Tobacco methods. Some examples are: Smoking in public was, for a long time, reserved for men, and when done by women was sometimes associated with promiscuity; in Japan, during the Edo period, prostitutes and their clients often approached one another under the guise of offering a smoke. The same was true in 19th-century Europe. Following the American Civil War, the use of tobacco, primarily in cigars, became associated with masculinity and power. Today, tobacco use is often stigmatized; this has spawned quitting associations and antismoking campaigns. Bhutan is the only country in the world where tobacco sales are illegal. Due to
Tobacco smoke plasma levels of nicotine occur 2–10 min after smoking tobacco. Nicotine undergoes a large first-pass effect during which the liver metabolizes 80–90%. Protein binding ranges from 4.9% to 20%. The apparent volume of distribution varies between 1 and 3 l/kg. The metabolites include isomethylnicotinium ion, nornicotine, cotinine, and nicotine-1-N-oxide. Nicotine passes into breast milk in small quantities. In addition to nicotine, tobacco smoke contains small amounts of the alkaloids anatabine, anabasine, nornicotine, N-methylanabasine, anabaseine, nicotine N'-oxide, myosmine, β-nicotyrine, cotinine, and 2,3'-bipyridyl. The nicotine molecule contains two nitrogen atoms with basic properties. The nicotine molecule can thus add one proton to