Tratamento para cessação do tabagismo

Ir em baixo

Tratamento para cessação do tabagismo

Mensagem  Amanda Freire Vieira em Seg Abr 13, 2015 11:15 pm


Pharmacotherapy for smoking cessation aims to reduce the symptoms of nicotine withdrawal, thereby making it easier for a smoker to stop the use of cigarettes. The main medications that have demonstrated efficacy as smoking cessation aids include nicotine replacement, varenicline, and bupropion. Smokers who wish to quit should be managed with a combination of behavioral therapy and pharmacotherapy as the combination of counseling and pharmacologic therapies produces higher quit rates than either one alone


Smoking cessation clinical guidelines from the United States Public Health Service consider the following drugs to be first-line agents for tobacco cessation: combination nicotine replacement therapy (transdermal nicotine patch combined with nicotine gum, lozenge, inhaler, and/or nasal spray), varenicline, and bupropion. Other medications have been evaluated for smoking cessation but have less established efficacy than first-line agents.
With a few exceptions, choice of first-line medication is generally based on patient preference after discussion with a clinician.

The general principle of replacement therapies is to present the patient with a safer and more therapeutically manageable form of the drug that directly alleviates the signs and symptoms of withdrawal and craving. NRT is modeled after those originally developed to treat dependence on heroin and other opiates. A variety of non-tobacco-based delivery systems provide potentially effective means for nicotine replacement.

Nicotine polacrilex Gums
The next systematic approach was the development of nicotine polacrilex gum. The weaning from nicotine actually begins with the switch from cigarette to gum in that nicotine polacrilex produces slower-rising plasma nicotine levels than cigarette and reduces the inhaled nicotine bolus effect believed to contribute to nicotine's addictive potential in smoke. The same mechanism applies to other replacement approaches including nicotine trans-dermal delivery, nasal nicotine solution (NNS) and smoke-free nicotine cigarettes. The different forms allow variation in delivery (dose and speed), which may influence effectiveness, relief of withdrawal, patient acceptance and outcome.
Although guidelines for selecting different NRT have not been established, clinicians should individualize the treatment based on the patient characteristics and adverse effect profile of each product. NRT attenuates the tobacco withdrawal symptoms and approximately doubles the success rate of quitting smoking relative to smoking.
“Nicotine resin complex” commonly known as nicotine gum, is a nicotine delivery system in which the nicotine is incorporated into an ion exchange resin base, which permits release of nicotine in the proper environment (i.e., saliva in the mouth) when appropriate physical pressure (i.e., chewing) is applied. At 20-30 min of proper chewing results in the release of approximately 90% of nicotine, although there are multiple determinants of how much nicotine actually is absorbed. 10-15 min of chewing results in the release of approximately 50-60% of nicotine in a piece of gum. Variability exists both within and across subjects. Swallowed nicotine is approximately 70% detoxified because of its first pass through the liver. 2 mg and 4 mg nicotine polacrilex gum has been used. 2 mg piece nicotine polacrilex chewing gum is the only one form of nicotine replacement strategy approved by the FDA of United States.
Nicotine-specific withdrawal symptoms, which interfere with successful cessation, can be prevented or attenuated by nicotine replacement. This therapy promotes cessation as well as prevents relapse. Nicotine gum does not fully replace the nicotine provided by cigarette smoking. 4-mg nicotine gum produces plasma nicotine level approximating that of a 1.2 mg-nicotine-yield cigarette. When nicotine polacrilex gum is chewed, drug levels of plasma rise slowly and peak in around 20-30 min, whereas 4-mg gum replaces nicotine more completely. However, effective nicotine replacement strategies may not require the same range of nicotine blood levels as those produced by cigarette smoking. Perhaps because of this, only the 2-mg dose has been approved. The 2-mg nicotine polacrilex gum increases nicotine cessation rates significantly in several placebo-controlled studies.Nicotine gum is quickly absorbed and closely approximates the course of plasma nicotine levels observed after cigarette smoking.
Studies show that nicotine polacrilex gum reduces symptoms of withdrawal in comparison to placebo controls. The degree of relief is directly related to the dose of nicotine that is actually obtained when the polacrilex gum is used.The urge to smoke (craving) is not reliably decreased by nicotine replacement.
Weight gain, is a significant problem in smoking-cessation. It can be reduced by NRT. A 2-mg nicotine gum dose has been found to produce significantly less weight gain.
Craving, often described as an increased urge or desire to use a drug often forces an individual to use a drug. Craving generally is not relieved by NRT. However, to some extent, relief of craving has been reported with 2-mg nicotine polacrilex gum compared with placebo controls in some outcome trials.
4-mg nicotine polacrilex gum improved success rate for more highly dependent tobacco smokers, whereas 2-mg nicotine polacrilex gum is found better in less dependent smokers. In general, 2 mg gum pieces are used for consumers who use <25 cigarettes/day and 4 mg gum pieces for those who smoke >25 cigarettes/day. One gum piece every 1-2 h is used for the first 6 weeks and then one piece every 2-4 h for 2 weeks (7th-9th week) and then one piece every 4-8 h for another 2 weeks. Nicotine from the gum is absorbed through the buccal mucosa, with peak nicotine plasma concentration reached within 15-30 min, when compared with 1-2 min after smoking a cigarette.[53] Acidic beverages like coffee and juices should be avoided before and after the use of nicotine gum, because they decrease the absorption of nicotine. Nicotine gum also provides substitute oral activity during tobacco abstinence.

Nicotine trans-dermal patch
A trans-dermal delivery system can eliminate some of compliance and chewing problems associated with nicotine polacrilex gum. Steady-state administration expected from such a system may be more effective in preventing withdrawal symptoms. Since the patch does not allow for self-administration in response to the smoking urge, it could potentially be used in combination with the other rapidly absorbed forms of nicotine replacement. Nicotine trans-dermal system acts better when used in conjunction with a support programme such as counseling, group therapy or behavior therapy.
The nicotine patch is available for 16- or 24-h delivery systems. For the 24-h delivery system the recommended dose of trans-dermal patch for those who smoke >10 cigarettes/day, 21 mg patch is used every day for the first 6 weeks, then 14 mg every day for the next 2 weeks and then 7 mg patch every day for another 2 weeks. If the cigarette consumption is lesser than 10 cigarettes a day, 14 mg patch/day for first 6 weeks and then 7 mg patch/day for another 2 weeks is used . For the 16-h delivery system, where the patch is taken off before going to sleep, the recommended dose is 15 mg/day for 6 weeks. A meta-analysis shows no benefit of using the nicotine patch longer than 8 weeks.With the nicotine patch, nicotine is absorbed slowly, with peak levels reaching 4-8 h after application and nicotine levels are about half those obtained through smoking. The nicotine patch is easy to administer, requires less frequent dosing, with fewer adverse effects and better compliance. The disadvantage of the patch is the lack of acute (rescue) dosing for craving episodes, which can be provided with other NRTs.In fact, the nicotine patch may be combined with other NRTs to increase its efficacy in treatment resistant cases.

The use of nicotine chewing gum or trans-dermal nicotine patches during smoking cessation delays weight gain until NRT is stopped. However, neither nicotine gum nor the patch combined with smoking cessation provides any long-term benefit of attenuating weight gain.

It is an anti-depressant in a SR form with its action as a neuronal reuptake inhibitor of dopamine and noradrenalin. It was observed that the depressives treated with bupropion spontaneously stopped smoking. The dopaminergic and noradrenergic properties of bupropion hydrochloride provide a theoretical benefit in smoking cessation, in treating the neurochemical changes resulting from nicotine addiction and withdrawal. Bupropion hydrochloride has the benefit of being an oral non-nicotine therapy. Studies demonstrated the efficacy of Bupropion SR for the treatment of tobacco dependence. FDA approved its therapeutic use in 1997 as a first-line treatment for tobacco cessation. Bupropion is equally effective in smokers with or without a history of depression however, this drug could be a better choice in the smokers with the history of depression. The depressives already being treated with some anti-depressants and wish to quit smoking can be given bupropion additionally.
Bupropion is chemically unrelated to nicotine or other agents currently used in the treatment of tobacco dependence. It is a week but selective inhibitor of the neuronal reuptake of dopamine and noradrenalin, with a very minimal effect on serotonin and does not inhibit MAO. Abstaining effect of bupropion is presumably related to its dopaminergic and/or adrenergic properties and to involve the two pathways in the brain that are important in the addiction process. It is hypothesized that dopaminergic activity of bupropion affects the area implicated in the reinforcing properties of the addictive drug and the development of dependence - the reward pathway, or mesolimbic system - while its noradrenergic activity in the locus ceruleus plays a role in withdrawal from nicotine.
Bupropion increases the levels of extracellular dopamine in the nucleus accumbens and enhances dopaminergic activity in the ventral tegmental area of the midbrain via inhibition of reuptake. These effects of dopamine are responsible for overcoming the dependence on nicotine and helping to reduce the craving associated with nicotine dependence. Bupropion decreases the firing rate of noradrenergic neurons in the locus ceruleus; enhances noradrenergic activity, which account for the reduction in nicotine withdrawal symptoms. Bupropion also produces an acute functional blockade of human nicotine receptors.
Bupropion treatment is started while the patient is still smoking and a target date to stop smoking is fixed within 2 weeks of onset of therapy. This is done to allow the time for plasma levels of bupropion to reach steady state and, hence, for the drug to start working effectively. The initial dose should be 150 mg daily for 3 days, increasing to 150 mg twice a day to a remainder of 2 months course (maximum length of treatment 9-12 weeks). However, some clinicians recommend treatment up to 6 months.[62] The length of treatment for tobacco use cessation depends upon many factors, including severity of addiction and the presence or absence of co-morbidities. It is important that the patients complete the full treatment course prescribed in order to maximize the likelihood of long-term abstinence from smoking and so that any patient who fails to quit smoking on the “stop date” can set a new one with the possibility of quitting later in the treatment course. There should be an interval of at least 8 h between successive doses. Maximum single dose should not exceed 150 mg and the total daily dose should not exceed 300 mg.
Similar to other anti-depressants, bupropion also lowers the seizure threshold and should not be used in those with history of seizure disorder, serious head trauma, eating disorders (bulimia or anorexia nervosa) and in those who receive other medications that may lower seizure threshold.

It is an analogue of cyticine, reported to have the benefit in smoking cessation. Varenicline has high and selective activity at alfa4-beta2 receptor. It is a partial agonist at this receptor in vivo producing lesser response than that of nicotine (30-60%) but also blocks the effect of any nicotine added to the system. It stimulates the central nervous mesolimbic system, the neuronal mechanism underlying reinforcement and reward experienced upon smoking. Thus, varenicline maintains a moderate level of dopamine release, which reduces craving and withdrawal symptoms during abstinence. It also blocks the reinforcing effects of nicotine obtained from cigarette smoke in the case of relapse.Varenicline is the non-nicotine containing medication developed with the purpose of treating nicotine addiction. The recommended treatment begins 1-2 weeks before the quit date. For the first 3 days 0.5 mg daily dose is given and on the 4th day the dose is increased to 0.5 mg twice daily up to 7th day. The dose is further increased on 8th day to 1 mg twice a day up to the end of 12 weeks. A further treatment for another 12 weeks with 1 mg twice a day is recommended to prevent relapse. The efficacy of varenicline has been demonstrated in various clinical trials. The main adverse effects such as nausea, headache, vomiting, flatulence, insomnia and abnormal dreams, generally mild in nature are observed which diminish over time. Varenicline is found to have significant effectiveness in long-term relapse prevention. Increased cessation rates have been demonstrated both in long-term and short-term therapy.[70] In India where use of smoke-less tobacco is quite common,varenicline was found to be effective in a double-blind placebo controlled randomized trial for the treatment of smokeless tobacco dependence. Varenicline was also found to be safe for treating smoke-less tobacco dependence.


Amanda Freire Vieira

Mensagens : 10
Data de inscrição : 14/03/2015

Ver perfil do usuário

Voltar ao Topo Ir em baixo

Voltar ao Topo

- Tópicos similares

Permissão deste fórum:
Você não pode responder aos tópicos neste fórum