nadolol oral (INV102 oral) / Chronic Airway Therap - LARVOL DELTA

Drugs for hypertension. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Hypertension

Impact of green tea catechin ingestion on the pharmacokinetics of lisinopril in healthy volunteers. (PubMed, Clin Transl Sci) - "Green tea consumption may reduce the risk of cardiovascular outcomes and total mortality, whereas green tea or its catechin components has been reported to decrease plasma concentrations of a hydrophilic β blocker, nadolol, in humans. These results suggest that the extent of intestinal absorption of lisinopril was significantly impaired in the presence of GTE, while it had no major effect on the absorption rate and renal excretion of lisinopril. Concomitant use of lisinopril and green tea may decrease oral exposure to lisinopril, and therefore result in reduced therapeutic efficacy."

Clinical • Journal • PK/PD data • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension

Eptinezumab (Vyepti) for migraine prevention. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • CNS Disorders • Migraine

Sorption of pharmaceuticals on the surface of microplastics. (PubMed, Chemosphere) - "The aim of this study was to evaluate the sorption capacity of nine pharmaceuticals, commonly used in human and veterinary medicine, which constitute known ubiquitous water pollutants: enrofloxacin (ENR), ciprofloxacin (CIP), norfloxacin (NOR), 5-fluorouracil (5-FU), methotrexate (MET), flubendazole (FLU), fenbendazole (FEN), propranolol (PRO) and nadolol (NAD), on the surface of the most often identified microscopic plastic particles in the aquatic environment, i.e. polypropylene (PP), low density polyethylene (LD-PE), high density polyethylene (HD-PE) and polyvinyl chloride (PVC). The obtained results suggest a complex nature of sorption, including both hydrophobic and electrostatic interactions. However, since the ionic strength of the medium was found to be a significant factor influencing the sorption potential, minute interactions are observed in conditions common for the natural environment."

Journal • CNS Disorders • Psychiatry

Protective effects of morphine in a rat model of post-traumatic stress disorder: Role of hypothalamic-pituitary-adrenal axis and beta- adrenergic system. (PubMed, Behav Brain Res) - "The glucocorticoid receptor antagonist RU486 (20 mg/kg), the mineralocorticoid receptor antagonist spironolactone (50 mg/kg), and the corticosterone synthesis inhibitor metyrapone (50 mg/kg) were injected 90 min before morphine administration to block the HPA axis activity. The propranolol, and nadolol did not prevent the effect of morphine on anxiety-like behaviors, but the propranolol prevented morphine effects on fear extinction in SPS animals. These findings together suggest that the protective effects of morphine on PTSD-like symptoms in rats require a certain level of the HPA axis and central beta - adrenergic activity and any alteration in the function of these systems can impede the protective effects of morphine."

Journal • Preclinical • Anesthesia • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry

The effects of β and β adrenergic receptor blockade on the exercise-induced mobilization and ex vivo expansion of virus-specific T cells: implications for cellular therapy and the anti-viral immune effects of exercise. (PubMed, Cell Stress Chaperones) - "Healthy participants (n = 12) completed 30 min of steady-state cycling exercise after ingesting a placebo, a β AR antagonist (nadolol) or a β AR antagonist (bisoprolol). We conclude that exercise-induced enhancements in VST mobilization and expansion are at least partially β AR mediated, thus highlighting a role for the β AR in targeted therapy for the augmentation of VST immune cell therapeutics in the allogeneic adoptive transfer setting. Moreover, long-term regular exercise may provide additional viral protection in the host through frequent β AR-dependent mobilization and redistribution of VSTs cumulated with each bout of exercise."

Journal • Preclinical • Cytomegalovirus Infection • Immunology • Transplantation

Cardiac influence of the β3-adrenoceptor in the goldfish (Carassius auratus): a protective role under hypoxia? (PubMed, J Exp Biol) - "Under normoxia, the β3-AR-selective agonist BRL (10 to 10 mol l) elicited a concentration-dependent increase of contractility that was abolished by a specific β3-AR antagonist (SR; 10 mol l), but not by α/β1/β2-AR inhibitors (phentolamine, nadolol and ICI118,551; 10 mol l)...Under both normoxia and hypoxia, adenylate cyclase and cAMP were found to be involved in the β3-ARs-dependent downstream transduction pathway. Our findings suggest the presence of functional β3-ARs in the goldfish heart, whose activation modulates the basal performance and contributes to the hypoxia-dependent increase of contractility."

Journal

[VIRTUAL] Viral Illness Precipitating Cardiac Arrest in a Patient with Congenital QT Prolongation (ATS-I 2020) - "AHA 2015 guidelines recommend initiation of beta-blockade (preferably nadolol or propranolol) for patients with congenital prolonged QT. Other treatment options include placement of ICD, mexiletine use, or left cardiac sympathetic denervation...Close monitoring of hospitalized individuals on QT prolonging medications is required to prevent TDP & cardiac arrest. Other than medications, electrolytes & congenital predisposition, acute viral illnesses can result in prolonged QT & predispose sudden cardiac arrest."

Clinical • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Heart Failure • Musculoskeletal Pain • Pain

[VIRTUAL] A Unique Case of Treatment-Resistant Beta-Blocker Toxicity (ATS-I 2020) - "Case presentation A 59 year old male with a medical history significant for major depressive disorder and alcohol abuse presented with nausea, vomiting and abdominal pain after consuming an unknown quantity of atenolol with an intention for suicide. Due to its favorable dialyzability characteristics, hemodialysis can be used for beta-blocker toxicity which is resistant to conventional therapy as seen in our case. Additionally, other low lipid soluble and low protein binding beta-blockers namely nadolol and sotalol can also benefit from being dialyzable in the same way."

Clinical • Cardiovascular • CNS Disorders • Depression • Hypotension • Mood Disorders • Pain • Psychiatry • Respiratory Diseases

β-blocker therapy for infantile haemangioma. (PubMed, Expert Rev Clin Pharmacol) - "We review the indications, dosing regimens, duration of treatment, efficacy and adverse effects of propranolol and therapeutic alternatives including oral atenolol and acebutolol, nadolol, intralesional propranolol injections, topical propranolol and timolol, and oral captopril. More research is required to understand the optimal dosing and duration, efficacy and safety of these alternative therapies. Recent demonstration of propranolol's actions mediated by non-β-adrenergic isomer R-propranolol on stem cells, offers an immense opportunity to harness the efficacy of β-blockers, to induce accelerated involution of IH, while mitigating their β-adrenergic receptor-mediated adverse effects."

Journal

Molecular characterization of the calcium release channel deficiency syndrome. (PubMed, JCI Insight) - "Nadolol, propranolol, and flecainide reduced erratic activity by 8.5 fold, 6.8 fold, and 2.4 fold, respectively from ISO challenge. Unlike the gain-of-function mechanism observed in RYR2-mediated CPVT, the homozygous multi-exon duplication precipitates a dramatic reduction in RYR2 transcription and RyR2 protein translation, a loss-of-function in calcium handling, and a calcium-induced calcium release apparatus that is insensitive to catecholamines and caffeine."

Journal • Cardiovascular • Ventricular Tachycardia

Inherited cardiac arrhythmias. (PubMed, Nat Rev Dis Primers) - "Management relies on pharmacological therapy, mostly β-adrenergic receptor blockers (specifically, propranolol and nadolol) and sodium and transient outward current blockers (such as quinidine), or surgical interventions, including left cardiac sympathetic denervation and implantation of a cardioverter-defibrillator. All these arrhythmias are potentially life-threatening and have substantial negative effects on the quality of life of patients. Future research should focus on the identification of genes associated with the diseases and other risk factors, improved risk stratification and, in particular for Brugada syndrome, effective therapies."

Journal • Review • Atrial Fibrillation • Cardiovascular • Rare Diseases • Ventricular Tachycardia

A large deletion in RYR2 exon 3 is associated with nadolol and flecainide refractory catecholaminergic polymorphic ventricular tachycardia. (PubMed, Pacing Clin Electrophysiol) - "Treatment options in a patient like ours are therefore limited and sympathectomy and ICD insertion should be considered early in the treatment course as was done in this patient. In contrast to other CPVT patients who do not usually have structural cardiac abnormalities, these patients are at a high risk of developing left ventricular non-compaction or dilated cardiomyopathy and therefore might benefit from cardiac imaging at regular intervals."

Journal • Cardiomyopathy • Cardiovascular • Ventricular Tachycardia

Chronic Stress Exposure Suppresses Mammary Tumor Growth and Reduces Circulating Exosome TGF-β Content via β-Adrenergic Receptor Signaling in MMTV-PyMT Mice. (PubMed, Breast Cancer (Auckl)) - "Chronic β-adrenergic receptor (β-AR) blockade with nadolol abrogated stress-induced alterations in tumor burden and cleaved caspase-3 expression, lung MDSC frequency, and exosomal TGF-β content...Unexpectedly, β-blockade in nonstressed mice increased lung metastatic lesions and splenic MDSC frequency, suggesting that in MMTV-PyMT mice, β-AR activation also inhibits tumor progression in the absence of stress exposure. Together, these results suggest stress exposure can act through β-AR signaling to slow primary tumor growth in MMTV-PyMT mice."

Journal • Preclinical • Breast Cancer • Hematological Disorders • Hormone Receptor Positive Breast Cancer • Immunology • Oncology • Solid Tumor • CASP3 • IL6

Pharmacokinetic variability of beta-adrenergic blocking agents used in cardiology. (PubMed, Pharmacol Res Perspect) - "Based on AUC, metoprolol, propranolol, carvedilol, and nebivolol showed high pharmacokinetic variability (highest first), whereas bisoprolol, atenolol, sotalol, labetalol, nadolol, and pindolol showed low to moderate variability (lowest first). We have shown a high interindividual pharmacokinetic variability that varies markedly in different beta-adrenergic blocking agents; the extreme being steady state ratios as high as 30 in metoprolol. A more personalized approach to the medical treatment of patients may be obtained by combining known pharmacokinetic information about variability, pharmaco-genetics and -dynamics, and patient characteristics, to avoid adverse events or lack of treatment effect."

Journal • PK/PD data

Microscale Thermophoresis as a Screening Tool to Predict Melanin Binding of Drugs. (PubMed, Pharmaceutics) - "MST categorized the compounds into extreme (chloroquine, penicillin G), high (papaverine, levofloxacin, terazosin), intermediate (timolol, nadolol, quinidine, propranolol), and low melanin binders (atropine, methotrexate, diclofenac) and displayed good correlation with binding parameter values obtained with the conventional binding study and LC/MS analytics. This method represents a useful and fast approach for classification of compounds regarding melanin binding. Thus, the method can be utilized in various fields, including drug discovery, pharmacokinetics, and toxicology."

Journal • Melanoma • Oncology • Ophthalmology • Solid Tumor

Use of beta-blockers for rosacea-associated facial erythema and flushing: a systematic review and update on proposed mode of action. (PubMed, J Am Acad Dermatol) - "Oral β-blockers could be an effective treatment option for rosacea patients with facial erythema and flushing that does not respond to conventional therapy. Larger prospective trials with objective outcome assessment are needed to validate the promising results of these studies."

Journal • Review • Cardiovascular • Dermatology • Dermatopathology • Hypotension • Rosacea

Pharmacologic prevention of variceal bleeding and rebleeding. (PubMed, Hepatol Int) - "This review provides a background on the most important aspects of the treatment of portal hypertension in patients with compensated and decompensated liver cirrhosis. However, despite the great improvement in the prevention of variceal bleeding over the last years, further therapeutic options are needed."

Journal • Review • Biosimilar • Cardiovascular • Fibrosis • Immunology • Venous Thromboembolism

Stress-induced Norepinephrine Downregulates CCL2 in Macrophages to Suppress Tumor Growth in a Model of Malignant Melanoma. (PubMed, Cancer Prev Res (Phila)) - "An in vitro assay confirmed that NE down-regulates CCL2 production in both mouse and human macrophages, and that pre-treatment with the pan-β-adrenergic receptor inhibitor nadolol rescues this activity. Furthermore, RST had no effect on tumor growth in transgenic CCL2-deficient mice. This study suggests that stress reduces malignant melanoma by reducing recruitment of tumor promoting macrophages by CCL2."

Journal • Melanoma • Oncology • Solid Tumor • CCL2

Drug Induced QT Prolongation With Arsenic Trioxide in the Treatment of Acute Promyelocytic Leukemia (ACC 2017) - "...Nadolol was initiatied at 20mg daily and titrated to a resting heart rate of 50 bpm... QT prolongation is a known side effect of therapy with As2O3. There is a proven survival benefit with the addition of As2O3 to ATRA therapy for APL in relapsed individuals or those with the t(15:17) gene rearrangement. Strategies which allow patients to receive this curative regimen include keeping magnesium >1.8 mg/dL and potassium >4 mEq/L, frequent ECGs to monitor QTc, and avoidance of additional drug-induced QT prolongation."

Clinical • Biosimilar • Cardiovascular • Hematological Malignancies • Leukemia • Oncology

Non-precision Medicine: Mexiletine Useful For More Than Just Long QT Syndrome Type 3 (RHYTHM 2020) - "Initially trialed on nadolol, she transitioned to propranolol due to side effects and nonadherence, but had a breakthrough syncopal event with a QTc >500 msec prompting ICD placement. Concomitant use of mexiletine for compound potassium channel mutations in LQTS2 and 5 was effective in shortening the QT interval and may provide an adjunctive approach to reduce clinical events."

Atrial Fibrillation • Cardiovascular

Activated Cardiac Fibroblasts Control Contraction of Human Fibrotic Cardiac Microtissues by a β-Adrenoreceptor-Dependent Mechanism. (PubMed, Cells) - "Fibrotic phenotype of cardiac microtissues was inhibited by treatment with TGF-β-receptor type 1 inhibitor SD208 in a dose-dependent manner...However, in the absence of exogenous agonists, the β-adrenoreceptor blocker nadolol decreased beating rate of fibrotic cardiac microtissues by prolonging relaxation time. Thus, our data suggest that in fibrosis, activated cardiac fibroblasts could promote cardiac contraction rate by a direct stimulation of β-adrenoreceptor signalling. In conclusion, a model of fibrotic cardiac microtissues can be used as a high-throughput model for drug testing and to study cellular and molecular mechanisms of cardiac fibrosis."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology

Characterization Of The Calcium Release Channel Deficiency Syndrome Secondary To A Homozygous, Multi-exon Duplication In Ryr2 (RHYTHM 2020) - "We demonstrate that the homozygous multi-exon RYR2 duplication-mediated CRCDS leads to a pathogenic substrate that is prone to DAD arrhythmic activity. While flecainide alone partially rescued the phenotype, both nadolol and propranolol were able to fully rescue the ISO treated patient iPSC-CMs by significantly reducing the arrhythmic activity of the cells below the baseline arrhythmic level of the control iPSC-CMs."

Cardiovascular

Verapamil Efficacy For Recurrent Torsades De Pointes In A Child With Homozygous Tango-2 Deletion (RHYTHM 2020) - "He was stabilized on esmolol, which was transitioned to nadolol. Verapamil could be life-saving during ventricular tachyarrhythmias in children with TANGO-2 deletion."

Clinical • Atrial Fibrillation • Cardiovascular • Heart Failure • Pediatrics

Nadolol or Propranolol Are the ONLY Beta-Blockers That Should Be Used in LQT (RHYTHM 2020) - "Furthermore there is a lack of clarity on why a given beta-blocker may be beneficial for certain pathogenic genotypes. To identify which beta-blockers should be used in LQT To identify which beta-blockers should absolutely not be used in LQT To understand when to change beta blockers in LQT To understand which beta blockers may be more genotype specific than others"