PubMed Health⌕ Search

Biomedical subjects

D H Waters

Publications and source records attributed to D H Waters.

16 recordsLinked to original sources
PubMed1987

Steady state absorption kinetics and pharmacodynamics of furosemide in congestive heart failure.

Furosemide, a potent loop diuretic, is commonly used in the treatment of congestive heart failure (CHF). Unpredictability in the diuretic effect following oral doses has been attributed to variable and incomplete absorption and to variability in the pharmacodynamic response to furosemide. The present study is undertaken to investigate the absorption kinetics and pharmacodynamics of furosemide in patients with CHF during chronic medication. Ten patients with congestive heart failure were maintained on 40 to 160 mg furosemide for a month. The final dose at the end of this period was administered on an empty stomach. Plasma and urine were collected and assayed for furosemide, potassium, chloride, sodium and creatinine. Urine flow was also measured as a function of time. Plasma furosemide concentration-time data were fit to a two-compartment model with either two consecutive, discontinuous first order absorption rate constants or with a single monoexponential input; the former absorption model describing the data better than the latter. Average values of the half-life (205 +/- 28 min) and renal clearance (0.8 +/- 0.09 ml/min/kg) were similar to those reported by previous investigators. Drug excretion-response curves were lower and shifted to the right compared to data reported for normal subjects. Furthermore, a clockwise hysteresis was evident indicating acute within-dose tolerance.

Aged↗
PubMed1986

Absorption and disposition of aluminum in the rat.

The kinetics of aluminum were determined in the rat. Intravenous bolus and oral doses of 8.1-mg/kg of aluminum as the chloride salt were administered to six rats. Serial blood samples and total urine and feces were collected and assayed for aluminum by atomic absorption spectrophotometry. The fraction absorbed orally (mean +/- SEM) was 0.27 +/- 0.03; the half-life was 5.29 +/- 0.47 h; the steady-state volume of distribution was 38.4 +/- 6.4 mL/kg, and the clearance was 8.87 +/- 1.76 mL X h-1 X kg-1. It was found that aluminum did not significantly penetrate the cellular components of blood. Plasma protein binding was determined to be approximately 98%. Sixty percent of the intravenous dose was excreted in the urine and the remaining 40% was excreted in the feces.

Administration, Oral↗
PubMed1983

Demonstration of central nervous system tolerance to ethanol in mice: consequent effects on smooth muscle in vitro.

Mice were given ethanol (9 g/kg) or saline (57 ml/kg) daily in three divided doses for periods of 1 and 4 days to study the effects of such ethanol (ETOH) exposure on central nervous system (CNS) and peripheral smooth muscle (vasa deferentia) function. After 1 day, ETOH-treated mice were functionally tolerant to the hypothermic (3 g/kg, intraperitoneal), but not to the hypnotic (3.25 g/kg, intraperitoneal) effect of ETOH. Functional tolerance to both CNS effects of ETOH was demonstrated in mice after the 4-day ETOH exposure. Norepinephrine (NE) and high K+-depolarizing solutions each elicited dose-dependent contractions in the mouse vasa deferens preparation in vitro that consisted of a phasic and tonic component. The tonic components of the NE and K+ responses were more dependent upon extracellular Ca2+ (Ca2+ext) than the phasic components. Addition of ETOH (120 to 480 mM) or the Ca2+ channel-antagonist nifedipine (1 X 10(-9) to 3 X 10(-7) M) to the preparation selectively inhibited the tonic component of the NE and K+ responses, suggesting that both agents acted to inhibit the responses by interfering with the translocation of Ca2+ext. Vasa deferentia isolated from ETOH-treated mice did not exhibit altered reactivity to NE in the phasic or tonic component of the response. The isolated smooth muscle from mice centrally tolerant to ETOH did not appear to be tolerant to inhibitory effect of ETOH or cross-tolerant to the inhibitory effect of nifedipine on stimulant-induced contractions.

Animals↗
PubMed1982

gamma-Aminobutyric acid action in guinea-pig ileal myenteric plexus.

The responses of the guinea-pig ileum myenteric plexus-longitudinal muscle preparation to gamma-aminobutyric acid (GABA) and several analogs were examined in direct and electrically stimulated preparations. GABA, muscimol and 3-aminopropane sulfonic acid (3-APS), but not baclofen, produced a transient, concentration-dependent contraction followed by relaxation. These responses were antagonized by atropine, tetrodotoxin, bicuculline methiodide and picrotoxin. Responses to GABA and 3-APS exhibited a marked tachyphylaxis. GABA and baclofen, but not muscimol or 3-APS, exerted a relaxant effect on contractions induced by supramaximal field stimulation in the longitudinal muscle. These responses were insensitive to bicuculline, bicuculline methiodide and picrotoxin, and were unaffected by other pharmacological agents including adrenergic, cholinergic and histamine antagonists. The results suggest that GABA and its analogs act at a population of excitatory receptors mediating the release of acetylcholine from enteric neurons, and at a population of inhibitory receptors which inhibit the stimulated release of acetylcholine.

Amino Acids↗
PubMed1980

Responses to noradrenaline of portal vein strips from normotensive and spontaneously hypertensive rats.

1 Responses to noradrenaline of isolated portal vein strips from 5-7 week and 15-17 week Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) have been examined. 2 15-17 week SHR tissue exhibited a greater sensitivity (lower ED50) to noradrenaline but only at reduced Ca2+EXT levels. 3 pA2 values for the alpha-adrenoreceptor antagonists WB 4101 and prazosin were significantly lower in 5-7 week SHR consistent with some change at the adrenoreceptor level. 4 Veins from SHR relaxed more rapidly in CA2+-free saline following removal of noradrenaline than did veins from WKY. 6 D600 is a competitive antagonist of the Ca2+EXT-dependent component of the noradrenaline response but K1 values were not significantly different in SHR and WKY.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

The effect of activated charcoal on mouse sleep times induced by intravenously administered hypnotics.

The effect of orally administered activated charcoal (AC) on the sleep times of mice following intravenous injection of various hypnotics was investigated. Preliminary studies with phenobarbital (Pb) showed that a linear relationship exists between the Pb-induced sleep time and the logarithm of the Pb dose in both control and AC treated mice. Half-lives of Pb in the two groups were estimated to be 8.1 and 0.9 h, respectively. A linear decline in Pb-induced sleep time with increasing dose of AC was observed up to a maximum effective dose of AC beyond which dose increments caused no further reduction in sleep time. A similar relationship was observed between sleep time and the concentration of sodium sulfate in which the AC was suspended. AC treatment resulted in an 82-88 per cent reduction in sleep time induced by administration of phenobarbital, methyprylon, glutethimide, ethchlorvynol, and methaqualone. AC had no significant effect on sleep time following amobarbital or pentobarbital administration.

Administration, Oral↗
PubMedDate not supplied

Removal of sulfonamides by hemofiltration.

Hemofiltration is a relatively new technique for removing toxic substances from the body. Unlike hemodialysis or hemoperfusion, the driving force behind hemofiltration is ultrafiltration. There have been several studies examining the clearance of drugs by hemofiltration but to date no study has investigated in a systematic way the effects of protein binding, perfusate flow, transmembrane pressure, and the duration of treatment on drug clearance by hemofiltration. The influence of these factors on the hemofiltration clearance of three sulfonamides with differing degrees of protein binding was investigated. It was found that hemofiltration drug clearance decreased with the duration of hemofiltration and protein binding but increased with perfusate flow and transmembrane pressure.

Animals↗
PubMedDate not supplied

A comparative study of uranyl nitrate and cisplatin-induced renal failure in rat.

Renal dysfunction can have substantial effects on the pharmacokinetics and pharmacodynamics of drugs. A wide variety of animal models have been developed in an attempt to mimic conditions seen in human renal failure. In reality, no single animal model would be completely satisfactory because the etiology and development of renal failure are diverse. During recent years injection of uranyl nitrate has been found to be the most effective and easiest method to produce renal dysfunction in laboratory animals. Changes over the last 10 years in government regulations on the production and use of radioactive substances make the compound less available. There is, therefore, a need for a more accessible compound comparable to uranyl nitrate as an inducer of renal failure. The present study compares the effects of another known nephrotoxin, cisplatin, with uranyl nitrate in the rat. Cisplatin was chosen because of its ability to produce kidney damage and its identical site and mechanism of action on the kidneys as uranyl nitrate. In the present study, rats were given different i.v. doses of uranyl nitrate or cisplatin dissolved in 0.9% of saline solution. The effects of nephrotoxins were evaluated on the basis of changes in body weight, creatinine and blood urea nitrogen (BUN) concentrations. It was found that the degree of renal damage produced by uranyl nitrate and cisplatin is a function of the administered dose. With increasing dose there is evidence of more severe kidney damage, as measured by substantially increased plasma concentrations of creatinine and BUN. The time required to return to normal creatinine and BUN concentrations was also a function of dose. Furthermore, plasma alanine aminotransferase (ALT) activity was measured as an index of hepatocellular damage. The ALT test showed that a single dose does not affect the liver function. From dose-response curves a dose of 4 mg/kg body weight of uranyl nitrate or cisplatin was chosen to produce acute renal failure in animals for pharmacokinetic study of barbital. Barbital (100 mg/kg) was administered on the fifth day (the day of maximum renal dysfunction) to uranyl nitrate, cisplatin-treated and control rats. The elimination rate constant (k), elimination half life (t1/2), volume of distribution at steady state (Vss), total (CLt) and renal clearance (CLr) were significantly different in treated groups of rats from control, however no such difference was detected between uranyl nitrate and cisplatin-treated group of rats. In short, cisplatin is comparable to uranyl nitrate in producing renal failure in the rat and can be considered a suitable alternative.

Acute Kidney Injury↗
PubMedDate not supplied

The influence of diffusional barriers on presystemic gut elimination.

A number of drugs undergo biotransformation in the gut wall or lumen. In many cases drug extraction is greater after oral administration compared with parenteral administration. This may indicate that the diffusional clearance of drug across the blood-mucosa interface is less than that across the lumen-mucosa interface. The consequence of diffusional barriers in the gut on presystemic gut elimination (PGE) have been investigated by computer simulation of a physiological pharmacokinetic model. The following was found regarding a diffusional barrier of the blood-mucosa interface: 1) it enhances PGE, 2) it invalidates certain pharmacokinetic methods to assess PGE, 3) it makes PGE sensitive to changes in drug binding in the blood, and 4) if the diffusional barrier exists for the generated metabolite but not for the drug, methods to assess drug absorption by comparing area under the curve relationships of the metabolite after oral and iv drug administration are inaccurate.

Computer Simulation↗