Dependent Effects of Atropine

Atropine is absorbed orally and crosses the placental barrier, whereupon it causes fetal tachycardia. Atropine has been used to examine the functional integrity of the placenta. 

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The effect of atropine upon chromosomal abnormalities24 has been studied. A significant dose-dependent reduction of heart rate and blood pressure has been observed.25 A possible effectiveness of atropine on Prinzmetal s variant form of... 

Although some steroids have been reported to reduce the toxic effects of some insecticides, the steroid ethylestrenol decreased the rate of recovery of depressed cholinesterase activity in disulfoton- pretreated rats (Robinson et al. 1978). The exact mechanism of this interaction was not determined. Ethylestrenol alone caused a small decrease in cholinesterase activity, and, therefore, resulted in an additive effect. Rats excreted less adrenaline and more noradrenaline when given simultaneous treatments of atropine and disulfoton compared with rats given disulfoton alone (Brzezinski 1973). The mechanism of action of disulfoton on catecholamine levels may depend on acetylcholine accumulation. In the presence of atropine, the acetylcholine effect on these receptors increases the ability of atropine to liberate catecholamines. 

Drug abuse and dependence In recommended doses, diphenoxylate has not produced addiction and is devoid of morphine-like subjective effects. At high doses, it exhibits codeine-like subjective effects therefore, addiction to diphenoxylate is possible. A subtherapeutic dose of atropine may discourage deliberate abuse. 

In the cardiovascular system the effect on the heart rate is prominent. The depressive influence of the nervus vagus on the pacemaking activity in the heart is concentration dependently reduced and thereby the heart rate increases. This can be therapeutically useful in various forms of bardycardia, especially if they are caused by a vagus overstimulation, for example in the carotis-sinus syndrom. There is hardly any effect on the vasculature except a vasodilatation in the thoracic region after very high doses of 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... 

Dryness of mucous membranes is a common side effect of anticholinergic drug use and is due to dose-dependent inhibition of glandular secretion. In one study, oral administration of atropine caused tear secretion to fall from 15 to 3 mcl/min.A similar dose of atropine given subcutaneously gave a nearly 50% reduction in lacrimal secretion. Scopolamine at a dose of 1 to 2 mg orally reduced tear secretion from 5 to 0.8 mcl/min. Atropine combined with diphenoxylate (Lomotil) has been reported to cause severe keratoconjimctivitis sicca in susceptible individuals. 

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). 

Signal Transduction Model The pharmacological effects of drugs may be mediated by a time-dependent signal transduction process, which involves multiple steps. Sun and Jusko proposed a signal transduction model to account for the delayed effect of pharmacodynamic responses. This model has been used to characterize the parasympathomimetic activity of scopolamine and atropine in rats. ... 

The effect of acetylcholine, dopamine, and bradyki-nin on vascular tone has been examined in interlobular arteries and superficial afferent and efferent arterioles isolated from rabbit kidney [141]. Acetylcholine caused a dose-dependent relaxation of norepinephrine-induced tone in all three vessel types. Significant relaxation was observed with 10(-8) M acetylcholine and higher concentrations caused complete relaxation. In afferent and efferent arterioles dopamine caused a dose-dependent relaxation that was indistinguishable from the one caused by acetylcholine. Dopamine was much less effective on interlobular arteries. In afferent arterioles atropine blocked the effect of acetylcholine, and metoclopramide selectively inhibited dopamine-induced relaxation. Bradykinin caused a dose-dependent relaxation of norepinephrine- induced tone only in efferent arterioles. Bradykinin, either in the bath or lumen, had no effect on the preglomerular microves-... 

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