Biomedical subjects

R L Stiller

Publications and source records attributed to R L Stiller.

At least 37 records · Page 2Linked to original sources

PubMed1992

Pharmacodynamics of pemoline in attention deficit disorder with hyperactivity.

The onset, duration, and offset of pemoline action to improve cognitive performance is examined intensively in 25 prepubescent males suffering from attention-deficit disorder with hyperactivity (ADDH). The purpose was to characterize the pharmacodynamics of pemoline in ADDH patients through correlation of plasma pemoline concentration with psychometric measures of memory search efficiency and paired-associates learning, with the physiological effect of pemoline on dopaminergic transmission concurrently measured by analysis of plasma prolactin response. The effect of pemoline on neuroprocessing is apparent within the first 2 hours after administration with an inverse relationship between plasma pemoline and prolactin concentration present at hour one only (r = 0.84; p = 0.005). Pemoline therapy for 3 weeks does not significantly affect area under the curve for pemoline or prolactin nor did the effect on memory search efficiency decrease, suggesting no apparent tolerance.

Attention↗

PubMed1991

Acute effects of nicotine on hunger and caloric intake in smokers and nonsmokers.

The inverse relationship between smoking and body weight may be due in part to nicotine's effects on reducing hunger and eating. Male smokers and nonsmokers (n = 10 each), abstinent overnight from smoking and food, participated in four sessions, involving consumption of a liquid caloric load or water followed by nicotine (15 micrograms/kg) or placebo via nasal spray every 20 min for 2 h. Hunger and satiety ("fullness") ratings were obtained prior to each dose presentation. At the end of the two sessions involving the caloric load (simulating breakfast), subjects were also presented with typical lunch/snack food items varying in sweet taste and fat content for ad lib consumption. Results indicated that, for both smokers and nonsmokers, the hunger-reducing effects of nicotine occurred only following caloric load consumption, and there was no effect of nicotine on hunger afer water consumption. Smokers unexpectedly reported greater satiation than nonsmokers following the caloric load regardless of nicotine or placebo condition. Nicotine also resulted in less caloric intake during the meal, and the decrease was not specific to consumption of sweet, high-fat foods. These results indicate that nicotine reduces appetite, possibly helping to explain the influence of smoking on body weight.

Adult↗

PubMed1991

Effects of dose, gender, and level of physical activity on acute metabolic response to nicotine.

The acute thermogenic effect of nicotine was examined in cigarette smokers under conditions of rest and two levels of low-intensity physical activity comparable to that normally engaged in by sedentary adults. Male and female smokers (n = 10 each) each received 0 (placebo), 7.5, 15, or 30 micrograms/kg nicotine via measured-dose nasal spray once every 30 min for 90 min, with each dose presented on a separate occasion. After each dose presentation, subjects engaged in 10 min of rest or low-intensity activity at 30 or 60 watts (W) using a bicycle ergometer. For males, results indicated that expenditure attributable to nicotine was more than twice as large during 60-W activity compared with rest, while that during 30-W activity was intermediate. For females, expenditure attributable to nicotine was generally similar to that of males during rest and 30-W activity but was significantly lower during 60-W activity, indicating an apparent "inverted-U" relationship with activity intensity. The enhanced effect of nicotine was specific to energy expenditure, since heart rate showed dose-dependent changes that were generally similar regardless of activity level. These findings confirm a mediating influence of physical activity level on the acute metabolic effect of nicotine, especially in males, and may have implications for explaining individual differences in body weight changes due to tobacco smoking and cessation.

Adult↗

PubMed1991

Acute tolerance to the cardiovascular effects of nicotine.

Acute tolerance to cardiovascular effects of nicotine was examined by presenting to male smokers a single administration of each of three different doses of nicotine (0.5, 1.0, 2.0 mg) or a placebo (0 mg) in a brief series of nasal spray boluses to mimic nicotine intake via smoking. Each dose was presented on a separate occasion. Changes in heart rate, systolic and diastolic blood pressure, finger pulse amplitude (peripheral vasoconstriction) and, in a subsample, plasma nicotine concentration were assessed during and after dose administration. Acute tolerance to nicotine was determined by comparing responses at ascending plasma nicotine concentrations during dose administration with the responses at comparable descending plasma concentrations following administration. For each nicotine dose, there was substantial acute tolerance to blood pressure, but less tolerance to heart rate (except for 0.5 mg), and little tolerance to pulse amplitude responses. These findings indicate that cardiovascular adaptation to nicotine during cigarette smoking may be rapid but variable in magnitude depending on the response being measured.

Administration, Intranasal↗

PubMed1991

Pharmacokinetics and pharmacodynamics of doxacurium in normal patients and in those with hepatic or renal failure.

We determined the pharmacokinetics and duration of action of a bolus dose of doxacurium (15 micrograms/kg) in 27 patients anesthetized with isoflurane and nitrous oxide. Nine patients had normal renal and liver functions and were undergoing a variety of surgical procedures, nine were undergoing cadaveric kidney transplantation because of end-stage renal disease, and nine were undergoing cadaveric liver transplantation because of end-stage hepatocellular disease. Plasma concentrations of doxacurium were measured for 6 h after administration using a sensitive and specific capillary gas chromatographic assay. Plasma concentration versus time data were analyzed by a noncompartmental method based on statistical moments. Neuromuscular blockade was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. The degree of neuromuscular blockade after doxacurium administration was described as the percent of control of the first train-of-four response. The pharmacokinetic variables were (normal vs hepatic failure vs renal failure, respectively): volume of distribution at steady state (220 +/- 110 vs 290 +/- 60 vs 270 +/- 130 mL/kg [mean +/- SD]), plasma clearance (2.7 +/- 1.6 vs 2.3 +/- 0.4 vs 1.2 +/- 0.7 mL.kg-1.min-1), mean residence time (95.2 +/- 57 vs 129.4 +/- 30 vs 270 +/- 210 min), and elimination half-life (99 +/- 54 vs 115 +/- 31 vs 221 +/- 156 min). Plasma clearance and mean residence time differed significantly between patients with renal failure and control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Effects of alpha-1-acid glycoprotein on the cardiovascular toxicity of nortriptyline in a swine model.

Tricyclic antidepressant toxicity is a frequently encountered and life-threatening problem in emergency medicine. This trial investigated the effect of alpha-1-acid glycoprotein (AAG), an acute phase reactant with a high affinity for basic drugs, on the clinical and pharmacological manifestations of nortriptyline (NT) toxicity. Fourteen pentobarbital-anesthetized swine (10-13 kg) were given a 10-min loading dose followed by a 45-min maintenance infusion of NT to achieve a plasma level of approximately 1000 ng/ml. At the end of the infusion, 7 control (C) animals were given 50 ml of 0.9% saline and 7 AAG animals were given 50 ml of 10% AAG, both over 15 min. Heart rate, QRS duration, QTc interval, blood pressure, temperature, arterial blood gases, albumin, and plasma-free and plasma-bound NT levels were measured at baseline and at every hour for 4 h. One death was noted in the AAG group and none in the C group (p = NS). Mean total NT levels after infusion in the C group was 1240 +/- 1118 ng/ml and in the AAG group 804 +/- 194 ng/ml (p = NS). No significant differences were found in the plasma-free fractions between groups at any time interval. However, significantly shorter QTc intervals were found during treatment with AAG compared to controls (P = 0.02). A trend toward increased systolic blood pressure (p = 0.09) and shorter QRS duration (p = 0.09) was noted during AAG treatment. No significant changes were shown between groups with respect to heart rate, arterial blood gases, or albumin measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Alfentanil pharmacokinetics in piglets with increased intra-abdominal pressure.

Increased intra-abdominal pressure (IAP) occurs in pediatric patients with end-stage liver disease and ascites, as well as in children following surgery for diaphragmatic hernia, omphalocele, gastroschisis and orthotopic liver transplantation. Although the hemodynamic response to increased IAP is well described, little information is available regarding the effects of IAP on drug distribution and elimination. We studied the effects of increased IAP (20 mm Hg) on the pharmacokinetics of alfentanil in piglets and compared these findings with those in control animals. Increased IAP appears to have no significant effect on the volume of distribution (0.46 +/- 0.06 vs. 0.61 +/- 0.23 liter/kg), mean residence time (68.8 +/- 27.8 vs. 62.3 +/- 27.8 min) and elimination half-life (47.7 +/- 19.0 vs. 43.2 +/- 19.3 min).

Abdomen↗

PubMed1990

Behavioral performance effects of nicotine in smokers and nonsmokers.

Performance on finger-tapping and handsteadiness, tasks opposite in response requirements, was compared between male smokers and nonsmokers (n = 10 each) on two occasions, once following intake of nicotine (15 micrograms/kg) by measured-dose nasal spray and once following placebo. Compared with nonsmokers, smokers had significantly greater increase in finger-tapping speed due to nicotine. On the other hand, smokers tended to have improved performance on handsteadiness (i.e., less involuntary movement) due to nicotine, while nonsmokers had impaired performance, although this difference was not significant. Nicotine-induced changes in performance on each task were inversely related, suggesting specificity of the behavioral effects of nicotine depending on task demands, rather than a generalized effect. These effects of nicotine on behavioral performance may be important in understanding the reinforcing value of nicotine intake, and differences in effects as a function of smoking history may suggest chronic adaptation to nicotine.

Adult↗

PubMed1990

Perception and hedonics of sweet and fat taste in smokers and nonsmokers following nicotine intake.

Nicotine's effects on reducing perception and/or hedonics of sweet and fat taste may lead to less intake of sweet tasting, high-fat foods by smokers, helping to explain their generally lower body weights. Smokers and nonsmokers (n = 10 males each) rated perception (intensity and sensitivity) and hedonics (liking) of sweet/fat taste in milk samples varying both in sucrose (0, 5, 10, 20% w/w) and fat (0.1, 3.5, 11.7, 37.6% w/w) concentration on two occasions, once following intermittent presentation of nicotine (15 micrograms/kg) via measured dose nasal spray and the other following placebo. Nicotine significantly reduced perceived intensity of fat but not sweet taste and had no effect on sensitivity to either taste. There was no effect of nicotine on hedonics of sweet/fat taste. On the other hand, although there were no differences between smokers and nonsmokers in perception of sweet or fat, hedonics of sweet/fat taste was reduced in smokers regardless of nicotine or placebo intake. Thus, nicotine may acutely decrease fat taste perception without influencing sweet/fat hedonics, while long-term exposure (i.e., being a smoker) may produce chronically decreased taste hedonics without altering perception.

Adolescent↗

PubMed1990

A brief technical communication: detection of fentanyl in urine.

A reliable and sensitive method to analyze fentanyl in urine was developed using radioimmunoassay (RIA). Fentanyl, a highly lipophilic drug (pKa 7.7), has become a common drug of abuse. We evaluated three analytical techniques to detect fentanyl in urine. This paper reports the best of the three - a modified solvent extraction combined with a fentanyl RIA.

Fentanyl↗

PubMed1990

Metabolic effects of nicotine after consumption of a meal in smokers and nonsmokers.

The thermogenic effect of nicotine intake after calorie consumption was investigated to determine if nicotine influences metabolic response to a calorie challenge. Smokers and nonsmokers (10 males in each group), matched for body weight, age, and physical fitness, each participated in four sessions that involved consuming a liquid calorie load (4.77 kcal/kg body wt) or water, followed by nicotine (15 micrograms/kg body wt) or placebo via nasal spray every 20 min for 2 h. Energy expenditure was significantly increased above baseline resting metabolic rate (RMR) over the 2 h by nicotine alone (6.5% of RMR, p less than 0.01). However, the combined effect of nicotine after calorie load (20.1% of RMR, p less than 0.001) was not significantly greater than the effect of calorie load alone (18.4% of RMR, p less than 0.001). Smokers and nonsmokers did not differ in baseline RMR or in response to nicotine or calorie load. These results confirm the thermogenic effect of nicotine but suggest that the effect of nicotine after calorie consumption is less than additive.

Administration, Intranasal↗

PubMed1990

Cardiovascular effects of nicotine during physical activity and following meal consumption.

1. In two separate studies using healthy male smokers as subjects, the acute cardiovascular effects of a measured dose of nicotine (15 micrograms/kg) were examined in conjunction with light physical activity and following consumption of a meal, conditions typical of nicotine intake via smoking. 2. Increases in heart rate and systolic blood pressure attributable to nicotine were similar during rest, physical activity, and following eating, demonstrating additivity with the cardiovascular effects of activity and a caloric load. Diastolic blood pressure was less affected by nicotine. 3. These results indicate that cardiovascular activity is acutely increased following nicotine (smoking) regardless of other influences on the cardiovascular system. Such effects may help explain increased risks of acute cardiac abnormalities due to smoking.

Adolescent↗

PubMed1990

Influence of gestational age on pharmacokinetics of alfentanil in neonates.

Alfentanil's small volume of distribution and short elimination half-life, coupled with its preservation of hemodynamic stability, make it a potentially useful drug for analgesia and anesthesia in neonates. The pharmacokinetics of alfentanil were studied in 5 infants born at 26-35 weeks' gestation and in 5 infants of greater than 36 weeks. All infants were studied in the first 3 days of life. After injection of 25 micrograms/kg alfentanil, there was no significant change in blood pressure or heart rate. No significant difference was observed in volume of distribution (0.84 +/- 0.48 l/kg vs. 0.82 +/- 0.30 l/kg), clearance (1.35 +/- 0.69 ml.kg-1.min-1 vs. 1.7 +/- 0.47 ml.kg-1.min-1), or effective half-life (455 +/- 111 min vs. 328 +/- 48 min) between the two groups. The pharmacokinetic values reported here for both preterm and full-term infants are significantly different from data reported for older children.

Alfentanil↗

PubMed1990

Neuromuscular and cardiovascular effects of high-dose vecuronium.

The effects of bolus administration of large doses of vecuronium on the onset and duration of neuromuscular blockade and histamine release were studied during fentanyl-nitrous oxide anesthesia. Forty adults were randomly assigned to receive a bolus injection of either 0.1, 0.2, 0.3, or 0.4 mg/kg of vecuronium. The evoked electromyogram of thumb adduction to train-of-four stimulation was monitored. The time of onset and clinical duration (mean +/- SEM) after each dose were as follows: 0.1 mg/kg, 164 +/- 27 s and 42 +/- 5 min; 0.2 mg/kg, 120 +/- 17 s and 68 +/- 8 min; 0.3 mg/kg, 88 +/- 17 s and 111 +/- 19 min; 0.4 mg/kg, 78 +/- 19 s and 115 +/- 19 min. Both time of onset and duration after doses of 0.3 or 0.4 mg/kg were significantly different from values after the lower doses. No dose-related changes in blood pressure, heart rate, or histamine release were observed. The authors conclude that large bolus doses of vecuronium can be safely used to speed the onset of blockade, but with a significantly prolonged duration of action.

Adolescent↗

PubMed1989

The effect of nicotine on energy expenditure during light physical activity.

The metabolic effects of nicotine have been implicated in the relation between smoking and lower body weight. This study examined whether the nicotine-induced increase in the metabolic rate observed at rest is also present during physical activity. We compared the energy expenditure of 10 male smokers receiving nicotine (15 micrograms per kilogram of body weight) with that of 10 male smokers receiving placebo on two occasions, each including a period of rest and a period of exercise on a modified bicycle ergometer at workloads designed to simulate and standardize light daily activity. All had abstained from cigarette smoking the night before the study. The excess energy expenditure attributable to nicotine was more than twice as great during exercise (difference between groups, 0.51 kJ per kilogram per hour, or 12.1 percent of the metabolic rate at rest; P less than 0.001) than during rest (0.23 kJ per kilogram per hour, or 5.3 percent of the metabolic rate at rest; P less than 0.05). In contrast, the expenditure was not affected by placebo during exercise or rest in the smokers or in a comparison group of 10 non-smokers, indicating that smoking status has no long-term metabolic effect in the absence of short-term nicotine intake. We conclude that the relatively small metabolic effect of nicotine when the subject is at rest is enhanced during light exercise. Our data also suggest that the weight gain that often follows smoking cessation may be influenced not only by nicotine intake but also by the level of physical activity a smoker typically engages in while smoking.

Adult↗

PubMed1989

Chronic and acute tolerance to the heart rate effects of nicotine.

Tolerance to the effects of nicotine reflects physiological adaptation and may be related to the development and persistence of smoking behavior. However, little is known about tolerance to nicotine in humans, in part due to methodological difficulties. This study examined chronic and acute tolerance to nicotine's effect on heart rate (HR) using a measured-dose nasal spray nicotine procedure. Eight "Light" smokers (less than 20 cigarettes per day) and ten "Heavy" smokers (greater than or equal to 20 per day) participated in two sessions on separate days in which they received four administrations (1 every 20 min) of a high nicotine dose (15 micrograms per kg body weight, equivalent to a typical cigarette) or a low nicotine dose (7.5 micrograms/kg) while HR was monitored during the 5 min following each administration. Compared with Light smokers, Heavy smokers had significantly smaller HR responses to the high dose, indicating greater chronic tolerance, but there was no difference between groups in response to the low dose. Acute tolerance to HR response across the four 5-min periods was not observed with either dose. However, subsequent examination of HR response in the first 2 min following each dose administration did suggest acute tolerance, particularly for the low dose, as this more acute HR response declined from the first to the last administration. These results demonstrate chronic and, to a lesser extent, acute tolerance to HR effects of nicotine and suggest that both may be dose dependent.

Adult↗

PubMed1989

Acute effects of nicotine on resting metabolic rate in cigarette smokers.

The acute effects of nicotine on resting metabolic rate (RMR) were examined to identify a mechanism that may help explain the inverse association between smoking and body weight. Multiple administrations of two nicotine doses (moderate [15 micrograms/kg body wt] and low [7.5 micrograms/kg body wt]) and a placebo (0 micrograms) were presented to 18 male smokers via nasal-spray solution on three separate occasions while RMR was assessed by computerized open-circuit indirect calorimetry. Plasma nicotine levels confirmed the reliability of dosing. RMR increases of 6% above base line after both moderate and low doses were significantly greater than the 3% increase after the placebo. Subsequent examination of the effects of smoking a nonnicotine cigarette suggested that the small placebo effect was due to acute metabolic consequences of inhalation. These results confirm that intake of nicotine, isolated from tobacco smoke, significantly increases RMR in humans. However, the results also indicate that non-pharmacological, behavioral aspects of smoking may also contribute to acutely increasing RMR in smokers.

Adolescent↗

PubMed1989

Pemoline-induced abnormal involuntary movements.

Plasma pemoline levels were measured in 6- to 12-year-old, severely hyperactive males coincident with onset of abnormal involuntary movements. Acute exposure to pemoline (2 mg/kg orally) was associated with choreoathetoid movements of face, limbs, and trunk in five of 20 subjects in an acute study of pemoline pharmacokinetics. Also reported is a series of four chronically treated patients who developed choreiform movements and dyskinesias after variable periods of exposure from 3 weeks to 3 months with pemoline (1.5-2.0 mg/kg/day). Abnormal movements following acute or chronic exposure to pemoline cleared after pemoline discontinuation. Pemoline pharmacokinetics does not seem to be a primary determinant in the development of abnormal involuntary movements after chronic exposure. Total amount of pemoline absorbed may play a role in the development of choreoathetoid movements following acute exposure.

Attention Deficit Disorder with Hyperactivity↗