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Nicotine

Nicotine. Chapter 7. History of Tobacco . Smoking practiced among the early Mayas, probably in the district of Tabasco, Mexico, as part of their religious ceremonies 86-161 AD Europeans’ first exposure from Columbus 1492. Exposure was not widespread. Tobacco was not well thought of at first.

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Nicotine

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  1. Nicotine Chapter 7

  2. History of Tobacco • Smoking practiced among the early Mayas, probably in the district of Tabasco, Mexico, as part of their religious ceremonies 86-161 AD • Europeans’ first exposure from Columbus 1492. Exposure was not widespread. Tobacco was not well thought of at first

  3. History of Tobacco 1560 - tobacco introduced to Europe Proponents of tobacco • Sir Francis Drake • Sir Walter Raleigh • Led to the fashionability of pipe smoking of tobacco

  4. History of Tobacco- not completely accepted in Europe King James I of England • 1604 - Pamphlet condemning tobacco • “bewitching of tobacco” Early 1700s Russia • “Westernization” of people • penalties for smoking (torture, Siberian exile, death)

  5. History of Tobacco- However…. By late 17th century • Tobacco in Europe to stay • In Western Europe, used as treatment for migraines • Japan & China stop enforcing prohibition of use • Russia opens door to West • Sultan of Turkey begins to smoke

  6. Tobacco & Nicotine In US • In U.S., tobacco became major commodity in early 1600s, used as currency • Financed Revolutionary War • Ben Franklin promised Virginia's tobacco to France • Had it not been for tobacco, no French assistance & no USA

  7. U.S. Tobacco Use in 20th Century Changing trends….cigarettes over other forms/usage • New emphasis on social manners • Public health issues of infectious disease • decrease in chewing except in small rural towns of U.S. • Women began smoking • But, 1904 NYC woman arrested for smoking in public • 1920s - “reach for a Lucky instead of a sweet” • Promoted weight loss effects • -cigarettes in WWI

  8. Tobacco & Nicotine In US-Negative reactions • 1890s - report no medicinal value for nicotine • dropped from U.S. pharmacopia • 1925 - 14 states banned smoking • 1938 - study linking cigarettes & lung cancer • 1954 - more stats relating smoking to lung cancer & cardiovascular disease • 1964 - first Surgeon General's report • advised smoking shortens life expectancy • 1988 - Surgeon General's report on smoking • Use declined • 2000 – Worldwide consumption on increase

  9. Nicotine Forms • Tobacco-Nicotiana tabacum • (&Nicotiana rustica) Smokeable • Cigarette • Pipe • Cigar • Leaf (Chewing) • Leaf (Dip) • Snuff (powdered) • Transdermal Patch…others

  10. Snuff • fine tobacco powder • European style- Pinch into nose & exhale with sneeze (cleared head of “superfluous humours”) • 1700s Europe– snuff overtook smoking as method of choice • Started in France & spread through rest of Europe

  11. Snuff Tobacco

  12. Chewing In U.S., snuffing replaced by chewing • Freed hands for working • Low cost - democratic custom all could have • “spitting” seen as nasty habit, also health issue • Major cause of spread of infectious disease (TB)

  13. “Chew”

  14. Cigar Smoking • Tight rolls of tobacco leaves • Flue-curing - process of heating tobacco leaves • changes their ph to alkaline.. increases absorption through mucous membranes of the mouth .

  15. Cigar puffing

  16. Pipe Smoking

  17. Modern alternate forms/ routes of administration

  18. And of course Cigarettes

  19. Cigarettes • Rolls of shredded tobacco wrapped in paper • 1614 – Invented by beggars in Seville, Spain from scrap of cigars • 1856 - Became popular with English soldiers in Crimean War - Spread throughout Europe U.S, not inclined to use it • Public image • Rumors of opium, arsenic laced paper, & camel dung, • Also image: cigarette - dainty & “sissy” vs. cigars - fat, long & dark

  20. Cigarettes 1881 - James Bonsack patented cigarette-making machine • Revolutionized tobacco industry • From 300 cigarettes per hour by hand to 3 machines producing 200 cigarettes per minute

  21. Cigarette Smoking Nicotine in a cigarette – about 7 mg Smoking – delivers about 1-3 mg to the smoker about 0.7 ug/puff Technique of smoker can increase nicotine (time smoke is in lungs, rapid puffing)

  22. Pharmacology and Relationship to Smoking • Smoking is quickest and most efficient way to get nicotine to the brain • Reinforcing effects are strongest • As nicotine blood levels fall, another puff is taken • Smokers may typically take about 20 puffs/cigg • Delivering in total about 13ug/kg

  23. Pharmacology Cont’d • Half-life of nicotine is about 2 hours • Metabolized mostly in the liver • Mild withdrawal during overnight and tolerance from previous day partially dissipates • Strong craving and best response in the morning (1st cigarette)

  24. Nicotine testing!

  25. Nicotine Pharmacology • Dose-dependent action- nicotinic acetylcholine receptors • Agonist – low doses • Antagonist – high doses • Although a stimulant, it is often used to relax • State-dependence? • Works in CNS and PNS

  26. Mechanisms of Action • Direct Agonism of Nicotinic cholinergic receptors • Ionotropic type receptors • When binds it opens a Na+ channel and depolarizes the cell membrane • May produce a secondary “Functional antagonism”

  27. Initial agonism may be followed by desensitization of the nicotinic ACH receptor

  28. Nicotine affects nicotinic Acetylcholine receptors at the autonomic ganglia and the NMJ to produce peripheral effects

  29. Peripheral Effects • A sympathomimetic- Adrenal glands release epinephrine and norepinephrine • Increases heart rate, blood pressure, respiration • A parasympathomimetic • Increases smooth muscle (GI tract) activity • Increases HCL production in stomach/nausea • Chronic diarrhea, Colitis • Body weight- appetite suppression, increased metabolic rates

  30. Nicotine Pharmacology- High concentrations of nicotine binding in: • cerebral cortex • Thalamus • locus coeruleus • Hippocampus • Cerebellum • Striatum • substantianigra Enhanced sensory and cognitive processes Disequilibrium, motor incoordination, dizziness Effects on Motor Performance

  31. High concentrations of nicotine binding in: • Raphe Nucleus • VTA Mood/reward

  32. Nicotine Binding in the Rat brain

  33. Central Effects • Arousal • Improves vigilance & rapid information processing • Improves mental performance & memory • Improved motor steadiness • Stress Reduction • Reward?

  34. Tolerance- to nausea, equilibrium and motor coordination effects • Develops rapidly • Within the first exposure for some effects • Can build up and dissipate over the course of a day • Chronic tolerance happens as well • Dispositional Tolerance • Some smokers clear nicotine faster

  35. Is Nicotine Addictive? • Self-administration- Corrigal, 1989 • Rats, mice, dogs and primates • Adolescent v. adult exposure

  36. Dependence- most people currently think that: • One of the most dependence-producing drugs • Pharmacology – Stimulates reward center influences ANS • Function – Weight control, coping with negative affect/stress, cognitive enhancement • Social Factors – Friends, habit, context

  37. Reinforcing Effects • Mediated by activation of mesolimbic dopamine system • High-affinity nicotinic receptors located in the VTA stimulate the firing of dopaminergic neurons, which causes increased DA release in the NA

  38. Is Nicotine Addictive?

  39. ??Physical Withdrawal Symptomsof Nicotine • irritability • impatience • hostility • anxiety • depressed mood • difficulty in concentrating • restlessness • decreased heart rate • increased appetite or weight gain

  40. Is Nicotine Addictive… Revisited

  41. Nicotine Is a Toxic Substance • 60 mg • Nicotine poisoning • Accidental swallowing • Excessive absorption • Exposure to pure nicotine • Symptoms • CNS effects: headache, dizziness, insomnia, abnormal dreams, nervousnessgastrointestinal (GI) distress: dry mouth, nausea, vomiting, dyspepsia, diarrhoeamusculoskeletal symptoms: arthralgias ( joint pain) , myalgia (muscle pain).

  42. Health Effects of Nicotine Addiction • Statistically higher Probability in smokers: • Cardiovascular Disease • Most likely killer • Cancer; esp lung cancer • Chronic Obstructive Pulmonary Disease

  43. Health Effects of Tobacco use-Compounds in Tobacco • Tar - sticky substance • Amount varies from 12 - 16mg to 6mg • Last 3rd of cigarette contains 50% of tar (final puffs more hazardous) • Prevents cilia from working, decreases cilia escalator • Increases carcinogens compounds to settle on tissue rather than being expelled

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