moxonidine Read all of this leaflet carefully before you start taking this medicine because it contains important information for you. - Keep this leaflet. You may need to read it again. - If you have any further questions, ask your doctor or pharmacist. - This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. - If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4. What is in this leaflet 1. What /.../ is and what it is used for 2. What you need to know before you take /.../ 3. How to take /.../ 4. Possible side effects 5. How to store /.../ 6. Contents of the pack and other information 1. What /…/ is and what it is used for /.../ is a medication used to reduce high blood pressure. They act through the central nervous system to lower the blood pressure. /.../ is used in the treatment of mild to moderate forms of high blood pressure that are not organ-related (essential hypertension). 2. What you need to know before you take /…/ Do not take /.../ - if you are allergic to the active substance moxonidine or to any of the other ingredients of this medicine (listed in section 6). - if you suffer from certain types of disturbances in heart rhythm (sick sinus syndrome or 2nd or 3rd degree atrioventricular block) - if your resting heart rate is very slow (less than 50 beats per minute at rest) (bradycardia) - if you suffer from heart failure or heart insufficiency (a condition in which the heart does not pump enough blood through the body, resulting in e.g.
    [Show full text]
  • New Zealand Data Sheet
    NEW ZEALAND DATA SHEET 1 PRODUCT NAME Bisoprolol 2.5 mg film coated tablet Bisoprolol 5 mg film coated tablet Bisoprolol 10 mg film coated tablet 2 QUALITATIVE AND QUANTITATIVE COMPOSITION For 2.5mg: Each film-coated tablet contains 2.5 mg Bisoprolol fumarate. For 5mg: Each film-coated tablet contains 5 mg Bisoprolol fumarate For 10mg: Each film-coated tablet contains 10 mg Bisoprolol fumarate For the full list of excipients, see section 6.1. 3 PHARMACEUTICAL FORM For 2.5mg: White to off white, round, biconvex, film coated tablets, debossed 'b1' on one side and break line on other side For 5mg: White to off white, round, biconvex, film coated tablets, debossed 'b2' on one side and break line on other side For 10mg: White to off white, round, biconvex, film coated tablets, debossed 'b3' on one side and break line on other side The tablet can be divided into equal halves. 4 CLINICAL PARTICULARS 4.1 Therapeutic indications • Treatment of stable chronic heart failure with reduced systolic left ventricular function in addition to ACE inhibitors, and diuretics, and optionally cardiac glycosides (for additional information see section 5.1). • Treatment of chronic, stable angina pectoris. • Treatment of essential hypertension. New Zealand Data Sheet Template v 1.1 March 2017 Page 1 of 12 NEW ZEALAND DATA SHEET 4.2 Dose and method of administration Stable chronic heart failure Standard treatment of CHF consists of an ACE inhibitor (or an angiotensin receptor blocker in case of intolerance to ACE inhibitors), a beta-blocker, diuretics, and when appropriate cardiac glycosides.
    [Show full text]