Atropine peripheral effects

Antimuscarinic drugs such as atropine have been used to modest effect in the treatment of PD for more than a century attenuating tremor and rigidity but with little effect on akinesia. Currently benzhexol and benztropine are sometimes added to levodopa therapy but peripheral effects such as dry mouth, blurred vision and constipation are unpleasant. They are also often used to counteract neuroleptic-induced extrapyramidal effects. 

The cholinergic hallucinogens all have common chemical constituents that are responsible for their pharmacological effects (Robbers et al. 1996). These are the tropane alkaloids hyoscyamine, scopolamine (or hyoscine), and atropine (figure 9.16). It is scopolamine, and not atropine or hyoscyamine, which primarily produces the central and hallucinogenic effects because it is the only one that passes the blood-brain barrier sufficiently. However, all three have peripheral effects. Datura stramonium contains 0.1-0.65% tropane alkaloids, which is principally... 

Atropine s peripheral effects on heart rate (Fig. 63) and blood pressure (not shown) are substantial and very rapid in onset, peaking at about 30-60 minutes. In this graph, baseline heart rate is shown as zero. Maximum heart rate at the ID50 is thus about 125 (60 + 65). It remains at this level for about 3 hours and returns to normal at about 9 hours. At the ID50, minor changes in the electrocardiogram were noted in a study by Hayes et al.. These changes rapidly revert to normal as HR declines. 

Goodman noted that the usual textbook estimates of the lethal dose of atropine (and scopolamine) are undoubtedly too low. With respect to scopolamine, for example, he found 9 cases that survived scopolamine doses of 225-267 mg, 3 cases that survived 324-384 mg and 2 who survived 500 mg.. (Abood also reported personal observation of two recoveries from large oral doses of scopolamine 350 mg and 500 mg, respectively.) These doses are close to the highest reported lethal range for atropine. Since scopolamine has about 7x the potency of atropine centrally, but roughly equal potency peripherally, one can infer that death from belladonnoid drugs is probably due to a peripheral effect - most likely cardiotoxicity. 

Symptomatic treatment in parkinsonism for the purpose of restoring a dopaminergic-cholinergic balance in the corpus striatum. Antiparkinsonian agents, such as benzatropine (p. 188), readily penetrate the blood-brain barrier. At centrally equi-effective dosage, their peripheral effects are less marked than are those of atropine. 

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. 

Many first-generation agents, especially those of the ethanolamine and ethylenediamine subgroups, have significant atropine-like effects on peripheral muscarinic receptors. This action may be responsible for some of the (uncertain) benefits reported for nonallergic rhinorrhea but may also cause urinary retention and blurred vision. 

Scopolamine [skoe POL a meen], another belladonna alkaloid, produces peripheral effects similar to those of atropine. However, scopolamine has greater action on the CNS and a longer duration of action in comparison to those of atropine. It has some special actions indicated below. 

Peripheral effects typical of atropine, such as flushing or dryness of the skin or mucous membranes, have not been observed with cyclopentolate in children or adults. Moreover, temperature, pulse, blood pressure, and respiration are generally not affected. Treatment of cyclopentolate toxicity is the same as that for atropine toxicity. Because toxic reactions occur more commonly with the 2% solution or with multiple instillations of the 1% solution, the smallest possible dose should be used. 

In the following accounts of drugs, the principal peripheral atropine-like effects of the drugs may be assumed differences from atropine are described. 

The unwanted peripheral effects of all atropine-like drugs include flushing of the skin, dryness of the mucous membranes with fever, tachycardia, reduced salivary secretion and dryness of the mouth, drying up of the gastrointestinal secretions and decreased gastric acidity, and reduced muscle tone in the gut and constipation. Bladder tone and frequency of micturition are reduced and acute urinary retention is a risk, especially in older men with prostatic hyperplasia. Nasal, bronchial, and lacrimal secretions are reduced. 

Exposure should be terminated as soon as possible either by removal of the patient or by fitting the patient with a gas mask if the atmosphere remains contaminated. Contaminated clothing should be removed immediately the skin and mouth should be washed with copious amounts of water. Gastric lavage should be conducted if necessary. Artificial respiration should be administered if required, and administration of oxygen may be necessary. If the convulsion persists, diazepam (5-10 mg intravenously) or sodium thiopental (2.5% intravenously) should be administered, and the patient should be treated for shock. Atropine should be administered in sufficiently large doses, but atropine is without any effect against peripheral neuromuscular activation and subsequent paralysis. Pralidoxime (1 or 2 g infused intravenously) should be administered for all the peripheral effects. 

CNS effects include nervousness, insomnia, and seizures in OD. Causes atropine-like peripheral effects and livedo reticularis. 

Causes atropine-like peripheral effects and livedo reticularis... 

Methylation of the nitrogen atom in atropine, on the other hand, increases intrinsic activity. Crum Brown and Fraser (26) were the first to study the pharmacology of atropine metho-salts they found that the peripheral atropine-like effects were retained in atropine methiodide and... 

Psilocybin, mescaline, and LSD have similar central (via serotonergic systems) and peripheral (sympathomimetic) effects. None of these hallucinogenic drugs have been shown to have teratogenic potential. Contrast this with the established potential for teratogenicity or other fetal toxicity with abuse of ethanol, amphetamines, and cocaine. Unlike most hallucinogens, phencyclidine acts as a positive reinforcer of self-administration in animals. Scopolamine is not a positive reinforcer but does exert atropine-like effects. The answer is (D). 

The drug exerts a potent anticholinergic effect and causes atropine-like effects peripherally. It has been observed that only at high dose levels it affords sympathetic blockade at the ganglionic sites. It can provide a long extendable action lasting upto almost 12 hours to contain the antispasmodic and... 

It is a quaternary ammonium antimuscarinic agent having marked and pronounced peripheral effects that are quite akin to those of atropine. It has been found that approximately 10-25% of the drug gets absorbed from the Gl-tract when administered orally. It penetrates the blood brain barrier (BBB) rather very poorly. It gets ultimately excreted in bile and urine. 

In some species, pharmacological effects other than muscle-relaxation may dominate. Thus, as already seen, the activity of S. erichsonii extracts appears to be due primarily to the presence of diaboline derivatives. Leaf extracts have analgesic properties, while stem-bark extracts have spasmolytic properties and augment the activity of the central nervous system (50). The bark alkaloids of S. glabra are reported to have central rather than peripheral effects (Table 1.4, footnote j). Sublethal doses of aqueous extracts from S. castelnaeana cause hypertension, tachycardia, and slight respiratory stimulation enhancement of the hypertension by atropine and its reduction by hexamethonium (mecamylamine) show that the extract has nicotinic activity. Evidently, the toxicity of the plant must be partly due to the tertiary bases it contains (314). 

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