TOBACCO
Information by Melisse Leung, Premedical Student
University of California, Berkeley

ROUTE OF ADMINISTRATION

Tobacco enters the body in three ways: by smoking cigarettes, a cigar, or a pipe; by inhaling a packet of snuff (a preparation of powdered tobacco with other substances) through the nose; or by chewing wads of tobacco.

EFFECT ON BODY (pathology, pathophysiology)

A single puff of cigarette smoke exposes the body to over 3,000 chemicals. Some of these are deadly, and almost all make the body unable to work properly. The three main harmful substances in tobacco smoke are nicotine, tar, and carbon monoxide. Nicotine is a drug in tobacco that speeds up the heartbeat and makes tobacco users crave more tobacco (makes it addictive). It can cause the dizziness and upset stomach that many beginning smokers feel. Tar is a thick, dark liquid that is formed when tobacco burns. This tar covers the linings of the lungs, where it can cause disease. Carbon monoxide is a poisonous gas that is produced when tobacco burns. All three of these substances are in tobacco smoke, whether the user is smoking a cigarette, a cigar, or a pipe. Tar and carbon monoxide are not in smokeless tobacco, but nicotine is.

When a person inhales cigarette smoke, the nicotine it carries reaches the brain, via the bloodstream, in about 8 seconds, which is less time than it would take to get there had the person injected it intravenously. By the time 15 to 20 seconds have elapsed, the nicotine has spread throughout the whole body, and has even made it to the body's last output, the big toe. More than 90 percent of the nicotine in inhaled cigarette smoke is absorbed by the lungs. Nicotine enters the body in the form of thousands of little droplets, each suspended in a solid particle of partially burned tobacco (tar). These nicotine droplets are so small that they can penetrate into the tiniest branches of the lungs, where they are picked up by blood that has been sent to the lungs to take up oxygen. From the lungs, it moves quickly to the left side of the heart, where nicotine is pumped out to every corner of the body.

With the first cigarette of the day, heart rate will increase by 10 to 20 beats per minute. Blood pressure will go up 5 to 10 points. Body temperature will drop in the fingertips as the blood vessels there are constricted. These effects do not increase by this much more with each cigarette smoked. But given the length of time nicotine persists in the bloodstream, an average smoker will go around all day and all night in an altered state. The level of nicotine in the bloodstream increases throughout the day in which waves of nicotine come with each cigarette and quickly pass, but the overall level of nicotine climbs gradually through the day and then falls during sleep. The level is high enough and its fall gradual enough, however, that for most smokers, nicotine is active in them 24 hours a day, and they are never off the drug.

Acetylcholine (ACH) is one of the body's most important neurotransmitters. It works at the synaptic junctions where nerves and muscles meet and it is very important in the body's autonomic nervous system, which controls involuntary bodily functions. It also works within the brain itself, helping to send messages from one part to another. Nicotine can mimic the effects of acetylcholine in an array of areas: where ACH will work as a neurotransmitter, nicotine will work in its place.

Since ACH works throughout the body, this also means that nicotine works throughout the body, wherever there are nicotinic receptors. One of its most important effects at these receptor sites is that it can stimulate the release of other neurotransmitters. The adrenal glands have nicotinic receptors on them, and when they get a dose of nicotine (or ACH) they release the neurotransmitters norepinephrine and epinephrine (adrenaline), which are responsible for some of the stimulating effects of nicotine. The increased blood pressure that results from the first cigarette of the day comes about because blood vessels themselves release norepinephrine when the nicotine comes in contact with them. The release of epinephrine and norepinephrine are stimulant responses to a drug, which provides plenty of blood at the heart for increased output. There is increased heart rate for the same reason, and less blood goes to the extremities in order to provide blood at the body's core. What results is increased blood pressure when the blood vessels on the periphery are narrowed. In effect, the body's "fight or flight" reaction is stimulated, and the body is primed for action. A similar effect takes place in the brain when a person smokes a cigarette: the brain moves to a state of higher arousal.

Contained within the brain stem, beginning at about the place where the neck meets the head, there is a group of cells called the reticular formation that is the most important area in human sensory arousal. The reticular formation sends nerve fiber projections up and out to all areas of the cerebral cortex. Stimulate certain parts of the reticular formation and the brain moves to a state of greater sensory arousal. One of the main things the reticular formation does is to act in giving a "wake-up call" to other parts of the brain when this sensory stimulation comes in. Nicotine seems to achieve much of its alerting effect on the brain by way of its action on the reticular activating system. This is because cells in the system contain nicotinic receptors that respond to nicotine as well as they would to the body's own neurotransmitter, acetylcholine.

Therefore, nicotine's effect can be explained by how it can serve the function of acetylcholine at many receptor sites. However, the bond nicotine makes with the receptor is stronger and longer lasting than ACH. In small doses, nicotine will stimulate transmission at nicotinic sites, but in large doses it begins to impede transmission by staying bound with the receptor. In this case, the synapse cannot be completely cleared for new transmission, and in huge doses, nicotine stops transmission altogether. This is how people can die from a nicotine overdose: their respiratory circuits simply cease to function because messages cannot get through.

Experiments have demonstrated that the more nicotine people had in their systems, the less aggressively they acted toward others. There is a decreased attack response and an increased escape response, similar to tranquilizers. Nicotine moderates mood shifts that are brought about by stressful influences. It seems to diminish aggression, while helping people to maintain sociability and an even tone. Just as important, it does these things without having a generalized numbing effect. Nicotine has a reputation as "one of the dirtiest drugs in pharmacology" because it does not have clean, isolated effects, but rather effects that vary according to dose and individual.

Tar produces chronic irritation of the respiratory system and is a major cause of lung cancer. Smoke particles irritate the lung airways, causing excessive mucus production. They also indirectly destroy the walls of the lungs' alveoli, which coalesce . Both factors reduce lung efficiency, and tar in tobacco smoke has a direct cancer-causing action. Cigarette smoke also contains carbon monoxide (CO), which may contribute to heart disease and also plays a role in the way that smokers process the air they breathe. Oxygen is carried to the various parts of the body by hemoglobin, a protein in red blood cells. As oxygen enters the bloodstream from the lungs, it binds with hemoglobin. When the hemoglobin reaches its destination, the oxygen splits off to be used within cells, and the hemoglobin returns to the lungs to pick up another partner. That partner, however, can just as easily be carbon monoxide as oxygen. Hemoglobin actually binds much more readily with carbon monoxide than with oxygen. The hemoglobin that binds with CO is unavailable to carry oxygen, and there are only so many hemoglobin molecules in the body at any given time, thus CO interferes with oxygenation of the tissues. Therefore, a fair number of hemoglobin molecules can be engaged in carrying poison rather than life-sustaining oxygen, preventing smokers from participating effectively in high-oxygen-requiring activities such as running a marathon. The body tries to respond to this chronic condition by creating more red blood cells, but the compensation is incomplete.

When carbon monoxide binds with hemoglobin, the result is a molecule called carboxyhemoglobin (COHb), and its level in the bloodstream is a pretty good way to judge a person's actual intake of cigarette smoke products. In the long run, persistently high levels of carbon monoxide in the blood (which usually occur in smokers) lead to hardening of the arteries, which increases the risk of coronary diseases.

ORGAN SYSTEMS MOST AFFECTED BY THIS SUBSTANCE

The respiratory and the circulatory system are most affected by tobacco use. The tar and other chemicals in smoke damage the bronchi, the passages through which air enters the lungs. The bronchi can become clogged, then infected, or sore and swollen; the infections may then lead to cancer. Smoke coats the bronchi and alveoli in the lungs, making the lungs work less efficiently and causing disease like cancer and emphysema. Lung cancer is probably the best known harmful effect of smoking. Since pipe and cigar smokers tend not to inhale tobacco smoke, they have a slightly lower risk of lung cancer, although the risk is still significantly greater than that of nonsmokers. Pipe and cigar smokers have a higher risk of cancer of the oral cavity and upper respiratory tract while tobacco chewers and those who use snuff risk cancer of the oral cavity. The other important respiratory diseases associated with smoking are chronic bronchitis and emphysema and combinations of the two. These diseases, features of which include increasing breathlessness and coughing up sputum, account for tens of thousands of deaths annually in the U.S. from respiratory failure. In addition, smoking also increases the risk of mouth cancer, lip cancer, and throat cancer.

Nicotine makes the heart work harder. Harmful gases in smoke cause the blood vessels to narrow, causing a greater risk of heart disease and stroke. Carbon monoxide passes from the lungs into the blood. Once in the blood, it works to stop the flow of oxygen to all parts of the body. The lack of oxygen causes the smoker to feel tired. Other chemicals in smoke clog the vessels that carry blood to and from the heart Thus, the other significant harmful effect of smoking is coronary heart disease, which is the most common cause of death in middle-aged men in Western countries. The risk of coronary heart disease in a young man who smokes 20 cigarettes a day is about three times that of a nonsmoker, and the risk increases proportionately with the number of cigarettes smoked. In addition to its effects on the coronary arteries, smoking damages arteries that supply other parts of the body and also raises blood pressure. Smoking seriously affects the arteries of the legs, leading to peripheral vascular disease; in severe cases of peripheral vascular disease, painful neuropathy, or gangrene, amputation may be necessary. Also affected by smoking are the arteries of the brain, which may result in a stroke.

Smokeless tobacco does not contain tar and carbon monoxide, but it does contain nicotine, which makes it just as addictive. The pH level in moist snuff products varies from a low of 5.24 to a high of 8.35. Increases in pH can increase the rate of absorption of nicotine from smokeless tobacco through the mouth into the bloodstream. Studies of nicotine and other addictive drugs suggest that the rate at which drugs are absorbed is an important determinant of their addiction potential.

The mean levels of unprotonated (free) nicotine vary from 0.01 milligram/gram to 6.23 milligram/gram, while the percentage of unprotonated (free) nicotine varies from a low of 0.23 percent to a high of 68.14 percent. Unprotonated (free) nicotine is the chemical form of nicotine that is most readily absorbed through the mouth and into the bloodstream.

People who use smokeless tobacco are much more likely to develop mouth and gum cancer. The juice made by chewing may cause white spots on the gums and on the inside of the cheeks, called leukoplakia, which often become cancerous. Chewing tobacco also harms the stomach, intestines, and bladder. Chewing raises the amount of watery saliva in the mouth, and when people who chew tobacco swallow this saliva, the poisons that were in the tobacco enter the body. These poisons can cause ulcers in the stomach and can damage the inner lining of the small intestine. Smokeless tobacco also causes bad breath and stains the teeth. Chewing makes it harder for the user to smell and taste certain foods. Because the tobacco leaf has dirt and grit, chewing wears down the teeth and damages the gums.

SECONDARY EFFECTS OF TOBACCO USE

Smoking is extremely harmful during pregnancy. The babies of pregnant women who smoke might be killed by the effects of smoking. Those who live are more likely to be smaller, have a lower birth weight, and become less likely to survive than those of nonsmoking mothers. Even after birth, there are hazards for the children of parents who smoke. These children are more likely to suffer from asthma or other respiratory diseases.

Smoke also harms the health of non-smokers by way of second-hand smoke. These "passive smokers" suffer considerable immediate discomfort in the form of coughing, wheezing, and watering eyes. The smoke coming from the burning tip of another person's cigarette is called sidestream smoke. Sidestream smoke contains twice as much tar and nicotine as does the smoke that the smoker breathes in because it does not pass through the length of the cigarette and cigarette filter.

We spend more time in our homes than anywhere else. So the thought of cancer-causing chemicals circulating throughout our houses and apartments can be quite unsettling. Yet, according to the Environmental Protection Agency, that is exactly what happens when someone lights a cigarette in your home. Those most affected by secondhand smoke are children. Because their bodies are still developing, exposure to the poisons in secondhand smoke puts children in danger of severe respiratory diseases such as asthma, and can hinder the growth of their lungs. On top of that, the effects can last a lifetime. These children are also more likely to become smokers themselves.

Ventilation systems in homes cannot filter and circulate air well enough to eliminate secondhand smoke. Blowing smoke away from children, going into another room to smoke, or opening a window may help reduce children's exposure but will not protect them from the dangers of secondhand smoke. The 1993 report from the Environmental Protection Agency (EPA), a comprehensive analysis of many respiratory studies on the health effects of environmental tobacco smoke (ETS), concluded that ETS caused lung cancer in adult nonsmokers and serious respiratory problems in children. On the basis of health hazards of ETS, EPA has classified secondhand smoke as a Group A carcinogen (known to cause cancer in humans).

CLINICAL ASPECTS OF THIS SUBSTANCE

Tobacco contains a variety of different poisonous substances, but the dangers of three of them are particularly important. Nicotine is the substance that causes addiction to tobacco. It acts as a tranquilizer, but also stimulates the release of epinephrine into the smoker's bloodstream that elevates his/her blood pressure. Carbon monoxide passes from the lungs into the bloodstream, where in competition with oxygen, is easily combines with hemoglobin and thus interferes with the oxygenation of tissues. In the long term, persistently high levels of carbon monoxide in the blood of the smokers will lead to hardening of the arteries, which increases the risk of coronary thrombosis. Tar in tobacco produces chronic irritation of the respiratory system and is the major cause of lung cancer

Thus, tobacco smoking is a sure way to damage the body. It contributes to about one death in seven in the US. The main harmful effects come from nicotine, carbon monoxide and tar. The first two contribute to heart disease, while tar causes lung disease and cancer.