Medical Uses

Dozens of clinical trials have shown that the patch approximately doubles success rates over placebo treatment. Placebo tests show a 5.9% success rate, in comparison to the 7.2% blind active tests, and the 10.8% open tests.

History

The first study of the pharmacokinetics of a transdermal nicotine patch in humans was published in 1984 by Jed E. Rose, Ph.D., Murray E. Jarvik, M.D., Ph.D. and K. Daniel Rose, and was followed by publication by Rose et al. (1985) of results of a study of smokers showing that a transdermal nicotine patch reduced craving for cigarettes. Frank Etscorn Ph.D. filed a patent in the United States on January the 23rd 1985 and was issued the patent on July 1, 1986. The University of California filed a competing patent application nearly 3 years after Etscorn's filing on February the 19th, 1988, which was granted on May 1, 1990. Subsequently, the U.S. Patent Office declared an interference action and, after a thorough review of conception, reduction to practice and patent filing dates, issued on September 29, 1993 a priority decision in favor of the Rose et al. patent.

Research

Nicotine patches are under study to help relieve the symptoms of post-surgical pain and treat early dementia. Studies are being conducted about the use of transdermal nicotine patches to treat anxiety, depression, and inattentiveness in subjects with ADHD. Transdermal nicotine patches can be used to relieve ulcerative colitis symptoms. However, this is not the case with Crohn's disease, a similar health condition, where smoking and nicotine intake in general worsen the disease's effects.

Medical Uses

Gum should not be used less than 15 minutes after eating or drinking as doing so will reduce absorption. Users are directed to chew the gum until it softens and produces a tingling sensation or "peppery" taste. The gum is then "parked," or tucked, in between the cheek and gums. When the tingling ends the gum is chewed again until it returns, and is then re-parked in a new location. These steps are repeated until the gum is depleted of nicotine (about 30 minutes) or the craving dissipates. Dosage suggested by the Dental-professional.com website is: weeks 1-6: 1 piece every 1 to 2 hours; weeks 7-9: 1 piece every 2 to 4 hours; weeks 10-12: 1 piece every 4–8 hours; no more than 24 pieces per day. Do not use for longer than 12 weeks. Pregnant women should neither smoke nor use NRT. Light smokers should use the 2 mg and heavy smokers the 4 mg; size of gum is the same for both doses.

Side effects

Chewing nicotine gum may increase the risk of heart disease, although this is still debated. Nicotine is a vasoconstrictor; it constricts arteries, which increases the resistance against which the heart has to pump blood, effectively making it harder for the heart to pump blood through the body. The result is enhanced shear stress on vessel walls, and repeated nicotine exposure contributes to accelerated health problems that are a function of chronic vascular injury such as coronary artery disease, acute cardiac ischemic events, and hypertension Studies have shown that nicotine exposure contributes to stroke, peptic ulcer disease, and esophageal reflux. Nicotine may also cause wounds to heal more slowly and may be associated with reproductive toxicity. Additionally, nicotine can cause the body to release its stores of fat and cholesterol into the blood. Nicotine has been correlated in vitro with increased expression of a gene associated with oral cancer; the researchers say their work "raises the possibility that nicotine could potentially increase the risk of mouth cancer. We want to stress, however, that further research is needed to conclusively determine whether this is indeed the case. There is no doubt however about the harmful effects of smoking, so smokers should make every effort to quit." Professor Robert West points out that there are no epidemiological studies showing a correlation between nicotine replacement therapy and oral cancer. There is evidence that nicotine has the potential to prevent and treat Alzheimer's disease. Nicotine has been shown to delay the onset of Parkinson's disease in studies involving monkeys and humans. A study has shown a protective effect of nicotine itself on neurons due to nicotine activation of α7-nAChR and the PI3K/Akt pathway which inhibits apoptosis-inducing factor release and mitochondrial translocation, cytochrome c release and caspase 3 activation. Research at Duke University Medical Center found that nicotine may improve the symptoms of depression. Nicotine appears to improve ADHD symptoms. Some studies have focused on benefits of nicotine therapy in adults with ADHD.

Muscle control

Two unpleasant symptoms which affect some new users and existing users who make excessive use of nicotine gum, are hiccups and a perceived constriction of the throat muscles, as accidental swallowing of saliva containing high amounts of nicotine may cause irritation.

Birth Defects

Women who use nicotine gum and patches during the early stages of pregnancy face an increased risk of having babies with birth defects according to a 2006 study that looked at about 77,000 pregnant women in Denmark. The study found that women who used nicotine-replacement therapy in the first 12 weeks of pregnancy had a greater risk of having babies with birth defects than women who did not.

Availability

Various policies exist worldwide as to the accessibility of these medications. Originally (in the 1980s) gum was sold only by prescription. In most of the EU and the USA, nicotine gum is currently available at pharmacies over-the-counter subject to the same restrictions on underage purchases as tobacco. Depending upon jurisdiction and pharmacy the purchaser may be directed to the pharmacist, or nicotine gum may be purchased off-the-shelf. If sold where tobacco products are also sold, the display of the nicotine therapy products may be adjacent to the tobacco display. In New Zealand (and now Australia) nicotine gum and patches are classified General Sale and can be sold in outlets other than pharmacies, e.g. petrol stations and supermarkets. This has resulted in a steep fall in the retail price, particularly from online New Zealand stores. This trend away from only being sold over the counter (S3) at pharmacies also followed in Australia with sharp price falls in the last year[ref=2010] and wide availability. Nicotine gum, lozenges and similar preparations can be now readily found on the shelf in the medicinal aisle of most major chain supermarkets and can be purchased alongside other grocery items. In the United Kingdom many NRT products are available in shops, supermarkets, petrol stations and even schools, although an age limit of 12 is required. Own-brand NRT products are available from some pharmacy chains. The National Health Service (NHS) provides NRT at a discounted price or free of charge. Nicotinell was one of the biggest selling branded over-the-counter medications sold in Great Britain in 2016, with sales of £31.2 million. In Hong Kong the large chain pharmacist shops usually, but not always, require the purchaser of the stronger therapy (4 mg dose) to sign a register with passport number or Hong Kong ID.

A nicotine lozenge is a tablet (usually flavored) that contains a dose of nicotine which dissolves slowly in the mouth to release the nicotine. The nicotine is absorbed through the lining of the mouth and enters the blood vessels. It is used as an aid in nicotine replacement therapy (NRT), a process for smoking cessation. People using the lozenge should not smoke because of the increased risk of nicotine poisoning. The effects of the lozenge may be diminished from drinking anything fifteen minutes prior to taking the lozenge.

Medical Uses

Varenicline is used for smoking cessation. In a 2009 meta-analysis varenicline was found to be more effective than bupropion (odds ratio 1.40) and NRTs (odds ratio 1.56). A 2013 Cochrane overview and network meta-analysis concluded that varenicline is the most effective medication for tobacco cessation and that smokers were nearly three times more likely to quit on varenicline than with placebo treatment. Varenicline was more efficacious than bupropion or NRT and as effective as combination NRT for tobacco smoking cessation. The United States' Food and Drug Administration (US FDA) has approved the use of varenicline for up to twelve weeks. If smoking cessation has been achieved it may be continued for another twelve weeks. Varenicline has not been tested in those under 18 years old or pregnant women and therefore is not recommended for use by these groups. Varenicline is considered a class C pregnancy drug, as animal studies have shown no increased risk of congenital anomalies, however, no data from human studies is available. An observational study is currently being conducted assessing for malformations related to varenicline exposure, but has no results yet.

Side effects

Mild nausea is the most common side effect and is seen in approximately 30% of people taking varenicline though this rarely (3%) results in discontinuation of the medication. Other less common side effects include headache, difficulty sleeping, and nightmares. Rare side effects reported by people taking varenicline compared to placebo include change in taste, vomiting, abdominal pain, flatulence, and constipation. In a recent meta-analysis paper by Leung et al., it has been estimated that for every five subjects taking varenicline at maintenance doses, there will be an event of nausea, and for every 24 and 35 treated subjects, there will be an event of constipation and flatulence respectively. Gastrointestinal side-effects lead to discontinuation of the drug in 2% to 8% of people using varenicline.[9][10] Incidence of nausea is dose-dependent: incidence of nausea was higher in people taking a larger dose (30%) versus placebo (10%) as compared to people taking a smaller dose (16%) versus placebo (11%).