Atropine tolerance

Previously published clinical observations of daily atropine and scopolamine effects usually did not include precise recording time of onset and recovery from each dose. At least one journal report, however, did note that a certain degree of tolerance to atropine developed in the course of daily use for several months or years. This may or may not be based on a mechanism similar to the second-dose effect that we observed with BZ. Conceivably, this might have military implications if the target population had previously been exposed to an attack with BZ on one or more occasions. The practical significance of the slightly earlier onset and recovery, however (Fig. 12), seems to be relatively minor. 

Pickford EJ et al. Infants and atropine A dangerous mixture. J Paediatr Child Health 1991 27 55-56. Ruckenstein MJ and Harrison RV. Motion sickness Helping patients tolerate the ups and downs. Postgrad Med 1991 89 139-144. 

The central anticholinergic drugs having a higher central versus peripheral cholinergic action ratio are useful. The drugs like atropine are much less effective than levodopa but they are used when levodopa is not tolerated or contraindicated or the patient is not benefitted by levodopa or drug induced parkinsonism. 

If muscarinic effects of such therapy are prominent, they can be controlled by the administration of antimuscarinic drugs such as atropine. Frequently, tolerance to the muscarinic effects of the cholinesterase inhibitors develops, so atropine treatment is not required. 

Atropine and the other tertiary agents are widely distributed in the body. Significant levels are achieved in the CNS within 30 minutes to 1 hour, and this can limit the dose tolerated when the drug is taken for its peripheral effects. Scopolamine is rapidly and fully distributed into the CNS where it has greater effects than most other antimuscarinic drugs. In contrast, the quaternary derivatives are poorly taken up by the brain and therefore are relatively free—at low doses—of CNS effects. 

Constriction of the pupils is seen with virtually all opioid agonists. Miosis is a pharmacologic action to which little or no tolerance develops (Table 31-3) thus, it is valuable in the diagnosis of opioid overdose. Even in highly tolerant addicts, miosis is seen. This action, which can be blocked by opioid antagonists, is mediated by parasympathetic pathways, which, in turn, can be blocked by atropine. 

Opiate preparations, usually given as paregoric, are effective and fast acting antidiarrheal agents. These agents are also useful postoperatively to produce solid stool following an ileostomy or colostomy. A meperidine derivative, diphenoxylate, is usually dispensed with atropine and sold as Lomotil. The atropine is added to discourage the abuse of diphenoxylate by narcotic addicts who are tolerant to massive doses of narcotic but not to the CNS stimulant effects of atropine. 

Meperidine shows certain relationships to both morphine and atropine in its action. Similar to morphine, it exerts a generalized depression of the CNS but, in ordinary doses, does not affect the cough reflex. Similar to morphine, it induces euphoria, and its continued use leads to tolerance and addiction. However, its euphoric and sedative effects are less than that of morphine addiction due to meperidine is more serious than that due to morphine. Meperidine is an effective analgesic,... 

Anticholinergics. Antagonists at muscarinic cholinoceptors such as benztropine and bi-periden (p. 110) can be used to suppress the sequelae of the relative predominance of cholinergic activity in the striatum (in particular, tremor). Atropine-like peripheral side effects and impairment of cognitive function limit the tolerable dosage. Complete disappearance of symptoms cannot be achieved. 

A study investigating the use of atropine for treatment of amblyopia indicated it was as successful as patching therapy. Subjects were less than 7 years old and tolerated 1% atropine daily for 2 years without adverse effects. See Pediatric Eye Disease Investigator Group.A randomized trial of atropine vs patching for treatment of moderate amblyopia in children. Arch Ophthalmol 2002 120 268-278. 

The acute effects of the antl-ChEs are short-lived and do not outlast the Inhibition of the enzyme Indeed, some systems develop tolerance rapidly, so function returns to normal even before there la substantial regeneration of measurable enzyme activity It has been amply documented that, even with over 99X Inhibition of all ChEs, animals (and presumably humans) can survive without oxime or atropine treatment. If they are supported for a couple of hours by pharmacologic or nonphazmacologlc means, such as artificial respiration, (72) This recovery from the lrreverslble" effects of Inhibitors may depend on rapid regeneration of ChEs, particularly some AChE isoenzymes (114) desensltlzatlon of the postsynaptlc membrane, a phenomenon that limits the response to accumulated ACh or compensatory changes in presynaptlc and postsynaptlc receptors (115). 

For most substances, the mechanism of action will be the same in humans and other mammals. Therefore, quantitative rather than qualitative differences in response are most common. Humans may be more sensitive to some drugs than certain laboratory animals are, but in many cases some animal species are more sensitive than humans are. For example, the mouse is most sensitive to atropine, the cat is less sensitive, and the dog and the rabbit tolerate atropine at doses 100 times higher than does the human. 

There are many anticholinergic drugs, some structurally related to atropine, others quaternary ammonium compounds or tertiary amines. Although many of these products are claimed to have superior efficacy, specificity, or tolerance, few have ever been critically compared with others. The so-called freedom from adverse effects claimed for many of these compounds can often be traced to uncritical clinical work, the use of ineffective doses, or mere lack of activity of the compound. 

In contrast to isoflurane and desflurane, sevoflurane tends not to increase the heart rate, and is usually well tolerated for induction of anesthesia in young children. However, profound bradycardia was reported in four unpremedicated children aged 6 months to 2 years during anesthesia induction with sevoflurane 8% and nitrous oxide 66% (7). The episodes were not associated with loss of airway or ventilation. In three of the children there was spontaneous recovery of heart rate when the sevoflurane concentration was reduced the other child received atropine because of evidence of significantly reduced cardiac output. In a previous study of sevoflurane induction of anesthesia in children with atropine premedication there was also a low incidence of this complication (8), which is probably due to excessive sevoflurane concentrations. 

Atropine. Severely poisoned individuals may exhibit tolerance to atropine and require large doses. Oximes such as pralidoxime chloride (2-PAMCl) do not significantly increase the effechveness of atropine and in some cases may be contraindicated. 

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