Analysis of a Rare Case of Cerebral Infarction Secondary to Anaphylactic Shock Caused by Nicotinic Acid Injection / 中国药房

OBJECTIVE：To provide reference for safe use of Nicotinic acid injection in the clinic. METHODS ：The clinical pharmacist introduced the occurrence and treatment of cerebral infarction secondary to anaphylactic shock caused by Nicotinic acid injection in a patient with hypertension in the cardiovascular medicine department of our hospital. By consulting the relevant drug instructions and searching the relevant literatures ，the inducement and severity of ADR were evaluated ，and the rational drug use suggestions of Nicotinic acid injection were put forward. RESULTS & CONCLUSIONS ：According to the Management Measures for ADR Reporting and Monitoring ，the correlation between anaphylactic shock and Nicotinic acid injection was analyzed and evaluated as “very likely ”. Secondary cerebral infarction was mainly associated with a variety of risk factors （hypertension， hyperlipidemia，etc.），among which there was a greater possibility of secondary cerebral infarction due to insufficient cerebral perfusion caused by anaphylactic shock and sharp drop of blood pressure. The above symptoms could be life-threatening if not rescued in time ，which was defined as “severe ADR ”. Clinical pharmacists suggest that when using Nicotinic acid injection ，the patient’s allergy history should be inquired in detail ，the use should be started from a small dose ，and the patient ’s reaction should be closely monitored in the early stage of medication. For patients with high-risk factors of cerebrovascular diseases （hypertension， hyperlipidemia，etc.），if anaphylactic shock occurs ，the effective circulating blood volume should be restored as soon as possible. After the blood pressure rises ，drugs such as improving microcirculation can be used to prevent secondary cerebral infarction. Clinical pharmacists should timely carry out medication education for such patients ，and warn patients to inform doctors of the related drugs with severe ADR in the later stage of treatment ，so as to prevent the recurrence of anaphylactic shock and severe complications. At the same time ，when antihypertensive drugs and statins are combined ，the blood pressure monitoring and the monitoring of ADR such as muscle toxicity should be strengthened，so as to ensure the medication safety of patients.

A new lactone from Euscaphis konishii / 中草药

Objective: To study the chemical constituents of Euscaphis konishii. Methods: The chemical constituents from 95% EtOH extract of the stems of E. konishii were isolated by repeated chromatograph with silica gel, Sephadex LH-20 and semi-preparative RP-HPLC. The structure of the separated chemical components was identified by modern spectroscopy identification. Results: Eight compounds were isolated from the ethyl acetate fraction of 95% EtOH extract of E. konishii, and identified as 4 (R)-(4'-hydroxybenzoyl) dihydrofuran-2(3H)-one (1), 6-hydroxymellein (2), euscapholide (3), dehydrovomifoliol (4), ethyl gallate (5), tetraketide (6), p-hydroxybenzoic acid (7) and nicotinic acid (8). Conclusion: Except for compounds 3 and 6, they are all isolated for the first time in this genus, and all compounds are isolated for the first time in this plant. Among them, compound 1 is a new compound named konieuscaphide.

Improving Solubility of Famotidine by Cocrystal Synthesis with Nicotinic Acid / 中国药学杂志

OBJECTIVE: This study was focused on obtaining and characterizing cocrystal of famotidine to improve its solubility. METHODS: A new cocrystal of famotidine with nicotinic acid(FAM-NIC) was obtained by solution evaporation. And the FAM-NIC cocrystal was characterized by single crystal X-ray diffraction, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR). In addition, the solubility and stability of cocrystal were studied. RESULTS: The asymmetric unit of FAM-NIC consisted of one molecule of famotidine, nicotinic acid, and water, and they were connected through hydrogen bonds. FAM-NIC had unique thermal, spectroscopic, X-ray diffraction, and solubility properties that differed from famotidine. Dissolution studies of the cocrystal showed a 4.2-fold increase of famotidine solubility, and FAM-NIC didn′t change the stability of famotidine in artificial gastric juice, at high humidity, at high temperature, and under illumination. CONCLUSION: The new cocrystal of famotidine with nicotinic acid obviously enhanced the solubility of famotidine.And the RESULTS can be useful for improving solubility of drugs by cocrystal synthesis.

Assessment of Intake of Nicotinic Acid and Nicotinamide in Relation to Tolerable Upper Intake Levels

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the intake of niacin in the Norwegian population. NFSA has also requested that VKM conduct scenario calculations to illustrate the consequences of establishing separate maximum limits for nicotinic acid (1, 4, 8 or 10 mg/day) and nicotinamide (100, 500, 700 or 900 mg/day) in food supplements, by assessing these scenarios against existing tolerable upper intake levels (ULs). The current maximum limit for niacin added to food supplements is 32 mg/day, including nicotinic acid, nicotinamide and inositol hexanicotinate. The term niacin (vitamin B3) comprises the two main water-soluble forms nicotinic acid and nicotinamide (niacinamide). The human body can get niacin from the diet or synthesise it from the essential amino acid tryptophan. Dietary intakes are expressed as milligram niacin equivalents (NEs), which correspond to 1 mg of pure niacin or 60 mg of tryptophan. In the body, niacin primarily functions as a component of the coenzymes NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate) which are present in all cells. These coenzymes play essential roles for the functioning of a wide range of enzymes involved in the metabolism of carbohydrates, amino acids and fat. In addition to its function in coenzymes, niacin is involved in DNA repair and gene stability. Niacin has a half-life of 20-40 minutes in the human body. Late symptoms of severe niacin deficiency (pellagra) include fatigue, headache, apathy, depression, memory loss, dementia, pigmented skin rash after sun exposure, bright red tongue, vomiting, diarrhoea, and constipation. Flushing (burning and itching of the face, arms and chest) and stomach irritation are the main side effects of moderately high supplemental intake of nicotinic acid (>35 mg/day). Long-term use of high doses (≥3000 mg/day) of nicotinic acid as a cholesterol-lowering drug can also be toxic to the liver. Nicotinamide, however, does not have these effects. In general, the risk of nicotinamide toxicity appears to be quite low. VKM proposes to adopt the ULs of nicotinic acid and nicotinamide set by the Scientific Committee for Food Safety (SCF) in 2002, which are based on one human dose-response study (nicotinic acid) and several human dose-response studies (nicotinamide), respectively. Hence, the UL for supplemental nicotinic acid is suggested to 10 mg/day for adults and the UL for supplemental nicotinamide to 900 mg/day for adults. The ULs for children and adolescents have been derived on the basis of their body weights. The ULs set for nicotinic acid and nicotinamide concern only intake from supplements since intake of nicotinic acid and nicotinamide from regular foods is considered to be without risk of negative health effects. Therefore, VKM has not conducted or evaluated scenarios with intake from both diet and the separated new maximum limits for nicotinic acid and nicotinamide in food supplements suggested by NFSA. Dietary calculations, however, have been performed for niacin intakes (includes both nicotinic acid and nicotinamide) in various percentiles (P5, P25, mean, P50, P75 and P95) in children (2-, 4- and 9-year-olds), adolescents (13-year-olds) and adults as background information. Mean and median intakes of niacin from the diet alone are above or at the recommended intakes for all age groups. Because UL for supplemental nicotinic acid is 10 mg/day for adults, none of the suggested maximum limits in food supplements (1, 4, 8, or 10 mg/day) will lead to exceedance of this UL in adults. In 13-year-olds and 9-year-olds, supplements with 8 mg nicotinic acid per day will lead to exceedance of UL, and in 4-year-olds and 2-year-olds supplementation of 4 mg nicotinic acid per day will lead to exceedance of the UL for nicotinic acid. Because UL for supplemental nicotinamide is 900 mg/day for adults, none of the suggested maximum limits in food supplements (100, 500, 700 or 900 mg/day) will lead to exceedance of UL in adults. In 13-year-olds, supplements with 700 mg nicotinamide per day will lead to exceedance of UL. In 9-year-olds, 4-year-olds and 2-year-olds, supplementation of 500 mg nicotinamide per day will lead to exceedance of the UL for nicotinic acid.

Identification of the nicotinamide mononucleotide adenylyltransferase of Trypanosoma cruzi

The intracellular parasite Trypanosomacruzi is the aetiological agent of Chagas disease, a public health concern with an increasing incidence rate. This increase is due, among other reasons, to the parasite’s drug resistance mechanisms, which require nicotinamide adenine dinucleotide (NAD+). Furthermore, this molecule is involved in metabolic and intracellular signalling processes necessary for the survival of T. cruzithroughout its life cycle. NAD+biosynthesis is performed by de novo and salvage pathways, which converge on the step that is catalysed by the enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT) (enzyme commission number: 2.7.7.1). The identification of the NMNAT of T. cruziis important for the development of future therapeutic strategies to treat Chagas disease. In this study, a hypothetical open reading frame (ORF) for NMNAT was identified in the genome of T. cruzi.The corresponding putative protein was analysed by simulating structural models. The ORF was amplified from genomic DNA by polymerase chain reaction and was further used for the construction of a corresponding recombinant expression vector. The expressed recombinant protein was partially purified and its activity was evaluated using enzymatic assays. These results comprise the first identification of an NMNAT in T. cruziusing bioinformatics and experimental tools and hence represent the first step to understanding NAD+ metabolism in these parasites.

Electrochemical Behavior and Determination of Pyridoxine Hydrochloride at Graphene-Carbon Nanotubes/Poly(nicotinic acid) Modified Electrode / 分析化学

Graphene ( GN) and multiwalled carbon nanotubes ( MWCNT) composites were coated on glassy carbon electrode ( GCE ) and then poly ( nicotinic acid ) ( PNA ) was electrodeposited on the modified electrode. The electrochemical behavior of pyridoxine hydrochloride ( VB6 ) was investigated at the modified electrode by cyclic voltammetry ( CV ) and differential pulse voltammetry ( DPV ) . Results showed the oxidation current of VB6 at the GN-MWCNT/PNA/GCE was obviously larger than that at GCE, PNA/GCE and GN/MWCNT/GCE. The oxidation process of VB6 was an irreversible diffusion-controlled process involving one electron and two protons. The liner range between the peak current intensity of DPV and the concentration of VB6 was 0 . 05-200 μmol/L with a detection limit of 0 . 02 μmol/L ( S/N=3 ) . The modified electrode showed a good reproducibility with a relative standard deviation of 3 . 1% ( n=8 ) . The proposed method was applied to the analysis of vitamin B6 in vitamin B6 tablets and compound vitamin B tablets with recoveries between 96 . 1%-104 . 5%.

Valores de referencia de niacina para la población venezolana / Reference values of niacin for the Venezuelan population

La niacina es una vitamina hidrosoluble, conocida también como ácido nicotínico o vitamina B3. La nicotinamida es un derivado de la niacina (amida del ácido nicotínico), y es utilizada por el cuerpo para producir las coenzimas nicotinamida adenina dinucleótido (NAD) y nicotinamida adenina dinucleótido fosfato (NADP). En esta revisión de los requerimientos de niacina para Venezuela, encontramos que los datos nacionales no son suficientes para establecer las recomendaciones de consumo de este nutriente, por lo tanto, al igual que en la revisión del año 2000, las recomendaciones actuales se basan en las definidas para la población de Estados Unidos. Las Ingestas Dietéticas Recomendadas (RDAs) para Venezuela son: menores de 1 año (2-4 mg/día), niños entre 1 y 8 años (6-8 mg/día), niños entre 9 y 13 años (12 mg/día), adolescentes y adultos del sexo femenino (14 mg/día), adolescentes y adultos del sexo masculino (16 mg/día), embarazadas (18 mg/día) y lactancia (17 mg/ día). En cuanto al Requerimiento Promedio Estimado (EAR): 5-9 mg/día para niños, 11 mg/día para adolescentes y adultos del sexo femenino y 12 mg/día para adolescentes y adultos del sexo masculino, aumentado a 14 mg/día para embarazadas y a 13 mg/ día durante la lactancia. Los Niveles de Ingesta Máximos Tolerables (UL) son: niños entre 1 y 3 años (10 mg/día), niños entre 4 y 8 años (15 mg/día), niños entre 9 y 13 años (20 mg/día), adolescentes (30 mg/día) y adultos (35 mg/día). Es necesario realizar estudios donde se evalúe el estado nutricional de esta vitamina en diferentes grupos de la población, que incluya no solo la estimación del consumo, sino la utilización de indicadores bioquímicos, como la medición de los niveles de las coenzimas NAD y NADP en eritrocitos o sangre completa y la determinación de los principales metabolitos urinarios de la vitamina.

Niacin is a water soluble vitamin, also known as nicotinic acid or Vitamin B3. Nicotinamide is a derivative of niacin (amide of nicotinic acid), and is used by the body to produce the coenzyme nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). In preparing this review about the niacin requirements for Venezuela, it was found that there is not enough national data to establish recommendations, therefore, as in the 2000 review of the Venezuelan Recommended Dietary Allowances (RDAs), the actual recommendations for intake of niacin, are based on those reported for the United States population. The RDAs for Venezuela are: 2-4 mg/day for infants less than 1 year old, 6-8 mg/ day for children between 1 and 8 years, 12 mg/day for children between 9 and 13 years, 14 mg/day for adolescents and female adults, 16 mg/day for adolescents and adult males, 18 mg/day during pregnancy and 17 mg/day during lactation. The estimated average requirement (EAR) is: 6-9 mg/day for children, 11 mg/ day for adolescents and female adults and 12 mg/day for adolescents and adult males, increasing to 14 mg/day during pregnancy and to 13 mg/day during lactation. The niacin Tolerable Upper Intake Levels (UL) are: 10 mg/day for children between 1 and 3 years, 15 mg/day for children between 4 and 8 years, 20 mg/day for children between 9 and 13 years, 30 mg/day for adolescents and 35 mg/day for adults. It is necessary to perform studies where the nutritional status of this vitamin is evaluated for different population groups, including not only the estimation of consumption, but the use of biochemical indicators, such as measuring the levels of the coenzymes NAD and NADP in erythrocytes or whole blood and determination of the major urinary metabolites of the vitamin.

Study on chemical constituents from roots and rhizomes of Acorus tatarinowii / 中草药

Objective: To study the chemical constituents from the roots and rhizomes of Acorus tatarinowii. Methods: Using different chromatographic methods to isolate and purify the constituents of A. tatarinowii, and their structures were identified by physicochemical properties and spectroscopic technology. Results: Thirteen compounds were isolated and identified as fumaric acid (1), nicotinic acid (2), p-hydroxybenzonic acid (3), uracil (4), N-trans-feruloyltyramine (5), thymine (6), variecolorquinone A (7), butanedioic acid (8), tatarol (9), tataroside-12-β-D-glucoside (10), β-sitosterol (11), 2, 5-dimethoxy- benzoquinone (12), and 5-hydroxymethyl-2-furaldehyde (13). Conclusion: Compounds 1-7 are isolated from the plants in Acorus L. for the first time.

Studies on trigonelline from Moringa oleifera and its in vitro regulation by feeding precursor in cell cultures

Trigonelline (N-methylnicotinate) biosynthesized from nicotinate is one of the metabolically active pyridine alkaloid, widely distributed in plant kingdom. In the present study trigonelline has been isolated from various plant parts and callus cultures of Moringa oleifera Lam., Moringaceae, and was identified using TLC, GLC, GC-MS, which was comparable to that of the standard trigonelline. The trigonelline recovery was found to be maximum in the pods and minimum in flowers. In order to enhance the production of trigonelline in vitro grown cultures, different treatment doses of nicotinic acid (250, 500 and 750 mg L-1) were supplemented in the medium as precursor. Maximum increase (up to 1.10 fold) was observed in the treatment dose of 500 mg L-1 of nicotinic acid.

The status and prospects of niacin and its combination therapy with statins / 中国药理学通报

Niacin, a broad-spectrum lipid-regulating agent, can significantly lower plasma triglyceride and raise the high density lipoprotein-cholesterol.Extended-release niacin added to statins monotherapy could further modify the lipid profile and reduce residual cardiovascular risk.This combination therapy provides a safe, effective and economical treatment for clinicians and may be superior to other drugs combined with statins.

Preparation and Quality Control of Disinfectant for Venepuncture in Children / 中国药房

OBJECTIVE: To prepare the disinfectant for venepuncture in children and to establish the quality control for this preparation. METHODS: Nicotinic acid and racanisodamine were taken as the chief components for the preparation of this disinfectant, 75% alcohol as the solvent. Nicotinic acid were determined by ultraviolet and visible spectrophotometry(UV-Vis); racanisodamine were determined by nonaqueous titrations. RESULTS: The average recoveries of racanisodamine and nicotinic acid were 99.96%(RSD=0.04%) and 100.04%(RSD=0.16%) respectively, which all were in the range of 98.87%～100.8%. CONCLUSION: The disinfectant produced with the established method is simple in preparation, accurate in content determination, stable and reliable in quality.

Anti-oxygen free radicals and anti-lipoperoxidation of nicotinic acid on hyperlipodemia quail / 中国药理学通报

Aim To study the oxygen free radical scavenging activities and antilipid peroxidation of nicotinic acid. Methods High lipid models of quail were induced by high fat diet. Five groups were divided, namely control group, high lipid group, NA group(150 mg?kg-1 and 75 mg?kg-1), and Vit E group (100 mg?kg-1). The contents of TC,TG,MDA and activities of SOD were examined for 3 times in the plasma and liver after administering NA for 9 weeks. Results The results showed the increase of TC,TG and MDA contents and decrease of SOD activities in high lipid groups by 3 weeks high fat diet. After administering NA for 3 weeks, NA reduced TC,TG and MDA contents and increased SOD activities, revealing the relationship to dose-dependence. Conclusion NA is most likely to possess the capabilities of anti-oxygen free radicals and anti-lipoperoxidation to hyperlipodemia quail.

Investigation of the interaction of polyamidoamine dendrimers with nicotinic acid as solubility enhancer / 中国康复理论与实践

@#ObjectivePolyamidoamine(PAMAM) dendrimers enhance the solubility of nicotinic acid. MethodsPAMAM dendrimers of generation 1 to 6 were prepared and the effect of pH and concentration of the dendrimers on the solubility enhancement of nicotinic acid was investigated. ResultsThe pH and concentration of the dendrimers influence the solubility enhancement of nicotinic acid. Conclusions Electrostatic interaction between the carboxyl group of the nicotinic acid and the amine groups of the dendrimers is involved.

Investigation of the interaction of polyamidoamine dendrimers with nicotinic acid as solubility enhancer / 中国康复理论与实践

Objective Polyamidoamine(PAMAM) dendrimers enhance the solubility of nicotinic acid. Methods PAMAM dendrimers of generation 1 to 6 were prepared and the effect of pH and concentration of the dendrimers on the solubility enhancement of nicotinic acid was investigated. Results The pH and concentration of the dendrimers influence the solubility enhancement of nicotinic acid. Conclusions Electrostatic interaction between the carboxyl group of the nicotinic acid and the amine groups of the dendrimers is involved.

Formula and Preparation Technology of Gel Matrix Sustained Release Tablet of Nicotinic Acid / 中国药房

OBJECTIVE: To optimize the formula and preparation technology of gel-matrix sustained release tablet of nicotinic acid(GSTNA).METHODS: The formula of GSTNA was optimized by orthogonal experiment with the amount of hydrophilic gel-matrix material HPMC(K15M,E15-LV) and that of adjuvant calcium hydrogen phosphate(CHP) as factors and with the in vitro release rates as index.Meanwhile,the verification test on the intra-and inter-batch release rates of the samples was performed.RESULTS: The optimum formula could be seen as follows: the ratios of HPMC(K15M,E15-LV) and CHP were 4%,40% and 25% respectively.The GSTNA prepared in this formula achieved a sustained drug release of up to 12 h,and both the intra-batch homogenicity and the inter-batch reproducibility were satisfactory.CONCLUSION: The GSTNA is reasonable in formula and simple in preparation technology.

Role of nicotinic acid as modulator of liposomal microviscosity.

Using the fluorescent probe 1,6-diphenyl-1,3,5 hexatriene, we have investigated the effect of nicotinic acid, a derivative of the toxic alkaloid nicotine, on the fluidity profile and activation energy of diffusion in the liposomal system of several lipids. We have also studied how the fluidizing property of nicotinic acid affects the intermediate fluid condition induced by cholesterol in these liposomal systems.

A Study of the Effect of Nicotinic acid and Its Substitutes on Cutaneous Blood Flow / 대한피부과학회지

The ability of nicotinic acid and its substitutes to increase cutaneous blood flow has been measured by laser Doppler flowmeter in 30 healthy human volunteers. We applied nicotinarnide, nicotinic acid ethyl ester, nicotinic acid methyl ester, hexyl nicozinate each in an acqeous solution at a concentration of 10 mM/liter for 10 minutes occlusion on the forearm. The change of blood flow was serially checked at 5 to 10 minutes intervals for one hour. The study results were as follows : l. The relative maximum cutaneous blood flow response was in following order nicotinic acid methyl ester(100%), nicotinic acid ethyl ester(98%), hexyl nicotinate (84%) and nicotinic acid(63%). However, there was no statistically significant difference(p>0.05) between each drug. There was statististically significant difference between nicotinamide and all other nicotinic acid substitutes(p<0.05). 2. The time required to reach maximum blood flow response was 6.7 minutes for hexyl nicotinste, 10 minutes for nicotinic acid ethyl ester, 12.5 minutes for nicotinic acid methyl ester and 20 minutes for nicotinic acid. However, there was statistically significant difference between hexyl nicotinate and nicotinic acid only(p<0.05). 3. Significant decrease of cutaneous blood flow was observed one hour after the removal of the patches in all drugs.

Lipid-regulators and myopathy, rhabdomyolysis / 中国药理学通报

It is reported that lipid-regulators including statins, nicotinic acid and fibrates can induce severe adverse reactions such as myopathy, even rhabdomyolysis which endangers the patient's life. The authors have discussed the relationship between lipid-regulators and myopathy, rhabdomyolysis, how those drugs cause these adverse reactions and the major factors for myopathy and rhabdomyolysis in order to deepen the knowledge, prevent the happenness of these diseases and develop the more effective and safer lipid-regulators.

THE EFFECT OF VARIETY AND MILLING ON THE THIAMINE AND NICOTINIC ACID CONTENT OF RICE / 营养学报

The thiamine and nicotinic acid content of the husked rice (whole rice) samples from 9 representative varieties of paddy collected from Jiangsu and Zhejiang provinces were analyzed, and the effect of degree of milling on the content of these two vitamins were studied. The paddy samples were husked with wooden mill and the husked rice samples were milled with laboratory rice mill to 5 grades, namely, "96", "94", "92", "90" and "88" percent extraction (by 96% extraction we mean 96 grams of finished rice were derived from 100 grams of husked rice), and the thiamine and nicotinic acid content of each sample were determined. It is found that the thiamine and nicotinic acid content of the rice of different variety may vary considerably, and both were decreased with the increase of degree of milling. Generally, above the "94" grade, the loss of thiamine is higher than that of nicotinic acid, while down from the "92" grade, less thiamine and more nicotinic acid were lost. The rate of decrease in nicotinic acid content is relatively irregular as compared with that of thiamine, and different varieties are affected differently by the milling process.