AT1-Receptor Blockers: Differences That Matter
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Key Features of Candesartan Cilexetil and a Comparison with Other Angiotensin II Receptor Antagonists
Journal of Human Hypertension (1999) 13, (Suppl 1), S3–S10 1999 Stockton Press. All rights reserved 0950-9240/99 $12.00 Key features of candesartan cilexetil and a comparison with other angiotensin II receptor antagonists PS Sever Imperial College of Science, Technology & Medicine at St Mary’s Hospital, London, UK Current research on angiotensin II AT1-receptor antag- in patients with essential hypertension. Candesartan onists (AIIRAs) and selected studies presented at the cilexetil has a rapid onset of action (approximately 80% recent symposium held in Amsterdam, The Netherlands, of total blood pressure reduction within the first 2 on 6 June 1998, titled ‘Angiotensin II Receptor Antagon- weeks) and dose-dependent effects on blood pressure, ists are NOT all the Same’ are reviewed. AIIRAs offer a is comparable in efficacy to a number of classes of anti- number of potential advantages over alternative antihy- hypertensives, and is effective in combination therapy pertensive agents acting via the renin-angiotensin-aldo- (eg, with hydrochlorothiazide and amlodipine). This sterone system. They combine blood pressure-lowering favourable profile may be due in part to the highly selec- effects at least equivalent to those of angiotensin-con- tive, tight binding to and slow dissociation of candesar- verting enzyme (ACE) inhibitors, coupled with placebo- tan from the AT1 receptor. Preliminary studies suggest like tolerability. Candesartan cilexetil is a novel AIIRA that candesartan cilexetil also protects end organs that has demonstrated clinical -
Cysteinyl Leukotriene Receptor 1/2 Antagonists Nonselectively Modulate Organic Anion Transport by Multidrug Resistance Proteins (MRP1-4) S
Supplemental material to this article can be found at: http://dmd.aspetjournals.org/content/suppl/2016/04/11/dmd.116.069468.DC1 1521-009X/44/6/857–866$25.00 http://dx.doi.org/10.1124/dmd.116.069468 DRUG METABOLISM AND DISPOSITION Drug Metab Dispos 44:857–866, June 2016 Copyright ª 2016 by The American Society for Pharmacology and Experimental Therapeutics Cysteinyl Leukotriene Receptor 1/2 Antagonists Nonselectively Modulate Organic Anion Transport by Multidrug Resistance Proteins (MRP1-4) s Mark A. Csandl, Gwenaëlle Conseil, and Susan P. C. Cole Departments of Biomedical and Molecular Sciences (M.A.C., S.P.C.C.), and Pathology and Molecular Medicine (G.C., S.P.C.C.), Division of Cancer Biology and Genetics, Queen’s University Cancer Research Institute, Kingston, ON, Canada Received January 13, 2016; accepted April 7, 2016 ABSTRACT Active efflux of both drugs and organic anion metabolites is class of antagonists showed any MRP selectivity. For E217bG Downloaded from mediated by the multidrug resistance proteins (MRPs). MRP1 uptake, LTM IC50s ranged from 1.2 to 26.9 mMandweremost (ABCC1), MRP2 (ABCC2), MRP3 (ABCC3), and MRP4 (ABCC4) have comparable for MRP1 and MRP4. The LTM rank order inhibitory partially overlapping substrate specificities and all transport 17b- potencies for E217bGversusLTC4 uptake by MRP1, and E217bG estradiol 17-(b-D-glucuronide) (E217bG). The cysteinyl leukotriene versus PGE2 uptake by MRP4, were also similar. Three of four receptor 1 (CysLT1R) antagonist MK-571 inhibits all four MRP CysLT1R-selective LTMs also stimulated MRP2 (but not MRP3) homologs, but little is known about the modulatory effects of newer transport and thus exerted a concentration-dependent biphasic leukotriene modifiers (LTMs). -
The 5-HT6 Receptor Antagonist SB-271046 Selectively Enhances Excitatory Neurotransmission in the Rat Frontal Cortex and Hippocampus Lee A
The 5-HT6 Receptor Antagonist SB-271046 Selectively Enhances Excitatory Neurotransmission in the Rat Frontal Cortex and Hippocampus Lee A. Dawson, Ph.D., Huy Q. Nguyen, B.S., and Ping Li, B.S. Preclinical evidence has suggested a possible role for the 5-HT6 increases in extracellular glutamate levels in both frontal receptor in the treatment of cognitive dysfunction. However, cortex and dorsal hippocampus, respectively. These effects were currently there is little neurochemical evidence suggesting the completely attenuated by infusion of tetrodotoxin but mechanism(s) which may be involved. Using the selective unaffected by the muscarinic antagonist, atropine. Here we 5-HT6 antagonist SB-271046 and in vivo microdialysis, we demonstrate for the first time the selective enhancement of have evaluated the effects of this compound on the modulation excitatory neurotransmission by SB-271046 in those brain of basal neurotransmitter release within multiple brain regions regions implicated in cognitive and memory function, and of the freely moving rat. SB-271046 produced no change in provide mechanistic evidence in support of a possible basal levels of dopamine (DA), norepinephrine (NE) or 5-HT therapeutic role for 5-HT6 receptor antagonists in the in the striatum, frontal cortex, dorsal hippocampus or nucleus treatment of cognitive and memory dysfunction. accumbens. Similarly, this compound had no effect on [Neuropsychopharmacology 25:662–668, 2001] excitatory neurotransmission in the striatum or nucleus © 2001 American College of Neuropsychopharmacology. accumbens. Conversely, SB-271046 produced 3- and 2-fold Published by Elsevier Science Inc. KEY WORDS: 5-HT6 receptor; SB-271046; Microdialysis; sma et al. 1993; Ruat et al. -
Receptor Antagonist (H RA) Shortages | May 25, 2020 2 2 2 GERD4,5 • Take This Opportunity to Determine If Continued Treatment Is Necessary
H2-receptor antagonist (H2RA) Shortages Background . 2 H2RA Alternatives . 2 Therapeutic Alternatives . 2 Adults . 2 GERD . 3 PUD . 3 Pediatrics . 3 GERD . 3 PUD . 4 Tables Table 1: Health Canada–Approved Indications of H2RAs . 2 Table 2: Oral Adult Doses of H2RAs and PPIs for GERD . 4 Table 3: Oral Adult Doses of H2RAs and PPIs for PUD . 5 Table 4: Oral Pediatric Doses of H2RAs and PPIs for GERD . 6 Table 5: Oral Pediatric Doses of H2RAs and PPIs for PUD . 7 References . 8 H2-receptor antagonist (H2RA) Shortages | May 25, 2020 1 H2-receptor antagonist (H2RA) Shortages BACKGROUND Health Canada recalls1 and manufacturer supply disruptions may be causing shortages of commonly used acid-reducing medications called histamine H2-receptor antagonists (H2RAs) . H2RAs include cimetidine, famotidine, nizatidine and ranitidine . 2 There are several Health Canada–approved indications of H2RAs (see Table 1); this document addresses the most common: gastroesophageal reflux disease (GERD) and peptic ulcer disease (PUD) . 2 TABLE 1: HEALTH CANADA–APPROVED INDICATIONS OF H2RAs H -Receptor Antagonists (H RAs) Health Canada–Approved Indications 2 2 Cimetidine Famotidine Nizatidine Ranitidine Duodenal ulcer, treatment ü ü ü ü Duodenal ulcer, prophylaxis — ü ü ü Benign gastric ulcer, treatment ü ü ü ü Gastric ulcer, prophylaxis — — — ü GERD, treatment ü ü ü ü GERD, maintenance of remission — ü — — Gastric hypersecretion,* treatment ü ü — ü Self-medication of acid indigestion, treatment and prophylaxis — ü† — ü† Acid aspiration syndrome, prophylaxis — — — ü Hemorrhage from stress ulceration or recurrent bleeding, — — — ü prophylaxis ü = Health Canada–approved indication; GERD = gastroesophageal reflux disease *For example, Zollinger-Ellison syndrome . -
Download Leaflet View the Patient Leaflet in PDF Format
Package leaflet: Information for the user Candesartan cilexetil 2 mg tablets Candesartan cilexetil 4 mg tablets Candesartan cilexetil 8 mg tablets Candesartan cilexetil 16 mg tablets Candesartan cilexetil 32 mg tablets candesartan cilexetil Read all of this leaflet carefully If you are going to have an operation, before you start taking this tell your doctor or dentist that you are medicine because it contains taking Candesartan cilexetil. This is important information for you. because Candesartan cilexetil, when - Keep this leaflet. You may need combined with some anaesthetics, to read it again. may cause an excessive drop in - If you have any further questions, blood pressure. ask your doctor or pharmacist. - This medicine has been Children and adolescents prescribed for you only. Do not Candesartan Cilexetil has been pass it on to others. It may harm studied in children. For more them, even if their signs of illness information, talk to your doctor. are the same as yours. Candesartan Cilexetil must not be - If you get any side effects, talk to given to children under 1 year of your doctor or pharmacist. This age due to the potential risk to the includes any possible side effects developing kidneys. not listed in this leaflet. See Other medicines and Candesartan section 4. cilexetil What is in this leaflet Tell your doctor or pharmacist if you 1. What Candesartan cilexetil is and are taking, have recently taken or what it is used for might take any other medicines. 2. What you need to know before you take Candesartan cilexetil Candesartan cilexetil can affect the 3. -
Binding Mode Exploration of B1 Receptor Antagonists' by the Use of Molecular Dynamics and Docking Simulation—How Different T
International Journal of Molecular Sciences Article Binding Mode Exploration of B1 Receptor Antagonists’ by the Use of Molecular Dynamics and Docking Simulation—How Different Target Engagement Can Determine Different Biological Effects Marica Gemei 1,*, Carmine Talarico 1 , Laura Brandolini 1, Candida Manelfi 1, Lorena Za 2, Silvia Bovolenta 2, Chiara Liberati 2, Luigi Del Vecchio 3, Roberto Russo 4 , Carmen Cerchia 4, Marcello Allegretti 1 and Andrea Rosario Beccari 1 1 Dompé Farmaceutici SpA, via Campo di Pile, 67100 L’Aquila, Italy; [email protected] (C.T.); [email protected] (L.B.); candida.manelfi@dompe.com (C.M.); [email protected] (M.A.); [email protected] (A.R.B.) 2 Axxam, Via Meucci 3, Bresso, 20091 Milano, Italy; [email protected] (L.Z.); [email protected] (S.B.); [email protected] (C.L.) 3 Ceinge Biotecnologie Avanzate, via G. Salvatore 486, 80145 Napoli, Italy; [email protected] 4 Department of Pharmacy, University of Naples “Federico II”, via D. Montesano, 49, 80131 Napoli, Italy; [email protected] (R.R.); [email protected] (C.C.) * Correspondence: [email protected]; Tel.: +34-06-465916 Received: 26 August 2020; Accepted: 12 October 2020; Published: 16 October 2020 Abstract: The kinin B1 receptor plays a critical role in the chronic phase of pain and inflammation. The development of B1 antagonists peaked in recent years but almost all promising molecules failed in clinical trials. Little is known about these molecules’ mechanisms of action and additional information will be necessary to exploit the potential of the B1 receptor. -
The Selective Serotonin2a Receptor Antagonist, MDL100,907, Elicits A
BRIEF REPORT The Selective Serotonin2A Receptor Antagonist, MDL100,907, Elicits a Specific Interoceptive Cue in Rats Anne Dekeyne, Ph.D., Loretta Iob, B.Sc., Patrick Hautefaye, Ph.D., and Mark J. Millan, Ph.D. Employing a two-lever, food-reinforced, Fixed Ratio 10 5-HT2B/2C antagonist, SB206,553 (0.16 and 2.5 mg/kg) and drug discrimination procedure, rats were trained to the selective 5-HT2C antagonists, SB242,084 (2.5 and recognize the highly-selective serotonin (5-HT)2A receptor 10.0 mg/kg,) and RS102221 (2.5 and 10.0 mg/kg), did not antagonist, MDL100,907 (0.16 mg/kg, i.p.). They attained significantly generalize. In conclusion, selective blockade of Ϯ Ϯ criterion after a mean S.E.M. of 70 11 sessions. 5-HT2A receptors by MDL100,907 elicits a discriminative MDL100,907 fully generalized with an Effective Dose stimulus in rats which appears to be specifically mediated (ED)50 of 0.005 mg/kg, s.c.. A further selective 5-HT2A via 5-HT2A as compared with 5-HT2B and 5-HT2C receptors. antagonist, SR46349, similarly generalized with an ED50 of [Neuropsychopharmacology 26:552–556, 2002] 0.04 mg/kg, s.c. In distinction, the selective 5-HT2B © 2002 American College of Neuropsychopharmacology antagonist, SB204,741 (0.63 and 10.0 mg/kg), the Published by Elsevier Science Inc. KEY WORDS: Drug discrimination; Interoceptive; 5-HT2A stimulus (DS) properties of several 5-HT2 agonists and receptors hallucinogens, such as mescaline (Appel and Callahan 1989), lysergic acid diethylamide (LSD) (Fiorella et al. Drug discrimination procedures have been extensively 1995) and quipazine (Friedman et al. -
Blocking the Tissue Renin-Angiotensin System: the Future Cornerstone of Therapy
Journal of Human Hypertension (2000) 14, Suppl 2, S23–S31 2000 Macmillan Publishers Ltd All rights reserved 0950-9240/00 $15.00 www.nature.com/jhh Blocking the tissue renin-angiotensin system: the future cornerstone of therapy T Unger1, M Azizi2 and GG Belz3 1Institute of Pharmacology, Christian Albrechts University, Hospitalstrae 4, 24105 Kiel, Germany; 2Centre D’Investigations Cliniques, Hoˆ pital Broussais, 96 Rue Didot – 75674, Paris Cedex 14, France; 3Zentrum fuer Kardiovaskulaere Pharmakologie, ZeKaPha GmbH, Mathildenstrae 8, D-55116, Mainz-Wiesbaden, Germany The development of angiotensin-converting enzyme antagonist, is characterised by its tight binding to and inhibitors and selective angiotensin type 1 (AT1)- slow dissociation from the AT1 receptor, and high antag- receptor antagonists has provided new insights into onistic potency, resulting in long-lasting antagonistic understanding the mechanism of the renin-angiotensin effects. It is anticipated that these pharmacological system (RAS) in the pathophysiology of cardiovascular characteristics may bring additional benefits to patients, disease. There is good evidence from meta-analyses not only for the management of essential hypertension that shows that inhibition of the RAS achieves organ but also for the management of end-organ damage. protection features that go beyond blood pressure con- Journal of Human Hypertension (2000) 14, Suppl 2, S23– trol. Candesartan cilexetil, a new angiotensin II receptor S31 Keywords: renin-angiotensin system; angiotensin-converting enzyme inhibitor; angiotensin type 1 receptor; angiotensin receptor antagonist; candesartan cilexetil Introduction Blocking the RAS in essential Hypertension is a major risk factor for myocardial hypertension infarction, stroke, and renal and peripheral vascular Angiotensin II, the key effector peptide of the RAS, disease. -
THE DOSE an Estimation of Equivalent Doses Between Arbs and Aceis
THE DOSE An estimation of equivalent doses between ARBs and ACEIs ARBs still currently available as of Jan 26, 2020: Twynsta (telmisartan/amlodipine): 40/5mg. 40/10mg, 80/5mg, 80mg/ 10mg Note: ~$0.73/tablet (ODB covered) Candesartan/Hydrochlorothiazide:16mg/12.5mg, 32mg/12.5mg, 32mg/25mg Irbesartan/Hydrochlorothiazide: 150/12.5mg, 300/12.5mg, 300/25mg Olmesartan/Hydrochlorothiaizde: 20/12.5mg, 40/12.5mg Valsartan/Hydrochlorothiazide: 80/12.5mg, 160/12.5mg, 160/25mg, 320/12.5mg, 320/25mg Note: Availability changes daily. Some pharmacies are able to get candesartan (4mg, 8mg, and 32mg) and irbesartan (300mg). Considerations Patients renal function and hepatic function should be taken into consideration Patients should have blood pressure, lytes and SCr checked with rotation from ARB to ACEI as clinically indicated in 1-4 weeks ACEIs can cause a dry cough in 5-35% of patients and carry a risk of angioedema (0.1-0.2%) Comparable dosages between ACEIs and ARBs- Summary of trials Lisinopril 20mg Enalapril 20mg Perindopril 4mg Ramipril 10mg Candesartan 16mg 8mg 16mg Irbesartan 150mg Telmisartan 80mg 40-80mg 40mg ~80mg Valsartan 160mg 80mg Note: There are variations for approximate equivalent dosages between ACEIs and ARBs in clinical trials. Approximate equivalent doses of ACEI for blood pressure lowering Drug Approximate Initial Daily Dose Usual Daily Maintenance Dose Maximum Daily Duration of Dose Dose Action Equivalence Between ACEIs Cilazapril 2.5mg 2.5-5mg 2.5-5mg dailya 10mg 12-24 hr Enalapril maleate 5mg 2.5-5mg 10-40mg daily (or divided bid)a 40mg 12-24 hr Fosinopril 10mg 10mg 10-40mg daily (or divided bid)a 40mg 24hr Lisinopril 10mg 2.5-10mg 10-40mg daily 80mg 24hr Perindopril 2mg 2-4mg 4-8mg daily 8mg 24hr Quinapril 10mg 5-10mg 10-20mg dailya 40mg 24hr Ramipril 2.5mg 1.25mg-2.5mg 2.5-10mg daily (or divided bid)a 20mg ~24hr a: Some patients may experience a diminished antihypertensive effect toward the end of a 24-hour dosing interval. -
COZAAR (Losartan Potassium) Tablets, for Oral Use
HIGHLIGHTS OF PRESCRIBING INFORMATION • Increase dose to 100 mg once daily if further blood pressure These highlights do not include all the information needed to use response is needed. (2.3) COZAAR safely and effectively. See full prescribing information for COZAAR. --------------------- DOSAGE FORMS AND STRENGTHS --------------------- Tablets: 25 mg; 50 mg; and 100 mg. (3) ® COZAAR (losartan potassium) tablets, for oral use ------------------------------- CONTRAINDICATIONS ------------------------------- Initial U.S. Approval: 1995 • Hypersensitivity to any component. (4) • Coadministration with aliskiren in patients with diabetes. (4) WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning. ----------------------- WARNINGS AND PRECAUTIONS ----------------------- • Hypotension: Correct volume or salt depletion prior to administration When pregnancy is detected, discontinue COZAAR as soon as of COZAAR. (5.2) possible. Drugs that act directly on the renin-angiotensin system • Monitor renal function and potassium in susceptible patients. (5.3, can cause injury and death to the developing fetus. (5.1) 5.4) --------------------------- RECENT MAJOR CHANGES --------------------------- ------------------------------ ADVERSE REACTIONS ------------------------------ Warnings and Precautions Hyperkalemia (5.4) 10/2018 Most common adverse reactions (incidence ≥2% and greater than placebo) are: dizziness, upper respiratory infection, nasal congestion, ----------------------------INDICATIONS AND USAGE ---------------------------- and back pain. (6.1) COZAAR is an angiotensin II receptor blocker (ARB) indicated for: • Treatment of hypertension, to lower blood pressure in adults and To report SUSPECTED ADVERSE REACTIONS, contact Merck children greater than 6 years old. Lowering blood pressure reduces Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., at 1-877- the risk of fatal and nonfatal cardiovascular events, primarily strokes 888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. -
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 -
COZAAR® (LOSARTAN POTASSIUM TABLETS) Page 1 of 28
COZAAR® (LOSARTAN POTASSIUM TABLETS) Page 1 of 28 COZAAR® (LOSARTAN POTASSIUM TABLETS) USE IN PREGNANCY When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, COZAAR® should be discontinued as soon as possible. See WARNINGS, Fetal/Neonatal Morbidity and Mortality. DESCRIPTION COZAAR (losartan potassium) is an angiotensin II receptor (type AT1) antagonist. Losartan potassium, a non- peptide molecule, is chemically described as 2-butyl-4-chloro-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]imidazole- 5-methanol monopotassium salt. Its empirical formula is C22H22ClKN6O, and its structural formula is: Losartan potassium is a white to off-white free-flowing crystalline powder with a molecular weight of 461.01. It is freely soluble in water, soluble in alcohols, and slightly soluble in common organic solvents, such as acetonitrile and methyl ethyl ketone. Oxidation of the 5-hydroxymethyl group on the imidazole ring results in the active metabolite of losartan. COZAAR is available as tablets for oral administration containing either 25 mg, 50 mg or 100 mg of losartan potassium and the following inactive ingredients: microcrystalline cellulose, lactose hydrous, pregelatinized starch, magnesium stearate, hydroxypropyl cellulose, hypromellose, and titanium dioxide. COZAAR 25 mg, 50 mg and 100 mg tablets contain potassium in the following amounts: 2.12 mg (0.054 mEq), 4.24 mg (0.108 mEq) and 8.48 mg (0.216 mEq), respectively. COZAAR 25 mg, COZAAR 50 mg, and COZAAR 100 mg may also contain carnauba wax.