Nicotine Replacement Therapy


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Smoking cessation – Nicotine Replacement Therapy (NRT)

Regarding treatment for smoking cessation, the combination of pharmacotherapy and counseling intervention achieves higher quit rates compared with each method separately. The most effective medications for smoking cessation include nicotine replacement products, bupropion and varenicline. Below are listed the different formulations of nicotine replacement therapy:

  • Dermal nicotine patches
  • Nicotine gum
  • Nicotine lozenges
  • Nicotine inhaler
  • Nicotine Nasal Spray

Nicotine replacement therapy (NRT)

For individuals who wish to use nicotine substitutes, it is proposed the use of a combination of a long-acting product and a short-acting product.

The aim of nicotine replacement therapy is to administer nicotine to the smoker without having to smoke it. In this way, NRT reduces withdrawal symptoms from nicotine as the smoker stops smoking. The use of nicotine substitutes in place of cigarettes, helps avoiding exposure to carbon monoxide which causes hypoxia, to oxidotic gases that cause atherosclerosis and to tar which is carcinogenic.

The various nicotine substitutes differ in their pharmacokinetics and how quickly they release nicotine into the blood and therefore the brain. However, no product releases nicotine as fast as smoking itself, which contributes significantly to the dependence caused by cigarette smoke. In particular, the transdermal patch, has a long action and releases nicotine slowly and steadily for about 24 hours. The patient compliance is high, but has the disadvantage that the user does not control how much nicotine is released at any time. So if you have a strong desire to smoke any time of day, despite the use of the patch, you will relapse to smoking if you use only a patch as a monotherapy for smoking cessation.

In contrast, the nasal spray and oral formats (lozenges, chewing gum, inhaler) have a short action and faster increase in blood nicotine levels, which allow the user greater flexibility in the case he has a strong desire to smoke. However, the nasal spray and inhaler form require repeated doses during the day and lead to unstable blood levels of nicotine, while the instructions for dosage is more complex than the patch.

Research has shown that all five nicotine replacement products were more effective than placebo, achieving double quit rates. However, only few studies have compared nicotine substitutes to each other.

Combinations of different products are more effective compared with monotherapy. It is also worth noting that rates of smoking relapse among smokers who use NRT are similar than those who try other methods to stop smoking without the use of these products.

The dose of nicotine replacement products varies depending on the number of cigarettes someone smokes everyday. Usually the dose is decreased as the withdrawal symptoms gradually subside. Generally speaking, the use of nicotine replacement is recommended for 2 to 3 months. However, in patients with a high degree of dependence, it is acceptable to use them for a longer period of time.

Smokers often worry that using nicotine substitutes, they may remain dependent on them when they quit smoking. This can actually happen but is rare. The dose of nicotine taken with these products is lower and the release of nicotine slower compared with smoking, so long term dependence is avoided.

The main side effect of nicotine replacement therapy depends on each individual product. NRT, used in combination, is safe, as the products release lower blood levels of nicotine compared with those produced by smoking one pack of cigarettes a day. Additionally, if a smoker feels any side effects, he can reduce the dose of the substitute and therefore, reduce side effects.

The nicotine replacement therapy is safe for people with known cardiovascular disease. Even smokers suffering from acute coronary syndrome do not seem to have an increased cardiac toxicity of nicotinic substitutes. Furthermore, the benefits to a smoker who will stop smoking by taking these products, are much greater than the relative risk of developing a cardiac toxicity.

Transdermal patch

This is the simplest product of NRT. It provides continuous dose of nicotine, but does not allow modification of nicotine according to the momentary needs and symptoms of the smoker. Starting the quit day, patients who smoke > 10 cigarettes per day (half a package) are proposed to use the higher dose patch (21 mg / day) for 6 weeks followed by 14 mg / day for 2 weeks and finally 7 mg / day for the last 2 weeks (ie a total of 10 weeks). Smokers who weigh less than 45 kg or those smoking ≤ 10 cigarettes per day, it is proposed to take the patch of 14-mg / day for 6 weeks, and then, that of 7 mg / day for another 2 weeks (total 8 weeks).

The use of the patch is very simple. The smoker sticks the patch on a hairless area of ​​the body every morning. He removes it and replace it by a new one next morning. The stick point on the skin should be changed daily to avoid creating local irritation of the area, which is the most common complication. Insomnia and vivid dreams are also described as side effects, which disappear by removing the patch at bedtime.

Nicotine gum

The nicotine gum containing nicotine is united in a resin and a buffer. The cigarette withdrawal symptoms generally are not prevented by the use of chewing gum, but these may reduce in intensity. Furthermore, as blood levels of nicotine are lower compared with those prevailing in smoking, both the euphoria and the feeling of dependence on nicotine are less, than those of smoking cigarettes.

The gum of 4 mg is recommended for smokers who smoke 25 or more cigarettes a day. The gum of 2 mg is recommended for use by lighter smokers. The smoker is proposed to chew the gum whenever he has the feeling that he wants to smoke. By chewing gum, nicotine is released and is absorbed by the oral mucosa. The highest concentration of nicotine in blood is obtained 20 minutes after starting chewing. A smoker can chew a gum every 1 to 2 hours for a period of 6 weeks and then gradually reduce the dose for another 6 weeks (12 weeks of total treatment).

The proper technique of chewing gum is important to have positive results. If someone chews too fast, nicotine is released much faster than can be absorbed through the oral mucosa, and thus eventually swallowed rather than absorbed. In this case, nicotine can cause irritation of the esophagus and stomach. Moreover, nicotine absorbed by the gastrointestinal tract is metabolized by the liver and eventually inactivated. Correct chewing technique is as follows: The gum is chewed until the person feels the taste of nicotine and then he deposits the gum inside his mouth behind his cheeks until he does not taste nicotine anymore. Once this is done, the person can chew another gum etc. This cycle is repeated for about 30 minutes because in 30 minutes all the nicotine will be released. So after half an hour, the gum is removed from the mouth anyway.

The acidic beverages (eg coffee, soft drinks) should be avoided before and during the chewing of gum, because they lower the pH of the mouth and eventually reduce the absorption of nicotine.

Side effects are mainly the result of excess nicotine released after intense chewing and usually include nausea, vomiting, abdominal pain and constipation, hiccups, headache, salivation, pain in jaw and mouth irritation with presence of ulcers in the oral mucosa. People with temporomandibular joint disease, poor dental and oral hygiene and people wih dentures should avoid the use of nicotine gum.

Nicotine lozenges

The action of nicotine lozenges resembles that of chewing gum. In contrast, however, they are not chewed, so it is easier to use. In addition, the groups mentioned above that are contraindicated to use the chewing gum (eg, poor oral hygiene, dentures, etc.), they can use the lozenges, instead. The lozenge is placed in the mouth and is left to dissolve for 30 minutes. They are available in 2 and 4 mg. The lozenge of 4 mg is recommended for smokers who lit the first cigarette of the day within the first 30 minutes from the time they wake up (index of high nicotine dependence). The lozenge of 2 mg is recommended for the remaining smokers. The plan resembles that of chewing gum, one lozenge every 1 to 2 hours for 6 weeks and then dose reduction for the next 6 weeks. The maximum dose is 5 lozenges every 6 hours, or 20 lozenges in 24 hours. Adverse effects of nicotine lozenges include irritation and ulcers in the mouth, abdominal pain, nausea and vomiting, diarrhea, headache and palpitations.

Inhaled nicotine

When the smoker inhales through the nicotine inhaler, nicotine is released in the form of steam and deposited inside the oropharynx and then absorbed by the oral mucosa. The nicotine does not reach the lungs but remains locally in the oropharynx. Nicotine levels achieved in blood are approximately 1/3 of those during smoking cigarettes. The recommended dose is 6 to 16 inhalations per day for the first 6 to 12 weeks and then gradually decrease for another 6 – 12 weeks. The local irritation of the mouth and throat are common, especially during the first days of use. Also, nicotine inhaler can potentially cause bronchoconstriction, so it is not recommended to people with airway hyperresponsiveness as asthmatics.

Nicotine Nasal Spray

It provides nicotine in aqueous solution for absorption by the nasal mucous membranes. The blood levels of nicotine rise faster with nasal spray compared with the gum, lozenge and inhaler form, and reach a maximum in 10 minutes. The recommended dosage is one or two puffs of spray every hours, and for a duration of approximately 3 months. The maximum dosage is 10 puffs per hours or 80 puffs in 24 hours. Typically, its use is limited by irritation of the nose and throat, fever, sneezing and tear production. Especially, the irritation of the nose is very common and is found in about 81% of users, after 3 weeks of therapy.

Combined nicotine replacement therapy

It is proposed that combination therapy with long- and short-action products, to be the initial option for nicotine replacement therapy. The patch is the main product of long-action and is combined with some of the short-action products when there is a strong desire to smoke and withdrawal symptoms. The choice of short-acting formulation depends on patient preference and other medical history.
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