Treatments and Disease Management

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)

Figure 1: A graphic listing the physiological effects of nicotine upon the body. The capability to affect systems in strikingly different ways is a hallmark of Acetylcholine receptor modifying molecules. (Google images 2009)
Figure 1: A graphic listing the physiological effects of nicotine upon the body. The capability to affect systems in strikingly different ways is a hallmark of Acetylcholine receptor modifying molecules. (Google images 2009)

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.

Figure 1: Commercial saliva test for the presence of continine within a patient, can be used for both addiction treatment or emergent diagnoses. (Google images 2012)
Figure 2: Commercial saliva test for the presence of continine within a patient, can be used for both addiction treatment or emergent diagnoses. (Google images 2012)

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.

2 Replies to “Treatments and Disease Management”

  1. Hi Anthony! Nice job with your webpages. I have a few questions (I have left one comment here but these questions may aply to other pages too):
    1. I’m slightly confused on how a SNP in CHRNA that causes increased binding affinity to nicotine would predispose you to addiction. It seems like if the drug is binding more easily, you can get a greater impact with less drug and would therefore need to take less of it. Can you clarify this?
    2. Can you explain how the “Activated charcoal” therapy works? You say it helps with stomach symptoms, but what is the biochemistry behind this treatment? How is it administered? Also, you mentioned that children are at increased risk for nicotine toxicity–would they be able to use this treatment? Are the treatments different for children vs adults?
    3. Does nicotine toxicity have long term effects or just these acute symptoms? Can you be impacted later in life? When children are exposed to nicotine either in utero or as babies, does that negatively impact their development or their health later in life?
    Thanks 🙂

    1. Hey Kelly,

      Thanks for reading! The understanding I got regarding the CHRNA5 SNP modification is that the increased binding affinity of nicotinoids to nAChR allowed for greater downstream propagation of dopamine secondary to Ach, which in turn fosters the manic pleasureable states which engender addiction.

      Activated charcoal therapy works by creating a large surface area within the digestive system so as to alternatively absorb toxins before the body proper does. While emesis and foul taste exist as side-effects, the treatment is approximately a lesser version of “pumping the stomach”, and as such is more suitable for youth and those with poor constitution.

      Nicotine toxicity in the acute form has primarily limited effects, although depending on the degree of poisoning and the effects (i.e cardiac/respiratory tissue death) there may be chronic health conditions which occur later in life. Chronic effects of nicotine predominantly revolve around addiction and the neurotransmitter imbalances (specifically dopamine and seratonine) that go along with such a condition. As such, nicotine in utero not only has the capability to fatally poison a child, but also cause lasting damage by way of acetylcholine imbalance or modification of homeostatic levels of brain neurotransmitters. Children’s size makes them susceptible to acute effects, as the unfortunate literature on children consuming cigarette butts shows.

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