Iodide atropine with

Clinical experience with the use of PAM-2 iodide, given with atropine and diazepam, in the treatment of the victims of the Tokyo sarin attack in 1995 was extremely favourable (Stojdjkovic and Jokanovic, 2005). Still, 2-PAM should not be recommended as the drug of choice due to its lack of efficacy against tabun and soman (Kassa, 2005). 

Homatropine Methylbromide, USP. Homatropini methylbromidc. 3a-hydroxy-8-methyl-1 aN.Sa/f-tropanium bromide mandelate (Novatropine, Mesopin), occurs as a bitter. white, odorless powder and is affected by light. Tbe compound is readily soluble in water and alcohol but insoluble in ether. The pH of a 1% solution is 5.9 and that of a 10% solution is 4.5. Although a solution of the compound yields a precipitate with alkaloidal reagents, such as mercuric potassium iodide test solution, addition of alkali hydroxides or carbonates does not cause the precipitate thil occurs with nonquatemary nitrogen salts (c.g.. atropine, homatropine). 

The majority of casualties were assessed at St. Luke s International Hospital, which is located within 3 km of five of the affected subway stations, although a further 568 patients were assessed at five other hospitals (Kato and Hamanaka, 1996 Masuda et al, 1995 Nozaki et al, 1995 Suzuki et al, 1995 Yokoyama et al, 1995,1996). Doctors at St Luke s were notified at 08 16 hours of an explosion and fire at a nearby subway system (Matsui et al, 1996 Okumura et al, 1996) and, twelve minutes later, the first victims arrived on foot at the emergency department. A casualty in cardiopulmonary arrest was brought in by private car at 08 43 hours. In all, 640 casualties were assessed at St Luke s Hospital on 20 March 1995, with the Chapel being used as the main treatment area (Okumura et al, 1996). Initially (at 09 12 hours), the Fire Department identified acetonitrile as the suspected agent. However, medical staff discounted this diagnosis as all casualties had marked miosis and atropine was therefore administered pralidoxime iodide was first given at 10 00 hours. Miosis appeared to be a more sensitive early indicator of exposure than erythrocyte acetylcholinesterase activity (Nozaki et al, 1997). 

Fig. 5. Effect of 1 /.ig/ml hemicholinium-3 applied topically in the presence of 1 /fg/ml atropine on cortical ACh output and content without or with the previous topical application of echothiophate iodide in pretrigeminally sectioned non-anaesthetised cats. A, ACh output B, ACh content without echothiophate, and C, ACh content following the application for 30 min of 0.5 mg/ml echothiophate iodide. (Reproduced from Can. J. Physiol. Pharmacol. (1970), J. C. Szerb et al., 48, 780-790.)...

Fig. 5. AChE activities slightly more than 16 h after injection of the quaternary inhibitor 2-MPAM-ES iodide (0.325 mg/kg) administered subcutaneously in male rats treated with atropine. Enzyme activities are expressed as percentages of the normal. Bars denote scatter at 95% fiducial probability...

Fig. 6. A, ChE activity of homogenates from the cerebrum (white columns) and retina (hatched columns) of atropinized male rats 16 h after subcutaneous administration of 2-MPAM-ES iodide (0.325 mg/kg). Two hours prior to the administration of the inhibitor the animals were pretreated with subcutaneous injections of 2,4-dinitrophenol (10 mg/kg), ouabain (1 mg/kg), and X-ray irradiation, 5,000 rads, through the head. Enzyme activities are expressed as percentages of the normal. Erythrocyte ChE activity (not shown on the figure) was reduced to 24% (see also Fig. 3). B, Columns denoting ChE in the cerebrum and retina as in A, but from animals pretreated with paraoxon (0.3 mg/kg) intravenously. The left pair of columns represents control animals which were given no subsequent reactivator therapy, whereas the following 3 pairs of columns show the effect of the enzyme reactivators indicated on figure. The ChE reactivation is seen to be more pronounced in the retina than in the cerebrum. Reactivation of erythrocyte ChE (not shown) was materially complete in these experiments. For further details (reactivator dosage, number and time-spacing of doses, etc.) see text.

A number of a-methyl-tropic esters of tropine and -tropine, together with their methiodides and decamethylene di-iodides, have been prepared (102) showing some atropine-like effect. Derivatives of a-ecgonine methyl ester have also been synthesized, e.g., benzilic and p-aminobenzoyl esters and decamethylene salts. a-Ecgonine itself, if injected, proved a potent local anesthetic agent (103), at variance with earlier findings (104). 

Methohexital (1 mg/kg in 1% solution given at a rate of 1 mL/5 seconds) is used for induction of anesthesia lasting 5 to 7 minutes. Maintenance of anesthesia may be accomplished by intermittent injections of 1% solution or by continuous IV drip of a 0.2% solution. Intermittent injections of about 20 to 40 mg (2 to 4 ml of a 1% solution) may be given as required, usually every 4 to 7 minutes. For continuous drip, the average rate of administration is about 3 mL of a 0.2% solution/min (1 drop/second). Methohexital should not be mixed in the same syringe or administered simultaneously during IV infusion through the same needle with acid solutions, such as atropine sulfate, metocurine iodide, and succinylcholine chloride. 

The 0,AT-diacetylnorhyoscyamine has been prepared by the action of acetic anhydride upon the amine oxide of hyoscyamine (182). In acid the 0-acetate is hydrolyzed but in cold alkali, water is eliminated as well with the formation of V-acetyInorapoatropine (acetic anhydride upon the amine oxide of atropine reacts in an analogous fashion). Norhyoscyamine, like hyoscyamine, is easily racemized in alcoholic sodium hydroxide to the optically inactive noratropine (XXIV, R = H). Noratropine and norhyoscyamine are converted with methyl iodide respectively to atropine or Z-hyoscyamine and their methiodides (209). 

Tropin—CaHnNO—isa crystalline solid, fusible at 62° (143°.6 F.), Tery soluble in water. It reacts with methyl iodid to produce methyltropin. Tropin has the poisonous qualities of atropin, but does not dilate the pupil. 

Recommended doses of atropine are 2 mg in patients with mild symptoms that are primarily ocular, but without respiratory symptoms or seizures 4 mg in patients with moderate symptoms, including respiratory symptoms such as dyspnea and 6 mg in patients with severe symptoms, including seizures and respiratory arrest. The standard administration route should be intramuscular. As menhoned previously, intravenous administration of atropine in the treatment of severe symptoms such as hypoxemia can induce ventricular fibrillation thus, intramuscular administration is advised. Oxime agents such as 2-pralidoxime methiodide (2-PAM), or 2-formyl-l-methylpyridinium iodide oxime should also be given. The recommended dose for 2-PAM in... 

The next correlation was found in Scotland where Crum Brown and Fraser (1869) made a major discovery. They showed that several alkaloids, when quaternized, lost their characteristic pharmacological properties (many of them spasmogenic or convulsant) and acquired the muscle-relaxing powers of tubocurarine (2.6) (itself a quaternary amine), whose site of action had been shown to lie at the jimction between nerve and voluntary muscle, a few years earlier, by Claude Bernard (1856). Strychnine, bruceine, thebaine, codeine, morphine, nicotine, atropine, and coniine were quaternized into curarimimetic substances, by reaction with methyl iodide. The Scottish authors wrote There can be no reasonable doubt that a relation exists between the physiological action of a substance and its... 

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