Caffeine drug reaction with

This technique may be used in two distinct ways. The drug may be labeled at a specific site(s) and the mass spectra of metabolites derived from the labeled compound compared with those obtained from the unlabeled drug. Recent examples of this application include reports on the metabolism of oxybutynin,tocainide, and ketamine. Alternatively, a heavy isotope (usually H) is introduced into the metabolite of interest by reaction with a labeled derivatizing reagent. For example, perdeutero-methylation results in a mass difference of 3 daltons between labeled and unlabeled derivatives per methyl group. Structures of metabolites obtained from caffeine and phenytoin have been confirmed by this technique. Tri(deuteromethyl)silylation has been employed in the identification of metabolites of carbamazepine and afloqualone. ... 

Many drugs, including quinine, codeine, caffeine, and amphetamine, are amines. Like other amines, these substances are weak bases the amine nitrogen is readily protonated upon treatment with an acid. The resulting products arc called add salts. If we use A as the abbreviation for an amine, the acid salt formed by reaction with hydrochloric acid can be written AH Cl. It can also be written as A-HCI and referred to as a hydrochloride. Amphetamine hydrochloride, for example, is the acid salt formed by treating amphetamine with HCk... 

As with adults, the primary organ responsible for drug metabolism in children is the liver. Although the cytochrome P450 system is fully developed at birth, it functions more slowly than in adults. Phase I oxidation reactions and demethylation enzyme systems are significantly reduced at birth. However, the reductive enzyme systems approach adult levels and the methylation pathways are enhanced at birth. This often contributes to the production of different metabolites in newborns from those in adults. For example, newborns metabolize approximately 30% of theophylline to caffeine rather than to uric acid derivatives, as occurs in adults. While most phase I enzymes have reached adult levels by 6 months of age, alcohol dehydrogenase activity appears around 2 months of age and approaches adult levels only by age 5 years. 

Caffeine (Fig. 11.3), widely used by humans as a stimulatory drug, has so far been detected only in a few plant species. The biological roles of caffeine are believed to be in defense against herbivory or as an allelopathic response to potential competitors.83 Caffeine is derived from the purine alkaloid xanthosine. From xanthosine, three methylations are necessary to produce caffeine. First, xanthosine is methylated on N7 by 7-methylxanthosine synthase (MXS or 7NMT) to produce 7-methylxanthosine, which is enzymatically hydrolyzed to produce 7-methylxanthine and ribose.85,86 The methylations of N1 and N3 of 7-methylxanthine to produce 1,3,7-trimethylxanthine (caffeine) occur in young leaves of tea, and the same enzyme, caffeine synthase, apparently catalyzes both reactions.55 In coffee plants, caffeine is mainly found in the beans but also occurs in the leaves. Caffeine is stored in the vacuoles of coffee leaves as a complex with polyphenols such as chlorogenic acid.87 In contrast to tea, coffee plants appear to have separate enzymes for each step of N-methylation.57... 

Disposition in the Body. Rapidly absorbed after oral administration bioavailability almost 100%. Metabolic reactions include V-demethylation and oxidation to uric acid derivatives. About 85% of a dose is excreted in the urine in 48 hours with up to 40% of the dose as 1-methyluric acid, 10 to 15% as 1-methylxanthine and up to 35% as 5-acetylamino-6-formylamino-3-methyluracil and 5-acetylamino-6-amino-3-methyluracil other metabolites excreted in the urine include theophylline, 1,7-dimethylxanthine (paraxanthine), 7-methylxanthine, and 1,3-dimethyluric acid. Less than 10% is excreted in the urine as unchanged drug. The extent of V-acetylation is genetically determined. Caffeine, theophylline, theobromine, and paraxanthine are found in plasma from dietary sources especially coffee, tea and cocoa. An average cup of coffee or tea contains approximately 100 mg of caffeine. 

Complicating our ability to evaluate toxic reactions to MDMA is the fact that tablets sold on the street as MDMA often contain other drugs that in some cases may also be toxic. Adulterants are so common in street Ml MA that one website (www.dancc-safe.org) posts a page with pictures of commonly. sold MDMA tablets along with the results of their chemical analysis. Many different compounds have been revealed in these analyses, but among the more common adulterants in samples posted in the last half of 2005 were methamphctaminc, caffeine, and dextromethorphan. Interestingly, many of the samples contained no active chemical at all (sec Parrott, 2004) ... 

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