• Nicotine is highly addictive substance: Essentially it signals via the central nicotinic receptors in the ventral tegmental area --> nucleus accumbens --> prefrontal cortex via dopamine release, crucial in reward pathways
• Therefore tobacco uses aim to maintain steady state of nicotine concentration in blood - prevent withdrawal, maintain pleasure/ arousal/ modulate mood
• Users self titrate by taking more frequent ciggs/ smoke more intensely (deeper breaths)
• A 2 pronged problem - should therefore look at both these aspects
  • Physiological effects of nicotine on reward pathways
  • Behavioural aspects of addiction --> behavioural therapies
• Pharmacological treatment
  • NRT
  • partial nicotine receptor agonists
    • varenicline
    • cytisine
  • psychotropics
    • sustained release bupropion
• Information regarding trials in smoking cessation
  • patients recruited tend to be more motivated, cognitive therapy tends to be more intensive
  • Drug treatment only trialled for 12 weeks, but dependency is a chronic disease
• Note in patients who are <50, smoking is often the only and most important risk factor, with similar prevalence between gender

• It is often thought that NRT is contraindicated after a myocardial infarction
  • patients with cardiovascular disease were often excluded in the efficacy trials
  • From retrospective reviews, NRT does not appear to elicit cardiovascular events in healthy patients, increase risk of first MI or increase 1 year mortality in ACS patients
  • Bupropion is well tolerated and safe in ACS patients - there is one small study in outpatients that yielded positive results
  • With respect to varenicline, there was a study of 714 patients with stable cardiovascular disease that yielded positive results. verenicline did not increase cardiovascular mortality or all-cause mortality but some cardiovascular events were more common
• In terms of neuropsychatric effects - see EAGLES trial published in LANCET 2016. 
  • Essentially trial was done because neuropsychiatric effects were generalised from post marketing data, observational studies and patients with neuropsychiatric comorbidities were excluded from the study
  • There was no increased mod-severe neuropsychiatric effect in either of NRT/ varenicline/ buproprion in people with or without a past/ present history of psychiatric comorbidity. 
  • There was NO increase in suicidal ideation or behaviour
  • This study recruited patients who were STABLE and not unstable
  • Buproprion does have medication interactions and can lower the seizure threshold