1. A Small Dose of Nicotine – 2/23/04 An Introduction To The Health Effects of Nicotine A Small Dose of Nicotine Mayan priest in Central America, 1000 B.C.

2. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology N CH 3 N What Is This?

3. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology N CH 3 N Nicotine

4. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology Question Have you every tried nicotine? What were the immediate effects?

5. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology  2,000 years ago (maybe 6,000) - natives of the Americas used tobacco as a medicine, in religious ceremonies, and as offerings to spirits.  1492 - Christopher Columbus introduce tobacco and nicotine to Spain Historical Awareness

6. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology  1612 - British colony at Jamestown, Virginia, exporting tobacco to England – became an essential source of money  1700-1800’s - Farms used slaves to cultivate tobacco Historical Awareness

7. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology 1614 – Cigarettes were invented by beggars in Seville, Spain (from scrap of cigars) 1763 – Nicotine used as an insecticide 1828 – Nicotine isolated from tobacco leaves 1850s – Cigarettes increased in popularity 1880 – Machine to roll cigarettes patented (10,000 per hour) – cigarettes get cheaper Historical Events

8. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology Quote - Quitting “To cease smoking is the easiest thing I ever did. I ought to know, I've done it a thousand times." Mark Twain

9. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology Sir Walter Raleigh Sir Walter Raleigh popularized pipe smoking in England. He was beheaded on October 28, 1618 but before his head dropped he requested to smoke a final bowl full of tobacco.

10. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology 1964 – U.S. surgeon general linked cigarette smoking with lung cancer and coronary artery disease. 1996? – FDA finds that nicotine is addictive 1999? – US Supreme Court rules that FDA can not regulate nicotine 2000? – Tobacco companies required to pay billions to compensate for health effects 2000 – World wide tobacco consumption continues to increase Modern Events

11. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology Tobacco CEOs

12. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology  Nicotine in a cigarette – 8 to 10 mg  Smoking – delivers about 1 mg to the smoker  Technique of smoker can increase nicotine (time smoke is in lungs, rapid puffing) Smoking

13. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology  Lung (nicotine enters brain in 7 seconds)  Skin (slower absorption, more constant blood levels)  Stomach poor (nicotine is strong base – stomach is acid)  Intestine better Nicotine Absorption

14. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology  Acute nicotine exposure (From – insecticide sprays or tobacco) Nausea, vomiting, salivation, diarrhea, dizziness, mental confusion, weakness  Fatal exposure (60 mg fatal for adult) Decreased blood pressure, difficulty breathing, irregular pulse, convulsions, respiratory failure and death Acute Adverse Effects

15. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology Fetal Effects  Chronic nicotine exposure to developing fetus  Decreased birth weight  Attention deficit disorder  Cognitive impairment

16. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology Withdrawal Effects  Restlessness  Anxiety, hostility  Irritability, impatience  Difficulty concentrating  Increased appetite (weight gain)  Depression

17. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology  Cotinine - Major metabolite  Lung – First site of metabolism  Liver – Major site  Half-life – about 2 hours Metabolism

18. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology  Nicotine and metabolites  Primarily in urine  Breast milk (heavy smoker 0.5 mg per liter of milk (infant is small = large dose)  Insurance companies look for cotinine (longer half-life) Excretion

19. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology  Low dose – Stimulation Binds nicotinic receptors (cholinergic)  High dose – Blocks receptors Mechanism Of Action

20. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology Mechanism Of Action

21. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology Nicotine as Insecticide Mimics the action of acetylcholine  Muscle tremor  Convulsions  Death (respiratory paralysis)

22. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology  Don’t use tobacco  Handle nicotine insecticides carefully Reducing Exposure

23. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology  Addiction to nicotine  Gum recession  Sores in the mouth  Cancer of the mouth  Increased blood pressure  Heart disease  Ulcers  Generally not good Smokeless Tobacco & Health

24. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology  In the U.S.  Sales - 112.2 million pounds sold in 2001  Revenues - $2.13 billion in 2001  Advertising $236.7 million in 2001 U.S. Federal Trade Commission – Smokeless Tobacco Report for the years 2000 to 2001 Smokeless Tobacco & Money

25. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology March 22, 2000 The United States Supreme Court ruled in a 5-4 decision that the U.S. Food and Drug Administration (FDA) cannot regulate tobacco products. Regulatory Status

26. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology Nicotine is toxic and addictive Don’t Start Summary

27. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology A Small Dose of Nicotine Questions or Comments?

28. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology Additional Information  Web Sites World Health Organization (WHO). Online. (accessed: 2 April 2003). Covers tobacco and international efforts to track and reduce use of tobacco. Health Canada - Tobacco (CDC). Online. (accessed: 9 April 2003). Heath Canada information on the health effects of tobacco.

29. A Small Dose of Nicotine – 2/23/04 A Small Dose of Toxicology Authorship Information For Additional Information Contact Steven G. Gilbert, PhD, DABT E-mail: smdose@asmalldoseof.org Web: www.asmalldoseof.org This presentation is supplement to “A Small Dose of Toxicology”