scholarly journals Risk of drug-induced cardiac arrhythmia during COVID-19 therapeutic treatment

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Antonio Vitiello ◽  
Francesco Ferrara
Keyword(s):  
Cardiac Electrophysiology ◽  
Adverse Reactions ◽  
Short Review ◽  
Therapeutic Treatment ◽  
Cardiac Damage ◽  
Long Qt ◽  
Drug Induced ◽  
Pharmacological Agents ◽  
Increased Risk ◽  
Pharmacologic Agents

AbstractTherapeutic treatment of severe COVID-19 infection involves the administration of multiple pharmacologic agents to reduce the risk of serious complications; this may result in drug interactions and possible adverse reactions and induced cardiotoxicity. The risk–benefit ratio associated with the use of medications to treat COVID-19 should be carefully monitored. In addition, the severe COVID-19 patient may experience cardiac damage, and alteration of normal cardiac electrophysiology function. Severe COVID-19 with cardiac involvement and the risk of drug-induced adverse reactions may cause cardiac arrhythmias, including long qt syndrome, which in some cases may lead to sudden death. In this short review we briefly review the pharmacological agents used to treat severe COVID-19 with increased risk of causing long qt forms.

scholarly journals Spotlight on endothelial progenitor cell inhibitors: short review

2005 ◽  
Vol 10 (1_suppl) ◽  
pp. S59-S64 ◽  
Author(s):  
Thomas Thum ◽  
Johann Bauersachs
Keyword(s):  
Drug Targets ◽  
Short Review ◽  
Systemic Circulation ◽  
Endothelial Progenitor ◽  
Drug Induced ◽  
Molecular Events ◽  
Increased Risk ◽  
Novel Drugs ◽  
Bone Marrow Derived Cells ◽  
Artery Disease

Endothelial progenitor cells (EPCs) are bone-marrow-derived cells that enter the systemic circulation to replace defective or injured mature endothelial cells. EPCs also contribute to neovascularization and limit the progression of atherosclero sis. Patients with reduced EPC levels or dysfunctional EPCs are at increased risk for coronary artery disease. Drug-mediated improvement of the mobilization, differenti ation, function and homing of EPCs to sites of ischemia or injured endothelium may therefore be a promising novel therapeutic approach for various cardiovascular dis eases. On the other hand, endogenous inhibitors of EPCs could also be valuable drug targets. The identification of EPC inhibitors and the development of novel drugs that can efficiently regulate production or elimination of these molecules may also be a promising approach for the future treatment of atherosclerosis. In the present review we summarize potential endogenous and exogenous inhibitors of EPCs, such as oxidized low-density lipoproteins, angiotensin II, glucose, cigarette smoke and others. Whenever possible, we also describe the underlying molecular events. Drug- induced mobilization and improvement of EPC function, as well as reduction of EPC inhibitors, is likely to enhance endothelial function and reduce atherosclerotic processes.

scholarly journals Spotlight on endothelial progenitor cell inhibitors: short review

2005 ◽  
Vol 10 (2_suppl) ◽  
pp. S59-S64 ◽  
Author(s):  
Thomas Thum ◽  
Johann Bauersachs
Keyword(s):  
Drug Targets ◽  
Short Review ◽  
Systemic Circulation ◽  
Endothelial Progenitor ◽  
Drug Induced ◽  
Molecular Events ◽  
Increased Risk ◽  
Novel Drugs ◽  
Bone Marrow Derived Cells ◽  
Artery Disease

Endothelial progenitor cells (EPCs) are bone-marrow-derived cells that enter the systemic circulation to replace defective or injured mature endothelial cells. EPCs also contribute to neovascularization and limit the progression of atherosclerosis. Patients with reduced EPC levels or dysfunctional EPCs are at increased risk for coronary artery disease. Drug-mediated improvement of the mobilization, differentiation, function and homing of EPCs to sites of ischemia or injured endothelium may therefore be a promising novel therapeutic approach for various cardiovascular diseases. On the other hand, endogenous inhibitors of EPCs could also be valuable drug targets. The identification of EPC inhibitors and the development of novel drugs that can efficiently regulate production or elimination of these molecules may also be a promising approach for the future treatment of atherosclerosis. In the present review we summarize potential endogenous and exogenous inhibitors of EPCs, such as oxidized low-density lipoproteins, angiotensin II, glucose, cigarette smoke and others. Whenever possible, we also describe the underlying molecular events. Drug-induced mobilization and improvement of EPC function, as well as reduction of EPC inhibitors, is likely to enhance endothelial function and reduce atherosclerotic processes.

scholarly journals HLA-DRB1*08:02 Is Associated with Bucillamine-Induced Proteinuria in Japanese Rheumatoid Arthritis Patients

2014 ◽  
Vol 9 ◽  
pp. BMI.S13654 ◽  
Author(s):  
Hiroshi Furukawa ◽  
Shomi Oka ◽  
Kota Shimada ◽  
Shoji Sugii ◽  
Atsushi Hashimoto ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Reactions ◽  
Drug Hypersensitivity ◽  
Human Leukocyte ◽  
Drug Induced ◽  
Leukocyte Antigen ◽  
Increased Risk ◽  
Gold Salts ◽  
Drug Hypersensitivity Reaction ◽  
Preliminary Study

Background Drug-induced proteinuria can occur in rheumatoid arthritis (RA) patients treated with d-penicillamine, gold salts, or bucillamine (Buc), and represents a drug hypersensitivity reaction. Striking associations of human leukocyte antigen (HLA) alleles with adverse reactions have recently been reported for many drugs. Methods We investigated the association of HLA class II with Buc-induced proteinuria (BI-Pro) in 485 Japanese RA patients treated with Buc, of whom 25 had developed BI-Pro. Results and Conclusion This preliminary study showed a highly significant association of DRB1*08:02 with BI-Pro ( P = 1.09 × 10−6, corrected P [ Pc] = 1.96 × 10−5, odds ratio [OR] 25.17, 95% confidence interval [CI] 7.98-79.38). DQB1*04:02 was also significantly associated with increased risk of BI-Pro ( P = 2.44 × 10−5, Pc = 2.69 × 10−4, OR 10.35, 95%CI 3.99–26.83). These findings provide useful information for promoting personalized medicine for RA.

scholarly journals Female Gender as a Risk Factor for the Development of Drug-Induced Diseases

2021 ◽  
Vol 9 (2) ◽  
pp. 85-94
Author(s):  
D. A. Sychev ◽  
O. D. Ostroumova ◽  
A. P. Pereverzev ◽  
A. I. Kochetkov ◽  
T. M. Ostroumova ◽  
...  
Keyword(s):  
Sex Steroids ◽  
Adverse Reactions ◽  
Volume Of Distribution ◽  
The Body ◽  
Lower Percentage ◽  
Cytochrome P450 Enzymes ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Protein Activity ◽  
Drug Induced ◽  
Increased Risk

Gender is an important factor affecting the risk of drug-induced adverse reactions in patients. According to scientific literature, the risk of drug-induced symptoms, syndromes, and diseases is 1.5–1.7 times higher in women than in men. The aim of the study was to analyse and systematise data on the factors responsible for increased risk of drug-induced diseases in women. It was demonstrated that the increased risk of complications in women following the use of certain pharmacological classes of drugs is associated with a combination of factors that affect pharmacokinetics and pharmacodynamics. These factors include anatomical and physiological characteristics, specificity of enzyme and transport protein activity/expression. Women, compared to men, have higher percentage of adipose tissue and lower percentage of water in the body, which affects the volume of distribution of lipophilic agents, such as opioids and benzodiazepines, resulting in their accumulation in the body. Women have a lower rate of renal excretion and elimination, as compared to men, which may lead to adverse reactions following the use of medicines with predominantly urinary excretion. Changes in the endocrine profile in women taking sex steroids as replacement therapy or a contraceptive measure, as well as fluctuations in endogenous sex steroids during the menstrual cycle, pregnancy, perimenopause, influence the volume of distribution, the activity of cytochrome P450 enzymes, and the glomerular filtration rate, and, thus, may affect the pharmacokinetics and pharmacodynamics of other medicinal products, which, in turn, affect the safety of pharmacotherapy. In order to increase the safety of pharmacotherapy in women, it is necessary to consider the revealed specific pharmacokinetic and pharmacodynamic parameters of the medicine in a given group of patients when selecting the treatment regimen, including the dosage regimen and routes of administration.

Obstructive respiratory events transiently impair electromechanical coupling and increase premature ventricular contraction rate in a drug-induced Long-QT-2 pig model

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Linz ◽  
M Flethoj Madsen ◽  
M Hotbjerg Hansen ◽  
E Melis Hesselkilde ◽  
A Saljic ◽  
...  
Keyword(s):  
Electromechanical Coupling ◽  
Left Ventricular ◽  
Ventricular Repolarization ◽  
Funding Source ◽  
Long Qt ◽  
Drug Induced ◽  
Premature Ventricular Contractions ◽  
Respiratory Events ◽  
Obstructive Sleep ◽  
Increased Risk

Abstract Background Obstructive sleep apnea (OSA) is characterized by intermittent negative thoracic pressure fluctuations and intermittent hypoxemic events. Recent findings associate OSA with impaired ventricular repolarization during sleep and increased risk of sudden cardiac death, which may have special implications for Long-QT-2-syndrome patients. Therefore, we elucidated changes in ventricular repolarization and electromechanical coupling (electromechanical window; EMW) during either obstructive respiratory events simulated by intermittent negative upper airway pressure (INAP) or hypoxemic events simulated by intermittent hypoxia (IH) in vehicle (VEH) and dofetilide (DOF) treated pigs, as a simulation of drug induced Long-QT-2 syndrome. Methods In sedated spontaneously breathing pigs, either VEH or DOF (50 μg/kg) was perfused and INAP was applied by a negative pressure device connected to the intubation tube. For IH-application the device was connected and left turned off. INAP or IH was maintained for 75 seconds followed by a ten-minute resting period. In order to evaluate the electromechanical window, the time difference between electrical (QT-duration) and mechanical systole (Q-wave to the end of left ventricular pressure signal, QLVPend) was measured before (pre-INAP/-IH), during and 60 seconds after INAP/IH (post-INAP/-IH). Incidence rates of premature ventricular contractions (PVC) and ventricular tachycardia were compared pre- to post-INAP/-IH. Results In VEH-pigs, EMW shortened throughout INAP and post-INAP periods steadily (VEH: pre-INAP: 81.69±2.31ms; INAP: 55.65±6.13ms; post-INAP: 38±8.89ms. p=0.008). EMW shortening during post-INAP was associated with an increase in PVCs (VEH: pre-INAP 5.41±1.87 vs. post-INAP 26.5±8.15; p=0.04). In DOF-pigs, INAP-associated EMW-shortening was further potentiated (DOF: pre-INAP: 61.16±7.18ms; INAP: 38.09±9.84ms; post-INAP: 14.93±9.24ms. p=0.016), which was associated with an increase in PVCs (DOF: pre-INAP 4.75±2.36 vs. post-INAP 36.58±10.92; p=0.017). Administration of Atenolol could prevent post-INAP shortening of the EMW and decrease counts of premature ventricular contractions. While desaturations were comparable in INAP and IH, IH did not result in EMW-shortening or increased arrhythmia risk. Conclusion Transient dissociation of the ventricular electromechanical coupling during a simulated obstructive apnea, but not during IH, creates a dynamic and sympathetically driven arrhythmogenic substrate. Apnea associated ventricular electromechanical uncoupling was aggravated in a drug-induced Long-QT-2 simulation. Whether OSA represents a modifiable arrhythmogenic risk factor in Long-QT-2-patients warrants further studies. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Novo nordisk fonden

Subclinical Thyroid Dysfunction and the Risk of Cardiovascular Disease

2020 ◽  
Vol 26 (43) ◽  
pp. 5617-5627
Author(s):  
Mirjana Stojković ◽  
Miloš Žarković
Keyword(s):  
Cardiovascular Disease ◽  
Risk Factor ◽  
Cardiac Electrophysiology ◽  
Vascular System ◽  
Density Lipoprotein ◽  
Thyroid Stimulating Hormone ◽  
Normal Limits ◽  
Developing Heart ◽  
Treatment Indications ◽  
Increased Risk

The prevalence of subclinical hypothyroidism (SH) is 3-10%. The prevalence of subclinical hyperthyroidism (SHr) is 0.7-9.7%. Thyroid hormones affect cardiac electrophysiology, contractility, and vasculature. SH is associated with an increased risk of coronary heart disease (CHD), especially in subjects under 65. SHr seems to be associated with a slightly increased risk of CHD and an increase in CHD-related mortality. Both SH and SHr carry an increased risk of developing heart failure (HF), especially in those under 65. Both SH and SHr are associated with worse prognoses in patients with existing HF. SH is probably not associated with atrial fibrillation (AF). SHr, low normal thyroid-stimulating hormone (TSH) and high normal free thyroxine (FT4) are all associated with the increased risk of AF. An association between endothelial dysfunction and SH seems to exist. Data regarding the influence of SHr on the peripheral vascular system are conflicting. SH is a risk factor for stroke in subjects under 65. SHr does not increase the risk of stroke. Both SH and SHr have an unfavourable effect on cardiovascular disease (CVD) and all-cause mortality. There is a U-shaped curve of mortality in relation to TSH concentrations. A major factor that modifies the relation between subclinical thyroid disease (SCTD) and mortality is age. SH increases blood pressure (BP). SHr has no significant effect on BP. Lipids are increased in patients with SH. In SHr, high-density lipoprotein cholesterol and lipoprotein( a) are increased. SCTD should be treated when TSH is over 10 mU/l or under 0.1 mU/l. Treatment indications are less clear when TSH is between normal limits and 0.1 or 10 mU/L. The current state of knowledge supports the understanding of SCTD’s role as a risk factor for CVD development. Age is a significant confounding factor, probably due to age-associated changes in the TSH reference levels.

Genetic susceptibilities and prediction modeling of carbamazepine and allopurinol-induced severe cutaneous adverse reactions in Vietnamese

2020 ◽  
Author(s):  
Dinh van Nguyen ◽  
Hieu Chi Chu ◽  
Christopher Vidal ◽  
Richard B Fulton ◽  
Nguyet Nhu Nguyen ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Surrogate Marker ◽  
Hypersensitivity Syndrome ◽  
Stevens Johnson Syndrome ◽  
Strongly Correlated ◽  
Drug Induced ◽  
Johnson Syndrome ◽  
Severe Cutaneous Adverse Reactions ◽  
Systemic Symptoms ◽  
Cutaneous Adverse Reactions

Aims: To determine genetic susceptibility markers for carbamazepine (CBZ) and allopurinol-induced severe cutaneous adverse reactions (SCARs) in Vietnamese. Methods: A case control study was performed involving 122 patients with CBZ or allopurinol induced SCARs and 120 drug tolerant controls. Results: HLA-B*58:01 was strongly associated with allopurinol-induced SCARs and strongly correlated with SNP rs9263726. HLA-B*15:02 was associated with CBZ-induced Stevens–Johnson syndrome/toxic epidermal necrolysis but not with drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms. No association was found between HLA-A*31:01 and CBZ-induced SCARs. HLA-B*58:01 and rs3909184 allele A with renal insufficiency were shown to increase the risk of allopurinol-induced SCARs. Conclusion: HLA-B*58:01 and HLA-B*15:02 confer susceptibility to allopurinol-induced SCARs and CBZ-induced SJS/TEN in Vietnamese. Single nucleotide polymorphism rs9263726 can be used as a surrogate marker in identifying HLA-B*58:01.

scholarly journals Bittersweet: infective complications of drug-induced glycosuria in patients with diabetes mellitus on SGLT2-inhibitors: two case reports

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Caroline Bartolo ◽  
Victoria Hall ◽  
N. Deborah Friedman ◽  
Chloe Lanyon ◽  
Andrew Fuller ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Fungal Infections ◽  
Case Reports ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Urogenital Tract ◽  
Hypoglycemic Agents ◽  
Drug Induced ◽  
First Case ◽  
Increased Risk

Abstract Background Sodium-glucose co-transporter 2 (SGLT2) inhibitors are novel hypoglycemic agents which reduce reabsorption of glucose at the renal proximal tubule, resulting in significant glycosuria and increased risk of genital mycotic infections (GMI). These infections are typically not severe as reported in large systematic reviews and meta-analyses of the medications. These reviews have also demonstrated significant cardiovascular benefits through other mechanisms of action, making them attractive options for the management of Type 2 diabetes mellitus (T2DM). We present two cases with underlying abnormalities of the urogenital tract in which the GMI were complicated and necessitated cessation of the SGLT2 inhibitor. Case presentations Both cases are patients with T2DM on empagliflozin, an SGLT2 inhibitor. The first case is a 64 year old man with Candida albicans balanitis and candidemia who was found to have an obstructing renal calculus and prostatic abscess requiring operative management. The second case describes a 72 year old man with Candida glabrata candidemia who was found to have prostatomegaly, balanitis xerotica obliterans with significant urethral stricture and bladder diverticulae. His treatment was more complex due to fluconazole resistance and concerns about urinary tract penetration of other antifungals. Both patients recovered following prolonged courses of antifungal therapy and in both cases the SGLT2 inhibitor was ceased. Conclusions Despite their cardiovascular benefits, SGLT2 inhibitors can be associated with complicated fungal infections including candidemia and patients with anatomical abnormalities of the urogenital tract may be more susceptible to these infections as demonstrated in these cases. Clinicians should be aware of their mechanism of action and associated risk of infection and prior to prescription, assessment of urogenital anatomical abnormalities should be performed to identify patients who may be at risk of complicated infection.

scholarly journals Elucidating the role of Cavin1 in drug-induced long QT syndrome (diLQTS)

2021 ◽  
Vol 13 (2) ◽  
pp. 228-229
Author(s):  
Z. Al Sayed ◽  
C. Pereira ◽  
C. Jouve ◽  
J. Hulot
Keyword(s):  
Long Qt Syndrome ◽  
Long Qt ◽  
Drug Induced ◽  
Qt Syndrome
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