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Education
ClinicalReview
Learning objectives
• Understand smoking and
its effect on medications
and other substances used,
such as caffeine, and to
be able to understand
and differentiate nicotine
withdrawals from “side
effects” of smoking
cessation products
• Provide evidence-based
behavioural advice for
smoking cessation and
maintaining abstinence
Competencies addressed:
1.3, 1.5, 4.2, 4.3, 6.1, 6.2, 6.3,
7.1, 7.2, 7.3
Stubbing out smoking
It has been decades since the advent of pharmacotherapies to help smokers
quit. There have been many errors made, from within the pharmaceutical
industry, to poor understanding about those errors in the eyes of the public
and health professionals.
P
rimarily, there is
confusion around the
symptoms of nicotine
withdrawal and the
wrongly assigned or misdiagnosed
side effects of the medications
used to quit smoking.
Symptoms such as aggression,
agitation, depression, sleeplessness
and constipation have been well
described prior to the advent
of any pharmacotherapies for
smoking cessation.
Examples of smoking
interfering with the metabolism of
commonly used substances lead to
a misinterpreting of side effects
from the drugs used to help the
smoker quit.
For example, it has long
been known that when smoking
tobacco, inhaled polycyclic
aromatic hydrocarbons (PAHs)
induce P450 CYP1A2 and CYP2B6
liver enzymes. Most students of
pharmacy will remember this, as
this may have significant effects
on antipsychotics such as clozapine
and olanzapine. Those old enough
may remember learning the
effects this has on theophylline
and aminophylline. Dosage of
these medications need to be
increased in a smoker by almost
double to affect clinical outcome
and halved in a smoker quitting
to avoid symptoms of overdose of
these drugs. There are now a great
deal more medications that are
>
AUTHOR
Associate Professor Renee Bittoun,
Smoking Research Unit Brain and Mind
Research Institute, Sydney Medical School
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PN0713_042.pdf
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Education
affected by PAHs and consulting
MIMs is important to keep up-todate with the ever increasing list of
medications that are affected when
quitting smoking. As these effects
are not nicotine-related, neither
Nicotine Replacement Therapy
(NRT) nor varenicline have an
effect on PAHs .
Caffeine toxicity
Less well known, but clinically
very important, is the fact that
a smoker’s caffeine and alcohol
intake affect the drugs used to quit.
Smokers are, on average, prodigious
users of caffeinated beverages
(intake at least twice as much as
non-smokers).
Smoking reduces the potency
of caffeine due to PAHs induction
of P450 CYP1A2 and quitting
increases its potency. It is not
unusual for smokers to describe
agitation, nervousness and an
inability to sleep when quitting
smoking. It is common for a smoker
using pharmacotherapies such
as nicotine replacement patches.
varenicline or other medications
to assign these as side effects of
smoking cessation products rather
than symptoms that can occur due
to the reduction of PAHs.
This error has often been
reinforced by pharmacists who
describe these symptoms as an
“overdose” of nicotine or a side
effect of varenicline.
Nicotine toxicity or overdose is
extremely rare. Caffeine toxicity
is far more common and symptoms
include agitation, nervousness and
sleeplessness. Many wrongly think
these symptoms are caused by
wearing a nicotine patch.
Underdosing
Underdosing is a major concern
in the use of NRTs. In clinical
practice, we commonly titrate NRT
against symptoms of withdrawals,
particularly urges to smoke.
Psychiatric patients have higher
plasma levels of nicotine and
may require much more nicotine
replacement therapy in order to
“replace” the nicotine plasma
levels achieved by their smoking.
Among psychiatric disorders,
patients currently or formerly
dependent on alcohol and those
with depression have been shown
to have higher plasma levels of
nicotine. These diagnoses must
be factored in when giving advice
regarding adequate NRT.
There is no evidence to support
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“
Nicotine toxicity or
overdose is extremely
rare. Caffeine toxicity
is far more common.”
cutting down doses of nicotine
patch. In the 1980s, Hurt and his
colleagues at the Mayo Clinic in
Rochester, US, were aware that
many smokers remained on the
higher dose of patches (then 21mg)
and were able to abruptly quit
using these patches after several
months without the need to taper
off to lower doses. The researchers
noted that there was no evidence
that supported cutting down patch
doses to wean a smoker off nicotine.
There is no evidence to support
starting a patient on lower doses of
NRT in relation to the number of
cigarettes they smoke per day.
Some NRT patch information
states that smoking lower amounts
of cigarettes/day warrants lower
patch strengths. As we now
know, most smokers titrate their
inhaled nicotine content and
compensate for less cigarettes/
day by dragging harder and
holding their breath longer (this
is called the “topography” of their
smoking). These smokers are able
to compensate for smoking less
cigarettes per day and achieve
adequate blood plasma levels of
nicotine using very few cigarettes.
Thus numbers of cigarettes smoked
per day have no bearing on the
amount of nicotine received in
the body. Titrating nicotine
replacement therapy against
urges to smoke is the best and
most valid method of determining
concentration of NRT required.
This might necessitate multiple
forms and combinations of NRTs.
Metabolising nicotine
There is now good evidence
showing that individuals all
metabolise nicotine differently.
The liver enzyme P450 CYP2A6
metabolises nicotine and smokers
may range from faster to slower
metabolisers within this liver
enzyme group. It has been difficult
to determine which individuals
are faster than others however
Benowitz et al have devised an
indirect method using nicotine’s
major metabolite, cotinine.
The ratio of cotinine to its
metabolite 3 Hydroxycotinine
correlates significantly with the
speed of nicotine excretion. This
test can be carried out on the urine
of individuals who have nicotine in
their circulation (from smoking or
use of any other nicotine-containing
product), however the tests are not
yet routinely used.
Individual responses to
nicotine are important, as slow
metabolisers do well on NRT
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“
Ethnic variations
must be considered
when recommending
NRTs.”
and fast metaboliser do not. Fast
metabolisers may need more NRT.
Groups such as the Japanese
(among other Asians) have a high
prevalence of smoking but their
metabolism is slow. Caucasians
are relatively fast metabolisers,
African-Americans are slower.
These ethnic variations must be
considered when recommending
NRTs.
Nicotine is also metabolised
60% faster in pregnancy due to
increased induction of CYP2A6.
Metabolising other
pharmacotherapies
Both bupropion and nortryptyline
are dependent upon their
substrates for their effects. Poor
metabolisers may not do well
in smoking cessation on these
medications.
NRT considerations
Regular use of NRT will help
reduce urges to smoke.
It must, however, be used
consistently for at least three
months to support a quit attempt
and prevent relapse – even if
the person has managed to stop
smoking in this period.
This is because smokers need to
learn “how to behave” without a
cigarette, and that takes time.
Some evidence-based tips:
All advice or tips given to smokers regarding behavioural changes should be
evidence-based.
• Always smoke outside from today.
• All friends and family smoke outside from today.
• Step out of your car to smoke from today.
• Halve caffeine intake, including all colas and energy drinks (check the labels).
Do not stop caffeine intake altogether.
• Separate smoking from other activities (eg, coffee inside, smoking outside:
read inside, smoke outside).
• No alcohol for the first two weeks of a quit attempt.
• Sweet things help with urges and withdrawals, especially after a meal.
Glucose tablets, grapes help.
• Short (one-minute) forms of exercise (walking up the stairs or around the
block) can help with urges.
• Decide whether to keep a cigarette pack or throw it away.
The most common problem with
NRT is using doses that are too low
to reduce cravings effectively.
The strongest patch (21mg) only
delivers the nicotine equivalent to
approximately ¼ of a cigarette!
Increasing the dose to a point
where the individual no longer feels
the urge to smoke is important.
This may mean wearing more
than one patch and/or using
multiple other forms of nicotine
replacement therapies.
Combining different NRT
options is also important.
Layering a patch with a fasteracting (or ‘pulsatile’) form of NRT
such as gums, lozenges or a mist
will further quell an urge to smoke
and support a quit attempt.
NRT should be kept handy for
months, even after quitting.
Other key considerations include:
NRT & cardiovascular
• All forms of NRT can be used
by people with heart disease.
Caution is advised for those in
hospital for acute cardiovascular
events but, if the alternative is >
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Education
“
Patches need to be
worn on a lean and
naturally hairless
part of the body.”
active smoking, NRT can be used
under medical supervision and is
by far the healthier option.
Pregnancy & breastfeeding
• NRT is safe for use in pregnancy,
however only forms used in
the day are recommended. As
mentioned earlier, pregnant
women metabolise nicotine
quickly and may thus need more
NRT.
• Lactating women pass nicotine
through breastmilk to their baby.
Any form of NRT, including a
24-hour patch, is suitable.
• Importantly, pregnant women (or
women attempting to conceive)
should not use patches but
mothers can safely wear them if
breastfeeding.
Speed of delivery
• After cigarettes, ‘pulsatile’ NRT
(eg, nasal sprays, inhalers and
44 | July 2013 | PharmacyNews
the mouth spray) are the fastest
ways to deliver nicotine and
give the closest approximation
of the nicotine peaks delivered
by a cigarette. They are also, of
course, safest overall.
• Patches help numb the overall
intensity of nicotine cravings
when attempting to quit
smoking. They should ideally be
worn 24 hours every day.
• A patch may take hours to peak,
so customers need to be aware
that they do take time to have an
effect.
• Low-dose patches should not be
commenced. The highest dose
patches only provide nicotine
equivalent to around ¼ of a
cigarette.
Quantity & timing
• One patch may not be enough
so it’s important to consider
increasing the number of
patches worn a day until the
individual no longer “thinks”
about smoking.
• Applying a 24-hour patch last
thing at night that reaches a
peak in the morning will help
with the powerful nicotine
cravings experienced on waking,
and may delay the time to
smoking the first cigarette. This
is important because it delays
the onset of the cycle of smoking
and withdrawals throughout the
day.
• They should be worn for many
months — at least three to really
do the job, even if the individual
has stopped smoking during that
period.
Where to wear them
• Patches need to be worn on a
lean and naturally hairless part
of the body, not just a shaved
area. They can be attached with
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tape for added security and they
do not ‘leak’.
• Patches can safely be worn over
the heart.
Other points
• It is safe to smoke while wearing
a patch. In fact, this combination
can help achieve long-term
cessation and is better for the
smoker overall, as they draw less
on the cigarette, which reduces
the amount of harmful smoke
taken deep into the lungs.
• There is no evidence that
weaning off patches of high
strengths is required. We
recommend people stay on the
high doses.
Gums and lozenges:
• These should be chewed
or sucked slowly, without
swallowing too much. Nicotine is
absorbed into the bloodstream
via the lining of the mouth, not
the stomach.
• Gums and lozenges can be used
frequently. About 15 a day is a
good number; one for every time
someone would normally smoke.
• Using them on waking, while
still in bed (when the strongest
nicotine cravings occur), as well
as in anticipation of a need
to smoke, will help to reduce
cravings (eg, just after a meal or
when making a coffee).
• Nicotine gum is ‘empty’ after
30 minutes and should be
discarded.
• Lozenges should be sucked until
they disappear.
• Chewing or sucking too fast can
cause hiccups or stomach upsets
but these don’t do any harm.
• Fluids and food should not
be taken just before or while
chewing the gum or sucking a
lozenge (liquids wash away the
nicotine).
Making the most of mists
The nicotine mist produced by mouth
sprays and inhalers is absorbed in
the mouth, not the lungs.
These should also be used
frequently, without liquids or food.
The mists can be used in the
same circumstances as gums and
lozenges.
Varenicline (Champix).
Our earlier experiences with
varenicline showed that many
smokers stopped taking it as
they had urges to smoke on the
appointed ‘quit date’.
“
Nausea is a very
common side effect
of varenicline; about
40% of users
experience this.”
Some had delayed positive
responses days or weeks after the
appointed date.
We now recommend that
smokers persist with varenicline for
a full month before a decision to
discontinue is made.
Nausea is a very common side
effect of varenicline; about 40%
of users experience this. Tablets
should not be taken on an empty
stomach.
It is recommended that patients
take the tablets within a meal
rather than after, and that tablets
are taken with a full glass of water.
If urges to smoke have been
eliminated and the patient has
quit, the full three-month course of
varenicline should be taken and,
if there is a history of relapse, a
second three months should be
recommended.
To date, varenicline is
contraindicated in pregnancy.
Further considerations
• Women may need higher doses
as they metabolise nicotine
faster than men.
• Certain ethnicities also
metabolise nicotine faster or
slower than average.
• Important comorbidities to
consider are mental health issues
and pregnancy.
• Individuals who also drink coffee
or alcohol should be advised to
reduce their intake by at least
half while giving up smoking.
Nicotine desensitises the body to
the effects that these substances
have. Thus, when nicotine intake
is reduced during a quit attempt,
their effects are felt much more
than while smoking.
PN
References available upon request
Renee Bittoun is Adjunct Associate Professor
at the University of Sydney’s Smoking
Cessation Unit, head of the Smokers’ Clinics of
Sydney Local Health District, president of the
Australian Association of Smoking Cessation
Professionals (AASCP) and will chair the
National Smoking Cessation Conference in
Sydney this November.
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CPD Questions
Joint and Bone Health: Accreditation No. A1307PN0
1. The four key areas of focus for raising
awareness to promote better management
by the Joint and Bone Decade 2000–2010
were?
a) osteoporosis, back pain, rheumatoid
arthritis and osteoarthritis
b) osteoporosis, arthritis, back pain and road
trauma
c) arthritis, road trauma, neck pain and back
pain
d) bones, joints, ligaments and tendons
2. Select the incorrect statement regarding
osteoarthritis.
a) 97% of hip and knee replacements due to
arthritis are performed on patients with
osteoarthritis
b) Therapeutic management centres on pain
relief rather than disease modification
c) Strontium ranelate has recently shown
beneficial effects on symptoms of
osteoarthritis
d) All patients with osteoarthritis should be
trialled on 2g daily of strontium ranelate to
prevent joint space narrowing
3. Select the correct statement regarding
omega-3 fatty acid supplementation.
a) Plant-derived omega-3-fatty acids are
preferred as they contain preformed
docosahexanoic acid and eicosapentaenoic
acid
b) The alpha linolenic acid found in marinederived omega-3-fatty acids are readily
converted to DHA and EPA in humans
c) Krill oil is a natural source of astaxanthin,
a carotenoid pigment believed to
reduce inflammation and contribute to
cardiovascular health
d) Vitamin deficiencies and insulin resistance
may contribute to the relative inefficiency of
EPA and DHA conversion to ALA
4. Which of the following is not true regarding
osteoporosis?
a) An osteoporotic fracture is often the first
sign of the disease
b) 60% of Australian women aged 40 years
and older are affected by osteoporosis
c) A third of Australian men aged 60 years and
older are affected by osteoporosis
d) Osteoporosis costs the Australian
community approximately $7 billion
annually
5. Which of the following negatively affect
bone mineral density?
a) low alcohol intake
b) smoking
c) exercise
d) both (a) and (b)
6. Select the correct statement regarding
osteoporosis treatments.
a) Bisphosphonates inhibit bone resorption
b) Denosumab requires dose reduction in renal
impairment
c) Strontium ranelate increases bone resorption,
decreases bone formation markers and
maintains bone microarchitecture
d) Strontium is available on the PBS to
postmenopausal women only
7. Vitamin D deficiency is of concern in a
number of chronic conditions including all but
which of the following?
a) rheumatoid arthritis
b) multiple sclerosis
c) asthma
d) schizophrenia
8. Which of the following is true according
to guidelines for daily intake of calcium per
gender and age?
a) A woman aged 51 should consume 1300mg
b) A man aged 29 should consume 2000mg
c) A man aged 75 years should consume
500mg
d) A woman aged 35 years should consume
1300mg
9. Which of the following affect intestinal
calcium absorption?
a) advanced age
b) high caffeine diet
c) long-term corticosteroid use
d) all of the above
10. Which of the following nutrients has not
been linked to bone health?
a) calcium
b) selenium
c) protein
d) vitamin K
Smoking Cessation: Accreditation No. A1307PN1
1. Which of the following is true regarding
smoking and caffeine intake?
a) Smoking reduces the potency of caffeine by
induction of CYP1A2 by polycyclic aromatic
hydrocarbons
b) Symptoms of caffeine toxicity include
agitation, nervousness and sleeplessness
c) The reduced induction of CYP1A2 by
polycyclic aromatic hydrocarbons related
to smoking cessation can induce caffeine
toxicity
d) all of the above are true
2. Select the incorrect statement regarding
dosing nicotine replacement.
a) Nicotine replacement therapy is commonly
titrated to symptoms of withdrawal,
particularly urges to smoke
b) Nicotine replacement therapy should
be titrated according to the number of
cigarettes smoked daily
c) There is no evidence to support the cutting
down or weaning of nicotine replacement
therapy
d) Psychiatric patients have higher plasma
levels of nicotine and usually require higher
doses of nicotine replacement therapy when
quitting
3. Select the true statement regarding
nicotine metabolism.
a) The ratio of cotinine to 3-hydroxycotinine
is correlated with the speed of nicotine
excretion
b) Slow metabolisers of nicotine do not do as
well on NRT as fast metabolisers
c) Nicotine is metabolised by CYP1A2
d) Caucasians are relatively slow metabolisers
whereas African-Americans are relatively
fast metabolisers
4. Select the correct statement.
a) Nicotine is metabolised 60% slower in
pregnancy due to changes in CYP2A6
b) NRT should be used for at least three
months to allow for the quitter to change
their behaviours related to smoking
c) No more than one form of NRT should be
used at a time
d) Nicotine is not passed to a baby in
breastmilk
5. Which of the following is false?
a) A 21mg nicotine patch delivers the nicotine
equivalent to approximately a quarter of a
cigarette
b) Combining different forms of NRT, such as
a patch and a pulsatile form, may better
support a quitter’s attempt to stop
c) NRT is contraindicated in heart disease
d) Daytime forms of NRT are safe to use in
pregnancy
6. Nicotine patches
a) help to numb the overall intensity of
nicotine cravings and are ideally worn 24
hours a day
b) usually take 30 minutes to reach a peak
c) should be worn for many months, even after
the quitter has stopped smoking during that
period
d) (a) and (c) are true
7. Select the false statement regarding gums
and lozenges.
a) Gum and lozenges should be chewed or
sucked quickly to achieve a quick burst of
nicotine
b) Nicotine is absorbed through the lining of
the mouth, not the stomach
c) Nicotine gum is ‘empty’ after 30 minutes
and should be discarded
d) Food and fluids should be avoided just
before or while chewing nicotine gum to
prevent the nicotine being washed away
8. Nicotine patches
a) can be safely worn over the heart
b) can be safely worn by lactating mothers
c) need to worn on a lean and naturally
hairless part of the body
d) all of the above are correct
9. Select the incorrect statement regarding
varenicline.
a) Nausea is a very common side effect of
varenicline
b) Varenicline is contraindicated in pregnancy
c) Varenicline should be taken within a meal,
rather than afterwards
d) The course of varenicline may be stopped
once the urge to smoke has been eliminated
10. Which of the following is not true?
a) Men metabolise nicotine faster than women
and may need higher doses of NRT
b) Patients attempting quitting should be
advised to reduce their alcohol and caffeine
intake by about half
c) Certain ethnicities metabolise nicotine
faster or slower than others and NRT should
be tailored accordingly
d) Quitters with a mental illness may require
higher doses of NRT to successfully quit
Each of these activities has been accredited for 1 Group One CPD credit. This can be converted to 2
Group Two CPD credits upon successful completion of the corresponding assessment,
for inclusion on an individual pharmacists’ CPD record.
Complete the assessment and elect to submit answers to your Guild Pharmacy Academy ‘My CPD’
record. Australian College of Pharmacy members can submit their answers online at www.acp.edu.au.
To submit answers, go to pharmacynews.com.au, click on “education”
46 | July 2013 | PharmacyNews