Chemistry

Nicotine is an alkaloid that is produced by the tobacco plant to protect it from destruction by animals. Nicotine is also produced by 66 other plant species, all of which are members of the nightshade family. Regarding its chemical properties, nicotine is a basic, water-miscible and lipophilic compound which dissolves readily in basic solutions. Originally, the home of nicotine was in the Americas. Tobacco was first introduced to Europe in the early 16th century by Fernando Cortes. Nicotine was named after Jean Nicot, a French diplomat who first sent tobacco to France in 1560 and popularized the substance as an effective remedy for the treatment of headaches (Leete, 1969).

Social acceptance of cigarette smoking
Cigarette smoking is becoming less and less accepted socially. The declining social acceptance of nicotine is manifested by the strict anti-smoking rules in government offices and public spaces which are now enforced in many countries worldwide. Additionally, some firms have employment practices that discriminate against smokers because smokers can increase insurance costs forcing the employers to pay higher premiums, they get sick more often and may cause more damage in the workplace due to the odors and burns associated with smoking. Cigarette smoking is also prohibited in many social events such as sports and not many people like it when others smoke inside their homes and they usually take issue with smokers. To further underline the decline in the social acceptance of cigarette smoking, marriage prospects of smokers are comparatively less promising and are often limited to other smokers (ACS, 2010).

Addictive Properties of Nicotine
When taken in small doses, nicotine is a stimulant which enhances the alertness, activity and memory of people. When used frequently, it induces a physical dependence on the users. According to the US Surgeon General report (1988), the addictive properties of nicotine resemble those of heroin and cocaine. Nicotine crosses the blood brain barrier and is quickly distributed in the brain where it causes its pleasurable effects. These effects do not last for long but they wear off after a short time. This causes the smoker to yearn for more of the pleasurable effect hence to smoke more cigarettes so as to maintain the levels of nicotine. With the continued smoking, the nicotine receptors become up-regulated as a result of desensitization and elevated levels of nicotine in the brain (George  OMalley, 2004 Benowitz, 1999 Stoleman  Jarvis, 1995).

Scientific evidence suggests that the addictive properties of nicotine derive from the observation that it induces the release of dopamine, a chemical that causes pleasure. It is also addictive as it can act as a stimulant (DOH, 1998 USDHHS, 2000 RCP, 2000 Stoleman  Jarvis, 1995).

Nicotine in the Cigarette Smoke
When inhaled, nicotine is first absorbed by the alveoli into the pulmonary circulation. It then gets into the systemic circulation and is quickly distributed in the body. When taken in by mouth, nicotine is absorbed through the buccal cavity and from here it gets into the small intestine. From the small intestine, it is absorbed into the systemic circulation and once it reaches the liver, it undergoes the hepatic first pass effect where it is broken down by the liver. The total bioavailability of nicotine when absorbed through the buccal cavity is 30-40.

Nicotine crosses the blood brain barrier and gets distributed in the brain within 11 seconds of its inhalation (Benowitz, 1999). Once here, it attaches to the nicotinic acetylcholine receptors, causing the release of norepinephrine, epinephrine and dopamine. Nicotine is an agonist of acetylcholine it binds on the receptors and prevents the attachment of acetylcholine while mimicking its actions. Two types of nicotinic receptors have been described. These are central nervous system (CNS) and the peripheral nervous system (PNS) receptors. The receptors are ligand-gated (Benowitz, 1999 George  OMalley, 2004).

Nicotine is metabolized in the kidneys, liver and lungs. Excretion by the kidney is dependent on the pH and flow and is responsible for between 5 and 10 of the total excretion. Elimination follows the first order kinetics and generally, nicotine has a half life of 2 hours although this differs from person to person. The compound is degraded by the p450 cytochromes and the aldehyde oxidase enzymes (figure 1). A large percentage (70) of nicotine is converted to cotinine, 4 to nicotine-N-oxide and 17 to nornicotine and nicotine isomethonium ion. Cotinine has a half life of 16 hours and 17 of cotinine is excreted in that form via the renal system. The remaining 83 is further metabolized to cotinine-N-oxide or to trans-2-hydrocortinine (Giddings, n.d Anon, 2007. This is depicted in figure 1 below.
Adverse Health Effects of Smoking

Smoking has been associated with many adverse health effects. Lung cancer is perhaps the best known disease thats associated with cigarette smoking. Smoking is also a risk factor for many other types of cancers such as cancers of the kidney, mouth, esophagus, stomach, liver, larynx and pharynx. Cancers aside, smoking is also associated with pneumonia. According to the American Society of Cancer (ACS, 2010), people who smoke are many times likely to contract chronic obstructive pulmonary disease or COPD (USDHHS, 1998 DOH, 1998).

Statistics also show that people who smoke are 2 times more prone to heart attacks than those who dont smoke. Smoking also causes the blood vessels which supply the limbs to constrict leading to peripheral vascular disease. It also has the same effect on carotid arteries and smokers are more prone to erectile dysfunction (USDHHS, 1998 DOH, 1998).

Blindness is yet another condition which has been associated with cigarette smoking. According to the American Society of Cancer (ACS, 2010), smoking leads to macular degeneration which is a leading cause of blindness in the aged. Smoking is also associated with higher mortality rates. According to the American Society for Cancer (2010), men who smoke lose over 13 years of life while women who smoke live 14.5 years shorter than their counterparts who dont smoke. More than 50 of smokers end up dying from a disease that is related to smoking. Estimates also indicate that 20 of all deaths in the U.S are related to smoking (CDC, 2000 USDHHS, 1998 DOH, 1998).

Besides having adverse effects on the health of smokers, smoking can also harm the health of non-smokers who get into contact with the cigarette smoke. This is referred to as second-hand or passive smoking. As reported by the American Cancer Society (2010), smoking is associated with the deaths of thousands of people who are otherwise healthy but get exposed to second-hand smoke. The deaths are mainly due to lung cancer and heart diseases that are caused by smoking. Respiratory distress, GIT distress, emesis, hypothermia, seizures and hypertension are the other untoward effects associated with nicotine (USDHHS, 1998 DOH, 1998).

In women, smoking exerts many adverse and long term effects on their health and that of their babies. Studies show that women who smoke and are aged more than 35 years are more prone to contracting deep vein thrombosis (DVT), heart attack and stroke. Women who smoke are also more prone to miscarriages and on average they give birth to children who are underweight. This is not good because underweight children are likelier to experience difficulties in learning than those children who are born with a normal weight. Additionally, underweight children usually have more physical problems (USDHHS, 1998 DOH, 1998).

Children who are born by mothers who smoke also have higher chances of contracting asthma than those born by non-smoking mothers. Additionally, studies have shown a correlation between mothers who smoke and the sudden infant death syndrome (SIDS). As reported by the American Society of Cancer (2010), children who are born and brought up in homes where others smoke usually experience more colds, breathing difficulties, and ear infections (USDHHS, 1998, DOH, 1998).

Smoking Cessation Products
A number of products have been developed to help smokers stop the habit. Nicotine replacement products refer to a group of compounds that have nicotine as the active ingredient. However, they do not contain the other harmful substances that are normally found in cigarette smoke. These products allow the smokers to take in nicotine in much fewer quantities in place of cigarettes. With time, the quantities of nicotine taken reduce until they are weaned off nicotine completely. When they start taking these products, they are able to quit using cigarettes. This is because the replacement products provide a significantly slower uptake of nicotine than do the cigarettes. The nicotine replacement products come in several different forms such as nicotine gum, nicotine lozenges, nicotine inhaler, transdermal patches and nicotine nasal spray. Whereas the nicotine gum is an over the counter product that can be bought without a doctors prescription, nasal sprays and inhalers are prescription only medicaments (Benowitz, 1999 George  OMalley, 2004).

Nicotine patches are self-adhesive strips that are stuck on the skin by users to release small quantities of nicotine into the systemic circulation. Side effects of the patches are local skin irritation and insomnia. Lozenges are candies that dissolve in the mouth and are absorbed into the circulation through the buccal cavity. Common side effects of lozenges are stomach upsets and throat irritation, insomnia and sore gums. Nasal sprays have nicotine aerosols and is associated with sneezing, watery eyes, coughs and irritation of the throat. The inhaler allows administration of nicotine through the nose and is commonly associated with problems in digestion, runny nose, irritation of the mouth lining and coughs (Benowitz, 1999 George  OMalley, 2004).

Besides the nicotine replacement products, there are also some non-nicotine pills available for smoking cessation. Unlike the nicotine replacement products, these pills do not contain nicotine. Zyban is the trade name of a popular non-nicotine pill. It is a sustained release (SR) pill which contains bupropion hydrochloride which is a stimulant for the release of norepinephrine and dopamine. Norepinephrine and dopamine induce a feeling of euphoria and enhances their energy, occurrences that are similar to the action of nicotine. This drug is usually taken twice every day, and smokers are advised to start taking it before they stop smoking. Zyban is a prescription-only medicine and contraindications for its use include lactating or pregnant women, anorexic, epileptic and bulimic subjects and patients under other medications that contain bupropion hydrochloride. Common side effects of Zyban are a dry mouth and insomnia. However, these drugs are not sufficient to help one totally stop smoking and they are often used as part of an elaborate and well thought out smoking program whose key theme is usually behavior modification.

Manufactured and marketed by Pfizer, Chantix is the brand name for a popular anti-smoking and non-nicotine product whose active ingredient is varenicline tartrate. The chemical name for varenecline is 7,8,9,10-tetrahydro-6,10-methano-6H-pyrazino2,3-h3benzazepine, (2R,3R)-2,3-dihydroxybutanedioate. Varenecline is a partial agonist for 42 nicotinic acetylcholine receptors. It acts by binding to these receptors to generate agonist activity and prevent the attachment of nicotine to the receptors (Anon, 2007 Pfizer, 2009 Pfizer, 2009b).

Commonest side effects of Chantix are nausea, insomnia, dyspepsia, constipation, vomiting, abdominal pain and flatulence. The drug is also associated with headaches, respiratory disorders and appetite disorders (Pfizer, 2009b). Other less common but potent side effects include aggression, suicidal thoughts, depression, paranoia, anxiety, panic, hallucinations, anger and mania and serious skin reactions such as rashes (Pfizer, 2009). Neuropsychiatric effects aside, the drug is also associated with angioedema and hypersensitivity reactions. Less common disorders associated with chantix are anemia, and eye, ear, endocrine and cardiac disorders.

Contraindicated for pregnant women, people on asthma, blood thinning and insulin medications. Studies show that Chantix is more efficacious than preparations containing sustained release bupropion hydrochloride (Pfizer, 2009b).

Nicotine is an addictive compound as it can act as a stimulant and as an anxiolytic. Social acceptance of cigarette smoking is at an all time low. Nicotine has many adverse health effects and the most dangerous include lung cancer, cardiovascular diseases, stroke, COPD, pneumonia, pregnancy complications among others. Medications for smoking cessation are expensive and are ridden with potentially lethal side effects. On their own, they cannot be effective solutions for smoking cessation but need to be incorporated as part of a wider behavior modification plan.