Drugs online research references
J Hum Hypertens. 1996 Sep;10 Suppl 3:S143-6.
Efficacy of different antihypertensive drugs in the emergency department.
Hirschl MM, Seidler D, Mullner M, Kurkciyan I, Herkner H, Bur A, Laggner AN.
Department of Emergency Medicine, University of Vienna, Austria.
Hypertensive crises are a commonly observed problem in an emergency department. The aim of the study was to evaluate the efficacy and safety of different antihypertensive agents in the treatment of patients with hypertensive crises. 168 patients (mean age: 52 +/- 12 years) admitted to the emergency department with a hypertensive urgency (systolic (SBP) blood pressure > 210 mm Hg and/or diastolic (DBP) blood pressure > 110 mm Hg) or a hypertensive emergency (DBP > 100 mm Hg and evidence of end-organ damage) were included into the study protocol. Blood pressure (BP) was measured every 5 min automatically using a noninvasive BP measurement unit. After a resting period of 30 min the patients received the following drugs: 5 mg enalaprilat intravenous (n = 43) or 25 mg urapidil intravenous (n = 48) or 10 mg nifedipine-capsule sublingual (n = 47) or 2 x 5 mg nifedipine-spray sublingual (n = 30). The aim of treatment was to reduce SBP below 180 mm Hg and DBP below 95 mm Hg within 45 min after start of treatment. When evaluating the response rates the highest rate was observed in the urapidil group (96%). The response rate of enalaprilat and both preparations of nifedipine were similar (70-72%). The rate of major side effects was higher in the urapidil compared to the other drugs (4% vs 2% in the nifedipine-group or 0% in the enalaprilat-group). All four drugs are suitable in the treatment of patients with hypertensive crisis in the emergency department. Urapidil should be used as a first choice drug in critically ill patients with hypertensive crisis due to its higher response rate.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8872847&dopt=Abstract
J Med Chem. 1986 Sep;29(9):1596-603.
Oxidation of 4-aryl- and 4-alkyl-substituted 2,6-dimethyl-3,5-bis(alkoxycarbonyl)-1,4-dihydropyridines by human liver microsomes and immunochemical evidence for the involvement of a form of cytochrome P-450.
Bocker RH, Guengerich FP.
4-Substituted 2,6-dimethyl-3,5-bis(alkoxycarbonyl)-1,4-dihydropyridines are important because of their roles as calcium channel blockers. The mixed-function oxidation of 14 4-aryl- and four 4-alkyl-substituted derivatives by human liver microsomes was examined. The major product of enzymatic oxidation of all the 4-aryl compounds was the pyridine derivative containing the 4-aryl group. The 4-alkyl compounds, in contrast, formed a pyridine derivative in which a hydrogen atom was present at the 4-position and the alkyl group was lost; these compounds also inactivated cytochrome P-450 and caused the loss of nifedipine oxidase activity after enzymatic oxidation. All of these reactions were extensively inhibited by an antibody raised to purified human liver nifedipine oxidase cytochrome P-450 (P-450NF), indicating a major role for this enzyme in the oxidation of these compounds. Oxidation of the 4-alkyl compounds led not only to the loss of P-450NF but also to decreases in catalytic activities of cytochrome P-450 isozymes catalyzing other reactions (phenacetin O-deethylation and hexobarbital 3'-hydroxylation). The results indicate that P-450NF (or closely related enzyme forms) is responsible for the oxidation of these nifedipine-related compounds in human liver microsomes and that metabolism is highly dependent upon 4-substitution; with alkyl substituents, radicals are postulated to leave P-450NF to attack other proteins.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3746811&dopt=Abstract
J Pharmacol Exp Ther. 2002 Feb;300(2):668-72.
Tenidap, an anti-inflammatory agent, inhibits DNA and collagen syntheses, depresses cell proliferation, and lowers intracellular pH in cultured human gingival fibroblasts.
Matsumoto H, Fujii A.
Department of Pharmacology, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.
The effect of tenidap [(+/-)-5-chloro-2,3-dihydro-3-(hydroxy-2-thienylmethylene)-2-oxo-1H-indole-1-carboxamide], a new anti-inflammatory agent, was investigated on DNA synthesis by means of [(3)H]thymidine incorporation, collagen synthesis by means of [(3)H]proline incorporation, cell proliferation, and intracellular pH in nicardipine-reactive human gingival fibroblasts. Tenidap significantly inhibited [(3)H]thymidine incorporation at concentrations greater than 20 microM on the 4th and 8th day of treatment. Tenidap also significantly inhibited [(3)H]proline incorporation at a concentration greater than 50 microM on the 4th day and at more than 20 microM on the 8th day of treatment. The presence of 1 microM nifedipine or 1 microM nicardipine did not alter the depressing effect of tenidap. Tenidap (20 microM) also lowered intracellular pH. These results suggest that tenidap might be effective for the prevention of gingival overgrowth caused by calcium channel blockers.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11805231&dopt=Abstract
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