Drug Interactions During Smoking Cessation

because฀they฀are฀now฀metabolised฀more฀slowly฀ [69] .฀“Overdoses”฀resulting฀from฀this฀phe- nomenon฀have฀been฀described฀for฀theophylline,฀imipramine,฀haloperidol,฀tacrine,฀caffeine,฀ phenacetin,฀phenylbutazone,฀oestradiol฀and฀pentazocine฀ [68] .฀The฀absorption฀of฀insulin฀ given฀by฀subcutaneous฀injection฀is฀also฀reduced฀by฀smoking,฀with฀the฀result฀that฀higher฀ doses฀are฀required฀in฀smokers.฀After฀smoking฀cessation,฀this฀process฀is฀reversed฀reduction฀ of฀the฀insulin฀dose.฀Similarly,฀because฀smoking฀is฀known฀to฀increase฀catecholamine฀secre- tion,฀the฀higher฀doses฀of฀b-receptor฀blockers฀required฀in฀smokers฀may฀need฀to฀be฀reduced฀ after฀smoking฀cessation.฀Clozapine,฀a฀neuroleptic฀drug฀used฀in฀psychiatric฀medicine,฀slows฀ the฀metabolism฀of฀nicotine,฀as฀has฀been฀demonstrated฀on฀the฀basis฀of฀raised฀plasma฀coti- nine฀concentrations฀ [70] .

11.1.12 Contraindications for the Use of Nicotine Products

Sometimes,฀on฀the฀basis฀of฀misconceptions฀concerning฀the฀effects฀of฀nicotine฀on฀the฀cardio- vascular฀system,฀the฀prescribing฀information฀for฀nicotine฀products฀lists฀numerous฀contraindi- cations฀and฀warnings฀that฀require฀revision.฀The฀vasoconstrictor฀effects฀in฀the฀nicotine-dependent฀ smoker฀are฀attributable฀more฀to฀the฀inhaled฀combustion฀products,฀including฀CO,฀than฀to฀nico- tine฀itself฀ [71] .฀The฀same฀thinking฀also฀possibly฀applies฀for฀the฀administration฀of฀nicotine฀ products฀ during฀ pregnancy฀ [72] .฀ The฀ contraindications฀ listed฀ include:฀ recent฀ myocardial฀ infarction,฀cardiac฀arrhythmias,฀recent฀stroke฀and฀unstable฀angina.฀The฀following฀are฀cur- rently฀regarded฀as฀relative฀contraindications:฀stable฀angina,฀severe฀hypertension,฀cerebrovas- cular฀disease,฀vasospasms,฀severe฀heart฀failure,฀hyperthyroidism,฀insulin-dependent฀diabetes฀ mellitus,฀acute฀gastrointestinal฀ulceration฀and฀severe฀renal฀and฀hepatic฀impairment.฀Additional฀ relative฀ contraindications฀ listed฀ for฀ nicotine฀ chewing฀ gum฀ include฀ inlammation฀ of฀ the฀ mouththroatoesophagus.฀For฀the฀nicotine฀patch,฀the฀list฀includes฀chronic฀generalised฀derma- tological฀disorders฀psoriasis,฀chronic฀dermatitis฀and฀urticaria฀and฀for฀the฀nicotine฀nasal฀ spray฀nose฀bleed฀and฀chronic฀diseases฀of฀the฀nose. Nicotine฀products฀are฀not฀currently฀recommended฀for฀use฀during฀pregnancy฀and฀lacta- tion,฀unless฀the฀woman฀is฀unable฀to฀stop฀without฀nicotine฀products,฀and฀only฀after฀consult- ing฀a฀physician฀however,฀see฀ [73] .฀It฀was฀stated฀in฀many฀expert฀reviews฀that฀NRT฀is฀the฀ agent฀of฀choice฀for฀smoking฀cessation฀in฀pregnancy฀as฀the฀safety฀of฀other฀therapies฀in฀preg- nancy฀have฀not฀yet฀been฀proved฀ [74] .฀However,฀it฀also฀needs฀to฀be฀mentioned฀that฀while฀ NRT฀avoids฀exposure฀to฀the฀myriad฀compounds฀present฀in฀tobacco฀smoke,฀nicotine฀itself฀ causes฀damage฀to฀the฀developing฀nervous฀system฀ [75] .

11.1.13 Nicotine Formulations as OTC Products

Various฀nicotine฀formulations฀are฀sold฀as฀OTC฀products฀in฀several฀European฀countries฀e.g.฀ patch฀and฀gum฀in฀Germany.฀The฀rationale฀is฀that฀smokers฀absorb฀nicotine฀from฀cigarettes฀ in฀ higher฀ doses,฀ developing฀ higher฀ blood฀ levels฀ than฀ following฀ administration฀ of฀ NRT฀ products฀see฀Sects.฀ 11.1.2 – 11.1.6 ;฀Figs.฀ 11.2 ฀and฀ 11.3 .฀The฀current฀regulatory฀framework฀ restricts฀access฀to฀NRT฀without฀adequately฀considering฀that฀the฀likely฀consequence฀will฀be฀ the฀continued฀dependence฀on฀the฀use฀of฀nicotine-containing฀tobacco,฀which฀is฀extremely฀ harmful฀and฀universally฀available.฀With฀the฀aim฀of฀achieving฀harm฀reduction฀in฀smoking฀ children,฀ pregnant฀ women฀ and฀ patients฀ with฀ cardiovascular฀ diseases฀ or฀ diseases฀ of฀ the฀ respiratory฀tract฀e.g.฀COPD,฀all฀these฀categories฀of฀people฀should฀be฀permitted฀to฀use฀ NRT฀not฀only฀for฀smoking฀cessation,฀but฀also฀for฀reducing฀the฀daily฀cigarette฀consumption฀ to฀an฀optimum฀of฀10฀cigarettesday.฀A฀critique฀of฀the฀current฀situation฀in฀the฀UK฀was฀ published฀in฀2001฀by฀McNeill฀et฀al.฀ [76] . In฀one฀large฀meta-analysis,฀the฀effects฀of฀prescription฀and฀OTC฀settings฀were฀compared฀ in฀terms฀of฀their฀eficacy฀in฀achieving฀smoking฀cessation.฀The฀studies฀compared฀the฀use฀of฀ patch฀and฀gum฀formulations฀of฀nicotine.฀OTC฀success฀rates฀were฀consistently฀higher฀than฀ prescription฀rates฀at฀6฀weeks฀for฀both฀patch฀OR฀=฀1.45;฀CI:฀1.05–1.98฀and฀gum฀OR฀=฀ 2.92;฀CI:฀1.58–5.40,฀and฀remained฀signiicant฀at฀6฀months฀for฀the฀patch฀OR฀=฀3.63;฀CI:฀ 1.74–7.61฀but฀not฀for฀gum฀OR฀=฀1.37;฀CI:฀0.73–2.58฀ [73] .฀Among฀OTC฀and฀prescription฀ gum฀users,฀16.1฀vs.฀7.7฀were฀abstinent฀at฀6฀weeks฀and฀8.4฀vs.฀7.7฀at฀6฀months,฀respec- tively.฀Among฀OTC฀and฀prescription฀patch฀users,฀abstinence฀rates฀were฀19.0฀vs.฀16.0฀ after฀6฀weeks฀and฀9.2฀vs.฀3.0฀after฀6฀months฀ [77] .฀The฀authors฀claim฀that฀NRT฀use฀within฀ clinical฀studies฀does฀not฀follow฀“real-world”฀prescription฀practices.฀Indeed,฀many฀physi- cians฀prescribe฀NRT฀products฀to฀their฀smoking฀patients฀with฀only฀a฀few฀comments฀con- cerning฀their฀administration฀and฀use.฀In฀this฀way,฀lower฀success฀rates฀will฀be฀achieved฀than฀ if฀physicians฀provide฀comprehensive฀advice฀to฀their฀smoking฀patients฀over฀several฀consul- tations฀cf.฀ Chap.฀15 .฀In฀contrast,฀the฀meta-analysis฀is฀correct฀in฀concluding฀that฀there฀is฀ no฀difference฀in฀eficacy฀between฀OTC฀and฀“real-world”฀prescribing.฀If฀the฀OTC฀method฀ of฀supplying฀NRT฀were฀to฀be฀spread฀across฀larger฀population฀segments,฀this฀would฀dra- matically฀increase฀the฀number฀of฀abstaining฀smokers,฀and฀this฀in฀turn฀would฀have฀a฀sub- stantial฀public฀health฀impact.฀In฀the฀United฀States,฀a฀20฀increase฀in฀quit฀rates฀was฀achieved฀ [78] .฀The฀OTC฀method฀resulted฀in฀fewer฀smoking-attributable฀deaths฀and฀in฀increased฀life฀ expectancy฀ [79,฀80] .฀Worldwide,฀NRT฀must฀become฀more฀accessible฀to฀smokers฀by฀remov- ing฀regulatory฀barriers฀e.g.฀France,฀Australia,฀Brazil,฀and฀early฀results฀suggest฀a฀favour- able฀public฀health฀impact฀ [81] .฀Differences฀between฀European฀countries฀concerning฀the฀ sale฀of฀nicotine฀formulations฀are฀listed฀in฀Table฀ 11.5 .฀While฀most฀nicotine฀formulations฀are฀ OTC฀products,฀bupropion฀is฀available฀only฀on฀prescription. An฀interesting฀question฀is฀whether฀the฀change฀in฀NRT฀sales฀from฀prescription฀to฀OTC฀ status฀ affected฀ smoking฀ cessation.฀ To฀ assess฀ this฀ issue,฀ the฀ 1993–1999฀ Massachusetts฀ Tobacco฀Surveys฀were฀used฀to฀compare฀data฀from฀adult฀current฀smokers฀and฀recent฀quit- ters฀before฀and฀after฀the฀OTC฀switch฀ [83] .฀Interestingly,฀no฀signiicant฀change฀over฀time฀ occurred฀in฀the฀proportion฀of฀smokers฀who฀used฀NRT฀at฀a฀quit฀attempt฀in฀the฀past฀year฀ 20.1฀pre-OTC฀vs.฀21.4฀post-OTC,฀made฀a฀quit฀attempt฀in฀the฀past฀year฀48.1฀vs.฀ 45.2,฀or฀quit฀smoking฀in฀the฀past฀year฀8.1฀vs.฀11.1.฀Fewer฀non-Whites฀used฀NRT฀ after฀the฀switch฀20.7฀pre-OTC฀vs.฀3.2฀post-OTC,฀p฀=฀0.002,฀but฀the฀proportion฀of฀ Whites฀using฀NRT฀did฀not฀change฀signiicantly฀20.6฀vs.฀24.0.฀It฀was฀therefore฀con- cluded฀ that฀ there฀ may฀ be฀ no฀ increase฀ in฀ smokers’฀ rates฀ of฀ using฀ NRT,฀ making฀ a฀ quit฀ attempt,฀or฀stopping฀smoking฀after฀NRT฀became฀available฀for฀OTC฀sale.฀There฀appear฀to฀ be฀other฀barriers฀to฀the฀use฀of฀NRT฀besides฀visiting฀a฀physician,฀especially฀among฀minor- ity฀smokers฀ [83] .