Article Author:
Amritpal Sandhu
Article Editor:
Abdolreza Saadabadi
10/10/2019 1:39:37 PM
PubMed Link:


Nicotine replacement therapy (NRT) is for those who want to quit smoking, as quitting abruptly can cause withdrawals and cravings. Nicotine withdrawal occurs after smoking cigarettes is suddenly discontinued. 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 used to get from cigarettes. Using these forms of NRT increases chances of success of quitting smoking and are 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 highly recommended 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, which is 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 nicotine is inhaled 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 is linked to delivering 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. Directions should be followed for each form of NRT. Even though there are different brands and forms, evidence shows no greater effectiveness of one type of NRT compared to another.  Studies also show that there is no benefit for using NRTs longer than eight weeks. Heavier smokers should use increased strength/dose of nicotine therapy.

  • Nicotine patches come in different brands, where some patches are designed for a 24-hour period 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 need to be applied 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.
  • Nicotine gum is available in different doses as well, at 2 mg and 4 mg. Gum is to be chewed 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.
  • Nicotine lozenges are available in 1-mg, 1.5-mg, 2-mg, and 4-mg doses. Allow 20 to 30 minutes to dissolve slowly. Do not chew or swallow. Recommended is 8 to 12 lozenges daily.
  • Nicotine sublingual tablet comes in a 2-mg dose.
  • Nicotine inhalation cartridge comes in 10 mg. The cartridge should be inserted into inhaler then popped into place. Inhale deeply or puff consecutively in short breaths.
  • Nicotine nasal spray comes in 0.5 mg per spray. Blow nose prior to use. Tilt head back and insert the tip of the bottle and spray once in each nostril.

Do not use 2 doses back to back. If a dose is missed, take it as soon as possible. If it is close to the time of the next dose, skip the missed dose.

Adverse Effects

Known adverse effects of nicotine include headaches, depression, back pain, and dizziness. Others include nervousness, drooling, shakiness, cold sweats, diarrhea, hypertension, increased heart rate, and vivid dreams.

  • With the oral/nasal mucosa absorbing NRT’s, nose and mouth ulcers and irritation has been reported. Some had dyspepsia and hiccups as well. Other side effects include swelling of the lips, throat, and tongue.
  • Transdermal patches have caused some people skin rash or irritation.

Inform a doctor immediately if any of the above side effects occur.


  • Hypersensitivity to nicotine. People allergic to soy should not use the Nicorette lozenge.
  • Nicotine also has drug interactions with adenosine, cimetidine, and varenicline. Adenosine may increase tachycardia effect of nicotine. Cimetidine may increase the serum concentration of nicotine. Varenicline can induce some of the nicotine side effects.
  • Pregnant women should also quit smoking during pregnancy. Nicotine is shown to cross the placenta as well as breast milk. NRT is not recommended 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 get first pass metabolism by the liver, and bioavailability would only be about 20%. This 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. This lets the nicotine enter through the oral or nasal mucosa, or skin and bypass the GI system for longer 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 makes toxicity from nicotine much less likely and prevents any GI side effects from happening. Symptoms in the rare event that nicotine is overdosed, 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 can be combined 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)


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