Treatments and disease management:
Nicotine toxicity acts via two discrete paths in sequence: overstimulation of acetylcholine secretions at low to moderate acute doses, and resultant inhibition of acetylcholine secretion factors upon chronic or high acute doses. As acetylcholine is responsible for proper neural signaling of muscle contractions, overstimulation and impeding acetylcholine production each pose their own negative effects upon such diverse targets as cardiac, respiratory, and skeletal muscle systems. (Hukkanen 2005)
In the event of acetylcholine overstimulation by way of stimulating nAChR, cardiac and respiratory muscles contract frequently and irregularly, leading to difficulty breathing and potential cardiac faults. Additionally, less severe symptoms also include jitteriness, hypertension, chest pain, muscle aches, and gastrointestinal distress. Depending on whether the nicotine was consumed via ingestion or direct skin contact, activated charcoal may be used to contain absorption within the stomach. At this stage, palliative care is the most useful. (Montalto 1994)
In the event of severe nicotine poisoning, the inhibitory effects at the nAChR complexes lead to a cascade of marked acetylcholine reduction, which reduces the propensity for muscle contractions system-wide. In cardiac and respiratory tissues this presents the emergent problems of cardiac and respiratory failure, in addition to secondary effects of decreased cardiac and respiratory output including hypotension and low blood oxygen content. (Montalto 1994)
In the case of chronic ingestion over a long period of time, nicotine dependence can take hold by way of inhibiting the reuptake of dopamine within the body. Such increased levels of dopamine can correspond directly to toxicity for neurons, contributing to oxidative damage and Parkinson’s disease.
Diagnosis and Treatment:
For ease of diagnosis, various blood and saliva tests to determine the presence of cotinine (a nicotine metabolite) within the blood serves as an excellent marker for increased levels of nicotine within the body. In the absence of undigested toxins within the body, medical efforts focus upon external stabilizing of respiratory and cardiac functions so as to preserve systemic health (Feyerabend 1990). Recently, there has been research in the expression of autoxidation mediated by the CYP2A6 gene (Saccone 2007), which affects downstream effects of nicotine poisoning in neurotransmitter production, specifically inhibiting the retention of dopamine and preventing some of the symptoms of neurotoxicity and Parkinson’s disease, as well as inhibiting the principal agent of addiction (dopamine reuptake inhibition). Unfortunately, as nicotine works upon the acetylcholine pathway in two disparate ways depending upon concentration, and there are severe penalties for disrupting homeostasis of acetylcholine production, there are no current drugs which allow for suppression of nicotine binding activity at the nAChR complex.
Due to the emergent nature of severe nicotine toxicity, a rapid acting drug that either increases or decreases the quantity of acetylcholine available within the body could pose major threats elsewhere within the body, such as the brain. Corresponding irregularities in acetylcholine-mediated action potentials within the brain has the potential for seizures in the case of increased activity, as well as memory related deficits in the event of suppressed activity. In summary, supportive care is the best treatment for episodes of nicotine toxicity, due to the potential for severe and long lasting damage upon alteration of acetylcholine receptor efficiency.