Caffeine INDEX

In 1990, Vatten et al.51 in Norway subsequently reviewed data on breast cancer risk from a cohort of 14,593 women with 152 cases of breast cancer during a follow up of 12 years on subjects who were between 35 and 51 years old at the beginning of the study and between 46 and 63 years at the end. They reported no overall statistically significant correlation between breast cancer and coffee consumption, but when body mass index was taken into account, lean women who consumed >5 cups per day had a lower risk than women who drank two cups or less. In obese women, however, there was a positive correlation between coffee intake and breast cancer. In a 1993 study, though, Folsom and associates52 failed to find an association between caffeine and postmenopausal breast cancer in 34,388 women in the Iowa Women s Health Study, with a median caffeine intake of 212 mg/day in women who developed breast cancer and 201 mg/day for women who did not and in Denmark, Ewertz53 studied... 

The therapeutic treatment of obesity with caffeine is another controversial area of interest. Many over-the-counter diet aids contain caffeine, but it has not yet been determined whether there is a medically safe way to use caffeine as a fat fighter. A 2000 study showed that a combination of herbal ephedra and caffeine lowered participants body weight by both decreasing fat and decreasing the body mass index (BMI). Losses were 15 and 7 pounds for those taking the herbal supplement and a placebo, respectively. 

In the study described the time-dependence and reversibility of the enzyme induction was not studied. Also the enzyme substrate used as a marker for the CYP 1A2 activity was caffeine, which although frequently encountered in the target population and commonly used as a marker for CYP 1A2 activity, is not a drug with a narrow therapeutic index used by the target population. The enzyme substrate used as a marker for the CYP 3A4 activity, urinary 6- 3-hydroxy-cortisol and free cortisol, although readily amenable to inclusion in studies, is not a drug and is also known to be a relatively insensitive marker for CYP 3A4 induction. Also urinary 6- 3-hydroxy-cortisol and free cortisol does not differentiate between intestinal and liver CYP 3A4 activities. 

It is common knowledge that coffee contains caffeine (a methylxanthine compound) and inspection of the Compound Index yields the following entry ... 

Hartleb M, Romanczyk T, Becker A, et al. (1992) The theophylline disposition after caffeine administration in liver cirrhosis an index of liver function. 

The effects of cisapride 0.2 mg/kg tds on acid gastroesophageal reflux in 32 formerly preterm infants receiving respiratory stimulation with caffeine have been stndied using 24-hour esophageal pH monitoring (27). Cisapride significantly reduced the reflux index and the freqnency of reflnx without impairing the systemic availability or therapentic effects of caffeine. 

A 41-year-old woman presented with pain and pallor in the leg and a sensation of coolness exacerbated by exercise (34). For many years she had been taking a formulation containing ergotamine 1 mg plus caffeine 100 mg, at a dose of one or two tablets daily, for both prophylaxis and treatment of migraine. For 7 days she had also taken clarithromycin (dose is not stated) for a chest infection. Her legs were cool and cyanosed, with no palpable popliteal or foot pulses and an ankle-brachial index of only 0.6 (normal >0.8). 

Very few fatalities have ever been reported (or studied), but it appears that the therapeutic index for ephedrine is very great. A 1997 case report described a 28-year-old woman with two prior suicide attempts, who died after ingesting amitriptyline and ephedrine. The blood ephedrine concentration was 11,000 ng/mL, and the liver concentration was twice that value (kidney, 14 mg/kg brain, 8.9 mg/kg). The amitriptyline concentration was 0.33 mg/kg in blood and 7.8 mg/kg in liver (131). Values in a second case report (where methylephedrine concentrations were nearly 6000 ng/mL) may or may not be relevant to the problem of ephedrine toxicity, as the individual in question took massive quantities of a calcium channel blocker, and it is not known whether methylephedrine exerts all the same effects as ephedrine (132). Baselt and Cravey mention the case of a young woman who died several hours after ingesting 2.1 g of ephedrine combined with 7.0 g of caffeine, but tissue findings were not described. Her blood ephedrine level was 5 mg/L, whereas the concentration in the liver was 15 mg/kg (133). 

What is the solubility of caffeine in water Merck Index or CRC Handbook)... 

The stored Ca + can be released by either caffeine orlPg. Many studies (e.g., Endo eta/., 1977 Saida and Nonomura, 1978 Itoh et al, 1982a,b Saida, 1982) used the transient tension response elicited by the released Ca2+ as a measure of Ca + uptake into the SR. In order to observe a contractile effect, a solution with a weak Ca + buffering capacity (0.1 mM EGTA) has to be used so that Ca + released from the store, instead of being bound by the buffer system, is made available to the contractile elements. The limitations of this index of Ca + uptake have been discussed previously (Meisheri et al, 1985 Yamamoto and van Breemen,... 

Using The Merck Index or Handbook of Chemistry and Physics or a suitable site found on the web, look up the temperature at which caffeine sublimes at standard atmospheric pressure. 

Mnscnloskeletal The risk of hip and total fractures has been determined in 75 747 women Irom the Women s Health Initiative Observational Study [23. After adjustment for covariates such as age, protein, vitamin D, vitamin K, calcium, caffeine, and alcohol intake, body mass index use of therapeutic hormones, smoking, and ethnicity, the association between vitamin A and retinol intake and the risk of fi actures was not statistically significant. However, there was an association with the highest dose of retinol in conjunction with low vitamin D status. Women with lower vitamin D intake had a modest increased risk of total fracture if they were in the highest quintile of vitamin A intake (HR = 1.19 95% Cl = 1.04, 1.37) and retinol intake (HR = 1.15 95% O = 1.03,1.29). 

From metabolic studies, an isotopic caffeine breath test has been developed that detects impaired liver function using the quantitative formation of labeled carbon dioxide as an index. From the urinary excretion of an acetylated uracil metabolite, human acet-ylator phenotype can be easily identified and the analysis of the ratio of the urinary concentrations of other metabolites represents a sensitive test to determine the hepatic enzymatic activities of xanthine oxidase and microsomal 3-methyl demethylation, 7-methyl demethylation, and 8-hydroxylation. Quantitative analyses of paraxanthine urinary metabolites may be used as a biomarker of caffeine intake. Fecal excretion is a minor elimination route, with recovery of only 2-5% of the ingested dose. 

The most extensively investigated and most firmly established clinical application of caffeine is the control of neonatal apnoea in premature infants. The respirogenic properties of theophylline were first reported, and caffeine is increasingly being used as a substitute for theophylline because of its wider therapeutic index. For infants with a body weight of 2.5 kg, the therapeutic loading doses varied from 5 to 30mgkg, followed by a maintenance dose of 3 mg kg per day. Plasma caffeine levels must be controlled carefully to reach 10-20 mg... 

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