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Biomedical subjects

R V Fant

Publications and source records attributed to R V Fant.

At least 19 recordsLinked to original sources
PubMed2001

Combination nicotine replacement therapy for smoking cessation: rationale, efficacy and tolerability.

Currently available nicotine replacement therapy (NRT) medications provide effective treatment for tobacco dependence, typically doubling success rates compared with placebo. A strategy for further improving the efficacy of NRT is to combine one medication that allows for passive nicotine delivery (e.g. transdermal patch) with another medication that permits ad libitum nicotine delivery (e.g. gum, nasal spray, inhaler). The rationale for combining NRT medications is that smokers may need both a slow delivery system to achieve a constant concentration of nicotine to relieve cravings and tobacco withdrawal symptoms, as well as a faster acting preparation that can be administered on demand for immediate relief of breakthrough cravings and withdrawal symptoms. This article reviews 5 published studies that have examined the effectiveness of combination NRT compared with monotherapy in providing withdrawal relief and smoking cessation, and examines other factors relevant to the promotion of combination NRT for treating tobacco dependence. The data show that there are conditions under which combinations of NRT products provide greater efficacy in relieving withdrawal and enabling cessation than monotherapy, but the findings are not robust and additional research is warranted to better understand the magnitude and generality of the benefits of combination therapy. There are also regulatory and commercial obstacles that must be considered. Nonetheless, combination NRT has the potential to provide effective treatment of tobacco dependence in persons whose dependence is refractory to currently available treatments.

Humans↗
PubMed2000

A pharmacokinetic crossover study to compare the absorption characteristics of three transdermal nicotine patches.

We compared the pharmacokinetic profiles of the highest marketed doses of three different patch systems using a crossover study design. Specifically, each of the 25 subjects was assigned to receive the Pharmacia-Upjohn (McNeil) 15-mg, 16-h patch, the Novartis 21-mg, 24-h patch, and the Alza (SmithKline Beecham) 21-mg, 24-h patch. Subjects used each patch for 3 consecutive days, applying a new patch each morning. Plasma nicotine concentrations were measured 15 times during the first 24-h period and at 48, 48.5, 49.5, and 51 h following initial patch application. Measures of total nicotine absorbed (AUC), maximum plasma nicotine concentration (C(max)) and minimum plasma nicotine concentration (C(min)), were higher for the 21-mg, 24-h patches than for the 15-mg, 16-h patch during both the first day of dosing and during the modeled steady-state period (48-72 h after initial application). Within the 21-mg, 24-h patch systems, the Alza patch produced significantly higher AUC and C(max) values during acute dosing and during steady state, but there was no difference between C(min) values. The time to reach C(max) (T(max)) was fastest for the Alza patch system; the Pharmacia-Upjohn patch produced a faster T(max) than the Novartis patch. These results indicate that there are significant differences between the pharmacokinetics of the currently marketed patch systems, which may be important for effective relief of withdrawal symptoms and cigarette craving.

Administration, Cutaneous↗
PubMed2000

Tobacco dependence. Global public health potential for new medications development and indications.

Current trends indicate that approximately 500 million of the world's existing cigarette smokers will prematurely die of causes that could be prevented by treatment of their addiction to tobacco delivered nicotine. Initial pharmacologically based treatment offerings and approaches have proven the concept that increasing the accessibility and diversity of treatment modalities helps more people quit smoking. These treatments have also shown, however, that the vast majority of smokers continues to find treatment less attractive and less accessible than cigarettes whose appeal is constantly stimulated by new formulations, marketing strategies, and implied claims of reduced risk. There appears to be considerable untapped potential public health benefit, as well as commercial opportunity, for medication developers to reach an increasing fraction of smokers who find current treatments unacceptable, inaccessible, or ineffective. The global opportunities to serve public health via medication development are growing even more rapidly as country after country recognizes the impending economic and health care problems posed by tobacco dependence and are opening their doors to treatment. Three areas of medications development offer particular promise: new forms of nicotine delivery, non-nicotine based medications, and new indications to reach those who are unable or unwilling to completely quit. This article discusses the biobehavioral rationale for medication development, the opportunities, and some of the prominent technical and regulatory challenges.

Humans↗
PubMed1999

Nicotine replacement therapy.

Physicians can help their patients quit smoking by recommending to all of their patients that they quit smoking with the help of nicotine replacement medications. Currently available forms of nicotine medications include gum, patch, nasal spray, and vapor inhaler. Nicotine replacement medications aid smokers in their cessation efforts by relieving the physiologic symptoms of nicotine withdrawal. Because nicotine medications do not deliver the myriad toxins and carcinogens cigarettes deliver, these medications are safe when used as directed. This article discusses the rationale behind nicotine replacement therapy in the context of tobacco dependence, the available medications, and the public health benefits of these medications.

Administration, Cutaneous↗
PubMed1999

Nicotine concentration, smoke pH and whole tobacco aqueous pH of some cigar brands and types popular in the United States.

The present study examined characteristics relating to nicotine delivery of 17 cigar brands, which included small cigars, cigarillos, and large premium cigar brands. The cigars selected for analysis were intended to represent the range of cigar products currently available and in popular use. In addition to cigar characteristics previously studied such as size, nicotine content, and pH of their tobacco, the present study examined smoke pH on a puff-by-puff basis. The tobacco content of the cigars ranged in weight from 0.53 to 21.5 g. There was considerable variation in total nicotine content, which ranged from 5.9 to 335.2 mg per cigar. The aqueous pH of the tobacco from the cigars also varied widely with values ranging from 5.7 to 7.8. The smoke pH values of the smallest cigars was generally acidic, changed little across puffs, and more closely resembled the profiles previously reported for typical cigarettes. Interestingly, the smoke pH of smaller cigars and cigarillos became acidic after the first third of the cigar was consumed and then remained acidic thereafter, whereas larger cigars became acidic during the first third, then became quite alkaline during the last third. Because of wide variations in nicotine content of the tobacco across brands and of similarly wide variations in smoke pH, cigar size is not an accurate predictor of the nicotine delivery capacity of a particular cigar brand, although, in general, larger cigars are capable of providing larger total nicotine delivery with extraordinarily high delivery levels being possible from many of the large premium cigars. These results demonstrated that the popular cigars in this study contained enough nicotine for the development of dependence when smoking as few as one or two of the larger cigars per day.

Administration, Inhalation↗
PubMed1999

Pharmacodynamic effects of new de-nicotinized cigarettes.

The effects of cigarette smoking result from the delivery of nicotine, other components of smoke, and sensory stimulation. In the present study, pharmacological effects of new tobacco-derived de-nicotinized cigarettes (controls) were compared with standard cigarettes. The de-nicotinized cigarettes had the appearance, draw and taste of standard cigarettes but contained and delivered virtually no nicotine (< 0.06 mg), but delivered tar and carbon monoxide (CO). They were compared with cigarettes that delivered nicotine, CO and tar. Subjects (n = 20: 10 men, 10 women) participated in four experimental sessions in which they smoked either a standard cigarette or a de-nicotinized cigarette after either 3 or 12 h of tobacco deprivation. Heart rate, blood pressure, and EEG were recorded before, and for 1 h after, ad lib smoking. Plasma nicotine concentrations verified that de-nicotinized cigarettes did not deliver nicotine. The de-nicotinized cigarettes did not increase heart rate or activate the EEG. The subjects preferred the cigarettes that delivered nicotine compared to the de-nicotinized cigarettes. However, both types of cigarettes reduced subjective measures of tobacco craving and withdrawal. These data extend previous research that suggested the process of smoking and components of tobacco smoke other than nicotine mediate some effects of cigarette smoking. The de-nicotinized cigarettes may prove useful in evaluating effects of smoking independent of the delivery of nicotine.

Adult↗
PubMed1999

Tobacco use as drug addiction: the scientific foundation.

Tobacco use is strongly driven by the pharmacological actions of nicotine in the central nervous system. This review will summarize some of the seminal research findings relating to nicotine dependence and will highlight fundamental questions that must yet be answered. The evidence that nicotine is an addictive drug was summarized in the 1988 Report of the Surgeon General which concluded that nicotine fulfills the criteria for a dependence-producing drug. More recently, research has further characterized the pharmacological effects of nicotine in the brain and elucidated the basic pathophysiology of nicotine addition. Moreover, research shows that nicotine replacement therapy, such as nicotine patch or gum, can prevent or reverse withdrawal symptoms. It is also clear that the form of nicotine delivery is a major determinant of addiction potential and that cigarettes and smokeless tobacco products are both highly engineered drug delivery devices that act not only to provide users with controllable doses of nicotine, but also to maximize the addictive effects of nicotine. Along with the understanding of the dependence process has come a rapidly expanding arsenal of treatment for the disorder. There are many major questions about the nature and course of nicotine addiction that remain unanswered and must be addressed if we are to continue to improve our ability to prevent tobacco dependence as well as to provide more effective and acceptable options for treatment and disease prevention in those who are already addicted.

Animals↗
PubMed1999

Pharmacokinetics and pharmacodynamics of moist snuff in humans.

INTERVENTION: Four brands of moist snuff and a non-tobacco mint snuff were tested. Subjects reported to the laboratory for five experimental sessions. After baseline measurement of dependent variables, each subject placed 2 g of one of the brands of snuff (or one Skoal Bandits pouch) between the cheek and gum for 30 minutes. The subjects remained in the experimental laboratory for an additional 60 minutes. SUBJECTS: Ten volunteers who were daily users of smokeless tobacco. MAIN OUTCOME MEASURES: Plasma nicotine concentration, cardiovascular effects, and subjective effects. RESULTS: Large amounts of nicotine were delivered rapidly to the bloodstream. The amount of nicotine absorbed and the rate of absorption were related to the pH of the snuff product in aqueous suspension. Cardiovascular and subjective effects were related to the amount of nicotine absorbed. CONCLUSIONS: Snuff products are capable of rapidly delivering high doses of nicotine, which can lead to dependence. Long-term use of snuff can lead to a number of adverse health effects including oral cancers, cardiovascular diseases, and gingival diseases. For these reasons, it is important that the public health community considers oral snuff use as a burden on public health in the same way that cigarette smoking is recognised.

Adult↗
PubMed1998

Acute and residual effects of marijuana in humans.

Marijuana continues to be the most commonly abused illicit drug in the United States. Because many people abuse marijuana during the evening and on weekends and then go to work or school the next day, more research is needed on the residual effects of marijuana. The current study sought to examine both acute and residual subjective. physiologic, and performance effects of smoking a single marijuana cigarette. Ten healthy male volunteers who reported recent use of marijuana resided on a residential research ward. On three separate days, subjects smoked one NIDA marijuana cigarette containing either 0%, 1.8%, or 3.6% delta9-tetrahydrocannabinol (THC) according to a paced puffing procedure. Subjective, physiologic, and performance measures were collected prior to smoking, five times following smoking on that day, and three times on the following morning. Subjects reported robust subjective effects following both active doses of marijuana, which returned to baseline levels within 3.5 h. Heart rate increased and the pupillary light reflex decreased following active dose administration with return to baseline on that day. A new finding was that marijuana smoking acutely produced decrements in smooth pursuit eye tracking. Although robust acute effects of marijuana were found on subjective and physiological measures, and on smooth pursuit eye tracking performance, no effects were evident the day following administration, indicating that the residual effects of smoking a single marijuana cigarette are minimal.

Adult↗
PubMed1998

Effects of cigarette smoking through a partially occluded filter.

The effects of a commercially available corn syrup solution that is applied to the filter end of a cigarette causing an occlusive barrier to cigarette smoke were evaluated. The manufacturer claims that the solution reduces exposure to nicotine, carbon monoxide (CO), and other constituents of tobacco smoke and may aid in smoking cessation by providing a means of gradual nicotine dose reduction. Nineteen volunteers (10 men) smoked commercial cigarettes treated with 0, 1, 2, or 3 drops of the corn syrup solution in a double-blind, crossover experiment. Increases in plasma nicotine after smoking averaged 13.3, 10.5, 9.7, and 6.0 ng/ml in the 0, 1, 2, and 3 drop conditions, respectively. In the 3 drop condition, there was a significant reduction in exhaled CO levels. Subjects reported increased difficulty in cigarette draw and a trend toward decreased strength as a function of the number of drops applied. Cardiovascular and EEG measures of smoking were not significantly affected by the application of the drops. Cigarettes treated with 0, 1, 2, or 3 drops of the solution were machine smoked using methods of the Federal Trade Commission (FTC); nicotine yields were 1.0, 1.0, 0.78, and 0.73 mg of nicotine. These results indicate that Take Out drops reduce exposure to nicotine and other constituents of tobacco smoke from a single cigarette.

Adult↗
PubMed1998

Endocrine effects of nicotine administration, tobacco and other drug withdrawal in humans.

The focus of this manuscript is on the effects of smoking and tobacco withdrawal on the hypothalamic-pituitary axis (HPA). A variety of studies have shown that nicotine administered intravenously or through intense cigarette smoking can induce changes in hormones associated with the HPA. Administration of, and abrupt cessation from, other drugs of abuse has also been shown to affect levels of these hormones. Additionally, many of the symptoms of stress and tobacco withdrawal overlap suggesting that the hormonal changes seen during periods of stress may be observed during tobacco abstinence. These findings led to a study of the effects of tobacco withdrawal on plasma ACTH, cortisol, and prolactin levels. The results indicated tobacco cessation caused small and transient effects on plasma hormone levels which were not significantly influenced by nicotine replacement and were not related to other signs of withdrawal.

Animals↗
PubMed1998

Delayed auditory feedback during smoking cessation.

Delays between speech production and hearing, delayed auditory feedback (DAF), reduce speech and reading rates. Smoking cessation in heavy smokers causes subjective reports of difficulty in concentration, decrements in cognitive performance, and EEG changes. The purpose of the present study was to determine if tobacco cessation disrupts linguistic processing as modeled by the DAF paradigm. Smokers (n = 14) were tested on 3 d of ad libitum smoking and 3 d no smoking. At each session, they read a word list (24 words) and a story (about 57 words) with and without delay (220 msec). The delay significantly decreased reading speed of the story from 3.4 to 2.9 words per second (wps) and of list from 2.1 to 1.7 wps. However, tobacco cessation had no significant effect on reading speed and no interaction with DAF. Although tobacco withdrawal slows performance on cognitive tasks, linguistic processing modeled by DAF is preserved. DAF may prove useful for the study of other drug classes and drug withdrawal states.

Adult↗
PubMed1997

Evaluation of cranial electrostimulation therapy on short-term smoking cessation.

The effects of cranial electrical stimulation (CES) on short-term smoking cessation were evaluated in a double-blind study of cigarette smokers who wished to stop smoking. Subjects were randomly assigned to a CES- (n = 51) or a sham-treated group (n = 50). On 5 consecutive days subjects received CES treatments (30-microA, 2-msec, 10-Hz pulsed signal) or no electrical current (sham). There were no significant differences between groups on daily cigarettes smoked, exhaled carbon monoxide, urinary cotinine levels, treatment retention, smoking urges, or total tobacco withdrawal scores, although subjects in the CES group had less cigarette craving and anxiety during the first 2 experimental days. The ineffectiveness of CES to reduce withdrawal symptoms and facilitate smoking cessation are similar to results of other clinical studies of CES in drug dependence, although positive effects of CES in animal studies have been reported.

Adult↗
PubMed1997

Effects of mecamylamine on spontaneous EEG and performance in smokers and non-smokers.

In a previous study, mecamylamine, a centrally active nicotine antagonist, exacerbated EEG signs of tobacco abstinence in abstinent smokers. In the present study, the effects of mecamylamine were compared in non-smokers and nondeprived smokers. Mecamylamine (0, 5 and 10 mg, p.o.) was administered to six smokers and six non-smokers; eight of these subjects were also given a 20 mg dose. Before drug administration, resting EEG was similar in both groups. In both groups, mecamylamine caused dose-related decreases in alpha frequency and increases in delta frequency; beta frequency was increased by the 5 and 10 mg doses. The similarity of effects in smokers and non-smokers suggests a direct pharmacological action rather than precipitated nicotine withdrawal. Significant baseline differences existed between smokers and non-smokers in systolic blood pressure, pulse rate, skin temperature and pupil diameter. Response time slowed in both vigilance and distractibility tasks and delayed recall was impaired. Mecamylamine increased ratings of: "relaxed," "nodding," "sleepy" and "coasting." This small-sample study tentatively suggests that nicotinic cholinergic mechanisms modulate brain electrical activity and cognitive function in smokers and non-smokers. Disruption of these neural systems could mediate the symptoms of tobacco withdrawal and be involved in the pathophysiology of Alzheimer's disease.

Adult↗
PubMed1997

Effects of abused drugs on psychomotor performance.

Some abused drugs have been reported to alter performance on naturalistic tasks such as driving and also on laboratory tasks. The performance effects of several drug classes were examined using a repeated measures design. Eight volunteers were administered 2 doses of ethanol, marijuana, amphetamine, hydromorphone, pentobarbital, or placebo on separate days. The larger dose of each increased subjective drug strength; however, only ethanol and pentobarbital impaired performance on circular lights, digit symbol substitution, and serial math tasks. Both ethanol and pentobarbital impaired performance on card-sorting tasks; impairment was evident at lower doses as the cognitive load increased. Results illustrate differences among drugs in producing performance impairment at doses that cause subjective effects. Increasing cognitive requirements uncovered performance impairment at lower doses.

Adult↗
PubMed1997

Smokeless tobacco: an addicting drug.

In 1986, the Surgeon General concluded that smokeless tobacco is an addictive drug sharing many qualities with other drugs of abuse such as morphine and cocaine. Smokeless tobacco can be used to deliver psycho-active and dependence-producing levels of nicotine. Tolerance develops with repeated use, causing the user to increase nicotine dosing through increased use and/or switching to products with higher nicotine yields. Clinical signs of nicotine withdrawal develop upon cessation of use. Recent data show that smokeless tobacco products vary widely in their nicotine dosing capabilities. Low-dose products tend to be those commonly marketed toward, and used by, young people without previous smokeless tobacco experience. Many of these people develop dependence and switch to high-dose products. The present article discusses each of these qualities of smokeless tobacco in greater detail. The article also discusses qualities of smokeless tobacco that make it an effective nicotine delivery device that leads to addiction.

Behavior, Addictive↗
PubMed1997

Inhibition of prostaglandin synthesis and effects of ethanol and pentobarbital in humans.

Results from animal research suggest that pretreatment with prostaglandin synthesis inhibitors (PGSIs) may inhibit physiological and behavioral effects of moderate ethanol ingestion. We examined the effects of ethanol and pentobarbital in humans with and without pretreatment with indomethacin, a potent PGSI. Ten male subjects with histories of recreational use of ethanol and sedative/hypnotics participated in this inpatient study. The effects of indomethacin alone (0.66 mg/kg), indomethacin (0, 0.17, 0.33, 0.66 and 1.33 mg/kg) in combination with ethanol (0 and 1 g/kg) and indomethacin (0 and 0.66 mg/kg) in combination with pentobarbital (0, 1.33 and 4 mg/kg) were tested. On test days, subjects swallowed capsules containing indomethacin or placebo. One hour later, they swallowed capsules that contained pentobarbital or placebo and a large drink (500 ml) of tonic water that contained ethanol or placebo (tonic water with 2 ml of ethanol floated on top). Both ethanol and pentobarbital affected subjective ratings, performance measures and heart rate. However, indomethacin pretreatment had no influence on drug-induced changes to ethanol and pentobarbital. The results of this study illustrate the relationship between depressant drugs and human performance, but they do not support the hypothesis that inhibition of prostaglandin synthesis diminishes the effects of ethanol and pentobarbital in humans.

Adult↗