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Pharmacotherapeutic group: Drug used in nicotine dependence. ATC code: N07B A01.
Pharmacology: Pharmacodynamics: Abruptly interrupted use of tobacco products after a long period of daily use may give characteristic withdrawal symptoms comprising four or more of the following: dysphoria or depressed mood, insomnia, irritability, frustration or aggression, anxiety, difficulty in concentrating, restlessness or impatience, reduced heart rate, increased appetite or increase in weight. Urge to smoke is recognized as a clinically relevant symptom, and is an important part of the withdrawal symptoms when giving up smoking.
Clinical studies have shown that nicotine replacement products can help smokers abstain from or reduce their smoking by relieving these withdrawals symptoms.
Pharmacokinetics: The amount of nicotine absorbed from a piece of nicotine chewing gum depends on the quantity of nicotine that is released into the oral cavity and the amount that is lost via swallowing. The greater part of nicotine that is released is absorbed through the oral mucosa. The systemic bioavailability of swallowed nicotine is lower because of first-passage elimination. The high and rapidly rising nicotine concentrations that are seen with smoking are seldom reached with treatment with chewing gum.
In normal case, approximately 1.4mg of nicotine is released from a 2mg piece of chewing gum and approximately 3.4mg nicotine from a 4mg piece of chewing gum. Maximum blood concentration is achieved after 30 minutes of chewing and is then comparable to the concentration 20-30 minutes after smoking a cigarette of medium strength. The volume of distribution after intravenous administration of nicotine is around 2 to 3 L/kg and the half-life is approximately 2-3 hours.
The major eliminating organ is the liver, although the lungs and brain also metabolise nicotine to a small extent. The enzyme primarily involved in biotransformation of nicotine is CYP2 A6. Seventeen metabolites of nicotine have been identified, all of which are believed to be less active than the parent compound. The primary metabolite of nicotine in plasma, cotinine, has a half-life of 14-20 hours and concentrations that exceed nicotine by 10-fold. The plasma protein binding of nicotine is considered to be low, about 5%.
Other diseases or concomitant use of other drugs which affect the level of plasma proteins are not expected to have a significant effect on the nicotine kinetics. The main metabolites in urine are cotinine (10-12% of the dose) and trans-3-hydroxy cotinine (28-37% of the dose). Approximately 10-15% of the nicotine is excreted unchanged with the urine. Up to 23% may be excreted with the urine via increased diuresis and acidification of the urine below pH 5.
Greatly impaired renal function is assumed to affect total clearance of nicotine. Elevated nicotine levels have been seen in smoking subjects undergoing haemodialysis.
The pharmacokinetics of nicotine are unaffected in liver cirrhosis patients with mild impairment of liver function (Child-Pugh score 5) and reduced by about 40-50% in liver cirrhosis patients with moderate impairment of liver function (Child-Pugh score 7).
A smaller reduction in total clearance of nicotine has been shown in healthy elderly users, however, not justifying adjustment of the dose.
No difference in nicotine kinetics has been observed between men and women.
