Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this investigation was to evaluate the contribution of hypertrophy, the length-tension phenomenon, and inotropism to adaptation of the left ventricle (LV) to volume overload of up to 3 yr duration. Overload was produced in dogs by heart block, and contractile state was evaluated with a Walton-Brodie arch. Recording of contractile force (CF) in grams vs. muscle length from the LV indicated that dogs with hypertrophy were functioning at a higher point on the ascending limb of the length-tension curve than normals (76 percent Lmax in hypertrophy vs. 61 percent Lmax in normal). Additionally, in hypertrophy, all points on the length-tension curve above 80 percent Lmax were significantly elevated. None of these changes were seen in dogs in which block was induced on the day of the experiment. When CF was normalized for hypertrophy and expressed as CF/cm2, the length-tension curves were practically superimposable. These data suggest that adaptation was accomplished by hypertrophy, a shift up the length-tension curve without a depression of inotropic state.
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PMID:Contractile state of hypertrophied left ventricle in long-standing volume overload. 14 36

The "discovery" of alpha 2-receptors permits the explanation of the mechanism of xylazine that was hitherto poorly understood. The substance can be classified as an alpha 2-adrenoceptor agonist. In the near future two new alpha 2-adrenoceptor agonists will be available in Germany: medetomidine for small animals and detomidine for large animals. Also a new alpha 2-adrenoceptor antagonist will be introduced: atipamezole. alpha 2-adrenoceptor agonists cause sedation, analgesia and muscle relaxation. Notable side effects are bradycardia, heart block and a dose dependent respiratory depression. A comprehensive survey on the pharmacology of the alpha 2-adrenoceptor agonists is given. The previous literature is summarized and discussed, including own studies and clinical experience. An attempt is made to assess the clinical importance of the new drugs. For certain indications medetomidine alone may not be satisfying and combination with other drugs becomes necessary. If sedation is inadequate, the combination with benzodiazepines or propofol is advised; if analgesia is poor, the combination with ketamine or an opioid is recommended.
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PMID:[Old and new alpha 2-adrenoceptor agonists. 1. Xylazine and medetomidine]. 135 76

Paroxysmal supraventricular tachycardia is the most common sustained cardiac arrhythmia in pregnant women. Because nearly 50% of these supraventricular tachyarrhythmias fail to respond to vagal maneuvers, other therapies are used, including electrocardioversion and pharmacologic agents. Propranolol, verapamil, and adenosine have Food and Drug Administration-approved labeling for acute termination of supraventricular tachycardia. Verapamil has been the most commonly used agent in the general population but it has several shortcomings, such as its potential to cause or exacerbate systemic hypotension, congestive heart failure, bradyarrhythmias, and ventricular fibrillation. In addition, verapamil readily crosses the placenta and has been shown to cause fetal bradycardia, heart block, depression of contractility, and hypotension. Adenosine has several advantages over verapamil, including rapid onset, brevity of side effects, theoretical safety, and probable lack of placental transfer. Adenosine ultimately may prove to be the preferred agent for termination of paroxysmal supraventricular tachycardia in the gravid woman.
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PMID:Adenosine in the treatment of maternal paroxysmal supraventricular tachycardia. 149 12

Tricyclic antidepressants (TCAs) are currently used in the treatment of mental depression and nocturnal enuresis. Clinically, these drugs are useful; however, cardiotoxicity can occur even with therapeutic dosages. For example, TCAs are known to alter myocardial function, induce arrhythmias, and produce heart block in individuals with a normal cardiovascular history. The present study was undertaken to establish a culture system of spontaneously contracting adult primary myocardial cells for toxicologic testing and to examine their contractility, morphology, and lactate dehydrogenase release (LDH) after treatment with one of the most cardiotoxic TCAs, amitriptyline. Primary myocardial cell cultures were obtained from approximately 60- to 90-day-old Sprague-Dawley rats. After the cells had been grown in culture for 11 days, they were treated with amitriptyline (1 x 10(-3), 1 x 10(-4), and 1 x 10(-5) M) for 2 to 24 h. The highest concentration of amitriptyline (1 x 10(-3) M) completely destroyed the cardiac muscle cells. In addition to moderate and severe vacuole, granule, and pseudopodia formation, all contractile activity was inhibited as early as 2 h after exposure to the intermediate concentration of 1 x 10(-4) M amitriptyline. Significant LDH release did not occur until 8 h after treatment with this intermediate concentration. Even though there was no significant LDH release at all 3 time points tested, there was a 50% decrease in beating activity (154 +/- 9 to 77 +/- 5 beats/min) and initiation of vacuole formation by 2 h with the lowest concentration of amitriptyline (1 x 10(-5) M). This study presents a new apparatus for the isolation of adult cardiac myocytes for the establishment of primary cell cultures for toxicologic testing. Furthermore, these data demonstrate that amitriptyline induces a concentration- and time-dependent cardiotoxic profile in a model of spontaneously contracting adult cardiac muscle cells in culture.
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PMID:A primary culture system of adult rat heart cells for the study of toxicologic agents. 175 97

In order to assess the efficacy and tolerability of gallopamil (D-600, CAS 16662-47-8) by long-term venous infusion in the treatment of spontaneous angina, 15 consecutive patients were studied in a single-blind, self-controlled trial versus placebo. Following a 24-h Holter ECG recording of the patients receiving a saline infusion (run-in phase), i.v. administration of gallopamil was started at a dose of 0.02 mg/kg/h preceded by a 0.03 mg/kg bolus. After 24 h, the dosage was increased to 0.03 mg/kg/h and the infusion was maintained for another 48 h. The Holter ECG recording was repeated in the last 24 h of treatment and after 6 h from withdrawal (washout phase). The reduction in the number of angina attacks, as shown by a comparison between the average of the two placebo periods (run-in and washout phases) and the three days of treatment, was 68.2%, 92.5%, and 87%, respectively. Consumption of glyceryl trinitrate decreased by 92.5% on each one of the three days of treatment. The reduction in the number of ischemic episodes (IEs) with symptomatic (-91.6%) and silent (-98.0%) ST elevation, and with symptomatic (-100%) and silent (-90%) ST depression, also proved significant. Heart rate decreased only moderately. One patient showed a mild first-degree heart block, while another suffered a transient episode of isorhythmic A-V dissociation. In conclusion, when administered by venous infusion, gallopamil has been found to be well tolerated and highly effective in the treatment of spontaneous angina.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Administration of gallopamil by long-term venous infusion in spontaneous angina. A single-blind, self-controlled study versus placebo. 178 98

Poisoning is a significant problem in the elderly. The majority of poisonings in older people are unintentional and may result from dementia and confusion, improper use of the product, improper storage or mistaken identities. Depression is also common in the elderly and suicide attempts are more likely to be successful in this age group. The elderly patient's recuperative abilities may be inadequate as a result of numerous factors including impaired hepatic or renal function as well as chronic disease processes. General management of poisoning in the elderly parallels management of younger adults, but it is especially important to ascertain underlying medical conditions and concurrent medications. In most poisonings, activated charcoal and cathartic are sufficient. Haemodialysis or haemoperfusion may be required at lower plasma drug concentrations in elderly patients. While the specific indications for antidotes are the same for all age groups, dosage alterations and precautions may need to be considered in the elderly. Drugs most often implicated in poisonings in the elderly include psychotherapeutic drugs, cardiovascular drugs, analgesics and anti-inflammatory drugs, oral hypoglycaemics and theophylline. Cardiovascular and neurological toxicities occur with overdoses of neuroleptic drugs and, more frequently and severely, with cyclic antidepressants. Patients with pre-existing cardiovascular disease are at particular risk of worsening ischaemic heart disease and congestive heart failure. Benzodiazepines only appear to produce significant toxicity during long term administration or in combination with other CNS depressants. Digoxin can cause both chronic and acute intoxication, most seriously cardiac toxicity including severe ventricular arrhythmias, second or third degree heart block or severe refractory hyperkalaemia. Immune Fab antibody is indicated for the management of digoxin toxicity, although patients dependent on the inotropic effect of digoxin may develop heart failure after digoxin Fab antibody administration. Nitrates can cause toxicity including headache, vomiting, hypotension and tachycardia from excessive sublingual, transdermal or intravenous doses. Conduction disturbances and hypotension occur with overdoses of antihypertensive drugs; these effects are mild with angiotensin converting enzyme (ACE) inhibitors, occasionally severe with beta-blockers and of significant concern with calcium channel antagonists. The elderly commonly use aspirin and other salicylates, are more likely to develop chronic intoxications to these agents, and are more susceptible to severe complications such as pulmonary oedema. Salicylate poisoning, recognition of which is often delayed, should be considered in elderly patients with neurological abnormalities or breathing difficulties, especially in the setting of acid-base abnormalities. The clinical effects of NSAID overdose are mild and usually involve the central nervous system and gastrointestinal tract.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Poisoning in the elderly. Epidemiological, clinical and management considerations. 179 7

Although many cases of beta-adrenoceptor antagonist (beta-blocker) poisoning are uneventful, a proportion develop serious and sometimes fatal cardiovascular system depression with severe hypotension. As beta-adrenergic tone is not essential for cardiovascular function in health, there is no physiological reason why total beta-adrenoceptor blockade should have serious consequences in the resting individual. The toxic actions of beta-blockers appear to be related to properties such as membrane depressant activity and possibly due to actions on beta-adrenoceptors distinct from those in the cardiovascular system. Most reports of serious adverse effects following overdosage concern beta-blockers with significant membrane depressant activity, and in particular propranolol and oxprenolol, with which progressive heart block and bradycardia are features. Sotalol toxicity, with its unique electrophysiological action, is a special case. Animal experiments confirm that beta-blockers with membrane depressant activity are more toxic than the newer more selective ones, such as atenolol and nadolol. However, experimental models also reveal that artificial ventilation markedly reduces the toxicity of all beta-blockers tested, suggesting a respiratory depressant action with very high doses. Treatment of serious overdosage in man should include maintenance of adequate ventilation. High dose intravenous glucagon is recommended, because its inotropic action depends on direct stimulation of adenylate cyclase. beta-Agonists such as isoprenaline (isoproterenol) or prenalterol may be effective, but the nature of agonist-competitive antagonist interactions may necessitate the use of unrealistically large doses to overcome very high tissue beta-blocker concentrations.
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PMID:The management of acute poisoning due to beta-adrenoceptor antagonists. 256 23

A 25-month-old boy ingested six sustained-release verapamil tablets, each containing 240 mg of drug. Charcoal and cathartic were given but were never passed per rectum. Third-degree heart block, hypotension, and hypocalcemia were only transiently responsive to calcium infusions, inotropic agents, and epicardial pacing. Cardiopulmonary arrest with electromechanical dissociation ensued. Standard cardiopulmonary bypass was used to allow sufficient time for liver detoxication. Serum levels of verapamil fell during the bypass procedure, and the patient's cardiac status improved. However, continued absorption of drug after bypass resulted in a level of 4 mg/L, unresponsive circulatory failure, and death. Early, aggressive gut decontamination and the potential value of cardiopulmonary bypass procedures in poisoning that lead to cardiac depression are emphasized.
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PMID:Extracorporeal bypass for the treatment of verapamil poisoning. 266 72

Adverse effects of beta-adrenergic receptor blocking drugs can be divided into two categories: 1) those that result from known pharmacological consequences of beta-adrenergic receptor blockade; and 2) other reactions that do not appear to result from beta-adrenergic receptor blockade. Adverse effects of the first type include bronchospasm, heart failure, prolonged hypoglycemia, bradycardia, heart block, intermittent claudication, and Raynaud's phenomenon. Neurological reactions include depression, fatigue, and nightmares. It is not yet proven whether the beta 1-selective adrenergic blockers or those with partial agonist activity reduce the overall frequency of adverse reactions seen with propranolol. Patient age does not appear, in itself, to be associated with more beta-blocker side effects. Side effects of the second category are rare. They include an unusual oculomucocutaneous reaction and the possibility of oncogenesis. There are also many drugs that interact with beta-blockers, which may increase toxicity. Finally, there are specific patient characteristics where one beta-blocker may be more effective and safer than another.
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PMID:Beta-adrenergic receptor blockers. Adverse effects and drug interactions. 289 72

Direct myocardial depression plays a role in the cardiovascular toxicity of local anesthetic agents, but this role is obscured by concomitant cardiac, systemic, and CNS events: seizures, hypoxia, acidosis, sympathetic activation, bradycardia, and A-V heart block. Direct injection of small bolus doses of lidocaine and bupivacaine into a branch of the left coronary artery was used to minimize these systemic effects. Regional contraction in the zone supplied by the coronary artery was measured with a sonomicrometer. Both agents caused a dose-dependent reduction in the extent of systolic contraction, and a 4.9:1 (lidocaine:bupivacaine) dose ratio produced a 50% depression of contraction. The duration of depression, taken as the time for 95% recovery of systolic contraction, was about 25% (P less than 0.05) longer with bupivacaine for an equal degree of depression. Coronary blood flow was reduced modestly by both agents. These results suggest that differences in the magnitude or duration of direct myocardial depression cannot explain the clinical perception that the cardiovascular toxicity of bupivacaine is greater than that of lidocaine.
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PMID:The magnitude and duration of direct myocardial depression following intracoronary local anesthetics: a comparison of lidocaine and bupivacaine. 291 63


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