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Nicotine replacement therapy (NRT) is a medically-approved way to take nicotine by means other than tobacco.[2] It is used to help with quitting smoking or stopping chewing tobacco.[1][3] It increases the chance of quitting smoking by about 50% to 70%.[4][needs update] 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 more than one type of NRT at a time may increase effectiveness.[5][6]

Nicotine replacement therapy
Nicoderm.JPG
A nicotine patch is applied to the left arm
Clinical data
Trade namesNicoderm, Commit, Nicorette, Nicotrol, others[1]
AHFS/Drugs.comMonograph
Pregnancy
category
  • US: D (Evidence of risk) [1]
Identifiers
CAS Number
PubChem CID
ChemSpider

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.[4] There are possible harms to the baby if used during pregnancy.[1][7] Nicotine replacement therapy works by reducing cravings due to nicotine addiction.[1][8]

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, the most effective and safe medicines needed in a health system.[9] They are available as generic medication.[1] In the United States a month of patches or gum is between 100 and 200 USD while the other forms are more expensive.[10]

Contents

Medical usesEdit

 
Nicotine pastilles

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.[4] Studies have shown that nicotine replacement therapy is as effective as medications, such as bupropion, in helping people quit smoking for at least 6 months.[11] Studies have also shown that 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.[12] It is important to note that using a few different nicotine replacement methods in combination may improve success rates in stopping tobacco use.[11] Additionally, using nicotine replacement with counseling has been proven to improve tobacco abstinence rates.[13]

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.[14]

EffectivenessEdit

Evaluation of NRT in real-world studies produces more modest outcomes than efficacy studies conducted by the 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.[15]

The claims for high efficacy and cost-effectiveness of NRT have not been substantiated in real-world effectiveness studies.[16][17][18] 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).[18] 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.[19] 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 1 year. Younger smokers, females, pregnant smokers and more deprived smokers had lower quit rates than other groups.

DosingEdit

Using 4 mg nicotine gum versus 2 mg gum increases the likelihood of successful smoking cessation.[20]

Combining nicotine patch treatment with a faster nicotine-delivery means, like nicotine gum or spray, improves the likelihood of treatment success.[20]

Side effectsEdit

 
Possible side effects of nicotine.[21]

Some side effects are caused by the nicotine, and are common to NRT products.[22][23] 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] Nasal sprays commonly cause nasal irritation, watering eyes, and coughing.[22]

Serious risks include nicotine poisoning and continued addiction.[1]

Limited evidence exists regarding long-term NRT use, and concerns exist that long-term NRT use could raise cancer risk, due in part to the generation of carcinogens.[24]

PregnancyEdit

Nicotine is not safe to use in any amount during pregnancy.[25] Nicotine crosses the placenta and is found in the breast milk of mothers who smoke as well as mothers who inhale passive smoke.[26] There are possible harms to the baby if NRT is used during pregnancy.[1][7] Thus, pregnant women and those who are breastfeeding should also consult a physician before initiating NRT.[27] 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.[28][29]

Strong evidence suggests that nicotine cannot be regarded as a safe substance of cigarette use.[30] 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.[30] There is evidence that nicotine negatively affects fetal brain development and pregnancy outcomes.[31] There is also risk of stillbirth and pre-term birth.[32] Nicotine use will probably harm fetal neurological development.[33] Risks to the child later in life from nicotine exposure during pregnancy include type 2 diabetes, obesity, hypertension, neurobehavioral defects, respiratory dysfunction, and infertility.[23] 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.[28]

YouthEdit

In people under the age of 18, a physician is often consulted before starting NRT.[27] The evidence suggests that exposure to nicotine between the ages of 10 and 25 years causes lasting harm to the brain and cognitive ability.[34] Most tobacco users are under-eighteens when they start, and almost no-one over the age of 25 starts using.[35]

Cardiovascular conditionsEdit

While there is no evidence that NRT can increase the risk of heart attacks,[4] individuals with pre-existing cardiovascular conditions or recent heart attacks should consult a physician before initiating NRT.[27]

Mechanism of actionEdit

 
An oral nicotine spray

Nicotine replacement therapy works by reducing cravings due to nicotine addiction.[1][8] 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.[13] The more quickly a dose of nicotine is delivered and absorbed, the higher the addiction risk.[36] It is possible to become dependent on some NRTs.[37]

Nicotine patches are applied to the skin and continuously administer a stable dose of nicotine slowly over 16–24 hours.[13][29] Nicotine gum, nicotine sprays, nicotine sublingual tablets, and nicotine lozenges administer nicotine orally with quicker nicotine uptake into the body but lasting a shorter amount of time. Nicotine inhalers are metered-dose inhalers[citation needed] that administer nicotine through the lungs and mucous membranes of the throat quickly but lasting 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.[13][38]

FormulationsEdit

In 2015, the United States Public Health Service listed seven agents for the stopping of tobacco, which included 5 nicotine replacement treatments (nicotine patches, gum, lozenges, inhalers, and nasal sprays) and 2 oral medications (bupropion and varenicline). Other NRT options are available, including nicotine mouth sprays and sublingual tablets.[39]

Trade names include Nicotex, Nicorette, Nicoderm, Nicogum, Nicotinell, Thrive and Commit Lozenge.

Society and cultureEdit

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, the most effective and safe medicines needed in a health system.[9] They are available as generic medication.[1] In the United States a month of patches or gum is between 100 and 200 USD while the other forms are more expensive.[10]

EconomicsEdit

In the United States, a month of patches or gum is between 100 and 200 USD as of 2015 while the other forms are more expensive;[10] in the UK lozenges are the cheapest. In the United States, a month of patches is about 170 USD.[1]

Not approved as NRTsEdit

Snus and nasal snuff also allow for nicotine administration outside of tobacco smoking.[40]

In 2015, NRT sales fell for the first time since 2008 while sales for e-cigarettes continued to increase at a substantial rate. This had led to speculation that UK smokers are trying to quit with e-cigarettes rather than NRT methods.[41]

E-cigarettes are often, although not always, designed to look and feel like cigarettes. They have been marketed as less harmful alternatives to cigarettes,[42] 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.[43]

The U.S. Food and Drug Administration (FDA) has a list of additional tobacco products they are seeking to regulate, including electronic cigarettes.[44] The FDA has approved nicotine inhalers as a form of NRT.[45]

See alsoEdit

ReferencesEdit

  1. ^ a b c d e f g h i j k l m n o p q r s t u v w "Nicotine". The American Society of Health-System Pharmacists. Archived from the original on 2015-12-18. Retrieved Dec 2015. Check date values in: |accessdate= (help)
  2. ^ Jain, R; Majumder, P; Gupta, T (2013). "Pharmacological intervention of nicotine dependence". BioMed Research International. 2013: 278392. doi:10.1155/2013/278392. PMC 3891736. PMID 24490153.
  3. ^ Smith, KD; Scott, MA; Ketterman, E; Smith, PO (April 2005). "Clinical inquiries. What interventions can help patients stop using chewing tobacco?". The Journal of family practice. 54 (4): 368–9. PMID 15833231.
  4. ^ a b c d Stead, LF; Perera, R; Bullen, C; Mant, D; Hartmann-Boyce, J; Cahill, K; Lancaster, T (Nov 14, 2012). Stead, Lindsay F (ed.). "Nicotine replacement therapy for smoking cessation". The Cochrane Database of Systematic Reviews. 11: CD000146. doi:10.1002/14651858.CD000146.pub4. PMID 23152200.
  5. ^ McDonough, M (August 2015). "Update on medicines for smoking cessation". Australian prescriber. 38 (4): 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
  6. ^ Cahill, K; Stevens, S; Perera, R; Lancaster, T (31 May 2013). "Pharmacological interventions for smoking cessation: an overview and network meta-analysis". The Cochrane Database of Systematic Reviews. 5: CD009329. doi:10.1002/14651858.CD009329.pub2. PMID 23728690. Combination NRT also outperformed single formulations
  7. ^ 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.
  8. ^ a b "Nicotine Replacement Therapy for Smoking Cessation or Reduction: A Review of the Clinical Evidence". Canadian Agency for Drugs and Technologies in Health. 16 January 2014. PMID 24741730.
  9. ^ a b "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
  10. ^ a b c Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 441. ISBN 9781284057560.
  11. ^ a b Cahill, K; Stevens, S; Perera, R; Lancaster, T (2013). "Pharmacological interventions for smoking cessation: an overview and network meta-analysis". The Cochrane Database of Systematic Reviews. 5: CD009329. doi:10.1002/14651858.CD009329.pub2. PMID 23728690.
  12. ^ Hajek, Peter; West, Robert; Foulds, Jonathan; Nilsson, Fredrik; Burrows, Sylvia; Meadow, Anna (1999). "Randomized Comparative Trial of Nicotine Polacrilex, a Transdermal Patch, Nasal Spray, and an Inhaler". Archives of Internal Medicine. 159 (17): 2033. doi:10.1001/archinte.159.17.2033.
  13. ^ a b c d Rigotti, NA (Feb 2002). "Clinical practice. Treatment of tobacco use and dependence". The New England Journal of Medicine. 346 (7): 506–12. doi:10.1056/nejmcp012279. PMID 11844853.
  14. ^ "Nicotine replacement therapy". MedlinePlus. U.S. National Library of Medicine. Archived from the original on 9 January 2015. Retrieved 28 October 2014.
  15. ^ "Action on Smoking & Health, 2008" (PDF). Archived (PDF) from the original on 24 September 2015. Retrieved 27 August 2015.
  16. ^ Doran et al. (2006), pp. 758–766
  17. ^ Ferguson; et al. (2006). Addiction: 59–69. Missing or empty |title= (help)
  18. ^ a b Pierce & Gilpin (2002) JAMA 288 pp. 1260–1264
  19. ^ Bauld; et al. (2010). "The effectiveness of NHS smoking cessation services: a systematic review". J Public Health (Oxf). 32: 71–82. doi:10.1093/pubmed/fdp074. PMID 19638397.
  20. ^ a b Lindson N, Chepkin SC, Ye W, Fanshawe TR, Bullen C, Hartmann-Boyce J (April 2019). "Different doses, durations and modes of delivery of nicotine replacement therapy for smoking cessation". The Cochrane Database of Systematic Reviews. 4: CD013308. doi:10.1002/14651858.CD013308. PMID 30997928.
  21. ^ Detailed reference list is located on a separate image page
  22. ^ a b "Nicotine Side Effects". Drugs.com. Retrieved 2009. Check date values in: |accessdate= (help)
  23. ^ a b Schraufnagel, Dean E.; Blasi, Francesco; Drummond, M. Bradley; Lam, David C. L.; Latif, Ehsan; Rosen, Mark J.; Sansores, Raul; Van Zyl-Smit, Richard (2014). "Electronic Cigarettes. A Position Statement of the Forum of International Respiratory Societies". American Journal of Respiratory and Critical Care Medicine. 190 (6): 611–618. doi:10.1164/rccm.201407-1198PP. ISSN 1073-449X. PMID 25006874.
  24. ^ Wilder, Natalie; Daley, Claire; Sugarman, Jane; Partridge, James (April 2016). "Nicotine without smoke: Tobacco harm reduction". UK: Royal College of Physicians. p. 58. Archived from the original on 2016-05-05.
  25. ^ Alawsi F, Nour R, Prabhu S (August 2015). "Are e-cigarettes a gateway to smoking or a pathway to quitting?". British Dental Journal. 219 (3): 111–5. doi:10.1038/sj.bdj.2015.591. PMID 26271862.
  26. ^ "State Health Officer's Report on E-Cigarettes: A Community Health Threat" (PDF). California Tobacco Control Program. California Department of Public Health. January 2015.
  27. ^ a b c "FDA 101: Smoking Cessation Products". U.S. Food and Drug Administration. Archived from the original on 3 November 2014. Retrieved 28 October 2014.
  28. ^ a b Bruin, Jennifer; Gerstein, Hertzel; Holloway, Alison (2 April 2010). "Long-Term Consequences of Fetal and Neonatal Nicotine Exposure: A Critical Review". Toxicological Sciences. 116 (2): 364–374. doi:10.1093/toxsci/kfq103. PMC 2905398. Archived from the original on 25 October 2014.
  29. ^ a b Oncken, MD, MPH, Cheryl; Dornelas, Ph.D., Ellen; Kranzler MD, Henry (28 October 2014). "Nicotine Gum for Pregnant Smokers". Obstetrics. 112 (4): 859–867. doi:10.1097/AOG.0b013e318187e1ec. PMC 2630492. PMID 18827129.CS1 maint: Multiple names: authors list (link)
  30. ^ a b Bruin, Jennifer E.; Gerstein, Hertzel C.; Holloway, Alison C. (April 2010). "Long-Term Consequences of Fetal and Neonatal Nicotine Exposure: A Critical Review". Toxicological Sciences. 116 (2): 364–374. doi:10.1093/toxsci/kfq103. ISSN 1096-6080. PMC 2905398. PMID 20363831.
  31. ^ "The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General, Chapter 5 – Nicotine" (PDF). Surgeon General of the United States. 2014: 107–138. PMID 24455788.
  32. ^ "The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General, Chapter 9 – Reproductive Outcomes" (PDF). Surgeon General of the United States. 2014: 107–138. PMID 24455788.
  33. ^ England, Lucinda J.; Kim, Shin Y.; Tomar, Scott L.; Ray, Cecily S.; Gupta, Prakash C.; Eissenberg, Thomas; Cnattingius, Sven; Bernert, John T.; Tita, Alan Thevenet N.; Winn, Deborah M.; Djordjevic, Mirjana V.; Lambe, Mats; Stamilio, David; Chipato, Tsungai; Tolosa, Jorge E. (31 December 2010). "Non-cigarette tobacco use among women and adverse pregnancy outcomes". Acta Obstetricia et Gynecologica Scandinavica. 89 (4): 454–464. doi:10.3109/00016341003605719. ISSN 1600-0412. PMC 5881107. The use of any products containing nicotine likely will have adverse effects of fetal neurological development.
  34. ^ U.S. Department of Health and Human Services, Public Health Service Office of the Surgeon General Rockville, MD (2016). "E-Cigarette Use Among Youth and Young Adults: A Report of the Surgeon General". Retrieved 15 November 2018. Evidence for this report was gathered from scientific research that included one or more of three age groups. These age groups included young adolescents (11–13 years of age), adolescents (14–17 years of age), and young adults (18–24 years of age). Some studies refer to the younger groups more generally as youth... Of concern with regard to current trends in e-cigarette use among youth and young adults, the evidence suggests that exposure to nicotine during this period of life may have lasting deleterious consequences for brain development, including detrimental effects on cognitionCS1 maint: Multiple names: authors list (link)
  35. ^ U.S. Department of Health and Human Services, Public Health Service Office of the Surgeon General Rockville, MD (2016). "E-Cigarette Use Among Youth and Young Adults: A Report of the Surgeon General". Retrieved 15 November 2018. The majority of tobacco users start before they are 18 years of age, and almost no one starts after age 25CS1 maint: Multiple names: authors list (link)
  36. ^ Parrott AC (July 2015). "Why all stimulant drugs are damaging to recreational users: an empirical overview and psychobiological explanation" (PDF). Human Psychopharmacology. 30 (4): 213–24. doi:10.1002/hup.2468. PMID 26216554.
  37. ^ Hughes, J. R. (1989). "Dependence potential and abuse liability of nicotine replacement therapies". Biomedicine & Pharmacotherapy. 43 (1): 11–17. ISSN 0753-3322. PMID 2659095.
  38. ^ Package insert monograph with Nicorette® inhaler
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  40. ^ Phillips, CV; Heavner, KK (2009). "Smokeless tobacco: The epidemiology and politics of harm". Biomarkers. 14 (Suppl 1): 79–84. doi:10.1080/13547500902965476. PMID 19604065.
  41. ^ "E-cigarettes Spark Nicotine Replacement Therapy Mutiny". Newswire. 2015-07-29. Archived from the original on 2015-10-02. Retrieved 2015-10-01.
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  43. ^ McRobbie, Hayden; Bullen, Chris; Hartmann-Boyce, Jamie; Hajek, Peter; McRobbie, Hayden (2014). "Electronic cigarettes for smoking cessation and reduction". The Cochrane Library. 12: CD010216. doi:10.1002/14651858.CD010216.pub2. PMID 25515689.
  44. ^ "Archived copy". Archived from the original on 2014-11-17. Retrieved 2014-11-06.CS1 maint: Archived copy as title (link)
  45. ^ Drummond, MB; Upson, D (February 2014). "Electronic cigarettes. Potential harms and benefits". Annals of the American Thoracic Society. 11 (2): 236–42. doi:10.1513/annalsats.201311-391fr. PMC 5469426. PMID 24575993.

External linksEdit