Tobacco and Nicotine: History, Effects, and Addiction - Prof. David W. Pittman, Study notes of Pharmacology

Download Tobacco and Nicotine: History, Effects, and Addiction - Prof. David W. Pittman and more Study notes Pharmacology in PDF only on Docsity! 1 1Tobacco / Nicotine Where are we going today? • Tobacco History & Types of Tobacco • Tobacco Routes of Administration • Nicotine Absorption & Distribution • Metabolism & Excretion • Neurophysiological Effects • Behavioral Effects • Adverse Effects • Tolerance & Withdrawal • Addiction & Treatment 2History of Tobacco • Originated in the Americas • Brought to Europe – Spain & France 1500’s • 1559: Jean Nicot – introduced snuff to the royalty of France – popularization • 1809 – nicotine named as active ingredient • 1604 – King James I – anticipated the adverse health effects of smoking tobacco • Very popular in England despite King’s Taxes and cost of import from Spain 3Tobacco – a CA$H crop • 1616 – John Rolfe in Virginia colony grew Spanish tobacco seeds with great success • Supply and Demand = $MONEY$ – governmental taxes of tobacco became an integral source of revenue in early 1600’s • Continued popularity until the 1960’s when the harmful effects of tobacco became public 4Tobacco – a drug? • Nicotine is unregulated by the FDA • FDA –defines drug as intended to affect a structure or function of the body or used as a treatment, cure, or disease prevention 5Administration – Oral (Transdermal) • Tobacco chewed in the mouth – nicotine absorbed transdermally into blood stream – rarely consumed through digestive system – nicotine = highly toxic poison • produces nausea & vomiting • metabolized fast in the liver – 1st pass metabolism cuts down on nicotine entering blood supply when digested • Differences in curing process manipulated the pH of tobacco for better absorption in mouth! 6Types of Tobacco • Chewing tobacco – cured: air-cured dark – pH: 8 = < 50% ionization • Pipe & Cigar tobacco – drying process: air-cured light – pH: 8.5 = < 50% ionization • Cigarette tobacco – drying process: flue-cured or bright – pH: 5.3 = close to 100% ionized – why? 2 7Administration - Inhalation • Snuff – fine powder absorbed through the nasal mucus membrane (stomach / lungs) TRANSDERMAL • Smoke – vaporized nicotine dissolves in the mucus membrane of the lungs into the blood – similar to administration of anesthesia – ammonia or other additives can facilitate nicotine release and absorption 8Administration - Inhalation • Nicotine from lungs to heart → brain • Rapid effect • Chemicals in smoke are different – drug cannot be exhaled • Large dose per puff – little metabolism 9Administration - Inhalation • Rapid absorption in the lungs – Amount of nicotine absorption per cigarette influenced by the number of puffs from a cigarette – 0.3 mg to 3.2 mg (8-9 mg cigarette) – Duration of smoke in lungs plays little role increasing nicotine absorption – CHAIN SMOKING 10Rates of Absorption • Comparison of absorption rates per admin. Route • Exposure time and rate 11Blood Concentration • Remember this during treatment section • Effectiveness of administration route on blood concentration 12Distribution • Route of administration effects distribution • Inhalation = increased concentration in brain • Transdermal = more equal distribution through blood stream • After 30 minutes: – higher concentrations of nicotine in the salivary glands and stomach due to pH – higher concentrations of nicotine in the kidneys and liver due to metabolism 5 25Adverse Effects • Heart Disease – 200,000 (noncancer) • Lung Disease – 82,000 (noncancer) • Cancer – 115,000 (lung) & 30,000 (nonlung) • -14 minutes per cigarette & 50 million US 26Cardiovascular Effects • Carotid artery wall thickness • N: nonsmoker • P: past smoker • C: current smoker • +E: environmental exposure • -E: environmental exposure 27Heart Disease - multiple effects 28Lung Disease – 70% related • Ash and tars are deposited on the lung tissue • 2 mechanisms of removal – cilia agitate pollutants until coughed out – phagocytes surround and destroy particles • Both systems become compromised in chronic smoking – partially reversible – susceptible to bacteria and viruses – chronic bronchitis – emphysema: irreversible lung damage 57k 29Cancer – 112,000 US deaths • Nicotine is not a carcinogenic but the other components of tobacco and smoke are! • Benzo[a]pyrene 20-30 ng per cigarette is one of the most potent mutagens and carcinogens • Metabolized to BPDE = ultimate carcinogen • BPDE damages a cancer suppression gene resulting in mutagensis of cells in lung tissue • Not just lung cancer - mouth, voice box, throat • >50% 10K bladder cancer & two-fold increase in uterine cervix cancer How much? How long? 30Reproductive Effects • Nicotine crosses the placental barrier and is excreted in lactation • Prenatal exposure slows cognitive development – seen as late as 7 years old • Both low level of oxygen and chemical concentrations (nicotine) in the blood 6 31Tolerance • Little evidence of tolerance – compensatory mechanisms that become activated • Increased rate of metabolism by liver – upregulation of enzymes that produce cotinine & nicotine-l’-N-oxide metabolites Changes with increased use (not tolerance) • Learning of administration patterns to maintain blood levels of nicotine and compensate for differential nicotine levels 32 Withdrawal - Acute & Chronic • Both physical and psychologically severe • Heroin users report smoking withdrawal worse Symptoms: • Decreased cardiovascular functioning • Increased appetite / lowered cognitive function • Increased negative mood – anxiety, anger, aggression, and depression • Disrupted sleep patterns – REM increase • Duration ≈ 1 month, 25% smokers ≈ 6 months • 2 components physiological & behavioral 33Treatment Options • Psychological compulsion – very severe – only 1 of 10 successfully quit – 2/3 of smokers want to quit & 80% regret • Behavioral replacement – denicotinized cigarette / other oral behavior (eating) • Physiological replacement – nicotine admin. – Nicotine Nasal Spray – fastest, most similar but uncomfortable application – Transdermal Nicotine patch – Nicotine Gum 34Treatment - Effectiveness • Nicotine Gum • Slow onset and difficult to maintain adequate dose • Oral administration • 20-30 pieces = ½ dose • Patch – no behavioral component but constant effective doses 35Treatment Success Rates • Combination therapies are most successful • Patch and Gum or Patch and Drug Wellbutrin aka Zyban (antidepressant) 36 ON THURSDAY: E-mail me or bring questions