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)

Sotalol is a unique beta-blocker that prolongs repolarization. Its use in 626 patients with complex ventricular ectopic activity, as reported in the literature, resulted in suppression of arrhythmia in 50 to 60% of treatment attempts. Detailed analysis of data on arrhythmias in 356 patients that were entered prospectively into a database revealed a median reduction in ventricular premature beats of 76%, compared to a median suppression of repetitive ventricular ectopic activity of 91% and of episodes of nonsustained ventricular tachycardia of 97% (p = 0.002 vs reduction of ventricular premature beats). This marked antiarrhythmic potency of sotalol in repetitive ventricular arrhythmias is thought to be due to its class III activity. Drug efficacy was independent of age, sex, the presence or absence of organic heart disease and the degree of sotalol-induced prolongation of corrected QT interval. Evaluation of left ventricular function in 215 patients treated with the drug demonstrated that depression of left ventricular ejection fraction occurred far less frequently than expected with conventional beta-blockers. Even patients with severely depressed pump function tolerated sotalol surprisingly well. There is a propensity of the drug to aggravate arrhythmia, which resulted in serious proarrhythmic events in 30 (3.5%) of 853 patients. These often consisted of torsades de pointes (9 of 30 patients). Proarrhythmia occurred primarily within the first 3 days of dosing, and exhibited a dose-dependence. In conclusion, sotalol is an effective and well-tolerated antiarrhythmic drug in patients with complex ventricular ectopic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Efficacy and safety of sotalol in patients with complex ventricular arrhythmias. 128 7

The efficacy and safety of bepridil hydrochloride (200 to 400 mg/day) were evaluated in patients with chronic stable angina refractory to maximal tolerated doses of diltiazem (median 360 mg/day) in a randomized, multicenter, double-blind, parallel study. Baseline diltiazem data were obtained during a 2-week period, after which 86 patients were randomized to bepridil (n = 46) or diltiazem (n = 40). Angina frequency, nitroglycerin consumption and ischemic manifestations induced by exercise treadmill testing were evaluated over 8 weeks. Bepridil significantly (p less than 0.05) increased time to angina onset, time to 1 and 2 mm of ST-segment depression, total exercise time and total work over baseline values. Changes in time to angina onset and time to 1 mm of ST-segment depression were significantly (p less than 0.05) greater for bepridil than for diltiazem. Angina frequency and nitroglycerin consumption did not differ significantly between groups. Compared with baseline, bepridil significantly (p less than 0.001) decreased heart rate (mean 4 beats/min) and prolonged QTc (mean 35 ms). The most frequent adverse effects in both groups were nausea, asthenia, dizziness, headache and diarrhea. Four patients taking bepridil and 1 taking diltiazem withdrew from the study because of adverse reactions. No sudden deaths, myocardial infarctions or instances of sustained ventricular tachycardia or torsades de pointes occurred in either group. The data indicate that bepridil provided safe and effective antianginal and antiischemic therapy in patients with chronic stable angina who exhibited less than optimal response to maximal tolerated doses of diltiazem.
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PMID:Comparative efficacy and safety of bepridil and diltiazem in chronic stable angina pectoris refractory to diltiazem. The Bepridil Collaborative Study Group. 185 72

Four patients, 64-80 years of age, with severe renal dysfunction and heart disease received conventional doses of procainamide as treatment for cardiac arrhythmias. Serum procainamide concentrations at these times ranged from 6.2 to 13.3 micrograms/ml and were within the recently expanded therapeutic range for resistant ventricular arrhythmias. All 4 patients demonstrated marked and delayed accumulation of the active metabolite N-acetylprocainamide, with highest observed serum concentrations ranging from 42.0 to 59.4 micrograms/ml. Cardiotoxicity associated with these levels included progressive widening of the QRS and corrected Q-T intervals, induction of polymorphic non-sustained ventricular tachycardia (torsades de pointes), and severe depression of left ventricular function which appeared to be important factors in the deaths of these patients. The use of lower procainamide doses and careful anticipatory monitoring of serum concentrations of procainamide and N-acetylprocainamide are essential in this high-risk group.
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PMID:Lethal accumulation of procainamide metabolite in severe renal insufficiency. 242 35

The study of the tapes of ambulatory patients who died while wearing Holter devices allows us to know the terminal electrical events of death in these cases and which are the electrical triggering mechanisms leading to the terminal event. From the evaluation of seven published series with 10 or more cases, we can see that the most frequent causes of sudden death are ventricular tachyarrhythmias (84% of cases) and bradyarrhythmias (16%). VF was the most frequent ventricular tachyarrhythmia, usually secondary to VT. The rest were due to torsades de pointes in patients often without heart disease but who were taking antiarrhythmic drugs. The VT leading to VF was often preceded by sinus tachycardia or new atrial tachyarrhythmia. Only a small percentage of patients presented ischemic ST changes. In patients who died due to bradyarrhythmias, this was more often due to sinus depression than to atrioventricular block.
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PMID:Ambulatory sudden cardiac death: mechanisms of production of fatal arrhythmia on the basis of data from 157 cases. 291 68

To determine the frequency and severity of cardiac arrhythmias in intracranial subarachnoid hemorrhage, 120 nonselected patients were prospectively studied by 24-hour Holter monitoring. Arrhythmias were found in 96 of 107 patients (90%) with adequate Holter recording: ventricular premature complexes in 49, nonsustained ventricular tachycardia in 5, supraventricular premature complexes in 29, paroxysmal supraventricular tachycardia or atrial fibrillation in 9, sinoatrial block and arrest in 29, second-degree atrioventricular block in 1, atrioventricular dissociation in 4 and idioventricular rhythm in 2. Life-threatening ventricular arrhythmias (torsades de pointes-type ventricular tachycardia) occurred in 4 patients, degenerating into either ventricular flutter or fibrillation in 2. ST-segment changes suggestive of acute transitory myocardial ischemia were found in 8 patients (1.5 mm or more of ST depression in 7 patients and 1.5 mm or more of ST elevation in 1 patient). The frequency and severity of arrhythmias were significantly higher in patients studied within 48 hours of subarachnoid hemorrhage; serious ventricular arrhythmias were associated with QTc prolongation more than 550 ms and with hypokalemia less than 3.5 mEq/liter. No correlation was found between age, clinical condition, site and extent of subarachnoid hemorrhage and either the occurrence or severity of arrhythmias. The results of our study indicate an extremely high incidence of arrhythmias, sometimes serious, in subarachnoid hemorrhage, especially in the first 48 hours after hemorrhage. Continuous electrocardiographic monitoring is therefore mandatory.
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PMID:Holter detection of cardiac arrhythmias in intracranial subarachnoid hemorrhage. 382

Marked QT prolongation with induction of polymorphous ventricular tachycardia ("Torsades de Pointes") is a well-described phenomenon during quinidine therapy, frequently occurring at low plasma quinidine concentrations, low serum potassium, and slow heart rates. We have therefore assessed the dose-electrophysiological effects of quinidine as a function of extracellular potassium and cycle length in canine Purkinje fibers, using standard microelectrode techniques. Quinidine (1 microM) prolonged action potential at 90% repolarization, while leaving phase zero upstroke slope (Vmax) unchanged at a cycle length 300-8000 msec; at 10 microM, Vmax depression became evident. Increases in the action potential at 90% repolarization were most marked at long cycle lengths and low extracellular potassium (in contrast to Vmax depression) and were partially reversed by tetrodotoxin (1 microM). The relationship between log of cycle length and action potential at 90% repolarization was linear (for cycle length 300-8000 msec) in the absence of quinidine. Quinidine increased the slope of this relationship in a concentration-related fashion, whereas increasing extracellular potassium shifted the curve rightward (without changing slope), regardless of the presence or absence of quinidine. Action potentials were also measured following pauses of 5-60 seconds. In the absence of quinidine, the action potential depolarization returned to its baseline value in a monoexponential fashion (time constant 36.0 +/- 4.9 sec, mean +/- SE, n = 10). In the presence of 1 microM quinidine, this return was better fit as a biexponential process (time constants 4.2 +/- 1.2 and 40.7 +/- 6.2 seconds, n = 14). At slow stimulation rates (cycle length greater than 4000 msec) in low extracellular potassium (2.7 mM), quinidine produced early afterdepolarizations in 7/14 (50%) of fibers at 1 microM and 14/18 (78%) at 10 microM. Early afterdepolarizations were eliminated by increasing stimulation rates, raising the extracellular the extracellular potassium concentration to 5 mM, or adding tetrodotoxin. These data suggest that prolongation by quinidine of action potentials at 90% repolarization is multifactorial, with both a "tonic" prolonging effect and a prominent frequency-dependent action potential shortening effect. At long cycle lengths and low extracellular potassium, low quinidine concentrations consistently produced early after-depolarizations. The parallels between this form of triggered activity and clinical arrhythmias induced by quinidine suggest that early afterdepolarizations may play a role in quinidine-induced Torsades de Pointes.
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PMID:Action potential prolongation and induction of abnormal automaticity by low quinidine concentrations in canine Purkinje fibers. Relationship to potassium and cycle length. 400 95

New tricyclic antidepressants such as amineptine and tianeptine have mild toxic effects while amoxapine is very toxic. Poisoning with new selective serotonin reuptake inhibitor antidepressants or monoamine-oxidase inhibitors type A (toloxatone, moclobemide) is usually not severe, but life-threatening serotonin syndromes may appear in case of drug combination with antidepressants. Loxapine and clozapine poisoning may lead to death while risperidone intoxication has usually a rather benign course. Substituted benzamide neuroleptics (amisulpride, sultopride) may induce seizures, QT prolongation and torsades de pointes. New hypnotics such as zolpidem and zopiclone have a mild toxicity similar to that of benzodiazepines, but coma and respiratory depression are observed if other drugs or ethanol are ingested or in case of chronic hepatic or respiratory insufficiency.
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PMID:[Acute poisoning by new psychotropic drugs]. 918 49

I believe there are four essential elements in the management of patients with irritable bowel syndrome (IBS): to establish a good physician-patient relationship; to educate patients about their condition; to emphasize the excellent prognosis and benign nature of the illness; and to employ therapeutic interventions centering on dietary modifications, pharmacotherapy, and behavioral strategies tailored to the individual. Initially, I establish the diagnosis, exclude organic causes, educate patients about the disease, establish realistic expectations and consistent limits, and involve patients in disease management. I find it critical to determine why the patient is seeking assistance (eg, cancer phobia, disability, interpersonal distress, or exacerbation of symptoms). Most patients can be treated by their primary care physician. However, specialty consultations may be needed to reinforce management strategies, perform additional diagnostic tests, or institute specialized treatment. Psychological co-morbidities do not cause symptoms but do affect how patients respond to them and influence health care-seeking behavior. I find that these issues are best explored over a series of visits when the physician-patient relationship has been established. It can be helpful to have patients fill out a self-administered test to identify psychological co-morbidities. I often use these tests as a basis for extended inquiries into this area, resulting in the initiation of appropriate therapies. I encourage patients to keep a 2-week diary of food intake and gastrointestinal symptoms. In this way, patients become actively involved in management of their disease, and I may be able to obtain information from the diary that will be valuable in making treatment decisions. I do not believe that diagnostic studies for food intolerances are cost-effective or particularly helpful; however, exclusion diets may be beneficial. I introduce fiber supplements gradually and monitor them for tolerance and palatability. Synthetic fiber is often better-tolerated than natural fiber, but must be individualized. In my experience, excessive fiber supplementation often is counterproductive, as abdominal cramps and bloating may worsen. Antidiarrheal agents are very effective when used correctly, preferably in divided doses. I use them in patients in anticipation of diarrhea and especially in those who fear symptoms when engaged in activities outside the home. I encourage patients to make decisions as to when and how much to use. However, almost always, a morning dose before breakfast is used (loperamide, 2 to 6 mg) and, perhaps again later in the day when symptoms of diarrhea are prominent. I prefer antispasmodics to be used intermittently in response to periods of increased abdominal pain, cramps, and urgency. For patients with daily symptoms, especially after meals, agents such as dicyclomine before meals are useful. For patients with infrequent but severe episodes of unpredictable pain, sublingual hyoscyamine often produces rapid relief and instills confidence. In general, I recommend that oral antispasmodics be used for a limited period of time rather than indefinitely, and generally for periods of time when symptoms are prominent. For chronic visceral pain syndromes, I recommend small doses of tricyclic antidepressants. These agents are especially effective in diarrhea-predominant patients with disturbed sleep patterns but may be unacceptable to patients with constipation. I educate patients that side effects occur early and benefits may not be apparent for 3 to 4 weeks. I consider using SSRIs in low doses in patients with constipation-predominant IBS; cisapride, 10 to 20 mg three times per day, also may be beneficial. When taken with drugs that inhibit cytochrome P450, cisapride has been associated with serious cardiac arrhythmias caused by QT prolongation, including ventricular arrhythmias and torsades de pointes. These drugs include the azole fungicides; erythromycin, clarithromycin, and troleandomycin; some antidepressants; HIV protease inhibitors; and others. In patients with IBS with mild to moderate co-morbid depression, I have found that the use of SSRIs such as paroxetine, fluoxetine, or sertraline may be beneficial. It is important to tell patients that anxiety and disturbed sleep may occur during the first 10 days and benefits may not occur for 3 to 4 weeks. I prescribe a small amount of a short-acting benzodiazepine such as alprazolam, 0.5 mg two times per day, to control these symptoms. For generalized anxiety without depression, buspirone or clonazepam may be useful. I have found that patients who also have associated panic disorder may benefit from a benzodiazepine, tricyclic antidepressant, or an SSRI. However, these patients are best managed in conjunction with a psychiatrist or psychologist. I consider the use of alternative therapies in patients who fail to respond to conventional measures and who are receptive to alternative strategies. These include general relaxation techniques such as biofeedback and hypnosis therapies.
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PMID:Irritable Bowel Syndrome. 1109 67

Emergency medical services (EMS) providers must often manage violent or combative patients. The data regarding violence against EMS personnel are poor, but according to studies conducted thus far, between 0.8% and 5.0% of incidents to which EMS personnel respond involve violence or the threat of violence. Physical or chemical restraint is usually the only option available to emergency care providers to control violent patients. Physical restraint, however, can lead to sudden death in otherwise healthy patients, possibly as a result of positional asphyxia, severe acidosis, or a patient's excited delirium. Chemical restraint has traditionally consisted of either neuroleptics or benzodiazepines, but those drugs also have drawbacks. Haloperidol and droperidol, the neuroleptics most frequently used for restraint, can cause serious side effects such as extrapyramidal symptoms or QTc (QT interval corrected for heart rate) prolongation. The Food and Drug Administration recently issued a black box warning regarding the use of droperidol, because the QTc prolongation associated with the drug has led to fatal torsades de pointes in some patients. Benzodiazepines are also associated with adverse effects, such as sedation and respiratory depression, especially when the drugs are mixed with alcohol. The atypical antipsychotics, a new option that may be available soon, are less likely to cause such effects and therefore may be preferred over the neuroleptics. Liquid and injectable formulations of various atypical antipsychotics are currently in clinical trials. Because few options are currently available to EMS personnel for managing violent patients outside of the hospital, more research regarding violence against emergency care providers is necessary.
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PMID:Management of the violent patient. 1254 Jan 43

A 70-year-old woman presented with acute pancreatitis and new-onset QT prolongation with subsequent torsades de pointes. Coronary catheterization was performed and was unremarkable. After persistent QT prolongation, despite temporary atrial pacing, a permanent dual chamber cardioverter defibrillator was implanted. In addition to the QT prolongation, significant depression in the left ventricular function was noted. Both resolved once the pancreatitis abated.
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PMID:New-onset QT prolongation and torsades de pointes accompanied by left ventricular dysfunction secondary to acute pancreatitis. 1287 13


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