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Wikipedia

Nicotine replacement therapy

Nicotine replacement therapy (NRT) is a medically approved way to treat people with tobacco use disorder by taking nicotine through means other than tobacco.[6] It is used to help with quitting smoking or stopping chewing tobacco.[1][7] It increases the chance of quitting tobacco smoking by about 55%.[8] Often it is used along with other behavioral techniques.[1] NRT has also been used to treat ulcerative colitis.[1] Types of NRT include the adhesive patch, chewing gum, lozenges, nose spray, and inhaler.[1] The use of multiple types of NRT at a time may increase effectiveness.[9][10]

Nicotine replacement therapy
A nicotine patch is applied to the left arm.
Clinical data
Trade namesNicoderm, Commit, Nicorette, others[1]
Other namesNRT
AHFS/Drugs.comMonograph
MedlinePlusa601084
License data
Routes of
administration
Oral, Inhalation, Transdermal,
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolitesCotinine
Excretionrenal
Identifiers
  • (S)-3-[1-Methylpyrrolidin-2-yl]pyridine
CAS Number
  • 54-11-5
PubChem CID
  • 89594
ChemSpider
  • 80863
UNII
  • 6M3C89ZY6R
Chemical and physical data
FormulaC10H14N2
Molar mass162.236 g·mol−1

Common side effects depend on the formulation of nicotine.[1] Common side effects with the gum include nausea, hiccups, and irritation of the mouth.[1] Common side effects with the patch include skin irritation and a dry mouth while the inhaler commonly results in a cough, runny nose, or headaches.[1] Serious risks include nicotine poisoning and continued addiction.[1] They do not appear to increase the risk of heart attacks.[8] There are possible harms to the baby if used during pregnancy.[1][11] Nicotine replacement therapy works by reducing cravings caused by nicotine addiction.[1][12]

They were first approved for use in 1984, in the United States.[1] Nicotine replacement products are on the World Health Organization's List of Essential Medicines.[13][14][15] They are available as generic medications.[1]

Medical uses edit

 
An oral nicotine spray
 
Nasal spray
 
Nicorette inhalator, a nicotine vapour inhalator with disposable cartridges

Nicotine replacement therapy, in the form of gum, patches, nasal spray, inhaler and lozenges all improve the ability of people trying to quit tobacco products.[8] Nicotine replacement therapy is as effective as medications, such as bupropion, in helping people quit smoking for at least six months.[16] All forms of nicotine replacement therapy, including nicotine gum, patches, nasal spray, inhalers, and lozenges, have similar success rates in terms of helping people stop smoking. However, the likelihood that someone will stick to a certain treatment varies, with compliance being the highest with nicotine patches, followed by nicotine gum, inhalers, and nasal sprays.[17] Using a few different nicotine replacement methods in combination may improve success rates in stopping tobacco use.[16][18] Additionally, using nicotine replacement with counseling has been proven to improve tobacco abstinence rates.[19][20] These other strategies include: creating a plan to quit and utilizing quit programs, a quit phone line, or app that provides tips and inspiration to help quit.[18]

Using nicotine replacement therapy to quit smoking should be considered for people who are severely dependent on nicotine.[21] People who are severely dependent include those who smoke: more than one pack per day, within five minutes of awakening, while ill, when they wake up in the middle of the night, to ease withdrawal signs and symptoms.[21]

Nicotine replacement products are most beneficial for heavy smokers who smoke more than 15 cigarettes per day. There are not enough studies to show whether NRT helps those who smoke fewer than 10 cigarettes per day.[20]

Effectiveness edit

Evaluation of NRT in real-world studies produces more modest outcomes than efficacy studies conducted by industry-funded trials. The National Health Service (NHS) in England has a smoking cessation service based on pharmacotherapy in combination with counseling support. An Action on Smoking and Health (UK) (ASH) report claims that the average cost per life-year gained for every smoker successfully treated by these services is less than £1,000 (below the NICE guidelines of £20,000 per QALY (quality-adjusted life year). However, the investment in NHS stop smoking services is relatively low. A comparison with treatment costs for illicit drug users shows that £585 million is committed for 350,000 problem drug users compared to £56 million for 9 million users of tobacco. This is £6.20 for each smoker, compared to £1,670 per illegal drug user.[22]

The claims for high efficacy and cost-effectiveness of NRT have not been substantiated in real-world effectiveness studies.[23][24][25] Pierce and Gilpin (2002) stated their conclusion as follows: “Since becoming available over the counter, NRT appears no longer effective in increasing long-term successful cessation” (p. 1260).[25] Efficacy studies, which are conducted using randomized controlled trials, do not transfer very well to real-world effectiveness. Bauld, Bell, McCullough, Richardson and Greaves (2009) reviewed 20 studies on the effectiveness of intensive NHS treatments for smoking cessation published between 1990 and 2007.[26] Quit rates showed a dramatic decrease between 4-weeks and one year. A quit rate of 53% at four weeks fell to only 15% at one year. Younger smokers, females, pregnant smokers and more deprived smokers had lower quit rates than other groups.

The efficacy for each of the formulations alone (lozenges, nasal spray, gum, and transdermal patch) to aid in smoking cessation is equal.[27] Efficacy increases 15% to 36% with combining treatments such as gum and lozenges. Higher doses increase the chance of stopping smoking for a period of six months and more. For patches, the most efficient doses were 25 mg worn over 16 hours or 21 mg worn over 24 hours. The evidence suggests that 4 mg nicotine gum leads to higher quit rates compared with 2 mg in heavy smokers.[28]

Toxicity edit

N-Nitrosonornicotine, a strong carcinogen present in unburned tobacco and cigarette smoke, has been found in the urine of some users of oral NRT products.[29] Nicotine patches is an alternative.

Side effects edit

 
Possible side effects of nicotine[30]

Some side effects are caused by the nicotine, and are common to NRT products.[31][32] Other common side effects depend on the formulation of nicotine.[1] Common side effects with the gum include nausea, hiccups, and irritation of the mouth.[1] Common side effects with the patch include skin irritation and a dry mouth while the inhaler commonly results in a cough, runny nose, or headaches.[1] To minimize local skin reactions from the patch, the application site should be moved daily.[33] The nicotine patch can also cause strange dreams if worn while asleep.[20] Nasal sprays commonly cause nasal irritation, watering eyes, and coughing.[31]

Serious risks include nicotine poisoning, which includes symptoms like visual disturbances, hyper-salivation, nausea, and vomiting; and continued addiction to nicotine products.[1] Avoiding smoking and other products with nicotine are recommended since it may lead to nicotine overdose.[34] Although overdose is rare, it can be problematic, especially in children and pets.[35] The symptoms of nicotine overdose include headache, pale skin and mouth, belly pain, weakness, diarrhea, tremors or seizures, agitation, confusion, restlessness, high or low blood pressure, fast or irregular heartbeat, fast breathing, and cold sweats.[21]

Limited evidence exists regarding long-term NRT use.[36]

Safety edit

Pregnancy edit

Nicotine is not safe to use in any amount during pregnancy.[37] Nicotine crosses the placenta and is found in the breast milk of mothers who smoke as well as mothers who inhale passive smoke.[38] There are possible harms to the baby if NRT is used during pregnancy.[1][11] Thus, pregnant women and those who are breastfeeding should also consult a physician before initiating NRT.[39] The gum, lozenge, and nasal spray are pregnancy category C. The transdermal patch is pregnancy category D. The transdermal patch is considered less safe for the fetus because it delivers continuous nicotine exposure, as opposed to the gum or lozenge, which delivers intermittent and thus lower nicotine exposure.[40][41]

Strong evidence suggests that nicotine cannot be regarded as a safe substance of cigarette use.[40] Nicotine itself could be at least partly responsible for many of the adverse after birth health results related to cigarette use while the mother was pregnant.[40] There is evidence that nicotine negatively affects fetal brain development and pregnancy outcomes.[42] There is also risk of stillbirth and pre-term birth.[43] Nicotine use will probably harm fetal neurological development.[44] Risks to the child later in life from nicotine exposure during pregnancy include type 2 diabetes, obesity, hypertension, neurobehavioral defects, respiratory dysfunction, and infertility.[32] Nicotine exposure during pregnancy can result in attention deficit hyperactivity disorder (ADHD) and learning disabilities in the child.[citation needed] It also puts the child at increased risk for nicotine addiction in the future.[40]

Pregnant women should consider behavioral therapy before NRT is considered.[1]

Youth edit

In people under the age of eighteen, a physician is often consulted before starting NRT.[39] The evidence suggests that exposure to nicotine between the ages of 10 and 25 years causes lasting harm to the brain and cognitive ability.[45] Evidence is unclear whether adolescents gain benefit from cognitive-behavioral therapy or smoking cessation over the long-term as of 2017.[46] Most tobacco users are under-eighteens when they start, and almost no-one over the age of 25 starts using.[47]

Cardiovascular conditions edit

While there is no evidence that NRT can increase the risk of heart attacks,[8] individuals with pre-existing cardiovascular conditions or recent heart attacks should consult a physician before initiating NRT.[39]

Smoking is known to cause cardiovascular diseases such as coronary heart disease, hypertension, heart attack, stroke, and peripheral artery disease. Cigarette smoking is the cause of 20% of all cardiovascular deaths in the United States, which is the leading cause of mortality.[48]

Other conditions edit

Nicotine replacement therapies should be used cautiously in individuals with the following conditions: severe reactive airway diseases (for nasal spray), chronic nasal disorders such as sinusitis, polyps, rhinitis, or allergy (for nasal spray), diabetes (insulin-dependent), gastrointestinal diseases such as esophagitis, active gastric or peptic ulcer disease, liver problems, hyperthyroidism,pheochromocytoma, phenylketonuria (for lozenges), renal problems, and skin conditions such as psoriasis or dermatitis (for the transdermal patch).[49]

Mechanism of action edit

Nicotine replacement therapy works by reducing cravings due to nicotine addiction.[1][12] Smoking cigarettes releases high doses of nicotine to the brain in a matter of seconds as opposed to low doses released over a period of minutes to hours by the various forms of nicotine replacement therapy.[33] Nicotine from NRT does not reach as high a concentration in the blood as does nicotine from smoke inhalation due to different absorption methods. NRT relies on systemic venous absorption, whereas nicotine from cigarettes reaches the arterial system.[33] Nicotine replacement products vary in the time it takes for the nicotine to enter the body and the total time nicotine stays in the body.[19] The more quickly a dose of nicotine is delivered and absorbed, the higher the addiction risk.[50] It is possible to become dependent on some NRTs.[51]

Nicotine patches are applied to the skin and continuously administer a stable dose of nicotine slowly over 16–24 hours.[19][41] Nicotine gum, nicotine sprays, nicotine toothpicks, nicotine sublingual tablets, and nicotine lozenges administer nicotine orally with quicker nicotine uptake into the body but lasting a shorter amount of time.[52] Nicotine inhalers are metered-dose inhalers[citation needed] that administer nicotine through the lungs and mucous membranes of the throat quickly, lasting for a short amount of time. For example, blood nicotine levels are the highest 5–10 minutes after using the nicotine nasal spray, 20 minutes after using a nicotine inhaler or chewing nicotine gum, and 2–4 hours after using a nicotine patch.[19][53]

Society and culture edit

NRT products were first approved for use in the United States in 1984.[1] Nicotine replacement products are on the World Health Organization's List of Essential Medicines..[13] They are available as generic medication.[1]

Formulations edit

 
Nicotine pastilles
NRT Type Device/package Availability How it works[54][55]
Patch Pouch Over-the-counter 16 or 24 hours sustained-release transdermal patch
Lozenge Blister pack Over-the-counter 20 to 30 minutes modified-release dosage tablet containing nicotine polacrilex
Sublingual tablets Blister pack Over-the-counter Quickly dissolves to releases nicotine through a hard candy
Gum Blister pack Over-the-counter Chewing the gum releases nicotine as a modified-release dosage
Mouth spray Mouth spray bottle Over-the-counter Spraying a mist into the mouth administers nicotine for buccal administration
Vapour inhalator Nicorette Inhalator: with 10 mg nicotine disposable cartridges Over-the-counter Resembles cigarettes; A disposable cartridge contains about 10 mg nicotine (about 40% is released). Multiple inhaling through the mouthpiece administers sufficient nicotine.
Pressurized Metered-dose inhaler (pMDI) Prescription Inhaling through the mouthpiece administers nicotine
Nasal spray Nasal spray bottle Prescription Spraying a pump bottle into the nose administers nicotine

The nicotine patch is a once-daily, longer-acting form of NRT. An advantage of the nicotine patch is its simple compliance; it does not require active use throughout the day.[33] The gum, lozenge, sublingual tablet, oral inhaler, oral spray, and nasal spray are acutely dosed products, providing the user with the benefit and ability of self-titrating based on cravings.[33]

Brand names include Commit Lozenge, Nicoderm, Nicogum, Nicorette, Nicotex, Nicotinell, and Thrive. NRT products contain similar pharmaceutical grade nicotine as is used in e-cigarettes.[citation needed]

Medicines edit

In 2015, the United States Public Health Service listed seven agents for the stopping of tobacco, which included five nicotine replacement treatments (nicotine patches, gum, lozenges, inhalers, and nasal sprays) and two oral medications (bupropion and varenicline). Other NRT options are available, including nicotine mouth sprays and sublingual tablets.[56]

Dosing edit

The dose of nicotine replacement therapy products is generally based on if the user is considered a heavy, average, or light smoker.[21]

General guideline[21]
Type of User Dose of NRT Amount of cigarettes Amount of smokeless tobacco
Light Lower <10 cigarettes daily <2 snuff cans or tobacco pouches weekly
Average Moderate 10-20 cigarettes daily 2-3 snuff cans or tobacco pouches weekly
Heavy Higher 1 or more pack of cigarettes daily >3 snuff cans or tobacco pouches weekly

A cigarette delivers an average of 1 mg to 3 mg of the nicotine contained in it. NRT products typically aim to parallel this, but the amount of nicotine absorbed by the user is less than the original dose.

Nicotine nasal sprays are formulated in doses of lowest strength, available in 0.5 mg and 1 mg strengths.

Nicotine lozenges deliver doses as low as 1 mg up to 4 mg. It is not chewed as the gum would be, and dissolves in approximately 30 minutes.[33] This formulation may be preferred by those individuals who do not find gum chewing to be acceptable.

Nicotine gum is available in doses of 2 mg and 4 mg. Using 4 mg nicotine gum versus 2 mg gum increases the likelihood of successful smoking cessation.[28] When using the gum, acidic beverages like soda, coffee, or beer should be avoided fifteen minutes prior and during use because they can impede proper absorption of nicotine.[33]

Nicotine inhalers come in 10 mg and 15 mg cartridge strengths and typically deliver around 4 mg in one dose.[57] The inhaler may be preferred in individuals who want to satisfy the hand-to-mouth ritual that smoking provides.[33]

Transdermal patches deliver between 5 mg and 52.5 mg of nicotine, which results in plasma levels similar to that of heavy smokers. Combining nicotine patch treatment with a faster nicotine-delivery means, like nicotine gum or spray, improves the likelihood of successful treatment.[28][8]

Not approved as NRTs edit

Some smokeless consumer products available can function as alternative nicotine delivery systems (ANDS)[58] but they have not received FDA approval as smoking-cessation therapy aids that are safe and effective.

Snus and nasal snuff also allow for nicotine administration outside of tobacco smoking.[59] Nicotine pouches are described as similar to or a tobacco-free variant of snus. They are pre-portioned and are held in the user's lip or cheek allowing for sublingual or buccal delivery of flavors and high doses of nicotine. The small pouches are not like chewing tobacco, as the user does not need to spit since the contents of the pouches stay inside during use. Swedish pouches have been available on the American consumer market since at least 2016[60] but their popularity and controversy surged in 2019 & 2020. In the US and UK concerns have been raised that nicotine pouches are seemingly too similar to banned snus products, is aimed at teenagers, further complicating the youth vaping trend,[61] falling into the hands of adolescents easily, and are discrete enough to easily pass for regular gums or lozenges.[62][63]

Nicotine infused toothpicks are another product that has been available in the United States since at least 2013. They can have a total nicotine delivery that is comparable to that of nicotine gum.[52] Nicotine toothpicks generally are infused with food-grade flavorings and 1–3 mg of nicotine, which is similar to that of other oral-delivery nicotine products and some cigarettes.[64] In spite of these similarities, as of 2018 they have been a subject of controversy. Online retailers have been under scrutiny for allowing their products to be too easily purchased by youth.[65][66][67] Various news outlets and school districts have expressed the concern that these products have a high appeal to minors wanting to experiment with nicotine due to; the multitude of sweet flavors offered, ease & speed of use, seeming innocuous, and having a discreet nature.[68][69][70] In 2015, NRT sales fell for the first time since 2008 while sales for e-cigarettes or electronic nicotine delivery systems (ENDS) continued to increase at a substantial rate. The evidence is that UK smokers are trying to quit with e-cigarettes rather than NRT methods.[71]

E-cigarettes are often, although not always, designed to look and feel like cigarettes. They have been marketed as less harmful alternatives to cigarettes,[72] but very few are as yet approved as NRTs in any jurisdiction. Some electronic cigarettes have coarsely adjustable nicotine levels. Some healthcare groups have hesitated to recommend e-cigarettes for quitting smoking, because of limited evidence of effectiveness and safety.[73] However, more recent review show the opposite, possibly because of newer types of e‐cigarettes have better nicotine delivery than older one.[73]

The U.S. Food and Drug Administration (FDA) has a list of additional tobacco products they are seeking to regulate, including electronic cigarettes.[74] Most approved NRT products have been approved for over 20 years,[75] however the FDA has also approved nicotine inhalers as a form of NRT.[76][77]

Future approaches of NRT could include nicotine preloading, a true pulmonary inhaler, and nicotine vaccines.[8] Nicotine preloading, otherwise known as pre-cessation or pre-quitting NRT, has found that using the patch for a few weeks before the quit date produces significantly higher quit rates than if it was started on the quit day.[8] The true pulmonary inhaler would deliver nicotine to the lungs in a manner that more resembles cigarette smoking, which would provide better relief of background cravings as well as acute cravings.[8] Nicotine vaccines are under investigation as a method to treat tobacco dependence through priming the body to mount an immune response against nicotine.[8]

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External links edit

  • "Nicotine". Drug Information Portal. U.S. National Library of Medicine.
  • Recommendations for special populations
  • "Nicotine Lozenges". MedlinePlus. 2018-08-15.
  • "Nicotine Nasal Spray". MedlinePlus. 2016-07-15.
  • "Nicotine Oral Inhalation". MedlinePlus. 2016-07-15.
  • "Nicotine Gum". MedlinePlus. 2017-10-15.
  • "Quit Smoking Therapy". 2baconil. 2020-07-12.

nicotine, replacement, therapy, medically, approved, treat, people, with, tobacco, disorder, taking, nicotine, through, means, other, than, tobacco, used, help, with, quitting, smoking, stopping, chewing, tobacco, increases, chance, quitting, tobacco, smoking,. Nicotine replacement therapy NRT is a medically approved way to treat people with tobacco use disorder by taking nicotine through means other than tobacco 6 It is used to help with quitting smoking or stopping chewing tobacco 1 7 It increases the chance of quitting tobacco smoking by about 55 8 Often it is used along with other behavioral techniques 1 NRT has also been used to treat ulcerative colitis 1 Types of NRT include the adhesive patch chewing gum lozenges nose spray and inhaler 1 The use of multiple types of NRT at a time may increase effectiveness 9 10 Nicotine replacement therapyA nicotine patch is applied to the left arm Clinical dataTrade namesNicoderm Commit Nicorette others 1 Other namesNRTAHFS Drugs comMonographMedlinePlusa601084License dataUS DailyMed NicotineRoutes ofadministrationOral Inhalation Transdermal ATC codeN07BA01 WHO Legal statusLegal statusUS OTC 2 3 4 5 Pharmacokinetic dataMetabolitesCotinineExcretionrenalIdentifiersIUPAC name S 3 1 Methylpyrrolidin 2 yl pyridineCAS Number54 11 5PubChem CID89594ChemSpider80863UNII6M3C89ZY6RChemical and physical dataFormulaC 10H 14N 2Molar mass162 236 g mol 1Common side effects depend on the formulation of nicotine 1 Common side effects with the gum include nausea hiccups and irritation of the mouth 1 Common side effects with the patch include skin irritation and a dry mouth while the inhaler commonly results in a cough runny nose or headaches 1 Serious risks include nicotine poisoning and continued addiction 1 They do not appear to increase the risk of heart attacks 8 There are possible harms to the baby if used during pregnancy 1 11 Nicotine replacement therapy works by reducing cravings caused by nicotine addiction 1 12 They were first approved for use in 1984 in the United States 1 Nicotine replacement products are on the World Health Organization s List of Essential Medicines 13 14 15 They are available as generic medications 1 Contents 1 Medical uses 1 1 Effectiveness 2 Toxicity 3 Side effects 4 Safety 4 1 Pregnancy 4 2 Youth 4 3 Cardiovascular conditions 4 4 Other conditions 5 Mechanism of action 6 Society and culture 6 1 Formulations 6 2 Medicines 6 3 Dosing 6 4 Not approved as NRTs 7 References 8 External linksMedical uses edit nbsp An oral nicotine spray nbsp Nasal spray nbsp Nicorette inhalator a nicotine vapour inhalator with disposable cartridgesNicotine replacement therapy in the form of gum patches nasal spray inhaler and lozenges all improve the ability of people trying to quit tobacco products 8 Nicotine replacement therapy is as effective as medications such as bupropion in helping people quit smoking for at least six months 16 All forms of nicotine replacement therapy including nicotine gum patches nasal spray inhalers and lozenges have similar success rates in terms of helping people stop smoking However the likelihood that someone will stick to a certain treatment varies with compliance being the highest with nicotine patches followed by nicotine gum inhalers and nasal sprays 17 Using a few different nicotine replacement methods in combination may improve success rates in stopping tobacco use 16 18 Additionally using nicotine replacement with counseling has been proven to improve tobacco abstinence rates 19 20 These other strategies include creating a plan to quit and utilizing quit programs a quit phone line or app that provides tips and inspiration to help quit 18 Using nicotine replacement therapy to quit smoking should be considered for people who are severely dependent on nicotine 21 People who are severely dependent include those who smoke more than one pack per day within five minutes of awakening while ill when they wake up in the middle of the night to ease withdrawal signs and symptoms 21 Nicotine replacement products are most beneficial for heavy smokers who smoke more than 15 cigarettes per day There are not enough studies to show whether NRT helps those who smoke fewer than 10 cigarettes per day 20 Effectiveness edit Evaluation of NRT in real world studies produces more modest outcomes than efficacy studies conducted by industry funded trials The National Health Service NHS in England has a smoking cessation service based on pharmacotherapy in combination with counseling support An Action on Smoking and Health UK ASH report claims that the average cost per life year gained for every smoker successfully treated by these services is less than 1 000 below the NICE guidelines of 20 000 per QALY quality adjusted life year However the investment in NHS stop smoking services is relatively low A comparison with treatment costs for illicit drug users shows that 585 million is committed for 350 000 problem drug users compared to 56 million for 9 million users of tobacco This is 6 20 for each smoker compared to 1 670 per illegal drug user 22 The claims for high efficacy and cost effectiveness of NRT have not been substantiated in real world effectiveness studies 23 24 25 Pierce and Gilpin 2002 stated their conclusion as follows Since becoming available over the counter NRT appears no longer effective in increasing long term successful cessation p 1260 25 Efficacy studies which are conducted using randomized controlled trials do not transfer very well to real world effectiveness Bauld Bell McCullough Richardson and Greaves 2009 reviewed 20 studies on the effectiveness of intensive NHS treatments for smoking cessation published between 1990 and 2007 26 Quit rates showed a dramatic decrease between 4 weeks and one year A quit rate of 53 at four weeks fell to only 15 at one year Younger smokers females pregnant smokers and more deprived smokers had lower quit rates than other groups The efficacy for each of the formulations alone lozenges nasal spray gum and transdermal patch to aid in smoking cessation is equal 27 Efficacy increases 15 to 36 with combining treatments such as gum and lozenges Higher doses increase the chance of stopping smoking for a period of six months and more For patches the most efficient doses were 25 mg worn over 16 hours or 21 mg worn over 24 hours The evidence suggests that 4 mg nicotine gum leads to higher quit rates compared with 2 mg in heavy smokers 28 Toxicity editN Nitrosonornicotine a strong carcinogen present in unburned tobacco and cigarette smoke has been found in the urine of some users of oral NRT products 29 Nicotine patches is an alternative Side effects edit nbsp Possible side effects of nicotine 30 Some side effects are caused by the nicotine and are common to NRT products 31 32 Other common side effects depend on the formulation of nicotine 1 Common side effects with the gum include nausea hiccups and irritation of the mouth 1 Common side effects with the patch include skin irritation and a dry mouth while the inhaler commonly results in a cough runny nose or headaches 1 To minimize local skin reactions from the patch the application site should be moved daily 33 The nicotine patch can also cause strange dreams if worn while asleep 20 Nasal sprays commonly cause nasal irritation watering eyes and coughing 31 Serious risks include nicotine poisoning which includes symptoms like visual disturbances hyper salivation nausea and vomiting and continued addiction to nicotine products 1 Avoiding smoking and other products with nicotine are recommended since it may lead to nicotine overdose 34 Although overdose is rare it can be problematic especially in children and pets 35 The symptoms of nicotine overdose include headache pale skin and mouth belly pain weakness diarrhea tremors or seizures agitation confusion restlessness high or low blood pressure fast or irregular heartbeat fast breathing and cold sweats 21 Limited evidence exists regarding long term NRT use 36 Safety editPregnancy edit Nicotine is not safe to use in any amount during pregnancy 37 Nicotine crosses the placenta and is found in the breast milk of mothers who smoke as well as mothers who inhale passive smoke 38 There are possible harms to the baby if NRT is used during pregnancy 1 11 Thus pregnant women and those who are breastfeeding should also consult a physician before initiating NRT 39 The gum lozenge and nasal spray are pregnancy category C The transdermal patch is pregnancy category D The transdermal patch is considered less safe for the fetus because it delivers continuous nicotine exposure as opposed to the gum or lozenge which delivers intermittent and thus lower nicotine exposure 40 41 Strong evidence suggests that nicotine cannot be regarded as a safe substance of cigarette use 40 Nicotine itself could be at least partly responsible for many of the adverse after birth health results related to cigarette use while the mother was pregnant 40 There is evidence that nicotine negatively affects fetal brain development and pregnancy outcomes 42 There is also risk of stillbirth and pre term birth 43 Nicotine use will probably harm fetal neurological development 44 Risks to the child later in life from nicotine exposure during pregnancy include type 2 diabetes obesity hypertension neurobehavioral defects respiratory dysfunction and infertility 32 Nicotine exposure during pregnancy can result in attention deficit hyperactivity disorder ADHD and learning disabilities in the child citation needed It also puts the child at increased risk for nicotine addiction in the future 40 Pregnant women should consider behavioral therapy before NRT is considered 1 Youth edit In people under the age of eighteen a physician is often consulted before starting NRT 39 The evidence suggests that exposure to nicotine between the ages of 10 and 25 years causes lasting harm to the brain and cognitive ability 45 Evidence is unclear whether adolescents gain benefit from cognitive behavioral therapy or smoking cessation over the long term as of 2017 46 Most tobacco users are under eighteens when they start and almost no one over the age of 25 starts using 47 Cardiovascular conditions edit While there is no evidence that NRT can increase the risk of heart attacks 8 individuals with pre existing cardiovascular conditions or recent heart attacks should consult a physician before initiating NRT 39 Smoking is known to cause cardiovascular diseases such as coronary heart disease hypertension heart attack stroke and peripheral artery disease Cigarette smoking is the cause of 20 of all cardiovascular deaths in the United States which is the leading cause of mortality 48 Other conditions edit Nicotine replacement therapies should be used cautiously in individuals with the following conditions severe reactive airway diseases for nasal spray chronic nasal disorders such as sinusitis polyps rhinitis or allergy for nasal spray diabetes insulin dependent gastrointestinal diseases such as esophagitis active gastric or peptic ulcer disease liver problems hyperthyroidism pheochromocytoma phenylketonuria for lozenges renal problems and skin conditions such as psoriasis or dermatitis for the transdermal patch 49 Mechanism of action editNicotine replacement therapy works by reducing cravings due to nicotine addiction 1 12 Smoking cigarettes releases high doses of nicotine to the brain in a matter of seconds as opposed to low doses released over a period of minutes to hours by the various forms of nicotine replacement therapy 33 Nicotine from NRT does not reach as high a concentration in the blood as does nicotine from smoke inhalation due to different absorption methods NRT relies on systemic venous absorption whereas nicotine from cigarettes reaches the arterial system 33 Nicotine replacement products vary in the time it takes for the nicotine to enter the body and the total time nicotine stays in the body 19 The more quickly a dose of nicotine is delivered and absorbed the higher the addiction risk 50 It is possible to become dependent on some NRTs 51 Nicotine patches are applied to the skin and continuously administer a stable dose of nicotine slowly over 16 24 hours 19 41 Nicotine gum nicotine sprays nicotine toothpicks nicotine sublingual tablets and nicotine lozenges administer nicotine orally with quicker nicotine uptake into the body but lasting a shorter amount of time 52 Nicotine inhalers are metered dose inhalers citation needed that administer nicotine through the lungs and mucous membranes of the throat quickly lasting for a short amount of time For example blood nicotine levels are the highest 5 10 minutes after using the nicotine nasal spray 20 minutes after using a nicotine inhaler or chewing nicotine gum and 2 4 hours after using a nicotine patch 19 53 Society and culture editNRT products were first approved for use in the United States in 1984 1 Nicotine replacement products are on the World Health Organization s List of Essential Medicines 13 They are available as generic medication 1 Formulations edit nbsp Nicotine pastillesNRT Type Device package Availability How it works 54 55 Patch Pouch Over the counter 16 or 24 hours sustained release transdermal patchLozenge Blister pack Over the counter 20 to 30 minutes modified release dosage tablet containing nicotine polacrilexSublingual tablets Blister pack Over the counter Quickly dissolves to releases nicotine through a hard candyGum Blister pack Over the counter Chewing the gum releases nicotine as a modified release dosageMouth spray Mouth spray bottle Over the counter Spraying a mist into the mouth administers nicotine for buccal administrationVapour inhalator Nicorette Inhalator with 10 mg nicotine disposable cartridges Over the counter Resembles cigarettes A disposable cartridge contains about 10 mg nicotine about 40 is released Multiple inhaling through the mouthpiece administers sufficient nicotine Pressurized Metered dose inhaler pMDI Prescription Inhaling through the mouthpiece administers nicotineNasal spray Nasal spray bottle Prescription Spraying a pump bottle into the nose administers nicotineThe nicotine patch is a once daily longer acting form of NRT An advantage of the nicotine patch is its simple compliance it does not require active use throughout the day 33 The gum lozenge sublingual tablet oral inhaler oral spray and nasal spray are acutely dosed products providing the user with the benefit and ability of self titrating based on cravings 33 Brand names include Commit Lozenge Nicoderm Nicogum Nicorette Nicotex Nicotinell and Thrive NRT products contain similar pharmaceutical grade nicotine as is used in e cigarettes citation needed Medicines edit In 2015 the United States Public Health Service listed seven agents for the stopping of tobacco which included five nicotine replacement treatments nicotine patches gum lozenges inhalers and nasal sprays and two oral medications bupropion and varenicline Other NRT options are available including nicotine mouth sprays and sublingual tablets 56 Dosing edit The dose of nicotine replacement therapy products is generally based on if the user is considered a heavy average or light smoker 21 General guideline 21 Type of User Dose of NRT Amount of cigarettes Amount of smokeless tobaccoLight Lower lt 10 cigarettes daily lt 2 snuff cans or tobacco pouches weeklyAverage Moderate 10 20 cigarettes daily 2 3 snuff cans or tobacco pouches weeklyHeavy Higher 1 or more pack of cigarettes daily gt 3 snuff cans or tobacco pouches weeklyA cigarette delivers an average of 1 mg to 3 mg of the nicotine contained in it NRT products typically aim to parallel this but the amount of nicotine absorbed by the user is less than the original dose Nicotine nasal sprays are formulated in doses of lowest strength available in 0 5 mg and 1 mg strengths Nicotine lozenges deliver doses as low as 1 mg up to 4 mg It is not chewed as the gum would be and dissolves in approximately 30 minutes 33 This formulation may be preferred by those individuals who do not find gum chewing to be acceptable Nicotine gum is available in doses of 2 mg and 4 mg Using 4 mg nicotine gum versus 2 mg gum increases the likelihood of successful smoking cessation 28 When using the gum acidic beverages like soda coffee or beer should be avoided fifteen minutes prior and during use because they can impede proper absorption of nicotine 33 Nicotine inhalers come in 10 mg and 15 mg cartridge strengths and typically deliver around 4 mg in one dose 57 The inhaler may be preferred in individuals who want to satisfy the hand to mouth ritual that smoking provides 33 Transdermal patches deliver between 5 mg and 52 5 mg of nicotine which results in plasma levels similar to that of heavy smokers Combining nicotine patch treatment with a faster nicotine delivery means like nicotine gum or spray improves the likelihood of successful treatment 28 8 Not approved as NRTs edit Some smokeless consumer products available can function as alternative nicotine delivery systems ANDS 58 but they have not received FDA approval as smoking cessation therapy aids that are safe and effective Snus and nasal snuff also allow for nicotine administration outside of tobacco smoking 59 Nicotine pouches are described as similar to or a tobacco free variant of snus They are pre portioned and are held in the user s lip or cheek allowing for sublingual or buccal delivery of flavors and high doses of nicotine The small pouches are not like chewing tobacco as the user does not need to spit since the contents of the pouches stay inside during use Swedish pouches have been available on the American consumer market since at least 2016 60 but their popularity and controversy surged in 2019 amp 2020 In the US and UK concerns have been raised that nicotine pouches are seemingly too similar to banned snus products is aimed at teenagers further complicating the youth vaping trend 61 falling into the hands of adolescents easily and are discrete enough to easily pass for regular gums or lozenges 62 63 Nicotine infused toothpicks are another product that has been available in the United States since at least 2013 They can have a total nicotine delivery that is comparable to that of nicotine gum 52 Nicotine toothpicks generally are infused with food grade flavorings and 1 3 mg of nicotine which is similar to that of other oral delivery nicotine products and some cigarettes 64 In spite of these similarities as of 2018 they have been a subject of controversy Online retailers have been under scrutiny for allowing their products to be too easily purchased by youth 65 66 67 Various news outlets and school districts have expressed the concern that these products have a high appeal to minors wanting to experiment with nicotine due to the multitude of sweet flavors offered ease amp speed of use seeming innocuous and having a discreet nature 68 69 70 In 2015 NRT sales fell for the first time since 2008 while sales for e cigarettes or electronic nicotine delivery systems ENDS continued to increase at a substantial rate The evidence is that UK smokers are trying to quit with e cigarettes rather than NRT methods 71 E cigarettes are often although not always designed to look and feel like cigarettes They have been marketed as less harmful alternatives to cigarettes 72 but very few are as yet approved as NRTs in any jurisdiction Some electronic cigarettes have coarsely adjustable nicotine levels Some healthcare groups have hesitated to recommend e cigarettes for quitting smoking because of limited evidence of effectiveness and safety 73 However more recent review show the opposite possibly because of newer types of e cigarettes have better nicotine delivery than older one 73 The U S Food and Drug Administration FDA has a list of additional tobacco products they are seeking to regulate including electronic cigarettes 74 Most approved NRT products have been approved for over 20 years 75 however the FDA has also approved nicotine inhalers as a form of NRT 76 77 Future approaches of NRT could include nicotine preloading a true pulmonary inhaler and nicotine vaccines 8 Nicotine preloading otherwise known as pre cessation or pre quitting NRT has found that using the patch for a few weeks before the quit date produces significantly higher quit rates than if it was started on the quit day 8 The true pulmonary inhaler would deliver nicotine to the lungs in a manner that more resembles cigarette smoking which would provide better relief of background cravings as well as acute cravings 8 Nicotine vaccines are under investigation as a method to treat tobacco dependence through priming the body to mount an immune response against nicotine 8 References edit a b c d e f g h i j k l m n o p q r s t u v Nicotine The American Society of Health System Pharmacists Archived from the original on 18 December 2015 Nicoderm CQ nicotine patch extended release DailyMed Retrieved 26 January 2022 Commit nicotine lozenge DailyMed Retrieved 26 January 2022 Nicorette nicotine polacrilex lozenge DailyMed Retrieved 26 January 2022 Nicorette White Ice Mint nicotine polacrilex gum chewing Nicorette Original nicotine polacrilex gum chewing Nicorette 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106 11 doi 10 18773 austprescr 2015 038 PMC 4653977 PMID 26648633 Evidence suggests that combinations of nicotine replacement therapy may be more effective than using a single formulation Cahill K Stevens S Perera R Lancaster T May 2013 Pharmacological interventions for smoking cessation an overview and network meta analysis The Cochrane Database of Systematic Reviews 5 5 CD009329 doi 10 1002 14651858 CD009329 pub2 PMC 8406789 PMID 23728690 S2CID 205199430 Combination NRT also outperformed single formulations a b De Long NE Barra NG Hardy DB Holloway AC December 2014 Is it safe to use smoking cessation therapeutics during pregnancy Expert Opinion on Drug Safety 13 12 1721 31 doi 10 1517 14740338 2014 973846 PMID 25330815 S2CID 207488115 a b Nicotine Replacement Therapy for Smoking Cessation or Reduction A Review of the Clinical Evidence Report Canadian Agency for Drugs and Technologies in Health 16 January 2014 PMID 24741730 a b World Health Organization 2019 World Health Organization 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