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Jun 17 10 7:53 AM
Below are additional papers relevant to this issue:
Does cigarette smokingcause stress?
Journal: The American Psychologist, October 1999, Volume 54(10), Pages 817-820.Author: Parrott AC.
Department of Psychology, University of East London, Great Britain. firstname.lastname@example.org
AbstractSmokers often report that cigarettes help relieve feelings of stress. However, the stress levels of adult smokers are slightly higher than those of nonsmokers, adolescent smokers report increasing levels of stress as they develop regular patterns of smoking, and smoking cessation leads to reduced stress. Far from acting as an aid for mood control, nicotine dependency seems to exacerbate stress. This is confirmed in the daily mood patterns described by smokers, with normal moods during smoking and worsening moods between cigarettes. Thus, the apparent relaxant effect of smoking only reflects the reversal of the tension and irritability that develop during nicotine depletion. Dependent smokers need nicotine to remain feeling normal. The message that tobacco use does not alleviate stress but actually increases it needs to be far more widely known. It could help those adult smokers who wish to quit and might prevent some schoolchildren from starting.
PMID: 10540594 [PubMed - indexed for MEDLINE]
Nicotine renal excretion rate influences nicotine intake during cigarette smoking.
Journal: The Journal of Pharmacology and Experimental Therapeutics, July 1985, Volume 234(1), Pages 153-155.Authors: Benowitz NL, Jacob P 3rd.
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.
Effect of grapefruit juiceon cytochrome P450 2A6 and nicotine renal clearance
Journal: Clinical Pharmacology and Therapeutics. 2006 November, Volume 80(5), Pages 522-530.Authors: Hukkanen J, Jacob P 3rd, Benowitz NL.
Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center, and Department of Medicine, University of California, San Francisco 94143-1220, USA.
AbstractBACKGROUND AND OBJECTIVE: Grapefruit juice is an inhibitor of the cytochrome P450 (CYP) 3A4 enzyme and transporters such as P-glycoprotein and organic anion transporting polypeptides, leading to clinically important interactions. Our objective was to study the effect of grapefruit juice on the pharmacokinetics of nicotine, which is primarily metabolized by the CYP2A6 enzyme. METHODS: Ten volunteers were given a 2-mg oral dose of deuterium-labeled nicotine on 3 occasions together with 1 L of water, full-strength grapefruit juice, or half-strength grapefruit juice. Concentrations of nicotine and its metabolites were analyzed in plasma and urine for 8 hours. RESULTS: Grapefruit juice inhibited the formation of cotinine from nicotine (area under the plasma cotinine concentration-time curve from 0 to 8 hours of 6807 min.ng/mL, 7805 min.ng/mL, and 8007 min.ng/mL for full-strength grapefruit juice, half-strength grapefruit juice, and water, respectively; repeated-measures ANOVA, P=.009). The time to peak plasma concentration of cotinine was delayed (216 minutes, 159 minutes, and 147 minutes, respectively; ANOVA, P=.011), and the peak plasma concentration was lower with grapefruit juice compared with water (18 ng/mL, 21 ng/mL, and 22 ng/mL, respectively; ANOVA, P=.010). Oral clearance, peak plasma concentration, and time to peak plasma concentration of nicotine were not affected. Grapefruit juice increased the renal clearance of nicotine (231 mL/min, 219 mL/min, and 123 mL/min, respectively; ANOVA, P=.045) and cotinine (19 mL/min, 14 mL/min, and 16 mL/min, respectively; ANOVA, P=.002). CONCLUSIONS: Grapefruit juice inhibits the metabolism of nicotine to cotinine, a pathway mediated by CYP2A6, and increases the renal clearance of nicotine and cotinine. Nicotine oral clearance is not affected by grapefruit juice because the inhibition of hepatic metabolism is offset by the increase in the renal clearance of nicotine. However, other compounds metabolized by CYP2A6, as well as other drugs excreted via renal clearance mechanisms similar to those of nicotine, may be susceptible to significant pharmacokinetic grapefruit juice interactions.
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