1. Fiore et al, U.S. Dept of Health and
“Difficult to identify any other condition that presents such a mix of lethality, prevalence, and neglect, despite effective and readily available interventions”
Fiore et al, U.S. Dept of Health and
Human Services, June 2000

2. “Smoking kills. If you're killed, you've lost a very important part of your life.”
Brooke Shields

3. Tobacco-related deaths within Australia compared with other causes – 2003 (AIHW)
Begg S, Vos T, Barker B, Stevenson C, Stanley L, Lopez AD. The burden of disease and injury in Australia PHE 82. Canberra: Australian Institute of Health and Welfare; 2007.

4. Smoking rates 2007 Young people aged 16-24 25-30%
Single parent (female) 45%
Aboriginal people 50%
People in prison 75% +
People with a mental illness 70-90%
Homeless adults %
Drug treatment groups %

5. Classification of nicotine dependence
305.1 Nicotine Dependence (substance use disorder)
Nicotine dependence and withdrawal can develop with all forms of tobacco
Cessation produces well-defined withdrawal syndrome
Use nicotine to relieve or avoid withdrawal symptoms on waking or after situation where use restricted
Continued use despite knowledge of medical problems related to smoking
Diagnostic & Statistical Manual of Mental Disorders (DSM-IV). (American Psychiatric Association)
Standard definitions of drug addiction have been adopted by various organizations including the World Health Organization and the American Psychiatric Association. Although these definitions are not identical, they have in common several criteria for establishing a drug as addicting. The central element among all forms of drug addiction is that the user’s behaviour is largely controlled by a psychoactive substance (i.e., a substance that produces transient alterations in mood that are primarily mediated by effects in the brain). There is often compulsive use of the drug despite damage to the individual or to society, and drug-seeking behaviour can take precedence over other important priorities. The drug is “reinforcing” - that is, the pharmacologic activity of the drug is sufficiently rewarding to maintain self-administration … Tobacco use and nicotine in particular meet all these criteria.
US Surgeon General (1988) The Health Consequences of Smoking: Nicotine Addiction

6. What Do They Say BUT... It’s different...
It’s population health issue...
Poor people got enough to deal with...
Got a right to smoke…
Have a choice to smoke…
Anyway the staff smoke…
Great way to form therapeutic relationship...
BUT...

7. Barriers to Tobacco Dependence Treatment
Lack of staff training
“not my role” – go to primary care
Staff fear that patient’s will misuse NRT or smoke while taking NRT
Staff who smoke – normalize smoking, staff may help patient’s access cigarettes, program may sell cigarettes
Restrictive formulary
Limited income and cannot afford OTC medications

8. Consequences & Costs of Not Treating Nicotine Dependence
Increased Mortality
Increased Morbidity
Increased use of health care resources
Decreased Quality of Life
Increased Societal Costs, including costs to employers

9. The Vicious Cycle of Smoking and Disadvantage
Social Disadvantage and Deprivation:
 Adverse circumstances (Unemployment, lone parenthood, homelessness etc)
 Stress
 Isolation
 Smoking as “normal”
 Unsafe neighbourhoods
Limited recreation
Makes Circumstances Worse:
 Less money for essentials
 Greater financial stress
 Poorer health and wellbeing
Creates Vulnerability to Smoking:
 As a means of coping with difficult circumstances
 As a response to stress and exclusion
 As an ‘affordable’ recreation
Smoking prevalence:
 Increased smoking
 Less quitting
 Higher relapse
(Cancer Council, 2008) 9

10. Motivating clients to stay smoke free
Health may not be primary motivator
Other factors might be:
-stigma related to being a smoker
-restricted access to places, activities
-cost of smoking
-being able to reduce medication
-relief from stress related to
neuroadaptation to nicotine, withdrawal,
topping up, withdrawal etc (addiction cycle)

11. Nicotine Dependence and Major Depressive Disorder (MDD) (Breslau et al 1993)
A clear relationship has been identified between smoking and depression.
Presence of MDD increases the probability of persistent smoking, decreases the rate of smoking cessation and increases the rate of relapse.
You may also need to use a depression measure , for example CES-D (NSW Government Action Plan , Mental Health for Emergency Departments 2001) if there is a history of depression. Other depression measures, such as the Beck Depression Scale may also be appropriate
  A clear relationship has been identified between smoking and depression.
·       Presence of a Major Depressive Disorder (MDD) increases the probability of persistent smoking, decreased the rate of smoking cessation and increases the rate of relapse.
·       Authors looked at a random sample of 995 subjects between 20 and 30, over a 14-month period. They found:
1.  Incidence of becoming a regular smoker was significantly higher for those with a history of MDD.
2.  Subjects with a history of MDD were twice as likely to progress to a more severe level of dependence.
3.  First incidence MDD was more common in persons with a history of nicotine dependence (3:1). Recurrent MDD was also more common in persons with a history of nicotine dependence. (Nicotine Dependence and Major Depressive Disorder (MDD) Breslau et al 1993)
  A more recent study (Leadbeater, 2004) found that teenage girls who smoked were 40% more likely to experience major depression than their non smoking peers.
  The presence of an anxiety disorder during adolescence is predictive of nicotine dependence in adulthood (Picciotto et al 2002).
Smokers have been found to score significantly higher on measures of anxiety than non-smokers
However, people who have quit smoking tend to have reduced levels of stress than current smokers (Parrot et al 1995).

12. Health Effects Smoking causes:
Heart attack
Stroke
Cancer
Emphysema
Bronchitis
Asthma
Ulcers
Premature ageing
Impotence
miscarriage

13. Drivers of smoking - physical addiction
The brain is ‘switched on’ by nicotine, releasing ‘feel good’ chemicals (dopamine), as nicotine hijacks the role of acetylcholine to release dopamine at the receptor
Can occur after smoking one cigarette per day over few days
Inhaled and delivered to blood in seven seconds
Hits the brain in ten seconds
Short ‘half-life’ of only 20 to 40 minutes, meaning smokers need to be constantly ‘topped up’
The cycle of ‘feel good’, withdrawal, and ‘top up’ reinforces addiction

14. Drivers of smoking - the behavioural aspect
Smoking-associated environmental stimuli (cues)play a role in reinforcing nicotine dependence8
Stressors and triggers may lead to unexpected cigarette use after quitting. These may lead to a full relapse and failed cessation attempts
The most effective treatment includes both pharmacological and behavioural therapy
Caggiula AR et al. Importance of nonpharmacological factors in nicotine self-administration. Physiol Behavior 2002; 77:683–687

15. How addictive is Nicotine?
“If it weren’t for the nicotine in tobacco smoke people would be little more inclined to smoke as they are to blow bubbles” MH Russell, tobacco researcher, 1974
Criteria for addiction?
Smoke to obtain blood level of nicotine - cease smoking - withdrawal symptoms - relapse
Continue to smoke despite negative consequences (social, medical, financial).
User: Addict ratio Alcohol: 20:1
Heroin: 5:1
Nicotine: 2:1

16. Genetic predisposition?
In the majority of cases, smokers attending the clinic will report at least one parent was a smoker.
Recent research has implicated the Beta-II subunit of the nicotinic receptor in smokers.
It has also been argued that neonates exposed to tobacco smoke develop upregulated nicotine receptors, leading to susceptibility to nicotine dependence.

17. Brief Intervention + Pharmacotherapy
Ask about tobacco use
Advise to stop smoking
Assess willingness to quit
Assist with quit plan
Arrange follow up
Clinical Practice Guidelines :Treating Tobacco Use and Dependence, U.S. Dept of Health and Human Services , Public Health Service 2000
Guideline analysis suggests that a wide variety of clinicians can implement these brief strategies effectively. The goals of these strategies are clear: to change clinical culture and practice patterns to ensure that every patient who uses tobacco is identified and offered treatment. The strategies underscore a central theme: it is essential to provide at least a brief intervention to all tobacco users at each clinical visit. Several observations are relevant to this theme. First, institutional changes in clinical practice are necessary to ensure that all patients who use tobacco are identified for intervention .Second, the compelling time limits on primary care physicians visits often require brief interventions, although more intensive interventions would produce greater success. Third, although many smokers are reluctant to seek intensive cessation programs, they nevertheless can receive a brief intervention every time they visit a clinician.
(http;//

18. ASK
Routine screening on forms - tick boxes for current smoker, non-smoker and ex-smoker (and when last smoked)
If a known smoker, ask “how do you feel about your smoking at present?”
ALWAYS RECORD!

19. ADVISE
Clear ,personalised, clinically-linked advice about quitting smoking from a health professional increases abstinence rates
“When you stop smoking, your diabetes/cardiac/respiratory symptoms will improve”
“The best thing for your health would be to quit smoking”
Clinical Practice Guidelines :Treating Tobacco Use and Dependence, U.S. Dept of Health and Human Services , Public Health Service 2000

20. ASSESS 1.Willingness to quit “are you interested in quitting?”
“would you be interested in a ‘cut down then stop’ approach?”
2.Level of dependence
-Fagestrom Test for Nicotine Dependence
-Shortened Fagestrom

21. Assessment 2 simple questions to assess for extreme dependence are:
“How soon after waking up do you smoke your first cigarette?”
“How many cigarettes a day do you smoke?”
When time and resources are limited and it is not practical to use the full FTND, nicotine dependence can be assessed using the 2 questions above, as these consistently return higher biochemical indicators of smoking (Heatherton et al 1989; Fagerstrom et al 1990)
In cases of extreme dependence smokers usually smoke within 30 minutes of waking and smoke at least 10 cigarettes, usually more
In cases where a longer intervention can be employed, you may also need to use a depression measure , for example CES-D (NSW Government Action Plan , Mental Health for Emergency Departments 2001) if there is a history of depression. Other depression measures, such as the Beck Depression Scale may also be appropriate
  A clear relationship has been identified between smoking and depression.
·       Presence of a Major Depressive Disorder (MDD) increases the probability of persistent smoking, decreased the rate of smoking cessation and increases the rate of relapse.
·       Authors looked at a random sample of 995 subjects between 20 and 30, over a 14-month period. They found:
1.  Incidence of becoming a regular smoker was significantly higher for those with a history of MDD.
2.  Subjects with a history of MDD were twice as likely to progress to a more severe level of dependence.
3.  First incidence MDD was more common in persons with a history of nicotine dependence (3:1). Recurrent MDD was also more common in persons with a history of nicotine dependence. (Nicotine Dependence and Major Depressive Disorder (MDD) Breslau et al 1993)
  A more recent study (Leadbeater, 2004) found that teenage girls who smoked were 40% more likely to experience major depression than their non smoking peers.
  The presence of an anxiety disorder during adolescence is predictive of nicotine dependence in adulthood (Picciotto et al 2002).
Smokers have been found to score significantly higher on measures of anxiety than non-smokers
However, people who have quit smoking tend to have reduced levels of stress than current smokers (Parrot et al 1995).

22. Assessment
Information about low nicotine products or reducing amounts of cigarettes are less relevant as people titrate to achieve their normal blood nicotine levels by:
smoking faster
taking deeper breaths
smoking more of the cigarette
In general, smokers become dependent on a specific nicotine blood level (usually 30-40ng/ml).
When smokers attempt to ‘cut down’ or switch to lower yielding brands subconscious ‘titration’ of the dosage of nicotine gained from each cigarette occurs.
In other words, smokers will inhale more deeply, or hold the smoke in their lungs for longer, in order to obtain an equivalent level of nicotine.
Consequent effects on health include increased carbon monoxide delivery and likelihood of permanent lung damage.
(“The Management of Nicotine Addiction” Renee Bittoun ,1998 Dept Psychological Medicine ,Uni. of Sydney)

23. ASSIST
Help includes:
-Information on why smoking/nicotine is addictive
-Regular sessions
-Empathy and support
- Advice on the use of a pharmacotherapy

24. ASSIST
Plan ahead
Triggers can happen quickly so have a plan on how to deal with them e.g. write the plan down and keep in wallet/purse to help in these situations
Make sure you have some oral NRT (if using) with you at all times to help with triggers and cravings
Ask what worked and what didn’t with previous quit attempts
Don’t quit before a party, wedding, or stressful event
Quit with a family or friend
Plan spending extra $$$ as a reward
Organise medication

25. The Fagerstrom test for nicotine dependence (full version)
Source: NSW Health (2005) “Let’s take a moment” quit smoking brief intervention – a guide for all health professionals. Sydney: NSW Health.

26. The Fagerstrom test for nicotine dependence (short version)
Source: NSW Health (2005) “Let’s take a moment” quit smoking brief intervention – a guide for all health professionals. Sydney: NSW Health.

27. Nicotine Withdrawal
Usually at worst in the first hours, then decline in intensity gradually over next 2 weeks.
Symptoms may include craving for tobacco (can be strong, but typically come in bursts - only last a short time) plus 4 (or more) of the following within 24 hours of cessation, often causing significant distress :
Dizziness
Coughing
Tingling sensations in extremities
Appetite changes
Constipation
Decreased heart rate
Insomnia
Depressed mood
Increased appetite or weight gain
Irritability, frustration or anger
Anxiety
Difficulty in concentrating
Restlessness
Recovery symptoms etc
In addition to craving for tobacco, the DSM-IV states that symptoms of nicotine withdrawal include four (or more) of the following within 24 hours of cessation or reduction of nicotine intake:-
depressed mood,
insomnia,
irritability frustration or anger,
anxiety,
difficulty in concentrating,
restlessness,
decreased heart rate,
increased appetite or weight gain.
(PLEASE NOTE; OTHER COMMON WITHDRAWAL SYMPTOMS ARE ADDED INTO THE SLIDE ABOVE)
These symptoms cause clinically significant distress, are not due to a general medical condition and are not better accounted for by another mental disorder.
Some smokers report that smoking helps relieve depression and conversely some smokers become severely depressed after stopping smoking. Neurochemical effects of nicotine, including release of dopamine, norepinephrine and serotonin resemble effects of some antidepressent medications (Degenhardt & Hall 2001).
(See Page 10 of ‘Guide for the management of nicotine dependent inpatients’)

28. ARRANGE FOLLOW-UP Is client returning to you for follow-up?
Do they need a referral to GP/Community Health/cessation expert?
Have you made Quitline fax referral?
If they don’t want a referral, have they taken a “Quitline” brochure?

29. Treatment of nicotine dependence
Commonly used methods for quitting smoking:
Cold turkey; although a high proportion of smokers attempt quitting this way, most will relapse and require multiple attempts to achieve permanent abstinence.
Hypnotherapy and acupuncture; There is no actual reported evidence that acupuncture has any effect on withdrawals or abstinence rates. Similar with hypnotherapy.

30. Nicotine Fading; Many smokers attempt to reduce nicotine intake to assist quitting. As mentioned earlier, smokers are likely to titrate their nicotine dose. Another consequence is the increased rewarding effect of each cigarette smoked.
Pharmacotherapies; Currently the most effective tool for treatment of nicotine dependency. NRT has been well evaluated and has shown efficacy well above placebo effect. Zyban and Champix good option for some pts

31. Treating the addiction
Approved pharmacotherapies
Nicotine replacement therapy (NRT)
Bupropion hydrochloride (Zyban)
Varenicline (Champix)

32. GENERAL INFORMATION about Nicotine Replacement Therapy products
NRT relieves cravings & withdrawal symptoms whilst the smoker deals with breaking their habits around smoking.

33. GENERAL INFORMATION about Nicotine Replacement Therapy products
A very low risk of nicotine toxicity from NRT.
A very low risk of addiction to NRT.
All the evidence states that nicotine obtained from NRT is safer than that obtained from smoking tobacco.
There is sufficient evidence that using NRT to abstain from smoking in situations where smoking is prohibited is well tolerated.

34. FOR HEAVY SMOKERS!! It is better to put patch on before going to bed so that the nicotine level in the blood is high on waking especially if you reach for cigarette on waking May need to put on another patch in the morning
Due to the fact that most smokers reach for their first cigarette as soon as they wake up in the morning, it is better for the patch to be applied at bed time so that the level of nicotine is high on waking. If the patch is not applied until awake, it takes some time for the nicotine level to rise, therefore making it hard to resist having the first cigarette.
Patches can cause dreams, but nicotine peaks during the night.
Heavy smokers may need a new patch on in the morning. Start on 21mgm patches.

35. NRT Side Effects - patch
Skin reaction / rash
Treat area with cortisone cream
Vivid dreaming / insomnia
Apply patch before retiring OR remove patch during sleeping hours
Pain in upper arm
Use alternate NRT mechanisms for a few days

36. NRT Side Effects - Gum Jaw pain, hiccups
Try alternate NRT products for a few days.
Nausea
Remind/educate on proper use….
(Remember – ‘mouth patch’).

37. CORRECT USE OF GUM Start immediately on waking
Liberal usage
Use as often as “feel” like smoking
Don’t chew - bite infrequently
Half an hour per gum, then discard
No drinks while gum in mouth
If enough gum is used, smoking will not be necessary
Heavy smokers need high gum usage
Nicotine gum comes from the tobacco plant
Nicotine stays in mouth even after gum has been thrown away – different from inhaled cigarette

38. NRT Side Effects - lozenge
Hiccups, heartburn, nausea
Alternate between delivery devices for a few days.
Check correct use – dissolve in mouth, DO NOT CHEW.

39. INHALER
Lets you control the amount of nicotine you get when you get a craving to smoke
Less concentrated &
less addictive than if you smoke
Leaves out the poisons found in cigarette smoke
Consists of a porous plug of polyethylene which contains nicotine and menthol. The plug is packaged in a transparent tube which is sealed at both ends with aluminium foil. Prior to use the tube is inserted in a mouthpiece and the seals are broken. When air is drawn through the plug gaseous nicotine and menthol are released.
The inhaler lets you control the amount of nicotine you get when you get a craving to smoke. By holding the inhaler between your fingers and puffing on it, you will get the nicotine your body needs to control your craving, but in a less concentrated – and less addictive – dose then when you smoke.
The process, as with patches and gums, does not release nicotine rapidly, but it does replicate some of the smoking rituals. After use, the device is spent and cannot be reused or recycled.

40. Inhaler
-attach the cartridge to the tube, and inhale for the next minutes. Throw cartridge out
You can put it down and pick it up during that time, but if you leave it for more than 1 hour , 1.5 hr max, the vapour (volatile substance) has gone and is not viable
People often use the one cartridge all day , but this is only a placebo effect.
Use 6-12 cartridges / day for best effect

41. Plasma nicotine levels – NRT vs. cigarettes925
Cigarette 20 15
Spray
Plasma nicotine (mg/ml) 10
Gum/Inhaler/Tablet
The cigarette is ‘a wonderfully efficient nicotine delivery device, delivering the optimum dose of nicotine, rapidly, to the dependent brain’.19
NRT products give lower peak-plasma concentrations of nicotine at a slower pace and, as a result, lack the rapid onset of pharmacological action achieved with a cigarette.19
As the slide shows, NRT products provide plasma nicotine levels of about a third to a half those achieved by cigarette smoking.9
REFERENCES
9. Royal College of Physicians of London. Nicotine addiction in Britain: A Report of the Tobacco Advisory Group of the Royal College of Physicians. London: Royal College of Physicians, 2000.
19. Moxham J Nicotine Addiction Br Med J 2000; 320: 5
Patch 10 20 30 40 50 60
Time (minutes)
9. Royal College of Physicians of London. Nicotine addiction in Britain: A Report of the Tobacco Advisory Group of the Royal College of Physicians.
London: Royal College of Physicians, 2000.

42. Changes to NRT indications20
More than one form of NRT can be used concurrently
NRT can be used by pregnant and lactating smokers
All forms of NRT can be used by patients with cardiovascular disease
All forms of NRT can be used by smokers aged 12 to 17 years
There have been some recent changes to the indications listed for NRT products as follows:20
More than one form of NRT can be used concurrently
- Patients with a history of failure of quit attempts using a single form of NRT should be offered a combination of 16 hour patch with 2mg gum (approved combination in Australia)
NRT can be used by pregnant and lactating smokers
- For pregnant women intermittent dosing products may be preferable as these usually provide lower daily dose of nicotine than patches, however, patches may be preferred if the woman is suffering from nausea
Patches should be used during the night time sleep
For lactating women, patches are not recommended
Women should breastfeed just before using an intermittent NRT product
All forms of NRT can be used by patients with cardiovascular disease
NRT should be offered in any case where the alternative is the patient resuming smoking
In patients with cardiovascular disease that is not stable or controlled by treatment, the decision to prescribe NRT should be made in consultation with the supervising physician
All forms of NRT can be used by smokers aged 12 to 17 years
Those prescribing or supplying NRT should check that the young person is:
nicotine dependent enough to warrant use of NRT
is committed to stopping smoking
willing to accept counseling
All patients using NRT should consult their GP prior to using NRT
REFERENCE
20. ASH Australia. Nicotine replacement therapy – Guidelines for Healthcare Professionals on using NRT for smokers not yet ready to stop smoking. February 2007.
20. ASH Australia. Nicotine replacement therapy – Guidelines for Healthcare Professionals on using NRT for smokers not yet ready to stop smoking. February 2007.

43. the evidence supports the following conclusions:
Cut down then stop21
the evidence supports the following conclusions:
Nicotine replacement helps smokers unwilling or unable to stop achieve sustained reduction in cigarette consumption
This reduction is accompanied by a reduction in smoke intake (biochemically validated)
There is minimal risk of significant adverse reactions to smoking concurrently with nicotine replacement
Smoking reduction using NRT increases motivation to stop smoking
Smoking reduction using NRT increases subsequent cessation
As most of you will have seen, some of the NRT companies have decided to try a different tack with their approach to smoking cessation – they’ve introduced ‘cut down then stop’.
New research suggests that cutting down first with NRT can increase the numbers of smokers who go onto stop completely. The evidence shows that if smokers who are not ready to stop use nicotine gum or inhaler to help them reduce their cigarette consumption by at least 50%, approximately 4% will actually stop smoking as a result. Given that about half of smokers are interested in cutting down rather than stopping at any one time, this could significantly increase the numbers of smokers that stop.21
REFERENCE
21. ASH Australia. Nicotine replacement therapy – Guidelines for Healthcare Professionals on using NRT for smokers not yet ready to stop smoking. February 2007.
Adapted from reference 21. ASH Australia. Nicotine replacement therapy – Guidelines for Healthcare Professionals on using NRT for smokers not yet ready to stop
smoking. February 2007.

44. Cut down then stop
Good for people who may not be ready to quit but who want to move towards it, or who smoke high volume
Smoker chooses one cigarette to miss, same time every day for a week or , using oral NRT instead
Next week, choose another cig to drop
Over 6 months aim to reduce by half
Stops smokers titrating dose and creating positive reinforcement

45. Combined NRT patch and bupropion
Combination therapy
Combined forms of NRT
Combine rapid onset form (e.g. gum, lozenge, inhaler) with slower delivery
form (e.g. patch)
More effective than single form of NRT in dependent smokers2
Offer if smoker experiences withdrawal symptoms, or quitting unsuccessful on single form of NRT
Combined NRT patch and bupropion
More effective than NRT patch alone
Consider if quitting unsuccessful with monotherapy
Combination of NRT delivery systems
In more dependent smokers combinations of different forms of NRT are more effective than one form alone.2
Though not approved in the product information for NRT formulations, rapid onset and slower onset nicotine delivery systems have been combined in a number of studies such as the transdermal patch, for a steady background nicotine, supplemented by gum for immediate relief of craving. A meta-analysis of combination therapies (Fiore et al, 2000) showed that combination therapy almost doubles cessation rates at 12 months compared to one form of therapy. Like other patients on NRT, patients on high-dose and combination therapy should be monitored for symptoms of under or overdosing.2
The Smoking Cessation Guidelines for Australian General Practice recommend that combination NRT should be offered if patients are unable to remain abstinent or continue to experience withdrawal symptoms using one type of therapy.
NRT (patch) plus bupropion2
The Smoking Cessation Guidelines for Australian General Practice recommend that combination treatment with bupropion and nicotine patch should be considered where a smoker has not been successful on an adequate trial of one of these therapies. Blood pressure should be monitored during treatment, as elevated BP was noted in some patients on combination therapy (especially those with pre-existing hypertension).
Combination with varenicline has not been studied and therefore is not indicated.
REFERENCE
2. Australian Government Department of Health and Aging. Smoking Cessation Guidelines For Australian General Practice. Practice Handbook Available from
Adapted from reference 2. Australian Government Department of Health and Aging. Smoking Cessation Guidelines For Australian General Practice.
Practice Handbook Available from

46. Bupropion is contraindicated in the following patients
Buproprion - Zyban
The most frequently reported adverse effects were insomnia, headache, dry mouth, nausea, dizziness and anxiety
Bupropion is contraindicated in the following patients
Past or current seizures
Known CNS tumours
Undergoing abrupt withdrawal from alcohol or benzodiazepines
Current or previous history of bulimia or anorexia nervosa
Those taking monoamine oxidase inhibitors or who have taken them within the last 14 days
The safety of bupropion in pregnancy has not been established
In the clinical trials, the most frequently reported adverse effects were insomnia, headache, dry mouth, nausea, dizziness and anxiety.
As with all drugs, Bupropion sustained release has contraindications and these need close monitoring.
To date the safety of bupropion in pregnancy has not been established.
REFERENCES
23. ZYBAN SR® (bupropion hydrochloride). Approved Product Information. eMIMS. Last updated Sept 2007.
23. ZYBAN SR® (bupropion hydrochloride). Approved Product Information. eMIMS. Last updated Sept 2007.

47. Varenicline (Champix®) designed for smoking cessation
Varenicline was designed specifically for targeting the nicotinic
receptor responsible for nicotine dependence: the 42 nicotinic
acetylcholine receptor24
First in class with novel mode-of-action
Champix® is PBS reimbursed in Australia
As previously mentioned, we know the pathway to addiction via the nicotine binding to the alpha4 beta2 receptor causes release of dopamine leading to the pleasure and rewarding effects of cigarette smoking. Varenicline was identified to address this and the unmet medical need for additional non-nicotine therapies.
It is a first in class with a novel mode of action which we will cover off briefly in the next few slides.
Champix® has received registration in Australia and is PBS-listed.
REFERENCE
24. Coe JW et al. Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. J Med Chem 2005; 48:
Adapted from 24. Coe JW et al. Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. J Med Chem 2005; 48:

48. Varenicline: A selective 42 acetylcholine receptor partial agonist25,26
Antagonist
Prevents stimulation of the receptor
by nicotine
This reduces the pleasurable effects
of smoking and potentially the risk of
full relapse after a temporary lapse
Partial agonist
Binds with high affinity to the 42
receptor, only partially stimulating
dopamine release
Provides relief from craving and
withdrawal symptoms
Varenicline was specifically engineered and designed to address nicotine addiction by targeting the α4β2 nicotinic acetylcholine receptor.
Nicotine in cigarette smoke reaches the brain within seconds of a single puff of a cigarette and attaches to acetylcholine receptors. The alpha4beta2 acetylcholine receptor is responsible for the development of nicotine addiction. These receptors are also up regulated by nicotine and increase in number with a prolonged history of smoking.
Varenicline binds with high affinity (higher than nicotine) to the alpha4 beta2 where it has a dual mechanism of action. By acting as a partial agonist, it releases dopamine, approx. 60% of the amount released by the union with nicotine, which results in the improvement of the symptoms of cravings and withdrawal. At the same time, it blocks the union of nicotine to the receptor, agonist action, reducing the rewarding and reinforcing effects of smoking.25
REFERENCES
25. Jorenby DE et al. Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation. JAMA 2006; 296:56-63.
26. Gonzales D et al. Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation. JAMA 2006;296:47-55.
25. Jorenby DE. et al. Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation.
JAMA 2006; 296:56-63.
26. Gonzales D et al. Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation.
JAMA 2006;296:47-55.

49. Safety and tolerability of varenicline
Varenicline has a favourable safety and tolerability profile. It can even be safely administered for up to one year28
The most frequently reported adverse events with varenicline were nausea, headache, insomnia and abnormal dreams29
Nausea was reported by approximately 30% of patients treated with varenicline 1mg bid25,26,29
discontinuation rate due to nausea was low (<3%) and generally described as mild or moderate and decreased over time
Varenicline has not been studied in pregnancy, childhood or in patients with history of, or intercurrent psychiatric illness
Serious neuropsychiatric symptoms have occurred in patients being treated with varenicline.
Although a causal association has not been established, in some reports the association cannot be excluded
All patients being treated with varenicline should be observed for neuropsychiatric symptoms
NICE Guidelines (July 2007, UK), stated that varenicline is recommended within its licensed indications as an option for smokers who have expressed a desire to quit smoking.
The most frequently reported adverse events during clinical trials (>10%) with varenicline were nausea, headache, insomnia, and abnormal dreams. Nausea was reported by approximately 30% of patients treated with varenicline 1 mg bid, with approximately a 3% discontinuation rate during 2 weeks of treatment. Nausea was generally described as mild or moderate and often transient. For some subjects, it was persistent over several months.26
Patients who cannot tolerate these adverse effects of varenicline may have the dose lowered temporarily or permanently to 0.5mg twice daily. This is from the European SPC and not the Australian PI for varenicline.
Varenicline has not been studied in pregnancy, childhood or in patients with history of, or intercurrent psychiatric illness .
Special considerations (based on current A.E. reports some of your delegates may ask about patient safety and Champix. Please answer any queries with the statement below and then refer to Pfizer medical information).
Serious neuropsychiatric symptoms have occurred in patients being treated with Champix. Some cases may have been complicated by the symptoms of nicotine withdrawal in patients who stopped smoking; however some of these symptoms have occurred in patients who continued to smoke. All patients being treated with Champix should be observed for neuropsychiatric symptoms including changes in behavior, agitation, depressed mood, suicidal ideation, and suicidal behavior. These symptoms, as well as worsening of pre-existing psychiatric illness, have been reported in patients attempting to quit smoking while taking Champix in the post-marketing experience. Patients with serious psychiatric illness such as schizophrenia, bipolar disorder, and major depressive disorder did not participate in the pre-marketing studies of Champix and the safety and efficacy of Champix in such patients has not been established. Patients attempting to quit smoking with Champix and their families and caregivers should be alerted about the need to monitor for these symptoms and to report such symptoms immediately to the patient’s healthcare provider.
REFERENCES
25. Jorenby DE et al. Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation. JAMA 2006;296:56-63.
26. Gonzales D et al. Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation. JAMA 2006;296:47-55
27. Tonstad S et al. Effect of maintenance therapy with Varenicline on Smoking cessation. JAMA 2006;296: Williams KE et al. A double-blind study evaluating the long-term safety of varenicline for smoking cessation. Current Medical Research and Opinion 2007;23 (4):
29. Champix® (varenicline tartrate) Approved Product information. Pfizer Australia Pty Ltd.
25. Jorenby DE et al. Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation. JAMA 2006; 296:56-63.
26. Gonzales D et al. Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation. JAMA 2006;296:47-55
29. Champix® (varenicline tartrate) Approved Product information. Pfizer Australia Pty Ltd

50. Varenicline tablets should be swallowed whole with water
Varenicline – dosing29
Varenicline is indicated as an aid for smoking cessation in adults over 18 years
The patient should set a date to stop smoking: varenicline dosing should start 1-2 weeks before this date
Varenicline tablets should be swallowed whole with water
Varenicline tablets can be taken with or without food
Varenicline tablets for oral use with titration as shown
Varenicline is supported with a patient support programme
Days 1-3
0.5mg once daily
Days 4-7
0.5mg twice daily
Day 8 – end of treatment
1mg twice daily
Patients will be started on a low-dose for 3 days with a slow increase over the next 7 days. Titrating the dose is important to improve tolerability.
Varenicline pharmacology29:
Half life about 24 hours
Cmax within 3 to 4 hours
Steady state reached within 4 days
Oral bioavailability unaffected by food
92% of drug is excreted unchanged
No inhibition of cytochrome P450 enzymes
No clinically meaningful drug interactions identified
No dose restrictions in patients with hepatic insufficiency
Dose adjustment required for severe renal impairment
No dosage adjustments necessary for elderly patients unless renal impairment
Use of varenicline in smoking cessation is likely to be cost effective
Varenicline is supported by a behaviour support programme – additional support increases the chances of quitting
REFERENCES
29. Champix® (varenicline tartrate) Approved Product information. Pfizer Australia Pty Ltd.
29. Champix® (varenicline tartrate) Approved Product information. Pfizer Australia Pty Ltd

51. Cue conditioning
Behavioural rituals closely associated with smoking provide opportunities for secondary conditioning
These rituals become associated with smoking and lead to craving.
Cue conditioning: when one stimulus is paired with another over a series of trials, the reaction to the initial stimulus can be elicited through the exposure to the second stimulus. E.g. pavlovs dog

52. Relapse factors In the first week of quitting
Partner or others at home smoke
Alcohol intake not modified(initial stages)
Person has “just one puff” or “just one cigarette”
More likely in afternoon/evening

53. Drug Interactions
Some medications need to be reduced as client reduces nicotine e.g. some anti-psychotics, antihypertensives, insulin.
Same meds will need to be increased if client relapses
halve caffeine intake
limit or stop alcohol for a couple of weeks(relapse factors)

54. Environmental Tobacco Smoke (ETS)
Sidestream smoke: drifts from the end of a burning cigarette
Mainstream smoke: breathed out by the smoker
Tobacco smoke contains over 4,000 harmful chemicals including 69 compounds known to cause cancer

55. Environmental Tobacco Smoke
Just because you can’t see it , that doesn’t mean that it can’t harm you.
Some components of smoke linger in the air for hours, breaking down into even more harmful chemicals.
Particulate matter (tiny pieces of solid material) can cling to clothing and be inhaled by the non-smokers
Gas and particle chemicals generated through smoking include irritants and toxicants such as:
hydrogen cyanide
Sulphur dioxide
Mutagens (which cause cells to mutate)
Carcinogens (which cause cancer)
Teratogens (reproductive toxicants which can cause birth defects)
Researchers from Columbus Children’s Hospital, Ohio found that even in homes where parents reported never having smoked inside the house , children still had measurable levels of cotinine (a by-product of nicotine) in their hair. This would be caused by close contact after the parent has finished smoking a cigarette.
This also means that smokers are inhaling the leftover harmful gases and particulate matter as well

56. Ventilation
Smoking by the back door or near an open window doesn’t remove the exposure to ETS
Total removal of tobacco smoke through ventilation or filtration is both technically and economically impractical
Vehicles are another enclosed space to consider
Despite the best modern filtration systems , many of the carcinogens and other dangerous components of tobacco smoke can be re-circulated through buildings’ ventilation systems and into non-smokers apartments or offices.
It is almost impossible to achieve separation from smoke, even outdoors if you are within a few metres of the ETS. The work of James Repace shows that you would need to have 50,000 litres of air per second to achieve separation or some degree of air purity. This is equivalent to a tornado.
Remember that any enclosed space poses a problem in terms of ETS. Cars are a place where people often smoke in the belief that the rush of air through the window will be sufficient ventilation, but this is not true.
ETS is worse from low tar filter cigarettes, being 20-30% more mutagenic. This is because the sidestream smoke is not going through the filter.

57. Quitline Fax Referrals
Takes advantage of smoker’s motivation at the time of a brief intervention
Can provide the high level of support needed at beginning of quitting process
Patient feels that some practical help has been offered

58. Emma 26 years old Smokes 20-30/day
Has had numerous attempts at stopping smoking
First cigarette aged 8, no break since that time
Partner smokes
2 months pregnant
History of depression, recalls becoming depressed after last quit attempt
What issues will you need to consider for this client?

59. John 55 y.o. Currently smokes 35-40/day
Diagnosed with schizophrenia age 20
Fagerstrom score 11/11
Drinks 4-5 cups of coffee and 2-4 cans of cola daily
Taking medication for mental illness
Some cognitive impairment
What issues will you need to consider for this client?

60. Martin 39 yrs old Single dadsmoking since age 12 20-30 cigs/day
On the methadone program
Has had only one serious quit attempt 2 yrs ago
Some nights drinks 5-6 cans of beer
What issues do we need to consider?