Therapeutic Monitoring in Smoking Cessation

and฀cotinine฀monitorings฀were฀compared฀ [156] ฀in฀self-reported฀ex-smokers:฀While฀cotinine฀ monitoring฀detected฀17฀smokers,฀CO฀monitoring฀detected฀smokers฀in฀only฀9.8฀of฀the฀ reported฀non-smokers฀ [156] .฀In฀a฀recently฀published฀smoking฀cessation฀study,฀the฀eficacy฀ of฀the฀three฀parameters฀was฀compared฀at฀three฀time฀points฀9,฀26,฀and฀52฀weeks฀from฀treat- ment฀initiation฀ [157] .฀The฀results฀suggested฀the฀cotinine฀analyses฀in฀urine฀may฀lead฀to฀more฀ accurate฀but฀lowered฀measured฀abstinence฀rates฀49,฀29,฀and฀26฀vs.฀38,฀26,฀and฀25,฀self- report฀plus฀CO฀vs.฀self-report฀plus฀cotinine,฀respectively฀ [157] . ETS฀and฀other฀environmental฀factors฀trafic฀pollution,฀fog฀may฀also฀be฀possible฀expla- nations฀for฀elevated฀CO.฀If฀an฀ex-smoker฀has฀not฀smoked฀for฀7฀days฀previously,฀plasma฀ cotinine฀levels฀should฀not฀exceed฀20฀ngml;฀neither฀do฀cotinine฀determinations฀in฀plasma,฀ saliva฀or฀urine฀indicate฀previous฀cigarette฀smoking.

11.5 Special Therapeutic Situations

11.5.1 Ischaemic Heart Disease

The฀two฀controlled฀studies฀conducted฀to฀date฀in฀patients฀with฀stable฀angina฀point฀to฀a฀favour- able฀inluence฀on฀progression฀or฀on฀the฀course฀of฀the฀disease.฀In฀smokers฀20฀cigarettes day฀with฀coronary฀heart฀disease,฀blood฀low฀in฀various฀myocardial฀regions฀is฀improved฀as฀ a฀sign฀of฀“smoking฀reduction”฀where฀cigarette฀consumption฀is฀replaced฀in฀part฀by฀nicotine฀ patches฀14฀and฀21฀mg฀strengths฀ [158] .฀With฀falling฀CO฀content฀of฀expired฀air,฀the฀under- perfused฀myocardial฀regions฀were฀reduced฀in฀size฀and฀the฀patients’฀exercise฀capacity฀was฀ increased฀despite฀higher฀nicotine฀levels฀compared฀with฀controls฀because฀cigarette฀con- sumption฀had฀fallen.฀One฀study฀indicated฀that฀nicotine฀had฀a฀“minimally฀harmful”฀effect฀on฀ the฀circulation,฀because฀even฀years฀of฀smokeless฀tobacco฀use฀did฀not฀increase฀either฀the฀risk฀ factors฀for฀the฀development฀of฀coronary฀heart฀disease฀or฀the฀atherogenic฀index฀ [159] . When฀cigarette฀consumption฀in฀patients฀with฀stable฀angina฀using฀nicotine฀patches฀14฀ and฀21฀mg฀was฀gradually฀reduced฀from฀20฀to฀7฀cigarettesday,฀only฀3฀out฀of฀77฀smokers฀ in฀the฀active฀treatment฀group฀compared฀with฀8฀out฀of฀79฀smokers฀in฀the฀placebo฀group฀had฀ to฀ discontinue฀ treatment฀ because฀ of฀ cardiovascular฀ events฀ [64] .฀ Transdermal฀ nicotine฀ administration฀does฀not฀increase฀either฀the฀frequency฀of฀angina฀attacks฀or฀the฀occurrence฀of฀ nocturnal฀attacks,฀arrhythmias฀or฀episodes฀with฀ECG฀evidence฀of฀ST-segment฀depression฀ [64] .฀Smoking฀cessation฀was฀achieved฀in฀36฀and฀22฀of฀patients฀active฀treatment฀vs.฀pla- cebo฀ [64] .฀Thus,฀the฀usefulness฀of฀NRT฀has฀been฀conirmed฀in฀smokers฀with฀stable฀angina.฀ Recommendations฀have฀now฀also฀been฀published฀concerning฀the฀treatment฀of฀ischaemic฀ heart฀disease฀ [160] ,฀indicating฀that฀nicotine฀patches฀clearly฀reduce฀the฀primary฀endpoints฀ death,฀ myocardial฀ infarction,฀ cardiac฀ arrest,฀ hospital฀ admission,฀ cardiac฀ arrhythmias฀ or฀ heart฀failure฀in฀CHD฀patients฀within฀14฀weeks฀5.4฀vs.฀7.9,฀active฀treatment฀vs.฀placebo฀ [160] .฀Nicotine฀treatment฀may฀thus฀be฀initiated฀as฀early฀as฀2–3฀days฀after฀an฀acute฀myocar- dial฀infarction,฀and฀NRT฀is฀indicated฀for฀smoking฀cessation฀in฀all฀patients฀with฀angina฀pec- toris฀and฀cardiac฀arrhythmias.฀Dosage฀recommendations฀are฀available฀for฀nicotine฀patches฀ and฀chewing฀gum,฀whereas฀no฀indings฀have฀yet฀been฀published฀for฀the฀inhaler.฀Details฀are฀ presented฀in฀Table฀ 11.7 .

11.5.2 Pregnancy

Women฀who฀smoke฀during฀pregnancy฀must฀expect฀their฀neonates฀to฀display฀signs฀of฀embry- otoxic฀and฀foetotoxic฀damage฀ [70] .฀Since฀the฀prescription฀of฀drugs฀is฀quite฀properly฀restricted฀ during฀pregnancy฀and฀lactation,฀controversy฀surrounds฀the฀use฀of฀nicotine฀products฀because฀ the฀harmful฀effects฀of฀the฀combustion฀products฀of฀cigarettes฀cannot฀be฀clearly฀separated฀ from฀the฀effects฀of฀nicotine.฀The฀accumulation฀of฀nicotine฀in฀breast฀milk฀is฀well฀known,฀but฀ heavy฀metals,฀CO฀and฀numerous฀carcinogens฀also฀pass฀into฀the฀mother’s฀milk.฀In฀spite฀of฀ this,฀it฀has฀been฀argued฀that฀it฀is฀better฀for฀smoking฀mothers฀to฀breast-feed฀their฀babies฀than฀ solely฀to฀expose฀them฀to฀the฀effects฀of฀passive฀smoking฀ [161] .฀Non-drug฀smoking฀cessation฀ programmes฀should฀be฀offered฀irst฀see฀Sect.฀10.11฀in฀ Chap.฀10 ,฀but฀NRT฀should฀be฀insti- tuted฀very฀promptly฀where฀non-drug฀interventions฀are฀found฀to฀be฀ineffective฀ [73] .฀Analysis฀ of฀the฀literature,฀including฀the฀results฀of฀experimental฀animal฀research,฀indicates฀that฀nico- tine฀does฀not฀cause฀any฀teratogenic฀or฀embryotoxic฀effects.฀The฀carcinogens฀detected฀in฀the฀ urine฀of฀neonates฀are฀derived฀from฀tobacco฀and฀are฀not฀metabolites฀of฀nicotine฀ [162] . Since฀pregnant฀women฀who฀smoke฀are฀heavily฀dependent,฀they฀incorporate฀the฀combus- tion฀products฀of฀tobacco฀as฀well฀as฀larger฀amounts฀of฀nicotine฀which฀reach฀the฀foetal฀brain฀ [163,฀164] ,฀and฀the฀binding฀capacity฀for฀the฀alkaloid฀has฀been฀shown฀to฀increase฀in฀foetal฀ brain฀structures฀between฀weeks฀12฀and฀19฀of฀pregnancy.฀Nicotine฀binding฀in฀the฀brainstem฀ attains฀peak฀levels฀at฀mid-gestation,฀with฀a฀subsequent฀fall฀at฀the฀time฀of฀delivery,฀indicating฀ that฀adverse฀effects฀of฀nicotine฀may฀be฀expected฀to฀occur฀during฀mid-to-late฀gestation฀ [164] .฀ Since฀ the฀ risk฀ of฀ malformations฀ and฀ obstetric฀ complications฀ is฀ demonstrably฀ higher฀ in฀ IndicationTreatment Proposal Proven฀use Indications Myocardial฀infarction Nicotine฀may฀be฀used฀2–3฀ days฀after฀infarction Nicotine฀was฀used฀up฀to฀2–3฀weeks฀ after฀myocardial฀infarction Arrhythmias Nicotine฀may฀be฀used฀in฀all฀ patients To฀date,฀no฀experience฀in฀patients฀with฀ severe฀ventricular฀arrhythmias,฀ second฀and฀third฀degree฀AV฀blocks฀ or฀hospitalised฀for฀arrhythmias฀up฀ to฀2฀weeks฀afterwards Treatment ³ 10฀cigarettesday ³ 15฀cigarettesday Nicotine฀patch 15฀mg16฀h฀8–12฀weeks 21฀mg24฀h a ฀in฀CHD฀patients฀proven฀ over฀5–10฀weeks Nicotine฀chewing฀gum 5–15฀pieces฀2฀mg฀eachday฀ 12–24฀weeks Not฀tested฀in฀CHD฀patients Table 11.7 ฀ ฀ ฀ Recommendations฀ on฀ the฀ use฀ of฀ nicotine฀ products฀ in฀ patients฀ with฀ cardiovascular฀ disease฀ [160] a Based฀on฀our฀own฀experiences,฀the฀use฀of฀nicotine฀patches฀overnight฀is฀not฀recommended฀because฀ of฀the฀occurrence฀of฀insomnia฀etc.