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High Blood Pressure & Cardiovascular... Jul 2023Hypertensive disorders in pregnancy are associated with increased risk of maternal, fetal, and neonatal morbidity and mortality. It is important to distinguish between... (Review)
Review
Hypertensive disorders in pregnancy are associated with increased risk of maternal, fetal, and neonatal morbidity and mortality. It is important to distinguish between pre-existing (chronic) hypertension and gestational hypertension, developing after 20 weeks of gestation and usually resolving within 6 weeks postpartum. There is a consensus that systolic blood pressure ≥ 170 or diastolic blood pressure ≥ 110 mmHg is an emergency and hospitalization is indicated. The selection of the antihypertensive drug and its route of administration depend on the expected time of delivery. The current European guidelines recommend initiating drug treatment in pregnant women with persistent elevation of blood pressure ≥ 150/95 mmHg and at values > 140/90 mmHg in women with gestational hypertension (with or without proteinuria), with pre-existing hypertension with the superimposition of gestational hypertension, and with hypertension with subclinical organ damage or symptoms at any time during pregnancy. Methyldopa, labetalol, and calcium antagonists (the most data are available for nifedipine) are the drugs of choice. The results of the CHIPS and CHAP studies are likely to reduce the threshold for initiating treatment. Women with a history of hypertensive disorders in pregnancy, particularly those with pre-eclampsia, are at high risk of developing cardiovascular disease later in life. Obstetric history should become a part of the cardiovascular risk assessment in women.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Hypertension, Pregnancy-Induced; Hypertension; Pre-Eclampsia; Antihypertensive Agents; Blood Pressure; Labetalol
PubMed: 37308715
DOI: 10.1007/s40292-023-00582-5 -
Kidney360 Oct 2023Hypertensive disorders of pregnancy complicate up to 10% of pregnancies and remain the major cause of maternal and neonatal morbidity and mortality. Hypertensive... (Review)
Review
Hypertensive disorders of pregnancy complicate up to 10% of pregnancies and remain the major cause of maternal and neonatal morbidity and mortality. Hypertensive disorders of pregnancy can be classified into four groups depending on the onset of hypertension and the presence of target organ involvement: chronic hypertension, preeclampsia, gestational hypertension, and superimposed preeclampsia on chronic hypertension. Hypertension during pregnancy is associated with a higher risk of cardiovascular disease and kidney failure. Early diagnosis and proper treatment for pregnant women with hypertension remain a priority since this leads to improved maternal and fetal outcomes. Labetalol, nifedipine, methyldopa, and hydralazine are the preferred medications to treat hypertension during pregnancy. In this comprehensive review, we discuss the diagnostic criteria, evaluation, and management of pregnant women with hypertension.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Antihypertensive Agents; Labetalol; Nifedipine
PubMed: 37526641
DOI: 10.34067/KID.0000000000000228 -
Journal of Hepatology Sep 2023Drug-induced liver injury (DILI) can mimic almost all other liver disorders. A phenotype increasingly ascribed to drugs is autoimmune-like hepatitis (ALH). This article... (Review)
Review
Drug-induced liver injury (DILI) can mimic almost all other liver disorders. A phenotype increasingly ascribed to drugs is autoimmune-like hepatitis (ALH). This article summarises the major topics discussed at a joint International Conference held between the Drug-Induced Liver Injury consortium and the International Autoimmune Hepatitis Group. DI-ALH is a liver injury with laboratory and/or histological features that may be indistinguishable from those of autoimmune hepatitis (AIH). Previous studies have revealed that patients with DI-ALH and those with idiopathic AIH have very similar clinical, biochemical, immunological and histological features. Differentiating DI-ALH from AIH is important as patients with DI-ALH rarely require long-term immunosuppression and the condition often resolves spontaneously after withdrawal of the implicated drug, whereas patients with AIH mostly require long-term immunosuppression. Therefore, revision of the diagnosis on long-term follow-up may be necessary in some cases. More than 40 different drugs including nitrofurantoin, methyldopa, hydralazine, minocycline, infliximab, herbal and dietary supplements (such as Khat and Tinospora cordifolia) have been implicated in DI-ALH. Understanding of DI-ALH is limited by the lack of specific markers of the disease that could allow for a precise diagnosis, while there is similarly no single feature which is diagnostic of AIH. We propose a management algorithm for patients with liver injury and an autoimmune phenotype. There is an urgent need to prospectively evaluate patients with DI-ALH systematically to enable definitive characterisation of this condition.
Topics: Humans; Chemical and Drug Induced Liver Injury; Expert Testimony; Hepatitis, Autoimmune; Nitrofurantoin; Congresses as Topic
PubMed: 37164270
DOI: 10.1016/j.jhep.2023.04.033 -
Journal of Neural Transmission (Vienna,... Nov 2023Advanced Parkinson's disease is characterized by periods of poor mobility, dyskinesia and progressive decline in functional independence of the affected person despite... (Review)
Review
Advanced Parkinson's disease is characterized by periods of poor mobility, dyskinesia and progressive decline in functional independence of the affected person despite the manipulation of levodopa doses and the introduction of supplemental therapies such as catechol-O-methyl transferase inhibitors, monoamine oxidase-B inhibitors and dopamine agonists. The implementation of drug delivery systems allows to bypass problems related to irregular and often unpredictable intestinal absorption of oral levodopa, which significantly affects its bioavailability and contributes to the development and persistence of motor complications. Subcutaneous apomorphine and levodopa/carbidopa jejunal infusion systems have been available for many years and their efficacy is confirmed by randomized studies and long-term experience in many centers worldwide. Recently, a new formulation of levodopa/carbidopa infusion gel that includes the catechol-O-methyl transferase inhibitor Entacapone has been introduced to the market. The use of entacapone allows to reduce total daily dose of administered levodopa. Two different soluble formulations of levodopa/carbidopa (ND0612 and ABBV-951) have completed clinical development, and both can ensure subcutaneous delivery by a portable pump infusion system. ABBV-951 uses a foslevodopa/foscarbidopa formulation, both prodrugs to improve absorption and tolerability. Both systems provide effective improvement of motor complications and are likely to expand the therapeutic options in advanced patients. Future efforts should focus on the earlier detection of patients who are candidates for device-aided therapies, increasing appropriate referral and broadening the availability of these treatments globally.
Topics: Humans; Parkinson Disease; Levodopa; Carbidopa; Antiparkinson Agents; Catechol O-Methyltransferase; Catechols; Dopamine Agonists; Drug Combinations
PubMed: 37672049
DOI: 10.1007/s00702-023-02693-8 -
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 -
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 -
Frontiers in Cardiovascular Medicine 2023Hypertensive disorders of pregnancy (HDP) are rising in prevalence and associated with adverse maternal and infant health outcomes. Current guidelines recommend...
Hypertensive disorders of pregnancy (HDP) are rising in prevalence and associated with adverse maternal and infant health outcomes. Current guidelines recommend labetalol, nifedipine, and methyldopa as acceptable first-line agents to treat HDP in outpatient settings. However, the current practice regarding antihypertensive medication usage and selection remain unclear. A retrospective, observational cohort study was conducted in 1,641 patients with a physician diagnosis of HDP who delivered at two academic medical centers in North Carolina from 2014 to 2017. Use of any antihypertensive medication, and the agent selected, at any encounter during pregnancy or on the delivery date was collected from the electronic health record. Proportions were compared across HDP diagnosis (eclampsia/severe preeclampsia, chronic hypertension with superimposed preeclampsia, preeclampsia, gestational hypertension) by Chi-square tests and multivariable logistic regression. Antihypertensive medications were used in 1,276 (77.8%) patients overall. Among treated patients, labetalol (74.9%) was the most frequently used medication followed by nifedipine (29.6%) and hydralazine (20.5%). Methyldopa was used infrequently (4.4%). HDP type was the strongest factor associated with use of an antihypertensive agent. Relative to gestational hypertension, antihypertensive use was significantly more likely [odds ratio (95% CI)] in patients with severe preeclampsia [5.94 (3.85-9.16)], chronic hypertension with superimposed preeclampsia [4.99 (3.46-7.19)], and preeclampsia [2.13 (1.61-2.82)]. In a real-world setting, antihypertensive medication use among HDP patients was common, labetalol, nifedipine, and hydralazine were the most commonly selected agents, and increasing HDP severity was associated with a higher likelihood of antihypertensive use. Future studies comparing medication effectiveness in pregnant patients with distinct HDP diagnoses are needed.
PubMed: 37485273
DOI: 10.3389/fcvm.2023.1225251 -
Hypertension in Pregnancy Dec 2024Preeclampsia (PE) is a pregnancy disorder that represents a major cause of maternal and perinatal morbidity and mortality. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preeclampsia (PE) is a pregnancy disorder that represents a major cause of maternal and perinatal morbidity and mortality.
METHODS
This network meta-analysis was registered with PROSPERO. We searched the PubMed, ClinicalTrials.gov. and Embase databases for studies published from inception to the 31 of March 2023. RevMan5.3 software provided by the Cochrane Collaboration was used for direct meta-analysis (DMA) statistical analysis. Funnel maps, network meta-analysis (NMA), the surface under the cumulative ranking curve (SUCRA) to rank the different interventions and publication bias were generated by STATA 17.0 software.
RESULTS
We included eight randomized controlled trials (RCTs) involving a total of 1192 women with PE; two studies were of high quality and six were of moderate quality. Eight interventions were addressed in the NMA. In the DMA, we found that blood pressure in the Ketanserin group were significantly higher than those in the Nicardipine group. NMA showed that blood pressure in the Dihydralazine group was significantly higher than that in the Methyldopa, Labetalol, Nicardipine and Diltiazem groups. And the blood pressure in the Labetalol group was significantly lower than that in the Nicardipine group. SUCRA values showed that Diltiazem was more effective in lowering blood pressure than other drugs looked at in this study.
CONCLUSION
According to the eight RCTs included in this study, Diltiazem was the most effective in reducing blood pressure in PE patients; Labetalol and Nicardipine also had good effects. Diltiazem is preferred for the treatment of patients with severe PE and high blood pressure.
Topics: Pregnancy; Female; Humans; Antihypertensive Agents; Labetalol; Pre-Eclampsia; Diltiazem; Nicardipine; Network Meta-Analysis
PubMed: 38488570
DOI: 10.1080/10641955.2024.2329068