Nicotinic acid diabetes with

Nicotinic acid has a hyperglycemic action (SED-13, 1330), and is therefore not recommended as a first-line hypolipidemic drug in patients with type 2 diabetes melli-tus (26). 

Nicotinic acid is approved for the treatment of hyper-cholesterolemia, hypertriglyceridemia, and familial combined hyperlipidemia (Fredrickson s type lla, Mb, IV, and V) (Table 30.2) in patients who have not responded to diet, exercise, and other nonpharmacological methods. It also is approved for nutritional supplementation, the prevention of pellagra, and as adjunct therapy for peripheral vascular disease and circulatory disorders. It is contraindicated in patients with hepatic disease and peptic ulcer disease. Additionally, because of its ability to elevate glucose and uric acid levels, especially when taken in large doses, nicotinic acid should be used with caution in patients who have or are predisposed to diabetes mellitus and gout (15,20,21). 

Contraindications Thiamine patients with renal dysfunction Riboflavin patients with renal dysfunction Niacin or nicotinic acid hypersensitivity to niacin or tartrazine active peptic ulcer, severe hypotension, hepatic dysfunction, arterial hemorrhaging Caution diabetes mellitus, gallbladder disease, gout, history of jaundice or Uver disease. Pyridoxine IV therapy in cardiac patients Caution megadosage in pregnancy... 

Shepherd J, Betteridge J, Van Gaal L European (Consensus Panel Nicotinic acid in the management of 4 slipidaemia associated with diabetes and metabolic syndrome a position paper developed by a European Consensus Pinel. CurrMedRes Opin (2005) 21, 5-82... 

The electron density map of pyridine (see IOC) clearly shows a high concentration of electron density (more red) on the nitrogen. Note that pyridine has been implicated in male sterility, although some claim this is a myth. Nonetheless, it is reasonable to exercise caution when pyridine is used. Several important pyridine derivatives have substituents on the aromatic ring, including 2,6-lutidine (11) and picolinic acid (12). Many derivatives of pyridine are found in pharmaceutically active compounds. One is nicotinic acid (niacin, 13), which is vitamin Bg and is found in liver, yeast, and meat. A deficiency in this vitamin can lead to pellagra (a wasting disease). Nicotinamide (14, niacinamide) is one of the two principal forms of the B-complex vitamin niacin. Nicotinamide may be useful for individuals with type 1 (insulin-dependent) diabetes. 

Picolinic carboxylase was discovered to undergo adaptive changes in level (336). The level is increased markedly in diabetes and other conditions leading to increased adrenal hormone secretion. This can be correlated with the depression of nicotinic acid formation from tryptophan that occurs in diabetic animals (336). The increase in picolinic acid carboxylase is dependent on the presence of adrenal hormones. 

The increased plasma kynuremne pool and the induced xanthurenic acid urinary excretion have several implications in the assessment of diazinon noncholinergic toxicity. An increase in xanthurenic acid formation may alter glucose metabolism. Xanthurenic acid has been reported to form a complex with insulin and damage pancreatic P cells. Elevated plasma kynurenin may alter kynurenin transport into the brain. Since more than 40% of brain kynurenin originates from the systemic circulation, cerebral biosynthesis of neuroactive kynurenin metabolites such as quinolinic acid and kynurenic acid may change. Finally, the availability of L-iryptophan for other L-lryptophan-dependent processes may be reduced. Tryptophan is the metabolic precursor for. serotonin and nicotinic adenine dinucleotidc. Diabetes, bladder cancer, and neurological disorders may be the toxic consequences of diazinon-altered L-tryptophan metaboli.sm (Seifert and Pewnim, 1992 Pewnim and Seifert, 1993). 

The vascular endothelium in its healthy state is antiatherogenic, antiproliferative, regulates vascular tone, and maintains blood flow. Diseases such as diabetes, atherosclerosis, hypertension, coronary artery disease, and stroke are associated with vascular endothelial dysfunction (VED). Under experimental conditions, administration of uric acid or nicotine or sodium arsenite for extended periods to rats produced VED by impairing the integrity of vascular endothelium and decreasing serum and aortic concentrations of nitrite/nitrate. The acetylcholine-induced endothelium-dependent relaxation was attenuated. Concurrent treatment of these rats with... 

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