Search PubMed⌕ Search

Biomedical subjects

N L Benowitz

Publications and source records attributed to N L Benowitz.

At least 217 records · Page 12Linked to original sources
PubMed1985

Nicotine renal excretion rate influences nicotine intake during cigarette smoking.

We examined the hypothesis that rate of elimination of nicotine affects nicotine intake during cigarette smoking. Elimination rate was altered by administering ammonium chloride or sodium bicarbonate throughout the day. Nicotine intake during unrestricted cigarette smoking was measured using metabolic clearance data obtained after i.v. nicotine infusion together with blood and urinary nicotine concentrations measured during 24-hr periods of cigarette smoking. Compared with placebo treatment (urine pH 5.6), urinary acidification (pH 4.5) increased (208%) renal clearance and, to a lesser extent (41%), total clearance and increased (by 7.2 mg) daily urinary excretion of nicotine. Urinary alkalinization (pH 6.7) resulted in a decrease (78%) in renal clearance with a small decrease (3.7 mg) in daily nicotine excretion. Average blood nicotine concentrations were similar in placebo and bicarbonate treatment conditions, but were 15% lower during acid loading. Daily intake of nicotine was 18% greater during acid loading. The compensatory increase in nicotine consumption was only partial, replacing about half the excess urinary nicotine loss. This is the first direct demonstration that rate of elimination can influence self-determined drug consumption in humans.

Adult↗
PubMed1984

Determination of cocaine in plasma by automated gas chromatography.

A rapid and sensitive gas chromatographic method is described for the determination of cocaine in plasma. A close structural analogue of cocaine, m-toluylecgonine methyl ester, is used as an internal standard. The simplicity of the extraction scheme and the use of an automatic sampler makes the method convenient for large numbers of samples generated in pharmacokinetic studies.

Autoanalysis↗
PubMed1984

Trazodone-oral cocaine interactions.

Depression and dysphoria can follow the long-term use of cocaine. Little is known about the interaction of antidepressant drugs with cocaine and similar stimulants in humans. The physiologic and subjective effects of an oral 2-mg/kg dose of cocaine hydrochloride were measured in eight healthy cocaine-using men after pretreatment with a single, 100-mg oral dose of the triazolopyridine antidepressant trazodone hydrochloride or placebo in a double-blind study. The cocaine-induced effects of increased BP, increased pupil size, and decreased skin temperature were diminished by trazodone pretreatment. Trazodone alone did not alter plasma epinephrine or norepinephrine levels. An increase in plasma epinephrine levels after cocaine administration was not altered by trazodone pretreatment, but the increase in the norepinephrine level was larger. Trazodone alone produced mild sleepiness. Cocaine-induced euphoria was not altered by trazodone pretreatment, although feelings of tension and shakiness after cocaine administration were diminished.

Administration, Oral↗
PubMed1984

Blood cotinine levels as indicators of smoking treatment outcome.

Pretreatment blood cotinine levels, expired carbon monoxide levels, and self-reported cigarette consumption were evaluated as predictors of smoking treatment outcome in 114 patients. Of these indices of nicotine intake, blood cotinine level was the most useful predictor. High blood cotinine level was the best predictor of dropping out before completion of treatment and of smoking at the end of treatment and at follow-ups. The usefulness of cotinine as a marker of tobacco dependence is discussed.

Adult↗
PubMed1984

Influence of nicotine on cardiovascular and hormonal effects of cigarette smoking.

To elucidate the importance of nicotine in determining the effects of cigarette smoking, we studied 10 healthy subjects on a research ward who were either smoking their usual brand of cigarettes, smoking high- (HN, 2.5 mg) or low- (LN, 0.4 mg) nicotine research cigarettes, or abstaining. Blood nicotine concentrations were four times as high smoking HN than LN cigarettes. Values while smoking their own brands were intermediate. Cigarette smoking increased mean (24-hr) heart rate (HR), but HR effect did not differ as a function of nicotine exposure. Analysis of the hourly HR pattern showed that smoking increased HR more over the first few hours of the morning, but then followed a circadian pattern similar to that during abstention. HR remained elevated all night even though no cigarettes were smoked. Blood pressures tended to be higher while smoking, but plasma cortisol concentrations throughout the day did not differ while smoking or abstaining. Thus the amount of nicotine consumed when assessed over the whole day has little influence on magnitude of cardiovascular responses to cigarette smoking. Insofar as nicotine contributes to risk, changing nicotine content per se may not alter the risk of sudden adverse cardiac events associated with cigarette smoking.

Adult↗
PubMed1984

Nicotine and carbon monoxide intake from high- and low-yield cigarettes.

We measured daily nicotine intake in 11 habitual smokers who smoked their usual brand or commercial high-yield (Federal Trade Commission [FTC] yield 1.2 mg nicotine, 16 mg tar) or low-yield (0.4 mg nicotine, 5 mg tar) cigarettes. Daily nicotine intake was measured from metabolic clearance data in conjunction with blood and urinary concentrations of nicotine during 24-hr smoking periods. On the average, subjects consumed 35 mg nicotine while smoking their usual cigarettes and 26 mg while smoking either high- or low-yield commercial cigarettes different from their usual brand. This level of nicotine consumption from low-yield cigarettes was because smokers obtained 60% more nicotine per cigarette than predicted by FTC yield and they smoked 25% more cigarettes a day. Although there was considerable variability in nicotine intake between subjects, there was a correlation within subjects between intake while smoking their usual brand and experimental cigarettes. Nicotine intake between the two commercial high- or low-yield cigarettes also correlated (r = 0.86). These findings are consistent with a minimal level of acceptable daily intake of nicotine for individuals that is related to usual intake. We suggest that our protocol provides a better quantitative estimate of the yield of different cigarette brands and potential health hazards than those currently provided by the FTC.

Adult↗
PubMed1984

Daily intake of nicotine during cigarette smoking.

Daily intake of nicotine in 22 subjects was estimated from metabolic clearance data obtained after intravenous infusion of nicotine and from blood and urinary nicotine concentration data obtained over 24 hr when the subjects were smoking cigarettes. Daily intake of nicotine averaged 37.6 mg (+/- 17.7, SD) but varied widely among subjects (10.5 to 78.6 mg). Men metabolized nicotine faster than did women, but daily intake of nicotine did not differ. Intake correlated strongly with cigarettes smoked per day (r = 0.59) but not with machine-determined yield. Nicotine intake per cigarette averaged 1.04 mg (+/- 0.36) but did not correlate with machine-determined yield. Correlations between several commonly used biochemical markers of tobacco smoke and nicotine intake were examined; the afternoon (4:00 P.M.) blood level of nicotine was the best marker.

Adult↗
PubMed1984

Unchanged absorption of digoxin tablets in patients with cardiac failure.

In 6 patients with severe left-sided cardiac failure the absorption of drug from digoxin tablets was assessed by simultaneous administration of a commercially available tablet and of an intravenous tracer dose before and during therapy. Lag time, peak time, and dose-normalized increase in plasma concentration did not change in spite of clinical improvement. Two independent measures of the extent of availability, based on plasma and urine measurements, also remained unchanged and their average was similar to that reported for normals. There was, however, a great interindividual variability in absorption. We conclude that the absorption of digoxin tablets is unchanged in patients with left-sided cardiac failure.

Absorption↗
PubMed1984

Changes in plasma catecholamines after tonic-clonic seizures.

Concentrations of circulating catecholamines increase after induced seizures in animals and electroconvulsive therapy in humans. We measured plasma epinephrine and norepinephrine concentrations after a single spontaneous tonic-clonic convulsion in 17 patients to determine whether similar changes occur and to determine their magnitude. Plasma epinephrine and norepinephrine rose sharply within 30 minutes of the seizure and then declined rapidly. The norepinephrine response was attributed to generalized sympathetic neural activation and was sufficient to exert a direct vasoconstrictor effect. The epinephrine response was presumably due to adrenal activation and was large-enough to have cardiovascular or metabolic consequences.

Adult↗
PubMed1984

Motor paralysis increases brain uptake of lidocaine during status epilepticus.

The effect of pH on brain uptake of lidocaine during status epilepticus was studied by comparing blood and brain lidocaine concentrations and pH in paralyzed and nonparalyzed rats during pentylenetetrazol-induced status. Status produced both brain and blood acidosis; paralysis prevented the blood acidosis. Both brain and blood lidocaine concentrations were increased in the status animals. The increase in brain lidocaine was greatest (10-fold over control) in animals paralyzed during status. These findings probably reflect the fall in brain and blood pH during status affecting the partitioning of the weak base lidocaine (pKa 7.86). Paralysis prevents blood, but not brain, acidosis, thereby maximizing the pH gradient and partitioning of lidocaine into the brain.

Acidosis↗
PubMed1984

Benefit of hemoperfusion in acute theophylline intoxication.

Charcoal and resin hemoperfusion or hemodialysis can accelerate theophylline elimination. Their benefit in the treatment of poisoned patients has been accepted on the basis of case reports. We reviewed the treatment of 26 patients with acute theophylline intoxication to determine how much of an effect hemoperfusion or hemodialysis had on the hospital course and outcome of the overdose. Eighteen patients received supportive care and eight patients hemoperfusion (HP) or hemodialysis (HD). The HP/HD patients had more severe theophylline intoxication on the basis of admission and peak theophylline levels, degree of hypotension and occurrence of arrhythmias. During HP/HD, theophylline concentrations decreased, heart rate slowed, blood pressure increased and evidence of central nervous system effects diminished. Despite the severe intoxication in the HP/HD groups, duration of clinical toxicity was shorter (13.5 +/- 7.1 vs. 21.6 +/- 14.1 hr) than in the control group. Seizures occurred in patients in both groups, but there was higher mortality or neurological morbidity in the supportive care (3/4) than in the HP/HD (1/5) group. Our study provides evidence that HP/HD can reduce the duration of clinical intoxication and probably reduces mortality and morbidity in patients with severe theophylline intoxication.

Adolescent↗
PubMed1984

Environmental and drug-induced hyperthermia. Pathophysiology, recognition, and management.

Environmental heat illness may affect the aged and infirm as well as the athletic. In addition, intoxication with a variety of drugs and toxins can produce hyperthermia, which may be indistinguishable from environmental heat illness. This article reviews current concepts of the pathophysiology, recognition, and management of environmental and drug-induced hyperthermia.

Adaptation, Physiological↗
PubMed1983

Smokers of low-yield cigarettes do not consume less nicotine.

Advertisements suggest that smokers of cigarettes low in nicotine are exposed to less nicotine and tar. Nicotine yields are measured with smoking machines, but machines do not smoke cigarettes as people do. We therefore measured the actual nicotine content of commercial cigarettes with different nicotine and tar yields as determined with smoking machines, and also measured actual nicotine intake as indicated by blood concentrations of its metabolite, cotinine, in 272 subjects smoking various brands of cigarettes. We found that low-yield cigarette tobacco did not contain less nicotine; in fact, the nicotine concentration in tobacco inversely correlated (r = -0.53, P less than 0.05) with the concentration measured by smoking machines. Blood cotinine concentrations correlated with the number of cigarettes smoked per day but not with the nicotine yield measured by smoking machines. Only 3.8 to 5.0 per cent of total variance in blood cotinine was contributed by nicotine yield. We conclude that smokers of low-nicotine cigarettes do not consume less nicotine.

Adult↗