Key:SNICXCGAKADSCV-JTQLQIEISA-N Y N Y Nicotine is a stimulant and an found in the family of plants. Nicotine acts as an at most (nAChRs), except at two ( and ) where it acts as a. Nicotine is found in the leaves of, in amounts of 2–14%; in the plant,; in; and in. Nicotine constitutes approximately 0.6–3.0 of the dry weight of tobacco. It also occurs in edible plants, such as those in the family, which include, and for example, but at trace levels generally under 200 per gram, dry weight (less than.00002%). Nicotine functions as an; consequently, nicotine was widely used as an in the past, and, such as, are widely used. Nicotine is highly.
An average yields about 2 mg of absorbed nicotine; in lesser doses of that order, the substance acts as a in, while high amounts (50–100 mg) can be harmful. This stimulant effect is a contributing factor to the addictive properties of. Nicotine's addictive nature includes psychoactive effects, drug-reinforced behavior, compulsive use, relapse after abstinence, physical dependence and tolerance. Beyond addiction, both short and long-term nicotine exposure have not been established as dangerous to adults, except among certain vulnerable groups. At high-enough doses, nicotine is associated with and is potentially lethal. Nicotine as a tool for has a good safety history. There is inadequate research to show that nicotine itself is associated with cancer in humans.
Tobacco is an addictive substance because it contains the chemical nicotine. Learn how tobacco use can cause addiction at BeTobaccoFree.gov. Tobacco is a plant grown for its leaves, which are dried and fermented before being put in tobacco products. Tobacco contains nicotine, an ingredient that can lead to.
Nicotine in the form of is less of a cancer risk than. Nicotine is linked to possible birth defects. During pregnancy, there are risks to the child later in life for type 2 diabetes, obesity, hypertension, neurobehavioral defects, respiratory dysfunction, and infertility.
The use of, which are designed to be refilled with nicotine-containing, has raised concerns over nicotine overdoses, especially with regard to the possibility of young children ingesting the liquids. Contents. Psychoactive effects Nicotine's -altering effects are different by report: in particular it is both a stimulant and a relaxant. First causing a release of from the liver and (adrenaline) from the, it causes.
Users report feelings of, sharpness, and. When a is smoked, nicotine-rich blood passes from the to the within seven seconds and immediately stimulates; this indirectly promotes the release of many chemical messengers such as, and in parts of the brain. Nicotine also extends the duration of positive effects of dopamine and increases the sensitivity of the brain's to. Most cigarettes contain 1–3 milligrams of inhalable nicotine.
Studies suggest that when smokers wish to achieve a stimulating effect, they take short quick puffs, which produce a low level of blood nicotine. Nicotine is unusual in comparison to most drugs, as its profile changes from to with increasing, a phenomenon known as 'Nesbitt's paradox' after the doctor who first described it in 1969. At very high doses it dampens. Uses Medical. A 21 mg applied to the left arm.
The finds that increases a quitter's chance of success by 50% to 70%. The primary therapeutic use of nicotine is in treating nicotine dependence in order to eliminate with the damage it does to health. Controlled levels of nicotine are given to patients through, lozenges, electronic/substitute cigarettes or nasal sprays in an effort to wean them off their dependence. Studies have found that these therapies increase the chance of success of quitting by 50 to 70%, though reductions in the population as a whole have not been demonstrated. Enhancing performance Nicotine is frequently used for its performance-enhancing effects on cognition, alertness, and focus. A meta-analysis of 41, -controlled studies concluded that nicotine or smoking had significant positive effects on aspects of fine motor abilities, alerting and orienting attention, and episodic and working memory.
A 2015 review noted that stimulation of the is responsible for certain improvements in attentional performance; among the subtypes, nicotine has the highest at the α4β2 receptor (k i=1 nM), which is also the biological target that mediates nicotine's properties. Nicotine has potential beneficial effects, but it also has, which may be due to its inverted U-shape or features. Recreational Nicotine is commonly consumed as a recreational drug for its stimulant effects. Recreational nicotine products include, and. Adverse effects Limited data exists on the health effects of long-term use of pure nicotine, because nicotine is usually consumed via products. The long-term use of nicotine in the form of snus incurs a slight risk of cardiovascular disease compared to tobacco smoking.
Nicotine is one of the most rigorously studied drugs. The complex effects of nicotine are not entirely understood. Studies of continued use of in those who have stopped smoking found no from months to several years, and that people with were able to tolerate them for 12 weeks. The general medical position is that nicotine itself, in small doses , poses few health risks, except among certain vulnerable groups. A 2016 report found 'nicotine alone in the doses used by smokers represents little if any hazard to the user'. A 2014 policy statement found that some health concerns relate to nicotine. Experimental research suggests that adolescent nicotine use may harm.
Children exposed to nicotine may have a number of lifelong health issues. Administration of nicotine to guinea pigs has been shown to cause harm to cells of the inner ear. As medicine, nicotine is used to help with and has good safety in this form. Metabolism and body weight By reducing the and raising the, some smokers may as a consequence. By increasing metabolic rate and inhibiting the usual compensatory increase in appetite, the body weight of smokers is lower on average than that of non-smokers. When smokers quit, they gain on average 5–6 kg weight, returning to the average weight of non-smokers. Vascular system Human epidemiology studies show that nicotine use is not a significant cause of cardiovascular disease.
A 2015 review found that nicotine is associated with cardiovascular disease. A 2016 review suggests that 'the risks of nicotine without tobacco combustion products (cigarette smoke) are low compared to cigarette smoking, but are still of concern in people with cardiovascular disease.'
Some studies in people show the possibility that nicotine contributes to acute cardiovascular events in smokers with established cardiovascular disease, and induces pharmacologic effects that might contribute to increased. Prolonged nicotine use seems not to increase atherosclerosis. Brief nicotine use, such as nicotine medicine, seems to incur a slight cardiovascular risk, even to people with established cardiovascular disease.
Tobacco Nicotiana
A 2015 review found 'Nicotine in vitro and in animal models can inhibit and enhance, effects that raise concerns about the role of nicotine in promoting the acceleration of atherosclerotic disease.' A 2012 found no evidence of an increased risk of cardiovascular disease with nicotine replacement products. A 1996 using found that were not more frequent among smokers with cardiovascular disease.
A shows that consumption, which delivers nicotine at a dose equivalent to that of cigarettes, is not associated with. Hence, it is not nicotine, but tobacco smoke's other components which seem to be implicated in. Nicotine increases heart rate and blood pressure and induces abnormal heart rhythms. Nicotine can also induce potentially atherogenic genes in human coronary artery endothelial cells. Microvascular injury can result through its action on nicotinic acetylcholine receptors (nAChRs).
Nicotine does not adversely affect serum cholesterol levels, but a 2015 review found it may elevate serum cholesterol levels. Many quitting smoking studies using nicotine medicines report lowered with considerable benefit in HDL/LDL ratios. Nicotine supports clot formation and aids in plaque formation by enhancing.
Possible of nicotine. Although there is insufficient evidence to classify nicotine as a, there is an ongoing debate about whether it functions as a. Studies have associated it with cancer, but carcinogenicity has not been demonstrated. There is inadequate research to demonstrate that nicotine is associated with cancer in humans, but there is evidence indicating possible oral, esophageal, or pancreatic cancer risks. Nicotine in the form of nicotine replacement products is less of a cancer risk than. Nicotine replacement products have not been shown to be associated with cancer in the real world.
While no epidemiological evidence directly supports the notion that nicotine acts as a carcinogen in the formation of human cancer, research has identified nicotine's indirect involvement in cancer formation in and. Nicotine increases signalling and signalling in the case of colon cancer, thereby impeding apoptosis , promoting tumor growth, and activating and cellular factors such as (5-LOX), and (EGF). Nicotine also promotes cancer growth by stimulating and. In one study, nicotine administered to mice with tumors caused increases in tumor size (twofold increase), (nine-fold increase), and tumor recurrence (threefold increase).
(NNN), classified by the (IARC) as a, has been shown to form from in human saliva, indicating nornicotine is a carcinogen precursor. The IARC has not evaluated pure nicotine or assigned it to an official carcinogenic classification. In cancer cells, nicotine promotes the which makes the cancer cells more resistant to drugs that treat cancer. Fetal development In pregnancy, a 2013 review noted that 'nicotine is only 1 of more than 4000 compounds to which the fetus is exposed through maternal smoking. Of these, ∼30 compounds have been associated with adverse health outcomes. Although the exact mechanisms by which nicotine produces adverse fetal effects are unknown, it is likely that hypoxia, undernourishment of the fetus, and direct vasoconstrictor effects on the placental and umbilical vessels all play a role. Nicotine also has been shown to have significant deleterious effects on brain development, including alterations in brain metabolism and neurotransmitter systems and abnormal brain development.'
It also notes that 'abnormalities of newborn neurobehavior, including impaired orientation and autonomic regulation and abnormalities of muscle tone, have been identified in a number of prenatal nicotine exposure studies' and that there is weak data associating fetal nicotine exposure with newborn, and that there is no good evidence for newborns suffering from fetal exposure to nicotine. Effective April 1, 1990, the Office of Environmental Health Hazard Assessment (OEHHA) of the added nicotine to the list of chemicals known to cause developmental toxicity. Nicotine is not safe to use in any amount during pregnancy. Questions exist regarding nicotine use during pregnancy and their potential consequences on fetal growth and mortality. Nicotine negatively affects pregnancy outcomes and fetal brain development. Risks to the child later in life via nicotine exposure during pregnancy include type 2 diabetes, obesity, hypertension, neurobehavioral defects, respiratory dysfunction, and infertility.
Nicotine crosses the and is found in the breast milk of mothers who smoke as well as mothers who inhale. Reinforcement disorders. See also: and involves aspects of both and, since discontinuation of extended use has been shown to produce both affective (e.g., anxiety, irritability, craving, ) and somatic (mild motor dysfunctions such as ) withdrawal symptoms.
Withdrawal symptoms peak in the first day or two and can persist for several weeks. Nicotine has cognitive-enhancing effects at low doses, particularly in fine motor skills, attention, and memory. These beneficial cognitive effects may play a role in the maintenance of tobacco dependence. Nicotine is highly, comparable to heroin or cocaine. Nicotine activates the and induces long-term expression in the when inhaled or injected at sufficiently high doses, but not necessarily when ingested. Consequently, repeated daily exposure (possibly excluding ) to nicotine can result in accumbal ΔFosB overexpression, in turn causing nicotine addiction. In dependent smokers, smoking during withdrawal returns cognitive abilities to pre-withdrawal levels, but chronic use may not offer cognitive benefits over not smoking.
Use of other drugs. See also: In animals it is relatively simple to determine if consumption of a certain drug increases the later attraction of another drug. In humans, where such direct experiments are not possible, can show if the probability of a substance use is related to earlier use of other substances. In mice nicotine increased the probability of later consumption of and the experiments permitted concrete conclusions on the underlying alteration in the brain.
The biological changes in mice correspond to the observations in humans that nicotine consumption is coupled to an increased probability of later use of and cocaine. In rats cannabis consumption – earlier in life – increased the later self-administration of nicotine. A study of drug use of 14,577 US 12th graders showed that alcohol consumption was associated with an increased probability of later use of tobacco, cannabis, and other illegal drugs. Overdose.
Main article: Nicotine is regarded as a potentially poison. The of nicotine is 50 mg/kg for and 3 mg/kg for. 30–60 mg (0.5–1.0 mg/kg) can be a lethal dosage for adult humans. However, the widely used human LD 50 estimate of 0.5–1.0 mg/kg was questioned in a 2013 review, in light of several documented cases of humans surviving much higher doses; the 2013 review suggests that the lower limit causing fatal outcomes is 500–1000 mg of ingested nicotine, corresponding to 6.5–13 mg/kg orally. Nevertheless, nicotine has a relatively high in comparison to many other alkaloids such as, which has an LD 50 of 127 mg/kg when administered to mice. At high-enough doses, it is associated with nicotine poisoning. Today nicotine is less commonly used in agricultural, which was a main source of poisoning.
More recent cases of poisoning typically appear to be in the form of or due to accidental ingestion of or tobacco products or ingestion of nicotine-containing plants. People who harvest or cultivate tobacco may experience Green Tobacco Sickness (GTS), a type of nicotine poisoning caused by dermal exposure to wet tobacco leaves. This occurs most commonly in young, inexperienced tobacco harvesters who do not consume tobacco. People can be exposed to nicotine in the workplace by breathing it in, skin absorption, swallowing it, or eye contact. The (OSHA) has set the legal limit for nicotine exposure in the workplace as 0.5 mg/m 3 skin exposure over an 8-hour workday. The US (NIOSH) has set a (REL) of 0.5 mg/m 3 skin exposure over an 8-hour workday.
At environmental levels of 5 mg/m 3, nicotine is. It is unlikely that a person would overdose on nicotine through smoking alone. The US (FDA) stated in 2013 that 'There are no significant safety concerns associated with using more than one at the same time, or using an OTC NRT at the same time as another nicotine-containing product—including a cigarette.' The rise in the use of, many forms of which are designed to be refilled with nicotine-containing supplied in small plastic bottles, has raised concerns over nicotine overdoses, especially in the possibility of young children ingesting the liquids. A 2015 report noted an 'unconfirmed newspaper report of a fatal poisoning of a two-year old child' and two published case reports of children of similar age who had recovered after ingesting e-liquid and vomiting. They also noted case reports of suicides by nicotine. Where adults drank liquid containing up to 1,500 mg of nicotine they recovered (helped by vomiting), but an ingestion apparently of about 10,000 mg was fatal, as was an injection.
They commented that 'Serious nicotine poisoning seems normally prevented by the fact that relatively low doses of nicotine cause nausea and vomiting, which stops users from further intake.' Pharmacology Pharmacodynamics Nicotine acts as a at most (nAChRs), except at two ( and ) where it acts as a. Central nervous system. Effect of nicotine on dopaminergic neurons. By binding to in the brain, nicotine elicits its psychoactive effects and increases the levels of several in various brain structures – acting as a sort of 'volume control.'
Nicotine has a higher affinity for nicotinic receptors in the brain than those in, though at toxic doses it can induce contractions and respiratory paralysis. Nicotine's selectivity is thought to be due to a particular amino acid difference on these receptor subtypes. Nicotine activates nicotinic receptors (particularly ) on neurons that innervate the and within the where it appears to cause the release of. This nicotine-induced dopamine release occurs at least partially through activation of the in the.
Nicotine also appears to induce the release of that activate opioid pathways in the, since – an – blocks nicotine. These actions are largely responsible for the strongly reinforcing effects of nicotine, which often occur in the absence of; however, mild euphoria from nicotine use can occur in some individuals. Chronic nicotine use inhibits class I and II in the, where this effect plays a role in nicotine addiction. Sympathetic nervous system. Effect of nicotine on chromaffin cells. Nicotine also activates the, acting via to the adrenal medulla, stimulating the release of epinephrine. Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on nicotinic acetylcholine receptors, causing the release of epinephrine (and norepinephrine) into the.
Adrenal medulla By binding to in the adrenal medulla, nicotine increases flow of (epinephrine), a stimulating and neurotransmitter. By binding to the receptors, it causes cell depolarization and an influx of through voltage-gated calcium channels. Calcium triggers the of and thus the release of (and norepinephrine) into the. The release of (adrenaline) causes an increase in, and, as well as higher levels. Pharmacokinetics. Urinary metabolites of nicotine, quantified as average percentage of total urinary nicotine.
As nicotine enters the body, it is distributed quickly through the and crosses the reaching the within 10–20 seconds after inhalation. The of nicotine in the body is around two hours. The amount of nicotine absorbed by the body from smoking can depend on many factors, including the types of tobacco, whether the smoke is inhaled, and whether a filter is used. However, it has been found that the nicotine yield of individual products has only a small effect (4.4%) on the blood concentration of nicotine, suggesting 'the assumed health advantage of switching to lower-tar and lower-nicotine cigarettes may be largely offset by the tendency of smokers to compensate by increasing inhalation'. Nicotine has a half-life of 1–2 hours. Is an active metabolite of nicotine that remains in the blood with a half-life of 18–20 hours, making it easier to analyze.
Nicotine is in the by enzymes (mostly, and also by ) and, which selectively metabolizes ( S)-nicotine. A major metabolite is. Other primary metabolites include nicotine N'-oxide, nornicotine, nicotine isomethonium ion, 2-hydroxynicotine and nicotine glucuronide. Under some conditions, other substances may be formed such as. And oxidative metabolism of nicotine to cotinine are both inhibited by, an additive to, thus increasing the half-life of nicotine in vivo. Chemistry fire diamond. The fire diamond hazard sign for nicotine.
Nicotine is a, colorless to yellow-brown, oily liquid, that is readily soluble in alcohol, ether or light petroleum. Michigan, Midwestern United States. It is with in its form between 60 °C and 210 °C. As a, nicotine forms with that are usually solid and water-soluble. Its is 95 °C and its auto-ignition temperature is 244 °C. Nicotine is readily volatile ( 5.5 ㎩ at 25 ℃) and dibasic (K b1 = 1×10⁻⁶, K b2 = 1×10⁻¹¹). Nicotine is, having two forms. The naturally occurring form of nicotine is with a of α D = –166.4° ((−)-nicotine).
The form, (+)-nicotine is physiologically less active than (−)-nicotine. (−)-nicotine is more toxic than (+)-nicotine. The salts of (+)-nicotine are usually dextrorotatory. The hydrochloride and sulphate salts become optically inactive if heated in a closed vessel above 180 °C.
On exposure to ultraviolet light or various oxidizing agents, nicotine is converted to nicotine oxide, nicotinic acid (vitamin B3), and methylamine. Occurrence and biosynthesis.
Nicotine biosynthesis Nicotine is a natural product of tobacco, occurring in the leaves in a range of 0.5 to 7.5% depending on variety. Nicotine also naturally occurs in smaller amounts in plants from the family (such as, and ). The biosynthetic pathway of nicotine involves a coupling reaction between the two cyclic structures that compose nicotine. Metabolic studies show that the ring of nicotine is derived from (nicotinic acid) while the pyrrolidone is derived from N-methyl-Δ 1-pyrrollidium cation. Biosynthesis of the two component structures proceeds via two independent syntheses, the NAD pathway for niacin and the tropane pathway for N-methyl-Δ 1-pyrrollidium cation.
The NAD pathway in the genus begins with the oxidation of aspartic acid into α-imino succinate by aspartate oxidase (AO). This is followed by a condensation with and a cyclization catalyzed by quinolinate synthase (QS) to give.
Quinolinic acid then reacts with phosphoriboxyl pyrophosphate catalyzed by quinolinic acid phosphoribosyl transferase (QPT) to form niacin mononucleotide (NaMN). The reaction now proceeds via the NAD salvage cycle to produce niacin via the conversion of by the enzyme. The N-methyl-Δ 1-pyrrollidium cation used in the synthesis of nicotine is an intermediate in the synthesis of tropane-derived alkaloids. Biosynthesis begins with of by ornithine decarboxylase (ODC) to produce. Putrescine is then converted into N-methyl putrescine via by SAM catalyzed by putrescine N-methyltransferase (PMT). N-methylputrescine then undergoes into 4-methylaminobutanal by the N-methylputrescine oxidase (MPO) enzyme, 4-methylaminobutanal then spontaneously cyclize into N-methyl-Δ 1-pyrrollidium cation. The final step in the synthesis of nicotine is the coupling between N-methyl-Δ 1-pyrrollidium cation and niacin.
Although studies conclude some form of coupling between the two component structures, the definite process and mechanism remains undetermined. The current agreed theory involves the conversion of niacin into 2,5-dihydropyridine through 3,6-dihydronicotinic acid. The 2,5-dihydropyridine intermediate would then react with N-methyl-Δ 1-pyrrollidium cation to form pure (−)-nicotine. Detection in body fluids Nicotine can be quantified in blood, plasma, or urine to confirm a diagnosis of poisoning or to facilitate a forensic.
Urinary or salivary cotinine concentrations are frequently measured for the purposes of pre-employment and health insurance medical screening programs. Careful interpretation of results is important, since passive exposure to cigarette smoke can result in significant accumulation of nicotine, followed by the appearance of its metabolites in various body fluids. Nicotine use is not regulated in competitive sports programs.
Nicotine Addiction and Your Health. Why is nicotine addictive? When you use tobacco products, nicotine is quickly absorbed into your bloodstream.
Within 10 seconds of entering your body, the nicotine reaches your brain. It causes the brain to release adrenaline, creating a buzz of pleasure and energy. The buzz fades quickly though, and leaves you feeling tired, a little down, and wanting the buzz again.
This feeling is what makes you light up the next cigarette. Since your body is able to build up a high tolerance to nicotine, you’ll need to smoke more and more cigarettes in order to get the nicotine’s pleasurable effects and prevent withdrawal symptoms. This up and down cycle repeats over and over, leading to addiction. Addiction keeps people smoking even when they want to quit. Breaking addiction is harder for some people than others. Many people need more than one try in order to quit.
Research suggests that children and teens may be especially sensitive to nicotine, making it easier for them to become addicted. The younger smokers are when they start, the more likely they are to become addicted. In fact, about three out of four high school smokers will become adult smokers. When happens when I quit?
Tobacco and nicotine are addictive like alcohol, cocaine, and heroin. When you stop smoking or cutback your tobacco use, you experience withdrawal. When going through withdrawal you may experience:. Anxiety. Irritability. Headache. Hunger.
Cravings for cigarettes and other sources of nicotine Nicotine withdrawal is short-lived and symptoms pass in time, usually less than a week. Withdrawal is the most uncomfortable part of quitting, but the real challenge is beating long-term cravings and staying away from tobacco.
Learn more about quitting.