SMOKING AND HEALTH prof. MUDr. Drahoslava Hrubá, CSc. Mgr. Jana Fialová, Ph.D. Doc. Ing. Martin Krsek, CSc., MSc Department of Public Health Faculty of Medicine Masaryk Univerzity •Dear colleagues! •I have checked carefully the whole presentation. Where it was necessary, I added few comments or explanatory notes. I hope, that the presentation is quite self-explanatory now. If you have any questions, please, do not hesitate to ask me any question. I will do my best to answer them as well as I can. •My email is : krsek@med.muni.cz •Good luck! •Martin Krsek • WHO •SMOKING IS THE MOST IMPORTANT SINGLE PREVENTABLE (!) CAUSE OF MORBIDITY AND MORTALITY • •SMOKING CONTRIBUTES TO: • •MORTALITY: annually 6 mil. victims worldwide •MORBIDITY: at least to 25 different diseases •DISABILITY: the second leading factor • More people die every year •from smoking than from : murder, AIDS, suicide, drugs, car crashers and alcohol together! • GLOBAL BURDEN of DISEASES •ATTRIBUTABLE EFFECTS of 67 RISK FACTORS in 21 WORLD REGIONS •On DALYs (disability-adjusted life years) = •YLD (sum of years lived with disability) + •YLL (years of life lost) • •FIVE LEADING FACTORS: •(1) HYPERTENSION •(2) TOBACCO SMOKING •(3) ALCOHOL USE •(4) DIETARY – MALNUTRITION •(5) PHYSICAL INACTIVITY • The disability-adjusted life year (DALY) is a measure of overall disease burden, expressed as the number of years lost due to ill-health, disability or early death. It was developed in the 1990s as a way of comparing the overall health and life expectancy of different countries. Smoking •Inhalation of tobacco smoke, the most effective way for intoxication by nicotine •Tobacco products for smoking : • •CIGARETTES, PIPES, CIGARS •BIDIS, KRETEKS, STICS •WATER PIPES •SMOKELESS: SNUFF (MOIST, DRY), CHEWING TOBACCO • •NICOTINE DELIVERY SYSTEMS (e-cigarettes) •HEATED-NOT-BURN TOBACCO PRODUCTS (IQOS –PM), • • •ALL FORMS OF TOBACCO ARE ADDICTIVE AND LETHAL • 1. C:\Users\Mgr. Fialová\Desktop\Kouření\Kouření obrázky\inhalace tabákového kouře_files\1307128495_koureni.jpeg Obrázek - zdroj: ČTK/AP http://magazin.ceskenoviny.cz/zpravy/koureni-a-rakovina-aneb-nejde-jen-o-plice/1165944 Smoking •Nicotine content: •1 cigarette 1 - 3 mg of nicotine, •1 cigar cca 10 mg of nicotine • •Inhaling •into mouth only - absorbs 5% of nicotine, •deep inhalation – absorbs 70%, •very deep inhalation with holding breath - 95% of nicotine • •human lethal dose - cca 60 mg • •Nicotiana tabacum •Nicotiana rustica L. Tobacco plants C:\Users\Mgr. Fialová\Desktop\Kouření\Kouření obrázky\Nicotiana_tabacum_Blanco1.36.png French ambassador in Portugal, Jean Nicot de Villemain sent tobacco and seeds to Paris in 1560 Nicotiana tabacum - Virginia Tobacco; origin Mexico, probably a hybrid of wild species N. sylvestris and N. tomentosa. Nicotiana rustica L. - rustic tobacco - folk Machorka, one of the original botanical species. Nicotine •Plant alkaloid (from plant family Solanaceae – • potatoes, tomatoes, pepper,… - but no nicotine!!!) •Human lethal dose - cca 60 mg •Stimulating effects in nervous system •Increase digestive tract activity, increase blood pressure, cardiac acceleration, vasoconstrictor effects, related tissue and organ hypoxia •It is not a carcinogen itself •But - its metabolites are •E.g. NNK - nicotine-nitrosamine ketone: a strong mutagen and a carcinogen present in tobacco smoke, naturally occurring in tobacco leaves of industrially treated tobacco crops in the presence of light C10H14N2 Solanaceae: potatoes, eggplant, tomatoes, peppers… , but rich of nicotine is tobacco only NNK is a compound that is naturally synthesized in tobacco leaves that are exposed to light: the pyrrolidine ring in the nicotine opens and turns the nicotine into NNK. Most of the NNK found in tobacco smoke originates from nicotine burning.^[2] Sun-cured tobaccos (a.k.a. "Oriental") contain very little NNK and other TSNAs due to low-nitrate soil, lack of nitrate fertilizer, and sun-curing. Flue-cured tobacco (a.k.a. "Virginia" tobacco^[4]), especially when using an open flame, contains most of the NNK in American blended tobaccos^[5] although Marlboro's "virginia blend" had the lowest levels of NNK per nicotine out of many tested with the exception of Natural American Spirit.^[6] IN CIGARETTE SMOKE • •ABOUT 5.000 CHEMICALS with • •IRRITATION, • •TOXIC, • •CARCINOGENIC, • •TERRATOGENIC, EMBRYOTOXIC EFFECTS • • • Chemicals in tabacco smoke – few examples •WHO: Tobacco smoke is human carcinogenic mixture •arsenic - a toxic element, used since ancient times as a rat poison •benzene - carcinogenic, naturally occurring in oil, benzopyrene - a highly carcinogenic and mutagenic substance, a typical product of incomplete combustion •dioxins (a group of the strongest known poisons), DDT (a very effective insecticide, until the late 1960s used to kill harmful insects, then banned in most countries) - both highly persistent •formaldehyde - formerly used as an insecticide to kill moths, as a disinfectant and sterilizing agent, as a part of chipboard adhesives or in the manufacture of carpets •cadmium - heavy metal, strongly cumulative in kidneys, chemically similar to Zn - blockages and changes in biochemistry. cycles (insulin cycle), •hydrogen cyanide - one of the most poisonous gases (used in gas chambers during World War II, as well as a mouse poison) •nickel - a highly toxic element, highly teratogenic •lead - a toxic element, especially dangerous for children - causes slowing of mental development and behavioral disorders •TSNA - Tobacco-specific nitrosamines - a group of highly cancer-causing substances that are present only in tobacco products, are involved in many types of cancer, can damage reproductive organs • Arsenic-containing pesticides The tobacco plant contains nickel and several other toxic metals, most probably absorbed from the soil, fertilizing products or from pesticides Chemicals in tabacco smoke •Carbon monoxide (CO) - toxic gas; preferential binding to hemoglobin molecules - decreases the amount of oxygen-transferring oxygen, significantly lower overall oxygenation of the organism. The main component of exhaust gases. •Nitrogen dioxide (NO2) - highly toxic gas, airway inflammation - from light to lung edema. They are involved in the formation of acid rains and the formation of photochemical smog. •Nitric oxide (NO) - toxic gas, in the presence of corrosive moisture. In the human body it is formed in the cardiovascular and nervous system, it affects the vasodilatation, the signal molecule, the neurotransmitter function; in medicine, use in the release of smooth muscle cramps during asthma. At higher doses - heart weakness. Releases in exhaust gases and works in acid rain. •Tar - A mixture of chemicals (predominantly toxic and cancer-causing) such as polycyclic aromatic hydrocarbons (PAHs) or aromatic amines; has a dense oily or greasy consistency. In tobacco smoke it is dispersed in the form of an aerosol, 90% of which is deposited in the lungs of the smoker, 10% returns with exhaled smoke back to the atmosphere in its immediate vicinity. • SMOKING HAS * IMMEDIATE EFFECTS • • •ACTIVATION OF BRAIN RECEPTORS • •CARDIOVASCULAR CHANGES • •HYPOXEMIA • •IRRITATION • NICOTINE IN BRAIN • •NICOTINE REACHES THE BRAIN WITHIN 10-20 SECONDS AFTER THE PUFF (small molecule) • •WITHIN 20-30 MINUTES AFTER TRANSDERMAL/SALIVA 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) • Receptory v celém těle, některé jsou specifické pro nikotin An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter. Nicotinic acetylcholine receptors are particularly responsive to nicotine DENSITY of nAChRs • •IN THE BRAIN IS NOT HOMOGENOUS • •ACCUMULATION IN NUCLEUS ACCUMBENS => •LIMBIC AREA • •AFTER THEIR ACTIVATION => SERIES OF PHYSIOLOGICAL EVENTS • Limbic area – The structures and interacting areas of the limbic system are involved in motivation, emotion, learning, and memory (and addiction). The limbic system is where the subcortical structures meet the cerebral cortex.^[1] The limbic system operates by influencing the endocrine system and the autonomic nervous system. It is highly interconnected with the nucleus accumbens, which plays a role in sexual arousal and the "high" derived from certain recreational drugs. These responses are heavily modulated by dopaminergic projections from the limbic system. RELEASE OF NEUROTRANSMITTERS: • •DOPAMINE •SEROTONINE •ACETYLCHOLINE •EPINEPFRINE, NOREPINEPHRINE, •BETA-ENDORPHINE •ACTH (adrenocorticotropic hormone), •ADRENALINE • EFFECTS OF NICOTINE • •WELL BEEING (DOPAMINE) • •COPING THE STRESS (ACTH) • •BETTER SHORT-TERM PERFORMANCE (ACETYLCHOLINE, ADRENALINE) • THESE EFFECTS • •CAN PRODUCE MANY NATURAL DAILY EVENTS: • •FOOD, SEX • •MUSIC, SUCCESS • •FRIENDLY ENVIRONMENT • •We DO NOT need nicotine for these effects!!! • DUE TO THESE REWARDS • •SMOKERS REPEATE PUFFS, • •RAISE THE NUMBER DAILY SMOKING CIGARETTES • •LIGHT ON AUTOMATICALY IN SPECIFIC SITUATIONS • •DEVELOP ADDICTION • 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 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 (nicotine) AND BEHAVIORAL (the smoker lights a cigarette in certain situations – coffee, wine, friends) ADDICTION • Official status •Dg. F 17: • PSYCHOLOGICAL AND BEHAVIORAL DISORDERS CAUSED BY TOBACCO USE • •International statistic classification of diseases, 10th revision, 1991 • ALTERED DOPAMINERGIC SYSTEM •PREMATURAL ACTIVATION • OF FETAL RECEPTORS •(30-fold higher affinity for • the neurotransmitter Ach) • •DECREASED AMOUNT OF •NEURAL CELLS IN THE BRAIN • •SUDDEN INFANT DEATH SYNDROME • •IMPAIRED NEURO-PSYCHOLOGICAL DEVELOPMENT • •BEHAVIORAL and COGNITIVE PROBLEMS in later life • Jde o prenatální změny ALTERED SEROTONERGIC SYSTEM • •MAJOR PSYCHIATRIC DISORDERS (SCHIZOPHRENIA, DEPRESSION) • •2-3 times HIGHER FREQUENCY OF SUICIDES • • •SMOKING CAUSES DEPRESSION • •DEPRESSION CAUSES SMOKING • Dospělí – dlouho kouří, serotonin se už nevyplavuje - sebevraždy 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 • •BY QUICK ADMINISTRATION OF NICOTINE: • •ACTIVATION OF SYMPHATETIC NERVOUS SYSTEM • •RELEASE OF SUPRARENAL HORMONES (ADRENALINE, NORADRENALINE) • • VASOCONSTRICTION • •CONTINUES EVEN AFTER THE CIGARETTE IS SMOKED • •FOR ANOTHER 30 – 45 min • •AS NICOTINE IS PRESENT IN BLOOD • 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) • cyanide ion halts cellular respiration by acting as a non-competitive inhibitor for an enzyme in mitochondria called cytochrome c oxidase. IN PREGNANCY • •LOCAL PLACENTAL NECROSIS (caused by cadmium) • •POWERFULL AFFINITY OF FETAL HEMOGLOBIN TO CARBON MONOXIDE ENHANCES COHb LEVELS BY 25% (fetal x maternal blood) • OXIDATIVE STRESS • •IN PLACENTAL TISSUE IMPAIRES DEVELOPMENT AND FUNCTION DUE TO DAMAGES OF DNA, • • •INCREASING : APOPTOSIS AND CELLULAR DEATH • HYPOXEMIA and HYPONUTRITION • •FETAL GROWTH RETARDATION = FETAL TOBACCO SYNDROME => programing of OBESITY, LIPID AND GLUCOSE METABOLISMS • • =>RISE RISK of CVD • •RISK OF PRE-TERM BIRTH • •RISK OF INTRAUTERINE DEATH • PRENATAL EXPOSURE • •ALTERATES THE LUNG DEVELOPMENT • •MODIFIES THE REPRODUCTIVE DEVELOPMENT • •RISES THE RISK OF CONGENITAL MALFORMATIONS • • SUDDEN INFANT DEATH SYNDROME • HYPOXEMIA IN ADULTS •HEART ATTACK (IM) • •CEREBROVASCULAR ATTACK (STROKE) • •WRINKLING, PREMATURE AGEING • •IMPAIRED WOUND HEALING • •LEG AND HAND PAIN, GANGRENE – PERIPHERAL VASCULAR DISEASE • C:\Documents and Settings\prof. Hrubá\Plocha\starý kuřák.JPG C:\Documents and Settings\prof. Hrubá\Plocha\legss.jpg IRRITATION • •EYES: excessive tearing, blinking, stinging • •NOSE: bad smell, stinging, phlegm • •NASOPHARYNX: cough, chest could • • • •STRESS DUE TO DYSCOMFORT • SHORT/MIDL-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) • More important in children - undeveloped immune system Cigarette smokers had a significantly lower proportion of NK cells than did subjects who had never smoked MALE REPRODUCTION •IMPOTENCE (erectile dysfunction) • •IMPAIRED SPERMIOGENESIS: deformity, loss of motility, reduced number, aneuploid sperm cells • •INFERTILITY • •FETAL MALFORMATIONS • • SMOKING INCREASES ED • • •FROM 2005 (Austoni et al.) studies in many populations: China, Middle East, Europe, America • •OR = 1,4 – 3.1 with respect to other causes of ED • •Smoking effects on ED are dose dependent • OR – odds ratioes – relativní riziko MOLECULAR MECHANISMS •PARASYMPATHETIC NERVOUS SYSTEM INDUCES SMOOTH MUSCLE RELAXATION => ALLOWS ARTERIAL PRESSURE BLOOD INTO THE CORPUS CAVERNOSUM VIA ACTION of NITRIC OXIDE (NO) • •NICOTIN IS SYMPATICOMIMETIC, • •LEVELS OF NO – are altered by smoking • SMOKING CESSATION • • •NO CONSISTENT RESULTS ABOUT THE MAGNITUDE OF THE BENEFITS WITH REGARD TO ED • • •HISTORY OF SMOKING PRODUCE SILENT VASCULAR INSULT THAT PERSIST OVER TIME • BETTER PROGNOSIS • •IS BELIEVED FOR YOUNGER MEN WITHOUT SO LONG SMOKING HISTORY and •WITH LACK OF COMORBIDITIES. • •Kovac JR et al. Effects of cigarette smoking on erectile dysfunction •Andrologia 2014; •Doi: 10.1111/and.12393 • FEMALE REPRODUCTION • • •PAINFUL MENSTRUATION •EARLIER MENOPAUSE •INFERTILITY •ECTOPIC PREGNANCY •PLACENTA PRAEVIA •PREMATURE BIRTH •SPONTANEOUS ABORTION • BOTH ACTIVE AND PASSIVE SMOKING ARE RISKS (OR): •ACTIVE SMOKERS: • •ABORTIONS ……....1.16 •STILLBIRTHS………1.44 •ECTOPIC PREG. … 1.43 • PASSIVE SMOKERS ………..1.17 ………. 1.55 ………. 1.61 SMOKING • • •SEEMS TO BE PROTECTIVE for the development of • PREECLAMPSIA (high blood pressure, proteins in urine) • • •BUT IT IS NOT A REASON FOR KEEPING SMOKING DURING PREGNANCY!!!, AS OTHER RISKS PREVAILE THIS BENEFIT • OTHERS •HORMONAL DYSBALANCE CONTRIBUTES TO: • •DIABETES MELLITUS and COMPLICATIONS • •OSTEOPOROSIS • •HIP FRACTURES • •By the ANTIESTROGENIC EFFECT OF NICOTINE • BLOOD LIPIDS • •INCREASED LEVELS OF •- TOTAL CHOLESTEROL •- LDL – CHOLESTEROL -VLDL – CHOLESTEROL • • •DECREASED LEVELS OF •- HDL- CHOLESTEROL • LDL a HDL vznikají v nás, nejsou z potravy LDL:HDL – je důležitější než celková koncentrace cholesterolu HEMOCOAGULATION • • • •ENHANCED ACTIVITY OF THROMBOCYTES and • FACTOR VIII => • •ARTERIAL THROMBOSIS (IM, stroke, gangrene in periferies) • SMOKING IS RESPONSIBLE • •FOR 25% OF ISCHEMIC HEART DISEASES • •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) • EXPOSURE TO ETS (Environmental tobacco smoke) • •INCREASES THE RISK OF ACUTE CORONARY SYNDROM by 25 – 30 %: • •INCREASED THROMBOGENESIS and • LDL-CHOLESTEROL OXIDATION • •DECREASED ABILITY TO EXERCISE • •ACTIVE INFLAMMATORY PATHWAY • •IMPAIRED VASCULAR REPAIR • LDL oxidation – it is active again and this is the „bad“ one SMOKING CONTRIBUTES TO •STOMACH AND DUODENAL ULCERS • •GUM DISEASES – GINGIVITIS, PERIODONTITIS • •TEETH LOOSE • •PROGRESSION OF PRESBYACUSIS • •PSORIASIS and other skin diseases • •TREMOR • MENTAL HEALTH: • •Smoking negative influences: •- brain development, •- memory • •Smoking is a risk factor for Alzheimer disease • •Smoking is a protective factor for Parkinson disease • Významné u dětí, ale od 35 roku se u dospělých zhoršuje paměť * LONG-TERM EFFECTS • • •TOBACCO SMOKE CONTAINS OVER 5.000 CHEMICALS, • •67 OF WHICH ARE CONFIRMED or SUSPECTED HUMAN CARCINOGENS (within the list of appr. 73 confirmed human chemical carcinogens) • CARCINOGENS IN SMOKE • •POLYCYCLIC AROMATIC H. (benzo/a/pyrene) • •HEAVY METALS (Cd, As) • •RADIOACTIVE POLONIUM 210 • •INDUSTRIAL CARCINOGENS: beta-naphthylamine, 4-aminobiphenyle, benzene, formaldehyde • TOBACCO SPECIFIC NITROSAMINES •formed from nicotine and related compounds by a nitrosamine reaction that occurs during the curing and processing of tobacco: • •NNK: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone • •NNAL • •NNN • •And many others • NNK - very potent lung carcinogen, in tobacco others, which are not produced elsewhere When smoking – during puberty _ proliferation of breast tissue - lactation - end of pregnancy Everything gets worse 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 • U rakoviny prsů – dva typy studií 1)Protektivní – estrogenní působení někdy 2)rizikové – v prsní tkáni …. PAV na DNA – u kuřáků více LUNG CARCINOGENS • •ACTIVE SMOKING ……. 90 % • •PASSIVE SMOKING …… 4 % • •OCCUPATION …………. 5 % • (radiation, asbestosis, Cr, Ni, PAH, plast additives, benzin…) • •ENVIRONMENT ………. . 1 % • PATHWAYS • •GENOTOXICITY => INITIATION OF CARCINOGENESIS • •METABOLIC ACTIVATION – microsomal enzymes P 450 – HEREDITARY DETERMINATION • •EPIGENETIC EFFECTS •=>MODULATE CELLULAR FUNCTIONS •=> TUMOR PROMOTION and PROGRESSION • Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that function as monooxygenases.^[1]^[2]^[3] In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown. Cytochrom P450 (zkratka CYP) označuje rozsáhlou skupinu hemoproteinových enzymů, které nesou hemovou prosthetickou skupinu. Název cytochrom P450 vychází z faktu, že redukovaná forma enzymu v komplexu s oxidem uhelnatým vykazuje silné absorpční maximum v UV-VIS spektru při 450 nm zastávají klíčovou roli v metabolizmu xenobiotik. Podílejí se také na odbourávání endogenních látek, např. melatonin. Katalyzují oxidační, peroxidační a redukční reakce v I. fázi biotransformace látek. Aktivitou CYP 450 může docházet k detoxikaci cizorodých látek, tzn. že dojde ke ztrátě biologické aktivity dané látky nebo může docházet k tzv. bioaktivaci. CARCINOGENESIS •GENOTOXIC EFFECTS: • 1.INITIATION of DNA MUTAGENIC CHANGES 2. •2. REPLICATION • •EPIGENETIC EFFECTS: • • INFLUENCE ON APOPTOSIS •1. PROMOTION •2. PROGRESSION •3. METASTASES • CONSEQUENCES: PROMOTION • •CELL´S PROLIFERATION • •ANTI – APOPTOSIS • •PROTEIN SYNTHESIS • •MITOCHONDRIA DYSFUNCTION • •INCREASING of REPLICATIVE LIFESPAN of CARCINOGENIC CELLS • Mainly nicotin is responsible Proteine synthesis – the tumor is better nourished CONSEQUENCES: PROGRESSION and INVASION • •ANGIOGENESIS => • •SUPPORT FOR THE TUMOR GROWTH • •DECREASED CELLS´ ADHERENCE => • •METASTASIS • Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels,^[1]^[2]^[3] formed in the earlier stage of vasculogenesis ROLE OF microRNAs • •PROBABLY MORE THAN 1000 • •KNOWN MORE THAN 700 • •TISSUE SPECIFIC • •DETECABLE IN 12 BODY FLUIDS • •SOME OF THEM EARLIER MARKERS OF CARCINOGENIC CHANGES • A microRNA (abbreviated miRNA) is a small non-coding RNA molecule (containing about 22 nucleotides) found in plants, animals and some viruses, that functions in RNA silencing and post-transcriptional regulation of gene expression Early marker of some tumors - smoking affects them 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 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 • Doll – he also studied the effects of asbestos and other cancers The British Doctors' Study 1951 - 2001 The longest prospective study - addressed more than 34,000 British doctors (more than 2/3 get involved). Basic hypothesis - "Smoking is a major cause of lung cancer". In 1951-1971, the difference in life span of smokers and non-smokers was 5 years, after another 20 years 8 years, and the latest study found a 10-year loss of life for British doctors-smokers as compared to lifetime non-smokers. SMOKING KILLS NON-SMOKERS •MAIN STREAM (MS) •(when smoker puffs) -800-900o C -16% O2 -6,0-6,7 pH • SIDE STREAM (SS) (cigarete burning on its own) -600o C -2% O2 -6,7-7,5 pH DANGER FOR NON-SMOKERS • •SECONDHAND SMOKE • •ENVIRONMENTAL TOBACCO SMOKE • •PASSIVE SMOKING • •INVOLUNTARY SMOKING • •Side stream + smoker´s expiration + chemicals interaction • ETS – the rest - aging, changing SIMILARITIES and DIFFERENCES • •THE NUMBER OF CHEMICALS in MS and SS ARE THE SAME • •THE LEVELS OF CHEMICALS ARE HIGHER in SS COMPARRED TO MS • •DUE TO IMPERFEKT BURNING • RATIO SS : MS - IRRITANTS • • •ACROLEIN 8 – 15 •FORMALDEHYDE 10 – 15 •AMONIUM 73 •NITROGEN OXIDES 4 – 10 •FORMAMIC ACID 1,5 •NAFTALENE 16 • 8-15x víc v SS než v MS RATIO SS : MS - TOXINS • •CARBON MONOXIDE 2 – 5 • •TOLUENE 6 – 8 • •NICOTINE 2,6-3,3 • •NICKEL 13 – 30 • •POLONIUM 210 1 – 4 • •PCDD, PCDF (dioxins, furans) 2 • RATIO 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 (before the ban on smoking) • •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 (before the ban) • •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 • • •SOME CHEMICALS IN ETS ARE ABSORBED IN WALLS, CARPETS, CLOTHES, FURNITURE • • •AND ARE RE-EMITTED INTO THE INTERIER • THIRDHAND SMOKE • •NICOTINE + NITRIC ACID + NOX • •= > INTERACTIONS = > • •NITROSAMINES NNK, NNA, NNN • •(mutagenic, carcinogenic) • •CONTAMINATION OF CLOTHES, SKIN, CARPETS, FORNITURE for many hours, days, weeks, years • 1st EXPERIMENTAL STUDY: • •MICE EXPOSED TO THIRDHAND SMOKE • •LIVER: FIBROSIS, STEATOSIS • •BLOOD: INCREASED TOTAL and LDL CHOLESTEROL, DECREASED HDL CHOLESTEROL • •PRE-DIABETIC DEFECTS OF INSULIN METABOLISM • •LUNG: FIBROSIS, INCREASED NUMBER of MACROPHAGES => OXIDATIVE STRESS • •SKIN: KERATINOSIS, LESS FIBRILLAR COLLAGEN • •HYPERACTIVITY, ANXIETY •UNPLEASANT DYSCOMFORT • •IRRITATION • •IMPAIRED IMMUNITY • •RESPIRATORY INFECTIONS, ALERGY • •Sudden infant death syndrome • •LEUKEMIA, BRAIN TUMORS • •The most vulnerable group – immature biological structures, faster breathing frequency, lower breath zone, specific habits - climbing on four, licking hands ... • • EXPOSURE TO ETS - CHILDREN EXPOSURE TO ETS - ADULTS • •UNPLEASANT DYSCOMFORT • •IRRITATION • •ACCUTE CORONARY ISCHEMIA • •CHRONIC OBSTRUCTIVE PULMONARY DISEASE • •LUNG CANCER • HEALTH CONSEQUENCES OF 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 • BAN OF SMOKING ON PUBLIC PLACES • •18 months after implementation: •INCIDENCE of MI DECLINED BY 33% • from 150.8 to 100.7 / 100.000 • •INCIDENCE of SUDDEN CARDIAC DEATH DECLINED BY 17% from 109.1 to 92.0 / 100.000 • •Minnesota Study , Arch.Intern.Med. Doi: 10.1001/2013.jamainternmed.46 • •- Similar data in ČR • SMOKE-FREE LEGISLATION • •LOWERED RATES OF HOSPITAL ADMISSIONS for: • • RR •CORONARY EVENTS ……… 0.848 •OTHER HEART DIS. ………… 0.610 •CEREBROVASCULAR DIS. … 0.840 •RESPIRATORY DIS. ………… 0.760 • •Circulation 2012; 126: 2177 - 2183 • risk ratio (RR) or relative risk is the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group 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 • SMOKING CESSATION DEATH IN OLD AGE IS INEVITABLE, BUT DEATH BEFORE OLD AGE IS NOT Sir Richard Peto, 2006 https://is.muni.cz/www/2422/um Professor of Medical Statistics and Epidemiology at the University of Oxford, His career has included collaborations with Richard Doll beginning at the Medical Research Council Statistical Research Unit in London. He is a leading expert on deaths related to tobacco use. He was knighted for his services to epidemiology and to cancer prevention in 1999, Peto's paradox is the observation, named after Richard Peto, that at the species level, the incidence of cancer does not appear to correlate with the number of cells in an organism. Smoking epidemic/pandemic smoking is linked to the overall economic situation - when it gets better, the number of smokers increases; The pandemic began in North America and Western Europe, then continued into Southern and Eastern Europe, Japan ... THE RISK IS BIG •ABOUT HALF OF SMOKERS ARE KILLED • •THOSE KILLED IN MIDDLE AGE LOSE 10, 20, 30 OR MORE GOOD YEARS • •www.deathsfromsmoking.net STOPPING SMOKING WORKS •EVEN IN EARLY MIDDLE AGE (40y) THOSE WHO STOP, AVOID MOST OF THEIR RISK OF BEING KILLED BY TOBACCO • •STOPPING BEFORE MIDDLE AGE WORKS EVEN BETTER •The overall prevalence over the past 15 years: •30% (2012) - 25.2% (2017) •By gender: •Men 36%, Women 26% (2012) •Men 30%, Women 20% (2017) •By age: •under 15 - up to 33%, 15-24 years: 43%, 25-44 years: 33%, 45-64 years: 28%, over 65: 20% (2012) •15-24 years: 36%, 25-44 years: 27%, 45-64 years: 26%, over 65 years: 15% (2017) Prevalence of smoking in the Czech Republic Prevalence of smoking in the Czech Republic •The use of other tobacco products than cigarettes: • •pipes, cigars, water pipes • 2 - 2.5% (2012) 4.7% (2017) • •e-cigarettes 1.7% (2012), 5.2% (2017) • •Smokeless tobacco: 2.5% (2017) • SZÚ 2017: http://www.szu.cz/uploads/documents/szu/aktual/uzivani_tabaku_2017.pdf IMMIDIATE BENEFITS OF STOPPING •WITHIN 20 - 30 MINUTES: • •THE BLOOD PRESURE AND HEART RATE WILL DROP TO THE REST VALUES • •THE SKIN TEMPERATURE (LEGS) RAISES BY 2o C • SHORT-TERM BENEFITS OF STOPPING •WITHIN 6 – 8 HOURS •COHb LEVELS WILL DROP TO THE NORMAL VALUES (< 1%) •WITHIN 72 HOURS •PULMONARY FUNCTIONS WILL IMPROVE (1sec forced expiration) Pulmonary function – bronchokonstrikční látky ( test na astma) MIDDLE-TERM BENEFITS OF STOPPING •WITHIN 2 MONTHS •MALE SPERM DAMAGES CAUSED BY SMOKING WILL BE REPAIRED • •WITHIN THE 1st TRIMESTER •THE RISK OF PREGNANCY PROBLEMS AND FETAL BODY POOR DEVELOPMENT WILL DECREASE MIDDLE-TERM BENEFITS OF STOPPING •WITHIN 1st YEAR • •THE BLOOD LIPID PROFILE WILL BE IMPROVED, • •THE PARAMETERS OF HEMO-COAGULATION WILL BE IMPROVED • •THE RISK OF AC. CARDIAC ISCHEMY and STROKE WILL DECREASE LONG-TERM BENEFITS •WITHIN 5 YEARS • •THE RISK OF CVD DEATH WILL BE SIMILAR AS FOR NEVER-SMOKERS • •THE RISK OF SMOKING-RELATED CANCERS WILL START THE DECREASED TRENDS CVD – zlepšení už po roce – není CO a vasokonstrikce, snížení akutních srdečních příhod LONG-TERM BENEFITS •WITHIN 10 – 20 YEARS • •THE RISKS OF SMOKING-RELATED CANCER´S DEATH WILL BE SUBSTANTIALLY DECREASED, ALMOST TO THE LEVELS FOR PEOPLE WHO NEVER SMOKED C:\Documents and Settings\prof. Hrubá\Plocha\Graf Stopping smoking.gif LONG-TERM BENEFITS CONCLUSIONS •THE RISK IS BIG • •STOPPING SMOKING WORKS • • EFFECTIVE SUPPORT OF SMOKING CESSATION WILL CHANGE THE DEATH EPIDEMIC WITHIN 10-20 YEARS SMOKERS ARE: •AT THE BEGINNING: •CURIOSITY SEEKING PEOPLE. •UNHAPPY, UNSUCCESSFUL PEOPLE • LAZY PEOPLE • •LATER ON: • DEPENDENT PEOPLE CRITERIA OF ADDICTION •USING THE DRUG LONGER THAN EXPECTED • •USING THE DRUG DESPITE OF HEALTH PROBLEMS • • A LOT OF TIME PER DAY IS SPENT BY EFFORT TO OBTAIN THE DRUG /or BY USING THE DRUG CRITERIA - continue •USER NEGLECTS SOME ACTIVITIES WHERE USING OF DRUG IS BANNED • •SHORT-TERM ABSTINENCE RESULTS IN THE REPEATEDLY OCCURING WITHDRAWAL SYMPTOMS and RELAPSE TOLERABILITY •THE SAME DOSE CAUSES LOWER EFFECTS • •FOR THE SAME EFFECTS THE INCREASED DOSE IS NECESSARY WITHDRAWAL SYMPTOMS (WS) •EXCITABILITY, NERVOUS, STRESSED • •ATTENTION DISABILITY • •COGNITIVE PROBLEMS • •DEPRESSION • •ANXIETY • WITHDRAWAL SYMPTOMS •POORER WEIGHT CONTROL -> OVERWEIGHT • •EXPECTORATION • •CONSTIPATION WS – TIMING •WITHIN 2 HOURS AFTER THE LAST CIGARETTE • •WAVES WITH DIFFERENT FREQUENCY AND INTENSITY • •SEVERAL DAYS – WEEKS – MONTHS - YEARS WS - CAUSES •LACK OF NICOTINE • •LACK OF SOCIAL CONTACTS • •CRAVING FOR SMOKING • • • •INCREASED FOOD INTAKE • •DECREASED BASAL METABOLISM WITHDRAWAL SYMPTOMS •ARE NOT HARMFUL FOR HEALTH • •ARE THE MANIFESTATION OF THE DRUG ELIMINATION • •ARE THE MOST FREQUENT CAUSE OF RELAPS POWER OF DEPENDENCE •IS SIMILAR AS FOR HEROINE or COCAINE: 80-85 % of current users, • •32 % of occas.smokers, 20 % of occasional users of cocaine/heroine • •ADOLESCENTS ARE MORE VULNERABLE (the pleasure effects of smoking are percieved after lower levels of nicotine) • ADDICTION TO SMOKING •IS A PEDIATRIC PROBLEM • •SMOKERS USUALY START SMOKE BEFORE the age 18 YEARS • •TIME DISCREPANCY OF LIMBIC and FRONTAL CORTEX MATURATION => • •DISPOSITION TO RISK and • LOW RESPONSIBILITY WHAT TO DO? •KEEPING SMOKERS´ RIGHTS: • -TO BE INFORMED ABOUT HAZARD - -TO BE EXCLUDED FROM RISK SITUATIONS - -TO BE MOTIVATED TO DECISSION - -TO BE SUPPORTED IN THEIR EFFORT TO STOP SMOKING Smokers have the right to smoke, but not anytime, anywhere They have the right to help WHAT IS THE BEST WAY? •THE „5A“ PROGRAMME: 1.ASK 2.ADVICE 3.ASSESS 4.ASSIST 5.ARRANGE FOLLOW-UP 6. •http://apps.who.int/iris/bitstream/handle/10665/112836/9789241506946_eng.pdf;jsessionid=9CF5056D2A 25D72B74145B5B7B1B49F2?sequence=1 1. ASK EVERY PATIENT: •DO YOU SMOKE? •HOW MANY CIGARETTES DAILY? •HOW MANY YEARS? •AT WHICH AGE DID YOU START? •AT WHICH MORNING TIME DO YOU LIGH YOUR FIRST CIGARETTE? •WOULD YOU LIKE TO STOP? •HAVE YOU SOME EXPERIENCES WITH STOPPING? 1A: CONGRATULATION •TO EVERYBODY WHO: • •HAS NEVER SMOKE • •HAS STOPPED SMOKING: • - ASK HIM/HER ABOUT PROBLEMS, - -SUPPORT HIS/HER EFFORT TO BE NON-SMOKER 2. ADVICE •TO EVERY SMOKER TO STOP, because • •FAMILY HISTORY (HEREDITARY VULNERABILITY) • •SMOKER´S HEALTH HISTORY • •CURRENT HEALTH STATUS • •SOCIAL IMAGE, MODEL ROLE • •HIS/HER CHILDREN HEALTH ADVICE IS ESSENTIAL •PEOPLE KNOW THE SMOKING HAZARD IN GENERAL • •PEOPLE FEEL PERSONAL IMMUNITY AGAINST THE DAMAGES • •SUCH FEELINGS ARE FALSE, ERRORNEOUS AND VERY DANGEROUS SUPPORT OF ADVICE •USE THE BOOKLETS, LEAFLETS, PICTURES, … • •FOR TARGET POPULATION OF SMOKERS (CHILDREN, TEENAGERS, PREGNANT WOMEN, WORKERS, MINORS, SENIORS…) • •RECOMMEND THE SPECIAL CENTRE MOTIVATION TO QUIT-5Rs •PERSONAL RELEVANCE TO A PATIENT • •RISK OF SMOKING COULD BE STRESSED • •EMPHASIZE REWARDS (health, money) • •ROADBLOCKS (identify barriers) • •REPETITION EACH TIME OF VISIT • Road blocks - schedule - even during smoking - when and where I smoke; have only 1 box; make it harder to smoke - it's cold, I don't want to smoke outside, put a box on a closet, just have 1 cigarette he must get angry - what does smoking do with him 3. ASSESS THE LEVEL OF DEPENDENCE •FAGERSTROM´S QUESTIONNAIRE: •6 QUESTIONS •MAXIMUM 10 „BAD POINTS“ •4 LEVELS OF DEPENDENCE • • •LOSS OF AUTONOMY • • THINKING ABOUT TREATMENT FAGERSTROM´S QUESTIONNAIRE •1. How soon after you wake up do you smoke your first cigarette? •After 60 minutes 0 •31-60 minutes 1 •6-30 minutes 2 •Within 5 minutes 3 •2. Do you find it difficult to refrain from smoking in places where it is forbidden? •No 0 •Yes 1 •3. Which cigarette would you hate most to give up? •The first in the morning 1 •Any other 0 •4. How many cigarettes per day do you smoke? •10 or less 0 •11-20 1 •21-30 2 •31 or more 3 •5. Do you smoke more frequently during the first hours after awakening than during the rest of the day? •No 0 •Yes 1 •6. Do you smoke even if you are so ill that you are in bed most of the day? •No 0 •Yes 1 FAGERSTROM´S QUESTIONNAIRE •Under 3 •Your level of nicotine dependence is still low. You should act now before your level of dependence increases. •4-5 •Your level of nicotine dependence is moderate. If you don't quit soon, your level of dependence on nicotine will increase until you may be seriously addicted. Act now to end your dependence on nicotine. •6-10 •Your level of dependence is high. You aren't in control of your smoking– it is in control of you! When you make the decision to quit, you may want to talk with your doctor about nicotine replacement therapy or other medications to help you break your addiction. • http://www.healthnz.co.nz/DiFranzalasc.htm https://www.umassmed.edu/globalassets/attocpenn/the_hooked_on_nicotine_checklist.pdf?_t_id=1B2M2Y8A sgTpgAmY7PhCfg%3D%3D&_t_q=HONC&_t_tags=language%3A%2Csiteid%3Ab5a143c9-b51e-4bac-9eab-62560b986673& _t_ip=192.197.205.213&_t_hit.id=UMassMedicalSchool_Models_Media_GenericMedia/_5988cfa9-f23e-48dc-81 17-5a8bb1754254&_t_hit.pos=2 Already one positive answer = reduction of autonomy, you are in it 4. ASSIST WITH THE START •HELP TO CHOOSE THE STRONGEST MOTIVE • •INICIATE TO CHOOSE THE DAY „D“ • •EVALUATE THE RISK SITUATIONS: „TO KILL TIME“, „PLEASURE“, „STRESS“ • ASSIST - continue •CHOOSE THE REPLACEMENT IN THE RISK SITUATIONS: WHAT TO DO WITHOUT CIGARETTE? • •THE DIFFICULT AVAILABILITY • •CHANGE THE ATTITUDES: CIGARETTE IS NOT A FRIEND, BUT THE WORST ENEMY MEDICAL SUPPORT - NRT •REPLACING NICOTIN FROM SMOKING BY OTHER SOURCES: •CHEWING GUMS: -NICORETTE – 2, 4 mg: RULES FOR RIGHT CHEWING - •PATCHES: •- NICORETTE – 16 hours – 5, 10, 15 mg •- NIQUITINE – 24 hours – 7, 14, 21 mg • - Smoking - physiological as well as behavioral addiction - NRT will remove the physiological addiction, the behavioral dependency will be dealt with later. NRT - continue •INHALERS • •SUBLINGUAL TABLETS • •ORAL/NASAL SPREY HOW TO USE NRT? •„AD LIBIDUM“ at the beginning (1 – 3 months) • •GRADUALLY LOWERING THE DOSAGE (next 3 months; each new lower dosage kept for 1 week, at least) E-CIGARETTES / ENDS •POOR CONTROL OF INHALED NICOTINE • •OTHER HARMFUL CHEMICALS, EVEN IN LOWER LEVELS THAN IN TRADITIONAL CIGARETTES • •KEEPING THE SMOKING BEHAVIOR RITUALS • •NO KNOWLEDGE ABOUT THE HEALTH RISKS NRT´S SAFETY AND HAZARD •DECREASED WITHDRAWAL SY. • •SLOW RELEASE OF NICOTINE WITHOUT VASOCONSTRICTION • •CROSS PLACENTAL BARRIERE • •ANTENATAL ACTIVATION nAChRs -> NEUROTERRATOGENIC EFFECTS • •MULTIPLE CARCINOGENICITY Even e-cigarettes have those 30 minutes before they work There is no vasoconstriction - can be used by cardiacs nicotine crosses the placenta NICOTIN IS A COMPLETE CARCINOGEN •NICOTIN IS NOT MUTAGENIC! • • IT CAN BE PARTIALLY METABOLISED TO NNK => INDIRECT INITIATOR OF CARCINOGENICITY • •REVASCULARISATION OF CARCINOMA/METASTATIC TISSUES => HIGHER PROGRESSION (epigenetic carcinogen) Tabacco specific nitrosamins – NNK - nicotine-derived nitrosamine ketone Epigenetic carcinogen – even nicotine on its own- revascularisation BUPROPION •ANTIDEPRESSIVE DRUGS: • ZYBAN, WELLBUTRINE • •COMBINATION WITH NRT VARENICLINE - CHAMPIX •AGONIST OF NICOTINE: • •ACTIVATION of nAChRs •- > RELEASE OF DOPAMINE - > •- > CIGARETTE IS NOT ONLY UNIQUE SOURCE OF PLEASURE • • ONE WEEK BEFORE STOPPING I start taking it while I smoke - reducing the number of cigarettes CONTRAINDICATIONS •IN PREGNANCY – CATEGORY C (all the supportive drugs) neuroterratogenic effect is possible (latest studies - no?) • •CHILDREN, ADOLESCENTS – NO EXPERIENCES YET (with bupropion, vareniclin) Category C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. NEW RECOMMENDATION •TO EXCLUDE PERSONS WITH PSYCHIATRIC DISORDERS • •NEUROPSYCHOLOGICAL OBSERVATION OF VARENICLINE USERS • •CARDIOVASCULAR EVENTS According to studies, it is good to watch psychiatric patients CV problems - can occur VACCINATION •AFTER UNSUCCESSFUL ATTEMPTS: THE HIGH-MOLECULAR COMPLEX • • NICOTINE + ANTIBODIES = > • •IMPOSSIBILITY TO REACH THE BRAIN A large molecule does not reach the brain FIRST RESULTS: •BIVALENT VACCINE •5 DOSES of 400 ug •IN ONE MONTH INTERVALS • •SAFE, SPECIFIC, RARE SIDE EFFECTS •HIGH INDIVIDUAL VARIABILITY IN PRODUCTION OF ANTIBODIES • But the production of antibodies may not be sufficient - enough for 2-3 cigarettes and then no longer works Duration and success of cessation •Treatment of min. 6 months Abstinence longer than a year - 2 - 3% of smokers can abstain alone and without help • •With counseling (treatment under professional supervision) + psychotherapy = increased success rate up to 30% • •75 - 85% of smokers would like to stop 30-35% are trying to (repeatedly) 5 - 10% of smokers will succeed FUTURE RESEARCH •OPTIMAL TIME-SCHEDULE • •OPTIMAL DOSES with the respect to • GENETIC POLYMORPHISM of CYP2A6 • •QUICK RELEASE OF NICOTIN • •COMBINATION • •NEW TREATMENT • •NEW (safe sources of) ADDICTION Time schedule - in general - nicotine decomposition of different speed - individualize Cytochrome P450 2A6 (CYP2A6) is the principal enzyme involved in the metabolic activation of tobacco-specific nitrosamines to their ultimate carcinogenic forms and metabolism of nicotine. Quick release - no need for those patches Quick release - spray, inhaler? RELAPS •TO TRY „ONLY ONE“ PUFF • •COFEE, VINE •FRIENDS • •SEEK THE MORE PLEASURE • •STRESS • •EASY AVAILABILITY OF TOBACCO Nicotine / cigarette still in the subconscious - never even 1 cigarette! 5. ARRANGE FOLOW-UP •RELAPS MAY BE STRESSFUL FOR SMOKER • •TO ENHANCE SMOKER´S RECENT MOTIVATION TO STOP OR FIND NEW ONE • •BETTER ARRANGEMENT More help Rethink, reinforce, or replace the old motivation Usually up to 5.-6. the attempt is successful BAN OF SMOKING ON PUBLIC PLACES • •18 months after implementation: •INCIDENCE of MI DECLINED BY 33% • from 150.8 to 100.7 / 100.000 • •INCIDENCE of SUDDEN CARDIAC DEATH DECLINED BY 17% from 109.1 to 92.0 / 100.000 • •Minnesota Study , Arch.Intern.Med. Doi: 10.1001/2013.jamainternmed.46 • SMOKE-FREE LEGISLATION • •LOWERED RATES OF HOSPITAL ADMISSIONS for: • • RR •CORONARY EVENTS ……… 0.848 •OTHER HEART DIS. ………… 0.610 •CEREBROVASCULAR DIS. … 0.840 •RESPIRATORY DIS. ………… 0.760 • •Circulation 2012; 126: 2177 - 2183 • risk ratio (RR) or relative risk is the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group CONCLUSION •THE RISK IS BIG •STOPPING SMOKING WORKS •THE EARLIER START OF STOPPING, => •THE BETTER RESULTS -FOR SMOKER -FOR SMOKER´S RELATIVES -FOR THE WHOLE SOCIETY •NOT FOR THE TOBACCO COMPANIES C:\Documents and Settings\prof. Hrubá\Plocha\amputee.jpg RECOMMENDATION •FOR NO - SMOKERS: • •DO NOT START TO SMOKE • •DO NOT ALLOW TO BE A VICTIM OF RUTHLESS SMOKERS MY RECOMMENDATION • FOR SMOKERS: •DO RESPECT THE NO-SMOKERS´ RIGHTS TO BREATHE THE CLEAN AIR !!! •DO CLEAN THE TOXIC WASTAGE (butts) • •DO MAKE THE RIGHT DECISION (TO STOP SMOKE) •DO KEEP IT BECAUSE … • THE LIFE WITHOUT TOBACCO IS •MORE FREE •MORE MODERN •MORE CLEAN •MORE AROMATIC •MORE SENSUOUS •MORE ….