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Pharmacology of Nicotine

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Pharmacology of Nicotine. Colleen Miller. Lesley-Ann Giddings. What is nicotine? plant alkaloid ... http://www.biomedcentral.com/1472-6807/2/1. Releases ACh, ... – PowerPoint PPT presentation

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Title: Pharmacology of Nicotine


1
Pharmacology of Nicotine
  • Colleen Miller
  • Lesley-Ann Giddings

2
What is nicotine?
  • plant alkaloid
  • derived from nicotinic acid

http//www.scs.leeds.ac.uk/cgi-bin/pfaf/arr_html?N
icotianatabacum
3
How does nicotine act on receptors?
  • nicotinic acetylcholine
  • receptors
  • mimics acetylcholine
  • (agonist)
  • opens ion channel
  • depolarizes

4
Nicotine and Acetylcholine
http//www.biomedcentral.com/1472-6807/2/1
5
  • Releases ACh, NE, DA, S, glutamate, and GABA

6
Effects of Nicotine
Positive Anxiolysis Cognitive Enhancement Cerebro
-vasodilation Neuroprotection Analgesia Anti-psych
otic
Negative Gastrointestinal Distress Hypothermia Em
esis Hypertension Seizures Respiratory Distress
7
Nicotine Administration
  • Inhalation
  • Cigarettes (1.0 mg)
  • Inhaler
  • Nasal
  • Nasal spray
  • Oral
  • Gum
  • Lozenges
  • Tablets
  • Transdermal
  • Patch

8
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

9
Pharmacokinetics
  • Inhalation of nicotine is the most addictive

10
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

11
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

12
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
13
Buccal Absorption
  • Absorbed in small intestine
  • Carried to blood
  • Undergoes pre-systemic metabolism by liver
  • 30-40 bioavailability

14
Elimination
  • First order
  • Half-life averages 2 hours
  • Metabolized in liver, lung and kidney

15
How is nicotine eliminated?
  • P-450 and aldehyde oxidase enzymes in liver

16
Therapeutic Opportunities
  • Cognitive Dysfunction/ Attention Disorders
  • Neurodegenerative disorders (Alzheimers,
    Parkinsons)
  • Pain
  • Schizophrenia
  • Depression

17
  • Epilepsy
  • Tourettes Syndrome
  • ADHD
  • Anxiety
  • Vestibular Function
  • Gastric Disorders

18
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
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