Over-atropinization

Atropine is an antidotal treatment. It is used to reverse the muscarinic signs, but it will not reverse the nicotinic effects (muscular weakness, diaphragmatic weakness, etc.). Atropine blocks the effects of accumulated acetylcholine (ACh) at the synapse and should be continued until the nerve agent is metabohzed (Midthng et al, 1985). Over-atropinization can cause hyperthermia, tachycardia, agitation, mydriasis, and ileus, which can be life threatening in the horse (Meerstadt, 1982). 

These structural features allow the Ipratropium molecule to attain a relatively selective bronchodilator effect on the cholinergi-cally innervated airways. By the inhalation route of application, this poorly absorbable quaternary ammonium derivative becomes selective to primarily affect the airway smooth muscle. Another advantage of ipratropium over atropine is that, in contract to the latter, it does not suppress mucociliary function. 

Inhalation and dermal absorption Atropine (2 mg) IV repeat q 5 min, titrate until effective, average dose 6 to >f5 mg -use IM in the held before IV access (establish airway for oxygenation). Pralidoxime chloride (2-PAMC1) 600-f800 mg IM or 1.0 g IV over 20-30 min (maximum 2 g IM or IV per hour). 

Efficacy of oximes grows up, when they are combined with atropine sulfate. HI-6 reserves for itself superiority over other H-oximes. 

In any event, the results of the Japanese treatment were only modest. Although the investigators reported substantial improvement in clinical status, they actually classified only about 35% as slightly or significantly improved. This suggests that the reported success of atropine coma therapy by Forrer et al. may also have been overly sanguine. 

My own practice was to refer to agents such as BZ or other related glycolates as similar to belladonna or atropine - belladonnoids if you will. Since the terms atropine and belladonna were also unfamiliar to many volunteers, I said that the effects would vary from person to person, but generally, they would include dryness of the mouth, sleepiness, difficulty in solving problems, and altered perceptions. I assured them that both the nursing staff and I would monitor them closely. I explained that extensive pre-clinical studies in several animal species had revealed no permanent ill effects. I told them we believed the drug to be safe, and would discuss the effects in detail after the test was over. Very few volunteers chose to withdraw after this orientation. 

Antagonists. Most of the so-called Hi-antihistamines also block other receptors, including M-cholinoceptors and D-receptors. Hi-antihistamines are used for the symptomatic relief of allergies (e.g., bamipine, chlorpheniramine, clemastine, dimethindene, mebhydroline pheniramine) as antiemetics (meclizine, dimenhydrinate, p. 330), as over-the-counter hypnotics (e.g., diphenhydramine, p. 222). Promethazine represents the transition to the neuroleptic phenothiazines (p. 236). Unwanted effects of most Hi-antihistamines are lassitude (impaired driving skills) and atropine-like reactions (e.g., dry mouth, constipation). At the usual therapeutic doses, astemizole, cetrizine, fexofenadine, and loratidine are practically devoid of sedative and anticholinergic effects. Hj-antihistamines (cimetidine, ranitidine, famotidine, nizatidine) inhibit gastric acid secretion, and thus are useful in the treatment of peptic ulcers. 

Over the course of the past few decades, a number of synthetic atropine-like substances with more spasmolytic and less anticholinergic action and causing fewer side effects have been used clinically in treating stomach ulcers, pylorospasms, and hyperperistaltics. 

Rarely did the intramuscular or intravenous doses exceed 1.5 times the Incapacitating dose. Inhalation doses were higher, but potencies were lower by this route (usually about 60 percent of that by the Intravenous or intramuscular route). Compared with doses described in the scientific literature on atropine coma therapy 18-23 or scopolamine therapy, the BZ doses to which volunteers were exposed appear modest. As much as 20 times the ID50 of atropine and 30-40 times the ID50 of scopolamine have been administered in the past by clinicians—often to older and less robust patients. Many patients received multiple exposures of this magnitude over a period of days or weeks. These therapeutic procedures, reported several decades ago in refereed journals, actually stressed and advocated the benefits of such treatment, despite occasional deaths (most of which appear to have been caused by hyperthermia). 

Individuals on very small amounts of heroin are prescribed diazepam for anxiety, agitation or craving, zopiclone or zolpidem for insomnia, hyoscine butylbromide (Buscopan) for stomach cramps, and diphenoxylate/atropine (Lomotil) for diarrhoea, over a seven-day period. The medication schedule provided to the user explains which drug is for which symptoms, and the maximum doses of each that can be taken in a day, which for diazepam varies during the course. The basic medication regime is included in the Appendix. 

This drug is only approved for oral administration in some countries. It is effective for conversion of atrial flutter or fibrillation or ischaemia-induced ventricular arrhythmias. It has significant anticholinergic properties (10% of the potency of atropine) that can offset its direct depressant effects on sinus and AV nodes. It has a pronounced negative inotropic effect and should be administered with caution to patients with a history of congestive heart failure. For acute treatment of perioperative arrhythmias it is given intravenously 0.2 mg-kg-1 over 10-15 min, then 0.2 mg-kg-1 over the next 45 min and a maintenance infusion of 0.4 mg-kg-l-h-1. 

Unfortunately, children, especially infants, are very sensitive to the hyperthermic effects of atropine. Although accidental administration of over 400 mg has been followed by recovery, deaths have followed doses as small as 2 mg. Therefore, atropine should be considered a highly dangerous drug when overdose occurs in infants or children. 

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