scholarly journals Tolerability and Efficacy of Long-term Medical Therapy in Primary Aldosteronism

2021 ◽  
Author(s):  
Fengjie Tang ◽  
Lih M Loh ◽  
Roger S Foo ◽  
Wann J Loh ◽  
Dawn S T Lim ◽  
...  
Keyword(s):  
Side Effects ◽  
Medical Therapy ◽  
Primary Aldosteronism ◽  
Treatment Duration ◽  
Male Gender ◽  
Monitoring Strategy ◽  
Biochemical Control ◽  
Limited Efficacy ◽  
Dose Dependent

Abstract Introduction Patients with primary aldosteronism (PA) have increased cardiovascular risk, and some studies find medical therapy less effective than surgery. This may be due to side effects and limited efficacy of medications at tolerable doses. Methods We conducted a retrospective study on 201 patients with PA treated with medical therapy (spironolactone, eplerenone or amiloride) for PA from 2000-2020 at two tertiary centres. Patients were assessed for efficacy to achieve clinical and biochemical control, and for side effects. Results Amongst 155 patients on long-term medications, 57.4% achieved blood pressure <140/90mmHg, 90.1% achieved normokalemia(48.0% achieved potassium≥4.3mmol/L), and 63.2% achieved renin>1ng/ml/hr. Concordance of biochemical control using potassium and renin levels was 49.1%. 52.3% of patients experienced side effects, with 10.3% switching to another medication, 22.6% decreasing dose, and 11.0% stopping medications. Risk factors for side effects were spironolactone use, dose≥50mg, treatment duration ≥1year, male gender and unilateral PA. Patients with unilateral PA, compared to bilateral PA, used higher spironolactone doses, 57mg vs 50mg, P<0.001, and had more side effects, 63.2% versus 41.8%, P=0.008. Amongst 46 patients with unilateral PA who underwent surgery after initial medical therapy, surgery further improved systolic and diastolic BP, from 141 to 135mmHg, P=0.045, and from 85 to 79mmHg, P=0.002, respectively. Conclusion Dose-dependent side effects limit the efficacy of medical therapy in PA. Future prospective studies should assess the best monitoring strategy for biochemical control during long-term medical therapy. For unilateral PA, surgery remains preferable to medications, as surgery leads to better control with less long-term side-effects.

scholarly journals Tolerability and Efficacy of Long-Term Medical Therapy in Primary Aldosteronism

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A301-A302
Author(s):  
Troy Puar ◽  
Fengjie Tang ◽  
Lih-Ming Loh ◽  
Roger Foo ◽  
Wann Jia Loh ◽  
...  
Keyword(s):  
Side Effects ◽  
Medical Therapy ◽  
Primary Aldosteronism ◽  
Male Gender ◽  
Monitoring Strategy ◽  
Biochemical Control ◽  
Duration Of Treatment ◽  
Limited Efficacy ◽  
Dose Dependent

Abstract Introduction: Patients with primary aldosteronism (PA) have increased cardiovascular risk and studies have found that medical therapy fails to ameliorate this. This may be due to side effects and limited efficacy of medications at tolerable doses. Methods: We conducted a retrospective study on 201 patients with PA treated with medical therapy (spironolactone, eplerenone or amiloride) for PA from 2000–2020 at two tertiary centres. Patients were assessed for efficacy to achieve clinical and biochemical control, and for side effects. Results: 53.7% of patients achieved blood pressure <140/90mmHg, 44.6% achieved serum potassium ≥4.3mmol/L, and 63.2% achieved renin levels >1ng/ml/hr. Concordance between biochemical control as assessed by potassium and renin levels was 49%. 45.3% of patients experienced side effects, with 8.5% switching to another medication, 18.9% decreasing dose, and 10.0% stopping medications altogether. Risk factors for side effects were spironolactone use, dose ≥50mg, duration of treatment ≥1 year, male gender and unilateral PA. Patients with unilateral PA, compared to bilateral PA, used higher median doses of spironolactone, 75mg vs 50mg, P<0.001, but more had persistent hypokalemia, 20.5% versus 6.4%, P=0.007. 44 patients with unilateral PA underwent surgery after initial medical therapy, which further improved systolic and diastolic BP, from 142 to 134mmHg, P<0.001, and from 85 to 79mmHg, P<0.001, respectively. Conclusion: Dose-dependent side effects limit the efficacy of medical therapy in PA. Future prospective studies should assess the best monitoring strategy for biochemical control during long-term medical therapy. In patients with unilateral PA, surgery remains a better option compared to life-long medications.

scholarly journals Long-Term Use of Aldosterone-Receptor Antagonists in Uncontrolled Hypertension: A Retrospective Analysis

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Pieter M. Jansen ◽  
Koen Verdonk ◽  
Ben P. Imholz ◽  
A. H. Jan Danser ◽  
Anton H. van den Meiracker
Keyword(s):  
Blood Pressure ◽  
Multivariate Analysis ◽  
Essential Hypertension ◽  
Primary Aldosteronism ◽  
Treatment Duration ◽  
Uncontrolled Hypertension ◽  
Receptor Antagonists ◽  
Aldosterone Receptor

Background. The long-term efficacy of aldosterone-receptor antagonists (ARAs) as add-on treatment in uncontrolled hypertension has not yet been reported.Methods. Data from 123 patients (21 with primary aldosteronism, 102 with essential hypertension) with difficult-to-treat hypertension who received an ARA between May 2005 and September 2009 were analyzed retrospectively for their blood pressure (BP) and biochemical response at first followup after start with ARA and the last follow-up available.Results. Systolic BP decreased by22±20and diastolic BP by9.4±12 mmHg after a median treatment duration of 25 months. In patients that received treatment >5 years, SBP was33±20and DBP was 16 ± 13 mmHg lower than at baseline. Multivariate analysis revealed that baseline BP and follow-up duration were positively correlated with BP response.Conclusion. Add-on ARA treatment in difficult-to-treat hypertension results in a profound and sustained BP reduction.

scholarly journals Corticosteroid-Sparing Effect of Chromoglycate Sodium and Nedocromil

1994 ◽  
Vol 3 (7) ◽  
pp. S25-S30 ◽  
Author(s):  
A. F. Capristo ◽  
M. Miraglia del Giudice Jr ◽  
C. Alfaro ◽  
N. Maiello
Keyword(s):  
Side Effects ◽  
Combined Treatment ◽  
Provocation Test ◽  
Double Bind ◽  
Hypertonic Solution ◽  
Inflammatory Drugs ◽  
Bronchial Hyper Responsiveness ◽  
Sparing Effect ◽  
Dose Dependent

The most appropiate management for bronchial asthma is the control of airway inflammation. Corticosteroids are the most effective anti-inflammatory drugs available, but they have a number of side effects; most of these are dose-dependent. In children, asthma control should be accomplished with low steroid doses possibly given by inhalation. In a double-bind placebo-controlled crossover study a group of children with mild to moderate asthma received NED 16 mg/day or BDP 400 μg/day. Values for FEV1, PEF, symptoms use ofbronchodilators overlapped, whereas bronchial hyper-responsiveness assessed by histamine bronchoprovocation challenge was better with BDP than NED. In another case, one boy with high bronchial hyper-reactivity assessed by provocation test with hypertonic solution, experienced a significant improvement only after 2 weeks of therapy with Deflazacort (2 mg/Kg/day) followed by 4 months on combined treatment with NED (16 mg/day) and BDP (300 μ/day). Authors conclude that NED could have a steroidsparing effect over long-term use.

scholarly journals Biochemical Control in Acromegaly With Multimodality Therapies: Outcomes From a Pituitary Center and Changes Over Time

2019 ◽  
Vol 105 (3) ◽  
pp. e532-e543 ◽  
Author(s):  
Alireza Ghajar ◽  
Pamela S Jones ◽  
Francisco J Guarda ◽  
Alex Faje ◽  
Nicholas A Tritos ◽  
...  
Keyword(s):  
Pituitary Surgery ◽  
Male Gender ◽  
Multimodality Therapy ◽  
Therapeutic Interventions ◽  
Biochemical Control ◽  
Adjuvant Therapies ◽  
Changes Over Time ◽  
Term Analysis ◽  
Over Time

Abstract Purpose To determine the prevalence of insulin-like growth factor-1 (IGF-1) normalization with long-term multimodality therapy in a pituitary center and to assess changes over time. Methods Patients with acromegaly (N = 409), with ≥1 year of data after surgery and at least 2 subsequent clinic visits were included in long-term analysis (N = 266). Biochemical data, clinical characteristics, and therapeutic interventions were reviewed retrospectively. Results At diagnosis, mean [standard deviation] age was 43.4 [14.3] years, body mass index was 28.5 (24.9–32.1) kg/m2 (median, interquartile range), serum IGF-1 index (IGF-1 level/upper limit of normal) was 2.3 [1.7–3.1], and 80.5% had macroadenomas. Patients with transsphenoidal surgery after 2006 were older [46.6 ± 14.3 vs 40.0 ± 13.4 years; P < 0.001]. Age and tumor size correlated inversely. Overall (N = 266), 93.2% achieved a normal IGF-1 level during 9.9 [5.0–15.0] years with multimodality therapy. The interval to first normal IGF-1 level following failed surgical remission was shorter after 2006: 14.0 (95% confidence interval, 10.0–20.0) versus 27.5 (22.0–36.0) months (P = 0.002). Radiation therapy and second surgery were rarer after 2006: 28 (22%) versus 62 (47.0%); P < 0.001 and 12 (9.4%) versus 28 (21.2%); P = 0.010, respectively. Age at diagnosis increased over time periods, possibly reflecting increased detection of acromegaly in older patients with milder disease. Male gender, older age, smaller tumor and lower IGF-1 index at diagnosis predicted long-term sustained IGF-1 control after surgery without adjuvant therapies. Conclusion The vast majority of patients with acromegaly can be biochemically controlled with multimodality therapy in the current era. Radiotherapy and repeat pituitary surgery became less frequently utilized over time. Long-term postoperative IGF-1 control without use of adjuvant therapies has improved.

scholarly journals A review study of targeting of AAK1 and JAK1/2 using baricitinib in COVID-19 infected human cells

2020 ◽  
Vol 16 (supplement) ◽  
pp. 9-15
Author(s):  
Abeer M Al-Humaidhi
Keyword(s):  
Side Effects ◽  
Inhibitory Effect ◽  
Term Treatment ◽  
Long Term Treatment ◽  
Pros And Cons ◽  
Experimental Trials ◽  
Pharmaceutical Agents ◽  
Dose Dependent ◽  
A Current

     The outbreak of a current public health coronavirus 2019 disease is a causative agent of a serious acute respiratory syndrome and even death. COVID-19 has exposed to multi-suggested pharmaceutical agents to control this global disease. Baricitinib, a well-known antirheumatic agent, was one of them. This article reviews the likely pros and cons of baricitinib in attenuation of COVID-19 based on the mechanism of drug action as well as its pharmacokinetics. The inhibitory effect of baricitinib on receptor mediated endocytosis promoter, AKK1, and on JAK-STAT signaling pathway is benefacial in inhibition of both viral assembling and inflammation. Also, its pharmacokinetic has encouraged the physicians toward the drug selection for COVID-19 treatment. On the other hand, most of baricitinib side effects are dose-dependent. In conclusion, targeting of AAK1 and JAK1/2 using baricitinib has predicted to be potential and effective with minimal side effects in management COVID-19 infected patients for a short therapeutic dosing period. Laboratory monitoring should be considered for some parameters. However, experimental trials are mandatory for a long-term treatment with a lower dose of baricitinib to evaluate its effectiveness and safety in patients with moderate COVID-19 infection.

scholarly journals Surgery as a Viable Alternative First-Line Treatment for Prolactinoma Patients. A Systematic Review and Meta-Analysis

2019 ◽  
Vol 105 (3) ◽  
pp. e32-e41 ◽  
Author(s):  
Amir H Zamanipoor Najafabadi ◽  
Ingrid M Zandbergen ◽  
Friso de Vries ◽  
Leonie H A Broersen ◽  
M Elske van den Akker-van Marle ◽  
...  
Keyword(s):  
Side Effects ◽  
Dopamine Agonist ◽  
Transsphenoidal Surgery ◽  
Dopamine Agonists ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Sensitivity Analyses ◽  
Biochemical Control ◽  
Disease Remission

Abstract Context The improved remission and complication rates of current transsphenoidal surgery warrant reappraisal of the position of surgery as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas. Objective To compare clinical outcomes after dopamine agonist withdrawal and transsphenoidal surgery in prolactinoma patients. Methods Eight databases were searched up to July 13, 2018. Primary outcome was disease remission after drug withdrawal or surgery. Secondary outcomes were biochemical control and side effects during dopamine agonist treatment and postoperative complications. Fixed- or random-effects meta-analysis was performed to estimate pooled proportions. Robustness of results was assessed by sensitivity analyses. Results A total of 1469 articles were screened: 55 (10 low risk of bias) on medical treatment (n = 3564 patients) and 25 (12 low risk of bias) on transsphenoidal surgery (n = 1836 patients). Long-term disease remission after dopamine agonist withdrawal was 34% (95% confidence interval [CI], 26-46) and 67% (95% CI, 60-74) after surgery. Subgroup analysis of microprolactinomas showed 36% (95% CI, 21-52) disease remission after dopamine agonist withdrawal, and 83% (95% CI, 76-90) after surgery. Biochemical control was achieved in 81% (95% CI, 75-87) of patients during dopamine agonists with side effects in 26% (95% CI, 13-41). Transsphenoidal surgery resulted in 0% mortality, 2% (95% CI, 0-5) permanent diabetes insipidus, and 3% (95% CI, 2-5) cerebrospinal fluid leakage. Multiple sensitivity analyses yielded similar results. Conclusions In the majority of prolactinoma patients, disease remission can be achieved through surgery, with low risks of long-term surgical complications, and disease remission is less often achieved with dopamine agonists.

Potential Usefulness of Leukotriene B4 (LTB4) on Mobilization of Hematopoietic Progenitor Cells (HPC).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5271-5271
Author(s):  
Yeung-Chul Mun ◽  
Seung-Eun Lee ◽  
Kyung-Eun Lee ◽  
Eun-Sun Yoo ◽  
Eun Suk Kang ◽  
...  
Keyword(s):  
Side Effects ◽  
Synergistic Effects ◽  
Leukotriene B4 ◽  
Lipid Mediator ◽  
Control Group ◽  
Optimal Timing ◽  
Dependent Manner ◽  
Dose Dependent

Abstract The mechanisms on HPC mobilization seem to be multifactorial processes. Many cell adhesion molecules (VLA-4, ICAM-1, VCAM-1 etc), SDF-1/CXCR4, and proteases (ie, MMP-9) may be important players for this mobilization processes. However, finding more mechanisms on HPC mobilization is under intense scrutiny. So far, G-CSF is the best known cytokine for this purpose. Meanwhile, its limitation on using G-CSF is to take 4–6 days for the optimal mobilization at clinic and its side effects (ie; bone pain, high WBC counts) are not negligible. LTB4 is lipid mediator during the process of inflammation, having many roles (ie; inducer of chemotaxis, the production of nitric oxide, transepithelial migration of neutrophil). In present study, we focused on the roles of LTB4 on HPC mobilization and its feasibility on mobilization in vivo. Samples were collected from the peripheral blood via heart puncture and the bone marrow on time dependent manner (1hr, 4hr, 6hr, 12hr, 24hr, 48hr) after LTB4 injection which was given via intravenously and the dose dependent manner of LTB4 (0.5μg, 1μg, 2μg, 3μg). These data were compared with two other groups after G-CSF injection and normal saline injection. Collected total nucleated cells were analyzed for Sca-1+/Lin- using flow cytometry and CFU studies. There were definite increase of Sca-1+/Lin- cells after 1μg of LTB4 injection group (TNC: 29.55(±0.92)×105/ml and HPC: 3.72(±0.09) %). Its control group showed as follows: TNC: 14.55(±0.21)×105/ml, HPC: 0.41(±0.04) %, (p<0.05). Mobilization was optimal only after 4hours of LTB4 injection (TNC: 36.25(±2.90)×105/ml & HPC: 3.50(±0.37) %). After 4hours of LTB4 injection, there was a obvious down pattern. In terms of quantity, more than 20 fold of HPC mobilization after one LTB4 injection was observed. There were no immediate toxicity in the cohort, though long term potential side effects are under investigations. In conclusion, we showed the rapid mobilization of HPC with LTB4 at only 4 hours post-injection. This finding with LTB4 could be significant in terms of shortening the optimal period of mobilization comparing to that by G-CSF, which takes at least 4–6 days by repetitive injection to reach the optimal timing for collection. The possible synergistic effects of G-CSF with LTB4 for larger quantity of HPC and the cellular and molecular mechanism(s) of mobilization by LTB4 are being investigated in our lab.

scholarly journals Acitretin-Conjugated Dextran Nanoparticles Ameliorate Psoriasis-like Skin Disease at Low Dosages

2022 ◽  
Vol 9 ◽  
Author(s):  
Jiajia Lan ◽  
Yuce Li ◽  
Jingjing Wen ◽  
Yu Chen ◽  
Jing Yang ◽  
...  
Keyword(s):  
Side Effects ◽  
Skin Disease ◽  
Inhibitory Effect ◽  
Keratinocyte Proliferation ◽  
Psoriasis Treatment ◽  
Stat3 Phosphorylation ◽  
Term Administration ◽  
Dose Dependent ◽  
Systemic Drug

Psoriasis is a common chronic inflammatory skin disease mainly characterized by keratinocyte hyperproliferation and massive infiltration of inflammatory immune cells. Acitretin (ACT), an FDA-approved first-line systemic drug for psoriasis treatment, could suppress the proliferation of keratinocytes and downregulate the expression of inflammatory cytokines by modulating signal transducer and activator of transcription (STAT) signaling pathways. However, dose-dependent side effects of ACT limit its long-term administration in the clinic. Therefore, improving the therapeutic efficacy of ACT to reduce clinical dosage will benefit the patients. Here, we develop ACT-conjugated dextran nanoparticles (ACT-Dex NPs) and evaluated the potential for psoriasis treatment. Our results indicate that ACT-Dex NPs ameliorate psoriasis-like skin disease significantly at a low dosage which does not cause side effects, while neat ACT drugs at an equivalent dosage provide much less benefit. Moreover, we demonstrate that ACT-Dex NPs suppress keratinocyte proliferation more efficiently than neat ACT by enhancing the inhibitory effect on STAT3 phosphorylation. Thus, the proposed ACT-Dex NPs provide an effective and safe option for psoriasis treatment.

scholarly journals Need for improved monitoring in patients with acromegaly

2015 ◽  
Vol 4 (4) ◽  
pp. R59-R67 ◽  
Author(s):  
Julie M Silverstein
Keyword(s):  
Medical Therapy ◽  
Prolonged Exposure ◽  
Clinical Symptoms ◽  
Recurrent Disease ◽  
Therapeutic Monitoring ◽  
Biochemical Control ◽  
Endocrine Society ◽  
Optimal Monitoring ◽  
Appropriate Treatment

Acromegaly is a rare and insidious disease characterized by the overproduction of growth hormone (GH) and insulin-like growth factor 1 (IGF1) and is most commonly due to a pituitary adenoma. Patients with acromegaly who experience prolonged exposure to elevated levels of GH and IGF1 have an increased mortality risk and progressive worsening of disease-related comorbidities. Multimodal treatment with surgery, medical therapy, and radiotherapy provides biochemical control, defined by recent acromegaly clinical guidelines from the Endocrine Society as a reduction of GH levels to <1.0 ng/ml and normalization of IGF1 levels, to a substantial proportion of patients and is associated with improved clinical outcomes. Patients with acromegaly, even those without clinical symptoms of disease, require long-term monitoring of GH and IGF1 levels if the benefits associated with biochemical control are to be maintained and the risk of developing recurrent disease is to be abated. However, suboptimal monitoring is common in patients with acromegaly, and this can have negative health effects due to delays in detection of recurrent disease and implementation of appropriate treatment. Because of the significant health consequences associated with prolonged exposure to elevated levels of GH and IGF1, optimal monitoring in patients with acromegaly is needed. This review article will discuss the biochemical assessments used for therapeutic monitoring in acromegaly, the importance of monitoring after surgery and medical therapy or radiotherapy, the consequences of suboptimal monitoring, and the need for improved monitoring algorithms for patients with acromegaly.

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