treatment of nicotine addiction

1. Treatment of Nicotine Addiction Jill M. Siegfried, Ph.D. Professor Department of Pharmacology E1340 Biomedical Science Tower siegfriedjm@upmc.edu

2. Health Benefits of Smoking Cessation First 6 months: improved circulation, increased lung capacity, reduced respiratory symptoms 12 months: Risk of coronary heart disease 50% that of an active smoker Five-Ten Years: Risk of stroke reduced to that of a non-smoker; risk of lung cancer 50% that of an active smoker 15 Years: Risk of CHD equal to a never smoker

3. 70% of All Smokers Would Like to Quit Only 6-8% are able to do so without interventions

4. Characteristics of Addictive Substances Withdrawal: severity of unpleasant symptoms associated with cessation Reinforcement: ability to provoke further use, in preference to other substances Tolerance: Increase in exposure needed to satisfy craving Dependence: degree to which cessation is difficult, including psychological need Intoxication: degree and type of euphoria induced

6. Proportion of Dependent Users of Addictive Substances

7. Relative Addictiveness Scores(Health 1990) 100 Nicotine 98 Crack cocaine 93 Crystal metamphetamine 85 Valium 81 Alcohol 80 Heroin 72 Cocaine 21 Marijuana Based on expert panel rankings commissioned by the National Institute on Drug Abuse, taking into account euphoric effects, availability, and number and proportion of addicted users

8. Withdrawal from Nicotine Anger/irritability Anxiety Cravings Restlessness/Nervousness Difficulty concentrating Impaired task performance Sleep disturbance/fatigue Hunger/weight gain

9. Fagerstrom Test for Nicotine Dependence How many cigarettes daily Effect of first cigarette daily vs. others Smoking upon arising Difficulty refraining from smoking Smoking when ill Smoking in the morning vs other times Maximum 10 points, 4 points or more, sign of addiction

10. Pharmacogenetics of Smoking: Protective Alleles Dopamine transporter gene (SLC6A3) 9 repeat allele shows diminished dopamine reuptake Dopamine receptor genes DRD2 A2 allele higher density of dopamine reecptors DRD4-S allele shows increased dopamine affinity Cytochrome P450 2B6 gene Slow metabolism of nicotine

11. Methods of Smoking Cessation Non-pharmacologic Counseling Behavior modification techniques Pharmacologic Nicotine replacement therapy (NRT) Psychotropic drugs (bupropion FDA approved) Combination of NRT, bupropion and counseling/behavior modification yield quit rates of up to 35% Relapse rate at 12 months: up to 75%

12. Suggested Quitting Strategy Verifying patient is in the �preparation� stage�acknowledges the problem and is ready to tackle it. Only the patient can initiate change. Set a date for quitting and inform others, identify a support group Prepare environment by removing all smoking paraphernalia Identify smoking triggers to prepare how to avoid them or substitute other behaviors Select a nicotine replacement system Initiate bupropion one to two weeks before quit date

13. Nicotine Replacement Therapy Gum, patch, inhaler, nasal spray Use of any form doubles smoking cessation rate Use of tobacco with these agents can lead to nicotine toxicity Transdermal patch: 7 mg, 14 mg, 21 mg Can be removed at night if sleep disturbance occurs Used for 8-12 weeks with tapering Thought by some to have too little nicotine, 44 mg patch now available and shown to be safe

14. Nicotine Replacement Gums: chewed intermittently for buccal absorption, can be used for years Inhaler: puffing can replace holding a cigarette, need up to 2000 puffs/day Nasal spray: les frequent use required, but more cumbersome

15. Bupropion for Cessation Up to 30% 12-month quite rates when used with NRT Atypical antidepressant, inhibits reuptake of NE, serotonin, and dopamine Initiate before quitting and continue for 12 weeks after last cigarette Contraindicated in seizure disorders, anorexia, MAO inhibitor treatment

16. Psychotropic Drugs Under Evaluation Reboxetine: inhibits NE reuptake Naltrexone: opioid antagonist, attenuates nicotine craving Fluoxetine: serotonin reuptake blocked, may help smoking cessation in those with underlying depression

17. Smoking is a Common Symptom of Psychiatric Illness 83% of patients with schizophrenia are active smokers, have difficulty quitting 69% of patients with bipolar disorder are active smokers 46% of those with anxiety disorder are active smokers 37% of those with major depression are active smokers Common genetic etiology for nicotine dependence and psychiatric illness Alpha 7 nAchR subunit genetic variant found in schizophrenia, may reduce Ach signaling