Nervous system toxicity reflex action

While the dose-limiting toxicity for vinblastine usually is leukopenia, that for vincristine is most commonly neurotoxicity (58). Prominent manifestations of neurotoxicity are loss of the Achilles tendon reflex, paresthesias, loss of muscle strength (e.g., in the foot and wrist), and ataxia. Constipation and abdominal pain may occur and are thought to result, at least in part, from actions on the autonomic nervous system. Leukopenia and stomatitis are possible effects of vincristine treatment, but they occur relatively infrequently. Alopecia occurs with vincristine at a frequency comparable to that observed with vinblastine, and vincristine also is a potent tissue irritant. Vincristine may produce a syndrome of inappropriate secretion of antidiuretic hormone, and some manifestations of neurotoxicity, such as seizures, have been considered to be due to electrolyte disturbances associated with the relative excess of the antidiuretic hormone (58). 

Based on their studies of animals, scientists believe that, in general, when toxic vapors circulate to the brain, they depress the central nervous system. The action is similar to that of alcohol, sedatives, and anesthetics. Thus, many of the immediate physical changes inhalant users experience are similar to those caused by alcohol or anesthetics, including relaxation, slurred speech, slowed reflexes, lack of coordination, sleepiness, dizziness, headache, nausea, and vomiting. Abusers might also sneeze, cough, and drool. 

The action of toxic doses of atropine is observed on the central nervous system. There is a functional alteration of the brain as well as lower regions of the nervous system. There is neither an increase nor decrease of the reflexes except in the last stages corresponding to the coma, anesthesia, and profound depression of the brain. The bulbar respiratory center is stimulated, the respiration being increased in rate and amplitude during the stage of central stimulation. Cushny (120) stated that it is not known whether there is a direct action on the center or an indirect effect due to the products of metabolism such as carbon dioxide. But even small doses which cause no general excitation provoke a respiratory stimulation which makes it probable that there exists a direct action on the bulbar respiratory center (119). 

I. Mechanism of toxicity. PNU is believed to antagonize the actions of nicotinamide and, in a manner similar to that of alloxan and streptozocin, injure pancreatic beta cells. The mechanisms of autonomic neuropathy and central nervous system effects are unknown. Adrenergic neurons acting on blood vessels but not the heart are affected. As a result, orthostatic hypotension associated with an intact reflex tachycardia is the usual picture. 

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