Physostigmine injection

They gave twenty-one male and female patients suffering from various psychotic illnesses up to 12 doses of 30-100 mg of atropine. They injected physostigmine, in doses of 8-16 mg ( ) 3A hours after the onset of coma, supplemented by 2 mg every half hour until the patient regained consciousness. They then used supplemental small oral doses of physostigmine as necessary to maintain a clear sensorium (awareness of time, place, and person). 

Fortunately, Snooks was also a surprisingly patient man. He waited calmly while my assistant drew physostigmine into a syringe and handed it to me to inject. Even before it could take effect, Snooks quietly returned to his bed and made no further trouble. The thick, unhinged door, however, continued to lie flat on the floor a poignant tribute to his door-busting ability. 

Fig. 11 This subject was one of 8 volunteers who participated in Project Dork, previously described in Chapter 14. Performance scores dropped rapidly when physostigmine was withheld, but returned to near normal when resumed. Heart rate responded similarly. Total amount of physostigmine given was roughly 100 mg (expressed as oral dose equivalent). Note that physostigmine by injection is approximately 50% more effective than by the oral route (i.e., 2 mg i.m. 3 mg p.o.)...

Absorption of the quaternary carbamates from the conjunctiva, skin, and lungs is predictably poor, since their permanent charge renders them relatively insoluble in lipids. Thus, much larger doses are required for oral administration than for parenteral injection. Distribution into the central nervous system is negligible. Physostigmine, in contrast, is well absorbed from all sites and can be used topically in the eye (Table 7-4). It is distributed into the central nervous system and is more toxic than the more polar quaternary carbamates. The carbamates are relatively stable in aqueous solution but can be metabolized by nonspecific esterases in the body as well as by cholinesterase. However, the duration of their effect is determined chiefly by the stability of the inhibitor-enzyme complex (see Mechanism of Action, below), not by metabolism or excretion. 

Benita, S., Friedman, D., and Wainstock, M. (1986) Physostigmine emulsion a new injectable controlled release delivery systertnt. J. Pharm., 30 47-55. 

The available data cannot demonstrate that slowing the wing-beat frequency following injection of physostigmine is solely or even partly due to elevated levels of acetylcholine at... 

Figure 1. Wing-beat frequency of Locusta adults before (arrow on abscissa) and after injection of 5 ul/g H O (Ar-A) or 5 yg/g physostigmine ( — ). Reproduced with permission from Ref. 29. Copyright 1973, Pergamon Press.

After a single subcutaneous injection of 1 mg of physostigmine salicylate (equivalent to 0.67 mg base) to one subject, a peak plasma concentration of0.0036 fig/ml was achieved after 15 minutes (R. Whelpton, ibid.). 

Physostigmine salicylate in 0.5 % aqueous solution was determined by Teare and Borst by freeze-drying of samples of 0.2 ml, and conversion of the compound into its trimethyl silyl derivative by dissolving the residue in 5 yl of dry pyridine and 10 yl of N,0-bis(trimethyl -silyl)acetamide. The solution was allowed to stand for 1 h before injecting 1.2 yl into the gas chromatograph. A 3.8 % SE-30 on Diatoport S column and a temperature of 145°C was used for the analysis. The physostigmine THS and the salicylic acid TMS derivatives were eluted separately. Routine analysis over several days gave a precision of 11.5 %. 

Physostigmine trapping coluttm pre-column 20 pL injection loop (MF-6262, BAS)... 

This may call for maintenance of fluid intake, and if a marked increase in temperature occurs, cooling is indicated. If there is continued mental aberration then the antidote physostigmine can be given as 2-3 mg IM for alleviation, followed by repeat injections at 15-60 min intervals to prevent relapse, and if required a slow i.v. infusion. The dose should be determined by the clinical condition of the subject. Another antidote is 7-methoxytocrine (7-MEOTA). For mild intoxication an oral dose of 100 mg can be given. For more severe poisoning, IM dosing (50 mg) is more effective. 

Tuovinen and Hanninen (1999) investigated the protective action of carbamates, epastigmine, and physostigmine in mice. Intraperitoneal administration of epastigmine (0.9 mg/kg body weight) or physostigmine (0.1 mg/kg body weight) 10 minutes prior to administration of soman followed by subcutaneous injection of 37.5 mg/kg atropine... 

Nevertheless, reports36 37 of reversal by physostigmine of coma (produced by injected doses of atropine as high as 212 mg, as therapy for certain psychiatric disorders) reappeared during the 1950s. 

The intravenous injection of neostigmine at high doses (1(X) gg/kg) after ganglionic blockade in the anaesthetised dog elicits a pressor response [96], and McEwen [97] reported intravenous injections of physostigmine at doses of 1(X) pg to 1 mg in atropinised rats (approximating 0-5 to 5 mg/kg) to elicit... 

S. Benita. D. Friedman and M. Wei nstock. Pharmacological evaluation of an injectable prolonged release emulsion of physostigmine in rabbits. J. Phartn. Pharmacol.. 38 653-658. 1986. 

Recently, the attention of some researchers was focused on the potentiality of microemuhions as carriers for ophthalmic drugs (19). investigations on possible ocular application.s of microemulsions were stimulated by the discovery of their potentiality as injectable vehicles for lipophilic drugs such as physostigmine or diazepam (20-2JI). 

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