NicotineChapter 7

History of Tobacco History of Tobacco &

Nicotine• 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

History of Tobacco 1560 - Marked as 1st yr

tobacco officially introduced to Europe

Proponents of tobacco• Sir Francis Drake• Sir Walter Raleigh

– Led to the fashionability of pipe smoking of tobacco

History of Tobacco

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)

History of Tobacco

By 17th century

• Tobacco here 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

History of Tobacco

• 1828 - Nicotine was isolated

• Cigarettes first appeared in 1850s, but chewing still more popular

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

Tobacco Use in 20th Century

Future favored cigarettes over other 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

• Also cigarettes in WWI

Tobacco & Nicotine In US• 1890s - 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

• 1986 - Surgeon General's report on passive smoking

• Use continued to decline over past twenty years• 2000 – Worldwide consumption still on increase

Nicotine Forms

• Tobacco– Smokeable

• Cigarette• Pipe• Cigar

– Leaf (Chewing)– Leaf (Dip)– Snuff (powdered)

• Transdermal Patch

Snuff

• Grind tobacco into fine powder

• Pinch into nose & exhale with sneeze (cleared head of “superfluous humours”)

• 1700s – snuff overtook smoking as method of choice– Started in France & spread through rest of

Europe

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)

Cigar Smoking

• Tight rolls of tobacco leaves

• Flue-curing - process of heating tobacco leaves– to cure them, makes milder smoke

• Also new type of leaf– North Carolina #1 tobacco-growing center

• Mixed effects of chewing with ingestion of smoke

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 EuropeU.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

Cigarettes

1881 - James Bonsack patented cigarette-making machine

• Made cigarettes even more low-cost

• Revolutionized tobacco industry

- From 300 cigarettes per hour by hand to 3 machines producing 200 cigarettes per minute

Cigarette Smoking

Nicotine in a cigarette – 8 to 10 mg

Smoking – delivers about 1-3 mg to the smoker

Technique of smoker can increase nicotine (time smoke is in lungs, rapid puffing)

Nicotine Pharmacology• Biphasic action- nicotinic

acetylcholine receptors– Agonist – low doses – Antagonist – high doses

• Although a stimulant, it is often used to relax

• Works in CNS and PNS• One of the most toxic

dependence-producing psychoactive compounds overall– Nicotine acts to stimulate

dopamine release in mesolimbic dopamine pathway (reward center).

Nicotine Pharmacology

• One of most powerful poisons ingested by Americans

– LD50 60 mg

• Can't happen via inhalation

• Orally, two protections against death

1. quick first pass metabolism through liver

2. activation of vomiting center

Peripheral Effects

• A sympathomimetic– Increases heart rate, blood pressure,

respiration

• A parasympathomimetic– Increases smooth muscle (GI tract)

activity– Increases HCL production in stomach

Central Effects

• Arousal• Improves vigilance & rapid information

processing• Improves mental performance &

memory• Stimulates adrenalin and ADH release• Nicotine may reverse some deficits

caused by alcohol

Biotransformation/Excretion

• Broken down by lung and liver– >90% in liver

• Metabolization of nicotine and other toxins in cigarette smoking lowers blood levels of many important drugs.

• Excreted through kidneys (urine)• Lungs do some excretion

Tolerance• Develops rapidly

– Within the first exposure for some effects• Area Postrema

– Can build up and dissipate over the course of a day

– Chronic tolerance happens as well

• Dispositional Tolerance– Some smokers clear nicotine faster

Dependence

• 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

Withdrawal Symptomsof Nicotine

• Lethargy, decreased arousal

• Constipation

• Headaches

• Disrupted sleep cycles

• Irritability/anxiety

• Excessive hunger (blood sugar drop)

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

Compounds in Tobacco

Carbon Monoxide

• Odorless & tasteless, but extremely toxic

• Attaches to hemoglobin– Hemoglobin has greater affinity for CO than

oxygen• Accumulation of CO occurs• Leads to asphyxiation of body

Health Effects of Nicotine Addiction

• Cardiovascular Disease– Most likely killer

• Cancer– Approx 90% of all lung cancer

• Chronic Obstructive Pulmonary Disease– All long-term smokers get some level

of COPD– Emphysema most serious

Approaches to Treatment

• Self-help

• Behavioral intervention

• Pharmacotherapy

• Combined strategies

Nicotine Replacement

• Nicotine gum

• Transdermal nicotine

• Nicotine aerosols

Pharmacotherapy

• Clonidine

• SSRIs

• Zyban

Quitting Overall

• Combination of strategies works best

• Behavioral + replacement + pharmacotherapy

• Quitting reduces risk of all-cause mortality among other diseases

• Risk of lung cancer remains elevated but drops significantly