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TIK: Imnnaliorul Journal of the MdklfeM. 2l
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750HACMYNSKY
dence of developing coronary heart disease (CUD) It directly related t o ilic num
ber of cigarettes smoked;IHOM
imoklng more than 20 cigarettes a day and (hosewho begin smoki ng before the age of 20 are three to five times mo re likely to
suffer coronary bean disease than nonsmokers (Ramidale et al.). Up to 30% of
deaths from CUD can be attributed to cigarette smoking(MMWR, 1984;Cashin
et al., 1984). The expense of Heating diseases caused by smoking is currently
being assessed. Osier et at. (1984 ) estimate that "male heavy smokers between
the ages of 40 and 44 will generate, on Jth eJ average, over SSb,0 00 in additional
costs of illness duiiftg their lifetimes, while for wom tn. these costs will be over
$19,000" (p. 384).
The decision lo cease smoking does not ensure permanent cessation. Al
though definit ive data are n ot available, over ihe past decad e it has been esij.
mated that three-fourths of the smokers have tried to stop, but only about 20
to 25% actually succeed (Wliy People Smoke. 1983; Russell. 1971). Recidivism
among those who quit smoking equals that of heroin addicts 75% (Russell and
Feycribend, l9?8;Pomerleau, Adkins,and Piertschuk, 1978).
Clinical experience and a search of Ihe literature indicate that a decision toslap smoking often, means choosing a suppoit program (Hunt and Bcspaltc,
1981). This study r epoits encouraging results found in a pilot test of new medi-
cal protocols not previously described or repotted.
The program consists of a prescribed anticholinergic drug regimen aimed a i
eliminating physiological withdrawal symptoms. Treatment achieves positive
effects for persons who enroll in the program with the intention of remaining
nonsmokers. Drug inleiTCntion treatment reduces the extreme discomfort of
withdrawal usually experienced by smokers that urges them to return lo smok
ing. The scientific basis of this medical technique is described in the next sec
tion (Theory).This yearlong pilot study had four purposes:
1. To ttit through medical observation if a piesciibcd drug regimen does, in
effect, eliminate physiological withdrawal sym ptoms .
2. To identify and describe demographic characteristics common t o I sampl
ing of patienl tin the program.
3. To monitor Tor both expected and unexpected imme diat e eff ect.4. To track cessation behavior.
The underlying assumption held that the absence of uncomfortable physio
logical withdrawal sympt oms and the perception of (his relief serve is a positive
reinforcem ent for cessatio n, increasing the chance of a smoker' s changing his
behavior,
Research dining (he past decide has emphasized responsibility for one's
own health and the need t o educate Ihe public about the physical benefits of
ANTICHOLlNr.Hr.lC DKUGS FOR SMOKING CESSATION '9 1
smoking cessation. A number of approaches have been attempted including
electroshock, hypnosis, psychotherapy, and counselling through support groups
(Myrsten, Elegerot, and Edgren, 1977 ; Pedeison. SciSmgeour , and Ufc oe, 1979;
Crosz, 1978-1979).
However, it is well documented that a smoker desiring to cease smoking and
remain a nunimoker must address both physiological and psychosocial effects.
For best success, Ihe patient must have a specific motivational reason |SMR] to
slop smoking, and social reasons seem to impose sironger motivation than medi-
cal reasons (Russell and Feyerabend, 197 8; Elser and Sut ton , l 978 ;Ma Iot te
e l i ! . , 1981).
THEORY
Nicotine is addictive, having a neurobiochemlcal bails (Jarvik, 1979). Nico
tine has an agonistic action al the nicotine receptor sites in the cholinergic ner
vous system (Birdsall. Burgen, and Hulme. 1978; Rosecrans, 1979) (Fig. I).
lis primary action upon prolonged use is that of a blocking agent. While this
activity is less documented in the central than In the peripheral nervous syterm,the preponderance of such nicotine receptors appears to be located centrally
I the midbrain level (Welncr, l974 ;P opo t and Changeux. 1984) . With chronic
nicotine use, biochemical tolerance and physiological dependency are devel
oped by increased acetylcholine accumulation mediated by enzyme induction
und/or derepression thro ugh choline acetyl transferase (Brlmblecombe, 1974;
Wills, 1970; Dahlstrom, Booj, Heiwall, and Uisson, 1980; Kelchum el al.,
1973) (Fig. 2),
A "tobacco withdrawal syndrome" providing for nicotine abstinence thus
comes about by elimination of the nicotine blockade at specific nicotine-cholin
ergic synapses. Tolerance and dependency, developed by Increased acetylcho
line synthesis activity, are replaced by wllhdiawal, which results from excessive
acetylcholine rebound stimulation (Jarvik, 1979; Dahl str omel al., 1980; Ketch-
vmetal., 1973) (Fig. 3).
The final biochemical Interpretation of nicotine withdrawal is through
acetylcholine inter synaptic stimul ation of predominately muscarinic cholinergiclies at higher neuronal levels, including the cerebral cortex (Hfrschoin arid Rose-
can s, 1974). Usual clinical symptoms include a decrease in heart rate and blood
pressure, increased Irritability, nervousness, gastrointestinal disturbances, electro
encephalogram changes, and a temporary decrease in the ability to concentrate.
Tests of a variety of anticholinergic and other drugs found that only sco
polamine and d-amphetamine decreased smoking (puffing pattern) In monkeys.
By using animal paradigms ai a model for human nicotine dependency, Click,
JirvUc, and Naksmura (1970) showed the effecllvenesi of parasympathetic ner
vous system antagonists. Clinical data gathered from medical pat ients , as reported
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792
MUSCARINIC
RECtpTORS
NICOTINE
BtC tPTOHi
fNAPTlC
/ESICtL
Pig. 1. NpJl chrilnwglc Unimiiik>r.
ANTICHOLINERGIC DRUGS FOR SMOKING CESSATION 79J
NICOTINE
(SMOKl)
/BLOCIUNGX\ ACINI I
IN( REA5ED
SYNAPTIC
VISICLES
Pij. 2. NKolino blockjdo: tncicaiod nnuoui niinllt ci lyntheih.
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794 BACHYNSKY
mCRIAStOMUSCftBINIC" w wIHAmMISSION - ^ . - ^ V
R OTO RS - 1 ^ < (BOMMMlNrKU.LI IOi
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7 *BACHYNSKY
in this pilot study, demonstrate the usefulness of their research. Aniicholi nergic
drugs cT predominately at muscarinic sites In the cerebral cortex. By blocking
these sites, we prevent the ultimate Interpret ation o f the Inteisynapilc rebound
phenomenon caused by excessive acetylch oline stimu lation at lower ni cotine
mlilbnm-Uvel receptors cicated by cessation of chronic nicotine (tobacco) use
Since wit hdrawal symptoms to nicotine cessation are most pronounced dur
ing the first 24-48 hours, Immediate and high levels of anticholinergic activi ty
are achieved by injecting described anticholiner gic drugs in the subcutaneous
areas over the mastoids. Nicotine is eliminat ed in approxim ately 3 days. t ut It
may lake approximately 2 weeks to reduce withdrawal symptoms (Go)diiein
and Coldslcin, 1%B). Consequently, oral medication is recommended 10 main
tain a low level o f anticholinergic Activity Tor a peno J up to 2 weeks. This t ech
nique ii based on laboratoiy evidence that approximately 2 weeks arc required
for a significant decrease in enzyme synthesis of the end product (acetylcho
line).
The anticholinergic method helps patients develop an aversion to cigarettes
by also effe cting taste and sensory receptors. The effect of dry mou th, for ex*
ample, wh ile disadvantageous in many insta nces. Is hel pfu l where It is a come*
quence of therapeutic techniques.
M E T H O D S
For l l it i pilot st udy, leliospect ivc, longitudinal da\a were collected over a
2fc.year period, 1980 to mid-1983, using the smoking cessation protocol. For
purposes of this initial report, demographic and other characteristics of the pro
gram's seir-selectuig population were comhined to better profile the smoke- who
is likely to seek out and complete this approach to smoking cessation.
Pour primary variables were used to describe the program population and
(he pilot group:
Age at entran ce into the program
Sex
Number uf cigarettes smoked per day
Reason ftn wantli\g to slop smoking
The pilot study describes asingle treatment group consisting of a cohor t o f
500 adult patients from total study population of 3,700 patients tracked for a
12-mnnlh period (Tables I and 2), A systematic convenience sample was drawn
from patients' cherts and clinic recordings on follow-up log books. Patients Tot
the treatment program were sciT-refcrrais, those attracted by public advertise
ment media, and physician referrals. They paid for the program by private pay
ment or medical insurance coverage.
ANTICHOLINERGIC DRUGS TOR SMOKING CFSSATION M l
la
Smoking Ct tut Ion
blc I
Record {500 Co*ei>'
A6< (mala, 267;
female. 233)
''''""
No. ycus Ni. ci,;-1clit1 Noiuinoh*--. (mala, 267;female. 233)
''''""smoki ng srnuhed pei d*V aflu WmoDlhi
At e
srnuhed pei d*V
ranee Ca Years Cue s No. (lis. Ci Months Cam15-25 35 IS 19 1-10 2 O * 50026-35 158 6-10 71 11-20 70 2 * J536-45 141 11-13 86 21-30 H I 4 344
46-55 115 16-20 77 31-40 166 0 327
36-55 44 21-23 5) 41-63 99 1 102
66-75 6 26-30 98 6) 6) SC 12 199
76-80 1 31-40
41-50
76
12
Main- 39.9 yr Mean: 19.3 yr Ma n 35.4 ct&t Ued im: 6.5 aftf
SO: 11.4 SO: 10.9 SO: 14,9 nonsmoking time
D ili woie ga(heie4 iii aip iive ly fi om charts of ti n Physician*' Clinic.
Criteria for acceptance into the program ln:tuded:
1. The desire and will ingness to Hop smoking
2. No medical contra indicatio ns for the uie of anticholinergic drugs, as wit h
acute-angle glaucoma, prostatic hypertrophy, or cardiac arryirunias(Csln
ct al 1984)
The baseline screening protoco l Included but was not limit ed lo, these
checkpoints:
1. Assessment of medical history
2. Routine cltesl X-iay
3. Urinalysis
4. Electrocardiogram
5. Blood woi k, complete blood count, scru^i clcclrotyl cs. and an SMA-12
panel
6. Assessment of surgical history f or previous* occurre nce of idiosyn crat ic or
prolonged refr actory times in the dissipation of antkholi neigi c drug effects
LigneiAll pat ients meeting the program criteria ugned an Informed consent t o
treatment w hich spells out the expecte d effctjis as well as possib le-hu t not
necessarily anilcipated-uniowaid reaction-.
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BACHVNSKY
rb!t>2
Bsuhne Averagetof Yttri Smoktd tnd Numbir of Cl$amtct
Smohfd i>*f 0*y by StM _
Averse numbe; of
' Avenuje yo ui imoktxt descen t! imofccd pf i day
Male 21.4 37.8
Fomak 20.8 33.6
Tolal 21.1 35.5
THE PROTOCOLSOFTREATMENT
Having conu nlcd lo treatment wi th anticholinergi c drugs, patients submit
ted to the rollowiiu set of protocols:
1. The |nlii!f)i (Cixhes an iniikil intramuscular ii i jcclinn of u 2-ml lalbn solution with scopolamine 0.2 mg arid atropine 0.2 mg.
2. The patient o monitoicd In the physician's office with the room darkened
for u ni i i i im im pci iud of 5 ni inules, fol lowed by an BKSHUM1 of normal
pupillary const riction and mil d xerostomia ,
3. Given thai factors in Step 2 are within norm al limi ts, two additiona l injec
tions are adailmilcied subcutancously over each mastoid area. The tola]
drag icgimcr is atropine 0.2 mg, scopolamine 0.2 mg, and chloipi oma-
zinc 10 mg. OnebaJf of the tol al solution is injected in each site,
4. The patient again is monito red in itio physician's office for a min imu m
period of 5 rrinulct.
5. Given lha ( ifae response Is wi th in the sange of antici pate d effect s, the pa
tient Js allowed to leave the office w it h instru ctions not to drive, not lo
consume alcohol, and not lo lake medications wit h a synergistic effect for
24 hours. Arceplable anticipated effects include moderate xerostomia,
lightheadedness, and some dif fic ulty in focusing.
6. Day 2 thro uih Day 11, the patient is lo lake a prescribed oral anticho lin
ergic drug tin t is know n to act on the central , rather th an the periphera l,
nervous syslcu . The most commonl y used drugs arc trlhexp henid yl hydro
chlor ide, bcii i i io pinc mesylate, or scopolamine patches.
Tracking pat ents dur ing the 12 nion ih pe riod was a task sequiring syste
matic review. Subjects responded favoiably lo fo llow-u p activi ty, for periodic
contacts provided them with motivation lo continue cessation. Follow-up In
forma tion on smoking status was self-report ed by pat ients' responses to tele
phone contacts every 2 months and mailings util izing a brief, tersely worde d
ANTICHOLINERGIC DRUGS FOR SMOKING CESSATION 709
questionnaire (see the Appendix). Results were libuUed b/ staff of the Physi
cians' Clinic and entered into pat ient ch arts. The tnt eipl aj betwee n SMR andmedical inter vention c ould f urth er refine kn o wedge of fictor s thai enhance
or inhibit success and affect a smoker's chance "or bng-term cessation (Gold
stein and Goldstein, 1968).
R E S U L T S
1 . Prelim inary findings ind icate thai this (Jiatmrnl pnt oc ol is successful
for a large number o f paii enls. Success is desc.ibed at tv o points In lim e:
cross-sectionally, where (he patient has or has no. ceaied tc smoke, and longi
tudin ally, lo determi ne the length of smoking absthence over a 12-month
observation period. The use of anticholinergic drugs or smoking cessation is
a technique easily administered In the offic e oT ; private pacli l io nei and ac
cessible to most practicing physicians.
Future Intake should focus on a thorough physical assessment ( wor kup )
rinco t reatmen t Is by physical (chemical) means. Isy dol ogi cjl usscsmicnl muybe worthwhi le to determine SMRs, but this may >rovt a sei*-se|ect(on process
because paiienls w ould no i choose to participate vif hout a rood or immedia te
reason lo do so.
2. Findings support th e main purpose of thi stuly , indicating that 434
(86.8%) of the 500 patients of the pilot stud y stepped srmxi ng al 2 mont hs;
J99 (39.8%) r emained n onsmoker s at ihe end of the ysar. Results of the pro
gram arc higher than Ihe general popu lati on of snok e s who attempt lo stop
smoking (Cond iott e and Uch tens tein , 1981) (Fig . 5). Further study rs needed
lo repor l wi th c onfidence an znlicipa tcd program rucccss rat* for Ibis particu
lar smoking cessation prot oco l. If, however, the average smok ng cessation pro
gram finds an average of 20% of Ihe paii enls abstinent J! 6 raonlht ( Hunt and
Iksps fec, 19 81), this methodol ogy m ay offer the i inab ilit y of cessation lo a
greater percentage of smokers.
3. Table 3 summarizes motivatio nal charad eislt ct of subjects lesled at
the beginning of Ihe cessation program. The study (onesided hat in long -term
cessation, Ihe patient must perceive a specific motivational rrason (SMR] to
stop smoking. Smokers who could clearly identfy in SNR wire more success
ful in sm oking cessation than those who could not.S oca) reasons repiesenied
a SMR among 63.6% o f ihe paiienls who slopped anok-ng a "iil l 12 mou th s-
the need to satisfy a spouse, childre n, friends, or cmo loy e co ndiiiuns- wherea s
only 30.7% slopped w ho had medic al reasons for drin g :i>. SfcRs include such
concerns as (I ) social acceptance in a peer group; (2)inlcspcrsooal rela tionships;
(3) Intolerance in a work station or business she; (4) pessun from a sexual
partner; (S) parental disap proba tion; (6) cosmetic effects, (Deluding stained
iv.- ih and wrinkle d lips; and (7) co mplaints ab out Ihe (ten
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HOO BACHYNSKY
NUMBER
OF
'ATIENTS
500 Cases)
100-
?K>39. i
300
3787S.8H
3S571.C46
795
400 43*
MO
0 1 4 6 0 HOI
MONTHS NONSMOKING
Fig. 5. SucociifuIn DMjnokai.
TiMt J
Union to' Bn\Bilng thmProgum
Subjects
Male Female Total*
Koason A1 * rV % A' 7:
SocialMedicalMissing valuer
Tout
185 (37 0}62 (12,4)
35 (0?m
282 (56.4)
J (26.6)
54 (JO.6)
31 C06.2)
216 (43.6)
318
116
66
500
(6J.6)
(2i.2>
OJ.2)
(100.0)
ANTICHOLINERGIC DRUGS FOR SMOKING CESSATION goi
Table 4
, _ , _ . . AffcoCftw Lavcti at Builin* and7tvo Fillaw-Up Ptrlodi
Smoker 2 mo 12 mo
baiellne nonsmoker aonunokei
Nicotine fcml A* % N % N %
Low [0.3 mg) 388 57.6 244 56.9 J ? J 62.B
Hgl idJ mg) 212 42.4 191 43.1 74 37.)
4. Table 4 indicates Out a greater percentage of smokers of low-nicotine
cigarettes were able (o stop smoking for a period of 12 months than smokers
of high-nico tine cigaret tes. We ate cognizant of the fact Dial 60. 8% of the
participants enrolled in (he program enlered as smokers of low-nicotine cigar
ettes. (See Table 1.) Therefore, we encountered a design group with positive
motivation to slop smoki ng since (he majority had, in this way, demonstrated a
practic e intende d (o reduce nicoti ne dependency. In 1964 the World HeaUh
Organization substit uted the single term "depend ence" to describe physic*! or
psychological "Iwblluation" or "addiction." Physical dependence includes
"lolcruncc of the effects of .. . (a) drug due primirily to changes al synapses"
and "withdrawal symptoms resulting from reboind over-acdvity at synapses
when intake of the drug is reduced or dis continued" (Russell, 197 1, p. 2).
Nicotine dependency is characterized as Increase*! acetylcholine synthes is ac
tivity resulting from nicotine blockade at specific nicoiine-chollnerglc syn
apses. Chronic nicotine use causes increased acetylcholine accumulation. Smok
ers of low-nicotine cigarettes help themselves because lower levels of acetyl
choline buildup enable earlier and less painful wilhda wa).
5. Experience ui till* pilot gro up showed that 39.5% of those who stopped
smoking a period o f 12 months used regular cigait ties; but only ) 1% of thos e
who smoked mentholated cigarettes were able t o stop. It is possible thai smok
ers of mentho lated cigarettes may have a greater Isvel of nicotine dependency
because mentholatum has a soothing action on the respiratory membrane, thuspermi ttin g deeper inhalatio n and retentio n of smoke with higher levels of nico
tine titration and dependency.
CONCLUSIONS
I. Develop ment of a rigorous program of smoking cessation ujing anti
cholinergic drugs requires establishment of piotoccls for (1) patient selection,
(2) conduct of a physical examination, (3) administration of drugs, (4) follow-
up activity, and (5) evaluation of short-term and long-term success and failure.
The short-term measuie it completion and compllarce within ireatnsent of (he
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S02 IACHYNSKY
program. The intermediary, long-term measure requires follow-up of past Heal-
ment. By establishing criteria foi protocols and following these protocols inclinical practice, physicians could obtain data for a longitudinal study of smok
ing cessation based upon medical intervention techniques.
2. A sustained research effort is desirable In aspects of smoking cessation
with drug Intervention protocols. Specifically, medical science would benefit
from scientific reports treating the following concerns:
A prospective longitudinal stud y with supporting standardized Intervention,
recordkeeping , and administrative follow-up.
Improved behavioral modification supporl lo complement physical/medical
treatment.
Outcom e measures related to smoking cessation, including quit levels, pa
tient evaluations of the program (strong points and weak points), and
physiological measures (including self-reporting) such as improvements in
respiratory or cardiovjsculiir stains rc|K>r(cd in pus (c au ti on or self-worth
assays. Development of an operational definition of a program' s "success" or "fail
ure" at both (he Individual level and the clinic program level.
Articulati on of demographic sociopsychologlca) descript ors to afford more
precise intake data (patient profiles) and complementary follow-up informa
tion (changes in status).
APPENDIX
THE PHYSICIANS* CLINIC
6535 SOUTHWEST FREEWAY
HOUSTON.TEXAS 77074
SMOKING CESSATION PROGRAM
PATIENT FOLLOW-UP LETTER
Dear
In oui continuing follow-up lo determine the effectiveness of our Clinic's smok
ing treatment program, we ask that you answer the questions below.
ANTICHOLINERGIC DRUGS FOR SMOKING CESSATION 833
When you have completed this form, please return U lo us in the enclosed self-
addresied envelope.
Thank you.
1. Are you smoking now'
YES NO
2. If your answer lo quetllon I was "ye s," how many month s after comple t
ing the Clinic's treatment did you re-slarl?
I 2 4 S 6 7 S 9 10 I I 12
CIRCLE ONE
3. If you have re-starled snofcfng, why?
STRESS HABIT
(Chcet one or both)
Olher [Pbaseexplain]:
ACKNOWLEDGMENT
J. H. Glasser, PhD, Atsutint Professor of Biometry and Computer Design atthe University or Texas Heilth Science Center, Houston, Texas, was statistical
reviewer of dat a in this study. The auth or is grateful to Dr. Glasser for his pro
fessional insights in Ihe development of t his study and for his recommendat ions
for future research.
REFERENCES
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r^mUFir. JV