Sign Out
Pharmacology: Pharmacodynamics: The main pharmacological effect of nicotine is stimulation of the sympathetic and parasympathetic nervous system, which brings the about cardiovascular effects such as an increase in blood pressure and heart rate, and a cholinergic effect which stimulates the central nervous system, relaxes skeletal muscles, and raises gastrointestinal motility and secretion.
Depending on the patient's initial clinical status, the effects of nicotine during smoking are experienced as stimulating or relaxing, and can be controlled by the pattern of smoking.
Partial or complete tolerance to some effects of nicotine develops rapidly.
Application of Nicotinell TTS (20 cm2) to smokers abstinent overnight resulted in small increases in mean heart rate (up to 6 beats per minute) and systolic blood pressure and a decrease in stroke volume. The changes in heart rate and stroke volume were still present at day 10 after repeated application, suggesting that development of complete tolerance to the effects of nicotine did not occur. The effects were smaller in magnitude than those produced by cigarette smoking, whereas no changes in skin temperature of blood flow were observed compared with placebo control.
During tobacco withdrawal, symptoms such as craving, irritability, frustration, anger, restlessness, nervous tension, anxiety, feeling of hunger, weight gain, difficulties of concentration, and sleep disturbances have been observed. During placebo-controlled double-blind clinical studies, nicotine replacement with Nicotinell TTS in the first few weeks or months after stopping smoking increased the chances of successful abstinence with or without psychotherapeutic support. There was also a strong trend towards reduction of withdrawal symptoms.
Pharmacokinetics: Absorption: Nicotine is absorbed rapidly through the skin and mucous membrane, as well as by inhalation, and is distributed widely in the body tissue. In this transdermal therapeutic system, nicotine is used in the form of its free base.
After applying Nicotinell TTS, nicotine is absorbed continuously through intact skin.
Distribution: The absorption profile after single application of Nicotinell TTS to healthy abstinent smokers (subjects undergoing a course of smoking cessation therapy with the patch) shows an initial 1-2 hours delay followed by a progressive rise in plasma concentrations, plateaus being attained at about 8-10 hours after application. Peak plasma concentrations of 12.3 ng/mL were reached with Nicotinell TTS 30 cm2. After the system is removed, plasma concentrations decline more slowly than would be predicted by the 2-hour elimination half-life for this drug after an intravenous infusion. This is because about 10% of the total amount of nicotine that reaches the circulation is delivered from the skin after Nicotinell TTS is removed.
In comparison with an intravenous infusion, 76.8% of the nicotine released from Nicotinell TTS is systemically available. The pharmacokinetic values, in particular the area under the plasma concentration curve, are in linear proportion to the dosage. With repeated application of 20 cm2 and 30 cm2. Nicotinell TTS mean minimum and maximum plasma concentrations at steady state were 7.1 ng/mL and 12.0 ng/mL for the 20 cm2 patch and 10.3 ng/mL and 17.7 ng/mL for the 30 cm2 patch. These plasma concentrations were within the range observed during moderate cigarette smoking e.g. one cigarette an hour.
Nicotine is distributed widely in the body with a volume of distribution of approximately 180 L. It crosses the blood-brain barrier, the placenta, and is also found in breast milk. Plasma protein binding of nicotine is negligible, less than 5%. Total plasma clearance of nicotine ranges from 0.92 to 2.43 L/min.
Metabolism: Nicotine is eliminated mainly via hepatic metabolism, and the primary metabolites are cotinine and nicotine-1'-N-oxide. Neither of the principal metabolites is considered to be pharmacologically active.
Elimination: The elimination half-life of nicotine is about 2 hours, and plasma clearance is between 0.92 and 2.43 L/min.
Only small amounts of nicotine are eliminated in unchanged form via the kidneys. Renal excretion of the unchanged nicotine represents 5-10% of total excretion and is pH-dependent, being negligible under alkaline conditions. Cumulation is only slight.
