Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atrial fibrillation is a well-known heart disease in horses. The common therapy consists of administration of quinidine. More potent antiarrhythmic drugs have become available for human therapy and the use of these as alternatives to quinidine for equine antiarrhythmic therapy is a matter of interest. Amiodarone (AMD) is used in human medicine for treatment of many arrhythmias, including atrial fibrillation. Its disposition in horses has not yet been investigated. The purpose of this study was to measure the effect of single intravenous doses of amiodarone (5 and 7 mg/kg) on the surface electrocardiogram (ECG) of healthy minishetland ponies during the first 2 days after drug administration and to calculate pharmacokinetic parameters with a physiologically based pharmacokinetic model (PBPK) using amiodarone and desethylamiodarone (DAMD) plasma levels that were determined by high-performance liquid chromatography (HPLC). As expected for a K(+)-channel-blocker, the main effect on the measured ECG could be seen on the ventricular complex, as the QT interval and the T wave showed statistically significant alterations. The doses investigated were well tolerated clinically. Results from the pharmacokinetic model were found to compare well with literature data of rats, dogs, and humans. It showed a rapid distribution in the tissue, beginning with the rapidly perfused tissue, like the heart, followed by slowly perfused tissues, and finally an accumulation in fat. The half-life for total elimination was calculated to be 16.3 days with 99% eliminated by 97 days. The model predicts that approximately 96% of amiodarone is eliminated as desethylamiodarone in urine, 2% eliminated as desethylamiodarone in bile, and 2% as other metabolites.
 ...
PMID:Pharmacokinetics and pharmacodynamic effects of amiodarone in plasma of ponies after single intravenous administration. 1496 11

(1) The treatment aims in atrial fibrillation are to reduce patients' symptoms and to prevent both embolism and deterioration of any underlying heart disease. Therapy consists of anticoagulant or antiplatelet drugs, treatment of any underlying heart disease, and heart rate control. (2) Digoxin, betablockers, diltiazem and verapamil slow the heart rate but rarely restore sinus rhythm. Amiodarone, disopyramide, flecainide, quinidine and sotalol can be used to prevent relapse of atrial fibrillation after electrical cardioversion, but they all have potentially serious adverse effects. New trials of antiarrhythmic treatments have been published since our last review of this subject. (3) In one trial in 403 patients, amiodarone was more effective than sotalol and propafenone in restoring and maintaining sinus rhythm. After 15 months of follow-up, there were fewer strokes among patients treated with amiodarone, but there was no difference between the three drugs in the overall incidence of cardiovascular events. (4) A clinical trial with 4060 patients compared rhythm control (mainly with amiodarone, sotalol or propafenone; sometimes combined with electrical cardioversion) and rate control (with digoxin, betablocker, diltiazem or verapamil; systematically combined with anticoagulant therapy). The antiarrhythmic treatment restored sinus rhythm in more than half the patients in the long term. But rhythm control did not reduce the risk of death or serious cardiovascular events during a mean follow-up period of 3.5 years. Rhythm control caused more adverse events than rate control; subgroup analyses (weak evidence) suggest that rhythm control may also have caused more deaths among patients over 65 and among patients with coronary heart disease. (5) In another trial, electrical cardioversion followed by antiarrhythmic therapy (mainly sotalol) sustainably restored sinus rhythm in more than one-third of 522 patients. But, compared with rate control treatment plus anticoagulant therapy, rhythm control did not reduce the risk of cardiovascular events, and was associated with a larger number of serious adverse cardiac effects. (6) Other recent trials confirm the risk of serious adverse effects, including severe arrhythmia with sotalol (especially at the start of treatment), and adverse thyroid and pulmonary effects with amiodarone. (7) Combined radiofrequency ablation and cardiac stimulation improved symptoms in some patients with incapacitating atrial fibrillation who had not responded to other treatments. However, this approach carries a risk of serious adverse effects, and its impact on the risk of cardiovascular events and death is not known. (8) In practice, an attempt should be made to restore sinus rhythm with amiodarone and/or electrical cardioversion, in symptomatic, recent or paroxysmal atrial fibrillation in patients under 65 who have no signs or symptoms of coronary heart disease. In other situations, rate control is the first-line option, using digoxin, betablockers (other than sotalol) or calcium channel blockers (diltiazem or verapamil). Whatever the option, treatment must be combined with anticoagulant or antiplatelet therapy, and with treatment of any underlying heart disease.
 ...
PMID:Atrial fibrillation: rate control often better than rhythm control. 1514 84

Cardiovascular manifestations of thyrotoxicosis and thyroid dysfunction caused by amiodarone. The cardiovascular symptoms of thyrotoxicosis were described more than two hundred years ago and remained the basis of diagnosis in modern medicine. Myocardium, peripheral circulation and sympathetic nerve system, all affecting cardiovascular hemodynamics, are influenced by thyroid hormones in many ways. Sub-clinical hyperthyroidism is characterized by suppressed thyroid stimulating hormone and normal free triiodothyronine and free thyroxine levels. Cardiovascular symptoms: elevation of heart rate, myocardial contractility, stroke volume, myocardial oxygen consumption, systolic blood pressure and reduction in systemic vascular resistance and diastolic blood pressure can be often seen even in case of subclinical hyperthyroidism. Thyrotoxicosis exacerbates the symptoms of a preexisting heart disease, but it can also cause complaints in case of a structurally normal heart. The most common cardiac complications are arrhythmias (mainly atrial fibrillation), heart failure and hypertension. Amiodarone is used for the treatment and prevention of several arrhythmias. It is safely applicable even in case of left ventricular dysfunction. The more common application is limited by its side effects that can develop even at low doses and may involve several organs (thyroid gland, lungs, liver, heart, nerve system among others). The complex effect of amiodarone on thyroid function ranges from mild abnormalities of thyroid function tests to overt thyrotoxicosis or hypothyroidism.
 ...
PMID:[Cardiovascular manifestations of thyrotoxicosis and thyroid dysfunction caused by amiodarone]. 1563 34

Atrial fibrillation (AF) has been treated with DC shocks delivered transthoracically, but in 5-30% of patients, the procedures fail to restore sinus rhythm (SR). We hypothesized that applying high energy shock waves to the chest may overcome the inadequate penetration of electrical shock to the atrium. The aim of this study was to evaluate the efficacy of higher energy external DC shock for the treatment of refractory AF coexisting with cardiovascular disease using a synchronized double external defibrillator. Fifteen patients (mean age 65 +/- 8) with refractory AF to standard DC cardioversion (CV) underwent higher energy DC shock using a double external defibrillator. Concomitant heart disease was present in all patients. Warfarin and amiodarone (600 mg/day), were administered for at least three weeks duration before DC CV. Sedation was performed with IV midazolam. Two defibrillator paddles were positioned on the anterior and posterior chest wall in a right lateral decubitus position. Defibrillators were synchronized to the R waves and simultaneously 720 joules of energy was administered to the patients. Amiodarone (200 mg/day) was continuously administered after DC shock to maintain SR. Sinus rhythm was obtained in 13 patients. Sinus rhythm was persistent in 11 patients for six months duration. Creatine kinase MB fractions were normal at 4 (22 +/- 4 IU/L) and 12 hours (18 +/- 4 IU/L). None of the patients developed significant hemodynamic compromise or congestive heart failure, higher AV block, stroke, or transient ischemic cerebral events. The results indicate that higher energy DC shock application using a double external defibrillator is an effective and safe method for the cardioversion of refractory AF. We believe this procedure should be performed before internal atrial cardioversion.
 ...
PMID:Simultaneous double external DC shock technique for refractory atrial fibrillation in concomitant heart disease. 1565 68

Thyrotoxicosis is associated with increased cardiovascular morbidity and mortality, primarily due to heart failure and thromboembolism. Palpitations, caused by sinus tachycardia and occasionally by atrial fibrillation, are the most frequent cardiovascular symptom. As atrial fibrillation may be the only manifestation of thyrotoxicosis, thyroid hormone excess should routinely be excluded in patients with this rhythm disturbance. Heart failure occurs mostly in the presence of underlying heart disease or tachycardia-induced cardiomyopathy in patients with long-standing atrial fibrillation. On occasion, long-standing hyperthyroidism may lead to heart failure even in the absence of concomitant cardiac conditions. Beta-blockers offer symptomatic relief and at the same time slow the ventricular response in patients with atrial fibrillation. Amiodarone, and occasionally iodinated contrast agents, may cause iodine-induced thyrotoxicosis. Clinical suspicion is essential in the diagnosis of amiodarone-induced thyrotoxicosis (AIT), because the antiadrenergic effect of the drug may conceal symptoms. AIT should be considered in any patient on amiodarone in the presence of new-onset or recurrent atrial arrhythmias or unexplained weight loss. Beyond discontinuation of amiodarone, treatment options include propylthiouracil or methimazole, potassium perchlorate, steroids, lithium and, if pharmacological treatment fails, surgery. Amiodarone may potentially be used less frequently in the future since recent studies have shown that this drug is inferior to implantable cardioverter defibrillators in prevention of sudden cardiac death in patients with severe heart failure. In addition, non-iodinated amiodarone analogues are currently in advanced phase of clinical testing.
 ...
PMID:Thyrotoxicosis and the cardiovascular system. 1598 1

Amiodarone is one of the most efficient and safe antiarrhythmic drugs in the treatment of atrial fibrillation (AF). Yet, though rare, proarrhythmic effects remain a clinical problem. We present three cases of amiodarone-associated "Torsade de pointes" tachycardia (Tdp) in patients treated concomitantly with heart rate controlling medication for AF. Amiodarone loading therapy was started for the treatment of tachyarrhythmic AF in all the three patients. All presented with a history of coronary heart disease, resulting in a severely reduced left ventricular ejection fraction in two patients. One received oral amiodarone loading, in the others, amiodarone was administered intravenously because of hemodynamically relevant AF episodes. Amiodarone therapy was combined with a heart rate controlling medication including a beta-blocking agent and digitalis in all the cases. All the subjects suffered from clinically relevant Tdp in the early run after initiation of amiodarone loading (max. 48 hours). The mean QTc in all patients before induction of Tdp was prolonged. The present case reports imply that amiodarone in combination with beta-blocker/digitalis therapy may be associated with an elevated proarrhythmic risk in selected patients with structural heart disease and AF.
 ...
PMID:"Torsade de pointes" in patients with structural heart disease and atrial fibrillation treated with amiodarone, beta-blockers, and digitalis. 1665 Feb 63

The medical records of client-owned dogs in which amiodarone was used to manage atrial fibrillation (AF) were reviewed. Data analyzed included signalment, history of heart failure, presenting complaint, clinical diagnosis, prescription drug history, number of re-examinations, outcome, and laboratory analysis including serum biochemical analysis, CBC, and thyroid function testing. Specific data for amiodarone included loading and maintenance dose, duration of loading dose, adverse effects, and reason for decreasing dose or discontinuation of amiodarone therapy. Follow-up data for 17 dogs were included in the analysis. Various cardiac diseases including cardiomyopathy, valvular endocardiosis, and congenital heart disease were diagnosed in the dogs. Median loading and maintenance dosages of amiodarone were 16.5 and 9.0 mg/kg of body weight/d, respectively. A >20% decrease in heart rate was achieved in 13 dogs (76%). Conversion to sinus rhythm was achieved and maintained in 6 dogs (35%). Amiodarone was discontinued in 5 dogs, and the dose was decreased because of symptomatic bradycardia (n = 1), asymptomatic (n = 1) and symptomatic (n = 3) increases in hepatic enzyme activities, and for unknown reason (n = 1). On the basis of >20% decrease in heart rate in 76% of the dogs and conversion to sinus rhythm in 35%, it was concluded that amiodarone may be useful in managing AF in dogs. The use of amiodarone in the medical management of AF in dogs warrants further investigation.
 ...
PMID:Oral amiodarone therapy in dogs with atrial fibrillation. 1695 17

Nifekalant hydrochloride (NIF) is a novel intravenous class-III antiarrhythmic agent with a pirimidinedione structure that purely blocks the K+ channel without inhibiting beta-adrenergic receptors. The authors investigated the efficacy of NIF for refractory ventricular tachycardia/fibrillation (VT/VF). They studied 30 patients treated with an intravenous infusion of NIF [ 26 men, 4 women; age: 63 +/- 17 (mean +/- SD) years] at a dose of 0.19 +/- 0.14 mg/kg body weight per hour. Sixteen were patients with acute coronary syndrome (ACS), and 14 were patients with chronic structural heart disease (Chr-HD). Amiodarone and sotalol had already been administered to 9 patients with Chr-HD before the administration of NIF. The QT and T peak-end (Tp-e) intervals were measured and corrected by Bazett's method (QTc, cTp-e). The left ventricular ejection fraction was depressed (28 +/- 9%). NIF was effective for preventing VT/VF without proarrhythmia and hemodynamic deterioration in 21 patients (70%; 12 with ACS; 9 with Chr-HD), but ineffective in 4 patients (all with Chr-HD). The QTc prolongation in the responders was more pronounced than in the nonresponders (25% +/- 15% versus 5% +/- 7% increase; P < 0.05). Proarrhythmic torsade de pointes (TdP) developed transiently in the remaining 5 patients in whom the cTp-e was markedly increased compared with that in the responders (93% +/- 49% versus 37% +/- 41% increase; P < 0.05). In conclusion, these findings indicate that the intravenous administration of NIF is useful in the emergent treatment of inhibiting drug-refractory VT/VF, although proarrhythmic TdP owing to an enhancement of transmural dispersion of repolarization needs to be taken into account.
 ...
PMID:Prevention of life-threatening ventricular tachyarrhythmia by a novel and pure class-III agent, nifekalant hydrochloride. 1720 5

Amiodarone causes changes in thyroid function tests in about 15-20% of patients, inducing either hypothyroidism or thyrotoxicosis. The iodine load and the destructive thyroiditis caused by amiodarone produce thyrotoxicosis. We report a case of amiodarone-induced thyrotoxicosis diagnosed when investigating the reason for worsening of cardiac function. Prognosis and treatment of cardiac disorder were determined by thyrotoxicosis. The management needed a closed monitoring of thyroid function. Treatment was based on high doses of propylthiouracil and dexamethasone, but they couldn t control cardiac condition and surgery was warranted. When amiodarone-induced thyrotoxicosis is refractory to medical treatment, we believe surgery should be considered earlier.
 ...
PMID:[Difficult treatment of amiodarone-induced thyrotoxicosis: a case report]. 1827 64

Amiodarone is recommended for the cardioversion of atrial fibrillation and prevention of paroxysmal atrial fibrillation in patients with structural heart disease, coronary artery disease or left ventricular dysfunction. It has well-recognised side-effects on the skin, lungs, liver, thyroid and eyes. Neurological side-effects, including ataxia and neuropathy, also occur, and may be more prevalent in older patients. These side-effects are reversible after cessation of amiodarone. Monitoring of amiodarone therapy should include assessment of the central and peripheral nervous system especially in older patients.
 ...
PMID:Ataxia caused by amiodarone in older people. 1838 85


<< Previous 1 2 3 4 5 6 7 8 Next >>