DOCSLIB.ORG

Comparison of the Effects of Losartan Vs. Ramipril on Several Adipocytokines and Vascular Remodeling Biomarkers

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Comparison of the Effects of Losartan Vs. Ramipril on Several Adipocytokines and Vascular Remodeling Biomarkers Hypertension Research (2011) 34, 52–54 & 2011 The Japanese Society of Hypertension All rights reserved 0916-9636/11 $32.00 www.nature.com/hr COMMENTARY Comparison of the effects of losartan vs.ramipril on several adipocytokines and vascular remodeling biomarkers Junji Kobayashi, Tohru Noguchi, Atsushi Nohara and Hiroshi Mabuchi Hypertension Research (2011) 34, 52–54; doi:10.1038/hr.2010.209; published online 25 November 2010 ngiotensin II receptor antagonists, also resistin, visfatin, vaspin) and vascular remo- treatment mainly through visceral fat mass A known as angiotensin receptor blockers deling biomarkers (matrix metalloproteinase- reduction. In rats, visceral fat accumulation is (ARBs), AT1-receptor antagonists or sartans, 2 (MMP-2) and MMP-9), whereas ramipril suppressed by telmisartan treatment.7 Telmi- block the activation of angiotensin II AT1 had no effect on any of these parameters sartan also modulates adipocyte size and fat receptors. ARBs directly cause vasodilatation, (Figure 1), although those two drugs reduced accumulation, resulting in protection against reduce secretion of vasopressin, and reduce blood pressure to comparable levels. diet-induced visceral obesity. It is also the production and secretion of aldosterone. Several investigators have reported that likely that the increased expression of Angiotensin-converting enzyme (ACE) inhi- losartan treatment increased total serum mitochondrial energy expenditure genes in bitors block the conversion of angiotensin I to adiponectin and high-molecular-weight adi- skeletal muscle is the mechanism by which angiotensin II and inhibit the breakdown of ponectin in IFG/IGT3 or hypertensive telmisartan decreases visceral fat accumula- bradykinin, resulting in physiological benefits subjects.4 Telmisartan was also demonstrated tion, as previously shown in rat models. that confer cardioprotective and renoprotec- to increase serum adiponectin levels.1 In For the association between ramipril treat- tive properties. contrast, another study showed that 8 weeks ment and plasma adiponectin, on the other Both ARBs and ACE inhibitors are classes of telmisartan treatment had a neutral effect hand, previous findings are conflicting. ofdrugsfrequentlyusedforthetreatment on insulin resistance, as assessed by home- One study performed in a randomized, of hypertension in daily clinical practice. ostasis model assessment-insulin resistance in double-blind, placebo-controlled cross-over They have protective effects on the heart hypertensive subjects with metabolic syndrome. manner showed that 10 mg of ramipril, and kidney and also lower blood pressure as So what is the potential mechanism by 16 mg of candesartan or combination therapy well as improve insulin sensitivity. which these ARBs increased adiponectin increased plasma adiponectin levels when There are a number of studies on the levels? Is this directly related to AT1 receptor compared with baseline values.8 Another effects of either ARBs or ACE inhibitors on block? The most conceivable explanation for study has shown that 9-week treatment with metabolic parameters, cytokines or cardiovas- this is peroxisome proliferator-activated 10 mg of ramipril did not cause significant cular biomarkers.1 However, there are very receptor (PPAR) activation by these ARBs. changes in adiponectin levels in patients with few, if any, studies directly comparing the A subset of ARBs, including losartan, induce type 2 diabetes. effects of ARBs with those of ACE inhibitors the activity of PPAR by partial agonism.5 Derosa et al.2 also investigated the effects of on metabolic parameters. Of note, this activation was independent of losartan vs. ramipril treatment on several In the current issue of Hypertension AT1R expression and therefore not related to other metabolic parameters and vascular Research, Derosa et al.2 describe a study in AT1R-blocking properties.5 PPAR functions remodeling biomarkers. To the best of our which they recruited 228 Caucasian hyper- as a transcriptional regulator in adipose knowledge, there appears to be no previous tensive subjects (115 males and 113 females) tissue, where it regulates multiple genes report on the association of losartan and/or in a double-blind clinical trial. The authors involved in lipid and glucose metabolism. In ramipril treatment with changes in RBP-4, found that 14 months of treatment with the case of telmisartan, our group and others6 visfatin or vaspin. Also, there are very few losartan improved a wide range of metabolic have shown that telmisartan treatment pro- reports, if any, on the effect of treatment with parameters (M value and levels of adiponec- duced significant reductions in visceral fat these compounds on serum resistin levels. tin, retinol-binding protein-4 (RBP-4), areas but not in subcutaneous areas evaluated A small crossover study by a Norwegian by computed tomography in Japanese sub- group composed of 23 hypertensive patients Professor J Kobayashi, T Noguchi, A Nohara and jects with metabolic syndrome. As plasma showed that there was no significant differ- H Mabuchi are at the Department of Lipidology, adiponectin level is inversely associated with ence in blood levels of resistin (11.7±1.0 vs. Kanazawa University Graduate School of Medical ± À1 Science, Kanazawa, Japan. visceral fat accumulation, we presumed 11.3 0.7 ng ml ) between treatment with E-mail: [email protected] that adiponectin increased after telmisartan amlodipine 10 mg and that with losartan Commentary 53 Adiponectin ↑ compared the effects of valsartan (4909 Visfatin↑ patients), valsartan plus captopril (4885 adipocytes Vaspin → Insulin patients) and captopril (4909 patients) on sensitivity↑ Resistin ↓ death from any cause in subjects with acute myocardial infarction who had already RBP-4 ↓ Losartan undergone conventional therapy. The authors concluded that valsartan is as effective as captopril in patients who are at high risk MMP-2 ↓ Plaque macrophages stabilization↑ for cardiovascular events after myocardial MMP-9 ↓ infarction. Thus, none of these three large- scale RCTs concluded that ARBs are superior to ACE inhibitors with respect to long-term Figure 1 Proposed effects of losartan therapy on adipocytokine and metalloproteinase production, mortality, incidence of cardiovascular disease as clarified in the study by Derosa et al.2 or new onset of diabetes. Are the observed favorable effects in the 100 mg+amlodipine 5 mg, respectively. As study was performed with a b1 receptor current study pharmacological class effects or RBP-4, visfatin, vaspin and resistin are closely antagonist rather than a placebo as control. specific to the drugs studied? As mentioned related to insulin resistance, the altered levels HOPE and DREAM are placebo-controlled earlier, certain ARBs may utilize mechanisms of these molecules along with adiponectin in RCTs for investigating the long-term out- involved in PPAR activation that are inde- the losartan group compared with the rami- comes of ramipril use, with the former utiliz- pendent of AT1 R-blocking properties. pril group in the current study suggest that ing cardiovascular events as end points and Indeed, Derosa et al.10 reported very recently losartan may have considerable advantages with the latter utilizing new-onset diabetes or a study comparing the effects of 1-year over ramipril in the prevention of athero- death as end points. The use of ramipril vs. treatment with 8 mg dayÀ1 candesartan or sclerotic disease or diabetes. The present placebo is associated with a 22% reduction in 10 mg dÀ1 olmesartan on various metabolic finding that losartan but not ramipril caused cardiovascular events without significant parameters related to insulin resistance. They a reduction in both MMP-2 and MMP-9 after reduction in new-onset diabetes. report that candesartan but not olmesartan 14 months (Po0.05) also suggests that losar- So what about head-to-head RCT compar- caused favorable changes in M-value, adipo- tan more effectively prevents the destabiliza- ing ARBs vs. ACE inhibitors? nectin, visfatin, RBP-4 and C-reactive tion of plaques, as expected, as MMPs are key There are several RCTs comparing ARBs protein, although comparable reductions enzymes involved in degrading the extracel- vs. ACE inhibitors in terms of mortality, were observed in blood pressure. These lular matrix. However, a previous report9 morbidity or cardiovascular events as end results suggest that the observed changes in showed that 10 mg once daily during points, but not the use of losartan vs. ramipril metabolic parameters may be due to com- 24 weeks of ramipril treatment reduced specifically. In the ONgoing Telmisartan pound-specific effects rather than class gene and protein expression of both MMP-2 Alone and in Combination with Ramipril effects. In the future, to compare head-to- and MMP-9. Global Endpoint Trial (ONTARGET), 25 620 head long-term outcomes, studies should To what degree does losartan or ramipril subjects from 730 centers in 40 countries were consider specific ARBs or ACE inhibitors prevent the incidence of cardiovascular dis- high-risk patients with coronary, peripheral, rather than broadly compare ARBs vs. ACE ease or the onset of diabetes? The Losartan or cerebrovascular disease or diabetes with inhibitors. Intervention for Endpoint Reduction (LIFE), end-organ damage. Patients were randomized the Heart Outcomes Prevention Evaluation to groups treated with 80 mg of telmisartan, (HOPE) and the Diabetes REduction Assess- 10 mg of ramipril or both drugs and followed ment with ramipril and rosiglitazone
Load more

Recommended publications
  • Effects of Lacidipine, Ramipril and Valsartan on Serum BNP Levels in Acute and Chronic Periods Following Isoproterenol-Induced Myocardial Infarction in Rats
    Original Article Effects of Lacidipine, Ramipril and Valsartan on Serum BNP Levels in Acute and Chronic Periods Following Isoproterenol-Induced Myocardial Infarction in Rats Lasidipin, Ramipril ve Valsartanın Sıçanlarda Isoprotrenol ile Uyarılan Miyokard Infarktüsü Sonrası Akut ve Kronik Periyotta Serum BNP Seviyeleri Üzerine Etkileri Yasin Bayir1, Elif Cadirci2, Halis Suleyman2, Zekai Halici2, Mevlut Sait Keles3 1Ataturk University, Faculty of Pharmacy, Department of Biochemistry, Erzurum, Turkey 2Ataturk University, Faculty of Medicine, Department of Pharmacology, Erzurum, Turkey 3Ataturk University, Faculty of Medicine, Department of Biochemistry, Erzurum, Turkey Correspondence to: Elif Cadirci, Ph.D., Atatürk University, Faculty of Medicine, Department of Pharmacology, 25240, Erzurum, Turkey. Phone: +90.442.2316563, Fax: +90.442.2360968, e-mail: [email protected] Abstract Özet Objective. Myocardial infarction (MI) as a result of cardiovas- Amaç. Miyokard infarktüsü (Mİ) hem gelişmiş hem de cular disease is the principal cause of death in both developed gelişmekte olan ülkelerde kardiyovasküler hastalıklar sonucu and developing countries. Brain natriuretic peptide (BNP) is an oluşan ölümün esas sebebidir. Brain natriuretic peptide (BNP) important marker of cardiac failure. Cardioprotective activities kardiyak hasarın önemli bir göstergesidir. Antihipertansif il- of the antihypertensive drugs lacidipine (LAC), ramipril (RAM) açlar olan lasidipin (LAC), ramipril (RAM) ve valsartanın, izo- and valsartan (VAL), against isoproterenol
    [Show full text]
  • Summary of Product Characteristics 1. Name Of
    SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT Ramipril/Amlodipine Glenmark, 5 mg/5 mg, hard capsules Ramipril/Amlodipine Glenmark, 5 mg/10 mg, hard capsules Ramipril/Amlodipine Glenmark, 10 mg/5 mg, hard capsules Ramipril/Amlodipine Glenmark, 10 mg/10 mg, hard capsules 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Ramipril/Amlodipine Glenmark, 5 mg/5 mg, hard capsules: each capsule contains 5 mg ramipril and amlodipine besilate equivalent to 5 mg amlodipine. Ramipril/Amlodipine Glenmark, 5 mg/10 mg, hard capsules: each capsule contains 5 mg ramipril and amlodipine besilate equivalent to 10 mg amlodipine and . Ramipril/Amlodipine Glenmark, 10 mg/5 mg, hard capsules: each capsule contains 10 mg ramipril and amlodipine besilate equivalent to5 mg amlodipine. Ramipril/Amlodipine Glenmark, 10 mg/10 mg, hard capsules: each capsule contains 10 mg ramipril and amlodipine besilate equivalent to 10 mg amlodipine . For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Hard capsule Ramipril/Amlodipine Glenmark, 5 mg/5 mg, hard capsules: hard gelatin capsules with a length of 19 mm, cap: opaque pink colour, body: opaque white colour. Content of capsules: white or almost white powder. Ramipril/Amlodipine Glenmark, 5 mg/10 mg, hard capsules: hard gelatin capsules with a length of 19 mm, cap: opaque red - brown colour, body: opaque white colour. Content of capsules: white or almost white powder. Ramipril/Amlodipine Glenmark, 10 mg/5 mg, hard capsules: hard gelatin capsules with a length of 19 mm, cap: opaque dark pink colour, body: opaque white colour. Content of capsules: white or almost white powder.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • Angiotensin-Converting Enzyme (ACE) Inhibitors
    Angiotensin-Converting Enzyme (ACE) Inhibitors Summary Blood pressure reduction is similar for the ACE inhibitors class, with no clinically meaningful differences between agents. Side effects are infrequent with ACE inhibitors, and are usually mild in severity; the most commonly occurring include cough and hypotension. Captopril and lisinopril do not require hepatic conversion to active metabolites and may be preferred in patients with severe hepatic impairment. Captopril differs from other oral ACE inhibitors in its rapid onset and shorter duration of action, which requires it to be given 2-3 times per day; enalaprilat, an injectable ACE inhibitor also has a rapid onset and shorter duration of action. Pharmacology Angiotensin Converting Enzyme Inhibitors (ACE inhibitors) block the conversion of angiotensin I to angiotensin II through competitive inhibition of the angiotensin converting enzyme. Angiotensin is formed via the renin-angiotensin-aldosterone system (RAAS), an enzymatic cascade that leads to the proteolytic cleavage of angiotensin I by ACEs to angiotensin II. RAAS impacts cardiovascular, renal and adrenal functions via the regulation of systemic blood pressure and electrolyte and fluid balance. Reduction in plasma levels of angiotensin II, a potent vasoconstrictor and negative feedback mediator for renin activity, by ACE inhibitors leads to increased plasma renin activity and decreased blood pressure, vasopressin secretion, sympathetic activation and cell growth. Decreases in plasma angiotensin II levels also results in a reduction in aldosterone secretion, with a subsequent decrease in sodium and water retention.[51035][51036][50907][51037][24005] ACE is found in both the plasma and tissue, but the concentration appears to be greater in tissue (primarily vascular endothelial cells, but also present in other organs including the heart).
    [Show full text]
  • Hyponatremia Induced by Angiotensin Converting Enzyme Inhibitors and Angiotensin
    DOI: 10.7860/JCDR/2018/31983.11754 Original Article Hyponatremia Induced by Angiotensin Converting Enzyme Inhibitors and Angiotensin Pharmacology Section Receptor Blockers-A Pilot Study S BHUVANESHWARI1, PRAKASH VEL SANKHYA SAROJ2, D VIJAYA3, M SABARI SOWMYA4, R SENTHIL KUMAR5 ABSTRACT Results: Among all, 48% (24 out of 50) of the study population Introduction: Hyponatremia, serum sodium <135 mmol/L, can administered with ACEI and ARB developed hyponatremia. result in neurological manifestation in acute cases, may lead Predisposition to develop hyponatremia was high in males to seizures and coma. Angiotensin Converting Enzyme Inhibitor compared to females. Incidence of hyponatremia was 62.5% (10 (ACEI) and Angiotensin II Receptor Blockers (ARB) are drugs out of 16) in the age group of 56-75 years. Though, incidence of that have been commonly prescribed for the treatment of hyponatremia was 54.5% (18 out of 33) in ACEI group compared hypertension and cardiac diseases. It has become important to 35.2% (6 out of 17) in ARB group, but it was not statistically to evaluate and investigate the incidence of hyponatremia on significant. The study also revealed that metosartan had a higher consumption of these drugs. association with hyponatremia compared to other drugs. Aim: To determine the susceptibility of patients on ACEI and Conclusion: Hyponatremia was induced in nearly 50% of ARB to hyponatremia and to ascertain the drug producing patients taking ACEI and ARB. The incidence of hyponatremia notable hyponatremia among ACEI and ARB. among patients on these two drugs did not show statistical variation. Metosartan showed a higher incidence of Materials and Methods: The study was conducted in a tertiary hyponatremia compared to enalapril, ramipril, captopril, care hospital.
    [Show full text]
  • Telmisartan Vs Losartan Plus Hydrochlorothiazide in the Treatment of Mild-To-Moderate Essential Hypertensionfa Randomised ABPM Study
    Journal of Human Hypertension (2003) 17, 569–575 & 2003 Nature Publishing Group All rights reserved 0950-9240/03 $25.00 www.nature.com/jhh ORIGINAL ARTICLE Telmisartan vs losartan plus hydrochlorothiazide in the treatment of mild-to-moderate essential hypertensionFa randomised ABPM study JM Neutel1 , RE Kolloch2, PF Plouin3, TW Meinicke4 and H Schumacher5 for the OTELLOH Study Group 1Orange County Heart Institute & Research Center, Orange, CA, USA; 2Krankenanstalten Gilead, Bielefeld, Germany; 3Hoˆpital Broussais, Paris, France; 4Clinical Research Boehringer Ingelheim Pharma KG, Biberach, Germany; 5Medical Data Services Boehringer Ingelheim Pharma KG, Ingelheim, Germany The objective of this prospective, randomised, open- null hypothesis of a treatment difference of 43 mmHg. label, blinded-end point parallel-group, multicentre The reduction in mean 24-h systolic blood pressure was study was to show that telmisartan 80 mg is not inferior 13.2 7 10.2 mmHg with telmisartan and 17.1 7 10.3 to a fixed-dose combination of losartan 50 mg/hydro- mmHg with losartan/HCTZ. Both drugs provided effec- chlorothiazide (HCTZ) 12.5 mg in patients with mild-to- tive control over the 24-h dosing interval. Analyses of moderate hypertension. The criterion for noninferiority morning (0600–1159) ambulatory blood pressure mon- was a treatment difference of p3.0 mmHg in the reduc- itoring DBP means and trough cuff DBP confirmed the tion of 24-h mean ambulatory diastolic blood pressure noninferiority hypothesis of the protocol for telmisartan (DBP) from the end of the 4-week placebo washout 80 mg vs losartan 50 mg/HCTZ 12.5 mg. The reductions period to the end of the 6-week active treatment period.
    [Show full text]
  • Switching Ace-Inhibitors
    Switching Ace-inhibitors http://www.ksdl.kamsc.org.au/dtp/switching_ace_inhibitors.html Change to → Enalapril Quinapril Ramipril Change from ↓ (Once daily dosing) (Once daily dosing) (Once daily dosing) Captopril Captopril 12.5mg daily Enalapril 2.5mg1 Quinapril 2.5mg Ramipril 1.25mg Captopril 25mg daily Enalapril 5mg1 Quinapril 5mg Ramipril 1.25-2.5mg Captopril 50mg daily Enalapril 7.5mg1 Quinapril 10mg Ramipril 2.5-5mg Captopril 100mg daily Enalapril 20mg1 Quinapril 20mg Ramipril 5-10mg2 Captopril 150mg daily Enalapril 40mg Quinapril 40mg Ramipril 10mg Fosinopril Fosinopril 5mg daily Enalapril 5mg Quinapril 5mg Ramipril 1.25mg Fosinopril 10mg daily Enalapril 10mg Quinapril 10mg Ramipril 2.5mg Fosinopril 20mg daily Enalapril 20mg Quinapril 20mg Ramipril 5mg Fosinopril 40mg daily Enalapril 40mg Quinapril 40mg Ramipril 10mg Lisinopril Lisinopril 5mg daily Enalapril 5mg Quinapril 5mg Ramipril 1.25mg Lisinopril 10mg daily Enalapril 10mg Quinapril 10mg Ramipril 2.5mg Lisinopril 20mg daily Enalapril 20mg Quinapril 20mg Ramipril 5mg Lisinopril 40mg Enalapril 40mg Quinapril 40mg Ramipril 10mg Perindopril Perindopril 2mg daily Enalapril 5-10mg Quinapril 5-10mg Ramipril 2.5mg Perindopril 4mg daily Enalapril 10mg-20mg Quinapril 10mg-20mg Ramipril 5mg Perindopril 8mg daily Enalapril 20-40mg Quinapril 20-40mg Ramipril 10mg Trandolapril Trandolapril 0.5mg d Enalapril 5mg Quinapril 5mg Ramipril 1.25mg Trandolapril 1mg daily Enalapril 10mg Quinapril 10mg Ramipril 2.5mg Trandolapril 2mg daily Enalapril 20mg Quinapril 20mg Ramipril 5mg Trandolapril 4mg daily Enalapril 40mg Quinapril 40mg Ramipril 10mg There are few studies comparing equivalent doses of ACE-inhibitors, for specific indications. Therefore, the above recommendations are based on clinical experiences and are not specific for any indication.
    [Show full text]
  • Hypertension Protocol
    Hypertension Guidelines Overview Aim to reduce Blood Pressure to 140/90 or less (140/80 for diabetics), adding drugs as needed until further treatment is inappropriate or declined. N.B. patients do not need to be swapped immediately onto this pathway if stable on previous pathways Younger than 55 55 years or older or years African/Caribbean descent of any age Ramipril 2.5-10mg OD Amlodipine 5-10mg OD (Candesartan 8-32mg OD or (Lacidipine 2-6mg or Lercanidipine 10-20 mg if ankle swelling) Losartan 50-100mg if ACE not tolerated) Add Add Amlodipine 5-10mg OD Ramipril 2.5-10mg OD (or (or alternative as above) alternative as above) Add Indapamide 2.5mg OD Add Fourth Line Agent (Resistant Hypertension) i. Spironolactone 25mg OD (if potassium <4.5mmol/l) (unlicensed) ii. Bisoprolol 1.25 to 10mg OD iii. Doxazosin 1-16mg daily Consider an ACE Inhibitor first-line for patients with Diabetes or Impaired Glucose Intolerance. NB; Lisinopril could be used instead of Ramipril if practices prefer Review Date: January 2014 1 Review Date: January 2014 2 General Principles 1. Clinic BP >140/90 leads to Ambulatory Blood Pressure Monitoring (ABPM) 2. ABPM uses average of at least 14 readings taken during waking hours 3. Offer antihypertensive drug to all under 80 with Stage 1 hypertension with: o Target organ damage (high albumin:creatinine ratio, haematuria, raised creatinine, low eGFR, hypertensive retinopathy, LVH) o Established cardiovascular disease o Renal disease o Diabetes o 10 year Cardiovascular risk >20% 4. Offer antihypertensive drug to all with stage 2 hypertension 5.
    [Show full text]
  • AT1-Receptor Blockers: Differences That Matter
    Journal of Human Hypertension (2002) 16, S9–S16 2002 Nature Publishing Group All rights reserved 0950-9240/02 $25.00 www.nature.com/jhh AT1-receptor blockers: differences that matter AH Gradman Division of Cardiovascular Diseases, The Western Pennsylvania Hospital, Pittsburgh, Pennsylvania, USA The available angiotensin II type 1 (AT1)-receptor block- effect, and this finding is supported by the results of ers differ markedly in their pharmacological properties comparative clinical trials. Moreover, the prolonged and clinical efficacy. Losartan shifts the dose-response binding of candesartan to the receptor is reflected in a curve for angiotensin II to the right without affecting the longer duration of action, compared with losartan; the maximal response; this antagonism can be overcome by antihypertensive effect of candesartan persists for 48 h increasing concentrations of angiotensin II and thus los- after dosing, compared with approximately 24 h with artan acts as a surmountable antagonist. By contrast, losartan. Candesartan thus offers extended therapeutic other agents suppress the maximal response to angio- coverage, an important consideration since a majority tensin II to varying extents; this can not be overcome by of patients miss occasional doses of antihypertensive increasing angiotensin concentrations and hence these medication. There is currently no evidence that differ- agents are insurmountable antagonists. Receptor bind- ences in receptor binding between AT1-receptor block- ing studies have shown that candesartan has the high- ers translate into differences in tolerability. In summary, est affinity for the AT1-receptor, followed by irbesartan, therefore, pharmacological differences between AT1- valsartan and losartan, and that candesartan dis- receptor blockers are reflected in clinically important sociates from the receptor more slowly than other differences in maximal antihypertensive effect, antagonists.
    [Show full text]
  • Therapeutic Class Overview Angiotensin II Receptor Blockers (Arbs) – Combination Products
    Therapeutic Class Overview Angiotensin II receptor blockers (ARBs) – combination products Therapeutic Class • Overview/Summary: This review will focus on the angiotensin II receptor blocker (ARB) combination products.1-13 The renin-angiotensin-aldosterone system (RAAS) is the most important component in the homeostatic regulation of blood pressure.14,15 Excessive activity of the RAAS may lead to hypertension and disorders of fluid and electrolyte imbalance.16 Renin catalyzes the conversion of angiotensinogen to angiotensin I. Angiotensin I is then cleaved to angiotensin II by angiotensin converting enzyme (ACE). Angiotensin II can increase blood pressure by direct vasoconstriction and through actions on the brain and autonomic nervous system.14,16 In addition, angiotensin II stimulates aldosterone synthesis from the adrenal cortex, leading to sodium and water reabsorption. Angiotensin II exerts other detrimental cardiovascular effects including hypertrophy and remodeling.14,15 The RAAS plays an important role in the development and progression of heart failure.15 ACE inhibitors block the conversion of angiotensin I to angiotensin II, and also inhibit the breakdown of bradykinin, a potent vasodilator associated with dry cough.14-17 Since angiotensin II may also be generated through other pathways that do not depend upon ACE (e.g., chymase), blockade of angiotensin II by ACE inhibitors is incomplete.14,15 The ARBs block the angiotensin II receptor subtype AT1, preventing the negative effects of angiotensin II, regardless of its origin. ARBs do not appear to affect bradykinin. Amlodipine, a nondihydropyridine calcium channel blocker, inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Cardiac and vascular smooth muscle contraction depends on the movement of extracellular calcium ions into cells through specific ion channels.
    [Show full text]