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Health disorders related to tobacco use and passive

smokingAntigona Trofor Ph. D. M.D.

Clinic of Pulmonary Diseases, University of Medicine and PharmacyIasi, Romania

Complexity of the tobacco use effect on human health

• Biological effect of chemical compounds from tobacco smoke: carbon monoxide, nicotine, resin, irritants

• Risks for diseases• Target organs ( respiratory, cardiovascular diseases)• Addictive nature of nicotine: social and behavioral aspects,

psychological aspects

Scientific proofs – smoking is harmful

1) if no disease occurs: life expectancy shortens with 5-8 years!

2) if disease occurs: life expectancy shortens with 18-22 years!!

3) the adverse health effects of smoking are extensive and scientifically documented today;

• There is a strong dose-response relation with heavy smoking, duration of smoking and early uptake. This reflects in higher risks of smoking related diseases and mortality.

4)Mortality related to smoking: 1990 - 35% of deaths in men; 2002 – 4 million deaths; 2020 – 10 million deaths.

5) Useful for statistics: Relative Risk (RR) = risk of a smoker to develop a certain disease compared to the risk for the same disease a nonsmoker might have.

Biomarkers of smoking

• Biochemical validation allows to estimate the systemic exposure to toxins in tobacco smoke, when studying the risks of smoking.

• Evaluation:

Self – reported cigarette smoking;

Measurement of expired CO;

Determine cotinine (nicotine’s metabolite which is an objective proof of its presence in the body) in saliva,

urine, blood, hair, cervical fluid;

Elevated levels of serum thyocianate.M.S. Jaakkolla, 2000

Smoking and health• Short-term effects:

Psychoactive: memory, energy, disposal, emotions, attention, behavior, sleep disorders;Increasing heart rate and arterial pressure;Peripheral vasoconstriction;

Increasing respiratory rhythm.

• Long-term effects:Respiratory diseases;Cardiovascular diseases;Ophthalmological, digestive, oral, urinary and osteoarticulary diseases;Different cancers;Reduces immunity;Negative consequences on fertility, pregnancy and foetus.

Health disorders related to active smoking - classification

I. Severe diseases in which smoking is a certain risk factor

Chronic obstructive respiratory disorders (chronic bronchitis, emphysema);

Cardiovascular diseases: ischaemic heart disease, strokes, arterial aneurysms, systemic arterial hypertension, peripheral arteriopaty

Cancer : lung, larynx, oesophagus, throat and mouth, etc.

II. Diseases in which smoking is considered a possible risk factor or inhibits a good clinical evolution

Bronchial asthma; Infectious respiratory diseases: pneumonia, TB, etc; Other cancers: bladder, gastric, genito-urinary, pancreas; Cardiovascular diseases: cardiac disrhytmias, sudden

death, Alzheimer disease, leukemia, cataract, peptic ulcer, anxiety, periodontal disease,etc.

Chronic obstructive pulmonary disease (COPD)

Smokers are at higher risk of decreased FEV (7-33ml/yr) in a dose-response relationship;

• RR of COPD is 12,7 for smokers;• COPD occurs 6 times more often smokers, but only 20%of

smokers develop COPD, due to genetic determinants (α1 - antitripsine gene, α2 -macroglobuline genes, vitamin D - coupling gene) and phenotypic susceptibility (sex, bronchial hypersensitivity and atopy);

• Besides smoking, other causes of COPD: - Environmental risk factors in childhood + low

socioeconomic status;- Prenatal smoke exposure;- Air pollution - Repeated respiratory infection - Occupation

Ng.TP,Hui KP - 1993

• Active chemical compounds (toxic and irritants) from smoke induceinflammatoryinflammatory changes in changes in

the airwaysthe airways, in the lung lung parenchymaparenchyma

(neutrophilic infiltration, alveolitis) with damage

of the strucural and cellular defense system

impairment of the

mucociliary clearance of the airways.

Tobacco smoke COPD

COPD• Survival was estimated to 50%, at 5-10 yrs, when diagnosis revealed• FEV < 1l survival can be 1-3 yrs;• Smoking cessation – real benefit in COPD, as if not, COPD can

become the third leading cause of death in 2020!

Advantages of smoking cessation in COPD Even late cessation is benefic; Decreasing severe exacerbation rates; Better efficacy of bronchodilater inhaling therapy; Lower risk of associated cardio-vasculary complications; Decreasing COPD mortality.

Real problem! Smokers with COPD, continuing to smoke. Usually they

are heavy smokers, heavily addicted, males, low in come, poor education and not willing to quit.

Petty TL, 2000

Cardiovascular diseases (1)• Nicotine

• Both nicotine and carbon monoxide contribute to development of ateromatous plaques, which lead to a decreased elasticity of the arteries and opposing a higher resistance to blood flow. Andrikopoulus G, 2003

• Consequence

ATEROSCLEROSIS – basis of future cardiovascular dysfunction

Discontinuing blood flow (obstruction) in the vessels

Blood vesselsHTA, circulatory peripheral

defficiency, arterial aneurysms

Heart vessels (coronares)

ischaemic heart disease

Brain vessels: strokes

Cardiovascular diseases (2)

1. Systemic arterial hypertension – vascular (capilar) spasm leading to paroxistic blood pressure risk.

2. Peripheral obliterative arteriopaties Carbon monoxide from tobacco smoke is responsive for the lack of oxygen

delivered to brain and muscles. As a result of peripheral circulatory disorders, arteritis occur.

3. Ischaemic heart disease• Smoking is incriminated in 81% cases due toNicotine – producing great amount of cathecolamines which results in increased

blood hypertension and high heart rateCarbon monoxide - a negative role in oxygen intake to the brain, heart and skeletal

muscles vessels: 1/3 of deaths by cardiovascular diseases are atributed to smoking; RR for ishcaemic coronaropathy is 1,6; Favourable action: hyperlipidemia, hereditary factors, arterial hypertension;• The risk of heart attack is double over 60 yrs but can be five fold increased for

under 50 yrs. Andrikopoulus G, 2003

4.Strokes• Cerebro-vascular disturbances occur when systemic

aterosclerosis (expressed also at the carotid artery) goes together with systemic arterial hypertension.

• The disease is polimorphic: transitory cerebral ischaemia; silent brain infarctus; strokes; cerebral haemorrhagic accidents.5. Aneurysms Fogari et al, 1997• Smokers develop aortic aneurysms 5 times more frequently,

especially when heavy smokers, deep inhalers, with diastolic hypertension over 100 mmHg.

Active smoking and cancers

• Over 30% of deaths by different cancers are attributed to smoking.

• Main forms: lung, larynx, oesophagus, trachea, oral cavity.

• RRMajor RR for lung cancer - 15,

superior airways- 24.

Partial RR for oesophagian cancer:7,5.

Active smoking and cancer of the larynx

• Smoking is related to laryngeal cancer in 84%. Other risk factors:age (over 55), sex (4 times more frequent in men), black race, family history of head and neck cancer, occupation (exposure to nickel or asbestos, alcohol abuse).

• Prevalence in USA: 10.000 cases/year.• Cancer can locate any segment of the larynx:

vocal cords and glottis, supra or subglotic. Mainly, lesions begin in the glottis,then develop and invade locally the basic part of the tongue and then the lungs.

• Complexity and gravity of the clinical evolution, as larynx caters many functions: swallowing, breathing, talking.

Lung cancer and active smoking

• Evidence based causal relationship – over 39 years (early case control and prospective cohort studies.

• Origin: 2 reference studies – smoking is the main cause in LC (Wynder&Graham,

JAMA- 1950; Doll&Hill- BMJ, 1952) 40 years of follow-up of smokers in a prospective cohort study of male

British doctors- showing the impact of smoking on longevity and pathology at different levels of exposure (Doll&Peto, BMJ, 1994)

Obvious dose-response relationship between tobacco exposure and development of lung cancer : in Western countries risk for LC is 90% in males smokers and 80% in females smokers. The risk is lower in poor countries Also, the risk is reduce to those smoking <5 cig/days and increasing with the amount of cigarette.

• Carcinogens in tobacco smoke;• Only 10-155 of the smokers develop LC - genetic factors: glutation

transpherase, polymorphism, enzymatic equipment of CRS P456, tumoral mutations of p 53, genetic –induced nicotine dependency).

Risk is higher in relatives of patients with LC (RR= 2,4) and descendents of LC patients (RR = 5)

Lung cancer incidence is influenced by

• Tobacco consumption• Gender – RR: m/f = 1 / 2-4 1/1 1,2 - 1,7/1

(1950-1960) ( 1970-1980) (1990-2000)

- Women: lower risk: start later, inhale less deeply, smoke few.• Type of tobacco The yield of cigarettes filtered/ nonfiltered (RR is 2 in men and 2,5 in women) Pipe, cigars, narguile Light, ultralight, menthol cigarettes, long, super long.• Race• Passive smoking• Cessation Outdoor associated pollution • Diet• Genetic protection

Oral cancer and active smoking (OC)

• Incidence of (OC) varies: 2-18 times for smokers vs NS with a median fourfold increased risk

• Great risk for users of smokeless

alcohol consumers: ¾ of OC occur in both tobacco and alcohol consumers;

• OC = 3% of all cancers with a M/F ratio of 2/1;• Most common type: squamous cell carcinoma (9 of every 10 oral

malignancies)• 2/3 occur in the oral cavity and one third in the pharynx. Most

frequent locations: tongue (20%), gingiva, mouth’s floor, lip (11%), salivary gland (8%).

• Direct relationship with duration and intensity of tobacco exposure.• Important involvement: cigar and pipe users.

Smoking considered a risk factor in bronchial asthma (BA)

• Negative role of tobacco smoke Irritative compounds; Susceptibility to respiratory infections; Chronic inflamation and bronchial obstruction; Reducing aerian flow.• Indirect proofs: Intensifies symptoms and increases exacerbation rates; Passive smoking – as trigger; Higher incidence of (BA ) in children with passive tobacco exposure Clinical observations increased frequency of BA in a dose- response relationship; Lung Health Study - improvement of Clinical state after Smoking cessation Contradictory data: increasing BA incidence after cessation (Withdrawal

symptoms and subjective factors)Jaakkola MS, 2000

Active smoking and respiratory tract infections

Chemical substances in tobacco smoke damage human defense mechanisms at

• Morphological changes in the great airways – reconstruction of the bronchial mucosa in 10-20years:

nonciliated metaplastic epithelial cells, enable to remove small particles, microorganisms or mucus;

alterated composition mucus;• Neutrophilic infiltration in airway mucosa;• Inflammatory reaction with other bronchial mucosa cells: monocytes,

lymphocytes;• Intensive alveolar inflammatory reaction.

Consequence

structural level

cellular

More frequently

SMOKERS

Pneumonia

Bronchitis

Infectious exacerbations of chronic respiratory disorders

Predisposal to pulmonary TB

Local inflamation

Spectrum of respiratory tract infections in adults smokers

Smoking• frequent risk factor in community acquired pneumonia

(CAP) (RR –2 and 3,15 heavy smokers)• Cessation decreases risk to 50% after 5 years• CAP: atypical pathogens: Legionella, Chlamidia; associated with smoking related chronic diseases: Gramm

negative (Pseudomonas) or Pneumococcus, high risk of bacteriemia

• significant risk for severe pneumonia• strongest independent risk factor for invasive forms of

respiratory infections in immunecompromised hosts

Chronic bronchitis: - 50% of heavy smokers (10-20% of them develop chronic airflow distruction)

- reccurent infections exacerbation• COPD high rates of infections exacerbation result inworsening COPD symptoms

increasing airflow obstruction, sputum production

overall decline of quality of life

Severe forms FEV<35% , Enteric bacteria, Pseudomonas species

Usual acute exacerbation: Streptococcus pn.,

Haemophilus infl., Moraxella catarrhalis

Impact of active smoking an pulmonary TB

• Higher risk to develop TB especially in heavy smokers

• Comorbidity: alcohol, psychiatric disorders, diabetus

• unfavourable/delayed clinical outcome

Active smoking and other cancers

• Gastric cancer (72%) in smokers– other risk factors: alcohol, diet;

• Bladder cancer• Pancreas – 3 times more frequent in smokers • Genito-urinary renal

urinary bladder

col uterin double risk for smokers

Current Science, vol 81, no 5, september 2001

Active smoking and other cardio-vascular disorders

• Cardiac Disrhytmia (especially in association with coronaropathya)

• Sudden death – 3 times more frequent in heavy smokers

• Obliterative trombosis, obliterant trombangeitis (Buerger)

• Carotidian stenosis (especially when also hipercholesterolemia and arterial hypertension present)

Ocular effects of active smoking

• Cataract

• Especially in young people (cadmium)• Macular degeneration of the aged • Decrease in visual capacity

Surgeon General’s Report 2004

Bones and active smoking• Osteoporosis• Risk of fractures: hip

Endocrine and metabolic disorders and smoking

• Diabetus mellitus• Hypothyroidism

Surgeon General’s Report 2004

Other health disorders attributable to active smoking

• Alzheimer disease: smoking + family history + genetic predisposal to develop dementia

• Leukemia: carcinogens- benzen, toluen, 1-3 butadien achroleyne Gastric:

ulcer peptic infections with Helicobacter pilori• Hepatic – increasing pressure in the portal veine• Neuropsychiatric: anxiety- direct relationship to smoking schizophrenia, dysphoria, personality, memory or executory

functions disability

Trofor A., Radu-Loghin C., 2004

Tobacco effects in the mouth

• Leukoplakia • Smoker’s palate (nicotine stomatitis)• Smoker’s melanosis:• Tooth loss (67%) in S vs NS • Tooth abrasian:

Pindborg J.J et al, 1980

• Periodontal disease ( all conditions including supporting structures of the tooth)

destructive periodontitis (pocketing, bone loss and dental calculus) acute necrotizing ulcerative gingivitis (ANUG) focal gingival recession with periodontal attachment loss• Other tobacco-associated oral conditions gingival bleeding; dental calculus; leukoedema: hialitosis; chronic hyperplastic candidiasis (some studies suggest increased

frequency of oral Candida albicans in smokers hairy tongue (in heavy smokers)

• Possible tobacco-associated conditions dental caries dental plaque salivary changes reduced taste and smell acuity

Aesthetic conditions related to active smoking

• Yellow nails• Yellow teeth• Wrinkles• Tooth stains• Hypersalivation

Active smoking and sexual life

• Men: over 45, heavy smokers:

• Women:Secondary amenorheeaEarly climacterium (2-5 years)Infertility;Interactions to contraceptivesPregnancy difficulties: spontaneous abortion,

premature delivery,Low birth weight newborns, etc

decrease of sexual potency

Reduced fertility (number and motricity of spermatosoides)

Abnormal conditions which incriminate active smoking as a potential risk factor

• 1) Decreased serum bilirubine (known as an endogenous antioxidant) especially in men, heavy smokers, no filtered cigarettes;

• 2) Intensive eosinophilic inflammatory reaction in heavy smokers revealed by increasing eosinophils in BAL

bronchial hiperresponsiveness• 3) EEG – modifications: nicotine in cigarettes amplifies

electroenceplalogram’s frequency and produces a decrease in waves (denicotined cigarettes, releasing tar and very low levels of nicotine decreases spectral frequency of EEG)

Conclusions: Nicotine uptake in cigarette is influencing normal rhythm on EEG,

directly related to precocious registration of the brain’s activity during smoking

• 4) Visual activityNicotine is believed to improve space visual accuracy in smokersSmoking cessation determines loss of this capacity.Pascale GA et al; Pickworth WB, Hatakeyama Y. et al

Is cigar a better option?

• Almost the same spectrum of disease with certain particularities• RR is 2 for COPD; 1,5 for cardiovascular disease; 2,14 for lung cancer and 4 for superior

aero-digestive neoplasms.• Dependency• Dimensions of the cigar can influence amounts of toxic compounds in cigar

smoke,especially amonium and nitrates, also cadmium. Great concentrations of nitrates depends on the maturation processes tobacco leaves cigars are made of. Undergo.

• Specific risk:Oral, oesophagus, pharynx, larynx cancersPancreatic cancers;Stomatitis (due to iritative action of the heat burning cigar produces, as it persist longer in the mouthDental cavities;Tooth trauma

• Lung cancer risk: compared to non smokers - LC risk is 1,9 times bigger in pipe smokers, 3 times bigger in cigar smokers and 16 times higher in cigarette smokers (Higgris and col. ,1988)

• Advantages:• Occasional smokers• Rarely deeply inhaling smoke in lower airways

What about pipe?

• Risk of lung, oral, tongue cancers• Decreased mortality: SUA: 1991 1995 deaths –

pipe/year, 400000 deaths- cigarettes/ year• Advantages:

less dependent to nicotine;

Special relation – aesthetic factors (pipe, tobacco taste and flavour;

Costs;

Complexity and significance of the smoking behavior;

Easy to quit; less withdrawal symptoms

Narguile - a new trend?

• Advantages: washing tobacco process removes a lot of toxic compounds, as acroleine, aldehides, tar-fraction constitutes, phenols;

Less nicotine lower dependency;

More pleasure to smoke, flavoured, less toxic (recreative smoking);

• Disadvantages:

Dangerous concentration of carbon monoxide (better to smoke outside)

Risk of “ mouth to mouth” contamination.

Passive smoking (involuntary smoking, second-hand smoking)

History • 1970: first data- children and spouse’s exposure to

tobacco smoke;• 1980: - contradictory data - heterogenic methodology

of studies and lack of commonly accepted criteria of scientific quality in order to include data in such pooled analysis;

Definitions:• Passive smoking: exposure of a person to tobacco

combustion products from smoking by others.Also

• Exposure of a foetus to tobacco combustion products from active and passive smoking by the mother.

Passive smoking ETS (85%) • Exhaled mainstream smoke: tobacco smoke generated during puff (15%

inhaled from the burning tobacco product. This goes in to the smoker’s lungs and then goes aut exhaled in the environment;

• Sidestream smoke (85%) is composed of

Smoke released in the air directly during burning tobacco product

Smoke compounds which diffuse through the paper covering

tobacco products

ETS can be inhaled at work, at home, different closed public spaces.

Sidestream’s toxicity is due to great concentration of noxious chemicals (10-40 times more > mainstream)

Why?

Lower temperature of combustion

Poor oxygen distribution for burning

Greater duration of the break s between puffs

Constituents of ETS according to us environmental

Protection agency (US – EPA)Constituents Probable human carcinogens

Formaldehyde

Hydrazine

N- nitrosodimethylamine

N- nitrosodiethylamine

N- nitrosopyrrolidine

1,3- butadiene

Aniline

Benzo(a)pyrene

Cadmium

Irritant and toxic substances

Carbn monoxide mg

Acrolein

Acetone

Nitrogen oxides

Known human carcinogens

Benzene

2-naphtylamine

4- aminobiphenil

Polonium – 210 mBq

Nickel

Eur Respir Mon, 2002, 15, 323.European Respiratory Monograph

Assessment of ETS exposure

• Questionnaires;• Measurements of cotinine in body fluids;• Risk of exposure, ventilation of the room, volume of

air in the room;• Toxic compounds are nearly the same in mainstream

and sides team smoke, but in different amounts, as the burning conditions are not equal.

Most of those substances (including carcinogens) are found in side stream smoke at high levels, but we must be aware that side stream smoke is also diluted in a larger volume of air.

Lung cancer and passive smoking• 1981 – first association between exposure to tobacco smoke and lung

cancer (wives of smokers: Japan and Greece) • 1986 – 3 similar studies coming from US Surgeon General - 18

published undoubtable results about capacity of ETS to induce lung cancer.

• Thus, ETS became one of the KNOWN HUMAN CARCINOGENS.• 1999 – about 40 studies debated the issue.Conclusions were influenced by the including criteria, as passive

exposure was assessed depending on:Exposure at work, at home in social circumstances;Exposure from different origins in adulthood;Exposure from childhood;Cumulative exposure.

Martinet Y, 2003

Asthma and passive smoking

Can ETS exposure contribute to asthma development?Can ETS exposure contribute to asthma development?• 5 studies revealed increased risk for asthma, especially related to work

tobacco smoke exposure, with on without home exposure Greer (1993) USA - asthma diagnosis after 10 years of exposure at work OR

= 1,45 (10-100% young adults + 40-60% older adults); dose-response relationship - HU (1997) USA increased risk with number of

parents smokers; NG (1993) Singapore – in relation to heavy vs, light exposure; Lenenberger (Swiss) 1994 in relation to nr. hours of exposure/ day.

• 2 studies – no relevant association• Confusion – objective diagnosis of Asthma vs. self reporting diagnosed

asthma.ConclusionConclusion

ETS may cause Asthma in adulthoodRole of irritants in tobacco smoke chronic inflammation;Tobacco smoke is responsive for increased permeability of bronchial epithelium to allergens, leading to secondary allergic reactions.

Barnes DE, Bero LA, 1998

Effect of ETS on respiratory chronic and acute symptoms, in the absence of any

defined respiratory disease

• Acute iritative symptoms of the nose, throat, lower airways (more evident in atopic patients). Some patient may by allergic to tobacco leaves.

• Chronic symptoms: cough, sputum, dyspnoea, wheezing with an excess risk of 30-100% due to ETS exposure.Symptoms are variable according to: nr. of hours of exposure, nr.of smokers producing ETS in a room, duration of ETS exposure (years)

Impact of ETS on lung function

• Lebowitz (1984) USA: follow up of 2 years: 229 adults: no significant relationship between PEF and ETS even in asthmatic patients!

• Studies considering both home/workplace exposure, quantified actual level of exposure and child hood ETS exposure to reveale influence of ETS on lung function.

ConclusionConclusion: inconsequence of data more relevant significance of ETS role if adulthood exposure is correlated to early/childhood e exposure ( mother + spouse)

Thus, late adulthood ETS exposure seems not to dangerous, but during lung maturation period.

Cunningham J et al, 1994

Cardiovascular risk and passive smoking

• 2 - 4% time folds more frequent vs. never smokers

• 50% risk for myocardial infarctisation Associated risk factors: Arterial HypertensionDiabetus mellitusHyperholesterolemia

Glantz SA et al, 1991

ETS exposure in childhood• 1970: first alarm : effect of passive smoking on respiratory disorders in

children.• 1992: US report – causal relation ETS –illness in low respiratory tract.• Overview of 38 studies: conclude: ETS exposure in infancy and first years of

life by parental smoking generate lower respiratory illness• Wide spectrum: Bronchitis, pneumonia, Bronchiolitis (involving respiratory syncityal virus infection), Wheezing related disorders• OR for: lower respiratory tract infections diseases: 1,54 (if either parent smokers) Wheezing related disease: 1,55, but 2,09, respectively 1,53 if mothers smoke.• Great susceptibility to ETS in children – especially to infants and early

childhood. If low birth weight or lack of breast feeding is added – greater impact of ETS.

• Parental/family exposure: more influent - mother than father (other family members): smoking, mother's smoking during pregnancy

Casale R. et al., 1991

ETS role in causing respiratory symptoms in children

• One parent smoker risk for wheezing (24%), cough (40%)

• Attention:Respiratory infections contagious from ill smoking parents!Teenagers smoking without declaring!Atopy

AdjustAdjust

mentment

ETS exposure’s role on lung function in children

• Several studies suggest the importance of the “in utero” exposure to maternal smoking during pregnancy: small FEV deficits observed at school-age children.

• Addictive effect: parental smoking after birth, assessed by objective follow-up of lung-function growth in children.

• Poor prognosis: children with initially low values of lung function;

• Male children more vulnerable than female children;• Dose-response relation.

Lodrup Carlsen KC. et al, 1997, Sherrill D et al, 1998

Pharmacologic therapy of nicotine addiction

Classification

• Treatment with nicotinic substituents • Bupropion• Varenicline• Mecamylamine• Glucose• Antidepressives: Nortriptyline• Clonidine• Rimonabant• Nicotinic vaccine

Treatment with nicotinic substituents (TSN)

General landmarks:• a logical solution: the body continues to receive

the NICOTINE, but from another source.• the absorption is mainly venous: more reduced

blood level of NICOTINE, cerebral delayed affectation (minutes)

• duration of therapy: 3-6 months• side effects: minimum

TSN - general landmarks

• advantages: it can be administered to pregnant women, teenagers, old persons, patients with cardio-vascular or cerebral-vascular disorders, contraindications of Bupropion.

• precautions: pregnant women (negative influence on placentary function and the development of the fetus)

• young people <18 years old: counseling individualized programs

• cardio-vascular diseases: recent myocardial infarction, instable angina

What is nicotine?• nicotine represents the addictive component

of the cigarette, determining the addiction;• nicotine does not cause respiratory diseases

and it has not been proved that it would induce cancer.

What is NRT?• gradually, NRT provides about one third of

the nicotine of cigarettes, eliminating the noxious components of tobacco.

General presentation Nicotine Replacement Therapy

General presentation Nicotine Replacement Therapy

How does NRT function?• NRT provides the exact amount of nicotine

necessary to ameliorate the symptoms of abstinence and craving, but not enough to restore the addiction

How does NRT help?• NRT doubles the chance of success only by

personal will.

NRT - landmarks

• NRT is designed in order to «ease» the appetite to smoke and the symptoms of abstinence associated to giving up smoking, which some smokers experience when they quit.

• It has been clinically demonstrated that NRT doubles the success rate of smokers who want to quit – compared to simple will.

The portfolio of NRT products

Gum NRT Patch NRT

The portfolio of NRT products

NRT inhalator

NRT nazal spray

spray

NRT tablete

Therapeutic options of nicotinic substitution

CHEWING GUM: 2 and 4 mg• venous capillary oral absorptionPLASTERS: 16, 24 hours• cutaneous absorption• concentration: 7, 14, 21 mg, or 5, 10, 15 mg, or

15, 30 mg.• side effects: local irritations CHEWING GUM + PLASTERS: a combination

better adapted to the nicotine necessary of the body - risk of cumulating nicotinic toxicity.

SUBLINGUAL TABLETS NRT

• they are dissolved sublingually in 30 min, what remains is chewed/swallowed;

• oral and intestinal absorption;• optimum results if no more than 1 tb/hour is

consumed, doses are correlated to the degree of addiction, alkaline ph (acid ph inactivates the tablet)

• side effects: nausea, abdominal pain, cephalea, cough, tachycardia – rarely.

SPRAY NRT

• rapid absorption of NICOTINE in the blood-achieving a stable blood concentration for 30-60 min.

• a light discomfort is described in the first 2-3 days of administration

• care for patients with Bronchial Asthma /COPD (Roth and West mention the bronchial asthma crisis in a patient of 58 with HTA, COPD, chronic nicotinism)

• side effects: nasal irritations

INHALER NRT

• advantages: respects the cigarette model, provides NICOTINENICOTINE by inhalation;

• addresses the addiction of the smoking gesture.• a better control of the administered NICOTINENICOTINE dose • absorption: at the level of the mouth mucous membrane• the attained concentration of nicotine is optimum, if the

inhaler is used at room temperature • preferential indication: heavy smokers who are addicted to

the mimic of smoking • side effects: mouth irritations, throat irritations, cough,

cephalalgia, indigestions

NRT helps to cut down smoking.

The role of cutting down smoking

Cutting down smoking it self has probably few advantages but …

• it can increase the motivation of quitting later

• it can ease the subsequent quitting by reducing the nicotine addiction.

NRT – can help to…

• smoking reduction • increase of attempts to quit in those who achieve

smoking reduction• increase of successful attempts in those who try

smoking quitting.• NRT is used between the smoking episodes, in

order to prevent the acute abstinence syndrome occurring when a smaller amount of cigarettes is consumed.

BUPROPION (1997)

• antidepressant, which intervenes upon the neurological circuits involved in the nicotine addiction production, influencing the nervous transmittal by means of dopaminergic and noradrenergic- type mediators.

• side effects: headaches, insomnia, nausea, vomiting, mouth dryness;

• contraindications: ages<18, liver, kidney failure, pregnancy, anorexia/nervous bulimia, epilepsy, childhood convulsions, AVC, TCC, psychiatric disorders under IMAO treatment, concurrent administration of phenytoin, cortisone, cimetidine, antyarrhymics, teophyllines.

• dosage: 1 tb/day, 3 days, then 1tbx2/day, 7- 9 weeks (1 tb = 150mg)

• good effect upon sdr. withdrawal.• combination with nicotinic plasters – increased efficiency.

New approaches

• improved medication– ex : VARENICLINE

• better use of existent medication– combinations of various NRT products – administration of adjuvant NRT until quitting date – extended use of NRT, if necessary– NRT in order to help to smoke reduction

• better access to therapy/psychological support – pro-active help telephone lines– psychological support in primary and secondary

assistance

VARENICLINE

• new medicine, efficient, decreases the craving to smoke and diminishes the symptoms due to sdr. withdrawal.

• affinity for nicotinic receptor α4β2 (AGONIST) – stimulation of partial release of dopamine and (ANTAGONIST) - prevents stimulation of nicotinic receptor by the nicotine.

• maximum efficiency: 44%.• side effects: nausea, headaches, insomnia, sdr.

dyspeptic.• no significant medicine interactions.• sometimes – at the end of treatment: irritability,

insomnia, depression, tendency to resume smoking.• dosage: 0,5 mg/day 3 days, then 0,5mg x2/zi, 4 days,

then 1mgx2/day up to 12 weeks – treatment duration.

Other therapies • Nicotinic vaccine: the vaccination principle against

nicotine the main reason (Addiction) on account of which smoke

quitting fails. developed immunity depends on the dose of

vaccine/nicotine levels in the blood.• based on the vaccination principle against nicotine – the

main reason on account of which smoke quitting fails allowing for the development of antibodies in sufficient concentrations.

• the research revealed that developed immunity to smoke depends on the vaccine dose and on the nicotine levels in the blood. Practically, periodical vaccination would be necessary during the entire life – on this account, currently, the method does not rise the same enthusiasm as in the moment of its discovery.

Harm reduction

• Principle: ”the dependent subject is offered the substance in a pure form, administered by a certain modality, hygienically”* Desperate alternative to cigarette smoking

• products with quasi medicinal structure, also called recreational (containing only nicotine) procured mainly in the pharmaceutical circuit

Why “Harm reduction” is needed?

• Choose 1000 smokers• 700 wish to quit • 50/year succeed without medical help • 50/year succeed with medical help • 600 will not succeed – here those with severe

addiction are included.• 900 continue to smoke!!• How can we help them?