1. A Small Dose of Nicotine – 05/01/10 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 Toxicology A Small Dose of Nicotine – 05/01/10 N CH 3 N What Is This?

3. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10 What Is This?

4. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10 N CH 3 N Nicotine

5. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10 Question Have you every tried nicotine? What were the immediate effects?

6. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10  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

7. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10  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

8. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10 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

9. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10 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

10. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10 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.

11. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10 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

12. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10 Tobacco CEOs

13. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10  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

14. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10  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

15. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10  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

16. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10 Fetal Effects  Chronic nicotine exposure to developing fetus  Decreased birth weight  Attention deficit disorder  Cognitive impairment

17. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10 Withdrawal Effects  Restlessness  Anxiety, hostility  Irritability, impatience  Difficulty concentrating  Increased appetite (weight gain)  Depression

18. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10  Cotinine - Major metabolite  Lung – First site of metabolism  Liver – Major site  Half-life – about 2 hours Metabolism

19. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10  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

20. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10  Low dose – Stimulation Binds nicotinic receptors (cholinergic)  High dose – Blocks receptors Mechanism Of Action

21. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10 Mechanism Of Action

22. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10 Nicotine as Insecticide Mimics the action of acetylcholine  Muscle tremor  Convulsions  Death (respiratory paralysis)

23. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10  Don’t use tobacco  Handle nicotine insecticides carefully Reducing Exposure

24. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10  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

25. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10  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

26. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10 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

27. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10 Nicotine is toxic and addictive Don’t Start Summary

28. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10 A Small Dose of Nicotine Questions or Comments?

29. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10 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.

30. A Small Dose of Toxicology A Small Dose of Nicotine – 05/01/10 Authorship Information For Additional Information Contact Steven G. Gilbert, PhD, DABT E-mail: sgilbert@innd.org Web: www.asmalldoseof.org This presentation is supplement to “A Small Dose of Toxicology”