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Turk Kardiyoloji Dernegi Arsivi : Turk... Apr 2015Hyponatremia is the most prevalent electrolyte imbalance, and may be present in up to 30% of hospitalized patients. It is an important predictor of in-hospital... (Review)
Review
Hyponatremia is the most prevalent electrolyte imbalance, and may be present in up to 30% of hospitalized patients. It is an important predictor of in-hospital mortality. Irrespective of the reason underlying hyponatremia, water metabolism plays an important role. Arginine-vasopressin, which has cardiovascular effects and plays a role in water metabolism, is released from the posterior hypothalamus in response to an increase in plasma osmolality or a drop in the blood pressure, which are detected by osmoreceptors and baroreceptors respectively. Arginine-vasopressin has receptors located on vascular smooth muscle cells, the heart (V1a), the collecting ducts of the renal medulla (V2), the anterior pituitary gland (V1b) and many other organs. Arginine-vasopressin antagonists, known as "vaptans", have recently attracted attention for the treatment of chronic hypotonic hyponatremia. In this review, we focus on the diagnosis and classification of hyponatremia, current trends in its treatment in the light of guidelines, and the rationale of using vaptans in treating hyponatremia. We also briefly review cornerstone studies in the literature regarding vaptans, and the correct indications, contraindications and cautions in the use of "tolvaptan" and "conivaptan", two approved vaptans for this indication.
Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Contraindications; Humans; Hyponatremia; Tolvaptan
PubMed: 25906004
DOI: 10.5543/tkda.2015.71508 -
Monaldi Archives For Chest Disease =... Mar 2013The morbidity and mortality rates attributed to smoking are substantial and cigarette smoke remains the first preventable cause of premature death worldwide. Despite the... (Review)
Review
The morbidity and mortality rates attributed to smoking are substantial and cigarette smoke remains the first preventable cause of premature death worldwide. Despite the knowledge of the adverse consequences of smoking, many smokers struggle to quit. Cigarette smoking is the primary cause of chronic obstructive pulmonary disease, and smoking cessation represents the most effective way of stopping its progression. Varenicline is one of the first-line smoking cessation aids recommended in many Clinical Practice Guidelines and its efficacy and safety have been demonstrated in several clinical trials. Varenicline has a unique mechanism of action and clinical trials support its use as an effective and generally well-tolerated therapy. This article reviews the clinical pharmacological trials on smoking cessation published in recent years on varenicline, with particular attention to the outcomes used in the studies. MedLine, the Cochrane database and Embase were evaluated. Almost all the trials have, as a primary endpoint, the abstinence from cigarettes at 9-12 weeks of treatment. Only one study considers lung function spirometric changes as a secondary endpoint. No study has evaluated lung function. This marker could be very important as a way of evaluating, objectively, an improvement in lung function, which correlates also with subjective parameters, as dyspnea and fatigue.
Topics: Benzazepines; Clinical Trials as Topic; Humans; Lung; Nicotinic Agonists; Outcome Assessment, Health Care; Quinoxalines; Smoking; Smoking Cessation; Varenicline
PubMed: 23741942
DOI: 10.4081/monaldi.2013.105 -
Expert Opinion on Pharmacotherapy Aug 2011This review examines the postmarketing experience with varenicline, including case reports, newer clinical trials and secondary analyses of large clinical datasets. (Comparative Study)
Comparative Study Review
INTRODUCTION
This review examines the postmarketing experience with varenicline, including case reports, newer clinical trials and secondary analyses of large clinical datasets.
AREAS COVERED
Varenicline has been shown to be an effective treatment in a broad range of tobacco users with medical, behavioral and diverse demographic characteristics. Recent studies finding excellent safety and efficacy in groups of smokers with diseases including chronic obstructive pulmonary disease are particularly encouraging and call for increased use of this medication for smoking cessation. Despite case reports of serious neuropsychiatric symptoms in patients taking varenicline, including changes in behavior and mood, causality has not been established. Recent analyses of large datasets from clinical trials have not demonstrated that varenicline is associated with more depression or suicidality than other treatments for smoking cessation.
EXPERT OPINION
Now that additional clinical trials in specific populations and observational studies on treatment-seeking smokers outside of clinical trials have been published, we can be confident that varenicline remains the most efficacious monotherapy for smoking cessation and that its side-effect profile remains good. The risk-to-benefit ratio of receiving varenicline to quit smoking must include the increased chances of quitting smoking and avoiding the sizeable risks of smoked-caused disease and death that remain if tobacco addiction is not properly treated.
Topics: Animals; Benzazepines; Humans; Nicotine; Nicotinic Agonists; Quinoxalines; Smoking Cessation; Tobacco Use Cessation; Tobacco Use Disorder; Tobacco, Smokeless; Varenicline
PubMed: 21644843
DOI: 10.1517/14656566.2011.587121 -
Drug Design, Development and Therapy 2014Elevated heart rate could negatively influence cardiovascular risk in the general population. It can induce and promote the atherosclerotic process by means of several... (Review)
Review
Elevated heart rate could negatively influence cardiovascular risk in the general population. It can induce and promote the atherosclerotic process by means of several mechanisms involving endothelial shear stress and biochemical activities. Furthermore, elevated heart rate can directly increase heart ischemic conditions because of its skill in unbalancing demand/supply of oxygen and decreasing the diastolic period. Thus, many pharmacological treatments have been proposed in order to reduce heart rate and ameliorate the cardiovascular risk profile of individuals, especially those suffering from coronary artery diseases (CAD) and chronic heart failure (CHF). Ivabradine is the first pure heart rate reductive drug approved and currently used in humans, created in order to selectively reduce sinus node function and to overcome the many side effects of similar pharmacological tools (ie, β-blockers or calcium channel antagonists). The aim of our review is to evaluate the role and the safety of this molecule on CAD and CHF therapeutic strategies.
Topics: Animals; Benzazepines; Coronary Artery Disease; Heart Failure; Heart Rate; Humans; Ivabradine
PubMed: 24940047
DOI: 10.2147/DDDT.S60591 -
Advances in Pharmacology (San Diego,... 2014Despite the proven efficacy of current pharmacotherapies for tobacco dependence, relapse rates continue to be high, indicating that novel medications are needed.... (Review)
Review
Despite the proven efficacy of current pharmacotherapies for tobacco dependence, relapse rates continue to be high, indicating that novel medications are needed. Currently, several smoking cessation agents are available, including varenicline (Chantix®), bupropion (Zyban®), and cytisine (Tabex®). Varenicline and cytisine are partial agonists at the α4β2* nicotinic acetylcholine receptor (nAChR). Bupropion is an antidepressant but is also an antagonist at α3β2* ganglionic nAChRs. The rewarding effects of nicotine are mediated, in part, by nicotine-evoked dopamine (DA) release leading to sensitization, which is associated with repeated nicotine administration and nicotine addiction. Receptor antagonists that selectivity target central nAChR subtypes mediating nicotine-evoked DA release should have efficacy as tobacco use cessation agents with the therapeutic advantage of a limited side-effect profile. While α-conotoxin MII (α-CtxMII)-insensitive nAChRs (e.g., α4β2*) contribute to nicotine-evoked DA release, these nAChRs are widely distributed in the brain, and inhibition of these receptors may lead to nonselective and untoward effects. In contrast, α-CtxMII-sensitive nAChRs mediating nicotine-evoked DA release offer an advantage as targets for smoking cessation, due to their more restricted localization primarily to dopaminergic neurons. Small drug-like molecules that are selective antagonists at α-CtxMII-sensitive nAChR subtypes that contain α6 and β2 subunits have now been identified. Early research identified a variety of quaternary ammonium analogs that were potent and selective antagonists at nAChRs mediating nicotine-evoked DA release. More recent data have shown that novel, nonquaternary bis-1,2,5,6-tetrahydropyridine analogs potently inhibit (IC50<1nM) nicotine-evoked DA release in vitro by acting as antagonists at α-CtxMII-sensitive nAChR subtypes; these compounds also decrease NIC self-administration in rats.
Topics: Animals; Benzazepines; Dose-Response Relationship, Drug; Humans; Nicotinic Antagonists; Quinoxalines; Receptors, Nicotinic; Smoking; Tobacco Use Disorder; Treatment Outcome; Varenicline
PubMed: 24484986
DOI: 10.1016/B978-0-12-420118-7.00013-5 -
Canadian Family Physician Medecin de... Oct 2021An adolescent who smokes regularly came to my clinic for help quitting. While I am aware that bupropion is a first-line medication for smoking cessation among adults, is...
QUESTION
An adolescent who smokes regularly came to my clinic for help quitting. While I am aware that bupropion is a first-line medication for smoking cessation among adults, is it effective and safe for adolescents?
ANSWER
Most adolescent smokers in Canada would like to quit, but more than 90% of the attempts are unsuccessful. Bupropion appears to be more effective than other pharmacologic options in improving abstinence among adolescents who smoke in the short term; however, it is not approved by Health Canada for those younger than 18 years. Bupropion has not been associated with an increase in adverse events in smoking cessation trials. More research is needed on the long-term effectiveness and safety of bupropion in this population.
Topics: Adolescent; Adult; Benzazepines; Bupropion; Humans; Nicotinic Agonists; Quinoxalines; Smoking Cessation; Varenicline
PubMed: 34649897
DOI: 10.46747/cfp.6710743 -
Circulation Journal : Official Journal... Apr 2017
Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Diuretics; Furosemide; Heart Failure; Humans; Renal Insufficiency, Chronic; Tolvaptan
PubMed: 28420818
DOI: 10.1253/circj.CJ-17-0311 -
Revue Medicale de Liege Apr 2008Ivabradine (Procoralan), a new If inhibitor which acts specifically and in a dose-dependent manner on the pacemaker activity of the sinoatrial node, is a pure heart rate...
Ivabradine (Procoralan), a new If inhibitor which acts specifically and in a dose-dependent manner on the pacemaker activity of the sinoatrial node, is a pure heart rate lowering agent. It slows the diastolic depolarization slope of sinoatrial node cells and reduces heart rate at rest and during exercise. It has shown anti-ischaemic and anti-anginal activity at recommended doses of 5 and 7.5 mg bid in patients with stable angina. Ivabradine is as effective as atenolol and amlodipine to prevent or attenuate exercise-induced ischaemia in these patients. It is well tolerated, with transient visual symptoms being the main drug-related adverse event. These symptoms may be linked to the presence in the retina of ion channels similar to cardiac If channels and did not adversely affect the tolerability of the drug for most patients. In Belgium, ivabradine is currently reimbursed in patients with stable angina and normal sinus rhythm who do not tolerate beta-blockers and non-dihydropyridine calcium antagonists or in whom these treatments are contra-indicated.
Topics: Arrhythmias, Cardiac; Benzazepines; Exercise; Heart Rate; Humans; Ischemia; Ivabradine
PubMed: 18575078
DOI: No ID Found -
International Heart Journal Feb 2017The vasopressin receptor 2 (V2) receptor antagonist tolvaptan is an aquaretic agent that has been approved for heart failure patients with volume overload in Japan. In...
The vasopressin receptor 2 (V2) receptor antagonist tolvaptan is an aquaretic agent that has been approved for heart failure patients with volume overload in Japan. In this study (SMILE study), we investigated patient characteristics and effectiveness in both a 14 days and shorter treated group (14DS) and 15 days and longer treated group (15DL). The results showed that the patients in the 15DL group had low cardiac output with intensive diuretic administration (ie, diuretic resistance). The congestive symptoms were greatly improved within 14 days of treatment in both the 14DS and 15DL groups. Further improvements in lower limb edema, pulmonary congestion, dyspnea, third sound, and rales after 2 weeks were statistically significant in the 15DL group, but the amount of improvement was subtle and the 15DL group might have consisted of a considerable number of "non-responders". Therefore, identifying "responders" by biomarkers and conducting a prospective randomized study is required to validate our findings.
Topics: Aged; Aged, 80 and over; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Female; Heart Failure; Humans; Male; Middle Aged; Product Surveillance, Postmarketing; Prospective Studies; Tolvaptan; Treatment Outcome
PubMed: 28111410
DOI: 10.1536/ihj.16-249 -
European Journal of Heart Failure Oct 2017Heart rate (HR) is associated with cardiovascular outcomes in all the stages of the cardiovascular continuum as well as in patients with pulmonary, cerebrovascular, and... (Review)
Review
Heart rate (HR) is associated with cardiovascular outcomes in all the stages of the cardiovascular continuum as well as in patients with pulmonary, cerebrovascular, and renal disease, sepsis, cancer, and erectile dysfunction. In patients with cardiovascular disease, but also in the general population, increased HR represents an important indicator of mortality with each acceleration of HR over 70 b.p.m. increasing the risk. In patients in sinus rhythm with chronic heart failure with reduced ejection fraction (HFrEF), a HR >70 b.p.m. increased the risk of hospitalization, and >75 b.p.m. the risk of cardiovascular death as shown in the Systolic Heart Failure Treatment with the I Inhibitor Ivabradine Trial (SHIFT). Reducing HR with ivabradine by 11 b.p.m. (placebo-controlled) reduced the primary composite endpoint (cardiovascular death and hospitalization for worsening heart failure). Ivabradine was well tolerated showing benefit irrespective of age or diabetes status, and also in the presence of low systolic blood pressure and severe heart failure (SHIFT trial). Therefore, HR qualifies as a modifiable risk factor in heart failure. In patients with stable coronary disease, HR is a risk marker but HR reduction with ivabradine does not improve outcomes. The role of selective HR lowering remains unclear in patients with pulmonary, renal, cerebrovascular, and other diseases, as the potential benefit of interventions on HR has not been explored in these conditions. Future studies should scrutinize if HR reduction improves outcomes, defining HR as a potential risk factor and therapeutic target in other conditions beyond heart failure.
Topics: Benzazepines; Cardiovascular Agents; Chronic Disease; Heart Failure; Heart Rate; Humans; Ivabradine; Prognosis; Risk Factors
PubMed: 28627045
DOI: 10.1002/ejhf.902