Atropinization, effect

Leaves from Datura stramonium have been used in treating asthma for hundreds of years. Interest in the potential value of antimuscarinic agents increased with demonstration of the importance of the vagus in bronchospastic responses of laboratory animals and by the development of a potent antimuscarinic agent that is poorly absorbed after aerosol administration to the airways and is therefore not associated with systemic atropine effects. 

Based on the experience of Iranian physicians who treated sarin toxicity during the Iran-Iraq war (Newmark, 2004), PAM was not available on the front lines and atropine alone was used for treatment. The doses of atropine used were considerably higher than those used in the Tokyo subway sarin attack, or that are generally recommended in the USA (Medical Letter, 2002). The Iranian protocol called for initial administration of 4 mg intravenously. If no atropine effects (improvement in dyspnea or decrease in airway secretions) were seen after 1 to 2 min, 5 mg was then administered intravenously over 5 min while heart rate was monitored. A rise in heart rate of 20 to 30 beats per min was regarded as an atropine effect. In severe cases, 20 mg to 200 mg was given. Regardless of dose, the key to saving lives, in their opinion, was how soon the atropine was administered. 

Penetar, D. M. (1990). A brief review of atropine effects on physiology and performance. Drug Development Research, 20, 117—121. 

FIGURE 10.6 Posttreatment with galantamine/atropine effectively counteracts nerve agent and insecticide toxicity in guinea pigs. Lower the level of OP exposure, longer the time within which the antidotal therapy effectively maintains 100% survival of the animals with no signs of toxicity. (From Albuquerque, E.X. et al., Proc. Natl. Acad. Set USA, 103, 13220, 2006. With permission.)... 

Whishaw, I.Q. et ah, 1985. Disruption of central cholinergic systems in the rat basal forebrain lesions or atropine effects on feeding, sensorimotor behavior, locomotor activity and spatial navigation. Behav. Brain Res. 17, 103-115. 

No. Receptor sensitivity differs among the various organs, making atropine effects dose-de-pendent. The most sensitive receptors are those of the salivary, bronchial, and sweat glands. Next are the receptors in the eye and heart, followed by the receptors in the GI tract. 

Pupillary dilation, not constriction, is a characteristic atropine effect, as indicated by the origin of the name belladonna ( beautiful lady ) from the ancient cosmetic use of extracts of the At-ropa belladonna plant to dilate the pupils. The answer is (B). 

Atropine-like alkaloids colouration of urine. After long use melanosis of the rectum Atropine effects, such as drowsiness. Potentiation of anticholiner-... 

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). 

Isoproterenol. Isoproterenol hydrochloride is an nonselective P-adrenoceptor agonist that is chemically related to NE. It mimics the effects of stimulation of the sympathetic innervation to the heart which are mediated by NE. It increases heart rate by increasing automaticity of the SA and AV nodes by increasing the rate of phase 4 diastoHc depolarization. It is used in the treatment of acute heart block and supraventricular bradyarrhythmias, although use of atropine is safer for bradyarrhythmias foUowing MI (86). 

Atropine causes dilation of the pupil of the eye. A drop or two of an aqueous solution, containing 1 part in 130,000 parts of water, introduced into the eye of a cat is sufficient to produce this effect. When warmed with sulphuric acid and a small crystal of potassium dichromate, atropine develops a bitter almond odour. Evaporated to dryness on a water-bath with concentrated nitric acid, it gives a residue which becomes violet on adding a drop of sodium hydroxide solution in alcohol (Vitali s test). With a solution of mercuric chloride atropine gives a yellow to red precipitate of mercuric oxide. 

Phenylglycollyltropeine Mandelyltropeine, homatropine), CigHjiOjN. This is largely used as a substitute for atropine. It crystallises in prisms, m.p. 95-5-98-5°. The hydrobromide, the salt usually employed in medicine, is a crystalline powder, m.p. 217-8° (dec.) the hydrochloride, m.p. 224-5°, and the salicylate are also used. All tl ee are freely soluble in water. The methobromide has m.p. 192-6°. The aurichloride, B. HAUCI4, forms prisms and is sparingly soluble in water. Homatropine, unlike atropine, does not give the Vitali colour reaction (p. 70). Its mydriatic effect is more rapid and transient than that of atropine. 

A comparison of the activities of these three alkaloids lias been made by Graliam and Gunn using their antagonism to the effects of carbamjd-choline chloride on isolated mammalian intestine. The relative activities found were, atropine sulphate 1 I-hyoscyamine sulphate 2-4 hyoscine hydro bromide 1-5. The results of previous authors are discussed and reasons suggested for some of the differences found. 

Cushny has compared the action of d- and Z-hyoscyamines with that of atropine, and of d-homatropine with that of dZ-homatropine in antagonising the action of pilocarpine, and finds that the order of activity of the first three is in the ratio 1 40 20, and of the second two in the ratio 4 2-5. He drew attention also to the important influence of the acyl radical in the tropeines, which exercises the maximum effect when it is a hydroxyalkyl aromatic residue and is laevorotatory and in illustration of this point gives the following table of relative activities on the basis of capacity to antagnonise pilocarpine in the salivary fistula dog —... 

It resembles atropine in its range of activity but in particular types of action it may differ quantitatively thus its action on the pupil is equal to that of atropine but shorter in duration, and that is also true of its antagonisni to the effect of acetylcholine on the isolated perfused cat s COTt, but its activity on the salivary gland and the blood pressure of the. IS greater than that of atropine, while its action on smooth muscle... 

Pellotine is a convulsant in the frog and cat. Clerc, Janot and Paris, state that the intravenous lethal dose in dogs is 10 mgm./kilo. In chloralosed dogs 5 mgm./kilo slowed the heart and caused a fall in blood pressure the effects lasted for a few minutes and resembled those due to acetylcholine they were inhibited by atropine and increased by yohimbine and ergotamine. A few injections of this dose at short intervals produced convulsions and this effect was inhibited by phenobarbitone. 

The simplification of the local anesthetic phaimacophore of cocaine to an aryl substituted ester of ethanolamine has been described previously. Atropine (S2) is a structurally closely related natural product whose main biologic action depends on inhibition of the parasympathetic nervous system. Among its many other actions, the compound exerts useful spasmolytic effects. 

FIGURE 4.12 Effect of alcuronium on the binding of [3H] methyl-QNB (filled circles) and [3H] atropine (open circles) on muscarinic receptors. Ordinates are percentage of initial radioligand binding. Alcuronium decreases the binding of [3H] methyl-QNB and increases the binding of [3H] atropine. Data redrawn from [7]. 

An example of the procedure is shown in Figure 6.22. Specifically, a series of Schild analyses were done for the reference antagonist scopolamine in the presence of different concentrations of the test antagonist atropine. The resultant plot according to Equation 6.38 yields an estimate of the KB for atropine as the intercept (Log (k— 1) = 0). If atropine had secondary effects on the system, this procedure will cancel them and allow measurement of the receptor antagonism. An example of this procedure is given in Section 12.2.5. 

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