Pharmacology of Nicotine

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Pharmacology of Nicotine

• Colleen Miller
• Lesley-Ann Giddings

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What is nicotine?

• plant alkaloid
• derived from nicotinic acid

http//www.scs.leeds.ac.uk/cgi-bin/pfaf/arr_html?N
icotianatabacum
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How does nicotine act on receptors?

• nicotinic acetylcholine
• receptors
• mimics acetylcholine
• (agonist)
• opens ion channel
• depolarizes

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Nicotine and Acetylcholine
http//www.biomedcentral.com/1472-6807/2/1
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• Releases ACh, NE, DA, S, glutamate, and GABA

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Effects of Nicotine
Positive Anxiolysis Cognitive Enhancement Cerebro
-vasodilation Neuroprotection Analgesia Anti-psych
otic
Negative Gastrointestinal Distress Hypothermia Em
esis Hypertension Seizures Respiratory Distress
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Nicotine Administration

• Inhalation
• Cigarettes (1.0 mg)
• Inhaler
• Nasal
• Nasal spray
• Oral
• Gum
• Lozenges
• Tablets
• Transdermal
• Patch

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Chemistry of Nicotine

• basic compound
• water soluble
• lipophilic
• environments
• no absorption in acidic environments
• functions at blood pH 7.4 (31)
• absorption occurs readily in basic environments

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Pharmacokinetics

• Inhalation of nicotine is the most addictive

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Addiction via smoking

• cigarettes have additives that cause addiction
• sensory cues (heat, sight, and smell)
• smokers have greater number of nicotinic
  receptors
• inhalation from cigarettes causes nicotine to
  cross blood brain barrier more rapidly

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Nicotine absorption from cigarettes

• Readily absorbed through oral and nasal mucous
  membrane
• basic pipe or cigar smoke leads to rapid
  increases in nicotine without inhalation
• flue-cured cigarettes are acidic
• little buccal absorption
• need to absorb nicotine through inhalation

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Absorption through Inhalation

• absorption through the surface of alveolar
  capillary interface
• absorption into the pulmonary capillary blood
  flow
• circulates throughout entire blood volume

http//sln.fi.edu/biosci/systems/pulmonary.html
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Buccal Absorption

• Absorbed in small intestine
• Carried to blood
• Undergoes pre-systemic metabolism by liver
• 30-40 bioavailability

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Elimination

• First order
• Half-life averages 2 hours
• Metabolized in liver, lung and kidney

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How is nicotine eliminated?

• P-450 and aldehyde oxidase enzymes in liver

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Therapeutic Opportunities

• Cognitive Dysfunction/ Attention Disorders
• Neurodegenerative disorders (Alzheimers,
  Parkinsons)
• Pain
• Schizophrenia
• Depression

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• Epilepsy
• Tourettes Syndrome
• ADHD
• Anxiety
• Vestibular Function
• Gastric Disorders

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And the take home message is

• The pharmacokinetics are important for
  determining addictive potential of nicotine
• Inhalation of nicotine is the most addictive form
  of uptake
• There are many therapeutic opportunities to be
  developed