1. Nicotine Dependence and Smoking Cessation Presented by: A. Al-Ahdal Therapeutics III Clinical Pharmacy Department KAUU- 2006/2007

2. Why Smoking Cessation is Important? More than 500,000 smoking related deaths occur per year Nearly one in five deaths was attributable to smoking Tobacco is the leading preventable cause of illness and death Fifty billion dollars in medical expenses a year can be attributed to cigarette smoking Smoking contributes to and exacerbate many age- related diseases Chronic Obstructive Pulmonary Disease (COPD) Chronic Obstructive Pulmonary Disease (COPD) Asthma Asthma

3. Hypertension Hypertension Cardiovascular Disease Cardiovascular Disease Stroke Stroke Atherosclerosis Atherosclerosis Peptic Ulcer Disease Peptic Ulcer Disease Gastroesophageal Reflux Disease (GERD) Gastroesophageal Reflux Disease (GERD) Diabetes Diabetes Impotence Impotence Cancer: Lung, Oral, Larynx, Esophagus, Kidney, Bladder, Pancreas Cancer: Lung, Oral, Larynx, Esophagus, Kidney, Bladder, Pancreas Why Smoking Cessation is Important?

5. Why Quit Tobacco Use? Benefits “Improve Your Health & Lifestyle” Benefits “Improve Your Health & Lifestyle” 20 minutes: BP, HR, and temperature of hands and feet become normal 20 minutes: BP, HR, and temperature of hands and feet become normal 8 hours: O 2 and CO 2 levels in blood return to normal 8 hours: O 2 and CO 2 levels in blood return to normal 1 day: risk of heart attack begins to decrease 1 day: risk of heart attack begins to decrease 2 days: sense of smell and taste improves. Nerve ending starts to regrow. 2 days: sense of smell and taste improves. Nerve ending starts to regrow. mucous in airways begins to break up and clear out of your lungs mucous in airways begins to break up and clear out of your lungs 2 weeks to 3 months: Circulation becomes better and 2 weeks to 3 months: Circulation becomes better and

6. Why Quit Tobacco Use? breathing improves breathing improves 1 to 9 months: Coughing, sinus congestion, shortness of breath and fatigue decrease 1 to 9 months: Coughing, sinus congestion, shortness of breath and fatigue decrease 1 year: Risk of heart disease is less then half of one year ago 1 year: Risk of heart disease is less then half of one year ago 5 years: From five to fifteen years after quitting, stroke is reduced to that of people who have never smoked 5 years: From five to fifteen years after quitting, stroke is reduced to that of people who have never smoked 10 years: Risk of lung cancer drops to as little as one- half that of continuing smokers 10 years: Risk of lung cancer drops to as little as one- half that of continuing smokers 15 years: Risk of heart disease is similar to that of people who have never smoked 15 years: Risk of heart disease is similar to that of people who have never smoked Saves Money $$$$... Saves Money $$$$...

8. Neurochemistry of Nicotine Addiction Inhalation of nicotine  to the brain Stimulating the release of Dopamine in the midbrain  Nicotine activates the dopamine reward pathway (a network of nervous tissue in the middle of  the brain that elicits feeling of pleasure/arousal in response to stimuli)  key pathway area in the brain responsible for thinking, & judgment

9. Neurochemistry of Nicotine Addiction Chronic administration of nicotine increases number of nicotine receptors in specific regions of the brain  tolerance Continous smoking  more tolerance, & dependence Dependant smokers consume 10-40mg of nicotin/day to minimize symptoms of withdrawal

10. Pharmacology of Cigarette Smoke More than 4000 substances including some that are pharmacologically active, antigenic, cytotoxic, mutagenic, and carcinogenic have been identified in cigarette smoke The two cigarette components thought to cause greatest risk are nicotine and carbon monoxide Δ Clear Highly toxic weak base Δ Clear Highly toxic weak base Δ Ganglionic stimulant and depressant Δ Ganglionic stimulant and depressant Δ Effects mediated by catecholamine release Δ Effects mediated by catecholamine release Δ Increased serum conc. of glucose, cortisol, free fatty acids, Δ Increased serum conc. of glucose, cortisol, free fatty acids, and vasopressin and vasopressin 1.Nicotine

11. Pharmacology of Cigarette Smoke 1.Carbon Monoxide Δ Interferes with oxygen transport and utilization Δ leads to elevated carboxyhemoglobin levels Δ Chronic carboxyhemoglobin levels lead to mild polycythemia Metabolism – liver, & to a lesser extent kidney, lung. (70-80%) of Nicotine T1/2= (2hrs),  C otinine T1/2 =18-20hrs inactive metabolite, a marker of tobacco use, and exposure to 2 nd hand smoke Excretion – PH dependent, acidic urine  excretion nicotine and metabolites, found in breast milk, blood, & urine of nursing infants

12. Assessment of Nicotine Dependence Number, type (high vs. low nicotine) Fagerstrom Score  5min or less 6 to 30 min ½-1 hr > 1hr How soon after you wake up do you smoke your 1 st cigarette? YesNo Do you find it difficult to refrain from smoking in places where its forbidden? 1 st one in AM Anyother Which cigarette would you hate to give up most? >3021-3011-20<10 How many cigarettes do you smoke per day? YesNo Do you smoke more frequently during 1 st hr after waking than during the rest of the day? YesNo Do you smoke if you are so ill that you are in bed most of the day? Score >5 is high nicotine dependence

13. Nicotine Withdrawal Diagnostic Criteria for Nicotine Withdrawal American Psychiatric Association. DSM-IV A. Daily use of nicotine for at least several weeks B. Abrupt cessation of nicotine use, or reduction in the amount of nicotine used, fallowed within 24hrs by > or =4 of the following signs: Dysphoria or depressed mood Dysphoria or depressed mood Insomnia Insomnia Irritability, frustration, or anger Irritability, frustration, or anger Anxiety Anxiety Difficulty concentrating Difficulty concentrating Restlessness Restlessness Hunger/ weight gain Hunger/ weight gain Significant distress or impairment in social, occupational, and other important areas of functioning Significant distress or impairment in social, occupational, and other important areas of functioning

14. General Steps in Smoking Cessation Intervention Agency for health care policy and research (AHCPR) Clinical Practice Guidelines Step 1. Ask -Identify all tobacco users at every visit Step 2. Advise -Strongly advise all smokers to quit Step 3. Identify -all patients willing to quit (history) Step 4. Assist -the patient in quitting -Anticipate challenges to planned quit attempt -Anticipate challenges to planned quit attempt -Set a quit date -Set a quit date -Provide advice on how to successfully quit -Provide advice on how to successfully quit -All patients should be offered nicotine replacement therapy -All patients should be offered nicotine replacement therapy Step 5. Arrange -Schedule follow-up contact

15. Discuss Potential Problems This smoke contains many irritants and poisons. It is especially dangerous for babies and young children. Their lungs are delicate. Children who breathe this smoke are more likely than other children to get sick. They may have more mucus. The fluid in their middle ears may build up and cause ear infections. They may develop pneumonia, bronchitis and other lung infections. If they have asthma, it may get worse.

16. Patient Management Options Behavioral Therapy Behavioral Therapy Used to teach patients the problem-solving skills needed To deal with the cessation (Clinical Practice Guidelines) - Barriers/concerns - Coping skills - Barriers/concerns - Coping skills - Dealing with triggers - Others - Dealing with triggers - Others Increase long-term cessation rates by 1.5 to 2 fold over pharmacotherapy 1.5 to 2 fold over pharmacotherapy alone alone Should be strongly encouraged

17. Pharmacologic Therapy Nicotine Replacement Therapy (NRT) NRT Increases success for quitting by reducing the physical Withdrawal symptoms associated with nicotine cessation along with adjusting to behavioral changes, coping skills and physiological aspects of quitting, plus NRT slow onset of action vs. smoking nicotine

18. Nicotine Gum OTC (Nicorette ® ) ِ Appropriate use Adverse Effects Dosage - Fixed schedule - No > 30pc/day (2mg gum) -No > 20pc/day (4mg gum) -Chew slowly tingling sensation, park between cheeks (1pc. For 30’) -Wait 15’ ø food/drink -No any nicotine use Mouth/jaw soreness Mouth/jaw soreness Hiccups Hiccups Dyspepsia Dyspepsia incorrect chewing  incorrect chewing  - N/ V - N/ V - lightheadedness - lightheadedness - throat & mouth - throat & mouth irritation irritation 2mg,4mg;regular,mi nt,orange ≥25 cig/ day: 4mg <25 cig/ day: 2mg Week 1-6: 1 piece Q 1-2hrs Week 7-9: 1 piece Q 2-4hrs Week 10-12: 1 piece Q 4- 8hrs Duration Up to 12wks

19. Transdermal Nicotine OTC Light smoker Heavy Smoker [ ≤ 10-15 cigs/day] Nicoderm CQ ® or Nicoderm CQ ® or Habitrol ® Habitrol ® -14mg x 2weeks - 7mg x 2 weeks [ ≤ 5 cigs/day] NRT not necessary Duration 8-10wk [>10-15 cigs/day] Nicoderm CQ ® (16 to 24hr) Nicoderm CQ ® (16 to 24hr) 7mg, 14mg, 21mg 7mg, 14mg, 21mg -21mg x 6 weeks -14mg x 2weeks -7mg x 2 weeks Habitrol ® (24hr) -21mg x 6 weeks -14mg x 2-4weeks -7mg x 2-4 weeks

20. Transdermal Nicotine OTC DisadvantagesAdvantagesProduct Can not titrate dose 24hr release system Allergy to adhesive Longer onset to peak plasma conc. (6-12hr) One step process No oral S.E. Easy to use Few non-compliance Nicoderm CQ ® Allergy to adhesive Longer onset to peak plasma conc. (6-12hr) Provide 24-hr SS conc. No oral S.E. Easy to use Few non-compliance Habitrol ® ِ Adverse Effects- Vivid Dreams, Local skin reactions

21. Nicotine Nasal Spray Rx ConcernsAdvantageDosageProduct -Hot/Peppery sensation in nose/throat Sneezing/coughing -watery eyes -runny nose -Dependence -Dose easily titrated -Use to respond to cravings 1-2 doses/hr (8-40 doses/day) One dose=2sprays (one in each nostril) Start 8 doses/day No> 5doses/hr 40 doses/day Nicotrol NS ® NASAL spray 0.5mg nicotine in 50UL aq. Nicotin sol Duration: 3-6 mo - Ø Break habit - Dependence - Bad taste, cough -hiccups, HA -Dyspepsia-Rhinitis -nasal/throat irrit. -Dose easily titrated -Mimics act of smoking -Use to respond to cravings 6-16 cartridges/day Depleted after 20’ Open cartridge retains potency for 24hrs Use @ least 6/day Nicotrol ® Oral Inhaler 10mg cartridge delivers 4mg inhaled nicotine vapor Duration: up to 6 mo

22. Bupropion SR Rx Zyban ® Sustained-release tablet, Dose: 150mg PO Q AM x3 day, then  to 15omg po BID, 8-12 wk - Set quit date 1-2 weeks after initiation of therapy. -Do NOT exceed 300mg/day - Allow at least 8 hours between doses -Avoid bedtime dosing to minimize insomnia MOA: unknown, but thought Neurochemistry, enhancing dopamine level in themesolimbic system (pleasure center), nicotine addiction is due to dopaminergic S.E. Dry mouth, Insomnia, Nervousness/difficulty concentrating Duration: up 6 mo

23. Bupropion Cont. side effects: Anxiety, restlessness and insomnia. At high doses, it may cause seizures, so it is not a good choice for individuals with epilepsy or brain injuries. Cont. side effects: Anxiety, restlessness and insomnia. At high doses, it may cause seizures, so it is not a good choice for individuals with epilepsy or brain injuries. Usage: You must take Bupropion two or three times a day to limit its side effects, although an extended- release form is available that can be used once or twice a day. This drug may cause seizures when taken in large amounts.

24. Smoking and pregnancy It is well known that smoking during pregnancy can damage the baby and even cause a miscarriage. Compared with non-smokers, smoking during pregnancy can cause: Reduced birth weight Increased risk of the baby dying just before or just after birth just before or just after birthUrinary