Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac failure is often associated with disturbances in cardiac output, autonomic nervous system activity, central and systemic venous pressures, and sodium and water metabolism. These disturbances influence the extent and pattern of tissue perfusion, may lead to tissue hypoxia and visceral congestion, and may alter gastrointestinal motility. By these mechanisms, cardiac failure potentially affects absorption and disposition characteristics of drugs, which may necessitate adjustment in dosage regimen for optimum therapy. Lignocaine is the drug which has been studied most extensively in cardiac failure. Volumes of distribution and clearance are decreased. As a drug whose metabolism is largely limited by liver blood flow, decreased blood flow to the liver accounts for some of the change in clearance, but impaired hepatic metabolism appears also to play a role in some patients. Accumulation of active metabolites of lignocaine and procainamide in patients with cardiac failure can influence therapeutic and toxic effects. Theophylline metabolism, which is largely independent of blood flow, appears to be reduced significantly in patients with severe cardiac failure and necessitates reduction of dosage. In the presence of severe cardiac failure, digoxin clearance may be less than anticipated on the basis of estimates of renal function. Quinidine plasma levels may be higher after single doses due to reduced volume of distribution. Quinidine metabolites are believed not to be pharmacologically active but may create confusion with nonspecific assays. Specific assays are recommended in cardiac failure, especially complicated by renal insufficiency. Data are lacking relating pharmacokinetic alterations to haemodynamic measurements in patients with cardiac failure. Whereas the direction of change in pharmacokinetic parameters may be predicted, variability in the magnitude of change is so great that determination of drug concentration in blood remains as essential adjunct to therapy.
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PMID:Pharmacokinetics in patients with cardiac failure. 79 48

Host factors play an important role in the dosing requirements of theophylline. Theophylline metabolism and clearance depend principally on liver cell function rather than on hepatic flow. The effects of acute hypoxemia require more study; however, patients with chronic obstructive pulmonary disease who have chronic hypoxemia appear to have some impairment of clearance. Clearance is variably and sometimes drastically reduced in patients with liver disease and heart failure, and is reduced by some viral infections. It is not impaired by renal failure. Current split-virus vaccine mixtures do not appear to affect clearance. Clearance is increased in patients with cystic fibrosis and hyperthyroidism. The depressed clearance seen in the severely ill patients who require intensive care improves with improvement in the patient's condition, but the individual factors involved have not been identified. An area requiring more study is the effect of pH on the apparent distribution volume for theophylline. In the presence of liver disease, heart failure, or serious illness, caution must be applied in theophylline dosing, with frequent monitoring of serum levels. Stable patients also warrant an initially conservative dose until serum levels are obtained to guide further dose adjustments.
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PMID:Effect of disease states on theophylline elimination. 353 54

Theophylline is a medium-potency bronchodilator that is useful in the treatment of reversible airway obstruction from any cause. It also improves contraction of the diaphragm, accelerates mucociliary transport, lowers pulmonary artery pressures, and limits the release of the mediators of immediate hypersensitivity from mast cells. The pharmacologic effects correlate closely with the plasma concentration of this drug, and within the defined therapeutic limits, only minor adverse effects occur. The dose of theophylline required to achieve therapeutic plasma levels varies considerably between subjects, mainly because of differences in clearance. The latter varies with age, smoking, alterations in hepatic function, cardiac failure, viral infections, and concurrent administration of other drugs. For the treatment of acute symptoms, either intravenous administration or a rapidly absorbed compound such as uncoated tablets or liquids is required. For the long-term management of reversible airway obstruction, sustained-release theophyllines are available. These formulations maintain therapeutic serum theophylline concentrations for prolonged periods, permitting longer dosing intervals and improved patient compliance.
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PMID:Methylxanthine therapy and reversible airway obstruction. 408 94

Cardiac accidents induced by various types of drugs are examined and risk factors are identified in this article. Digitalis preparations are responsible for the largest number of accidents, but their frequency diminishes when prescription rules are respected. Overdoses are often announced by digestive complaints, while more serious problems arise at the stage of intoxication. Theophylline is used as a bronchial muscle relaxant but also has a cardiac effect. All antiarhythmics except bretylate are negative inotropes and can aggravate cardiac insufficiency. Beta-blockers were relatively well tolerated if the contraindications are respected. The main risks are decompensation for a cardiac insufficiency and aggravation of an auriculoventricular block. The risks of antiangina preparations are mostly provoked by their vasodilation action. Neurotropic drugs usually entail minimal alterations in the electrocardiogram but a variety of serious problems may arise with massive ingestion. Cardiotoxicity is rare in anticancer drugs and has mostly been noted in anthracyclinic products. Accidents with local anesthetics are not rare despite their daily use, while general anesthetics vary in their risk levels. A variety of other medications have been found or suspected to entail risks. Myocardial infarction in young, healthy oral contraceptive (OC) users has been observed but the mechanism of action is unclear. The necessity of ruling out risk factors before prescribing combined pills has been underlined. It is difficult to compile a complete list of all drugs having cardiovascular repercussions and the action of some drugs is probably still undiscovered. In most cases the complications are dose-related and predictable. Exceptions to this rule exist, as with OCs.
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PMID:[Drugs and the cardiovascular system]. 613 12

Bronchodilating drugs can be divided into three main groups: beta-adrenergic stimulants including specific beta-2 receptor agonists (salbutamol, terbutaline, fenoterol) which are the agents of this group used in everyday practice, theophylline and its derivatives, and atropine-like drugs (ipratropium bromide). Bronchodilators act chiefly upon the spasm observed at the bronchial level in reversible obstructive phenomena (mainly asthma), their effect upon inflammation and hypersecretion being slight or controversial. Beta-stimulants have a relatively specific mode of action at the bronchial level in the setting of use in pneumology; they exhibit cardiac effects only at high doses and when used by oral or parenteral routes. Relative to isoprenaline, they also have the advantage of being active orally and over a longer period of time. They are given in maintenance treatment of asthma, by parenteral or oral routes or as aerosols. Main side effects of adrenergic beta-stimulants are tremor with oral administration, and tachycardia with very high doses by parenteral or oral routes; when given as aerosols these agents may fail to control severe attacks. The bronchodilating properties of theophylline have been known for a long time; late advances concerning this drug result from better knowledge of its pharmacokinetics. Recent studies have discriminated between serum levels correlated with therapeutic effectiveness and those accompanied with mild or severe side effects; in addition, it has been clearly shown that the half life of this alkaloid varies from one person to another and with various physiopathologic (age, dietary habits, liver failure, heart failure...) or pharmacologic (drug interactions with enzyme inductors or inhibitors...) factors; these recent advances have led to improved individual adjustment of theophylline dosage using serum concentration assays if needed. Theophylline is used in acute attacks and in maintenance therapy of asthma. Main side effects are digestive intolerance and, with toxic doses, neurologic disorders. Atropine-like drugs inhibit the effects of the parasympathetic reflex which results from stimulation of receptors by irritation of the respiratory tract, through the action of mediators. In this group, ipratropium is the only drug given in aerosols; this, together with its pharmacologic specificity, contributes to its tolerance. In some instances, the bronchodilating effect of ipratropium bromide is comparable to that of sympathomimetics.
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PMID:[Bronchodilators]. 632 Apr 43

Routine intravenous aminophylline therapy was monitored by drug level measurements in 45 hospitalized patients with chronic obstructive bronchitis. Only 44% had theophylline serum concentrations (Cp) in the optimum range (10-20 mg/l), while in 36% of patients potentially toxic Cp values were observed. The incidence of side effects was related to theophylline serum concentration: 78% in cases with Cp greater than 30 mg/l against 24% in cases with Cp less than 20 mg/l. Theophylline toxicity occurred most frequently in elderly patients with cardiac failure, who had markedly reduced theophylline clearances. To avoid excessive drug accumulation the usual aminophylline dose should be reduced by 50% when clinical signs of cardiac failure are present. In addition, measurement of theophylline serum concentration is often necessary for optimum dosage adjustment.
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PMID:[Relation of dose, serum concentration and side effects in intravenous aminophylline therapy]. 733 Jun 56

Aminophylline [(theophylline ethylene diamine (TED)] reportedly improved cardiac hemodynamics by lowering vascular resistances and increasing contractility. TED as used clinically has not been compared to the vasodilator sodium nitroprusside (NP). To assess the relative hemodynamic effects of these two commonly used agents, the following comparison was made. Ten patients with congestive cardiomyopathy in chronic refractory heart failure [New York Heart Association (NYHA) class IV] were studied. All patients demonstrated cardiomegaly by chest x ray and echocardiography (LVd = 6.3 +/- 0.7 cm) and markedly abnormal hemodynamics during baseline observations (see Table I). Hemodynamic measurements at baseline were compared after TED infusion (mean blood level = 16 +/- 12 micrograms/m/TED) and during intravenous NP. No significant changes in heart rate occurred during either therapeutic intervention; a fall in mean arterial pressure of 10 mmHg (p < 0.01) was observed during NP therapy; atrioventricular (AV) block with ventricular fibrillation was successfully treated in one patient after TED. Theophylline ethylene diamine demonstrated no detectable cardiac hemodynamic effects 60--90 min post infusion despite proven blood levels, whereas NP exhibited distinctly beneficial effects in this patient group. Previous studies demonstrating improved hemodynamics occurring with TED have been limited to the time of infusion or within the following 40 min, a time when TED blood levels are maximum and therefore closest to toxicity. The results of this study suggest that TED demonstrates no beneficial hemodynamic effects in refractory heart failure as early as 1 h after infusion despite blood levels in the therapeutic range.
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PMID:Role of aminophylline in refractory heart failure: a comparison to the vasodilator sodium nitroprusside, the old and the new. 743 79

Theophylline is a bronchodilator used extensively in the management of obstructive pulmonary disease. Factors implicated in altered theophylline clearance include smoking, age, concomitant drug intake, liver disease and left ventricular heart failure. However, evidence now suggests that theophylline clearance may be altered by changes in severity of the pulmonary obstruction, hypoxia and variation in arterial pH. The in vitro disposition of theophylline has been evaluated in isolated rat livers and mouse hepatocytes. In vivo studies have assessed the metabolism of theophylline under hypoxia in rats, rabbits and dogs. In isolated mouse hepatocytes and rat livers, low oxygen concentrations resulted in higher theophylline concentrations, a longer elimination half-life and a decrease in the production of the metabolite 1,3-dimethyl uric acid, suggesting impaired metabolism of theophylline. In rabbits, hypoxia, hypercapnia and respiratory acidosis decreased total body clearance and increased plasma theophylline concentrations. On the other hand, experiments involving dogs showed no significant changes in theophylline concentrations or pharmacokinetic parameters with hypoxia. At present, animal studies remain inconclusive. This can be attributed to the use of different animal models and variations in study methodology, including the extent and duration of hypoxia and acidaemia, concurrent acid-base disorders such as hypercapnia, as well as the severity of pulmonary obstruction. Human studies assessing alterations in theophylline disposition secondary to the hypoxia present in pulmonary disease are few and include mostly case reports and observational studies. There is evidence suggesting decreased theophylline clearance and protein binding during acute illness and some consensus can be achieved using case reports and controlled studies. There is additional evidence that drug clearance decreases with age and that elderly patients may have a decreased theophylline clearance at baseline. However, the most obvious markers appear to be the severity of pulmonary disease and the rate of change in the patient's condition. Caution should be exercised when administering theophylline to elderly patients with chronic obstructive pulmonary disease presenting with acute exacerbations of a concomitant respiratory illness, as these patients appear to be most likely to exhibit altered theophylline metabolism. Therefore, they would be at increased risk for toxicity should conventional dosages be used during an acute respiratory event.
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PMID:Hypoxia, arterial pH and theophylline disposition. 826 13

The treatment of choice for chronic, symptomatic bradycardia is the placement of a cardiac pacemaker. Individuals who refuse or cannot tolerate pacemaker insertion usually require pharmacologic therapy. Hydralazine, prazosin, anticholinergics, and sympathomimetic agents have been administered for this indication, but adverse effects and limited data hinder routine, long-term use. Theophylline has emerged as a reasonable alternative strategy. For the medical management of bradycardia in the elderly, the literature supports theophylline dosages between 400 and 600 mg/d (approximately 8 mg/kg/d) administered in divided doses. This dosage range should result in a steady-state serum concentration between 5 and 15 mg/L. While some investigators recommend potentially higher initial doses (up to 12 mg/kg/d), lower dosages are more appropriate in the elderly due to decreased theophylline clearance. Initial dosage titration may be indicated and prolonged therapy is expected on the basis of the common etiologies of bradycardia in this patient group. Patient specifics such as altered theophylline metabolism (e.g., smoking), drug interactions (e.g., ciprofloxacin), and concomitant disease states (e.g., hepatic disease, heart failure) should always be considered in theophylline dosage recommendations. Clinicians should adjust the theophylline dose on the basis of patient response, including heart rate and clinical symptomatology, as well as measurement of occasional theophylline concentrations, if deemed appropriate. Theophylline should be avoided in the bradycardia-tachycardia manifestations of sick sinus syndrome or when ventricular ectopy is frequent. Additional investigation will further define the role of theophylline in elderly patients with chronic, symptomatic bradycardia.
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PMID:Theophylline for chronic symptomatic bradycardia in the elderly. 968 Nov 1