1	"The Guide to the Cardiovascular..." The Guide to the Cardiovascular Consequences of Smoking and the Benefits of Cessation Prof. Dr. Hany Ragy
2	Epidemiology of Smoking
3	"1.25 billion smokers Worldwide" 1.25 billion smokers Worldwide 30 million smokers added every year 84% of smokers live in developing countries Africa & Middle East (17% of World’s population) accounts for 7% of World’s total cigarette consumption 8 smokers die every minute
4
5	Tobacco – a major health problem now and for the future
6	Section 2: The Hazards of Smoking
7
8	Smoking: Multiplicative Risk Factor for Coronary Artery Disease
9	Smoking: Increased Progression of Aortic Atherosclerosis
10	Smoking: Increased Stroke Mortality Cigarette smoking increases the risk of mortality from stroke in men
11	Insulin Resistance and Smoking
12	Insulin Resistance Syndrome in Male Smokers A syndrome in which endogenous insulin fails to produce an adequate physiologic response from fat, muscle, and liver cells Compared with nonsmoking men of similar age and BMI, smokers had Insulin resistance Higher fasting levels of triglycerides Lower HDL-C Elevated C-peptide levels, consistent with compensatory increase in insulin release as a result of insulin resistance Larger adipose mass at the expense of lean body tissue without increased weight Lipid intolerance
13	Type 2 Diabetes Mellitus
14	Risk of Type 2 Diabetes Mellitus: Men
15	Risk of Developing Type 2 Diabetes: Men
16	Smoking Cessation and Risk of Type 2 Diabetes
17	Smoking-Associated Hyperglycemia: Pathophysiology Increase in free fatty acids might be cause of insulin resistance Cigarette smoking may release free radicals that could reduce insulin sensitivity Tobacco use can stimulate epinephrine and norepinephrine Direct toxic effect on pancreatic cells has been suggested
18	Summary: Smoking and the Endocrine System Postmenopausal bone loss is greater in smokers than in nonsmokers Women who smoke have an increased risk of developing Graves’ disease Smoking is associated with an increased incidence and clinical severity of Graves’ ophthalmopathy Male smokers have a higher incidence of insulin resistance than male nonsmokers Smokers are at increased risk of developing diabetes Risk of type 2 diabetes decreases with increased duration of smoking abstinence
19
20
21	Environmental Tobacco Smoke: Prevalence of Heart Disease
22	Importance of Not Smoking During Pregnancy
23	Hookah: Waterpipe Tobacco Smoking Shisha, a mixture of tobacco, molasses, and fruit flavors used in the hookah Water in the hookah does not diminish tobacco toxicity A 1-hour session of hookah smoking exposes the user to 100- 200 times the volume of smoke inhaled from a single cigarette Smoke produced contains high levels of carbon monoxide, heavy metals, and other carcinogens Delivers significant levels of nicotine
24	Why Quit? Potential Health Benefits of Quitting Smoking
25	Quitting at Any Age May Increase Life Expectancy Age Stopped Smoking: 45–54 Years Old
26	Nicotine Addictive or Just a Bad Habit??????
27	WHAT IS ADDICTION? ”Compulsive drug use, without medical purpose, in the face of negative consequences” Alan I. Leshner, Ph.D. Former Director, National Institute on Drug Abuse National Institutes of Health
28	Mechanism of Action of Nicotine in the Central Nervous System Nicotine binds preferentially to nAChRs in the central nervous system; one key area is the α4β2 nicotinic receptor in the VTA After nicotine binds to the α4β2 nAChR in the VTA, dopamine is released in the nAcc which is believed to be linked to reward
29	The Cycle of Nicotine Addiction Nicotine binding causes an increase in release of dopamine^1,2 Dopamine gives feelings of pleasure and calmness¹ Competitive binding of nicotine to nicotinic acetylcholine receptors causes prolonged activation, desensitization, and upregulation²
30	The Cycle of Nicotine Addiction ( continued) As nicotine levels decrease, receptors revert to an open state causing hyperexcitability leading to cravings^1,2 The dopamine decrease between cigarettes leads to withdrawal symptoms of irritability and stress¹ The smoker craves nicotine to release more dopamine to restore pleasure and calmness¹
31	Withdrawal Syndrome: A Combination of Physical and Psychological Conditions, Making Smoking Hard to Treat
32	The (DIFFICULT) DECISION to QUIT Faced with change, most people are not ready to act. Change is a process, not a single step. Typically, it takes multiple attempts.
33	Why Some Smokers May Need More Help to Quit It takes most smokers a number of quit attempts before they are finally smoke-free. Why Relapse? The nature of addiction, not the failure of the individual In the United States, of 19 million adults who tried to quit in 2005, only ~4%–7% were likely successful Although most relapse occurs early after the quit attempt, some relapse can happen months to years later
34	"The greatest risk of relapse..." The greatest risk of relapse is during the first three months after quitting. 37% have their first lapse between 8:00pm and midnight 50% are likely to relapse in the first month 67% are likely to relapse in the first three months
35	Many Health Organizations Emphasise the Important Role Physicians Can Play in Helping Their Patients Quit Smoking
36	US PHS Guideline – Treating Tobacco Use and Dependence: 2008 Update Tobacco Dependence Support – The “5 A’s”
37	US PHS Guideline – Treating Tobacco Use and Dependence: 2008 Update Tobacco Dependence Support – The “5 A’s” Ask about tobacco use at every visit Advise to quit in a clear, strong, and personalised manner Assess willingness to make a quit attempt Assist in quit attempt with counselling, pharmacotherapy, and social support Arrange follow-up through personal and telephone contact and continue supporting, encouraging, and treating the patient Referral to a specialist can also be valuable to Assist and Arrange smoking cessation treatment
38
39	US PHS Guideline – Treating Tobacco Use and Dependence: 2008 Update First-line Pharmacotherapies for Tobacco Dependence¹ Nicotine replacement therapy (NRT) Patch Gum Inhaler Nasal spray Sublingual tablets/lozenges Bupropion SR Champix (Varenicline)
40	Nicotine Gum Dosing Chew at least 9 pieces/day during first 6 weeks Chewing technique critical to correct use Use for 12 weeks Avoid alcohol and caffeinated beverages Side effects Local: irritation of tongue, mouth and throat, ulceration of oral mucosa, jaw-muscle ache Systemic: indigestion, nausea, dizziness
41	Nicotine Patch Dosing 1 patch/day worn for 16 or 24 hours Available doses range from 7-21 mg/patch Side effects Local: skin irritation, rash More marked reactions with 24-hour patch Systemic: insomnia, sleep disturbances, dyspepsia To limit sleep disturbances, e.g., vivid dreams, remove 24-hour patch before bedtime
42	Bupropion for Tobacco Dependence Mechanism of Action is still uncertain Reuptake inhibitor of dopamine in the nucleus accumbens and noradrenaline in the locus ceruleus May also act as weak antagonist of α4ß2 nicotinic receptors Dosing 300 mg (150 mg BID) Begin therapy while still smoking Side effects Dry mouth and insomnia Risk of seizure: approximately 1 in 1,000 Contraindicated for patients with seizure disorder or predisposing factors that increase seizure risk (head injury, active substance abuse, eating disorder)
43	CHAMPIXä (varenicline) A Selective a4b2 Nicotinic Acetylcholine Receptor Partial Agonist
44	Champix as a Partial Agonist In the absence of nicotine Champix has agonistic effects causing amelioration of nicotine withdrawal symptoms. It provides a low-to-moderate level of dopamine stimulation to reduce craving & withdrawal symptoms.
45	Champix as an Antagonist In the presence of nicotine, Champix is blocking nicotine-induced reward by having antagonistic blocking effects at a4b2 receptors. The antagonist effect blocks the reinforcing effects of nicotine & potentially reduces the risk that a lapse to smoking would turn into a full blown relapse.
46	Champixä (varenicline) Efficacy Measurements: CO-Confirmed 4-Wk Continuous Abstinence Rates Wks 9–12
47	Champix versus Transdermal Nicotine Patch for smoking cessation: 4-Wk Continuous Abstinence Rates
48	Post-Marketing Data
49	Champix Safety Profile Approximately 4000 individuals were exposed to Champix during placebo-controlled clinical trials¹ Discontinuations due to adverse events (AEs) were¹: 11.4% varenicline 1 mg 9.7% placebo Most common AEs (≥10%) with champix 1 mg vs placebo were¹: Nausea Abnormal dreams Insomnia Headache
50	Very Wide Experience around the World since the Launch
51