• Sign Up



Article Author:
Amritpal Sandhu
Article Author:
Seyed Alireza Hosseini
Article Editor:
Abdolreza Saadabadi
6/23/2020 9:14:00 PM
For CME on this topic:
Nicotine CME
PubMed Link:


Nicotine replacement therapy (NRT) is for those who want to quit smoking, as abruptly quitting can cause withdrawals and cravings. Nicotine withdrawal occurs after suddenly discontinuing smoking cigarettes. Typical withdrawal symptoms include mood changes, diaphoresis, headaches, insomnia, and poor cognition. These symptoms usually peak at two to three days after quitting smoking. Using NRT helps one to reduce the motivation of smoking cigarettes because the body still gets nicotine from another safer method. Evidence has shown that using NRT helps increase the chances of quitting by about 50% to 70%. Withdrawals include restlessness, more than usual hunger, feeling depressed or irritable, and craving another cigarette.[1][2][3][4]

  • Nicotine comes in a patch, lozenge, inhalers, spray, and gum forms and can provide the body the dose of nicotine that it previously got from cigarettes. Using these forms of NRT increases the chances of success of quitting smoking and is FDA approved.
  • NRT contains less nicotine than the average cigarette and has a slower effect on the body. It does not contain the harmful chemicals of cigarettes, such as tar.
  • It is a strong recommendation to start using an NRT 1 to 2 weeks before quitting or right after quitting cigarettes.
  • Bupropion is also an antidepressant with smoking cessation effects and can be combined with the nicotine patch for a higher chance of success.

Mechanism of Action

Nicotine is an alkaloid and only produced in tobacco. It is a tertiary amine that has pyrrolidine and pyridine rings. It binds selectively to nicotinic-cholinergic receptors in multiple locations. The brain, neuromuscular junctions, adrenal medulla, and the ganglia all have these receptors. When a person inhales nicotine through smoking cigarettes, it diffuses through the lungs into the circulation, eventually going to the brain. It affects the reward center in the limbic system as well as having a stimulating effect in the cortex. Dopamine in the frontal cortex, mesolimbic area, and corpus striatum is released - dopamine helps deliver the pleasurable experience. NRTs try to mimic the nicotine response from smoking. Higher doses of NRTs will have more of a rewarding feeling, whereas lower doses of nicotine have more of a stimulating effect.[5][6]


Forms of NRT do not need to be prescribed by a doctor; most are available over the counter. Patients should follow directions for each form of NRT. Even though there are different brands and forms, evidence shows no more significant effect of one type of NRT compared to another. Although some studies show that there is no benefit to using NRT for longer than eight weeks, others have found that longer duration of treatment with nicotine patch may be associated with improved smoking cessation rate. The initial dosing usually has its basis on the number of cigarettes smoked per day, and heavier smokers should use increased strength/dose of nicotine therapy. NRT products can be used if a patient is still smoking.

  • Nicotine patches come in different brands, where some patches are designed for 24 hours at 5-mg to 52.5-mg dosages, where the higher doses are for heavier smokers. Other patches are designed to be only worn 16 hours a day and come in 5-mg to 25-mg doses. Patches require an application to a non-hairy, dry, clean area of the arm or upper body. Press onto skin for 10 seconds. Apply to a different area each time. Treatment is for about 8 to 10 weeks. The highest dose is started for patients over 45 kg who smoke more than 10 cigarettes per day. The nicotine patch is the easiest NRT to use, and it provides the most continuous delivery of nicotine among all other NRT products.
  • Nicotine gum is available in different doses as well, at 2 mg and 4 mg. It is commonly used as a short-acting NRT. The patient chews the gum slowly until it tingles, and chew until the tingle disappears. Chew when the urge to smoke strikes. Recommended is 8 to 12 pieces of gum. To improve absorption, smokers should avoid acidic beverages such as coffee or carbonated drinks. 
  • Nicotine lozenges are available in 1-mg, 1.5-mg, 2-mg, and 4-mg doses. Users should allow 20 to 30 minutes to dissolve slowly and should not chew or swallow. Recommended is 8 to 12 lozenges daily.
  • Nicotine inhalation cartridge comes in 10 mg. The cartridge should be inserted into the inhaler then popped into place. Inhale deeply or puff consecutively in short breaths. This type of NRT addresses both the physical and behavioral aspects of dependence. Recommended is 6 to 16 cartridges per day.
  • Nicotine nasal spray comes in 0.5 mg per spray. The patient should blow their nose before use. Tilt the head back and insert the tip of the bottle and spray once in each nostril.
  • Nicotine sublingual tablet comes in a 2-mg dose and is not available in the United States.

Patients should understand not to use two doses back to back. If the patient misses a dose, they should take it as soon as possible. If it is close to the time of the next dose, they can skip the missed dose.

Adverse Effects

The known adverse effects of nicotine include:

  • Gastrointestinal symptoms: abdominal pain, dyspepsia, hiccups, diarrhea, nausea, vomiting
  • Central Nervous System: headache
  • With the oral/nasal mucosa absorbing NRT’s, nose and mouth ulcers and irritation have been reported. Other side effects include excess salivation and swelling of the lips, throat, and tongue.
  • Transdermal patches have caused some people skin rash or irritation. Topical hydrocortisone 1% cream or ointment is indicated for some patients to relieve skin irritation.
  • Other: depression, back pain, dizziness, nervousness, drooling, shakiness, cold sweats, hypertension, increased heart rate, and vivid dreams.

Patients should inform their physician immediately if any of the above side effects occur. Patients who worried about dependence should receive counsel that nicotine dependence is very rare.


  • Hypersensitivity to nicotine. People allergic to soy should not use the nicotine lozenge.
  • Nicotine also has drug interactions with adenosine, cimetidine, and varenicline. Adenosine may increase the tachycardia effect of nicotine. Cimetidine may cause an increase in the serum concentration of nicotine. Varenicline can induce some of the nicotine side effects.
  • Pregnant women should also quit smoking during pregnancy. Nicotine crosses the placenta as well into as breast milk. NRT is not a recommended therapy for breastfeeding mothers as the side effects could harm the infant.


Patients with cardiovascular or peripheral vascular disease should have the risks versus benefits weighed before deciding to start an NRT due to hypertension and increased heart rate side effects. Use caution when starting patients who have had angina or recent myocardial infarction. Discontinue if palpitations or irregular heartbeats occur.[7][8][9][10]


The liver metabolizes nicotine. Therefore, swallowing pills through the gastrointestinal (GI) system will be subject to first-pass metabolism by the liver, and bioavailability would only be about 20%. This process will reduce the bioavailability of nicotine in the system and possibly cause side effects of the GI. Hence, the only available methods for nicotine are in a non-pill form such as a lozenge, sublingual tablets, transdermal patches, gum, inhaler, and sprays. These dose forms let the nicotine enter through the oral or nasal mucosa or skin and bypass the GI system for more extended bioavailability. The route of absorption is pH-dependent. Acidic foods and drinks can lower the absorption of nicotine. The skin patch releases nicotine at a slower rate. This controlled delivery makes toxicity from nicotine much less likely and prevents any GI side effects from happening. Symptoms in the rare event that the patient overdoses nicotine include nausea, vomiting, diarrhea, dizziness, difficulty breathing, tachycardia, weakness, or rash.

Enhancing Healthcare Team Outcomes

All healthcare workers have a responsibility for educating patients on the harms of smoking. The patient should be told about the nicotine replacement therapies currently available. Evidence has shown that using NRT helps increase the chances of quitting by about 50% to 70%. Withdrawals include restlessness, more than usual hunger, feeling depressed or irritable, and craving another cigarette. Bupropion is also an antidepressant with smoking cessation effects, and clinicians can combine it with the nicotine patch for a higher chance of success. These patients need continual support and positive reinforcement. Unfortunately, with all therapies, relapse rates are very high. [Level V]


[1] Bellenguez Y,Chevalier F,Duhaut P,Colpart E,Dernoncourt A, [Smoking cessation in secondary prevention of acute coronary syndrome: The role of the electronic cigarette]. Annales de cardiologie et d'angeiologie. 2019 Jan 22;     [PubMed PMID: 30683484]
[2] Lee LJ,Li Q,Bruno M,Emir B,Murphy B,Shah S,Reynolds M,Marchant N,Park PW, Healthcare Costs of Smokers Using Varenicline Versus Nicotine-Replacement Therapy Patch in the United States: Evidence from Real-World Practice. Advances in therapy. 2019 Feb;     [PubMed PMID: 30569324]
[3] Kalkhoran S,Benowitz NL,Rigotti NA, Reprint of: Prevention and Treatment of Tobacco Use: JACC Health Promotion Series. Journal of the American College of Cardiology. 2018 Dec 11;     [PubMed PMID: 30522631]
[4] Liberman K,Van Schuerbeek P,Herremans S,Meysman M,De Mey J,Buls N, The effect of nicotine patches on craving in the brain: A functional MRI study on heavy smokers. Medicine. 2018 Sep;     [PubMed PMID: 30278517]
[5] Zhu J,Nelson K,Toth J,Muscat JE, Nicotine dependence as an independent risk factor for atherosclerosis in the National Lung Screening Trial. BMC public health. 2019 Jan 22;     [PubMed PMID: 30669994]
[6] Loukas A,Marti CN,Perry CL, Trajectories of Tobacco and Nicotine Use Across Young Adulthood, Texas, 2014-2017. American journal of public health. 2019 Jan 24;     [PubMed PMID: 30676800]
[7] Nethan ST,Sinha DN,Chandan K,Mehrotra R, Smokeless tobacco cessation interventions: A systematic review. The Indian journal of medical research. 2018 Oct;     [PubMed PMID: 30666002]
[8] Livingstone-Banks J,Ordóñez-Mena JM,Hartmann-Boyce J, Print-based self-help interventions for smoking cessation. The Cochrane database of systematic reviews. 2019 Jan 9;     [PubMed PMID: 30623970]
[9] Jackson SE,McGowan JA,Ubhi HK,Proudfoot H,Shahab L,Brown J,West R, Modelling continuous abstinence rates over time from clinical trials of pharmacological interventions for smoking cessation. Addiction (Abingdon, England). 2019 Jan 7;     [PubMed PMID: 30614586]
[10] Frank Wolf M,Bar-Zeev Y,Solt I, [INTERVENTIONS FOR SUPPORTING WOMEN TO STOP SMOKING IN PREGNANCY]. Harefuah. 2018 Dec;     [PubMed PMID: 30582312]