Pharmacology of Nicotine Colleen Miller Lesley-Ann Giddings Downloaded from

What is nicotine? plant alkaloid derived from nicotinic acid Downloaded from

How does nicotine act on receptors? nicotinic acetylcholine receptors mimics acetylcholine (agonist) opens ion channel –depolarizes Downloaded from

Nicotine and Acetylcholine Downloaded from

Releases ACh, NE, DA, S, glutamate, and GABA Downloaded from

Effects of Nicotine Positive: Anxiolysis Cognitive Enhancement Cerebro-vasodilation Neuroprotection Analgesia Anti-psychotic Negative: Gastrointestinal Distress Hypothermia Emesis Hypertension Seizures Respiratory Distress Downloaded from

Nicotine Administration Inhalation –Cigarettes (~1.0 mg) –Inhaler Nasal –Nasal spray Oral –Gum –Lozenges –Tablets Transdermal –Patch Downloaded from

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 Downloaded from

Pharmacokinetics Inhalation of nicotine is the most addictive Downloaded from

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 Downloaded from

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 Downloaded from

Absorption through Inhalation absorption through the surface of alveolar capillary interface absorption into the pulmonary capillary blood flow circulates throughout entire blood volume Downloaded from

Buccal Absorption Absorbed in small intestine Carried to blood Undergoes pre- systemic metabolism by liver 30-40% bioavailability Downloaded from

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

How is nicotine eliminated? P-450 and aldehyde oxidase enzymes in liver Downloaded from

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

Epilepsy Tourette’s Syndrome ADHD Anxiety Vestibular Function Gastric Disorders Downloaded from

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 Downloaded from