Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.
Nicotine use disorder is defined as the chronic (> 12 months) maladaptive use of tobacco.
- Most common substances: cigarettes, chewing tobacco
- Intoxication:
- Much milder symptoms than are present in intoxication with other substances
- Presents with mild restlessness/anxiety and increased GI motility
- Withdrawal:
- Development of a substance-specific syndrome due to the cessation (or reduction) of substance use
- Mild physical symptoms: weight gain, poor concentration
- Mild psychological symptoms: depression, perceived need to use the substance
- Tolerance:
- Need to increase the dose of the substance to achieve desired effect (diminished effect if using the same amount of the substance)
Pharmacology
Nicotine is the main psychoactive component of tobacco:
- Agonist at the nicotinic subtype of acetylcholine receptor in the central nervous system
- Activates the dopaminergic pathway from the ventral tegmental area to the cerebral cortex to produce its rewarding effects
- Leads to increasing circulation of the following neurotransmitters:
- Norepinephrine
- Epinephrine
- Beta-endorphin
- Adrenocorticotropic hormone
- Cortisol
Only 25% of inhaled nicotine enters the bloodstream, but it reaches the brain in 15 seconds.
Symptoms
Active nicotine use
- Immediate effects of nicotine include improved attention and elevated mood.
- Usually, there are no severe intoxication symptoms from tobacco use.
- Nicotine intoxication:
- Nausea/vomiting
- Diarrhea
- Tachycardia, elevated blood pressure
- Tremor
- Cold sweats
- Note: Nicotine is a CNS stimulant but a skeletal muscle relaxant.
Nicotine withdrawal
- Intense craving
- Dysphoria
- Anxiety
- Poor concentration
- Increased appetite, weight gain
- Irritability, restlessness, and insomnia
Management and Complications
Pharmacotherapy for nicotine use disorder
- Nicotine-replacement therapy:
- 1st-line treatment; doubles chances of cessation
- Available as transdermal patch, gum, lozenge, nasal spray, and inhaler
- Nicotine cessation:
- Varenicline:
- Partial agonist to the alpha-4 beta-2 (α4β2) nicotinic cholinergic receptor
- Mimics the action of nicotine
- Reduces the rewarding effects of nicotine
- Prevents withdrawal symptoms
- Side effects: sleep disturbance, depressed mood
- Bupropion:
- Inhibitor of dopamine and norepinephrine reuptake
- Helps reduce cravings and withdrawal symptoms
- Side effects: tachycardia, insomnia, headaches, seizures in bulimic patients (contraindicated in this group)
- Varenicline:
Psychotherapy and preventive measures for nicotine use disorder
- Behavioral counseling:
- Includes face-to-face or phone sessions, print materials, and software programs
- The goal is to help eliminate cues for smoking.
- Motivational interviewing:
- Offered by providers to patients to uncover internal reasons for tobacco cessation
- The 1st step is to set a “quit date.”
- Prevention and education are recommended in school-aged children and adolescents.
- Public health policies such as a ban on public smoking
Management of nicotine withdrawal
- Symptomatic treatment
- Supportive, psychosocial interventions (e.g., contingency management, groups, etc.)
Complications
- Smoking increases the risk for several types of cancers:
- Lung cancer: Tobacco smoking is the most common risk factor for the most deadly form of cancer in the United States.
- Chronic obstructive pulmonary disease (COPD): 90% of cases of COPD can be attributed to tobacco smoking.
- Esophageal cancer
- Gastric cancer
- Renal cell carcinoma
- Transitional cell carcinoma
- Salivary gland tumors
- Cervical cancer
- Cardiovascular diseases (atherosclerosis, angina)
- Vasculitis (Buerger disease)
- Pregnancy-related complications:
- Low birth weight
- Preterm labor
- Placental problems
- Intrauterine growth restriction
- Sudden infant death syndrome
- Ectopic pregnancy
- Secondhand smoke
- Refers to involuntary exposure to tobacco smoke
- Similar complications as above although in lower numbers
Benefits of smoking cessation
Short-term benefits (< 12 months):
- Lowered heart rate and blood pressure
- Return of blood carbon monoxide level to normal
- Improved circulation and lung function
- Decreased coughing and shortness of breath
- Women who stop smoking during the 1st trimester reduce their risk of low birth weight to that of women who never smoked.
Long-term benefits (> 12 months):
- Increased life expectancy
- Decreased risk of lung cancer, myocardial infarction, cerebrovascular diseases
- Decreased risk of oropharyngeal, bladder, cervical, lung, and pancreatic cancer
Differential Diagnosis
- Organophosphate poisoning: chemicals commonly found in insecticides, classified as irreversible cholinesterase inhibitors. When these chemicals are ingested in toxic amounts, symptoms include salivation, lacrimation, urination, diarrhea, GI upset, and emesis. These symptoms are similar to nicotine intoxication. However, the severity of symptoms observed in organophosphate poisoning is unlikely to occur from excessive tobacco consumption.
- Cannabis use disorder: cannabis is the most commonly used illicit substance worldwide. Intoxication symptoms include euphoria, laughter, lethargy, impaired reaction time, conjunctival injection, and increased appetite. Withdrawal symptoms include irritability, anxiety, insomnia, and decreased appetite. While the withdrawal symptoms of irritability and anxiety are similar in cannabis and tobacco use, appetite is usually increased during withdrawal from tobacco use. Careful history taking of the substance ingested will also help distinguish the diagnosis.