Biomedical subjects

R E Olmstead

Publications and source records attributed to R E Olmstead.

7 recordsLinked to original sources

PubMed2001

The nicotine inhaler: clinical pharmacokinetics and comparison with other nicotine treatments.

Nicotine inhaled in smoke is the most rapid form of delivery of the drug. With smoking, arterial boli and high venous blood nicotine concentrations are produced within seconds and minutes, respectively. The potency of nicotine as the primary reinforcement in tobacco addiction is attributed to this rapid rate of delivery. By design, nicotine treatments reduce the rate and extent of drug delivery for weaning from nicotine during smoking cessation. Theoretically, they prevent relapse by reducing withdrawal and craving associated with the abrupt cessation of cigarettes. The nicotine inhaler treats the complexity of smoking through weaning both from the drug and from the sensory/ritual components associated with smoking. The inhaler is 'puffed' but not lit and there is considerable 'puffing' required to achieve slower rising and lower nicotine concentrations. These factors allow it to be used as a nicotine reduction treatment. One inhaler contains 10 mg of nicotine (and 1 mg of menthol) of which 4 mg of nicotine can be extracted and 2mg are systemically available. Shallow or deep 'puffing' results in similar nicotine absorption. Nicotine is delivered mainly to the oral cavity, throat and upper respiratory tract with a minor fraction reaching the lungs. This was confirmed with positron emission tomography and by assessment of arterial concentrations. A single inhaler can be used for one 20-minute period of continuous puffing or periodic use of up to 400 puffs per inhaler. With controlled puffing in laboratory testing, venous plasma nicotine concentrations from a single inhaler puffed 80 times over 20 minutes averaged 8.1 microg/L at 30 minutes. Lower concentrations of 6.4 to 6.9 microg/L have been reported for self-administration under clinical conditions. The time to peak plasma concentrations varies but is always significantly longer than with cigarette delivery. Estimates of nicotine intake from cotinine concentrations were higher than expected (60 to 70% of baseline smoking concentrations). This elevation may be due to the swallowing of nicotine and subsequent first-pass biotransformation to cotinine. In general, venous blood nicotine concentrations are considerably lower than with smoking and are within the range observed for other nicotine reduction therapies. Efficacy trials show consistent superiority of the inhaler over placebo. Despite the 'cigarette-like' appearance of the inhaler and the associated sensory/ritual elements, little treatment dependence or abuse has been reported. This is attributed to the slow rise time and low nicotine blood concentrations. The inhaler is a valuable addition to treatment of tobacco dependence and can be used alone or with other treatments.

Absorption↗

PubMed2000

Nicotine blood levels and subjective craving for cigarettes.

This study examined cigarette craving and blood nicotine levels in 11 male heavy smokers who were observed during 16 h of tobacco abstinence. Subjects rated their urge to smoke on a new brief 10-item questionnaire, Urge to Smoke (UTS), Schuh and Stitzer's four-item Visual Analog Scale (SSI), and a Strength of Urge to Smoke (SUTS) item. Testing occurred: 1) after 16 h (1700 h the night before to 0900 h the next morning) of abstinence from smoking; 2) after an ad lib smoking period following the 16 h abstinence; 3) every hour during 6 hours of abstinence; 4) and finally, after the 6 h abstinence, another ad lib smoking period. Thus, subjects smoked twice in each session. Blood plasma nicotine levels were measured before, after, and every 2 h during the 6-h abstinence period for a total of six measures. Blood pressure and heart rate were measured prior to each blood draw. There was a significant negative correlation between blood nicotine levels and craving for cigarettes on all craving questionnaires (rs = -0.55 to -0.78; ps < 0.002). Carbon monoxide was shown to correlate highly with nicotine blood levels (rs = 0.83 to 0.98 across subjects; ps < 0.001). Results are consistent with the hypothesis that "urge to smoke" reflects nicotine seeking in continuing smokers.

Adult↗

PubMed2000

Bromocriptine reduces cigarette smoking.

AIMS: Animal studies have shown that nicotine releases dopamine, a neurotransmitter implicated in drug reinforcement. We hypothesized that bromocriptine would decrease smoking behavior in humans. DESIGN: The study was conducted double blind and subjects' order of dose exposure was randomized. PARTICIPANTS: The smoking behavior of 20 heavy smokers was recorded for 5 hours after ingesting placebo or one of two doses of bromocriptine (2.50 mg, 3.75 mg) over three sessions (one dose per session). FINDINGS: There was a significant negative linear trend by dosage indicating shorter total puffing time with increasing bromocriptine dosages (p < 0.02). Other significant negative linear trends by increasing dosage include fewer number of puffs, fewer number of cigarettes smoked and mean latency to smoke after 3 hours (expected CMAX on the drug (all ps < 0.05). There was a negative significant linear trend showing decreased plasma nicotine (p < 0.02) and cotinine (p < 0.005) with increasing dosages of bromocriptine. Shiffman/Jarvik Withdrawal Scale (SJWS) cigarette craving subscale scores decreased significantly across increasing dosages (linear trend p < 0.02). There was a significant negative linear trend (p < 0.05) on the Profile of Mood States (POMS) Vigor and Depression subscales, with subjects reporting decreased vigor and depression with increasing bromocriptine doses. No other mood effects were observed. CONCLUSION: These results support the hypothesis that dopaminergic mechanisms mediate cigarette smoking reinforcement.

Adolescent↗

PubMed1998

Olfactory thresholds for nicotine and menthol in smokers (abstinent and nonabstinent) and nonsmokers.

Nonsmokers and smokers were compared for olfactory sensitivity to two odors associated with cigarettes: nicotine and menthol. Smokers were tested twice--while nonabstinent, and after 16-20 h of smoking abstinence. Smokers showed a higher olfactory threshold for nicotine than did nonsmokers, but the same threshold for menthol. Furthermore, when the smokers were abstinent, they showed a lower olfactory threshold for nicotine than when they were nonabstinent, but again, the same threshold for menthol. These results suggest a nicotine specific olfactory deficit in smokers that is reduced during abstinence.

Administration, Inhalation↗

PubMed1997

Saliva cotinine levels as a function of collection method.

Saliva cotinine is commonly used to estimate nicotine intake but laboratories use different methods of collection. In three small trials, comparisons were made between (1) sugar vs. unstimulated saliva production (n = 29), (2) wax chewing vs. unstimulated production (n = 15) and (3) between two consecutive unstimulated saliva samples (n = 10). Sugar-stimulated saliva cotinine scores were 26% below unstimulated levels (p < 0.001); correlation between measures was high (r = 0.90; p < 0.001). Wax stimulated saliva yielded levels 6% below unstimulated (p < 0.05; correlation: r = 0.98; p < 0.001). No differences were observed between two unstimulated samples taken within a approximately 20-minute period (correlation: r = 0.99; p < 0.001). It is postulated that changes in salivary flow can account for the findings.

Biomarkers↗

PubMed1996

Efficacy of buspirone in smoking cessation: a placebo-controlled trial.

Buspirone, a non-sedating anxiolytic, has yielded contradictory results in smoking cessation pilot studies and trials. We tested buspirone (n = 51) versus placebo (n = 49) in a placebo-controlled, double-blind trial of smoking cessation. Survival analyses were performed with use of strict abstinence criteria for efficacy (carbon monoxide levels < or = 8 ppm; no self-reported slips to smoking). No treatment differences were observed between active and placebo groups. There were also no differences among "anxiety" level groups formed post hoc from high versus low, pre-quit anxiety test scores. A number of withdrawal symptoms increased significantly after subjects quit smoking for both the active drug and placebo groups, but these symptoms were not relieved by treatment. There appears to be little evidence that buspirone is effective in smoking cessation or in the relief of withdrawal associated with cessation in a general sample. Selecting for generalized anxiety or anxiety related to cessation is suggested for future testing.

Adult↗

PubMed1996

Clinical pharmacokinetics of nasal nicotine delivery. A review and comparison to other nicotine systems.

Rapid drug delivery (arterial "boli') and high drug concentrations occur with nicotine inhaled in smoke. These are believed to be key elements in producing addiction to cigarettes. Preparations which reduce the rate of delivery and/or concentration of nicotine have been introduced as treatments for smoking cessation. These nicotine medications work by relieving withdrawal and preventing relapse associated with abrupt cessation of smoking. The pharmacokinetics of each system are expected to affect efficacy and treatment dependence. Nasal administration systems have been developed to more closely approximate cigarette delivery for improved efficacy in clinical application and for more control in systematic testing of nicotine. With laboratory tested nasal application systems (clinical drug and experimental devices), venous plasma concentrations after a single dose range between 5 and 12 micrograms/L. Higher steady-state blood nicotine concentrations (16 to 29 micrograms/L) have been reported for ad libitum clinical self-administration with a nicotine nasal spray. Time to peak plasma concentration (tmax) with nasal administration is around 11 to 13 minutes for 1 mg doses. This rise time is slower than for cigarette delivery but faster than the other nicotine treatments. Venous plasma concentrations are considerably lower than tobacco product concentrations and fall within the range of the lower dose nicotine treatments (e.g. 2 mg gum vs 4 mg gum). The profile of nasal nicotine administration was designed for certain subsets of smokers. Efficacy trials show consistent superiority of nasal administration over placebo although the comparative efficacy among nicotine treatments remains to be determined. The more rapid onset and user control of nasal nicotine may impose a higher risk for treatment dependence compared with a slower, passive system such as the patch. It may not produce more dependence than other faster-acting treatment systems (e.g. nicotine gum).

Administration, Intranasal↗