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Advances in Chronic Kidney Disease Mar 2019Pregnancy-induced hypertension is a major cause of maternal and fetal morbidity and mortality. The overall strategies of defining and managing these conditions are aimed... (Review)
Review
Pregnancy-induced hypertension is a major cause of maternal and fetal morbidity and mortality. The overall strategies of defining and managing these conditions are aimed at preventing cardiovascular and cerebrovascular complications in the mother without jeopardizing fetal well-being. Our understanding of the origin of these disorders is evolving. Women with chronic hypertension should undergo a prepregnancy evaluation and close monitoring during and after pregnancy to ensure medication safety and to prevent end-organ damage. Based on available data, the current recommendation is that antihypertensive therapy should be initiated only in women with severe hypertension (defined as systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥105 mm Hg). It is now becoming more and more clear that hypertensive complications during pregnancy are potentially linked to cardiovascular, kidney, and metabolic diseases later in life. This review discusses the spectrum of hypertensive disorders of pregnancy, general management principles, and the need to monitor for long-term cardiovascular sequelae for decades afterward.
Topics: Antihypertensive Agents; Aspirin; Cardiovascular Diseases; Chronic Disease; Diuretics; Female; Humans; Hypertension; Hypertension, Pregnancy-Induced; Labetalol; Methyldopa; Nifedipine; Platelet Aggregation Inhibitors; Pre-Eclampsia; Preconception Care; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Care; Renal Insufficiency, Chronic; Risk Factors; Vasodilator Agents
PubMed: 31023448
DOI: 10.1053/j.ackd.2019.03.017 -
Molecules (Basel, Switzerland) Jan 2024Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis Sativa, has garnered increasing attention for its diverse therapeutic potential. This comprehensive... (Review)
Review
Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis Sativa, has garnered increasing attention for its diverse therapeutic potential. This comprehensive review delves into the complex pharmacokinetics of CBD, including factors such as bioavailability, distribution, safety profile, and dosage recommendations, which contribute to the compound's pharmacological profile. CBD's role as a pharmacological inhibitor is explored, encompassing interactions with the endocannabinoid system and ion channels. The compound's anti-inflammatory effects, influencing the Interferon-beta and NF-κB, position it as a versatile candidate for immune system regulation and interventions in inflammatory processes. The historical context of Cannabis Sativa's use for recreational and medicinal purposes adds depth to the discussion, emphasizing CBD's emergence as a pivotal phytocannabinoid. As research continues, CBD's integration into clinical practice holds promise for revolutionizing treatment approaches and enhancing patient outcomes. The evolution in CBD research encourages ongoing exploration, offering the prospect of unlocking new therapeutic utility.
Topics: Humans; Cannabidiol; Biological Availability; Hallucinogens; Cannabinoid Receptor Agonists; Cannabis; Carbidopa
PubMed: 38257386
DOI: 10.3390/molecules29020473 -
Clinical Neuropharmacology 2018D-Decarboxylase inhibitors, such as carbidopa or benserazide, have been used as adjunct therapy in Parkinson disease shortly after levodopa synthesis in the 1960s. These...
BACKGROUND
D-Decarboxylase inhibitors, such as carbidopa or benserazide, have been used as adjunct therapy in Parkinson disease shortly after levodopa synthesis in the 1960s. These compounds increase intracerebral drug concentration and decrease adverse effects by blocking peripheral conversion to dopamine. Skin rash as part of an allergic reaction was previously described in subjects who were using levodopa in combination with carbidopa or benserazide; however, etiology was never clear. Allergic reactions to carbidopa have not previously been reported.
METHODS
We report a case of a 77-year-old woman with a diagnosis of idiopathic Parkinson disease, who developed autonomic and dermatological signs: conjunctival injection, rhinorrhea, excessive sweating, hypertension, and pruritic generalized rash, among others, immediately after carbidopa/levodopa administration regardless of the manufacturer. Treatment with dexamethasone combined with chloropyramine hydrochloride resulted in complete resolution of the hypersensitivity reaction each time it presented. The autonomic and dermatological manifestations did not reappear after treatment was replaced with benserazide/levodopa.
CONCLUSIONS
To the best of our knowledge, this is the first case report of an allergic reaction specific to carbidopa. Our case highlights the importance of identifying the source of a hypersensitivity drug response, whether it is caused by the active component or by the excipients.
Topics: Aged; Antiparkinson Agents; Benserazide; Carbidopa; Drug Combinations; Drug Hypersensitivity; Female; Humans; Levodopa; Middle Aged; Parkinson Disease
PubMed: 29432287
DOI: 10.1097/WNF.0000000000000270 -
Analytical Sciences : the International... Aug 2022Levodopa (L-DOPA) is the most effective drug for Parkinson's disease; however, various side effects occur during therapy. L-DOPA metabolites and the high cumulative dose... (Review)
Review
Levodopa (L-DOPA) is the most effective drug for Parkinson's disease; however, various side effects occur during therapy. L-DOPA metabolites and the high cumulative dose of L-DOPA were responsible for its side effects. It is necessary to monitor the concentration of L-DOPA and its metabolites for individualized therapy. This review focuses on L-DOPA analysis by chromatography-based methods in biological matrices. Literature published up to September 2021 was collected in the PubMed, Web of Science, and Embase by using search strategy ("levodopa" OR "L-DOPA") AND ("chromatography"). A total of 1249 articles were identified and 32 articles were included. The contents for method development and validation were summarized and analyzed. Due to the instability of catecholamines (L-DOPA, dopamine, and 3-O-methyldopa) and carbidopa, antioxidation (0.5 mg sodium metabisulfite for 100 μL sample) and environment temperature control were used alone or in combination to enhance stability. Sample was mainly pretreated by protein precipitation (0.4-0.7 M perchloric acid). Separation was usually achieved using methanol or acetonitrile:water (with formic acid) on C18 columns. Mass spectrometry, electrochemical detector, ultraviolet-visible detector and fluorescence detector were used for detection. For L-DOPA, the calibration range was 2.5-10,000 ng/mL, the matrix effect and its coefficient of variation was 85-115 and -9.0-8.5%, and the recovery was 66.8-127.0%. Without stabilization strategy, L-DOPA was stable in plasma at room temperature for 1-7 h (4-6 h for most studies), at - 70 °C to - 80 °C for 10-20 days and after 3-5 freeze-thaw cycles. With stabilization strategies, the stability of L-DOPA in plasma was significantly improved. Metabolites of L-DOPA and enzyme inhibitors (carbidopa, entacapone, tolcapone and benserazide) were all stable in biological matrix. This study might be useful for researchers to develop their methods for individualized therapy of patients with Parkinson.
Topics: Carbidopa; Catecholamines; Enzyme Inhibitors; Humans; Levodopa; Parkinson Disease
PubMed: 35715690
DOI: 10.1007/s44211-022-00132-4 -
Biomedicine & Pharmacotherapy =... Jul 2020Pregnancy and time period right after labour are connected with some dangerous states, such as: pregnancy-induced hypertension (PIH), which afflict 6-10 % of pregnant... (Review)
Review
PURPOSE
Pregnancy and time period right after labour are connected with some dangerous states, such as: pregnancy-induced hypertension (PIH), which afflict 6-10 % of pregnant women and mood disorders where postpartum depression occurs among 10-15 % of women after labour and so-called baby blues afflicts around 43 % of them. Scientists tried to link those diseases which afflicts thousands of women per year, and the linking factor appears to be methyldopa which is the first choice treatment of PIH. Recent study showed that 778 % of pregnant women treated with methyldopa suffered to postpartum depression. Aim of this article is to delineate mechanisms through which methyldopa induce mood disorders.
METHODS
Authors reviewed following databases for randomized controlled trials and review articles published up to February 2019: Pubmed, Scopus, Google Scholar, Cochrane Database and ClinicalKey. Keywords used to research were: postpartum depression, methyldopa, depression, baby blues, pregnancy-induced hypertension, gestational hypertension, VEGF, nitric oxide, prolactin, hyperprolactinaemia. Selection of studies was based on relevance, year of publication, and reliability of methodology. Authors included every study contributory to assessment of scale of the problem of postpartum depression and baby blues, along with connection of those diseases with usage of methyldopa.
RESULTS
Methyldopa alterate neurotrophic factors levels, impairs cerebral blood flow, and through dopamine level reduction it impairs reward system and increase prolactin release. Moreover, methyldopa leads to catecholamines depletion which impairs neurons function and increase concentration of nitric oxide (NO) which have neurotoxic properties.
CONCLUSIONS
Epidemiological, as well as pharmacological studies confirmed important role of methyldopa in induction of postpartum depression and baby blues through hormone alteration, reduced cerebral blood flow and neurons function impairment. This study proves how important for women's health is this problem and how complex is its mechanism.
Topics: Animals; Antihypertensive Agents; Depression, Postpartum; Female; Humans; Hypertension, Pregnancy-Induced; Methyldopa; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 32413670
DOI: 10.1016/j.biopha.2020.110196 -
The Cochrane Database of Systematic... Oct 2021Hypertension is the leading preventable risk factor for cardiovascular disease and premature death worldwide. One of the clinical effects of hypertension is left... (Review)
Review
BACKGROUND
Hypertension is the leading preventable risk factor for cardiovascular disease and premature death worldwide. One of the clinical effects of hypertension is left ventricular hypertrophy (LVH), a process of cardiac remodelling. It is estimated that over 30% of people with hypertension also suffer from LVH, although the prevalence rates vary according to the LVH diagnostic criteria. Severity of LVH is associated with a higher prevalence of cardiovascular disease and an increased risk of death. The role of antihypertensives in the regression of left ventricular mass has been extensively studied. However, uncertainty exists regarding the role of antihypertensive therapy compared to placebo in the morbidity and mortality of individuals with hypertension-induced LVH.
OBJECTIVES
To assess the effect of antihypertensive pharmacotherapy compared to placebo or no treatment on morbidity and mortality of adults with hypertension-induced LVH.
SEARCH METHODS
Cochrane Hypertension's Information Specialist searched the following databases for studies: Cochrane Hypertension Specialised Register (to 26 September 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library; 2020, Issue 9), Ovid MEDLINE (1946 to 22 September 2020), and Ovid Embase (1974 to 22 September 2020). We searched the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov for ongoing trials. We also searched Epistemonikos (to 19 February 2021), LILACS BIREME (to 19 February 2021), and Clarivate Web of Science (to 26 February 2021), and contacted authors and funders of the identified trials to obtain additional information and individual participant data. There were no language restrictions.
SELECTION CRITERIA
Randomised controlled trials (RCTs) with at least 12 months' follow-up comparing antihypertensive pharmacological therapy (monotherapy or in combination) with placebo or no treatment in adults (18 years of age or older) with hypertension-induced LVH were eligible for inclusion. The trials must have analysed at least one primary outcome (all-cause mortality, cardiovascular events, or total serious adverse events) to be considered for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors screened the search results, with any disagreements resolved by consensus amongst all review authors. Two review authors carried out the data extraction and analyses. We assessed risk of bias of the included studies following Cochrane methodology. We used the GRADE approach to assess the certainty of the body of evidence.
MAIN RESULTS
We included three multicentre RCTs. We selected 930 participants from the included studies for the analyses, with a mean follow-up of 3.8 years (range 3.5 to 4.3 years). All of the included trials performed an intention-to-treat analysis. We obtained evidence for the review by identifying the population of interest from the trials' total samples. None of the trials provided information on the cause of LVH. The intervention varied amongst the included trials: hydrochlorothiazide plus triamterene with the possibility of adding alpha methyldopa, spironolactone, or olmesartan. Placebo was administered to participants in the control arm in two trials, whereas participants in the control arm of the remaining trial did not receive any add-on treatment. The evidence is very uncertain regarding the effect of additional antihypertensive pharmacological therapy compared to placebo or no treatment on mortality (14.3% intervention versus 13.6% control; risk ratio (RR) 1.02, 95% confidence interval (CI) 0.74 to 1.40; 3 studies; 930 participants; very low-certainty evidence); cardiovascular events (12.6% intervention versus 11.5% control; RR 1.09, 95% CI 0.77 to 1.55; 3 studies; 930 participants; very low-certainty evidence); and hospitalisation for heart failure (10.7% intervention versus 12.5% control; RR 0.82, 95% CI 0.57 to 1.17; 2 studies; 915 participants; very low-certainty evidence). Although both arms yielded similar results for total serious adverse events (48.9% intervention versus 48.1% control; RR 1.02, 95% CI 0.89 to 1.16; 3 studies; 930 participants; very low-certainty evidence) and total adverse events (68.3% intervention versus 67.2% control; RR 1.07, 95% CI 0.86 to 1.34; 2 studies; 915 participants), the incidence of withdrawal due to adverse events may be significantly higher with antihypertensive drug therapy (15.2% intervention versus 4.9% control; RR 3.09, 95% CI 1.69 to 5.66; 1 study; 522 participants; very low-certainty evidence). Sensitivity analyses limited to blinded trials, trials with low risk of bias in core domains, and trials with no funding from the pharmaceutical industry did not change the results of the main analyses. Limited evidence on the change in left ventricular mass index prevented us from drawing any firm conclusions.
AUTHORS' CONCLUSIONS
We are uncertain about the effects of adding additional antihypertensive drug therapy on the morbidity and mortality of participants with LVH and hypertension compared to placebo. Although the incidence of serious adverse events was similar between study arms, additional antihypertensive therapy may be associated with more withdrawals due to adverse events. Limited and low-certainty evidence requires that caution be used when interpreting the findings. High-quality clinical trials addressing the effect of antihypertensives on clinically relevant variables and carried out specifically in individuals with hypertension-induced LVH are warranted.
Topics: Adolescent; Adult; Antihypertensive Agents; Cardiovascular Diseases; Humans; Hypertension; Hypertrophy, Left Ventricular; Methyldopa
PubMed: 34628642
DOI: 10.1002/14651858.CD012039.pub3 -
The Medical Letter on Drugs and... Dec 2020
Comparative Study Review
Topics: Antiparkinson Agents; Carbidopa; Catechol O-Methyltransferase; Dopamine Agonists; Humans; Kidney Diseases; Levodopa; Monoamine Oxidase Inhibitors; Parkinson Disease
PubMed: 33647002
DOI: No ID Found -
Investigative Ophthalmology & Visual... Sep 2023Wet AMD (wAMD) is associated with cellular senescence. However, senescent cell-targeted therapies for wAMD have rarely been comprehensively studied. This study aimed to...
PURPOSE
Wet AMD (wAMD) is associated with cellular senescence. However, senescent cell-targeted therapies for wAMD have rarely been comprehensively studied. This study aimed to explore the therapeutic effects of senolytic agents on choroidal neovascularization (CNV).
METHODS
RNA sequencing datasets were obtained from the Gene Expression Omnibus database and used to explore the association between senescence and wAMD. We explored the effects of senescent adult RPE cell line-19 cells on the proliferation, migration, invasion, and tube formation of human umbilical vein endothelial cells. A laser-induced CNV animal model was used to study wAMD. We studied a senescent cell elimination therapy for CNV progression using two types of senolytics and a transgenic method.
RESULTS
Cells in the retinal pigment epithelium-choroid of the CNV model were enriched in senescence, inflammation, and angiogenesis gene sets. AP20187 was used to specifically eliminate senescent cells and proven to alleviate CNV progression in INK-ATTAC transgenic mice. Senescent adult RPE cell line-1 cells produced elevated levels of senescence-associated secretory phenotypes, including VEGFs; they also demonstrated increased proliferation, migration, invasion, and tube formation in human umbilical vein endothelial cells. The number of senescent cells increased in the laser-induced CNV rat model, and intravitreal injections of dasatinib with quercetin reduced the expression of p16 in CNV and alleviated neovascularization.
CONCLUSIONS
Senescent RPE cells can accelerate pathological neovascularization; thus, senescent cell-targeting therapy has great clinical potential for wAMD.
Topics: Adult; Humans; Mice; Animals; Rats; Dasatinib; Quercetin; Retinal Pigment Epithelium; Choroidal Neovascularization; Cellular Senescence; Choroid; Human Umbilical Vein Endothelial Cells; Methyldopa
PubMed: 37750741
DOI: 10.1167/iovs.64.12.39 -
Neurology Nov 2023Advanced therapies (ATs; deep brain stimulation [DBS] or pump therapies: continuous subcutaneous apomorphine infusion [CSAI], levodopa/carbidopa intestinal gel [LCIG])...
BACKGROUND AND OBJECTIVES
Advanced therapies (ATs; deep brain stimulation [DBS] or pump therapies: continuous subcutaneous apomorphine infusion [CSAI], levodopa/carbidopa intestinal gel [LCIG]) are used in later stages of Parkinson disease (PD). However, decreasing efficacy over time and/or side effects may require an AT change or combination in individual patients. Current knowledge about changing or combining ATs is limited to mostly retrospective and small-scale studies. The nationwide case collection Combinations of Advanced Therapies in PD assessed simultaneous or sequential AT combinations in Germany since 2005 to analyze their clinical outcome, their side effects, and the reasons for AT modifications.
METHODS
Data were acquired retrospectively by modular questionnaires in 22 PD centers throughout Germany based on clinical records and comprised general information about the centers/patients, clinical (Mini-Mental Status Test/Montréal Cognitive Assessment, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS], side effects, reasons for AT modification), and therapeutical (ATs with specifications, oral medication) data. Data assessment started with initiation of the second AT.
RESULTS
A total of 148 AT modifications in 116 patients were associated with significantly improved objective (median decrease of MDS-UPDRS Part III 4.0 points [ < 0.001], of MDS-UPDRS Part IV 6.0 points [ < 0.001], of MDS-UPDRS Part IV-off-time item 1.0 points [ < 0.001]) and subjective clinical outcome and decreasing side effect rates. Main reasons for an AT modification were insufficient symptom control and side effects of the previous therapy. Subgroup analyses suggest addition of DBS in AT patients with leading dyskinesia, addition of LCIG for leading other cardinal motor symptoms, and addition of LCIG or CSAI for dominant off-time. The most long-lasting therapy-until requiring a modification-was DBS.
DISCUSSION
Changing or combining ATs may be beneficial when 1 AT is insufficient in efficacy or side effects. The outcome of an AT combination is comparable with the clinical benefit by introducing the first AT. The added AT should be chosen dependent on dominant clinical symptoms and adverse effects. Furthermore, prospective trials are needed to confirm the results of this exploratory case collection.
CLASSIFICATION OF EVIDENCE
This study provides Class IV evidence that, in patients with PD, changing or combining ATs is associated with an improvement in the MDS-UPDRS or subjective symptom reporting.
Topics: Humans; Parkinson Disease; Antiparkinson Agents; Retrospective Studies; Prospective Studies; Carbidopa; Levodopa; Infusions, Subcutaneous; Drug Combinations; Gels
PubMed: 37914414
DOI: 10.1212/WNL.0000000000207858 -
Current Opinion in Endocrinology,... Apr 2019To review the recent findings that small 'drug-like' compounds block disease-specific human leukocyte antigen (HLA) molecules in type 1 diabetes (T1D). (Review)
Review
PURPOSE OF REVIEW
To review the recent findings that small 'drug-like' compounds block disease-specific human leukocyte antigen (HLA) molecules in type 1 diabetes (T1D).
RECENT FINDINGS
The predominant genetic risk for developing T1D, the immune-mediated form of diabetes, is conferred through HLA genes. One such gene, termed HLA-DQ8, is present in 50-60% of patients with T1D and those at-risk. DQ8 presents disease-relevant peptides to T cells, which mediate tissue-specific destruction of pancreatic islets. Using a structure-based approach to evaluate the 'druggability' of the DQ8 molecule, methyldopa, a clinically well-established oral antihypertensive agent, was discovered to bind DQ8. Methyldopa blocked the activation of DQ8-specific T cells responding to self-antigens such as insulin but not influenza. In a proof-of-concept clinical trial (NCT01883804), methyldopa was administered to recent-onset T1D patients with the DQ8 gene that confirmed the mechanism of action and diminished inflammatory T cell responses toward insulin.
SUMMARY
Methyldopa blocks the diabetes-specific function of HLA-DQ8, which represents a personalized medicine approach to treat the underlying autoimmunity in T1D. Clinical trials are warranted and underway to evaluate methyldopa in potentially preserving residual β-cell function in those with new onset and at risk for T1D.
Topics: Autoimmunity; Diabetes Mellitus, Type 1; HLA-DQ Antigens; Humans; Methyldopa; T-Lymphocytes
PubMed: 30694829
DOI: 10.1097/MED.0000000000000470