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

Octreotide, a long-acting somatostatin analogue has recently been introduced in the therapy of gastroenteropancreatic endocrine tumors, but home experience has been lacking. With the aim of drawing attention to this therapeutic possibility, a case of malignant carcinoid syndrome treated with octreotide for 18 months is reported. Despite the therapeutic attempts preceding the octreotide administration a gradual progression in clinical symptoms was observed and cardiac failure due to fibrotic and valvular heart disease developed. Cytotoxic chemotherapy, serotonin antagonists or repeated selective embolisation of the hepatic artery only resulted in a short transitional improvement. Octreotide in a dose of 100 micrograms three times daily by subcutaneous injection provided effective and rapid relief from episodic flushing and serious diarrhoea. Plasma level of serotonin and 24-hour urinary excretion of 5-hydroxyindolacetic acid decreased from 6 micrograms/ml to 2 micrograms/ml and from 800 mumol/day to 70 mumol/day, respectively. No changes in the number and extension of liver metastases could be seen after introducing the octreotide treatment. The patient's compensated cardiac status could be preserved and continuous therapy provided an acceptable quality of life.
 ...
PMID:[Treatment of carcinoid syndrome with a somatostatin analogue]. 137 69

Adenosine has recently become widely available for the treatment of paroxysmal supraventricular tachycardia. In order to evaluate its role in the management of arrhythmias, we have reviewed the literature on the cellular mechanisms, metabolism, potential for adverse effects, and clinical experience of the efficacy and safety of intravenous adenosine. Adenosine produces transient atrioventricular nodal block when injected as an intravenous bolus. This is of therapeutic value in the conversion to sinus rhythm of the majority of paroxysmal supraventricular tachycardias, which involve the atrioventricular node in a re-entrant circuit. The mean success rate was 93% from over 600 reported episodes. Compared with other antiarrhythmic agents, adenosine is remarkable for its rapid metabolism and brevity of action, with a half-life of a few seconds. It commonly produces subjective symptoms, particularly chest discomfort, dyspnea, and flushing, which are of short duration only. No serious adverse effect has been reported. Arrhythmias may recur within minutes in a minority of patients. Comparative studies have shown that adenosine is as effective as verapamil in the treatment of supraventricular tachycardia, and has less potential for adverse effects. Patients with supraventricular tachycardia should initially be treated using vagotonic physical maneuvers. Immediate electrical cardioversion is indicated if the arrhythmia is associated with hemodynamic collapse. Adenosine is the preferred drug in those patients in whom verapamil has failed or may cause adverse effects, such as those with heart failure or wide-complex tachycardia. The safety profile of adenosine suggests that it should be the drug of first choice for the treatment of supraventricular tachycardia, but only limited comparative data to support this view are available at present.
 ...
PMID:Adenosine and the treatment of supraventricular tachycardia. 160 47

We have treated with intravenous iloprost twelve patients suffering from cardiac insufficiency compensated under oral digoxin (NYHA class II) associated with severe limb ischaemia due to arterial insufficiency. Our aim was to study its possible interaction on digoxin levels and to evaluate the long-term efficacy of iloprost. Although iloprost slowed the digoxin absorption by approximately one hour, we found no clinically significant difference between the digoxin pharmacokinetic data before and during treatment by iloprost. Moreover, 11 out of the 12 patients had a good clinical fate after the treatment, which persisted at 6 months. The pain disappeared in 4 and diminished in 7; and all skin ulcers healed. This improvement has lasted up to two and a half years in two patients. The clinical tolerance of iloprost was acceptable despite frequent headache and flushing associated with hypotension and nausea. We conclude that iloprost seems to be a very promising treatment of severe limb ischaemia when no intervention on the proximal arteries is possible. The patients on digoxin can continue their treatment without dose alteration while starting on iloprost.
 ...
PMID:[Treatment with iloprost of critical ischemia of the lower limbs associated with cardiac insufficiency. Study of interaction with the pharmacokinetics of digoxin]. 172 27

Metastatic carcinoid tumor is often seen with flushing, diarrhea, and cardiac symptoms--the carcinoid syndrome. Cardiac failure is often associated with major morbidity and mortality in carcinoid disease. In this report, a case of successful cardiac valvar surgical intervention has resulted in prolonged alleviation of cardiac symptoms and survival.
 ...
PMID:Surgical management of carcinoid heart disease. 203 12

3-Deazaguanine (Dezaguanine), a purine antimetabolite, was evaluated in a phase I trial in 42 patients with advanced solid tumors. Dezaguanine was given as a weekly intravenous infusion for three consecutive weeks of a four-week cycle. The dose ranged from 30 to 2000 mg/m2; no consistent dose-limiting hematologic or gastrointestinal toxicity was observed. Some patients reported brief episodes of burning at the infusion site or transient facial flushing immediately following the administration of dezaguanine. Three patients experienced cardiac toxicity. Two patients, at doses of 1130 and 2000 mg/m2 respectively, developed congestive heart failure. In one case the heart failure was fatal; the second patient recovered within 8 weeks. The third patient had a progressive fall in left ventricular ejection fraction but did not develop clinical evidence of heart failure before his death from progressive cancer two months later. Postmortem cardiac pathology in the two patients who died early following therapy revealed nonspecific interstitial fibrosis without inflammatory cell infiltrates. The myocardium of the third patient, who died 20 months after receiving dezaguanine, was normal. Electron microscopic analysis of myocardium from the first patient did not show myofibrillar loss or mitochondrial disorganization characteristic of anthracycline cardiomyopathy. Due to the probable cardiotoxicity of dezaguanine in this study and the lack of objective antitumor response, further development of this agent has been discontinued.
 ...
PMID:3-Deazaguanine: report of a phase I trial and drug-related cardiac toxicity. 208 70

The complementary antihypertensive effects of the beta-blocker/calcium antagonist combination has to be weighed against their additive and potentially detrimental negative inotropic, chronotropic, and dromotropic effects inherent in both classes of drugs. We reviewed the main adversity, particularly electrophysiological and hemodynamic effects, of combined treatments with beta-blockers and the calcium antagonists verapamil, diltiazem, and nifedipine. In patients with coronary artery disease, a different picture emerged between the verapamil and nifedipine combination with a beta-blocker. Verapamil was more often associated with conduction problems (up to 9%) and dyspnea or heart failure (up to 8%). These problems had rarely been reported with nifedipine but ankle edema (up to 11%), flushing (up to 11%), and headaches (up to 7%) predominated. The cardiovascular unwanted effects led to withdrawal in 5-8% for the verapamil/beta-blocker or nifedipine/beta-blocker combination. Although there was little cardiac adversity with the nifedipine/beta-blocker combination, the intravenous administration of verapamil in patients on beta-blockers is contraindicated and the oral verapamil/beta-blocker combination should not be sought in patients with impaired left ventricular function and when conduction disturbances are likely to occur. In treating hypertensive patients without overt coronary artery disease, there is no argument against the use of the nifedipine/beta-blocker combination but there is a need for definitive studies of the verapamil/beta-blocker combination.
 ...
PMID:Review of the cardiovascular adversity of the calcium antagonist beta-blocker combination: implications for antihypertensive therapy. 241 10

The major antihypertensive mechanism of calcium antagonists is by decreasing the systemic vascular resistance, modified by the counter-regulatory responses of the baroreflexes and the renin-angiotensin-aldosterone system. In severe hypertension, the concept that calcium overload of the vascular myocyte could precipitate or aggravate peripheral vasoconstriction provides a logical basis for the use of these agents as first choice therapy; nifedipine, especially, has been well tested. As monotherapy for mild to moderate hypertension each of the three first-generation agents compares well with beta-blockers. Calcium antagonists may have a special role in the therapy of certain patient groups (elderly, black) or in those subjects whose life style involves intense physical or mental exertion (hemodynamics better maintained than with beta-blockade) or in patients with early end-organ damage such as left ventricular hypertrophy or renal insufficiency. However, the goal blood pressure may not be reached during monotherapy so that drug combinations may be required. Further indications for these compounds are as follows. Verapamil and diltiazem are frequently used in supraventricular tachycardias including acute and chronic atrial fibrillation. In the arrhythmias of the Wolff-Parkinson-White syndrome, there is the potential danger of provocation of anterograde conduction. Further indications for calcium antagonists, still under evaluation, include congestive heart failure (controversial), hypertrophic cardiomyopathy (verapamil), primary pulmonary hypertension (high doses required), Raynaud's phenomenon (nifedipine and diltiazem effective), peripheral vascular disease (proof not yet documented), cerebral insufficiency and subarachnoid hemorrhage (nimodipine promising), migraine, exertional bronchospasm, renal disease, atherosclerosis (experimental), and primary aldosteronism (nifedipine inhibits aldosterone release). Second-generation agents include dihydropyridines, such as nitrendipine, nicardipine, felodipine, amlodipine, nisoldipine, nimodipine, and isradipine. From these will be selected agents that are longer acting and provide higher vascular selectivity. New preparations of existing agents include slow-release formulations of nifedipine, verapamil, and diltiazem. Minor side effects include those caused by vasodilation (flushing and headaches), constipation (verapamil), and ankle edema. Serious side effects are rare and result from improper use of these agents, as when intravenous verapamil is given to patients with sinus or atrioventricular nodal depression from drugs or disease, or nifedipine to patients with aortic stenosis. The potential of a marked negative inotropic effect is usually offset by afterload reduction, especially in the case of nifedipine. Yet caution is required when calcium antagonists, especially verapamil, are given to patients with myocardial failure unless caused by hypertensive heart disease. Drug interactions of calcium antagonists occur with other cardiovascular agents such as alpha-adrenergic blockers, beta-adrenergic blockers, digoxin, quinidine, and disopyramide.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Calcium channel antagonists. Part III: Use and comparative efficacy in hypertension and supraventricular arrhythmias. Minor indications. 315 29

With the correct selection of drug and patient, the calcium antagonists as a group can be remarkably effective at relatively low cost of serious side effects. Almost all side effects are dose related. Minor side effects include those caused by vasodilation (flushing and headaches), constipation (verapamil), and ankle edema. Serious side effects are rare and result from improper use of these agents, as when intravenous verapamil (or diltiazem) is given to patients with sinus or atrioventricular nodal depression from drugs or disease, or nifedipine to patients with aortic stenosis. The potential of a marked negative inotropic effect is usually offset by afterload reduction, especially in the case of nifedipine which actually has the most marked negative inotropic effect. Yet caution is required when even calcium antagonists, especially verapamil, are given to patients with myocardial failure unless caused by hypertensive heart disease. Drug interactions of calcium antagonists occur with other cardiovascular agents such as alpha-adrenergic blockers, beta-adrenergic blockers, digoxin, quinidine, and disopyramide. The most marked interaction with digoxin is that with verapamil, which may raise digoxin levels by over 50%. Combination therapy of calcium antagonists with beta-blockers is increasingly common, and is probably safest in the case of dihydropyridines. Other combinations being explored are those with angiotensin-converting enzyme inhibitors and diuretics.
 ...
PMID:Calcium channel antagonists. Part IV: Side effects and contraindications drug interactions and combinations. 315 4

Calcium channel blocking drugs are a chemically heterogenous group, so it might be expected that their effects on vascular smooth muscle, cardiac contractility, and conduction tissue may differ. However, the majority of adverse reactions are predictable from their pharmacological actions and may be conveniently grouped in the following categories: 1) vasodilatation, 2) negative inotropic effects, 3) conduction disturbances, 4) gastrointestinal effects, 5) metabolic effects, and 6) drug interactions. Vasodilatory symptoms, namely, dizziness, headaches, flushing sensation, and palpitation, are more likely with nifedipine. Peripheral edema is also common with nifedipine, but the mechanism is uncertain. For a given degree of vasodilation, the greatest negative inotropic effect is seen with verapamil first, diltiazem second, and nifedipine last. Calcium channel blocking drugs are contraindicated in hypertensive patients with second and third degree heart block, sick sinus syndrome, and severe heart failure. Verapamil and diltiazem have a significant effect on cardiac conduction, whereas nifedipine, in therapeutic doses, does not. Local gastrointestinal symptoms, such as nausea and constipation, are common with verapamil. None of the calcium channel blocking drugs have been reported to adversely affect lipid or protein metabolism. However, nifedipine, verapamil, and diltiazem in high doses may inhibit liberation of insulin. The significance of this finding needs to be explored further in hypertensive diabetics. Serum digoxin levels have been shown to increase after administration of verapamil and nifedipine, but there is no evidence that this change has any clinical relevance.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Side effects of calcium channel blockers. 328 Apr 92

The combination of nifedipine and atenolol must be evaluated in terms of risks and benefits to the hypertensive patient. Disadvantages with single-agent therapy justify trials of combination regimens. beta-Blockers may be unacceptable to some patients because of gastrointestinal upset, musculoskeletal symptoms, tiredness, malaise, insomnia, depression or confusion, sweating, breathlessness or cold extremities. The side effect profile varies from patient to patient and between different beta-blockers. Calcium antagonists also have characteristic side effects, including severe headaches, flushing and oedema, tachycardia and possibly worrying palpitations, and polyuria. Combining a calcium antagonist and a beta-blocker can reduce some side effects; for example, tachycardia is offset by addition of beta-blocker to calcium antagonist therapy, and beta-blocker-induced cold extremities may be reversed with a drug such as nifedipine. Moreover, the antihypertensive efficacy is increased, which is useful in previously resistant patients. However, an excessive fall in blood pressure is a possible adverse effect of the combination. There is also the possibility of precipitating heart failure in patients with cardiomegaly and severely compromised left ventricular function. The combination of nifedipine and atenolol was evaluated in 25 patients in a randomised, crossover trial following a month's treatment with atenolol 50mg twice daily. Patients received either atenolol 50mg twice daily alone, or atenolol 50mg twice daily with sustained release nifedipine 20mg or 40mg twice daily, or placebo twice daily during three 4-week treatment periods. Additional antihypertensive benefit was obtained by addition of the low dose of nifedipine compared with atenolol alone, but no further advantage was obtained with the higher nifedipine dose.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Aims of combination therapy--improved quality of life or better blood pressure control? 337 14


1 2 3 4 Next >>