nicotine
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Introduction
Alkaloid found in Solanaceae family of plants, predominantly tobacco, with lower amounts in tomato, potato, eggplant, green pepper, coca. Nicotine constitutes 0.3-5% of dry weight of tobacco plant. Biosynthesis takes place in the roots, with nicotine accumulating in the leaves.[8]
Nicotine is potent neurotoxin, particularly to insects, this was widely used in the past as an insecticide. Derivatives of nicotine continue to be used as insecticides.
At low concentrations, nicotine is a stimulant.
Indications
- as an aid to smoking cessation all forms equally successful; success rate 20%[4]
* substantially lower levels of measured carcinogens & toxins than smoking (N-nitrosamine, ethylene oxide ...)[13]
Contraindications
(relative)
- pregnancy
- immediately post-myocardial infarction or unstable angina
- recent stroke or TIA
- FDA prohibits sale of nicotine products to individuals younger than 18 years of age; patients must show identification for proof of age prior to purchase of nicotine products
Benefit/risk
- smoking cessation
- number needed to treat = 15[11]
- number needed to harm
- 94 for chest pain or palpitations
- no increase in risk for cardiovascular events noted[11]
Pharmacokinetics
- most nicotine in smoke is destroyed by heat
- crosses blood-brain barrier, increased brain level in 7 seconds
- t1/2 of 2 hours
- cotinine N-glucuronide is the major urinary metabolite[8]
elimination via liver
elimination via kidney
Adverse effects
- mucosal burning
- light-headedness, dizziness
- nausea
- stomach ache, indigestion
- hiccups
- insomnia
- chest pain
- tachycardia
- hypertension
- induces transient increase in arterial stiffness[14]
- pruritus[11]
- rash at site of patch[11]
- use of patch with continued smoking aggravates cardiac problems
- withdrawal*
* Symptoms of nicotine withdrawal:
- may last 2 weeks, but craving for nicotine may last 5 years
- irritability
- frustration or anger
- anxiety
- depression
- difficulty concentrating
- restlessness
- decreased heart rate
- increased appetite
- weight gain (20% of patients may gain > 20 lbs)
- headache
- craving
- insomnia
- early nicotine withdrawal may increase pain reactivity[15]
* Nicotine replacement products do not appear to have significant potential for abuse or dependence[10] (which brings into question the claims of nicotine addiction &/or withdrawal)
Laboratory
Mechanism of action
- CNS stimulation in the cortex via the locus ceruleus producing alertness & increased cognitive performance,
- reward effect in the limbic system
- at low doses, stimulation occurs; at higher doses, reward effects predominate
- modulates stress
- regulates mood
- increases metabolism
- increases olfactory & gustatory senses
- produces physical dependence
- mediated via nicotinic receptor alpha4 beta2
- tolerance develops rapidly
More general terms
- solanaceous alkaloid
- pyridine
- parasympathomimetic (cholinergic agent)
- miscellaneous pharmacologic agent
Component of
- nicotine gum (Nicorette)
- nicotine patch; nicotine transdermal (Habitrol, Nicoderm, Nicotrol, ProStep)
- nicotine lozenge (Commit)
References
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 744
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
- ↑ 4.0 4.1 Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004
- ↑ Journal Watch 25(10):82-83, 2005 Moolchan ET, Robinson ML, Ernst M, Cadet JL, Pickworth WB, Heishman SJ, Schroeder JR. Safety and efficacy of the nicotine patch and gum for the treatment of adolescent tobacco addiction. Pediatrics. 2005 Apr;115(4):e407-14. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15805342 <Internet> http://pediatrics.org/cgi/content/full/115/4/e407
- ↑ American Medical News 2006; April 24
- ↑ Prescriber's Letter 13(5): 2006 CMS clarification of coverage of prescription niacin under part D Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220515&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 8.0 8.1 8.2 Wikipedia 2006
- ↑ PubChem: 408
- ↑ 10.0 10.1 Physician's First Watch, April 2, 2012 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
FDA for Consumers Nicotine Replacement Therapy Labels May Change http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm345087.htm - ↑ 11.0 11.1 11.2 11.3 11.4 Baker TB, Piper ME, Stein JH et al Effects of Nicotine Patch vs Varenicline vs Combination Nicotine Replacement Therapy on Smoking Cessation at 26 Weeks. A Randomized Clinical Trial. JAMA. 2016;315(4):371-379 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26813210 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2484340
- ↑ The NNT: Nicotine Replacement Therapy for Smoking Cessation. http://www.thennt.com/nnt/nicotine-replacement-therapy-for-smoking-cessation/
Stead LF, Perera R, Bullen C et al Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2012 Nov 14;11:CD000146. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23152200 - ↑ 13.0 13.1 Shahab L et al. Nicotine, carcinogen, and toxin exposure in long-term e-cigarette and nicotine replacement therapy users: A cross-sectional study. Ann Intern Med 2017 Feb 7; PMID: https://www.ncbi.nlm.nih.gov/pubmed/28166548
- ↑ 14.0 14.1 Boyles S, E-Cigs May Still Damage Blood Vessels Arterial stiffness increased immediately after vaping session. MedPage Today. September 10, 2017 https://www.medpagetoday.com/MeetingCoverage/ERS/67802
- ↑ 15.0 15.1 Ditre JW, Zale EL, LaRowe LR, Kosiba JD, De Vita MJ. Nicotine deprivation increases pain intensity, neurogenic inflammation, and mechanical hyperalgesia among daily tobacco smokers. J Abnorm Psychol 2018 May 21; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29781659
Database
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=942
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=6174
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=498080
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=212128
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=17784
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=89594
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=169012
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=6173