Nicotine & Metabolites

Diagnosis

Indications for Testing

• Document tobacco use (to assess compliance with smoking cessation programs and to qualify for certain medical procedures)

Laboratory Testing

• Urine testing recommended over serum/plasma to detect chronic use
  • Nicotine is metabolized into several compounds that are measurable in urine and serum; analytes are detectable in urine over a longer period of time to differentiate patient as the following
    • Active user
    • Abstinent >2 weeks
    • Passively exposed
    • Unexposed nonuser
  • Anabasine in urine indicates patient is actively using a tobacco product
    • Anabasine is not expected in nicotine replacement products
• Serum/plasma testing is required when a valid urine specimen cannot be obtained (anuretic or dialysis patient) or to detect recent use (within past 2 weeks)

Monitoring

Pharmacogenetics and Therapeutic Drug Monitoring

• Nicotine is extensively metabolized in the liver into the following
  • Cotinine – represents 70-80% of metabolized nicotine
    • Mediated by cytochrome P450 system (mainly CYP2A6 and CYP2B6)
  • Trans-3'-hydroxycotinine – a metabolite of cotinine
  • Nornicotine – a metabolite of nicotine
  • Anabasine – minor tobacco alkaloid
    • Check compliance with nicotine replacement therapy
      • Presence of anabasine suggests recent tobacco use or exposure
      • Absenceof anabasine is not definitive evidence that tobacco was not used because anabasine concentrations are expected to vary with tobacco preparations
• Plasma half life for nicotine is 0.4-1.5 hours; estimated detection window in urine is 3 days for nicotine and 1 week for cotinine

Clinical Background

Use of tobacco products, particularly smoking, is a leading but preventable cause of disease, disability and death.

Epidemiology

• Prevalence – 15-20% of adults are nicotine dependent
• Sex – M>F

Pathophysiology

• Nicotine is found in a variety of plants
• Principle source of exposure – tobacco products or nicotine replacement therapy
• Extensively metabolized by the liver
• Absorbed through oral cavity, skin, urinary tract and gastrointestinal tract
• Increases heart rate, blood pressure, mobilization of blood sugars and catecholamines

Clinical Presentation

• Cancers – lung, larynx, oral and nasal cavity, paranasal sinuses, esophagus, pancreas, liver, stomach, cervix, leukemia (AML, CML, CLL)
• Cardiac and neurologic disease – leading cause of coronary disease, stroke
• Pulmonary disease – chronic obstructive pulmonary disease (includes chronic bronchitis and emphysema), asthma, respiratory infections, overall decrease in pulmonary function
• Pregnancy – difficulty in conceiving, intrauterine growth retardation, low birth weight
• Second-hand smoke – a confirmed human carcinogen implicated in pulmonary disease, lung cancer and coronary artery disease in non-smokers

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory