SMOKING AND HEALTH SMOKING IS THE MAIN SINGLE PREVENTABLE FACTOR, ALL FORMS OF TOBACCO ARE ADDICTIVE AND LETHAL TYPES OF TOBACCO PRODUCTS • CIGARETTES, PIPES, CIGARS • BIDIS, KRETEKS, STICS • WATER PIPES, e-CIGARETTES • SMOKELESS: SNUFS (MOIST, DRY), CHEWING TOBACCO USING TOBACCO HAS: • IMMEDIATE EFFECTS • MIDLE- TERM EFFECTS • LONG-TERM EFFECTS • ON HUMAN HEALTH * IMMEDIATE EFFECTS • ACTIVATION OF BRAIN RECEPTORS • CARDIOVASCULAR CHANGES • HYPOXEMIA • IRRITATION NICOTINE IN BRAIN • NICOTINE REACHES THE BRAIN WITHIN 10-20 SECONDS AFTER THE PUFF, • WITHIN 20-30 MINUTES AFTER TRANSDERMAL TRANSPORT • NICOTINE OCCUPIES THE SPECIFIC CHOLINERGIC RECEPTORS AND INDUCES THEIR ACTIVATION ACETYLCHOLINE RECEPTORS - nAChRs • TWO UNITES: ALPHA, BETA • SEVERAL SUBUNITES • PRESENT ON NEURAL CELLS (both central and peripheral), and • ON TISSUE CELLS • SOME SUBUNITES ARE NICOTINE SPECIFIC (activated by nicotine) RELEASE OF NEUROTRANSMITTERS: • DOPAMINE • SEROTONINE • ACETYLCHOLINE • EPINEPFRINE, NOREPINEPHRINE, • BETA-ENDORPHINE • ACTH, ADRENALINE EFFECTS OF NICOTINE • WELL BEEING (DOPAMINE) • COPING THE STRESS (ACTH) • BETTER SHORT-TERM PERFORMANCE (ACETYLCHOLINE, ADRENALINE) TWO FACES OF TOBACCO COMPANIES • „NICOTINE IS THE ADDICTING AGENT IN CIGARETTES“ Private statement, Brown &Williamson official in 1983 „I BELIEVE THAT NICOTINE IS NOT ADDICTIVE“ Sworn testimory before the US Congress; CEOs of the seven leading tobacco companies in 1994 WHAT IS TRUE? • ALL FORMS OF TOBACCO CAN DEVELOP AN ADDICTION • THE DRUG IS NICOTINE • ITS PATHWAYS AND POWERTY IS SIMILAR AS THOSE OF HEROINE and COCCAINE US.Surgeon General Report, 1988 OFFICIAL STATUS • Dg. F 17: PSYCHOLOGICAL AND BEHAVIORAL DISORDERS CAUSED BY TOBACCO USE International statistic classification of diseases, 10th revision, 1991 SMOKING ADDICTION • 80 – 85% OF CURRENT SMOKERS WILL BE DEPENDENT, SIMILARLY LIKE CURRENT USERS OF HEROINE OR COCCAINE • ABOUT ONE THIRD OF OCCASSIONAL SMOKERS WILL BE DEPENDENT SMOKING IS A DISEASE • DEPENDENCE ON SMOKING IS NOT A LACK OF WILLING OR „BAD HABIT“ BUT • CHRONICAL, PROGRESSIVE AND RELAPSING DISEASE • BOTH PHARMACOLOGICAL AND BEHAVIORAL ADDICTION ALTERED DOPAMINERGIC SYSTEM • PREMATURAL ACTIVATION OF FETAL RECEPTORS • DECREASED AMOUNT OF NEURAL CELLS IN THE BRAIN • SUDDEN INFANT DEATH SYNDROME • IMPAIRED NEURO-PSYCHOLOGICAL DEVELOPMENT • BEHAVIORAL and COGNITIVE PROBLEMS ALTERED SEROTONERGIC SYSTEM • MAJOR PSYCHIATRIC DISORDERS (SCHIZOPHRENIA, DEPRESSION) • 2-3 times HIGHER FREQUENCY OF SUICIDES • SMOKING CAUSES DEPRESSION • DEPRESSION CAUSES SMOKING CARDIOVASCULAR CHANGES • VASOCONSTRICTION: SKIN, CORONARY, BRAIN, ABDOMINAL, VERTEBRAL, PLACENTAL ARTERIES • HIGHER BLOOD PRESSURE • HIGHER HEART RATE • HIGHER HEART VOLUME/MIN • DECREASED SKIN TEMPERATURE MECHANISMS OF ACTION • ACTIVATION OF SYMPATIC NERVOUS SYSTÉM • RELEASE OF SUPRARENAL HORMONES (ADRENALINE, NORADRENALINE) • BY QUICK ADMINISTRATION OF NICOTINE HYPOXEMIA • DECREASED AMOUNT OF BLOOD DUE TO VASOCONSTRICTION (caused by nicotine) • DECREASED AMOUNT OF OXYGEN IN BLOOD (caused by carbon monoxide – COHb) • DECREASED BLOOD-TISSUE TRANSPORT OF OXYGEN (caused by hydrogen cyanid HCN) IN PREGNANCY • LOCAL PLACENTAL NECROSIS (caused byl cadmium Cd) • POWERFULL AFFINITY OF FETAL HEMOGLOBIN TO CARBON MONOXIDE ENHANCES COHb LEVELS BY 25% (fetal x maternal blood) CONSEQUENCES OF HYPOXEMIA and HYPONUTRITION • FETAL GROWTH RETARDATION = FETAL TOBACCO SYNDROME • ALTERATION OF FETAL LUNG DEVELOPMENT • RISK OF PRE-TERM BIRTH • RISK OF INTRAUTERINE DEATH HYPOXEMIA IN ADULTS • HEART ATTACK (IM) • CEREBROVASCULAR ATTACK (STROKE) • WRINKLING, PREMATURE AGEING • IMPAIRED WOUND HEALING • LEG AND HAND PAIN, GANGRENE – PERIPHERAL VASCULAR DISEASE IRRITATION • EYES:excessive tearing, blinking, stinging • NOSE: bad smell, stinging, phlegm • NASOPHARYNX: cough, cold in the chest • STRESS DUE TO DYSCOMFORT * SHORT/MILD-TERM EFFECTS • IMPAIRED IMMUNITY • HORMONAL DYSBALANCE • IMPAIRED BLOOD LIPIDS • IMPAIRED HEMOCOAGULATION • CHRONIC INFLAMMATION IMMUNE SYSTEM • IMPAIRED RESISTANCE TO INFECTION • CONTRIBUTION TO ALLERGIES • INFANTS AND CHILDREN ARE THE MOST VULNERABLE POPULATION • IMPAIRED RESISTANCE TO CANCER (Natural Killers) MALE REPRODUCTION • IMPOTENCE • IMPAIRED SPERMIOGENESIS: deformity, loss of motility, reduced number, aneuploid sperm cells • FETAL MALFORMATIONS • INFERTILITY FEMALE REPRODUCTION • PAINFUL MENSTRUATION • EARLIER MENOPAUSE • INFERTILITY • ECTOPIC PREGNANCY • PLACENTA PRAEVIA • PREMATURE BIRTH • SPONTANEOUS ABORTION OTHERS • HORMONAL DYSBALANCE CONTRIBUTES TO • DIABETES MELLITUS and COMPLICATIONS • OSTEOPOROSIS and • HIP FRACTURES BLOOD LIPIDS • INCREASED LEVELS OF - TOTAL CHOLESTEROL - LDL – CHOLESTEROL - VLDL – CHOLESTEROL • DECREASED LEVELS OF - HDL- CHOLESTEROL HEMOCOAGULATION • ENHANCED ACTIVITY OF THROMBOCYTES and • FACTOR VIII => • ARTERIAL/CORONARY THROMBOSIS SMOKING IS RESPONSIBLE • FOR 25% OF ISCHEMIC HEART D. • FOR 25% OF VASCULAR DISEASES (stroke, Burger d., aneurysma, macular degeneration, cataracts) • FOR EARLIER ATHEROSCLEROSIS • FOR 75% OF CHRONIC OBSTRUCTIVE PULMONAL DISEASE (chr. Bronchitis, emphysema) SMOKING CONTRIBUTES TO • STOMACH AND DUODENAL ULCERS • TEETH LOOSE • GUM DISEASES – GINGIVITIS, PERIODONTITIS • PROGRESSION OF PRESBYACUSIS • PSORIASIS and other skin diseases • TREMOR * LONG-TERM EFFECTS • TOBACCO SMOKE CONTAINS OVER 5.000 CHEMICALS, • 67 OF WHICH ARE KNOWN OR SUSPECTED HUMAN CARCINOGENS CARCINOGENS IN SMOKE • POLYCYCLIC AROMATIC H. (benzo/a/pyrene) • HEAVY METALS (Cd, As) • RADIOACTIVE POLONIUM 210 • INDUSTRIAL CARCINOGENS:betanaphthylamine, 4-aminobiphenyle, benzene, formaldehyde TOBACCO SPECIFIC NITROSAMINES • NNK: 4-(methylnitrosamino)-1-(3-pyridyl)- 1-butanone • NNAL • NNN • And many others SMOKING IS RESPONSIBLE • FOR 90-95% OF ALL LUNG CA • FOR 40-60% OF HEAD/NECK CA • FOR 40-60% OF KIDNEY/BLADDER CA • FOR 30% OF CERVICAL CA • FOR 30% OF GASTRIC/PANCRETIC CA • FOR COLON, LIVER, BREAST CA PATHWAYS: • GENOTOXICITY => INITIATION OF CARCINOGENESIS • METABOLIC ACTIVATION – microsomal enzymes P 450 – HEREDITARY DETERMINATION • EPIGENETIC EFFECTS =>MODULATE CELLULAR FUNCTIONS => TUMOR PROMOTION and PROGRESSION GENOTOXIC CARCINOGENESIS: • INITIATION of DNA MUTAGENIC CHANGES • REPLICATION • PROMOTION • PROGRESSION • METASTASES ROLE of nACh RECEPTORS: • THEIR OVEREXPRESSION INDUCED BY SMOKING => • RELEASE of NEUROTRANSMITTERS, SIGNALISING PATHWAYS and GROWTH FACTORS => • MOLECULAR PATHWAYS ARE PROBABLY THE MOST IMPORTANT CONSEQUENCES: PROMOTION • CELL´S PROLIFERATION • ANTIAPOPTOSIS • PROTEIN SYNTHESIS • MITOCHONDRIA DYSFUNCTION • INCREASING of REPLICATIVE LIFESPAN CONSEQUENCES: PROGRESSION • ANGIOGENESIS • INVASION • METASTASIS EPIGENETIC CARCINOGENIC ACTIVITIES • MEDIATED THROUGH nAChR WERE FOUND FOR: - NICOTINE - NNK - POLYCYCLIC AROMATIC HYDROCARBONS nACh RECEPTORS: • CELL – TYPE – SPECIFIC • MODIFIED BY VARIOUS ENVIRONMENTAL FACTORS • UNDERSTANDING of MOLECULAR MECHANISMS => FUTURE DEVELOPMENT IN CANCER DIAGNOSES/THERAPIES SMOKING KILLS • HALF OF ALL LIFETIME USERS • HALF OF THEM WILL DIE BETWEEN 30-69 YEARS OF AGE • IN THE 20th CENTURY, 100 MILLION PEOPLE DIED FROM TOBACCO USE SMOKING KILLS IN 2000 • 4,8 MIL ANNUAL PREMATURE DEATH • 3,8 MILLION MEN • 1,0 MILLION WOMEN BY 2020 TOBACCO WILL KILL ABOUT • 10 MILLION PEOPLE EVERY YEAR SMOKING KILLS • TOBACCO WILL KILL 1 BILLION = 1 000 000 000 PEOPLE • IN THE 21st CENTURY SMOKING KILLS PHYSICIANS • British Medical Doctors Study (Doll, Lopez, Peto): smokers lost • 5 YEARS OF LIFE - 1951-1971 • 8 YEARS OF LIFE – 1971-1991 • 10 YEARS OF LIFE – 1991-2006 SMOKING KILLS NON- SMOKERS • MAIN STREAM - 800-900o C - 16% O2 - 6,0-6,7 pH • SIDE STREAM - 600o C - 2% O2 - 6,7-7,5 pH DANGER FOR NO-SMOKERS • SECONDHAND SMOKE • ENVIRONMENTAL TOBACCO SMOKE • PASSIVE SMOKING • INVOLUNTARY SMOKING Side stream + smoker´s expiration + chemicals interaction SS : MS - IRRITANTS • ACROLEIN 8 – 15 • FORMALDEHYDE 10 – 15 • AMONIUM 73 • NITROGEN OXIDES 4 – 10 • FORMAMIC ACID 1,5 • NAFTALENE 16 SS : MS - TOXINS • CARBON MONOXIDE 2 – 5 • TOLUENE 6 – 8 • NICOTINE 2,6-3,3 • NICKEL 13 – 30 • POLONIUM 210 1 – 4 • PCDD, PCDF 2 SS : MS - CARCINOGENS • BENZENE 5 – 10 • NITROSAMINES 20 – 100 • 2-NAFTYLAMINE 30 • 4-AMINOBIFENYLE 30 • BENZO/A/PYRENE 2,5 – 3,5 • TAR 1,7 INDOOR CONCENTRATIONS OF NICOTINE • WORK-PLACES 20 ug/m3 • CONFERENCE HALL 40 ug/m3 • RESTAURANTS 26-28 ug/m3 • CARS 40 ug/m3 • HOMES 7-11 ug/m3 • HOSPITALS 0,01- 4 ug/m3 INDOOR CONCENTRATIONS OF NITROSAMINE NNK • BARS 10 – 24 ug/m3 • RESTAURANTS 1 – 3 ug/m3 • TRAINS 5 ug/m3 • CARS 29 ug/m3 • OFFICES 26 ug/m3 • HOMES 2 ug/m3 THIRDHAND SMOKE • NICOTINE + NITRIC ACID + NOX • = > INTERACTIONS = > • NITROSAMINES NNK, NNA, NNN • (mutagenic, carcinogenic) • CONTAMINATION OF CLOTHES, SKIN, CARPETS, FORNITURE for many hours EXPOSURE TO ETS - CHILDREN • UNPLEASANT DYSCOMFORT • IRRITATION • IMPAIRED IMMUNITY • RESPIRATORY INFECTIONS, ALERGY • SIDS • LEUKEMIA, BRAIN TUMORS EXPOSURE TO ETS - ADULTS • UNPLEASANT DYSCOMFORT • IRRITATION • ACCUTE CORONARY ISCHEMIA • CHRONIC OBSTRUCTIVE PULMONARY DISEASE • LUNG CANCER HEALTH CONSEQUENCES OF INVOLUNTARY EXPOSURE TO ETS: • AN HOUR A DAY IN A ROOM WITH SMOKER • IS NEARLY A HUNDRED TIME MORE LIKELY TO CAUSE LUNG CANCER IN A NON-SMOKER • THAN TWENTY YEARS SPENT IN A BUILDING CONTAINING ASBESTOS Sir Richard Doll, 1989 ANTENATAL EXPOSURE • GROWTH RETARDATION • DELAYED LUNG DEVELOPMENT • ACTIVATION OF nAChs (by NICOTINE) = NEUROTERRATOGENICITY (CONDUCT DISORDERS, ADHD, REDUCED MENTAL / SCHOOL PERFORMANCES) PRENATAL PROGRAMING • EXPOSURE TO MATERNAL SMOKING • => CHANGES IN FETAL METABOLISM • OUTLAST AFTER DELIVERY • => OBESITY, HYPERTENSION, DAMAGES SERUM LIPIDS´ RATES in CHILDHOOD and ADULTHOOD CONCLUSSION • CIGARETTE IS UNIQUE ARM KILLING BY ITS BOTH ENDS • GLOBAL TOBACCO EPIDEMY IS WORSE TODAY THAN 50 YEARS AGO AND MAY BE WORSE IN ANOTHER 50 YEARS • SMOKING IS THE MOST IMPORTANT PREVENTABLE RISK FACTOR