Nitroglycerine elimination

Isosorbide is rapidly absorbed and undergoes rapid first-pass metaboHsm by the Hver. The bioavaUabUity of the subHngual and chewable tablets is 59% and 22%, respectively, for the regular tablet. Isosorbide is metabolized to isosorbide-2-mononitrate and isosorbide-5-mononitrate, both of which have pharmacologic activity. The elimination half-Hves of subHngual and po isosorbide dinitrate ate 1 and 4 h, respectively. Those of the 2- and 5-mononitrate metaboHtes are 1.5—3.1 h and 4—5.6 h, respectively. The two metaboHtes prolong the elimination half-life of the dinitrate. Adverse effects with isosorbide are similar to those described for nitroglycerin (99). 

As apart of Hie ongoing assessment, Hie nurse monitors the patient for Hie frequency and severity of any episodes of angina pain. With treatment, episodes of angina should be eliminated or decrease in frequency and severity. The nurse should report to Hie primary health care provider any chest pain that does not respond to three doses of nitroglycerin given every 5 minutes for 15 minutes. 

More in line with the predictive use of hazards analysis, however, is the experimental and theoretical assessment that the viscosity of the liquid significantly affects this mode of initiation. Such information allows redesign of the process to eliminate handling of low viscosity liquid explosives, and quantitative measurement of the sensitivity of the system to mild shocks as a function of viscosity may allow the optimum level to be selected. This is not necessarily a new concept, only quantified in a different manner. Thirty years ago transporters of neat nitroglycerine in the oil fields were paid 25 a day. The stipend for transporting jellied nitroglycerine was seven dollars, a practical comment on the understood difference in hazard. 

The increasing use of explosives in mining greatly increased coal output but numerous gas explosions occurred in mines where blackpowder was used. The development of nitroglycerine and more modern explosive compositions did not eliminate this hazard. As thejndustry developed and the demand for coal increased the safety of explosives used in mines become-so urgent and important a problem that in the nineteenth century many countries set up special commissions charged with its detailed analysis. 

The difficulties in obtaining a unifoim paste were completely eliminated when nitroglycerine or dinitrodiethyleneglycol was used in the form of an aqueous emulsion for mixing with nitrocellulose under water (see pp. 647 and 661). Nitrocellulose adsorbs nitroglycerine very uniformly from an aqueous medium, so the paste thus obtained may be utilized for further processing immediately after the removal of water. This is best achieved in centrifuges. They reduce the water content to about 30%, while for further reduction (to 8-10%) screw presses are preferable. 

The greater part of the add absorbed in the nitroglycerine is removed in the primary washing, which is carried out with cold water of about 15°C, usually in the same room as the nitrator. This primary washing is insufficient to remove the last traces of absorbed add which are very difficult to eliminate. The product is therefore washed again first with hot water, then with a dilute solution of sodium carbonate (2-4%), again with hot water and finally by a cold water wash. The temperature of the hot water and sodium carbonate solution should be held at such a level, e.g. 60-70°C, that the whole contents of the washing tank can be kept at a temperature of e.g. 45-50°C. The last cold wash, referred to as stabilization, is carried out in a separate room, into which acid vapour from the nitration room should not be allowed to penetrate. 

In the separator for continuous separation of nitroglycerine and acid originally used in the Schmid process, certain faults were detected, which were later eliminated in a new design of 1928 (Fig. 40). 

This direct neutralization has the advantage of eliminating the appreciable loss of the nitroglycerine which occurs with acidic wash water systems. No further washing of nitroglycerine is necessary after direct treatment with sodium carbonate solution. Tank (3) is supplied with sodium carbonate solution through an automatic outlet valve coupled with a pH-meter. To neutralize 100 kg of nitroglycerine ... 

Nitroglycerin (NTC) is distinguished by a high membrane penetrability and very low stability. It is the drug of choice in the treatment of angina pectoris attacks. For this purpose, it is administered as a spray, or in sublingual or buccal tablets for transmucosal delivery. The onset of action is between 1 and 3 minutes. Due to a nearly complete presystemic elimination, it is poorly suited for oral administration. Transdermal delivery (nitroglycerin patch) also avoids presystemic elimination. 

If absorption is slow, and the apparent absorption half-life is much longer than the elimination half-life, then the dose regimen can be based on the apparent half-life of the absorption phase. Changing the formulation is a relatively common approach that is taken for short-acting drugs to extend the duration of absorption. The elimination half-life of nitroglycerin is approximately 2 min. However, nitroglycerin from a transdermal formulation is slowly released, and therapeutic plasma concentrations can be maintained for 24 h. 

In this case, clearance is dependent on hepatic blood flow and independent of Q int and / . This is called blood-flow-dependent or non-restrictive elimination (e.g. nitroglycerin, propranolol and lidocaine). Drags with a non-restrictive elimination have a high extraction ratio (>0.7), and bound, as well as free, molecules are eliminated, since the affinity of the drag for the hepatic enzymes exceeds its... 

Bauer, J. A., and Fung, H.-L. (1993b). Effect of apparent elimination half-life on nitroglycerin-induced hemodynamic rebound in experimental heart failure. Pharm. Res. 10,1341-1445. 

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