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Biomedical subjects

M S Chow

Publications and source records attributed to M S Chow.

At least 73 records · Page 4Linked to original sources
PubMed1991

Characteristics of ceftriaxone binding to immunoglobulin G and potential clinical significance.

The interaction between immunoglobulin G (IgG) and ceftriaxone was studied. Using an ultrafiltration method, we performed dose ranging studies at a ceftriaxone concentration range of 1 to 720 micrograms/ml in the presence of various concentrations of human IgG, human serum albumin (HSA), and combinations of IgG and HSA at pH 7.4 and 37 degrees C. The results showed that ceftriaxone binding to IgG was nonlinear and was consistent with the presence of two binding sites that possess different binding capacities and affinities. Except for increased peak percent binding as the IgG concentration increased, the binding characteristics did not change with IgG concentration. Binding to HSA was consistent, with the presence of only one high-affinity binding site. A mathematical model based on the observed data was constructed; this model was used to predict protein binding at various concentrations of drug, IgG, HSA, or combinations of IgG and HSA in buffer and in plasma medium. Correlations between the observed versus the predicted values were excellent in both media. Simulations with the model indicated that patients with hypergammaglobulinemia have an increased potential of being exposed to prolonged subinhibitory concentrations of ceftriaxone if the drug is given once every 24 h.

Ceftriaxone↗
PubMed1991

The controversy of heparin therapy as an adjunct to thrombolysis in acute myocardial infarction.

Heparin is used routinely in the US as adjunct therapy for prevention of reocclusion after thrombolysis during acute myocardial infarction. A review of the literature shows controversy over the efficacy of heparin following thrombolysis. Both beneficial and a lack of beneficial effects have been reported with heparin. From a pathophysiologic viewpoint, there appears to be a need for full heparinization in the postlytic period because the residual stenosis is highly thrombogenic. However, optimal dose, time, and mode of heparin therapy has not been defined. Despite a lack of definitive data, it seems reasonable to administer intravenous heparin immediately after thrombolytic therapy to achieve a partial thromboplastin time 1.5-2.0 times control that is concurrent with an antiplatelet agent such as aspirin. These recommendations are consistent with the consensus opinion of the American College of Cardiology and the American Heart Association.

Drug Therapy, Combination↗
PubMed1991

Strategy for developing a safe and cost-effective H2-receptor antagonist program.

The pharmacy staff of a community tertiary-care hospital evaluated efficacy and safety before addressing cost considerations in the transition to a capitation program with cimetidine as the preferred H2-receptor antagonist. Safety concerns were resolved by permitting the use of an alternative drug certain patients considered to be at high risk. Despite initial resistance to mandatory participation in the program, the physician and nursing staffs have grown supportive, and the annual cost savings, which include the costs of labor and supplies as well as acquisition, have been substantial.

Cimetidine↗
PubMed1990

Achieving rational therapeutics through consensus-based protocols and follow-up.

In this exclusive Hospital Formulary interview, three key members of the therapeutics committee at Hartford Hospital, an 861-bed, private teaching hospital, discuss some of the techniques that they have used to ensure the development of a sound and effective formulary system within their institution. The committee emphasizes a policy-making approach that incorporates, up front, the expertise of key clinicians together with the best available information from the medical literature. Once committee policy has been set, implementation of drug use guidelines is largely automatic, and compliance is carefully monitored and reviewed.

Connecticut↗
PubMed1990

The time to reach steady state after the administration of intravenous bolus, constant infusion, and oral immediate-release and sustained-release preparations.

Based on one-compartment pharmacokinetic model, the equations to calculate the specific fractional steady-state of drug level achieved at any time (FSS) after administration of intravenous bolus, constant infusion, and oral immediate-release preparations are reviewed. Also the equation to calculate FSS after administering an oral sustained-release dosage form is derived. From these equations, it can be shown that the drug FSS after these routes of administration is dependent primarily on the elimination rate constant (K). However, for a sustained-release preparation, the FSS is dependent on K, drug release rate constant (Kr), as well as the fraction of sustained release (Fs) of the dosage form. Using the new derived equation for FSS, several simulations were performed to evaluate the effects of Kr K, and Fs. These indicate that the time to achieve a given FSS is prolonged as Kr or K becomes smaller and as Fs becomes large.

Administration, Oral↗
PubMed1989

Acute effects of combination of IB and IC antiarrhythmics for the treatment of ventricular tachycardia.

There are limited data on the effects of Class IB and IC antiarrhythmic drug combination for the treatment of ventricular tachycardia. The present study evaluated this combination in 12 patients who had sustained ventricular tachycardia (SuVT) during programmed electrical stimulation (PES) and failed IC antiarrhythmic therapy. Following combination of lidocaine and a IC agent (7 with encainide and 5 with flecainide), two had no inducible ventricular tachycardia (VT) and one had nonsustained VT (NSVT). In seven of nine patients who still had SuVT, the mean VT cycle length increased 40 +/- 25 msec post combination compared to IC antiarrhythmic therapy. Seven patients who had a favorable response to the initial combination (less than 10 beats of NSVT, or greater than or equal to 10 beats of VT with a greater than 100 msec increase in cycle length compared to baseline and no hemodynamic compromise) were then placed on IC + oral IB agent (5 with mexiletine, 2 with tocainide). Similar effects on VT inducibility and cycle length were observed following the oral combination. In conclusion, the addition of lidocaine to IC therapy produced favorable effects on induced ventricular tachycardia in 58% of patients compared to IC agent alone. Also, a positive PES response to lidocaine and IC therapy corresponded to a similar positive response when either mexiletine or tocainide was substituted for lidocaine.

Anilides↗
PubMed1989

Differences in systemic and myocardial blood acid-base status during cardiopulmonary resuscitation.

Simultaneous arterial (aortic), mixed venous (pulmonary artery), and myocardial venous (great cardiac vein) blood gas and lactate concentrations were obtained in 12 dogs before and during cardiac arrest and CPR. We observed marked mixed venous and myocardial venous acidosis and increased PaCO2 but normal pHa and reduced PaCO2. Furthermore, the pH was significantly lower and the PCO2 significantly higher at the myocardial venous site compared to the mixed venous site, and marked myocardial lactate production occurred during CPR. Calculated bicarbonate and CO2 content (CCO2) did not increase during CPR from any site compared to control values and actually decreased significantly in arterial and myocardial venous samples. Changes in hydrogen ion concentration in both mixed venous and myocardial venous blood correlated with changes in lactate concentration but not total CCO2. Our results during CPR demonstrate a) a significant discrepancy between arterial and mixed venous blood gases but also a large and significant discrepancy between mixed venous and myocardial venous blood gases, b) significant anaerobic systemic and myocardial metabolism, and c) that mixed venous and myocardial venous acidosis is possibly a result of lactic acidosis.

Acid-Base Equilibrium↗
PubMed1989

Epinephrine versus methoxamine in survival postventricular fibrillation and cardiopulmonary resuscitation in dogs.

Previous studies have indicated that methoxamine (an alpha adrenergic receptor agonist) may provide an advantage compared to epinephrine (a mixed alpha and beta adrenergic agonist) during cardiac arrest and CPR. To test this theory, we compared the effects of bolus injections of epinephrine vs. methoxamine on survival, hemodynamic variables, blood gases, and blood lactate concentrations during ventricular fibrillation and CPR in 12 dogs. Each dog underwent a 3-min fibrillatory arrest followed by 10 min of fibrillation and CPR, at which time the animals were defibrillated. Epinephrine (0.05 mg/kg, n = 6) or methoxamine (2 mg/kg, n = 6) was administered at the start of CPR. Both epinephrine and methoxamine produced identical survival rates (5/6) with no differences in coronary perfusion pressure gradients or blood gases (aortic, venous, or great cardiac venous pH, PaO2, or PaCO2) during CPR. Also, there were no differences between the two study groups in myocardial lactate or oxygen extraction ratios during CPR. We conclude that in the dosages tested in our experimental model, epinephrine and methoxamine produce similar results in the variables which we measured.

Animals↗
PubMed1988

Clinical and electrophysiologic effects of flecainide in patients with refractory ventricular tachycardia.

The electrophysiologic effects and antiarrhythmic efficacy of flecainide were evaluated by electrophysiologic study (EPS) in 20 patients with ventricular tachycardia (VT) refractory to an average 2.9 drugs. In 19 patients EPSs were performed with patients not receiving antiarrhythmic medications and receiving oral flecainide therapy at steady state (mean dose, 235 +/- 67 mg/day). Flecainide significantly increased the QRS complex duration (27%, P less than .001), PR interval (17%, P less than .001), and right ventricular effective refractory periods 8.5% and 21.1% (P less than .01) for the first and second extrastimuli, respectively. During baseline EPS, 17 patients were induced into VT and two were noninducible. Flecainide prevented EPS-induced VT in five patients and the induced VT became slow and hemodynamically stable in three. Two patients who failed flecainide monotherapy were induced into slow hemodynamically stable VT with flecainide in combination with amiodarone. The two noninducible patients, during baseline EPS, had suppression of spontaneous VT with flecainide. Overall, 13 of 20 patients received flecainide either alone or in combination with amiodarone for chronic therapy. Side effects encountered during the study consisted of blurred vision, dizziness, weakness, lethargy, nausea, worsened heart failure and bradyarrhythmias. After a mean 9-month follow-up (3 to 16 months) nine patients remain on flecainide therapy. There were three recurrences of slow, hemodynamically stable VT and no episodes of sudden death. Low-dose flecainide, either alone or in combination with other agents, is effective therapy for certain patients with refractory VT but heart failure remains a significant concern in patients with depressed left ventricular function.

Aged↗
PubMed1988

Clinical pharmacokinetics of controlled-release disopyramide in patients with cardiac arrhythmias.

UNLABELLED: The pharmacokinetics of the controlled-release preparation of disopyramide phosphate (Norpace CR, Searle Laboratories, Chicago, IL) were studied in ten patients with cardiac arrhythmias. Multiple-serum disopyramide concentrations were obtained after a 300-mg oral dose. Each patient then received chronic oral therapy with the controlled-release preparation (400 to 1000 mg/day) on an every-12-hour schedule. At steady state, disopyramide trough concentrations were obtained. Serum disopyramide concentrations were determined by high performance liquid chromatography. The regimen was well tolerated by all patients. The mean (+/- SD) time to maximum concentration, maximum concentration, and concentrations 11 and 24 hours after the initial dose were 5.5 +/- 1.3 hours and 2.8 +/- 0.8, 2.0 +/- 0.9, and 1.2 +/- 0.5 micrograms/mL, respectively. A low Cmax to trough concentration ratio of 1.35 +/- 0.26 was observed after the initial dose. Linear regression analysis of the serum disopyramide concentrations 11 hours after initial dose (trough) versus trough concentrations at steady state (dose adjusted) showed a strong correlation (r = 0.87, intercept = 0.03, and slope = 1.9). Regression analysis also showed a strong relationship between the area under the curve (AUC) from time 0 to 11 hours after the initial dose and the trough at steady state (r = 0.86). CONCLUSIONS: The controlled-release preparation of disopyramide, when administered every 12 hours in patients with cardiac arrhythmias, should produce low peaks to trough fluctuations. Because disopyramide concentrations after the initial dose correlate well with trough concentrations at steady state, these concentrations may provide a simple and convenient method for prospective monitoring of disopyramide therapy in patients receiving the controlled-release preparation.

Adult↗
PubMed1988

An evaluation of the pharmacokinetics, pharmacodynamics, and dialyzability of verapamil in chronic hemodialysis patients.

The pharmacokinetics and pharmacodynamics of verapamil were investigated in six chronic hemodialysis patients. A single oral 120-mg dose was administered both on a non-hemodialysis day and a hemodialysis day separated by greater than or equal to 7 days. Blood pressure and PR interval were measured simultaneously with each blood sample. Plasma verapamil and norverapamil concentrations were analyzed by high pressure liquid chromatography. The mean Cmax, tmax, AUC, apparent plasma clearance, and terminal t 1/2 were 190 +/- 108 ng/mL, 0.6 +/- 0.2 hour, 676 +/- 443 ng.hr/mL, 3926 +/- 1933 mL/min, and 11.4 +/- 4.0 hr, respectively, on the nonhemodialysis day. The dialysis clearance of verapamil and norverapamil was negligible. The t 1/2 during hemodialysis was 3.6 +/- 1.1 hr, compared with 3.4 +/- 0.7 hr during the same period of time postdose on the nonhemodialysis day (NS, P greater than .05). Systolic and diastolic blood pressure decreased for up to 4 hours postdose, whereas the PR interval tended to increase. Conclusions include: (1) the single oral-dose pharmacokinetics and pharmacodynamics of verapamil in chronic hemodialysis patients are similar to published data in normal subjects and cardiac patients and (2) verapamil and norverapamil are not significantly removed by hemodialysis, so that supplemental doses are not necessary.

Adult↗
PubMed1988

Effect of renal impairment on the pharmacokinetics of cibenzoline.

Sixteen subjects completed an open-label study designed to assess the effect of renal impairment on the disposition of cibenzoline. The study included 10 patients with mild or moderate renal impairment creatinine clearance less than 60 ml/min/70 kg) and six healthy subjects in the same age range, each of whom received a single 130 mg oral dose of cibenzoline. The pharmacokinetic parameters observed in the healthy volunteers were similar to those reported previously. Maximum plasma concentration, time of maximum concentration, and apparent volume of distribution after single doses in patients with renal impairment were in the same range as those observed in healthy volunteers. The elimination half-life increased with decreasing renal function from a mean value of approximately 8 hours in healthy volunteers to more than 20 hours in patients with moderate renal impairment. Renal clearance and the fraction of the dose excreted unchanged in the urine decreased with decreasing creatinine clearance. The results of this study suggest that the dosage of cibenzoline should be reduced or the dosage interval increased in patients with reduced renal function to avoid excessive drug accumulation.

Administration, Oral↗
PubMed1988

Rimantadine pharmacokinetics in healthy subjects and patients with end-stage renal failure.

The single-dose (two 100 mg doses) pharmacokinetics of rimantadine hydrochloride were compared in eight patients with end-stage renal disease who were on hemodialysis and seven age-matched healthy subjects. Plasma and urine rimantadine concentrations were determined by a GC/MS method. The plasma half-life (43.6 vs 27.5 hours) and AUC (9.9 +/- 2.1 vs 6.0 +/- 1.6 micrograms.hr/ml) were significantly (p less than 0.05) increased in the patient population. No significant differences were noted in the maximum rimantadine concentration, time of maximum concentration, or apparent volume of distribution. Urinary excretion of unchanged rimantadine accounted for 16% of the dose in the healthy subjects. Hemodialysis did not appreciably remove rimantadine. These findings suggest that rimantadine dosage may need to be reduced in patients with end-stage renal disease but supplemental doses on dialysis days are not required.

Adamantane↗
PubMed1988

Antifibrillatory effects of high dose bretylium and a lidocaine-bretylium combination during cardiopulmonary resuscitation.

Previous CPR studies from our laboratory have shown that a standard iv dose of lidocaine (2 mg/kg) has a rapid antifibrillatory effect, while a standard dose of bretylium (5 mg/kg) produces a delayed but more pronounced effect. In order to determine the optimal doses, we investigated the antifibrillatory effects of a) high dose bretylium (10 mg/kg) and b) a combination of lidocaine (2 mg/kg) and bretylium (5 mg/kg) during CPR in two groups of anesthetized dogs. Ventricular fibrillation threshold (VFT) was determined using a train method and CPR was performed by a pneumatic device. During both a control and drug phase, the VFT was determined in each dog before CPR, and after each of three consecutive 3-min CPR periods. The combination of lidocaine and bretylium (11 dogs) caused a significant increase in VFT compared to the control phase after each of the 3-min CPR periods and maintained this effect for greater than 2 h. Bretylium 10 mg/kg (eight dogs) significantly elevated the VFT only after the third 3-min CPR period. We conclude that the combination of standard doses of lidocaine and bretylium produces a rapid and prolonged antifibrillatory effect and may be the optimal regimen in the CPR setting. High dose bretylium has a delayed onset of effect and appears to produce no greater effect than standard doses of the drug.

Animals↗
PubMed1988

Propafenone: a new antiarrhythmic agent.

The chemical and pharmacologic properties, pharmacokinetics, drug interactions, clinical efficacy, adverse effects, and dosage of propafenone are reviewed. Propafenone is a class IC antiarrhythmic agent that is structurally similar to the beta blockers but that has only weak beta-blocking and calcium-channel-blocking activity. It is well absorbed after oral administration, but systemic bioavailability is only 12% after a 300-mg dose. Among extensive metabolizers (greater than 90% of the United States population), bioavailability seems to vary nonlinearly with dose and increases substantially with food; these effects are not seen in poor metabolizers. Elimination is primarily hepatic, with a mean elimination half-life after oral administration of 5.5 hours in extensive metabolizers and 17.2 hours in poor metabolizers. The relationship between plasma propafenone concentration and clinical response varies considerably among individual patients; therefore, plasma concentrations have limited usefulness in predicting efficacy or electrophysiologic effects. Propafenone is effective in treating ventricular tachycardia and in suppressing premature ventricular complexes (PVCs). It is less effective in the treatment of refractory ventricular tachycardia. Concurrent administration of digoxin, warfarin, or metoprolol with propafenone has been shown to increase the serum concentrations of those three drugs, while cimetidine slightly increases the propafenone concentrations. Additive pharmacologic effect can occur when lidocaine, procainamide, and quinidine are combined with propafenone. Overall, 21% to 32% of patients experience adverse effects, with 3% to 7% of these serious enough to warrant discontinuing therapy. The most common adverse effects are dizziness or lightheadedness, metallic taste, and nausea and vomiting; the most serious adverse effects are proarrhythmic events.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗