NEW TREATMENT APPROACHES İN SMOKİNG CESSATİON

1. NEW TREATMENT APPROACHES İN SMOKİNG CESSATİON Dr.Leyla Saglam Ataturk U. Medical Faculty Chest Disease Department

2. Directly or indirectly, I have no my connection to be; • Participation • studying • counselor • editor • author • Moderator • speaker with business organization. 2010 ERS Congress sponsorship - Chiesi

4. WHO • 2005 5.4 million deaths • 2015 6.4 million! • 2030 8.3 million ! • In High income countries is decreasing • In Low income countries is increasing

5. 80 % of smokers are want to quit • Most of them attempts to quit themselves • 2-3 % of them are successfull

6. AWARDİNG ABSTİNENCE SYN NEURUBİOL. CHANGES REİNFORCİNG TOLERANCE Dopamin-NA Norepinephrin-LC High stm ef High Cortical activ.

7. Nicotine Nicotinic cholinergic receptors dopamine secretion(nuc Accumbens) MAO B inhibisyonu Dopamin artışı Norepinephrine Glutamat Acetylcholine β endorphin gaba

9. Nicotine Nicotine vaccine Nicotin nAchn rec α 7 rec NRT CB1 rec Nicotinic receptor antagonists Glutamatergic N Dopaminergic N CB1 rec antagon. D3 rec MAO MAO inhibitors D3 rec antagon GABAergic N Dopamin neuronal reuptake inhibitors Cannabinoid 1 receptor antagonist D3 receptor antagonists

10. Pharmacholojic Treatment • First-line agents • Second-line agents • Agents, will can be use ın future

11. Nicotine Nicotine vaccine Nicotin nAchn rec α 7 rec NRT CB1 rec Nicotinic receptor antagonists Glutamatergic N Dopaminergic N CB1 rec antagon. D3 rec MAO MAO inhibitors D3 rec antagon GABAergic N Dopamin neuronal reuptake inhibitors Cannabinoid 1 receptor antagonist D3 receptor antagonists

12. Pharmacholojic Treatment • Nicotine Replacment Treatment (P cat D) • Gum • Lozenge • TTS ( Patch) • nasal spray • inhaler • Bupropion SR (P cat C) • Varenicline (P cat C)

13. Prefer of patient • comlpiance of patient • Experience of patient • Special condition of patient (other disease, level of deppendence) • cost

14. Nicotine replacement treatment

15. Nicotine Nicotine vaccine Nicotin α4β2 recres res α 7 rec NRT CB1 rec Nicotinic receptor antagonists Glutamatergic N Dopaminergic N CB1 rec antagon. D3 rec MAO inhibitors D3 rec antagon GABAergic N D Dopamin neuronal reuptake inhibitors Cannabinoid 1 receptor antagonist D3 receptor antagonists

17. products • Gum 2-4 mg (Cinnamon, mint, fruit, orange) • Lozenge 2-4 mg • TD patch 7, 14, 21 mg (24 h release) • Nasal spray (Metered) 0.5mg/50µl • Oral inhaler 10 mg cartridge (4mg inh nic vapor)

18. Gum (max 24 pc/day) • lozenge (max 20 pc/day) • 1-6 wk; 1 pc; 1-2 h • 7-9 wk; 1 pc; 2-4 h • 10-12 wk; 1 pc; 4-8 h

19. Adverse effects Mouth and jaw soreness, hiccups, dyspepsia, Hypersalivation Nausea, vomiting, throat and mouth irritation, Nicotine gum

20. Advantage Satisfy oral craving, delay weight gain, can titrate to manage withdrawal symp, flavors disadvantage Frequent dosing compromise compliance, dental problem, may not be socially acceptable Nicotine gum

22. Patch Adverse effects Local skin reactions, headache, sleep disturbances

23. Advantage Consistent nic levels, easy to use and conceal, fewer compliance problems disadvantage Can not titrate to manage withdrawal symp, allergic reactions, In Dermatologic disorders sholdnt be used Patch

24. NRT attention • Recent 2 weeks MI • Serious arrhytmias • Serious angina pectoris • Pregnancy and breastfeeding (Cat D) • Adolescents (younger than18)

25. GUM • Temporomandibular joint disease Nasal Spray • Chronic nasal disorders • Severe airway disease Oral inhaler • Bronchospastik disease

26. Treatment without nicotine Bupropion SR varenicline

28. Nicotine Nicotine vaccine Nicotin α4β2 recres res α 7 rec NRT CB1 rec Nicotinic receptor antagonists Glutamatergic N Dopaminergic N CB1 rec antagon. D3 rec MAO MAO inhibitors D3 rec antagon GABAergic N Dopamin neuronal reuptake inhibitors Cannabinoid 1 receptor antagonist D3 receptor antagonists Bupropion SR

29. Adverse effects ınsomnia Dry mouth Difficulty concentrating Nervousness Rash Constipation Seizures ( 0.1%) 150mg tb 1x1 d/for 3 day 2x1 Bupropion SR

30. Advantage Easy to use delay weight gain can be used with NRT may be benefical for depression disadvantage Seizure risk is increase Bupropion SR

31. Dont use • Seizure history • MAO inh • Anorexia nevrosa, blumia • Cranial trauma • Posttraumatic amnesia • Neuroleptic, alcohol use

32. Nicotine Nicotine vaccine α4β2 recres res α 7 rec NRT CB1 rec Nicotinic receptor antagonists Glutamatergic N Dopaminergic N CB1 rec antagon. D3 rec MAO MAO inhibitors D3 rec antagon GABAergic N Dopamin neuronal reuptake inhibitors Cannabinoid 1 receptor antagonist D3 receptor antagonists

33. Adverse effects Sleep disturbance Nausea Vomiting Constipation Flatulence Neurops. symptoms 0.5-1mg tb 0.5mgX1 3 day 0.5mgX2 4-7.d 1mgX2 cont Varenicline

34. Advantage Easy to use New mechanism disadvantage in 1/3 patients nausea neurops. symptoms Varenicline

36. Varenicline Criteria for Prescribing VA Center for Medication Safety, Tobacco Use Cessation Technical Advisory Group, Public Health Strategic Healthcare Group, VA Pharmacy Benefits Management Services, VISN Pharmacist Executives, and Medical Advisory Panel May 2008; Updated June 2008; Updated August 2008; Updated February 2010

37. V+B? Varenicline and bupropion sustained-release combination therapy for smoking cessation. Ebbert JO, Croghan IT, Sood A, Schroeder DR, Hays JT, Hurt RD.Nicotine Tob Res. 2009 Feb 25.

38. Dont use • Continual longtime drivers • Heavy vehicle drivers • Pilot • Airtraffic controller

42. NORTRİPTYLİNE (Tricyclic ad action, noradrenergic effect) 75-100mg/day Sedation Dizziness İmsomnia Blurred vision Constipation Nausea Dysrhytmia Hypertension Orth.hipotension tachycardia CLONİDİNE (hypertension td FDA) α2-adr agonist Withdrawal symp reduce 0.15-0.45 mg/day OR 0.1-0.3 mg/day patch Sedation Postural hypotension Dry mouth Bradycardiadizzines Constipation (β-blockers,calcium channel blockers,digitals) Second-line agents Black box

43. Will can be use in future? • Vaccines • New nicotine products • Naltrexone (Opioid rec.antagonist) • nalmefene • Moclobemide (MAO inh) • Selegiline (MAO inh) • Methoxsalen (CYP2A6 inh) • Bromocriptin • Mecamylamine (nicotin antagonist) • GTS-21(anabasine) • Rimonabant (cannabinoid-1 rec antagonist)

44. New product investigations • Nicotine vaccines • New nicotine products • MAO inhibitors • Dopamin D3 antagonists • Cannabinoidreceptor 1 antagonists

45. Nicotine vaccine Nicotin NRT Nicotinic receptor antagonists Dopaminergic N Glutamatergic N MAO MAO inhibitors GABAergic N Dopamin neuronal reuptake inhibitors Cannabinoid 1 receptor antagonist D3 receptor antagonists

46. Nicotine Small molecule need carrier protein (virus like particule, bacterial toxin components) Nicotine-antibody x blood-brain barrier

47. Nicotine vaccines Faz ı, ıı, ııı studies • Cytos AG (NIC002-Switzerland) • Celticpharma (UK-USA) • Nabi inc (USA) • Chilka lmtd • vs others

49. Cytos AG (NIC002-Switzerland • 2003 • 341 smokers (1/3 placebo) • 100 µg vaccine conjugate • 5 injection im • monthly

50. Local reactions • Fever • Flu-like symtoms • Muscle pain • headache • Disappeared within 24 hours