Post on 19-Mar-2016
description
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
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 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
Dopaminergic N Glutamatergic N
GABAergic N
NicotinNicotine vaccine
D3 receptor antagonists
Dopamin neuronal reuptake inhibitors
Cannabinoid 1 receptor antagonist
NRT
Nicotinic receptor antagonists
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
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
α4β2 recres res α 7 rec
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
Dopaminergic N Glutamatergic N
GABAergic N
MAO
Nicotine vaccine
D3 receptor antagonists
Dopamin neuronal reuptake inhibitors
Cannabinoid 1 receptor antagonist
NRT
Nicotinic receptor antagonists
MAO inhibitors
Nicotine
α4β2 recres res α 7 rec
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
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
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)
Ricardo P.and Neal L.B.trends in pharmacological science. Article in press
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)
Ricardo P.and Neal L.B.trends in pharmacological science. Article in press
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
Dopamin D3 antagonists
GSK598809 (Phase II)
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
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
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
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…..