Dose-related cardiovascular and endocrine effects of transdermal nicotine.
BACKGROUND
Transdermal nicotine in doses up to 21 mg/24 hr is used to facilitate smoking cessation. However, this dose does not achieve the nicotine plasma levels seen among heavy smokers, and underdosing may be one of the reasons for the limited efficacy of transdermal nicotine. There are some concerns about the adverse cardiovascular effects of nicotine, especially with concomitant smoking. Treatment with higher doses of transdermal nicotine has been proposed for highly dependent smokers, but the effects of such treatment on the cardiovascular system have not been determined. The objective of this study was to determine the cardiovascular effects of high-dose transdermal nicotine with concomitant smoking.


METHODS
Twelve healthy male smokers received three doses of transdermal nicotine (21, 42, and 63 mg/24 hr) and placebo, each for 5 days, in a balanced order. The subjects smoked during the first 4 days of each treatment and abstained from smoking during the fifth day. Ambulatory 24-hour daytime and nighttime heart rate and blood pressure values were determined for each treatment; plasma nicotine, cotinine, and carboxyhemoglobin levels and urinary catecholamines with aldosterone were measured on days 4 and 5. The data were compared by means of repeated-measures ANOVA.


RESULTS
There was no difference in heart rate or blood pressure and no changes in the pattern of circadian variations with various transdermal nicotine doses compared with smoking alone, consistent with the development of tolerance. Urinary epinephrine level was significantly higher (p < 0.05) with transdermal nicotine compared with no nicotine but was not higher with transdermal nicotine and smoking compared with smoking alone. No change was found in fibrinogen and lipid profiles with different nicotine doses.


CONCLUSIONS
High-dose nicotine treatment, even with concomitant smoking, caused no short-term adverse effects on the cardiovascular system.
Division of Clinical Pharmacology and Experimental Therapeutics, San Francisco General Hospital Medical Center, CA, USA.
S
S
Zevin
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P
Jacob
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NL
Benowitz
D000279:Administration, Cutaneous; D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D018592:Cross-Over Studies; D004703:Endocrine System / Q000187:drug effects*; D005731:Ganglionic Stimulants / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D016037:Single-Blind Method; D012907:Smoking / Q000009:adverse effects* / Q000097:blood
D005731:Ganglionic Stimulants; D009538:Nicotine