共查询到20条相似文献,搜索用时 0 毫秒
1.
E. D. Srivastava M. A. H. Russell C. Feyerabend J. G. Masterson J. Rhodes 《Psychopharmacology》1991,105(1):63-68
We studied the responses of smokers and life-long non-smokers to transdermal nicotine patches over 24 h in three groups of
subjects: non-smokers on a 15 mg patch (n=8), non-smokers on a 30 mg patch (n=8) and smokers on a 30 mg patch (n=8). Unexpectedly, the non-smokers appeared to absorb nicotine more rapidly. The increase in blood nicotine concentrations
of non-smokers over the first 2 h of patch use was double that of the smokers, with mean increases of 4.5 (SD=3.7), 10.9 (SD=4.2)
and 4.1 (SD=2.7) ng/ml in the three groups, respectively (P<0.005). The smokers had no pleasant or unpleasant effects from the 30 mg patch (
Cmax 13.9 ng/ml, SD=4.9; Tmax 8.75 h) but all eight non-smokers experienced mild nausea and lightheadedness (P<0.01) within the first hour, and seven dropped out (P<0.01) at 3–8 h due mainly to severe nausea, vomiting or headache (
Cmax 18.4 ng/ml, SD=4.9; Tmax 5.25 h). Only one non-smoker dropped out on the 15 mg patch, but five had transient nausea in the first hour (
Cmax 7.9 ng/ml, SD=3.0; Tmax 8.0). Our study provides evidence of chronic pharmacodynamic nicotine tolerance in smokers, but does not address whether
this is acquired or innate. The higher rate of transdermal nicotine absorption in non-smokers is unexplained and requires
replication. 相似文献
2.
Non-smokers show acute tolerance to subcutaneous nicotine 总被引:1,自引:1,他引:0
Michael A. H. Russell Martin J. Jarvis Gemma Jones Colin Feyerabend 《Psychopharmacology》1990,102(1):56-58
Plasma nicotine concentrations following subcutaneous (SC) injection were measured in six subjects who included three life-long nonsmokers. On average, a peak plasma level of 8.5 ng/ml (SD=3.1) was reached 15 min after the mean dose of 13.25 µg/kg nicotine base. Subjective effects were reported by five subjects. The peak heart rate response (mean boost 11 beats per min at 10 min) preceded and was already declining by the time plasma nicotine concentrations peaked. Hysteresis plots showed clear evidence of acute nicotine tolerance in subjects who had never smoked, indicating that acute tolerance is not an acquired phenomenon. The acquisition by smokers of chronic tolerance to nicotine has not yet been systematically demonstrated. Reliable dose-response studies in smokers and nonsmokers are needed, and use of the SC route for this purpose is discussed. 相似文献
3.
Two studies were conducted to replicate and extend previous demonstrations of smoking-induced, dose-related reports of euphoria, and to confirm this relationship using measures of plasma nicotine. In experiment 1, overnight-deprived subjects, in three different sessions, smoked ultralow-, high-nicotine, and usual-brand cigarettes. In experiment 2, ultralow-, medium-, and high-nicotine cigarettes were used, and plasma nicotine was measured. In both studies, subjects were asked to depress a button during euphoric sensations. Number of sensations for the ultralow-nicotine cigarette was significantly lower than for the high-nicotine cigarette in the first study, and than for both the medium- and high-nicotine conditions in the second; a significant linear trend was observed for number of sensations as a function of plasma nicotine level in the second study. For the high-nicotine cigarette, 19 of 22 subjects experienced at least one sensation (mean around three), starting around 2.5 min after lighting up. Together, these studies support the existence of a dose-response relationship for nicotine-induced euphoric sensations; suggest that they are more pronounced following overnight abstinence than following minimal deprivation, and in more dependent smokers; and characterize in detail the temporal features of these sensations. 相似文献
4.
Sex differences in the subjective and reinforcing effects of cigarette nicotine dose 总被引:3,自引:3,他引:0
RATIONALE: Some research with novel nicotine delivery methods suggests that nicotine itself may be less reinforcing in women than in men. However, sex differences in the reinforcing effects of nicotine dose via cigarette smoking have received little attention. OBJECTIVES: Sex differences in the subjective and reinforcing effects of smoking were examined as a function of two cigarette nicotine "dose" levels (moderate - subjects' preferred brand, > or = 0.7 mg yield; low - Carlton "ultra-light", 0.1 mg yield). METHODS: Male and female smokers ( n = 30) participated in three sessions, the first two involving independent assessment (only one brand available), and the third involving concurrent assessment (both brands available), of subjective ratings (e.g. "liking") and reinforcement for the two cigarette brands. Subjects were blind to the brand of each cigarette, and subjects abstained overnight prior to each session. Reinforcement was determined by responses on a computer task to earn single puffs on the designated cigarette. RESULTS: Subjective ratings differed between the low versus moderate cigarette nicotine dose under both independent and concurrent assessment conditions, as expected. Notably, this dose difference was smaller in women than in men (i.e. significant sex by dose interactions). The dose effect on smoke reinforcement also was smaller in women than men, but only under the independent and not concurrent assessment condition. CONCLUSIONS: These results indicate that cigarette nicotine dose is a less important influence on the subjective and, under some conditions, reinforcing effects of smoking in women than in men. 相似文献
5.
Shiffman S Cone EJ Buchhalter AR Henningfield JE Rohay JM Gitchell JG Pinney JM Chau T 《Pharmacology, biochemistry, and behavior》2009,91(3):380-384
Rationale
A clinically limiting feature of currently-available nicotine gum is its slow rate of nicotine delivery and consequently slow onset of therapeutic effects. Previous research suggested that a nicotine hydrogen tartrate gum (NHTG1) that delivered nicotine more rapidly provided more effective craving relief. A subsequent gum formulation (NTHG2) was developed to further increase speed of delivery.Objective
Compare the plasma nicotine absorption and clinical tolerability of NHTG2 to NHTG1 and Nicorette® FreshMint™.Methods
A single-dose, randomized, crossover study evaluated the early kinetics of nicotine absorption and tolerability of 4 mg NHTG2 compared to NHTG1 and Nicorette.Results
NHTG2 gum reached higher Cmax (p = 0.059 versus Nicorette; p = 0.006 versus NHTG1) and delivered significantly more nicotine than Nicorette or NHTG1 within the first 10-30 min of chewing (AUCs0-10, 0-30) and overall (AUC0-180). NHT gums and Nicorette were well tolerated, with little difference in their AE profiles.Conclusions
Study results indicate that NHTG2 gum provided more rapid uptake of nicotine in blood without notable decreases in tolerability. To the extent that rate of delivery and onset of therapeutic effects are related, these gums would be expected to provide more rapid therapeutic effects. 相似文献6.
David E. Morse 《Psychopharmacology》1989,98(4):539-543
Habitual smokers frequently report that when they are stressed smoking helps them to relax. One potential explanation for the reported stress ameliorating effect of smoking is that cigarette consumption (nicotine self-administration) may decrease the sympathetic autonomic nervous system activity which is associated with the stress response. In the present study, rabbits prepared with chronic vascular cannulae were used to study the effects of nicotine administation on plasma corticosterone, catecholamine (epinephrine, norepinephrine and dopamine) and glucose responses to physical restraint stress. Nicotine (0.025, 0.05 or 0.10 mg nicotine base/kg body weight) was administered for 10 days prior to the stress test to allow for the development of habituation/tolerance to its acute toxic effects. Independent administration of nicotine, or the application of the physical restraint stressor, resulted in increases in the plasma concentrations of corticosterone, epinephrine, norepinephrine, and glucose. Nicotine administration during restraint stress enhanced the increase in plasma corticosterone and epinephrine, as compared to the responses induced by either factor alone. The results suggest that the stress ameliorating effect of continued cigarette smoking, as reported by habitual smokers, is not due to a reduction in the activity of the peripheral sympathetic autonomic nervous system. 相似文献
7.
Transdermal administration of nicotine 总被引:1,自引:0,他引:1
The physiological response to nicotine topically applied to the skin was measured in an adult male volunteer. Nicotine base (9 mg) was applied in a 30% aqueous solution to intact skin on the underside of the forearm. Salivary nicotine, heart rate and blood pressure were monitored for 12 h after application of the nicotine. Within 30 min a significant level of nicotine was detected in the saliva (50 ng/ml), pulse had risen by 15 beats/min and systolic blood pressure had risen 10 mmHg. Nicotine levels remained elevated for 2 h and were comparable to levels of nicotine produced by cigarette smoking. Because previous research has shown nicotine to suppress smoking behavior, it may be fruitful to examine transdermal administration of nicotine as a smoking reduction and cessation aid. 相似文献
8.
Nicotine nasal spray (NNS) is generally considered to be an effective smoking cessation aid, but all studies to date of NNS
effectiveness have also utilized group therapy sessions or frequent laboratory visits to support their subjects’ stop smoking
efforts. We studied 50 volunteers before they attempted to quit smoking and again at 1, 2 and 3 months after they received
NNS to assist them in quitting smoking. No other stop smoking intervention was used, which more closely mimics the common
practice of many individuals trying to stop smoking with the aid of a nicotine replacement product but without other supportive
interventions. We found that 50% of the subjects quit smoking for the first month, 34% were still abstinent after 2 months
and 32% quit smoking for 3 months. Those who quit smoking for the entire 3 months and who continued regular NNS use throughout
had 67% cotinine replacement at the end of the first month, while another group which quit smoking for only the first month
with the aid of NNS had 42% cotinine replacement at the end of that month. Our data confirm that NNS is an effective smoking
cessation aid, but our abstinent rate at 3 months is slightly lower than in other studies in which group therapy was provided.
Our data also indicate that higher NNS-induced cotinine replacement during the first month of quitting smoking (suggesting
more frequent use of NNS) is associated with longer term quit-smoking success rate.
Received: 4 June 1997/Final version: 19 December 1997 相似文献
9.
Sipe RV Buck DC Hollinger JO 《Clinical and experimental pharmacology & physiology》2000,27(7):480-482
1. Several methods are used to provide predictable and effective nicotine to experimental animals in scientific studies. Due to the expense and technical challenges of these methods, we sought suitable alternatives. Consequently, the purpose of the present study was to develop a reliable experimental nicotine protocol in rabbits that included either Habitrol nicotine patches (Novartis Consumer Health Inc., Summit, NJ, USA) or nicotine nasal spray. 2. Administration of one of three doses of nicotine (2.5, 5, or 10 mg) was accomplished daily on 13 rabbits divided between either the patch or spray groups. Systemic nicotine and cotinine levels at 0 h, 15 min and 8 and 24 h were assayed. Data were analysed by a Fisher's protected least significant difference test at P = 0.05. 3. Rabbits treated with Habitrol patches exhibited consistent and predictable systemic nicotine levels. The nicotine nasal spray produced an immediate dose-dependent response with no measurable nicotine serum levels at 8 h. 4. For nicotine administration in rabbits, nicotine patches are easy to administer and provide a nicotine serum level between 5 and 25 ng/mL, which is consistent with the average daily level found in a patient who smokes cigarettes. 相似文献
10.
《Journal of addictive diseases》2013,32(1):95-100
Abstract A growing proportion of smokers are those who have failed prior treatments for cessation. We tested the efficacy of nicotine nasal spray and nicotine inhaler in two uncontrolled, open-label studies of 19 and 20 smokers who had previously failed nicotine patch therapy. As in the three prior studies of treatment failures, 6 month abstinence rates were extremely low both with the nasal spray (0%) and the inhaler (5%). We discuss possible treatments for and methodological issues in researching treatment-resistant smokers. 相似文献
11.
Guthrie SK Zubieta JK Ohl L Ni L Koeppe RA Minoshima S Domino EF 《European journal of clinical pharmacology》1999,55(9):639-643
Background and objectives: Arterial (A) and venous (V) plasma nicotine and cotinine concentrations were measured after nasal nicotine spray in tobacco
smokers of both genders. The hypothesis for this research was that a greater A/V difference in plasma nicotine would be present
in males than females because males have greater skeletal muscle mass to bind nicotine.
Subjects and methods: Nine male and nine female healthy adult smokers were studied. They all abstained from use of tobacco overnight for 10 h
or more prior to the study. Nicotine nasal spray was given in doses of 1–2.5 mg total, with half in each nostril while the
subject was supine. Both A and V blood samples were obtained prior to and 3, 6, 10, 15, 20, and 30 min post-nasal nicotine
spray.
Results and conclusions: Nasal nicotine administration produced greater A than V plasma levels. There were no gender differences in A/V nicotine
concentrations, disproving the above hypothesis, suggesting that other physiochemical factors besides skeletal muscle mass
must be involved. Heart rate increases correlated well with arterial plasma nicotine levels (r=0.77). Males had less variance than females in the expected increase in arterial plasma nicotine concentrations with increased
number of nasal sprays. Although there was considerable overlap, mean A cotinine concentrations were consistently slightly
larger than V concentrations.
Received: 15 February 1999 / Accepted in revised form: 17 August 1999 相似文献
12.
The use of nicotine chewing gum as an aid to stopping smoking 总被引:2,自引:0,他引:2
Two hundred and ten subjects entered a trial to test the use of a chewing gum containing nicotine as an aid to stopping smoking. They were divided into three groups: nicotine chewing gum, placebo chewing gum, and control. The trial was double blind between the two chewing gum groups. After 1 month the percentage of confirmed non-smokers in the nicotine gum group was 34%, in placebo chewing gum group 37% and the control group 24%. By 6 months most of the non-smokers had relapsed, but the nicotine gum group (23%) was more successful than the placebo (5% or the control group (14%). 相似文献
13.
R. D. Hurt K. P. Offord I. T. Croghan G. A. Croghan L. C. Gomez-Dahl T. D. Wolter L. C. Dale T. P. Moyer 《Psychopharmacology》1998,140(1):98-104
Nicotine nasal spray and nicotine gum have been found to be effective in relieving nicotine withdrawal symptoms. In this
randomized single-blind study, 91 cigarette smokers were randomly assigned to a single 1 mg dose of active nicotine nasal
spray (n = 29), active 4 mg nicotine gum (n = 31), saline placebo nasal spray (n = 16) or placebo gum (n = 15). Following overnight abstinence, subjects repeatedly completed visual analog scales for assessing nicotine withdrawal
symptoms over 30 min preceding (time -30 min to time 0) and 120 min following a single dose of study medication. This sequence
was performed 3 times during the day. Nicotine withdrawal symptoms were assessed on a 41-point visual analog scale (1 = no
withdrawal, 41 = extreme withdrawal). At the initial session only, blood samples for serum nicotine levels were taken at baseline,
then at 5, 10, 30 and 120 min following study drug administration. The mean (± SD) age of the subjects was 38.6 (±10.1) years,
48% were females, smoking rate was 24.5 (±7.8) cigarettes per day, and years of smoking was 19.9 (±10.0). A single 1 mg dose
of nicotine nasal spray provided more immediate relief for craving for a cigarette compared to a single 4 mg dose of nicotine
gum. Serum venous nicotine levels for the active nicotine nasal spray and nicotine gum were comparable at 5 and 10 min while
the levels were higher for nicotine gum at 30 and 120 min. Changes in withdrawal symptoms were not found to be related to
serum venous nicotine levels. Our findings provide a rationale for the as needed use of nicotine nasal spray to control withdrawal
symptoms, possibly in combination with other medications with longer acting effects.
Received: 18 February 1998/Final version: 1 May 1998 相似文献
14.
Alberg AJ Stashefsky Margalit R Burke A Rasch KA Stewart N Kline JA Ernst PA Avey A Hoffman SC 《Addictive behaviors》2004,29(9):83-1778
Nicotine replacement therapy (NRT) has added to the menu of options available to assist cigarette smokers in quit attempts, but cost remains a barrier to access. A quasi-experimental study was carried out to compare quit rates and continuous abstinence from smoking before (n=601) and after (n=311) free nicotine patches were offered to smokers who participated in the Washington County (Maryland) Health Department's "Stop Smoking for Life" group behavioral cessation program. After free NRT was offered, the quit rates upon completion of the program increased from 38% to 65% [difference 27%; 95% confidence limits (CL) 21%, 34%]. The difference in continuos abstinence from smoking between the two groups was no longer statistically significant after 6 months of follow-up, reflecting the more rapid rate of reversion to smoking that occurred during the 18-month follow-up period among the free NRT group who had quit [adjusted rate ratio (RR) 1.35; 95% CL 1.03, 1.78]. Enrollment during the first 18 months after free NRT was 37% greater than the program's first 18 months (P=.08). In conclusion, adding free nicotine patches to a smoking cessation program was associated with increased program enrollment and significantly increased short-term-but not long-term-quit rates. The rapid reversion to smoking in the group who received free nicotine patches could potentially be obviated if participants extend their use of nicotine patches after the free 6-week supply is exhausted. 相似文献
15.
Mecamylamine pretreatment increases subsequent nicotine self-administration as indicated by changes in plasma nicotine level 总被引:2,自引:2,他引:0
Acute administration of mecamylamine, a centrally active nicotinic cholinergic agonist, has been shown to increase amount of smoking as indicated by smoking topography (e.g., puff rate, puff duration), expired carbon monoxide changes, and other inferential measures. In the present study, subjects showed significantly greater increases in plasma nicotine following smoking of two high-nicotine research cigarettes when pretreated with mecamylamine than when pretreated with placebo, even though no significant differences in puff volume or puff number were detected. Interestingly, none of our subjects reported nausea, although some achieved plasma nicotine levels at which nausea would typically be expected. We attribute the observed increases in nicotine intake to compensatory behavior designed to overcome mecamylamine's blocking effects. 相似文献
16.
The relative bioavailability of nicotine from a nasal spray was assessed in 15 smokers suffering a common cold and rhinitis according to generally accepted criteria. The patients were given a single dose of 2 mg nicotine from the nasal spray with and without concurrent administration of a nasal vasoconstrictor decongestant, xylometazoline, in randomised order. Control session measurements were made in the disease-free state.Applying strict bioequivalence criteria, we found that common cold/rhinitis slightly reduced the bioavailability of nicotine, both in its rate and extent; the geometric mean of the ratio of Cmax, AUC and tmax were 0.81, 0.93 and 1.36, respectively. The nasal vasoconstrictor, xylometazoline, normalised the extent of the bioavailability of nicotine, but further prolonged the time for absorption to almost twice that measured in the disease-free state, increasing the tmax ratio to 1.72.The results suggest that a minor proportion of people stopping smoking with the help of a nicotine nasal spray may experience a minor reduction in the effect of the spray during common cold/rhinitis. However, the nicotine self-titration behaviour found with most smoking cessation products (except the nicotine patch) will automatically lead to an adjustment of the dosage to achieve the desired effect. 相似文献
17.
Puff-by-puff assessments of a range of sensory and subjective attributes were made for three cigarettes, with tar and nicotine yields of: 10.0 and 1.4; 17.0 and 1.7; and 8.8 and 0.8 mg/cigarette, respectively. Seven attributes were assessed: mouth impact, throat impact, chest effect, roughness, intensity of flavour, satisfaction and quality of flavour. Significant differences between the three cigarettes were obtained for most of these attributes. Principal component analysis of the data revealed three principal components related to the cigarettes under investigation. Components 1 and 2 accounted for approximately 47 and 28% of the total variance and component 3 only added a further 7%. Principal component 1 was a complex combination of intensity-related characteristics, i.e. mouth and throat impact, chest effect, intensity of flavour, roughness, while quality of flavour and satisfaction contributed to the separation of samples on principal component 2. However, the two major components could not be defined simply in terms of the yields of tar and nicotine for the products determined on a smoking machine. 相似文献
18.
Cigarette consumption, craving to smoke and smoking pleasure, subjective reasons for smoking, heart rate, motor activity, and nutrient intake were continuously assessed in 22 subjects. After ad lib smoking on the first experimental day, subjects had to abstain between 12:30 h and 17:30 h on the second day and to smoke twice the habituated number of cigarettes during the same period of the third day. Craving and smoking pleasure decreased during oversmoking and increased for the first cigarettes after abstinence. Activity adjusted heart rates decreased by about 5 bpm during abstinence. In the evenings, however, these parameters as well as smoking rates, subjective reasons for smoking, and nutrient intake remained completely unaffected by the previous manipulations. Also cardiac nicotine tolerance, as assessed by the increases of the averaged activity-adjusted heart rates after cigarette lighting, was identical for all three evenings, irrespective of the afternoon smoking condition. Furthermore, none of the subjective effects of the afternoon abstinence was observed for the longer lasting overnight deprivation. These results suggest that habituated temporal patterns play a role in cigarette smoking which is perhaps even more important than the need to maintain a constant plasma nicotine level. 相似文献
19.
Walter S. Pritchard John H. Robinson Thomas D. Guy Riley A. Davis Mitchell F. Stiles 《Psychopharmacology》1996,127(1-2):55-62
Thirty-two subjects were tested in five double-blind sessions (16 subjects in the morning following overnight smoking abstention,
and 16 in the afternoon following ad-lib smoking). In each session, subjects smoked one of five experimental (EX) cigarettes
having the following FTC nicotine/‘tar’ yields in mg: 0.08/8.5, 0.17/9.1, 0.37/9.8, 0.48/9.8, and 0.74/10.4. In a sixth session,
subjects smoked a 0.71/8.6 commercial ‘light’ (CL) cigarette that was their usual brand. Before and after smoking, subjects
subjectively rated their desire to smoke a cigarette of their usual brand and had blood smaples drawn. Following smoking subjects
rated the cigarette on a variety of sensory dimensions; they also rated smoking satisfaction. Analysis of variance indicated
that nicotine played an important sensory role for a variety of dimensions related to cigarette taste and sensory impact but
not perceived draw. Principal-components analyses indicated that sensory factors were at least as important as nicotine pharmacology
(indirectly indexed by the preto post-smoking rise in blood nicotine concentration) when considering smoking’s overall effects
on satisfaction, product acceptance, and reduction in desire to smoke.
A preliminary version of these data was presented at the International Symposium on Nicotine. The Effects of Nicotine on Biological
Systems II, Montreal, July 21–24, 1994. The authors thank Drs. Brad Ingebrethsen, Deborah Pritchard, and two anonymous reviewers
for comments on earlier drafts. 相似文献
20.
Objectives The aim of this study was to assess the potential of a novel delivery device for administering drugs that suffer from a high degree of first‐pass metabolism. Methods A tri‐layered buccal mucoadhesive patch, comprising a medicated dry tablet adhered to a mucoadhesive film, was prepared and characterized by its physicochemical properties and mucoadhesive strength. Nicotine was used as a model drug for the characterization of drug release and drug permeation. The influence of different adsorbents on the release of nicotine base from the patches was evaluated in vitro. Different molecular forms of nicotine (base and complex salt) were evaluated for their effect on release performance and permeation in vitro. Key findings Results demonstrated acceptable physicochemical and mucoadhesive properties for the tri‐layered patch. Rapid release of nicotine was observed when nicotine base was incorporated with calcium sulfate dihydrate as the adsorbent. Patches incorporating nicotine base showed distinct advantages over those containing nicotine polacrilex, in terms of drug release (complete drug release achieved at 30 vs 60 min) and transmucosal permeation (37.28 ± 4.25 vs 2.87 ± 0.26% of the dose permeating through mucosa within 120 min). Conclusions The novel tri‐layered patch can effectively adhere to, and deliver an active ingredient through the buccal mucosa, confirming its potential for buccal mucoadhesive drug delivery. 相似文献