Schizophrenic Patients Organic Depression and Schizophrenia

cigarette฀consumption฀in฀schizophrenic฀and฀non-schizophrenic฀patients฀because฀of฀admin- istration฀of฀haloperidol฀was฀measured฀on฀the฀basis฀of฀reliable฀parameters฀CO,฀nicotine฀ [200] .฀ The฀ combination฀ of฀ neuroleptics฀ and฀ smoking฀ reduces฀ the฀ frequency฀ of฀ parkin- sonism-like฀symptoms฀in฀these฀patients฀and฀can฀reduce฀the฀anticholinergic฀doses฀required฀ in฀some฀cases.฀On฀the฀other฀hand,฀the฀eficacy฀of฀haloperidol฀in฀these฀patients฀is฀reduced฀ because฀of฀raised฀elimination฀rates฀ [228–230] .฀Unfortunately,฀this฀interaction฀is฀usually฀not฀ taken฀ into฀ account฀ when฀ calculating฀ the฀ haloperidol฀ dosage.฀ Similarly,฀ smoking฀ also฀ increases฀the฀elimination฀of฀antidepressants฀amitriptyline,฀nortriptyline,฀imipramine฀and฀ desipramine฀ [220] ฀by฀inducing฀the฀hepatic฀breakdown฀of฀these฀substances฀via-CYP1A2.฀ Plasma฀protein฀binding฀by฀nortriptyline฀is฀clearly฀reduced฀as฀a฀result฀ [231] . Thus,฀smoking฀cessation฀can฀be฀expected฀to฀result฀in฀a฀paradoxical฀increase฀in฀the฀eficacy฀ of฀ neuroleptics฀ and฀ antidepressants:฀ this฀ is฀ manifested฀ most฀ particularly฀ in฀ an฀ increase฀ of฀ adverse฀effects฀e.g.฀parkinsonoid฀effects฀of฀neuroleptics,฀seizures฀caused฀by฀clozapine฀ [232] .

11.5.6 Pre-operative Smoking Cessation

Up฀to฀10฀of฀patients฀develop฀respiratory฀tract฀or฀cardiovascular฀complications฀during฀the฀ post-operative฀period.฀Men฀and฀women฀who฀smoke฀are฀especially฀at฀risk฀in฀this฀respect฀ [233] :฀they฀have฀a฀3฀to฀6-fold฀increased฀risk฀of฀intra-operative฀pulmonary฀complications฀ [234] ฀and฀there฀is฀a฀2฀to฀5-fold฀increased฀risk฀of฀perioperative฀complications฀in฀smokers฀ with฀chronic฀cardiovascular฀or฀pulmonary฀disease.฀The฀consequences฀of฀cigarette฀smoking฀ on฀the฀various฀organ฀systems฀are฀discussed฀in฀Chaps.฀5–7. Smoking฀disturbs฀post-operative฀wound฀healing฀ [235–237] ฀and฀increases฀the฀risk฀of฀ anastomotic฀leakage฀in฀colorectal฀surgery฀ [238] .฀To฀date,฀there฀exists฀only฀one฀evidence- based฀study฀conirming฀that฀pre-operative฀smoking฀cessation฀1฀or฀6–8฀weeks฀eliminates฀ Drug Interactive฀effects Benzodiazepines฀diazepam,฀ lorazepam,฀midazolam,฀ chlordiazepoxide No฀effect฀ [206–208] Bupropion No฀effect฀ [94] Chlorpromazine AUC฀ß฀−36,฀serum฀concentration฀ß฀−24;฀฀ clinical฀signiicance?฀ [209,฀210] Clorazepate AUC฀ß,฀t 0.5 ฀of฀N-desmethyldiazepam฀ß฀ [211] Clozapine Induction฀of฀CYP 1A2 ,฀clearance฀Ý,฀plasma฀concentration฀ß฀ −28฀ [205,฀212–215] Fluvoxamine Induction฀of฀CYP 1A2 ,฀metabolic฀clearance฀Ý,฀AUC฀ß฀−44,฀ plasma฀concentration฀ß฀−47฀ [216] Haloperidol Clearance฀Ý฀+44,฀serum฀concentration฀ß฀−70.฀Clinical฀ signiicance?,฀no฀observed฀differences฀in฀dose฀ [191,฀217,฀218] Imipramine Serum฀concentration฀ß,฀no฀clinical฀effect฀ [219] Nortriptyline Unclear,฀no฀clinical฀effect฀ [220,฀221] Olanzapine Induction฀of฀CYP 1A2 ,฀clearance฀Ý฀+98,฀great฀variability฀in฀ plasma฀clearance฀over฀a฀fourfold฀range฀ [222–224] Table 11.8 ฀฀฀Pharmacokinetic฀interactions฀between฀smoking฀and฀drugs฀inluencing฀the฀CNS