Myosis

Adverse effects with atropine therapy include dry mouth, myosis, loss of visual accommodations, constipation, and urinary retention. The dmg can also produce flushing, hyperthermia, delirium, tachycardia, and exacerbate glaucoma (85). 

Technical parathion held in the conjunctival sac of rabbit eyes produces local irritation and a marked myosis which is spontaneously reversible in 24 hours. No systemic effects were observed. 

Picrotoxinin is a sesquiterpene, which is found notably in the seeds Anamirta panicu-lata Coleb. (levant berries, Menispermaceae Fig. 46). This substance is toxic, and as little as 20 mg induces epileptiform convulsions, myosis, and dyspnea with more or less... 

Although myosis (pin-pointing of the pupils) may be an early sign of agent exposure, an injection shall not be administered when myosis is the only sign present. Instead, the individual shall be taken immediately to the medical facility for observation. 

As a matter of interest, we obtained a compound, diethyl phosphorofluoridite (IX), of a lower state of oxidation than the corresponding phosphorofluoridate by the action of phosphorus dichlorofluoride on ethyl alcohol. The new compound, unlike the phosphorofluoridate, was readily hydrolysed by water, was relatively non-toxic and did not produce myosis.1... 

In view of the greater toxicity often observed with derivatives of o-cresol compared with derivatives of phenol itself, it seemed worth while to prepare di-(o-methylcycZohexyl) phosphoro-fluoridate. At a concentration of 0-65 mg./l. only three out of a batch of twenty-three animals (rabbits, guinea-pigs, rats and mice) were killed. The animals which died (the rabbits) exhibited muscular twitchings, but myosis was not very marked. 

On pp. 2 and 43 reference was made to the intense myosis that we experienced when exposed to low concentrations of D.F.P. In fact, appreciable myosis is brought about by concentrations very much lower than that mentioned on p. 2. The author has frequently noted that, after dealing with D.F.P. and related compounds even under carefully controlled laboratory conditions (e.g. using fume cupboards, respirators, etc.), minute traces of material have adhered to clothing and some hours later gradually vaporized and were sufficient to cause myosis with its... 

It is some 15 years since the writer first experienced myosis with D.F.P. and related compounds, and one difference now noted during myosis is that white surfaces appear yellow. This phenomenon may well be due to changes in lens structure in the region of the optic axis. 

With higher concentrations than those mentioned above, animals exhibit, in addition to myosis, the following symptoms salivation, muscular weakness, loss of muscular co-ordination, gasping, diarrhoea and finally cessation of respiration. There is intense constriction of the bronchioles and the immediate cause of death is asphyxia. Respiration ceases before the heart stops beating. The L.c. 50 s for rats and for mice for a 10 min. exposure are respectively 0-36 and 0-44 mg./l. Air saturated with D.F.P. at ordinary temperatures contains about 8 mg./l. and this will kill mice within 1 min. During exposures for a limited time (e.g. 5 min.), rabbits appear to be more resistant to the inhaled vapour of D.F.P. than are other animals. It appears that the peculiar nasal structure of the rabbit is responsible for its great resistance. 

Symptoms produced by injection by various routes resemble those produced by inhalation. The l.d. 50 by intravenous injection into rabbits is O 5 mg./kg. The l.d. 50 by subcutaneous injection into mice is 5 mg./kg. It should be noted that myosis can occur after injection, and that 1-4 mg./kg. (body weight) applied to a rabbit s eye is immediately fatal. 

Effect on the eye. Leopold and Comroe4 recorded the actions of D.F.P. on the normal eye, expanding the earlier British work (pp. 2, 43). They confirmed the prolonged myosis lasting up to 3 weeks with a spasm of the ciliary muscle for 3-7 days. There is usually a decrease in the intra-ocular tension, although occasionally there may be a slight rise before a fall in pressure. The action outlasts that of common myotics, and a 0-1 per... 

We found that the toxicity and myotic activity of di-isopropyl phosphorofluoridate (XI) were far greater than that of di- propyl phosphorofluoridate. In Report no. 6 on fluoro-phosphonates to the Ministry of Supply3 we described the preparation of di aec.-butyl phosphorofluoridate (XII) by the hydrogen phosphite method (p. 6). The compound was found to be very toxic and to produce severe myosis in man and animals. The symptoms displayed during and after exposure were identical with those produced by di-isopropyl phosphorofluoridate. The L.c. 50 for di-sec.-butyl phosphorofluoridate for mice for deaths within 2 hr. was 0-6 mg./l., and that for deaths within 48 hr. was 0-54 mg./l. 

Four of us were exposed to a concentration of 1 part in 10 for 5min. A tightness acrossthe chestwas noticed.4 Some 5 min. after leavingthe chamber, myosis set in, and became intense and caused severe incapacitation which lasted for 5 days. One observer suffered from sickness and diarrhoea in addition tothemyoticeffect.5... 

Negligible sensory irritation was caused by di-isopropyl phosphorofluoridate at a concentration of 1 part in 10. This, coupled with the fact that the odour was practically undetectable, means that sufficient warning is not usually given at this concentration to suggest the use of respirators. Exposures at this concentration cause severe myosis which persists for several days and causes considerable incapacitation (Report no. 12 by McCombie and Saunders to Ministry of Supply, 4 August 1943). 

Di (l carbethoxyethyl) phosphorofluoridate (XV) was readily produced by the action of sodium fluoride on the corresponding phosphorochloridate obtained from di-(l -carbethoxyethyl) hydrogen phosphite, which in turn was obtained by the action of phosphorus trichloride on ethyl lactate. Although (XV) contained secondary groupings, it was found to be relatively nontoxic and to produce only slight myosis in the pupils of the eyes of rabbits and guinea-pigs. 

It was important to determine whether the fluorine atom must be attached directly to the phosphorus atom in order to produce phosphorofluoridate-like activity. For this purpose we treated the toxic di-sec.-butyl phosphorofluoridate1 with diazomethane and obtained a compound which was undoubtedly di- ec.-butyl fluoromethylphosphonate (XIX). Unlike the parent phosphorofluoridate, the fluoromethylphosphonate was only slightly toxic and produced negligible myosis. (It may be mentioned here that thionyl chloride and carbonyl chloride were converted by means of diazomethane into bis-(chloromethyl)-sulphoxide and S-dichloroacetone respectively.)... 

This ester, isopropyl methylphosphonofluoridate (X), is a colourless liquid. It is more toxic than D.F.P., but shows very similar physiological properties, intense myosis, respiratory collapse, powerful anticholinesterase activity, etc. The liquid passes rapidly through the skin. At the end of World War II, two plants were under construction in Germany for the production of the material on a large scale. 

Combination of fluoroacetate activity and certain other recognizable physiological effects have been successfully combined in fluoroaspirin (drugged sleep), triethyl-lead fluoroacetate (sternutation), difluoroethyl phosphorofluoridate (myosis, but not powerful). In general, quaternary ammonium... 

Since the main clinical use for antisympathotonics is in the treatment of essential hypertension, such drugs will be discussed in Chapter 20 in more detail. The alkaloid reserpine from Rauwolfia serpentina was the first drug used clinically to reduce sympathetic tone. Reserpine reduce the ability of storage and release of various transmitters (adrenaline, noradrenaline, serotonine and dopamine) by an irreversible destruction of the axonal vesicle membranes. The duration of the reserpine effect is actually determined by the de novo synthesis of these structure. Beside various central side effects like sedation, depression, lassitude and nightmares the pattern of unwanted effects of reserpine is determined by the shift of the autonomic balance towards the parasympathetic branch myosis, congested nostrils, an altered saliva production, increased gastric acid production, bardycardia and diarrhea. As a consequence of the inhibition of central dopamine release, reserpine infrequently shows Parkinson-like disturbances of the extrapyramidal system. 

Overdose results in blurred vision, seizures, myosis, mydriasis, severe muscle weakness, strabismus, respiratory depression, and vomiting. 

Another use for acetylcholinesterase inhibitors is in glaucoma, in which high intraocular pressure can lead to permanent damage to the optic disk, resulting in blindness. The local instillation of physostigmine (8.14) or echothiophate (8.19) solution in the eye results in a long-lasting decrease in the intraocular pressure as well as myosis (contraction of the pupil). 

The exactly opposite effects of drugs and dreams on pupillary aperture and reflex excitability are important examples of informative differences between the two states. REM sleep is off-line—that is, the brain is dissociated from inputs and outputs—precisely because access of afferent stimuli to the CNS is blocked (e.g., pupillary myosis), as is access of internally generated motor commands to the peripheral muscles (e.g., inhibited deep tendon reflexes). Were this not the case, REM sleep would be waking (or a hybrid state even more like drug psychosis). And if the converse were... 

When the structure in Fig. 29A is put into the fish muscle A-band unit cell (Fig. 29B note that the analysis of Hudson et al. [1997] defined the absolute orientation of the filament within the A-band lattice), it can be seen that the actin-binding sites on the myosi n heads are already close to... 

Myosis 3 levels based on mean pupil diameter measured in treated and control animals (1 unit =1/30 mm) + decrease > 10 units ++ decrease > 20 units +++ decrease > 30 units... 

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