Smoking, serum concentration

Sustained-release formulations can produce stable serum concentrations with once or twice daily dosage. Therapeutic effects occur at blood levels > 5 mg/1, and side effects increase considerably at levels > 15 mg/1. Smoking, alcohol, anticonvulsants, and rifampicin induce the drug-metabolizing enzyme system in liver and reduce the half-life of theophylline. On the other hand, heart and liver failure, sustained fever, old age and drugs such as cimeti-dine, ciprofloxacin, and oral contraceptives reduce theophylline clearance and thereby increase serum concentrations. 

Geriatric Considerations - Summary Increased risk of side effects in patients with CVD and hepatic dysfunction. Theophylline has a narrow therapeutic index and is associated with numerous drug interactions. Target serum concentrations are 5-20 mg/L, with adverse effects increasing between 15-20 mg/L. Hepatic metabolism and renal excretion declines with age and the half-life of theophylline increases by 3 to 9 hours in older adults. Smoking induces theophylline metabolism therefore, if a pa-tienf sfops smoking, empiric dosage reduction may be indicated and follow serum concenfrafions closely. 

Clozapine is metabolized by hepatic CYP 1A2 and, to a lesser degree, CYP 3A3/4 therefore, the drug is subject to changes in serum concentration when combined with medications that inhibit or induce these enzymes. Serum clozapine levels increase with coadministration of fluvoxamine or erythromycin and decrease with coadministration of phenobarbital or phenytoin and with cigarette smoking (Byerly and DeVane 1996). These pharmacokinetic interactions are particularly important because of the dose-dependent risk of seizures. 

White Phosphorus Smoke. No studies were located regarding absorption in humans or animals after inhalation exposure to white phosphorus smoke. White phosphorus smoke probably contains some residual unburnt white phosphorus (see Chapter 3 for composition information). Human serum concentrations of phosphate (relevance to absorption of white phosphorus smoke is unknown) following occupational inhalation exposure to white phosphorus are discussed in Section 2.3.3 (Metabolism). Health effects observed after inhalation of white phosphorus smoke are most likely portal of entry effects, and, therefore, do not indicate that absorption of white phosphorus occurred. However, the oxides and acids of white phosphorus that occur in the smoke are probably absorbed to an unknown degree. 

Thiocyanate is a metabolite of cyanide and in addition to its toxicological significance, measurement of blood-thiocyanate concentrations aids in the verification of an individual s compliance with an anti-smoking programme. Plasma concentrations in non-smokers range fi om 0.1 to 4 jJg/ml, whereas in smokers concentrations range from about 5 jJ g/ml up to 20 g/ml. Serum concentrations of up to about 200 g/ml have been recorded in fatalities. 

Most medications have shorter half-lives in children than in adults, and therefore children may need sustained-release products to maintain serum concentrations in the therapeutic range. For example, a sustained-release theophylline product may be needed for a child with asthma. It may need to be administered every 8h to the child as compared to every 12 h for a healthy, non-smoking adult to maintain therapeutic serum concentrations. When choosing a sustained-release theophylline preparation for a child, it must be remembered that because of differences in release properties, theophylline sustained-release products are not interchangeable. A product selected for the pediatric asthma patient should be reliably absorbed with a minimal serum concentration variation and not a preparation that has exhibited a difference in bioavailability when administered with or without food.[ > - ]... 

Jensen EJ, Rungby J, Hansen JC, Schmidt E, Pedersen B, Dahl R. Serum concentrations and accumulation of silver in skin during three months treatment with an anti-smoking chewing gum containing silver acetate. Hum Toxicol 1988 7(6) 535-40. 

A human phenotype in which a severe deficiency of ai-AT (10-15% of normal serum concentration) has been observed is designated PiZ. The risk of development of emphysema in PiZZ (homozygotic ZZ individuals) is 20 times that in PiMM (a normal genotype). In addition, cigarette smoking by PiZ individuals accelerates development of destructive lung disease for several reasons. 

Based on current information, inhibitors of CYP 1A2 have the greatest potential for causing interactions with olanzapine. Examples include cimetidine, fluvoxamine, and fluoroquinolone antibiotics (e.g., ciprofloxacin) to varying degrees. To date, however, no serious inhibition interactions have been reported with olanzapine, which may be a result of olanzapine s wide therapeutic index. Carbamazepine has been reported to increase olanzapine elimination by as much as 50%. Cigarette smoking is a potent inducer of CYP 1A2, and one would expect lower mean olanzapine serum concentrations in smokers compared to nonsmokers. 

Serum concentrations of thiocyanate are two to three times higher in smokers than in nonsmokers. In populations not exposed to excessive amounts of thiocyanate from diet or industrial environmental pollution, thiocyanate concentrations in serum can be used to identify and quantify tobacco smoking (Scherer, 2006 Butts etal., 1974). Because of the variability in cyanide generation from smoking a cigarette, the correlation between serum (or urine) concentration of thiocyanate and the number of cigarettes smoked per day is rather low (Foss and Lund-Larsen, 1986). 

In a Belgian study the levels of thiocyanate in serum from heavy smokers were not much different from the serum concentrations found in people in Central Africa with a high intake of cyanide from only partly detoxified cassava (Delange et al., 1980). Thus, heavy smoking may be as important in the generation of thiocyanate as... 

Benetello P, Furlanut M, Pasqui L, Carmillo L, Perlotto N, Testa G. Absence of effect of cigarette smoking on serum concentrations of seme anticonvulsants in epileptic patients. Clin Pharmacokinet( 9Z1) 12, 302-4. 

Haslemo T, Olsen K, Lunde H, Molden E. Valproic acid significantly lowers serum concentrations of olanzapine-an interaction effect comparable with smoking. Ther Drug Monit 2012 34(5) 512-7. 

A study of 398 male and 133 female civil servants in London, England, measured blood pressure, PbB, and serum creatinine concentration the study found no correlation between blood pressure and PbB after adjustment for significant covariates, including sex, age, cigarette smoking, alcohol intake, and body mass index in a stepwise multiple regression analysis (Staessen et al. 1990). 

Belin, R.M. et al., Smoke exposure is associated with a lower prevalence of serum thyroid autoantibodies and thyrotropin concentration elevation and a higher prevalence of mild thyrotropin concentration suppression in the third National Health and Nutrition Examination Survey (NHANES III), J. Clin. Endocrinol. Metab., 89, 6077, 2004. 

Korpilahde, T. et al. Smoking history and serum cotinine and thiocyanate concentrations as determinants of rheumatoid factor in non-rheumatoid subjects, Rheumatology (Oxford), 43, 1424, 2004. 

In vivo studies showed that in vitro proliferation of lymphocytes isolated from marijuana smokers is suppressed, especially with heavy marijuana smoking, and that the relative proportion of lymphocyte subpopulations was also altered. Concentrations of serum IgG are decreased and IgE concentrations are increased in marijuana smokers. Furthermore, phagocytic and bactericidal activity of alveolar macrophages from heavy marijuana smokers are decreased. These effects translate into reduced host resistance following administration of cannabinoids, including THC, in both humans and animals (Table 30.2). Increased susceptibility has been demonstrated to opportunistic microbes including HIV, Herpes simplex virus, Friend leukemia virus Listeria, Treponema pallidum, and Legionella. 

Levels of cyanide and its metabolite thiocyanate in blood serum and plasma, urine, and saliva have been used as indicators of cyanide exposure in humans, particularly in workers at risk of occupational exposures, in smokers or nonsmokers exposed to sidestream or environmental tobacco smoke, in populations exposed to high dietary levels of cyanide, and in other populations with potentially high exposures (see Section 5.6). The correlation between increased cyanide exposure and urinary thiocyanate levels was demonstrated in workers exposed to 6.4-10.3 ppm cyanide in air (El Ghawabi et al. 1975). In another study, blood cyanide concentrations were found to vary from 0.54 to 28.4 pg/100 mL in workers exposed to approximately 0.2-0.8 ppm cyanide in air, and from 0.0 to 14.0 pg/100 mL in control workers... 

Positive correlations between fetal umbilical serum thiocyanate levels and serum thiocyanate levels of smoking mothers (Bottoms et al. 1982 Hauth et al. 1984) and mothers exposed to environmental tobacco smoke in the home (Bottoms et al. 1982) have been reported. Hauth et al. (1984) found that the mean serum thiocyanate concentration (95 pmol/L 5.5 pg/mL) was significantly higher (p < 0.001) in smokers than in passive smokers (35.9 pmol/L 2.1 pg/mL) or nonsmokers (32.3 pmol/L 1.9 pg/mL). Similarly, the mean umbilical thiocyanate concentration in the newborn infants of smoking mothers (72 pmol/L ... 

Figure 22.6 How various factors increase the risk of atherosclerosis, thrombosis and myocardial infarction. The diagram provides suggestions as to how various factors increase the risk of development of the trio of cardiovascular problems. The factors include an excessive intake of total fat, which increases activity of clotting factors, especially factor VIII an excessive intake of saturated or trans fatty acids that change the structure of the plasma membrane of cells, such as endothelial cells, which increases the risk of platelet aggregation or susceptibility of the membrane to injury excessive intake of salt - which increases blood pressure, as does smoking and low physical activity a high intake of fat or cholesterol or a low intake of antioxidants, vitamin 6 2 and folic acid, which can lead either to direct chemical damage (e.g. oxidation) to the structure of LDL or an increase in the serum level of LDL, which also increases the risk of chemical damage to LDL. A low intake of folate and vitamin B12 also decreases metabolism of homocysteine, so that the plasma concentration increases, which can damage the endothelial membrane due to formation of thiolactone.

Saliva The use of saliva as a diagnostic fluid has been studied for many years [266]. While the ease and noninvasiveness with which a sample can be obtained make this matrix attractive to the medical community, the use of saliva to detect exposures of persons to environmental contaminants has not been investigated in many studies. However, it has been established that the measurement of cotinine, an indicator of exposure to environmental tobacco smoke, in saliva is correlated with concentrations of cotinine in serum [267]. 

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