new treatment approaches İn smokİng cessatİon

NEW TREATMENT APPROACHES İN SMOKİNG CESSATİON

Dr.Leyla SaglamAtaturk U. Medical FacultyChest Disease Department

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

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

80 % of smokers are want to quit

Most of them attempts to quit themselves

2-3 % of them are successfull

AWARDİNG

REİNFORCİNG

TOLERANCE

NEURUBİOL. CHANGES

ABSTİNENCE SYN

High stm ef High Cortical

activ.

Dopamin-NA Norepinephrin-LC

Nicotine

Nicotinic cholinergic receptorsdopamine secretion(nuc Accumbens)MAO B inhibisyonuDopamin artışı

NorepinephrineGlutamatAcetylcholineβ endorphingaba

Dopaminergic N Glutamatergic N

GABAergic N

Nicotin

MAO

Nicotine vaccine

D3 receptor antagonists

Dopamin neuronal reuptake inhibitors

Cannabinoid 1 receptor antagonist

NRT

Nicotinic receptor antagonists

MAO inhibitors

Nicotine

nAchn rec

α 7 rec

CB1 rec

CB1 rec antagon.

D3 rec antagon

D3 rec

Pharmacholojic Treatment First-line agents

Second-line agents

Agents, will can be use ın future


GABAergic N

Nicotin

MAO

Nicotine vaccine




NRT


MAO inhibitors

Nicotine

nAchn rec

α 7 rec

CB1 rec

CB1 rec antagon.

D3 rec antagon

D3 rec

Pharmacholojic Treatment Nicotine Replacment Treatment (P

cat D)1. Gum2. Lozenge3. TTS ( Patch)4. nasal spray5. inhaler Bupropion SR (P cat C) Varenicline (P cat C)

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

Nicotine replacement treatment


GABAergic N

NicotinNicotine vaccine




NRT


MAO inhibitors

Nicotine

α4β2 recres res α 7 rec

CB1 rec

CB1 rec antagon.

D3 rec antagon

D3 rec

D

Adverse effects Advantage Disadvant. Cost (daily)

gum Mouth,jaw soreness, hiccups, dyspepsia,HypersalivationNausea, vomiting, throat and mouth irritation,

Satisfy oral craving, delay weight gain, can titrate to manage withdrawal symp, flavors

Frequent dosing compromise compliance, dental problem, may not be socially acceptable

10 TL

lozenge Nausea, hiccups, cough,heartburn, headache, flatulans, insomnia

+ easy to use and conceal

Frequent dosing compromise compliance, GIS side effects

TD patch

Local skin reactions, headache, sleep disturbances

Consistent nic levels,easy to use and conceal, fewer compliance problems

Can not titrate to manage withdrawal symp, allergic reactions, In Dermatologic disorders sholdnt be used

2.77 TL

Nas spray

Nasal or throat irritation, rhinitis, tearing, sneezing, cough, headache

can titrate to rapidly manage withdrawal symp

Frequent dosing compromise compliance, patient must wait 5 min before driving or useing heavy machine,

Or inh throat and mouth irritation, cough, headache, rhinitis, dyspepsia, hiccups

can titrate to manage withdrawal symp

Frequent dosing compromise compliance, cartridge shoud not be very warm or cold conditions,

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)

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

Nicotine gum

Adverse effects Mouth and jaw soreness, hiccups, dyspepsia,HypersalivationNausea, vomiting, throat and mouth irritation,

Nicotine gum

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

Adverse effects Advantage Disadvant. Cost (daily)

gum Mouth,jaw soreness, hiccups, dyspepsia,HypersalivationNausea, vomiting, throat and mouth irritation,

Satisfy oral craving, delay weight gain, can titrate to manage withdrawal symp, flavors

Frequent dosing compromise compliance, dental problem, may not be socially acceptable

10 TL

lozenge Nausea, hiccups, cough,heartburn, headache, flatulans, insomnia

+ easy to use and conceal

Frequent dosing compromise compliance, GIS side effects

TD patch

Local skin reactions, headache, sleep disturbances

Consistent nic levels,easy to use and conceal, fewer compliance problems

Can not titrate to manage withdrawal symp, allergic reactions, In Dermatologic disorders sholdnt be used

2.77 TL

Nas spray

Nasal or throat irritation, rhinitis, tearing, sneezing, cough, headache

can titrate to rapidly manage withdrawal symp

Frequent dosing compromise compliance, patient must wait 5 min before driving or useing heavy machine,

Or inh throat and mouth irritation, cough, headache, rhinitis, dyspepsia, hiccups

can titrate to manage withdrawal symp

Frequent dosing compromise compliance, cartridge shoud not be very warm or cold conditions,

Patch

Adverse effects Local skin reactions, headache, sleep disturbances

Patch

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

NRT attention

Recent 2 weeks MI Serious arrhytmias Serious angina pectoris Pregnancy and breastfeeding (Cat D) Adolescents (younger than18)

GUM Temporomandibular joint disease

Chronic nasal disordersSevere airway disease

Nasal Spray

Oral inhaler Bronchospastik disease

Treatment without nicotine

Bupropion SRvarenicline

Adverse effects Advantage Disadvantage. Cost (daily)

Bupropion SR

İnsomniaDry mouthDifficulty concentratingNervousnessRashConstipationSeizures ( 0.1%)

Easy to use

delay weight gain

can be used with NRT

may be benefical for depression

Seizure risk is increase

2.28 TL

Varenicline Sleep disturbanceNauseaVomitingConstipationFlatulenceNeurops. symptoms

Easy to useNew mechanism (failed other agents)

in 1/3 patients nauseaneurops. symptoms

6.50 TL

Bupropion SR


GABAergic N

Nicotin

MAO

Nicotine vaccine




NRT


MAO inhibitors

Nicotine


CB1 rec

CB1 rec antagon.

D3 rec antagon

D3 rec

Bupropion SR

Adverse effectsınsomniaDry mouthDifficulty concentratingNervousnessRashConstipationSeizures ( 0.1%)

150mg tb 1x1 d/for 3 day 2x1

Bupropion SR

Advantage

• Easy to use• delay weight gain• can be used with

NRT• may be benefical for

depression

disadvantage

Seizure risk is increase

Dont use

Seizure history MAO inh Anorexia nevrosa, blumia Cranial trauma Posttraumatic amnesia Neuroleptic, alcohol use


GABAergic N

MAO

Nicotine vaccine




NRT


MAO inhibitors

Nicotine


CB1 rec

CB1 rec antagon.

D3 rec antagon

D3 rec

Varenicline

Adverse effectsSleep disturbanceNauseaVomitingConstipationFlatulenceNeurops. symptoms

0.5-1mg tb 0.5mgX1 3 day 0.5mgX2 4-7.d 1mgX2 cont

Varenicline

Advantage

• Easy to use• New mechanism

disadvantage

• in 1/3 patients nausea• neurops. symptoms

Brief Suicide/Violence Risk Assessment for All Patients Before Initial Prescription

1.Are you feeling hopeless about the present or future? 2.Have you ever had a suicide attempt?3.Have you had thoughts about taking your life or harming others in the past 12 months? (if Yes, ask question 4)4.Do you have a plan to take your life?

If YES to any question, do not prescribe varenicline. Refer to a mental health professional for a more comprehensive risk assessment. Note that any patient with active suicidality should receive an emergent evaluation.

Varenicline Criteria for PrescribingVA 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

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.

Dont use

Continual longtime drivers Heavy vehicle drivers Pilot Airtraffic controller

Second-line agentsNORTRİPTYLİNE

(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)

Black box

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)

New product investigations

Nicotine vaccines New nicotine products MAO inhibitors Dopamin D3 antagonists Cannabinoidreceptor 1 antagonists


GABAergic N

Nicotin

MAO

Nicotine vaccine




NRT


MAO inhibitors

NicotineSmall molecule

need carrier protein (virus like particule, bacterial toxin components)

Nicotine-antibody x blood-brain barrier

Nicotine vaccines Faz ı, ıı, ııı studies

Cytos AG (NIC002-Switzerland) Celticpharma (UK-USA) Nabi inc (USA) Chilka lmtd vs others

Cytos AG (NIC002-Switzerland

2003 341 smokers (1/3 placebo) 100 µg vaccine conjugate 5 injection im monthly

Local reactions Fever Flu-like symtoms Muscle pain headache

Disappeared within 24 hours

6. Months abstinence %

12.Months abstinence %

High responders

57 42

medium responders

32 21

low responders

32 26

placebo 31 21

Jacquaz Cornuz et al.PloS ONe. 2008:3(6):e2547. www.plosone org

Healthy volunteers 300 µg vaccine conjugate Weekly

Four times higher antibody

http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm093830.htm

http://www.clinicaltrials.gov/ct2/results?term=nicotine+vaccine

New nicotine product investigations

İnhaled aerossolized nicotin(ARD-1600 Aradigm Corporation)www.aradigm.com/products_1600.html Metered-dose skin spray(nicotine MDTS, Acrux Limited)www.acrux.com.au Nicotine orally-dissolving film(NAL2762 NALPharmaceuticals Ltd)www.aaps.org/meetings/annualmeet/am09/index.asp

Ricardo P.and Neal L.B.trends in pharmacological science. Article in press

Other nAChR partial agonists

Dianacline Sazetidine-A Cytisine (central, eastern europe,

short half-life, poor brain penetration, Inexpensive)


Cannabinoid R 1 antagonists

Rimonabanat (anti-obesity drug) Withdrew in 2007

Surinabanat (discontinued)

Taranabanat (did not improve CS and increased psychiatric adverse events,GIS discomfort, flushing)



GABAergic N

Nicotin

MAO

Nicotine vaccine




NRT


MAO inhibitors

Dopamin D3 antagonists

GSK598809 (Phase II)


GABAergic N

Nicotin

MAO

Nicotine vaccine




NRT


MAO inhibitors

MAO inhibitors (MAO-B)

EVT 302 (orally active Phase I succesfull but Phase II failed)

www.evotec.com

Selegiline (parkinsonda kul)Oral and transdermal 10 mg/day


GABAergic N

Nicotin

MAO

Nicotine vaccine




NRT


MAO inhibitors

Behavioral interventions

Interventionist -physician -nurse -other

Intensity -3min -10min

Setting of intervention

-hospital -workplace

Modality -group -individual

Curr Opin Psychiatry 2010; 23:151-156

Behavioral interventions

Interventionist -physician -nurse -other

Intensity -3min -10min

Setting of intervention

-hospital -workplace

Modality -group? -individual

Curr Opin Psychiatry 2010; 23:151-156

Teknology driven interventions Telephone counseling Web based

Mass media Radio,Tv Newspaper Billboards Posters Leaflets booklets

Curr Opin Psychiatry 23:151-156

Conclusion 1

Physician advice İntensive support Personalized treatment Monotherapy Combined therapy Monitoring 3 month therapy?

Conclusion 2

Behavioral interventions are very important

Products, be used in our day, have been effective

Vaccine studies gives hope

Thank You wery much…..

new treatment approaches İn smokİng cessatİon

Documents

throat irritation

mouth irritation

inh throat

jaw soreness

oral craving

dental problem

fewer compliance problemscan

delay weight gain