Sinus Node Dysfunction and Pulmonary Hypertension—“Double Trouble” with Lithium Therapy

2021 ◽  
Author(s):  
Shweta Vohra ◽  
Akshyaya Pradhan ◽  
Rishi Sethi ◽  
Monika Bhandari
Keyword(s):  
Pulmonary Hypertension ◽  
Side Effects ◽  
Case Reports ◽  
Sinus Node ◽  
Therapeutic Index ◽  
Lithium Therapy ◽  
Standard Drug ◽  
Important Concern ◽  
Pulmonary Hypertension Patient ◽  
Cardiac Illness

AbstractLithium is considered a gold standard drug for the management of bipolar disorder and is a widely used mood-stabilizing drug in psychiatry practice. However, its side effects are of important concern. The narrow therapeutic index of lithium predispose it to toxicity/side effects, but various case reports in literature have shown that adverse drug reactions can occur even in the therapeutic range. We present the case of a 56-year-old woman with no history of cardiac illness presenting with tachycardia-bradycardia syndrome along with moderate pulmonary hypertension. Patient reverted to sinus rhythm after withholding lithium therapy for 1 week while her mean pulmonary artery pressure remained the same at day 10 of drug withdrawal.

Lithium and EKG abnormalities. A review

2017 ◽  
Vol 41 (S1) ◽  
pp. S750-S750
Author(s):  
A. Ballesteros ◽  
Á.S. Rosero ◽  
H. Sáiz ◽  
E. García-Parreño ◽  
G. Carlos ◽  
...  
Keyword(s):  
Therapeutic Range ◽  
Case Reports ◽  
Sinus Node ◽  
Serum Levels ◽  
Lithium Therapy ◽  
Cardiac Complications ◽  
General Terms ◽  
Wave Morphology ◽  
Competing Interest ◽  
Bipolar Patients

IntroductionThe literature concerning possible cardio-toxic effects of lithium therapy in man is reviewed.MethodologyA review was conducted to clarify the mechanisms associated with the occurrence of conducting abnormalities when using lithium and investigating (if so) whether these alterations depend on the dose. The literature search was conducted in PubMed data reviewing articles between 1982 and 2015.Results(1) Related to pathopsychiology/risk factors: reports indicate T wave morphology changes with lithium therapy. Of particular concern are cases of sinus mode dysfunction or sinoatrial block and the appearance or aggravation of ventricular irritability. The incidence of cardiac complications, in general terms, may increase with age. Recent findings (a retrospective study of bipolar patients) of lithium-associated hypocalcaemia showed that hypocalcaemia resulting from medical diseases and bipolar patients with lithium-associated hypocalcaemia had significantly higher frequencies of conduction defects. (2) Related/unrelated to dose: therapeutic and toxic levels of lithium have infrequently been associated with serious cardiac dysfunction. Several case reports demonstrate two important points about Brugada syndrome unmasking: electrocardiograph abnormality severity may correspond to lithium levels and unmasking may occur in the therapeutic range of lithium. Other report shows a case of lithium induced sinus-node dysfunction in a patient with serum lithium levels in therapeutic range.ConclusionsLithium abnormalities are rare and mostly not related to dose. Conducting heart anomalies may occur, especially when several factors are present (such as age or co-morbid illnesses that affect calcium serum levels).Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Multisystemic Side Effects of an Indispensable Old Drug: A Case Report of Chronic Lithium Use (A Patient with Multiple Side Effects of Lithium)

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Levent Demirtas ◽  
Emin Murat Akbas ◽  
Husnu Degirmenci ◽  
Ali Gurel ◽  
Eren Duzgun
Keyword(s):  
Side Effects ◽  
Clinical Supervision ◽  
Health Care Professionals ◽  
Case Reports ◽  
Sinus Bradycardia ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Signs And Symptoms ◽  
Therapeutic Index ◽  
Clinical Signs And Symptoms

Presented here is a case of long-term lithium use, with multiple emerging lithium-associated side effects. An 82-year-old woman was brought into the emergency department because of loss of consciousness. According to the physical examination and laboratory analyses, patient was diagnosed with lithium-associated hypercalcemia, hyperparathyroidism, nephrogenic diabetes insipidus (NDI), symptomatic sinus bradycardia, and thyroid dysfunction. In the literature, there is a limited number of case reports with lithium induced multiple clinical conditions. Multiple clinical manifestations due to the side effects of chronic lithium use might be seen. Health care professionals should keep in mind that lithium-related side effects might trigger or exacerbate each other. To avoid toxicity, close follow-up and clinical supervision are important for the early diagnosis and treatment of these side effects, due to the narrow therapeutic index and obscure clinical signs and symptoms of toxicity.

Nanoparticle-based Drug Delivery Systems for Targeted Epigenetics Cancer Therapy

2020 ◽  
Vol 21 (11) ◽  
pp. 1084-1098
Author(s):  
Fengqian Chen ◽  
Yunzhen Shi ◽  
Jinming Zhang ◽  
Qi Liu
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Cancer Therapy ◽  
Drug Delivery Systems ◽  
Therapeutic Index ◽  
Delivery Systems ◽  
Epigenetic Therapy ◽  
Cancer Therapies ◽  
Therapeutic Benefits ◽  
High Therapeutic Index

This review summarizes the epigenetic mechanisms of deoxyribonucleic acid (DNA) methylation, histone modifications in cancer and the epigenetic modifications in cancer therapy. Due to their undesired side effects, the use of epigenetic drugs as chemo-drugs in cancer therapies is limited. The drug delivery system opens a door for minimizing these side effects and achieving greater therapeutic benefits. The limitations of current epigenetic therapies in clinical cancer treatment and the advantages of using drug delivery systems for epigenetic agents are also discussed. Combining drug delivery systems with epigenetic therapy is a promising approach to reaching a high therapeutic index and minimizing the side effects.

Synthesis and Investigation of Therapeutic Potential of Isoform-Specific HDAC8 Inhibitors for the Treatment of Cutaneous T Cell Lymphoma

2019 ◽  
Vol 19 (7) ◽  
pp. 916-934 ◽  
Author(s):  
Appavoo Umamaheswari ◽  
Ayarivan Puratchikody ◽  
Natarajan Hari
Keyword(s):  
Side Effects ◽  
Inhibitory Activity ◽  
Hydroxamic Acid ◽  
Histone Deacetylase Inhibitors ◽  
Therapeutic Potential ◽  
In Vitro Assays ◽  
Normal Cells ◽  
Standard Drug ◽  
In Silico Studies ◽  
Hdac8 Inhibitors

Background:The available treatment option for any type of cancer including CTCL is chemotherapy and radiation therapy which indiscriminately persuade on the normal cells. One way out for selective destruction of CTCL cells without damaging normal cells is the use of histone deacetylase inhibitors (HDACi). Despite promising results in the treatment of CTCL, these HDACi have shown a broadband inhibition profile, moderately selective for one HDAC class but not for a particular isotype. The prevalence of drug-induced side effects leaves open a narrow window of speculation that the decreased therapeutic efficacy and observed side effects may be most likely due to non specific HDAC isoform inhibition. The aim of this paper is to synthesis and evaluates HDAC8 isoform specific inhibitors.Methods:Based on the preliminary report on the design and in silico studies of 52 hydroxamic acid derivatives bearing multi-substituent heteroaromatic rings with chiral amine linker, five compounds were shortlisted and synthesized by microwave assisted approach and high yielding synthetic protocol. A series of in vitro assays in addition to HDAC8 inhibitory activity was used to evaluate the synthesised compounds.Results:Inhibitors 1e, 2e, 3e, 4e and 5e exerted the anti-proliferative activities against CTCL cell lines at 20- 100 µM concentrations. Both the pyrimidine- and pyridine-based probes exhibited μM inhibitory activity against HDAC8. The pyrimidine-based probe 1e displayed remarkable HDAC8 selectivity superior to that of the standard drug, SAHA with an IC50 at 0.1µM.Conclusion:Our study demonstrated that simple modifications at different portions of pharmacophore in the hydroxamic acid analogues are effective for improving both HDAC8 inhibitory activity and isoform selectivity. Potent and highly isoform-selective HDAC8 inhibitors were identified. These findings would be expedient for further development of HDAC8-selective inhibitors.

scholarly journals Suramin Targets the Conserved Ligand-Binding Pocket of Human Raf1 Kinase Inhibitory Protein

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1151
Author(s):  
Chenyun Guo ◽  
Zhihua Wu ◽  
Weiliang Lin ◽  
Hao Xu ◽  
Ting Chang ◽  
...  
Keyword(s):  
Side Effects ◽  
Ligand Binding ◽  
Mapk Pathway ◽  
Regulatory Protein ◽  
Therapeutic Index ◽  
Binding Pocket ◽  
Biological Macromolecules ◽  
Inhibitory Protein ◽  
Ligand Binding Pocket ◽  
Raf1 Kinase

Suramin was initially used to treat African sleeping sickness and has been clinically tested to treat human cancers and HIV infection in the recent years. However, the therapeutic index is low with numerous clinical side-effects, attributed to its diverse interactions with multiple biological macromolecules. Here, we report a novel binding target of suramin, human Raf1 kinase inhibitory protein (hRKIP), which is an important regulatory protein involved in the Ras/Raf1/MEK/ERK (MAPK) signal pathway. Biolayer interference technology showed that suramin had an intermediate affinity for binding hRKIP with a dissociation constant of 23.8 µM. Both nuclear magnetic resonance technology and molecular docking analysis revealed that suramin bound to the conserved ligand-binding pocket of hRKIP, and that residues K113, W173, and Y181 play crucial roles in hRKIP binding suramin. Furthermore, suramin treatment at 160 µM could profoundly increase the ERK phosphorylation level by around 3 times. Our results indicate that suramin binds to hRKIP and prevents hRKIP from binding with hRaf1, thus promoting the MAPK pathway. This work is beneficial to both mechanistically understanding the side-effects of suramin and efficiently improving the clinical applications of suramin.

scholarly journals Cutaneous Side Effects of BRAF Inhibitors in Advanced Melanoma: Review of the Literature

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Bilgen Gençler ◽  
Müzeyyen Gönül
Keyword(s):  
Side Effects ◽  
Metastatic Melanoma ◽  
Mapk Pathway ◽  
Case Reports ◽  
Mitogen Activated Protein Kinase ◽  
Braf V600e ◽  
Braf Inhibitors ◽  
Braf Mutations ◽  
Cutaneous Side Effects ◽  
Downstream Signaling

The incidence of melanoma has recently been increasing. BRAF mutations have been found in 40–60% of melanomas. The increased activity of BRAF V600E leads to the activation of downstream signaling through the mitogen-activated protein kinase (MAPK) pathway, which plays a key role as a regulator of cell growth, differentiation, and survival. The use of BRAF inhibitors in metastatic melanoma with BRAF mutation ensures clinical improvement of the disease. Vemurafenib and dabrafenib are two selective BRAF inhibitors approved by the Food and Drug Administration (FDA). Both drugs are well tolerated and successfully used in clinical practice. However, some adverse reactions have been reported in patients in the course of treatment. Cutaneous side effects are the most common adverse events among them with a broad spectrum. Both the case reports and several original clinical trials reported cutaneous reactions during the treatment with BRAF inhibitors. In this review, the common cutaneous side effects of BRAF inhibitors in the treatment of metastatic melanoma with BRAF V600E mutation were reviewed.

Methylene blue is not contraindicated to treat hemodynamic instability in pediatric and neonate patient

2021 ◽  
Vol 17 ◽  
Author(s):  
Walusa A. Gonçalves-Ferri ◽  
Agnes A.S. Albuquerque ◽  
Patricia Martinez Evora ◽  
Paulo R.B. Evora
Keyword(s):  
Methylene Blue ◽  
Side Effects ◽  
Infusion Rate ◽  
Case Reports ◽  
Hemodynamic Instability ◽  
Exclusion Criteria ◽  
Old Patients ◽  
Randomized Clinical Study ◽  
Dose Infusion ◽  
Administration Timing

: The present review was carried out to describe publications on the use of methylene blue (MB) in pediatrics and neonatology, discussing dose, infusion rate, action characteristics and possible benefits for a pediatric patient group. The research was performed on the data sources PubMed, BioMed Central, and Embase (updated on Aug 31, 2020) by two independent investigators. The selected articles included human studies that evaluated MB use in pediatric or neonatal patients with vasoplegia due to any cause, regardless of the applied methodology. The MB use and 0 to18-years-old patients with vasodilatory shock were the adopted criteria. Exclusion criteria were the use of MB in patients without vasoplegia and patients ≥ 18-years-old. The primary endpoint was the increase in mean arterial pressure (MAP). Side effects and dose were also evaluated. Eleven studies were found of which 10 were case reports and 1 was a randomized clinical study. Only two of these studies were with neonatal patients (less than 28 days-old), reporting a small number of cases (1 and 6). All studies described positive action of MB on MAP, allowing the decrease of vasoactive amines in several of them. No severe side effects or death related to the use of the medication was reported. The maximum dose used was 2 mg/kg, but there was no consensus on the infusion rate and drug administration timing. Finally, no theoretical or experimental basis sustains the decision to avoid MB in children claiming it can cause pulmonary hypertension. The same goes for the concern of a possible deleterious effect on inflammatory distress syndrome.

scholarly journals Inhaled Epoprostenol for Pulmonary Hypertension Treatment in Neonates: A 12-Year Experience

2018 ◽  
Vol 36 (11) ◽  
pp. 1142-1149 ◽  
Author(s):  
Frédérique Berger-Caron ◽  
Bruno Piedboeuf ◽  
Geneviève Morissette ◽  
David Simonyan ◽  
Philippe Chétaille ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Side Effects ◽  
Retrospective Cohort ◽  
Rebound Effect ◽  
Oxygenation Index ◽  
Pediatric Intensive Care ◽  
Primary Objective ◽  
Hypertension Treatment ◽  
Fraction Of Inspired Oxygen ◽  
Inspired Oxygen

Background Persistent pulmonary hypertension of the newborn (PPHN) occurs in 10% of neonatal respiratory insufficiency. To selectively reduce pulmonary vascular resistance, several treatments have been tried. Inhaled epoprostenol (iPGI2) has been used for 12 years in our institution for the management of refractory PPHN despite the gaps in the literature to support this use. Objectives The primary objective was to evaluate the efficacy of iPGI2 for PPHN. The secondary objectives were to describe its use in neonates and assess side effects. Study Design This retrospective cohort study included infants < 28 days with PPHN treated with iPGI2 in the neonatal or pediatric intensive care units of our institution between 2004 and 2016. Results We reviewed 43 patient' care episodes (mean gestational age of 36 weeks). This was an extremely ill population with 54% mortality rate. Oxygenation index improved significantly after 12-hour treatment (p = 0.047), with a rebound effect when discontinuing nebulization. By the end of the therapy, the fraction of inspired oxygen had significantly dropped (p = 0.0018). Echocardiographic markers tended to normalize during treatment. No potential side effects were reported. Conclusion In these sick newborns, we observed an improvement in PPHN under iPGI2 without significant adverse effects. To our knowledge, this is the largest neonatal cohort reported to have received iPGI2 for PPHN.

scholarly journals Involvement of Anti-Inflammatory, Antioxidant, and BDNF Up-Regulating Properties in the Antipsychotic-Like Effect of the Essential Oil of Alpinia Zerumbet in Mice: A Comparative Study With Olanzapine

2021 ◽  
Author(s):  
Fernanda Yvelize Ramos de Araújo ◽  
Adriano José Maia Chaves Filho ◽  
Adriana Mary Nunes ◽  
Gersilene Valente de Oliveira ◽  
Patrícia Xavier Lima Gomes ◽  
...  
Keyword(s):  
Weight Gain ◽  
Drug Therapy ◽  
Side Effects ◽  
Essential Oil ◽  
Negative Symptoms ◽  
Repeated Administration ◽  
Social Impairment ◽  
Standard Drug ◽  
Anti Inflammatory ◽  
Alpinia Zerumbet

Abstract The current drug therapy for schizophrenia effectively treats acute psychosis and its recurrence; however, this mental disorder’s cognitive and negative symptoms are still poorly controlled. Antipsychotics present important side effects, such as weight gain and extrapyramidal effects. The essential oil of Alpinia zerumbet (EOAZ) leaves presents potential antipsychotic properties that need further preclinical investigation. Here, we aimed to determine the effects of EAOZ in the prevention and reversal of schizophrenia-like symptoms (positive, negative, and cognitive) induced by ketamine (KET) repeated administration in mice and putative neurobiological mechanisms related to this effect. To this end, we evaluated antioxidant (GSH, nitrite levels), anti-inflammatory [interleukin (IL)-6], and neurotrophic [brain-derived neurotrophic factor (BDNF)] effects of this oil in hippocampal tissue. The atypical antipsychotic olanzapine (OLZ) was used as standard drug therapy. EOAZ, similarly to OLZ, prevented and reversed most KET-induced schizophrenia-like behavioral alterations, i.e., sensorimotor gating deficits and social impairment. EOAZ had a modest effect on the prevention of KET-associated working memory deficit. Compared to OLZ, EOAZ showed a more favorable side effects profile, inducing less cataleptic and weight gain changes. EOAZ efficiently protected the hippocampus against KET-induced oxidative imbalance, IL-6 increments, and BDNF impairment. In conclusion, our data add more mechanistic evidence for the anti-schizophrenia effects of EOAZ, based on its antioxidant, anti-inflammatory, and BDNF up-regulating actions. The absence of significant side effects observed in current antipsychotic drug therapy seems to be an essential benefit of the oil.

Sign in / Sign up

Export Citation Format

Share Document