History and Definition of Nicotine toxicity:
Nicotine toxicity is a broad term used to cover a host of metabolic actions and systemic actions arising from elevated levels of nicotine within the body. Nicotine itself is an alkaloid compound found naturally within tobacco plants as a pesticide agent, specifically pertaining to plants of the Solanacacae (nightshade) Family, and is indigenous to the Americas. In order to understand the history behind the current relatively common mechanisms of nicotine exposure in humans, one needs to first review the history of tobacco containing products. Prior to European arrival in the Americas, Nicotina Tabacum had been sought out and utilized by local religious practitioners and shamans for roles within ceremonies where it was consumed for its ability to induce altered states of consciousness. Additionally, the pain-killing effects of nicotine prompted light medicinal uses as a sedative. Due in part to the limited nature of Native American practices with tobacco products in the context of ceremonial settings, and the lack of recreational use, instances of chemical dependence appear to have been rarer than in later exposed populations. Upon exposure to the European populace in the early 1500’s, it rapidly grew in popularity due to its supposed medical uses passed along secondhand from New World traders, and supported by mainland European physicians. Additionally, the highly-addictive nature of nicotine found many victims whom were unaware of its trends towards chemical dependence in a more rapid fashion that that of other drugs at the time, such as alcohol. As plantation level quantities arose to meet demand, Eurasia was flooded with exposure to the potent new drug and tobacco rapidly became a common portion of European and south Asian culture. As individuals took to growing their own tobacco plants in southern Europe and south Asia, tobacco permeated the common culture for its potent stimulant qualities. For a period of time in the prior to the Civil War, tobacco excise tax was responsible for a full third of the United States internal revenue sources.
In a tobacco enveloped world, the identification of chronic health risks (particularly cancer) would take time before becoming a publicly noted concern, with major public knowledge about the risk of smoking only coming to the forefront in the middle of the 20th century. As nicotine itself is not conclusively linked to having carcinogenic properties, it has been perceived as safer than other compounds found within cigarettes, and has as such been less regulated then the carcinogenics and additives targeted by regulatory organizations.
With the rise of smoking cessation products on the market offering supplemental forms of nicotine combined with the emergence of electronic nicotine delivery systems (ENDS) over the past decade, possible sources of nicotine in more concentrated and less popularly understood forms have risen on the marketplace. As a result, incidences of accidental nicotine poisoning have risen, with the mechanism of delivery being the major changing factor.
Symptoms and of acute Nicotine toxicity:
Acting as a CNS stimulant, nicotine toxicity primarily is expressed clinically via hypertension, tachycardia, and bodily tremors (Schep, 2009). In late stages and high quantities of nicotine poisoning, slowed symptoms of the body including low blood pressure, slow heart rhythms, and difficulty breathing present themselves. These symptoms can be primarily attributed to its mechanism of action upon Nicotinic-type acetylcholingeric receptors (nAChR’s), which are responsible for proper muscle signaling.
nAChR’s are neuron receptor proteins which regulate and signal for muscle contraction within the body in response to chemical stimuli. Usually triggered by acetylcholine, nAChR’s are also found to have favorable binding interactions with nicotine, leading to opening of it’s non-selective cation channel. With the increased allowance in cation transfer, positively charged entities such as Sodium and Potassium are more freely able to cross and depolarize the plasma membrane of the cell. The resulting depolarization stimulates neurons to fire action potentials, being the mechanism by which the stimulant effects are most felt.
Like most natural systems, prolonged exposure to a stimulus can lead to decreased response to that stimulus in later iterations. In the context of nAChR’s, an abundance of nicotine binding to sites in place of acetylcholine can lead to poor mediation of gated cation channels, which in turn corresponds to a lack of action potentials. With this corresponding decrease in the number of action potentials within the musculoskeletal system, impairment of respiratory and cardiac muscles is followed by lethargy and systemic effects up to and including comas. These symptoms tend to be more serious than those of low-level nicotine use, as the drug moves from having primarily stimulatory effects upon the body to impairing wide-ranging effects of acetylcholine mediated processes.
Nicotine containing products maintain a unique place in the world of recreational drugs, as those which are inhalable (cigarettes, pipes) allow for determination by the user of the effect they wish to feel. Lower quantities of nicotine inhalation lightly act upon the acetylcholine receptors, and preferentially stimulate complexes responsible for releasing epinephrine and other stimulatory agents within the brain. In higher concentration ingestion instances of nicotine, nicotine begins to bind more to nAChr’s mediating dopamine and serotonin release then those involved in musculoskeletal and epinephrine release, leading to pain-relief properties and altered states of consciousness, as well as instigating nicotine dependence. (Griffiths, 1982)
With the rise of electronic cigarettes, liquid nicotine has become more accessible to the public. As nicotine is capable of being absorbed through the skin, this presents another avenue of risk, especially when considering that nicotine found in liquid state is of much higher concentration then nicotine found within a cigarette (up to 36 mg/ml versus ~1.06 mg nicotine per traditional cigarette) (Schroder 2014). With 120 ml bottles of pure 36 mg/ml nicotine retailing for 12 dollars online, and options for purchase of up to 1 gallon of nicotine concentrate, the capability for accidental misuse is incredibly present. For reference, a 10ml spill of high concentration nicotine on an ungloved hand would have the same potential effects as smoking 360 cigarettes, or 18 packs. As the LD50 for nicotine has been determined to be 6.5–13 mg/kg (Mayer 2014), this small spill would be potentially lethal for a person of 120lb.
In contrast to acute conditions, nicotine dependence is formed over time by way of continued stimulation of serotonin and dopamine levels in the brain. With the original rate of release of these chemicals disrupted, the brain initially responds in a heightened fashion to these stimulated levels before adjusting to the new levels as a baseline for activity. With this baseline established in the presence of nicotine, a lack of nicotine activity effecting the release of neurotransmitters leads to the brain under-producing those same chemicals. With decreased levels of dopamine and serotonin released, the individual can report a plethora of mental health concerns including depression, leading to urges to consume nicotine in order to return to normal operating levels of neurotransmitter activity.
As an acute disorder, nicotine toxicity presents symptoms in a rapid fashion. In lower quantities, excessive stimulation may be observed via increased physiological processes such as respiration and pulse, as well as behavioral changes consistent with an excited state such as more energy and physical activity in the individual. Nicotine toxicity in higher levels acts upon many of the same processes, and slowing down of respirations and pulse may be observed in critical scenarios. Additionally, dizziness and confusion consistent with an altered mental state may be observed in high levels of nicotine toxicity, leading to further implications of drug overdose in the patient.
Blood tests which inspect for cotinine, the predominant metabolite of nicotine, may also be used to effect in determining concentration of nicotine within an affected individual. With gas-liquid chromatography apparatus, samples can be analyzed in as little as 3 minutes, allowing for a quick and efficient determination of nicotine content within a patient’s blood (Feyerbend 1990).