Drug metabolism histamine

Il.b.l.1. Adverse effects of anti-secretory treatment. Histamine H2 antagonists and proton pump inhibitors are very safe as well as effective treatments. Cimetidine has small effects on hepatic drug metabolism which are only of clinical signiflcance with drugs used in doses close to toxic levels, notably phenytoin, aminophylline and warfarin. Other adverse effects such as headache, rash and thrombocytopenia are rare. 

Famotidine is a histamine H2 receptor antagonist. It does not affect drug metabolism and it has been claimed to be free of the antiandrogenic effect of cimetidine however in one woman who accidentally took double doses of the drug for some months it did cause hyperprolactinemia and breast engorgement (SEDA-18, 372). In other ways it bears a very close resemblance to cimetidine for example, headache and confusion with intravenous use are reported, as are thrombocytopenia and pancytopenia (SEDA-15, 395). 

Cyclic nucleotides now appear to be involved in the control of sperm activity euid motility and sperm capacitation and as mediators of viral infection , cellular growth (including that of bacteria ), the immune response " , inflammation , anaphylaxis , histamine release , hypersensitivity and neurotransmitter release , among the many other important cellular processes previously known. The potential of the cyclic nucleotides or their derivatives as drugs is already apparent in many areas including contraception , radioprotection , inhibition of drug metabolism and antagonism of anesthetics ... 

Contrary to other elicitors of non-immune anaphylactic reactions (radiocontrast media, neuromuscular blocking agents, non-steroidal anti-inflammatory drugs (NSAIDs)) where there are at least hypothetical concepts regarding the pathomecha-nism of these reactions via increased mediator release (e.g. histamine release, shift in arachidonic acid metabolism from prostaglandins towards leukotrienes, etc.) [26], there is almost no literature regarding the pathomechanism of these reactions after LA application. 

Important products derived from amino acids include heme, purines, pyrimidines, hormones, neurotransmitters, and biologically active peptides. In addition, many proteins contain amino acids that have been modified for a specific function such as binding calcium or as intermediates that serve to stabilize proteins—generally structural proteins—by subsequent covalent cross-hnk-ing. The amino acid residues in those proteins serve as precursors for these modified residues. Small peptides or peptide-like molecules not synthesized on ribosomes fulfill specific functions in cells. Histamine plays a central role in many allergic reactions. Neurotransmitters derived from amino acids include y-aminobutyrate, 5-hydroxytryptamine (serotonin), dopamine, norepinephrine, and epinephrine. Many drugs used to treat neurologic and psychiatric conditions affect the metabolism of these neurotransmitters. 

The methyl transferases (MTs) catalyze the methyl conjugation of a number of small molecules, such as drugs, hormones, and neurotransmitters, but they are also responsible for the methylation of such macromolecules as proteins, RNA, and DNA. A representative reaction of this type is shown in Figure 4.1. Most of the MTs use S-adenosyl-L-methionine (SAM) as the methyl donor, and this compound is now being used as a dietary supplement for the treatment of various conditions. Methylations typically occur at oxygen, nitrogen, or sulfur atoms on a molecule. For example, catechol-O-methyltransferase (COMT) is responsible for the biotransformation of catecholamine neurotransmitters such as dopamine and norepinephrine. A-methylation is a well established pathway for the metabolism of neurotransmitters, such as conversion of norepinephrine to epinephrine and methylation of nicotinamide and histamine. Possibly the most clinically relevant example of MT activity involves 5-methylation by the enzyme thiopurine me thy Itransf erase (TPMT). Patients who are low or lacking in TPMT (i.e., are polymorphic) are at... 

Cimetidine (Tagamet, 8.26), a histamine H2-receptor antagonist for ulcer and heartburn treatment, inhibits several isoforms of CYP CYP1A2, CYP2D6, and, most importantly, CYP3 A4 (Figure 8.5). If a patient takes cimetidine as well as a drug that is metabolized... 

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