- Cough as the sole manifestation of pericardial effusion. [Journal Article]
- BCBMJ Case Rep 2018 Feb 05; 2018
- A 59-year-old woman with paroxysmal atrial fibrillation (AF) presented with severe non-productive cough, malaise, low-grade fever and AF flare-up 3 weeks following pulmonary vein isolation with radio...
A 59-year-old woman with paroxysmal atrial fibrillation (AF) presented with severe non-productive cough, malaise, low-grade fever and AF flare-up 3 weeks following pulmonary vein isolation with radiofrequency catheter ablation. She denied chest pain or dyspnoea. Patient was haemodynamically stable. There was no pulsus paradoxus. Laboratories showed leucocytosis and elevated C-reactive protein. ECG showed sinus tachycardia. CT abdomen and pelvis showed a large pericardial effusion (PE). Shortly after admission, she developed AF with rapid ventricular response, responsive to intravenous amiodarone. Transthoracic echocardiogram revealed 2.4 cm posterior PE without tamponade physiology, non-amenable to pericardiocentesis via sub-xiphoid approach. Patient underwent left thoracoscopic pericardial window with removal of 250 cc bloody fibrinous fluid. Cough improved significantly and she was discharged on oral amiodarone and apixaban. Repeat CT chest after 2 weeks for recurrent cough showed a small PE, treated with oral prednisone for suspected postablation pericarditis, with complete resolution of cough. Amiodarone was stopped without recurrence of AF.
- A pharmacokinetic model for amiodarone in infants developed from an opportunistic sampling trial and published literature data. [Journal Article]
- JPJ Pharmacokinet Pharmacodyn 2018 Feb 12
- Amiodarone is a first-line antiarrhythmic for life-threatening ventricular fibrillation or ventricular tachycardia in children, yet little is known about its pharmacokinetics (PK) in this population....
Amiodarone is a first-line antiarrhythmic for life-threatening ventricular fibrillation or ventricular tachycardia in children, yet little is known about its pharmacokinetics (PK) in this population. We developed a population PK (PopPK) model using samples collected via an opportunistic study design of children receiving amiodarone per standard of care supplemented by amiodarone PK data from the literature. Both study data and literature data were predominantly from infants < 2 years old, so our analysis was restricted to this group. The final combined dataset consisted of 266 plasma drug concentrations in 45 subjects with a median (interquartile range) postnatal age of 40.1 (11.0-120.4) days and weight of 3.9 (3.1-5.1) kg. Since the median sampling time after the first dose was short (study: 95 h; literature: 72 h) relative to the terminal half-life estimated in adult PopPK studies, values of the deep compartment volume and flow were fixed to literature values. A 3-compartment model best described the data and was validated by visual predictive checks and non-parametric bootstrap analysis. The final model included body weight as a covariate on all volumes and on both inter-compartmental and elimination clearances. The empiric Bayesian estimates for clearance (CL), volume of distribution at steady state, and terminal half-life were 0.25 (90% CL 0.14-0.36) L/kg/h, 93 (68-174) L/kg, and 266 (197-477) h, respectively. These studies will provide useful information for future PopPK studies of amiodarone in infants and children that could improve dosage regimens.
- Population Impact of Drug Interactions with Warfarin: A Real-World Data Approach. [Journal Article]
- THThromb Haemost 2018 Feb 12
- CONCLUSIONS: Clinically potentially important interactions were observed in several study drugs. The majority of them, although confirmed, had little impact after adjusting for standard INR variability in the general population of warfarin users.
- Probable drug-drug interaction between erlotinib and amiodarone causes severe neurotoxicity in a patient with advanced lung cancer. [Journal Article]
- ADAnticancer Drugs 2018 Feb 07
- Drug-drug interactions (DDIs) are of great concern in the treatment of cancer, especially when target therapies, such as tyrosine kinase inhibitors, are being used. Here, we report a case of probable...
Drug-drug interactions (DDIs) are of great concern in the treatment of cancer, especially when target therapies, such as tyrosine kinase inhibitors, are being used. Here, we report a case of probable DDI between erlotinib and amiodarone leading to severe neurotoxicity. Amiodarone inhibits P-glycoprotein (P-gp), for which erlotinib is a substrate. P-gp is an important drug transporter that is involved in limiting the blood-brain barrier penetration of erlotinib. Clinicians should be aware of emerging data characterizing the effect of the P-gp transport system on drug exposure and its potential for DDI.
- Evaluation of autophagy inducers in epithelial cells carrying the ΔF508 mutation of the cystic fibrosis transmembrane conductance regulator CFTR. [Journal Article]
- CDCell Death Dis 2018 Feb 07; 9(2):191
- Cystic Fibrosis (CF) due to the ΔF508 mutation of cystic fibrosis transmembrane conductance regulator (CFTR) can be treated with a combination of cysteamine and Epigallocatechin gallate (EGCG). Since...
Cystic Fibrosis (CF) due to the ΔF508 mutation of cystic fibrosis transmembrane conductance regulator (CFTR) can be treated with a combination of cysteamine and Epigallocatechin gallate (EGCG). Since ECGC is not a clinically approved drug, we attempted to identify other compounds that might favourably interact with cysteamine to induce autophagy and thus rescuing the function of ΔF508 CFTR as a chloride channel in the plasma membrane. For this, we screened a compound library composed by chemically diverse autophagy inducers for their ability to enhance autophagic flux in the presence of cysteamine. We identified the antiarrhythmic Ca2+channel blocker amiodarone, as an FDA-approved drug having the property to cooperate with cysteamine to stimulate autophagy in an additive manner. Amiodarone promoted the re-expression of ΔF508 CFTR protein in the plasma membrane of respiratory epithelial cells. Hence, amiodarone might be yet another compound for the etiological therapy of CF in patients bearing the ΔF508 CFTR mutation.
- Whorl pattern keratopathies in veterinary and human patients. [Journal Article]
- VOVet Ophthalmol 2018 Feb 06
- The course travelled by corneal epithelial cells from their stem cell niche at the limbus toward the vertex of the cornea is normally not evident due to their transparency, but in certain conditions,...
The course travelled by corneal epithelial cells from their stem cell niche at the limbus toward the vertex of the cornea is normally not evident due to their transparency, but in certain conditions, the epithelial cells can be rendered visible to the clinician. In such cases, the pathway taken by epithelial cells can manifest as a whorl pattern described using a variety of terms including hurricane keratitis/keratopathy, vortex keratopathy, whorl keratopathy, cornea verticillata, and at times, named after causative agents as exemplified by amiodarone keratopathy. Here, we briefly discuss the terminology used and the spectrum of conditions that can result in keratopathies with whorl patterns in human patients. We review the manifestations of such patterns in veterinary patients and discuss the state of understanding of the underlying forces that create the whorl distribution of epithelial cells on the ocular surface.
- [Update Ventricular Tachycardia]. [Journal Article]
- DMDtsch Med Wochenschr 2018; 143(3):165-168
- Idiopathic ventricular tachycardia: Frequent monomorphic premature ventricular contractions or non-sustained ventricular tachycardia without underlying structural heart disease is not a rare conditio...
Idiopathic ventricular tachycardia: Frequent monomorphic premature ventricular contractions or non-sustained ventricular tachycardia without underlying structural heart disease is not a rare condition and may cause significant symptoms. A subgroup of patients develops IVT-associated cardiomyopathy. Current ESC guidelines recommend primary catheter ablation in symptomatic patients with right ventricular outflow tract IVT. Catheter ablation is also recommended in symptomatic patients with a left ventricular outflow tract (or other rare) origin, if antiarrhythmic drugs are ineffective or not desired.Ventricular tachycardia associated with structural heart disease: Scar-associated ventricular arrhythmias may cause sudden cardiac death in a variety of heart diseases. While ICD implantation has been shown to reduce mortality, repetitive ICD shocks impact on survival and quality of life. In a recent meta-analysis, both amiodarone and catheter ablation reduce the incidence of recurrent ICD shocks. Discontinuation of amiodarone due to side effects is common. Current ESC guidelines recommend both strategies (class 1 indication). Catheter ablation is also recommended in drug-resistant VT or electrical storm. A totally subcutaneous ICD is a novel option in patients not requiring pacing.
- Thyroid Hormone Receptor Antagonists: From Environmental Pollution to Novel Small Molecules. [Journal Article]
- VHVitam Horm 2018; 106:147-162
- Thyroid hormone receptors (TRs) are nuclear receptors which control transcription, and thereby have effects in all cells within the body. TRs are an important regulator in many basic physiological pr...
Thyroid hormone receptors (TRs) are nuclear receptors which control transcription, and thereby have effects in all cells within the body. TRs are an important regulator in many basic physiological processes including development, growth, metabolism, and cardiac function. The hyperthyroid condition results from an over production of thyroid hormones resulting in a continual stimulation of thyroid receptors which is detrimental for the patient. Therapies for hyperthyroidism are available, but there is a need for new small molecules that act as TR antagonists to treat hyperthyroidism. Many compounds exhibit TR antagonism and are considered detrimental to health. Some drugs in the clinic (most importantly, amiodarone) and environmental pollution exhibit TR antagonist properties and thus have the potential to induce hypothyroidism in some people. This chapter provides an overview of novel small molecules that have been specifically designed or screened for their TR antagonist activity as novel treatments for hyperthyroidism. While novel compounds have been identified, to date none have been developed sufficiently to enter clinical trials. Furthermore, a discussion on other sources of TR antagonists is discussed in terms of side effects of current drugs in the clinic as well as environmental pollution.
- DNA damage-induced apoptosis and mitogen-activated protein kinase pathway contribute to the toxicity of dronedarone in hepatic cells. [Journal Article]
- EMEnviron Mol Mutagen 2018 Feb 05
- Dronedarone, an antiarrhythmic drug, has been marketed as an alternative to amiodarone. The use of dronedarone has been associated with severe liver injury; however, the mechanisms remain unclear. In...
Dronedarone, an antiarrhythmic drug, has been marketed as an alternative to amiodarone. The use of dronedarone has been associated with severe liver injury; however, the mechanisms remain unclear. In this study, the possible mechanisms of dronedarone induced liver toxicity were characterized in HepG2 cells. Dronedarone decreased cells viability and induced apoptosis and DNA damage in a concentration- and time-dependent manner. Pretreatment of the HepG2 cells with apoptosis inhibitors (caspase-3, -8, and -9) or the necrosis inhibitor (Necrox-5), partially, but significantly, reduced the release of lactate dehydrogenase. Dronedarone caused the release of cytochrome c from mitochondria to cytosol, a prominent feature of apoptosis. In addition, the activation of caspase-2 was involved in dronedarone induced DNA damage and the activation of JNK and p38 signaling pathways. Inhibition of JNK and p38 by specific inhibitors attenuated dronedarone-induced cell death, apoptosis, and DNA damage. Additionally, suppression of caspase-2 decreased the activities of JNK and p38. Dronedarone triggered DNA damage was regulated by downregulation of topoisomerase IIα at both transcriptional and post-transcriptional levels. Taken together, our data show that DNA damage, apoptosis, and the activation of JNK and p38 contribute to dronedarone-induced cytotoxicity. Environ. Mol. Mutagen., 2018. © 2018 Wiley Periodicals, Inc.
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