-
Journal of Feline Medicine and Surgery Jul 2023The aim of the present study was to report the concurrent disorders and treatment success of cats with diabetes mellitus (DM) and arterial systolic hypertension (SH).
OBJECTIVES
The aim of the present study was to report the concurrent disorders and treatment success of cats with diabetes mellitus (DM) and arterial systolic hypertension (SH).
METHODS
A retrospective longitudinal study was conducted of 17 cats with DM and SH that were examined at a university teaching hospital between 1 January 2011 and 31 December 2021. The medical records of diabetic cats were searched for the keywords 'hypertension', 'blood pressure', 'amlodipine', 'benazepril' and 'telmisartan' to identify cats with SH, which was defined as systemic arterial blood pressure (SABP) ⩾160 mmHg, documented at least twice, over several days. Comorbidities, including chronic kidney disease and hyperthyroidism, were recorded. Medications used for the treatment of SH and the SABP response to treatment were also noted.
RESULTS
Most cats (13/17, 76%) with DM and SH had at least one other documented concurrent illness that could contribute to SH, including chronic kidney disease (12/17 cats, 71%), hyperthyroidism (4/17, 23%) and functional adrenocortical mass secreting either aldosterone alone (1/17, 6%) or glucocorticoids, and possibly also aldosterone (1/17, 6%). Out of 17 cats, 15 (88%) were treated with amlodipine, and none were treated with an angiotensin converting enzyme inhibitor or an angiotensin II receptor blocker. Mean SABP at the time of diagnosis of SH was 210 ± 23 mmHg and was significantly higher than the mean SABP at the first and second follow-up examinations after the introduction of amlodipine treatment (175 ± 33 mmHg, = 0.008 and 172 ± 26 mmHg, = 0.01, respectively).
CONCLUSIONS AND RELEVANCE
Cats with DM and SH should be evaluated for the presence of chronic kidney disease, hyperthyroidism and functional adrenal masses. Treatment with amlodipine appears to be effective in lowering SABP in cats with DM and SH.
Topics: Cats; Animals; Antihypertensive Agents; Aldosterone; Longitudinal Studies; Retrospective Studies; Isolated Systolic Hypertension; Hypertension; Amlodipine; Diabetes Mellitus; Renal Insufficiency, Chronic; Cat Diseases
PubMed: 37470682
DOI: 10.1177/1098612X231187691 -
Basic & Clinical Pharmacology &... Oct 2019The combination of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB) for the treatment of hypertension showed improved efficacy and safety.... (Clinical Trial)
Clinical Trial
The combination of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB) for the treatment of hypertension showed improved efficacy and safety. Amlodipine is mainly metabolized by cytochrome P450 (CYP) 3A4, whereas losartan is metabolized by CYP2C9 and CYP3A4. The potential pharmacokinetic interactions between amlodipine and losartan were assessed. An open-label, three-period, fixed-sequence trial was conducted. Amlodipine, losartan and combined amlodipine and losartan were administered to 24 healthy male participants during periods 1, 2 and 3, respectively, for 9 days each. The pharmacokinetics of amlodipine, losartan and EXP-3174, an active metabolite of losartan, were assessed at steady-state. Twenty participants completed the study without serious adverse events. Losartan did not influence the exposure of amlodipine at steady-state (AUC , 165.15 ng h/mL [amlodipine alone] vs 172.36 ng h/mL [combination], P = 0.389) [geometric mean ratio (GMR) (90% confidence interval [CI]), 1.060 (0.954-1.178)]. In addition, the exposure of EXP-3174 was not affected by amlodipine (AUC , 1159.46 ng h/mL vs 1105.10 ng h/mL, P = 0.295) (GMR [90% CI], 0.957 [0.891-1.027]). However, amlodipine significantly decreased the exposure of losartan at steady-state (AUC , 1241.50 ng h/mL vs 1082.02 ng h/mL, P = 0.006) (GMR [90% CI], 0.875 [0.813-0.942]) and increased oral clearance of losartan (84.65 L/h vs 97.26 L/h, P = 0.002). Combination use of two drugs caused additive haemodynamic changes compared to treatment of amlodipine or losartan alone. The co-administration of amlodipine and losartan was tolerable and did not cause substantial pharmacokinetic interaction, even though losartan disposition was affected. Combination use of the two drugs caused additive haemodynamic changes compared to monotherapy of amlodipine or losartan.
Topics: Administration, Oral; Adult; Amlodipine; Angiotensin Receptor Antagonists; Antihypertensive Agents; Calcium Channel Blockers; Drug Interactions; Drug Therapy, Combination; Healthy Volunteers; Hemodynamics; Humans; Hypertension; Losartan; Male; Middle Aged; Republic of Korea; Young Adult
PubMed: 31058419
DOI: 10.1111/bcpt.13244 -
Australian Journal of General Practice Dec 2019
Topics: Abdominal Pain; Adrenocorticotropic Hormone; Aldosterone; Amlodipine; Antihypertensive Agents; Catecholamines; Child; Deprescriptions; Diarrhea; Dietary Approaches To Stop Hypertension; Exercise; Headache; Humans; Hydrocortisone; Hypertension; Male; Renal Artery; Renin; Ultrasonography, Doppler; Vomiting
PubMed: 31774990
DOI: 10.31128/AJGP-08-19-5031 -
Advances in Therapy Nov 2023Patients with hypertension and additional cardiovascular risk factors pose a challenge by requiring more intensive blood pressure (BP) control. Single-pill combination... (Observational Study)
Observational Study
Real-World Effectiveness and Safety of a Single-Pill Combination of Olmesartan/Amlodipine/Hydrochlorothiazide in Korean Patients with Hypertension and Cardiovascular Risk Factors.
INTRODUCTION
Patients with hypertension and additional cardiovascular risk factors pose a challenge by requiring more intensive blood pressure (BP) control. Single-pill combination (SPC) therapy can benefit these patients by improving medication adherence.
METHODS
This prospective, multicenter observational study assessed the real-world safety and effectiveness of an SPC containing olmesartan, amlodipine, and hydrochlorothiazide (O/A/H) in South Korean patients with hypertension and cardiovascular risk factors. BP control rates, defined as the percentage of patients achieving systolic BP (SBP) < 130 mmHg and diastolic BP (DBP) < 80 mmHg for intensive BP control, and < 140 mmHg and < 90 mmHg, respectively, for standard BP control, were investigated across various cardiovascular risk groups, along with changes in SBP and DBP from baseline to week 24.
RESULTS
The most prevalent cardiovascular risk factor was age (≥ 45 years in men, ≥ 55 years in women, 86.1%), followed by cardiovascular diseases (64.4%), dyslipidemia (53.7%), body mass index ≥ 25 kg/m (53.5%), and diabetes mellitus (DM) (46.3%). Switching to O/A/H showed significant BP reduction, with a mean change of - 17.8 mmHg/- 9.3 mmHg in SBP/DBP within 4 weeks. The intensive BP control rate was 41.4% (95% confidence interval [CI] 39.5, 43.4), and the standard BP control rate was 73.3% (95% CI 71.5, 75.1), with better control rates in the risk age group (43.1% and 74.1%, respectively) and cardiovascular disease group (42.0% and 73.8%, respectively). The DM group had relatively lower control rates (37.5% for intensive control and 69.4% for standard control). Common adverse drug reactions included dizziness (2.91%), hypotension (1.51%), and headaches (0.70%).
CONCLUSION
The SPC therapy of O/A/H caused a rapid and sustained reduction in SBP/DBP in patients' hypertension and additional cardiovascular risk factors. The therapy was safe and well tolerated.
STUDY REGISTRATION NUMBER
KCT0003401 ( https://cris.nih.go.kr/cris/search/detailSearch.do/20795 ).
Topics: Male; Humans; Female; Middle Aged; Amlodipine; Hydrochlorothiazide; Cardiovascular Diseases; Antihypertensive Agents; Olmesartan Medoxomil; Prospective Studies; Risk Factors; Hypertension; Tetrazoles; Blood Pressure; Heart Disease Risk Factors; Republic of Korea; Drug Combinations
PubMed: 37651078
DOI: 10.1007/s12325-023-02632-9 -
BMC Pharmacology & Toxicology Dec 2023Previously, observational studies showed that amlodipine can mitigate calcineurin inhibitor- and contrast-induced acute kidney injury (AKI). Herein, we aimed to measure...
BACKGROUND
Previously, observational studies showed that amlodipine can mitigate calcineurin inhibitor- and contrast-induced acute kidney injury (AKI). Herein, we aimed to measure the effect of amlodipine on renal ischemia/reperfusion (I/R) injury and find the underlying mechanisms.
MATERIALS AND METHODS
Bilateral renal I/R was induced by clamping the hilum of both kidneys for 30 min. The first dose of amlodipine 10 mg/kg was gavaged before anesthesia. The second dose of amlodipine was administered 24 h after the first dose. Forty-eight hours after I/R, rats were anesthetized, and their blood and tissue specimens were collected.
RESULTS
Amlodipine significantly decreased the elevated serum levels of creatinine and blood urea nitrogen (BUN) and mitigated tissue damage in hematoxylin & eosin (H&E) staining. Amlodipine strongly reduced the tissue levels of malondialdehyde (MDA), interleukin 1β (IL1β), and tumor necrosis factor α (TNF-α). Amlodipine enhanced antioxidant defense by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2) and Sestrin2. Furthermore, amlodipine significantly improved mitochondrial biogenesis by promoting Sestrin2/peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α)/mitochondrial transcription factor A (TFAM) pathway. It also enhanced autophagy and attenuated apoptosis, evidenced by increased LC3-II/LC3-I and bcl2/bax ratios after renal I/R.
CONCLUSION
These findings suggest that amlodipine protects against renal I/R through Nrf2/Sestrin2/PGC-1α/TFAM Pathway.
Topics: Rats; Animals; NF-E2-Related Factor 2; Kidney; Reperfusion Injury; Ischemia; Apoptosis
PubMed: 38129888
DOI: 10.1186/s40360-023-00722-6 -
Journal of Clinical Hypertension... Sep 2023The authors performed this study to investigate the efficacy and safety of a rosuvastatin (RSV)/amlodipine (AML) polypill compared with those of atorvastatin (ATV)/AML... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized, multicenter, parallel, open, phase 4 study to compare the efficacy and safety of rosuvastatin/amlodipine polypill versus atorvastatin/amlodipine polypill in hypertension patient with dyslipidemia.
The authors performed this study to investigate the efficacy and safety of a rosuvastatin (RSV)/amlodipine (AML) polypill compared with those of atorvastatin (ATV)/AML polypill. We included 259 patients from 21 institutions in Korea. Patients were randomly assigned to 1 of 3 treatment groups: RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, or ATV 20 mg /AML 5 mg. The primary endpoint was the efficacy of the RSV 10.20 mg/AML 5 mg via percentage changes in LDL-C after 8 weeks of treatment, compared with the ATV 20 mg /AML 5 mg. There was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 10 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (full analysis set [FAS]: -7.08%, 95% CI: -11.79 to -2.38, p = .0034, per-protocol analysis set [PPS]: -6.97%, 95% CI: -11.76 to -2.19, p = .0046). Also, there was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 20 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (FAS: -10.13%, 95% CI: -15.41 to -4.84, p = .0002, PPS: -10.96%, 95% CI: -15.98 to -5.93, p < .0001). There was no significant difference in the adverse events rates between RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, and ATV 20 mg/AML 5 mg. In conclusion, while maintaining safety, RSV 10 mg/AML 5 mg and the RSV 20 mg/AML 5 mg more effectively reduced LDL-C compared with the ATV 20 mg /AML 5 mg (Clinical trial: NCT03951207).
Topics: Humans; Rosuvastatin Calcium; Atorvastatin; Amlodipine; Hypertension; Cholesterol, LDL; Dyslipidemias; Leukemia, Myeloid, Acute; Double-Blind Method; Treatment Outcome
PubMed: 37584254
DOI: 10.1111/jch.14715 -
Nutrients Aug 2021Curcumin, a curcuminoid known as the main bioactive compound of turmeric, is used in foods, cosmetics, and pharmaceutical products. Amlodipine is a general...
Curcumin, a curcuminoid known as the main bioactive compound of turmeric, is used in foods, cosmetics, and pharmaceutical products. Amlodipine is a general antihypertensive drug used in combination with various other antihypertensive agents. To date, no studies have examined the effects of the co-administration of amlodipine with curcumin. In this study, the vasodilatory effects of curcumin, amlodipine, and the co-administration of curcumin with amlodipine on isolated rat aortic rings pre-contracted with phenylephrine were evaluated, and the hypotensive effects were evaluated using the tail cuff method. To measure blood pressure, male spontaneously hypertensive rats were divided into four groups, each containing six rats, as follows: amlodipine 1 mg/kg alone treated, amlodipine 1 mg/kg with curcumin 30 mg/kg treated, amlodipine 1 mg/kg with curcumin 100 mg/kg treated, and amlodipine 1 mg/kg with curcumin 300 mg/kg treated groups. Amlodipine and curcumin were intraperitoneally injected, and systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at 1, 2, 4, and 8 h after administration. The combined administration of curcumin and amlodipine induced a stronger vasorelaxant effect than amlodipine alone. However, co-administration did not significantly lower SBP and DBP compared to the single administration of amlodipine. The results of this study suggest that hypertensive patients taking amlodipine can consume curcumin or turmeric for food or other medical purposes without inhibiting the blood pressure-lowering effect of amlodipine.
Topics: Amlodipine; Animals; Antihypertensive Agents; Blood Pressure; Curcumin; Drug Therapy, Combination; Hypertension; Male; Rats; Rats, Inbred SHR; Vasodilator Agents
PubMed: 34444956
DOI: 10.3390/nu13082797 -
Journal of Clinical Hypertension... Sep 2023The authors evaluated the efficacy, safety, and characteristics of patients who respond well to standard dose triple combination therapy including chlorthalidone 25 mg... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg in primary hypertension: A randomized, double-blind, active-controlled, multicenter phase 3 trial.
The authors evaluated the efficacy, safety, and characteristics of patients who respond well to standard dose triple combination therapy including chlorthalidone 25 mg with telmisartan 80 mg plus amlodipine 5 mg in hypertensive patients. This is a multicenter, double-blind, active-controlled, phase 3, randomized trial. Patients are randomized to triple combination (telmisartan 40 mg/amlodipine 5 mg/chlorthalidone 12.5 mg, TEL/AML/CHTD group) or dual combination (telmisartan 40 mg/amlodipine 5 mg, TEL/AML group) treatment and then dose up titration to TEL 80/AML5/CHTD25mg and TEL80/AML5, respectively. The primary endpoint is the change of mean sitting systolic blood pressure (MSSBP) at week 8. A Target BP achievement rate, a response rate, and the safety endpoints are also evaluated. Total 374 patients (mean age = 60.9 ± 10.7 years, male = 78.3%) were randomized to the study. The baseline MSSBPs/diastolic BPs were 149.9 ± 12.2/88.5 ± 10.4 mm Hg. After 8 weeks treatment, the change of MSSBPs at week 8 are -19.1 ± 14.9 mm Hg (TEL/AML/CHTD) and -11.4 ± 14.7 mm Hg (TEL/AML) (p < .0001). The achievement rates of target BP (53.8% vs. 37.8%, p = .0017) and responder rate (54.8% vs. 35.6%, p = .0001) at week 8 were significantly higher in TEL/AML/CHTD. There are no serious adverse event and no one discontinued medication due to adverse event. Among the TEL 80/AML5/CHTD25mg treatment group, patients of female or age ≥ 65 years old showed higher rate of target BP achievement than relatively young male. (61.4 vs. 46.8%, p = .042) Our study showed standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg is efficacious and safe in treatment of primary hypertension. Target BP achievement with triple therapy would be facilitated in female or old age.
Topics: Humans; Female; Male; Middle Aged; Aged; Telmisartan; Chlorthalidone; Amlodipine; Hypertension; Essential Hypertension; Leukemia, Myeloid, Acute
PubMed: 37614053
DOI: 10.1111/jch.14707 -
Nutrients Sep 2022High fructose intake has been implicated in obesity and metabolic syndrome, which are related to increased cardiovascular mortality. However, few studies have...
High fructose intake has been implicated in obesity and metabolic syndrome, which are related to increased cardiovascular mortality. However, few studies have experimentally examined the role of renin-angiotensin system blockers and calcium channel blockers (CCB) in obesity. We investigated the effects of valsartan (an angiotensin II receptor blocker) and amlodipine (a CCB) on lipolysis through the potential mechanism of PU.1 inhibition. We observed that high fructose concentrations significantly increased adipose size and triglyceride, monoacylglycerol lipase, adipose triglyceride lipase, and stearoyl-CoA desaturase-1 (SCD1), activating transcription factor 3 and PU.1 levels in adipocytes in vitro. Subsequently, PU.1 inhibitor treatment was able to reduce triglyceride, SCD1, and PU.1 levels. In addition, elevated levels of triglyceride and PU.1, stimulated by a high fructose concentration, decreased with valsartan and amlodipine treatment. Overall, these findings suggest that high fructose concentrations cause triacylglycerol storage in adipocytes through PU.1-mediated activation. Furthermore, valsartan and amlodipine treatment reduced triacylglycerol storage in adipocytes by inhibiting PU.1 activation in high fructose concentrations in vitro. Thus, the benefits of valsartan and amlodipine in lipolysis may be through PU.1 inhibition in fructose-induced adiposity, and PU.1 inhibition might have a potential therapeutic role in lipolysis in fructose-induced obesity.
Topics: Activating Transcription Factor 3; Adiposity; Amlodipine; Angiotensin Receptor Antagonists; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Fructose; Humans; Hypertension; Lipase; Lipolysis; Monoacylglycerol Lipases; Obesity; Stearoyl-CoA Desaturase; Tetrazoles; Triglycerides; Valsartan
PubMed: 36145135
DOI: 10.3390/nu14183759 -
Journal of Veterinary Internal Medicine May 2022Activity of the circulating renin-angiotensin-aldosterone system (RAAS) has not been comprehensively characterized in cats with systemic hypertension (SH) or...
BACKGROUND
Activity of the circulating renin-angiotensin-aldosterone system (RAAS) has not been comprehensively characterized in cats with systemic hypertension (SH) or cardiomyopathy (CM), and the effects of furosemide or amlodipine treatment on the RAAS have not been fully evaluated in cats.
HYPOTHESIS/OBJECTIVES
To document RAAS activity in cats with SH or CM compared to healthy cats and determine how RAAS profiles change with furosemide or amlodipine treatment.
ANIMALS
Sixty-six client-owned cats: 15 with SH (7 amlodipine-treated, 8 untreated), 17 with advanced CM (7 furosemide-treated, 10 not furosemide-treated), and 34 healthy cats.
METHODS
Equilibrium concentrations of RAAS peptides and aldosterone were quantified in serum samples by liquid chromatography-mass spectrometry. Variables were compared between groups using Kruskal-Wallis analysis with post hoc Holms-corrected Dunn's testing.
RESULTS
Compared with healthy cats, cats with CM had higher concentrations of angiotensin I, aldosterone, and plasma renin activity (all P < .01), and these differences remained significant (P < .03) after considering subgroups of untreated or furosemide-treated cats. Compared with healthy cats, untreated cats with SH showed no differences in RAAS biomarkers, whereas amlodipine-treated cats had higher concentrations of angiotensins I, II, III, IV, and 1-7, aldosterone, and plasma renin activity (all P < .03). Multivariable analysis determined that furosemide and amlodipine treatments were independent predictors of increased RAAS biomarker concentrations.
CONCLUSIONS AND CLINICAL IMPORTANCE
Cats with CM had increased RAAS activity, whereas cats with untreated SH did not. Furosemide and amlodipine both led to nonspecific activation of both classical and alternative RAAS pathways in cats.
Topics: Aldosterone; Amlodipine; Animals; Biomarkers; Cardiomyopathies; Cat Diseases; Cats; Furosemide; Hypertension; Renin; Renin-Angiotensin System
PubMed: 35285549
DOI: 10.1111/jvim.16401