Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Torsades de pointes (TdP) is a life-threatening ventricular tachycardia that occurs in the setting of a prolonged QT interval and is most frequently related to administration of antiarrhythmic drugs. Patients with organic heart disease, with low serum electrolyte levels, with a previous episode of TdP and with bradycardia or baseline QT prolongation may be at increased risk of developing TdP. After initiation of a QT prolonging therapy, the dosage should be modified if the QT interval reaches 560-600 ms. Cessation of medication and immediate hospitalization are indicated in the presence of lightheadedness, syncope, or increased frequency and complexity of ventricular premature beats. The conventional therapy of TdP with isoproterenol or cardiac pacing, although usually effective, has certain disadvantages. Isoproterenol is contraindicated in patients with hypertension or ischemic heart disease, whereas institution of cardiac pacing requires skilled personnel and fluoroscopy. Recently, infusion of magnesium sulfate has been shown to abolish TdP both in the clinical and experimental setting. Compared with conventional therapy, magnesium sulfate has the advantage of safety and simplicity of its administration. In doubtful cases, if does not aggravate a ventricular tachycardia that is not TdP, as may occur with isoproterenol. This advantage and the prompt effectiveness of the drug in four clinical series, including 31 patients, support the use of magnesium sulfate as the first line of therapy for TdP.
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PMID:Torsades de pointes: prevention and therapy. 185 60

The acute and chronic cellular electrophysiologic actions of ketanserin, a selective blocker of 5-hydroxytriptamine (5-HT2) receptor, were examined in the isolated rabbit ventricular muscle. This work was prompted by the recent observations that small numbers of patients treated with hypertension develop QTc prolongation, rarely associated with torsades de pointes. At 1.0 Hz stimulation, ketanserin, 10(-5) and 10(-4) M, prolonged the action potential duration (APD) (by 20% and 29%, respectively) and voltage-dependent refractoriness. At 10(-4) M, the maximal rate of rise of phase 0 of the action potential (Vmax) decreased 11%. Action potential amplitude and resting membrane potential were not affected by either concentration of ketanserin used (10(-6) to 10(-4) M). Trains of stimuli at rates of 1.0 Hz or higher led to an exponential decline in Vmax to a new plateau level. The time constant for the recovery of Vmax from the use-dependent block was 1.3 second. Chronic administration of ketanserin (40 mg/kg/day, intramuscularly) caused a significant prolongation of APD (106%; p less than 0.01) and voltage-dependent refractoriness without effects on the action potential amplitude, resting membrane potential, and Vmax. These data indicate that ketanserin exerts significant class I effects with mild class III effects when superfused acutely, whereas chronic administration of ketanserin exhibits marked class III effects. Both effects of the drug are likely to exert significant antiarrhythmic actions.
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PMID:Acute and chronic effects of ketanserin on the electrophysiologic properties of isolated rabbit ventricular myocardium: particular reference to repolarization. 337 40

Low potassium and magnesium concentrations not only cause cardiac arrhythmias, but also interfere with the efficacy or enhance the toxicity of drugs commonly used to treat patients with heart disease. Arrhythmias may develop in hypokalemia due to enhanced normal automaticity, abnormal automaticity, or slowed conduction; moreover, hypokalemia is associated with enhanced digitalis toxicity, quinidine-related Torsades de pointes, and interference with the antiarrhythmic activity of quinidine. Hypomagnesemia, especially in the presence of other electrolyte abnormalities, also affects automaticity and is associated with decreased efficacy of digitalis and with quinidine-related Torsades de pointes. Therefore, treatment that controls hypertension without causing electrolyte abnormalities is preferable for patients who are at risk of arrhythmias, or who are receiving drugs such as digitalis or quinidine.
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PMID:Effects of low potassium or magnesium concentrations on isolated cardiac tissue. 356 23

Three patients with primary aldosteronism were treated surgically between February and September 1984. All patients had suffered from hypertension with U waves in ECG and laboratory examinations revealed hypokalemia, hyperaldosteronemia and suppressed plasma renin activity. The localization of the adrenal tumor was diagnosed accurately in all 3 patients by adrenal vein sampling and in 2 of the patients by PRP, CT scan, adrenal scanning with 131I-iodo cholesterol and adrenal venography. Adrenal tumors were surgically removed by unilateral adrenalectomy through the flank approach in all cases. Histological examinations of removed specimens showed adrenocortical adenoma. Removal of the adenoma caused a prompt reversal of the laboratory serum abnormalities and hypertension was normalized within 2 weeks postoperatively in all cases. Severe ventricular tachycardia (Torsades de Pointes) was observed suddenly in one of the patients after about 5 hours postoperatively. Therapy including conventional antiarrhythmic drugs, such as lidocaine or procainamide, and potassium administration failed to prevent the arrhythmia. Ventricular tachycardia was successfully treated and disappeared with the use of magnesium sulfate (MgSO4) intravenously. The serum potassium concentration was normal during the episode and the serum magnesium concentration, which was not detected before or just after the operation, was under the limit of normal range (1.4 mEq/l) after the use of magnesium sulfate. Hypomagnesemia which is retrospectively thought to be the result of primary aldosteronism may be responsible for the episode of postoperative ventricular tachycardia.
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PMID:[Three cases of primary aldosteronism including one case with postoperative ventricular tachycardia]. 396 10

This is the first report of the successful use of magnesium sulfate (MgSO4) in 3 consecutive patients with torsades de pointes (TdP). In 1 patient, TdP was induced by a combination of quinidine and amiodarone, in the second by procainamide, and in the third by an overdose of imipramine. The QT intervals before TdP were 0.70, 0.64 and 0.56 second, respectively. A bolus of 1.0 to 2.0 g MgSO4 25% abolished the TdP in all 3 patients; but in the third patient, because of recurrent TdP, a second bolus of 1.0 g and a continuous 24-hour infusion of 1.0 mg/min were administered, preventing TdP. There was no immediate shortening in the QT interval in any patient after MgSO4. Magnesium can be given safely even in patients with acute myocardial infarction, angina pectoris or systemic hypertension, conditions in which isoproterenol is contraindicated; it can be applied faster than temporary cardiac pacing; and its use for TdP appears worthy of additional trials.
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PMID:Magnesium therapy for torsades de pointes. 669 82

Serotonin, or 5-hydroxytryptamine, is a naturally-occurring vasoactive substance found primarily in the brain, enterochromaffin tissue, and blood platelets. It has diffuse cardiophysiologic effects. The multiple effects of serotonin on blood vessels can be explained by the existence of 2 serotonergic receptor subtypes (the S1 receptor mediates vasodilation, and the S2 receptor vasoconstriction). Serotonin via the S2 receptor also augments the actions of several other vasoconstricting substances. Serotonin may be responsible for causing, or at least perpetuating, some forms of systemic hypertension through peripheral and central nervous system (CNS) actions. Ketanserin is a highly selective S2-serotonergic antagonist with additional alpha-adrenergic blocking activity, which has been proposed as a therapy for various cardiovascular diseases including hypertension. It has been shown to be more effective than placebo in treating hypertension and comparable in effectiveness to other antihypertensive drugs. Its major side effects relate to the CNS, and prolongation of the electrocardiogram QT interval has been described. Caution must be used when using ketanserin in patients receiving potassium- and magnesium-losing agents, because of the risk of torsades de pointes. Ketanserin has potential utility in the treatment of eclampsia, peripheral vascular disease, carcinoid syndrome, and "shock lung." The drug is not yet approved for clinical use in the United States.
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PMID:Serotonin and serotonin antagonism in cardiovascular and non-cardiovascular disease. 766 16

The therapeutic efficacy of magnesium has been studied during recent years in a number of cardiovascular diseases: supraventricular and ventricular arrhythmias (multifocal atrial tachycardia, Torsade de pointes-tachycardia, glycoside-associated arrhythmias, sustained ventricular tachycardia), acute myocardial infarction, heart failure and arterial hypertension. Although only a few of these arrhythmias were studied under controlled conditions, the therapeutic efficacy of intravenous magnesium given in a high dose in these arrhythmias seems to be established. By contrary, the efficacy of magnesium in acute myocardial infarction, congestive heart failure and arterial hypertension remains controversial up to now. Magnesium cannot be regarded as standard therapy for example for patients with acute myocardial infarction.
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PMID:[Magnesium: current studies--critical evaluation--consequences]. 906 59

Cisapride, a cytochrome P450 3A4 (CYP3A4) substrate, is widely prescribed for the treatment of gastrointestinal motility disorders. Prolongation of QT interval, torsades de pointes, and sudden cardiac death have been reported after concomitant administration with erythromycin or azole antifungal agents, but not with other CYP3A4 inhibitors. A possible drug interaction occurred in a 45-year-old woman who was taking cisapride for gastroesophageal reflux disorder and diltiazem, an agent that has inhibitory effect on CYP3A4, for hypertension. The patient was in near syncope and had QT-interval prolongation. After discontinuing cisapride, the QT interval returned to normal and symptoms did not recur. We suggest that caution be taken when cisapride is prescribed with any potent inhibitor of CYP3A4, including diltiazem.
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PMID:Prolongation of the QT interval related to cisapride-diltiazem interaction. 954 59

Magnesium is the fourth most abundant cation in the body and is present in more than 300 enzymatic systems, where it is crucial for adenosine triphosphate (ATP) metabolism. Deficiency states result in increased insulin resistance, as well as increased smooth muscle and platelet reactivity. Magnesium deficiency has been shown to correlate with a number of chronic cardiovascular diseases, including hypertension, diabetes mellitus, and hyperlipidemia. Intravenous magnesium has been used therapeutically in critical situations such as status asthmaticus, torsades de pointes, and preeclampsia. Few controlled studies exist regarding the therapeutic uses of oral magnesium supplementation in chronic cardiovascular diseases. Randomized clinical trials are urgently needed to determine whether magnesium supplementation will alter the natural history of these disease states.
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PMID:Magnesium: its proven and potential clinical significance. 1260 35

There are pharmacological differences between women and men that have important clinical consequences. For several drugs, there is a higher incidence in women of drug-induced QT prolongation and a potentially fatal arrhythmia, torsades de pointes. This may be a reflection of the longer baseline QT interval in women. A difference in cardiovascular disease between women and men is that women have a higher mortality rate after myocardial infarction (MI). Women also have a higher rate of hemorrhagic stroke after receiving thrombolytic therapy for an MI. Differences in effectiveness of analgesics have been demonstrated, with kappa opioids providing pain relief for women but not men. Drugs may have different pharmacokinetics in women and men because of differences in phase I and phase II enzymes that metabolize drugs. Conflicting results about biological sex differences have been reported for the major drug metabolizing enzyme, cytochrome P450 3A4 (3A4) and may be related to a role for P-glycoprotein, a cell membrane transporter, reported as two times higher in male livers than those of females. It has been reported that boys need a higher dose of 6-mercaptopurine, which is metabolized by thiopurine methyltransferase (TPMT). TPMT is reported to be 14% higher in male human liver biopsies than those from females. Verapamil, a drug for angina and hypertension, has different clearance and side effects in men and women. Ethnic/racial variations have also been demonstrated with the drug metabolizing enzymes, CYP2C9, 2C19, and 2D6.
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PMID:Biologic and molecular mechanisms for sex differences in pharmacokinetics, pharmacodynamics, and pharmacogenetics: Part I. 1239 93


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