Search PubMed⌕ Search

Biomedical subjects

V F Mauro

Publications and source records attributed to V F Mauro.

At least 37 records · Page 2Linked to original sources
PubMed1991

Simvastatin: a review of its pharmacology and clinical use.

Simvastatin, a chemical derivative of lovastatin, is an antihyperlipidemic medication that inhibits hydroxymethylglutaryl coenzyme A reductase. Animal and clinical data suggest simvastatin is twice as potent as lovastatin. It lowers serum cholesterol by inhibiting hepatic synthesis of cholesterol and, more importantly, by increasing the number of low-density lipoprotein (LDL) receptors present on hepatic cellular membranes. Simvastatin, when used at doses of 40 mg/d in patients with heterozygous familial hypercholesterolemia, significantly reduces total cholesterol (greater than 30 percent) and LDL cholesterol (35-45 percent) and tends to reduce triglycerides and raise high-density lipoprotein (HDL) cholesterol. The agent is also effective in patients with polygenic hypercholesterolemia, familial dysbetalipoproteinemia, and nephrotic syndrome. Addition of cholestyramine to simvastatin enhances the LDL cholesterol-lowering effect to approximately 55 percent. Common clinical adverse effects reported with simvastatin use include headaches and gastrointestinal complaints. Transient elevations in serum transaminases and creatine phosphokinase have also been seen. Based on data currently available, the drug's clinical activity and adverse-effect profile are similar to those of lovastatin. Therefore, there is no need for formularies to contain both medications. To choose between the two, one needs to consider the incidence of adverse effects and the daily cost of each product when used at equally effective doses. That information is now now available and, until it is, a clear recommendation cannot be made. Simvastatin, presently marketed in several countries, is investigational in the U.S. but is expected to be available soon.

Adolescent↗
PubMed1990

Effect of aluminum hydroxide gel on quinidine gluconate absorption.

The effect of aluminum hydroxide gel on quinidine gluconate bioavailability was studied in eight nonsmoking healthy male volunteers. Subjects were randomized to receive quinidine gluconate 648 mg with and without 30 mL of aluminum hydroxide gel. The mean area under the concentration-time curve (AUC) (23.11 +/- 5.21 mg.h/L), time to reach maximum concentration (tmax) (3.13 +/- 0.64 h), maximum serum concentration (1.44 +/- 0.41 mg/L), and elimination rate constant (0.069 +/- 0.010-h) observed during the control phase of the trial did not differ significantly (p greater than 0.05) from values obtained during the coadministration of aluminum hydroxide with quinidine gluconate (23.91 +/- 4.48 mg.h/L, 4.13 +/- 2.12 h, 1.53 +/- 0.34 mg/L, and 0.077 +/- 0.013-h, respectively). There was considerable individual variation in AUC with one subject demonstrating an increase of 35 percent and one subject demonstrating a decrease of 18 percent. There was a trend toward aluminum hydroxide delaying tmax with only one subject experiencing an earlier tmax with the coadministration of aluminum hydroxide. The results of this single-dose trial suggest that, although statistically the concurrent administration of aluminum hydroxide gel with quinidine gluconate does not significantly alter the extent of quinidine absorption, clinically significant individual variations may occasionally occur.

Adult↗
PubMed1989

Accuracy of two equations in determining normalized phenytoin concentrations.

The accuracy of two equations in normalizing total phenytoin concentrations in the presence of renal failure or hypoalbuminemia was evaluated in 11 renal failure and 23 hypoalbuminemic patients. Blood samples were obtained from hospitalized patients receiving phenytoin and were assayed for free and total phenytoin concentrations. Estimated normalized phenytoin concentrations based on free drug concentration were compared statistically with normalized concentrations calculated from the two equations via Student's t-test. The equation for normalizing phenytoin concentrations in hypoalbuminemic patients significantly underpredicted normalized phenytoin concentrations 15.7 +/- 8.5 versus 19.9 +/- 12.1 mg/L (p less than 0.001). In patients with renal failure, the mean phenytoin concentration from the respective equations and that based on free concentration were 14.1 +/- 6.2 and 14.0 +/- 7.9 mg/L, respectively. However, in 5 of 11 renal failure patients the equation resulted in over- or underprediction by at least 25 percent. Neither equation should be used clinically to normalize phenytoin concentrations in these patient populations.

Adult↗
PubMed1989

Organic nitrate-induced methemoglobinemia.

Metabolism of organic nitrates results in the formation of inorganic nitrites that can oxidize hemoglobin to methemoglobin. Clinical trials have investigated the risk of developing methemoglobinemia during the therapeutic use of organic nitrates. Based on the results of these trials, organic nitrate use does appear to increase methemoglobin content but not to a clinically significant extent. These elevations may be related to dose but study design prevents determination of any dose-response relationship. Despite these results, several case reports of patients experiencing clinically significant methemoglobinemia can be found in the literature. These patients generally received organic nitrates at doses greater than those used in the clinical trials, and several were diagnosed early during coronary surgery. Renal dysfunction and concurrent use of methemoglobin inducers may be contributing factors. Patients receiving organic nitrates should be monitored for symptoms suggestive of methemoglobinemia, especially while receiving large doses. Treatment of nitrate-induced methemoglobinemia consists of discontinuing the medication and, when necessary, administering methylene blue.

Animals↗
PubMed1988

Alteration of pentoxifylline pharmacokinetics by cimetidine.

Pentoxifylline, recently approved for the treatment of intermittent claudication, is hepatically cleared with a high degree of first-pass metabolism. Subsequently, the effect of cimetidine on pentoxifylline pharmacokinetics was studied in humans. Ten healthy subjects received, in random cross-over fashion, pentoxifylline 400 mg as a controlled-release tablet every 8 hours with and without cimetidine 300 mg four times a day for 7 days. Pentoxifylline and metabolite plasma concentrations over one dosing interval were measured on day 7 of each phase. The unavailability of an immediate-release pentoxifylline dosage form prevented a single dose trial. Cimetidine significantly increased (P less than .05) pentoxifylline area under the curve at steady state 26.2% from 675 +/- 97 (mean +/- SEM) to 852 +/- 108 ng. hr/mL. The average steady-state plasma concentration increased 27.4% from 84 +/- 12 to 107 +/- 14 ng/mL (P less than .05). Apparent oral clearance decreased 21.5% from 1309 +/- 304 to 1027 +/- 244 mL/min (P less than .02). Significant alterations in pentoxifylline metabolite concentrations were also observed. The results of this trial suggest cimetidine elevates pentoxifylline plasma concentrations, presumably by decreasing apparent oral clearance, although a reduction in total body clearance or an increase in gastric absorption could not be ruled out.

Adult↗
PubMed1988

Torsade de pointes in a patient receiving intravenous vasopressin.

A patient experienced hypertension, bradycardia, QT prolongation, and multiple episodes of torsade de pointes while receiving an iv vasopressin infusion. The dysrhythmias were attributed to vasopressin, but may have been potentiated by hypomagnesemia. Upon vasopressin discontinuation, ECG findings returned to normal before magnesium supplementation. Vasopressin may contribute to the development of torsade de pointes.

Esophageal and Gastric Varices↗
PubMed1987

Enhancement of phenytoin elimination by multiple-dose activated charcoal.

The effect of multiple-dose activated charcoal on the elimination of intravenously administered phenytoin was studied. Seven normal volunteers received phenytoin sodium 15 mg/kg IV with and without activated charcoal. During the charcoal phase, a total dose of 300 g was administered in repeated doses over 48 hours with sufficient sorbitol to produce one to two bowel movements per day. Serum phenytoin concentrations were determined from one to 72 hours after the infusions and were fitted to a one-compartment linear elimination model. The administration of multiple-dose activated charcoal reduced the phenytoin half-life from 44.5 to 22.3 hours. In addition, phenytoin area under the curve was decreased and the elimination rate was increased. Multiple-dose activated charcoal is effective in enhancing the elimination of phenytoin in normal volunteers. Although future studies are needed to determine its role in treating patients with phenytoin toxicity, multiple-dose activated charcoal may provide a readily available, inexpensive therapeutic intervention.

Adult↗
PubMed1987

Cefotetan-induced disulfiram-type reactions and hypoprothrombinemia.

A double-blind, placebo-controlled study in eight healthy male volunteers was conducted to study possible disulfiram-type reactions and hypoprothrombinemia associated with cefotetan administration. Three doses of cefotetan (2 g) or of placebo were administered at 12-h intervals. Ethanol (0.5 g/kg of total body weight) was ingested 1 h after the third dose. Blood ethanol, serum acetaldehyde, and prothrombin times were measured throughout the study. Heart rate, blood pressure, and clinical signs as well as symptoms suggestive of a disulfiram-type reaction were also noted. Five of eight volunteers that received cefotetan showed significant flushing. A significant increase in heart rate also was noted. No change in mean arterial pressure was observed during the cefotetan phase, and no one experienced nausea or vomiting. No statistical differences were observed between phases with respect to ethanol area under the time-concentration curve, elimination rate, or serum acetaldehyde concentrations. A slight but statistically significant increase in prothrombin time also was observed with cefotetan. This study suggests that patients receiving cefotetan might be at risk to develop disulfiram-type reactions and hypoprothrombinemia.

Acetaldehyde↗
PubMed1986

Early use of beta-adrenergic-blocking agents in acute myocardial infarction.

Of recent interest is the acute use of beta-adrenergic-blocking agents in patients who have suffered an acute myocardial infarction (AMI). Acute use of beta-blockers refers to initiation of therapy within hours following the onset of symptoms suggestive of AMI. The proposed goal of therapy is to alter the infarction process to improve mortality. Because of the hyperadrenergic activity present in patients during an infarction, beta-blockers are theoretically an attractive therapeutic intervention because of their sympatholytic properties. Acute use of beta-blockers has been shown to limit infarct size, as determined by cardiac enzyme activity, and reduce the incidence of major ventricular arrhythmias. Beta-blockers may also prevent infarction in patients with symptoms suggestive of infarction. However, the acute use of beta-adrenergic-blocking agents has not been shown to reduce short-term (less than or equal to 30 d) mortality. In view of this fact, the acute use of beta-adrenergic-blocking agents cannot be recommended.

Adrenergic beta-Antagonists↗
PubMed1986

Use of intermittent dobutamine infusion in congestive heart failure.

Dobutamine is a cardiac inotrope useful in the acute treatment of congestive heart failure. Dobutamine improves cardiac output, decreases pulmonary wedge pressure, and decreases total systemic vascular resistance with little effect on heart rate or systemic arterial pressure. Clinical benefit has been observed to continue for weeks to months following the discontinuation of dobutamine. In addition, tolerance to dobutamine has been observed when infusions last 72 hours or longer. This has led investigators to study the effectiveness of chronic intermittent infusions of dobutamine. Studies utilizing dobutamine doses ranging from 1.5 to 15 micrograms/kg/min for 4-48 h/wk have shown sustained clinical and hemodynamic improvement in patients suffering from congestive heart failure. The mechanism by which dobutamine creates this effect is not entirely known; however, studies suggest dobutamine exerts a physical conditioning effect similar to exercise. Dobutamine infusions have also been associated with morphological and metabolic changes in myocardial tissue consistent with improved myocardial structure and function. The intermittent use of dobutamine may be beneficial in the chronic treatment of congestive heart failure in patients who fail to respond to conventional therapy.

Dobutamine↗
PubMedDate not supplied

Impact of oral bases on aluminum absorption.

Control of hyperphosphatemia in renal failure is often difficult to achieve. Although calcium-containing phosphate binders have become the preferred phosphate binders, many patients require the addition of an aluminum-containing phosphate binder (APB). Enhanced aluminum absorption has been noted when APBs are administered with citrate-containing products such as citrate/citric acid solution (CCA). Alternative phosphate binders such as calcium acetate may also increase aluminum absorption. This study investigated the effect of CCAs on aluminum absorption when aluminum antacids (APBs) were administered concurrently and 2 hours apart. The effects of the alternative alkalinizing agent sodium bicarbonate and the alternate phosphate binding agent calcium acetate on aluminum absorption were also studied. During five 2-day phases, ten normal volunteers randomly received three times daily with standardized meals aluminum hydroxide alone and concurrently with NaHCO3, calcium acetate, CCA, or with CCA 2 hours postprandially. Twenty-four hour urines were collected on the second day of each phase and aluminum excretion was determined using inductively coupled plasma emission spectroscopy. Urine aluminum excretion was statistically significantly (P <.005) elevated in subjects receiving Al(OH)3 and CCA both with meals, 269.3 +/- 146.3 microg/d, and 2 hours after meals, 303.3 +/- 142.9 microg/d, compared with 79.2 +/- 52.0 microg/d during treatment with Al(OH)3 alone. Administration of CCA 2 hours after APB does not permit the safe use of these agents concurrently. Concomitant administration of sodium bicarbonate and calcium acetate with APBs appears to be safe, as aluminum absorption was not affected.

Absorption↗
PubMedDate not supplied

Misadventures with activated charcoal and recommendations for safe use.

OBJECTIVE: To review published reports of adverse effects associated with single- and multiple-dose activated charcoal therapy, and to formulate recommendations for safe use of activated charcoal therapy. DATA SOURCES: A manual search of Index Medicus from 1970 to December 1993 was conducted for English language articles; bibliographies of the resultant articles were also scanned. STUDY SELECTION: Cases were included if they were described in full detail, resulted in significant morbidity or mortality, and uniquely contributed to the formulation of recommendations for safe use of activated charcoal therapy. DATA SYNTHESIS: The major causes of morbidity and mortality secondary to activated charcoal therapy are aspiration of charcoal, gastrointestinal obstruction, and fluid and electrolyte abnormalities. Aspirations have occurred as a result of a number of circumstances that may be avoided. These include use in patients with unprotected airways, use of excessive charcoal dose, administration of inappropriately diluted charcoal, and administration of charcoal in the field. Gastrointestinal obstruction has occurred when multiple doses of activated charcoal have been administered without a cathartic and in cases in which a cathartic was administered if the patient had impaired peristalsis. Fluid and electrolyte abnormalities have occurred secondary to excessive cathartic administration. CONCLUSIONS: Activated charcoal therapy should be used judiciously so that related morbidity and mortality can be prevented. Adequate consideration for the patient's airway protection capability is necessary. Judicious dosing of charcoal and concomitant cathartic therapy, along with adequate monitoring of fluid and electrolyte status, abdominal physical assessment, and clinical condition are all vital to the safe use of activated charcoal therapy.

Charcoal↗