Atropine indications

Frutropium bromide is a derivative of atropine, indicated in the treatment of asthma and bronchitis. It has a cholinergic central effect it is also a muscarinic and histaminic antagonist (Figure 8.50). 

The glycosidic alkaloid veronamine [(— )-4a -L-rhamnosidothali-fendlerine] produces systemic hypotension and bradycardia and a reduction in pressure of the perfused hindlimb of anesthetized dogs (380). The systemic effects of veronamine are blocked by bilateral cervical vagotomy or pretreatment with atropine, indicating that these effects are mediated through cholinergic mechanisms. The effect of veronamine in the perfused hindlimb is not sensitive to atropine. 

Earlier studies with /-tubocurarine and atropine indicated that nicotinic and muscarinic ACh receptor blockers can modulate the release of ACh induced by an inhibitor of AChE (Carlson and Dettbam, 1987, 1988). The effects of these dmgs, whether inhibiting or stimulating ACh release, are concentration dependent and determined by the frequency of nerve activity (Bowman, 1980 Wessler et al, 1987a, b). Therefore, dmgs that reduce axonal hyperexcitability by decreasing amount of ACh released from the nerve terminals without interfering with normal transmission... 

Anticholinergic treatment (atropine derivatives) may sometimes be indicated, especially in patients with pronounced bradycardia. 

Mechanical Response. PTX (5 x 10" to 3 x 10 M) caused a concentration-dependent contraction of the guinea pig vas deferens. The configuration of contractile response indicated the presence of two components, an initial rapid component followed by a second slow component. The first component of the response to PTX was abolished after treatment with Mg (10 mM), Ca -free medium, or ouabain (10 M), but remained almost unaffected by phentolamine (10 M), reserpine, 6-OHDA, atropine, or mecamylamine (10" M). The second component of the response to PTX was also completely inhibited after the incubation in the high or Ca -free medium. Phentolamine, reserpine, or 6-... 

Pharmacologically, carbofuran inhibits cholinesterase, resulting in stimulation of the central, parasympathetic, and somatic motor systems. Sensitive biochemical tests have been developed to measure cholinesterase inhibition in avian and mammalian brain and plasma samples and are useful in the forensic assessment of carbamate exposure in human and wildlife pesticide incidents (Bal-lantyne and Marrs Hunt and Hooper 1993). Acute toxic clinical effects resulting from carbofuran exposure in animals and humans appear to be completely reversible and have been successfully treated with atropine sulfate. However, treatment should occur as soon as possible after exposure because acute carbofuran toxicosis can be fatal younger age groups of various species are more susceptible than adults (Finlayson et al. 1979). Carbofuran labels indicate that application is forbidden to streams, lakes, or ponds. In addition, manufacturers have stated that carbofuran is poisonous if swallowed, inhaled, or absorbed through the skin. Users are cautioned not to breathe carbofuran dust, fumes, or spray mist and treated areas should be avoided for at least 2 days (Anonymous 1971). Three points are emphasized at this juncture. First, some carbofuran degradation... 

If indicated, CPR should be started immediately. Mouth-to-mouth resuscitation should be used when approved mask-bag or oxygen delivery systems are not available. Do not use mouth-to-mouth resuscitation when facial contamination exists. CAUTION Atropine does not act as a prophylactic and shall not be administered until an agent exposure has been ascertained. 

Compared with neostigmine,2 D.F.P. produced side effects more commonly and these arose in spite of administration of atropine (0-01 gr.) in an attempt to control the gut symptoms. There were no changes in liver, kidney or haemopoietic function ascribed to D.F.P. Asthma was considered a contra-indication to the use of D.F.P. It can thus be seen that D.F.P. in therapeutic dosage is a safe medicament.3... 

The fact that the EP wants to replace old TEC methods with more selective, efficient, and sensitive separation methods provides the chance for the introduction of more CE methods. The continuous development of analytical methods is reflected in the national and international pharmacopoeias. This might be demonstrated for atropine sulfate. Whereas the Deutsches Arzneibuch, 7th Edition (DAB 7) only limits the tropic acid by extraction and titration with NaOH and phenolphthalein indication, the 4th edition of the EP looked for foreign alkaloids and decomposition products by means of TEC with a potassium iodobismuthate for detection. By intensity comparison of the obtained spots, it was possible to limit these impurities to 0.5%. The EP 5 utilizes an ion-pair HPLC method that is able to limit most of the impurities to less than 0.2%. To make the method more robust, an HPLC method using a polar embedded was applied, which might be the next step for the EP. However, recently the same authors have reported on a MEEKC method being as robust and precise as the latter HPLC method (see Eigure 6) but far more sensitive and, therefore, a future perspective for the EP. 

Journal reports by Bell and Gershon indicated that tetrahydroaminoacridine (THA), a cholinesterase inhibitor, was effective in reversing delirium induced by Ditran (JB-329) as a form of psychiatric treatment It is interesting that their use of Ditran for this purpose was similar to the atropine coma treatment method reported more than a decade earlier by Forrer, Miller et al. In our study, five subjects were given 5.0 mcg/kg of oral BZ on two occasions, 8-14 days apart 60 mcg/kg of THA was administered iv four hours after the time of the second BZ dose. We observed definite partial reversal of impairment soon after injection, but it was brief. An unexpected observation was the general tendency by the subjects to become impaired more rapidly and intensely by BZ on the second occasion - a finding that was later confirmed in a more careful study. 

Fig. 3.13 The ACE50 method demonstrated for a mixture of ligands at 1 tM per component to the M2 receptor at 5 pM concentration. (A) NGD-3350 requires the greatest competitor concentration to be competed from the receptor, indicating that it is the highest affinity ligand. (B) Ratio plots indicate direct binding competition with atropine. (C) Select compound structures. Reprinted from [39] with permission from the American Chemical Society.

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