Autonomic nervous system, toxicants

The results of the investigation of 58 adult persons who live on industry territory of North Crimea and 60 male teenagers at age 15 years and 84 children (2-14 years) in the Simferopol city showed that the children are more sensitive to the relatively low level of heavy metal concentrations than the adult (Evstafyeva et al., 2002). It is known that many toxic metals have neurotoxic effects (Arezzo et al., 1985). It was also shown that the effects of central and autonomous nervous systems of different... 

There is no significant correlation between the investigated toxic and essential metals content and the autonomous nervous system tone but some tendencies are shown for separate cardiovascular system parameters mode of cardio intervals and Cd, p = 0.09 VPR (vegetative parameters of rhythm by (Vein, 1991) and Pb, p = 0.06). 

The ICH S7A guidance states that "supplemental" studies are meant to evaluate potential adverse pharmacodynamic effects on organ systems functions that are not acutely essential for the maintenance of human life and not addressed by the "core battery" or repeated dose toxicity studies when there is a cause for concern.25 Examples of physiological functions that fall into that category include, but are not limited to, the renal/urinary, immune, GI, endocrine and autonomic nervous systems. This section focuses on the renal and GI systems based on their potential impact on the clinical development program. 

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). 

Lithium Mechanism of action uncertain suppresses inositol signaling and inhibits glycogen synthase kinase-3 (GSK-3), a multifunctional protein kinase No significant antagonistic actions on autonomic nervous system receptors or specific CNS receptors no sedative effects Bipolar affective disorder-prophylactic use can prevent mood swings between mania and depression Oral absorption, renal elimination half-life 20 h. narrow therapeutic window (monitor blood levels) Toxicity Tremor, edema, hypothyroidism, renal dysfunction, dysrhythmias pregnancy category D Interactions Clearance decreased by thiazides and some NSAIDs... 

Imipramine Mixed and variable blockade of NET and SERT Like SNRIs plus significant blockade of autonomic nervous system and histamine receptors Major depression not responsive to other drugs chronic pain disorders incontinence obsessive-compulsive disorder (clomipramine) Long half-lives CYP substrates active metabolites Toxicity Anticholinergic, G.-blocking effects, sedation, weight gain, arrhythmias, and seizures in overdose Interactions CYP inducers and inhibitors... 

The main dose-limiting toxicity is neurotoxicity, usually expressed as a peripheral sensory neuropathy, although autonomic nervous system dysfunction with orthostatic hypotension, urinary retention, paralytic ileus, or constipation, cranial nerve palsies, ataxia, seizures, and coma have been observed. While myelosuppression occurs, it is generally milder and much less significant than with vinblastine. The other potential adverse effect that can develop is the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). 

Acetylcholine is a neurotransmitter that functions in conveying nerve impulses across synaptic clefts within the central and autonomic nervous systems and at junctures of nerves and muscles. Following transmission of an impulse across the synapse by the release of acetylcholine, acetylcholinesterase is released into the synaptic cleft. This enzyme hydrolyzes acetylcholine to choline and acetate and transmission of the nerve impulse is terminated. The inhibition of acetylcholineasterase results in prolonged, uncoordinated nerve or muscle stimulation. Organophosphorus and carbamate pesticides (Chapter 5) along with some nerve gases (i.e., sarin) elicit toxicity via this mechanism. 

Although the Rauwolfia alkaloids show a low degree of acute toxicity, their continued use may be accompanied by serious side effects. One of the most troublesome symptoms observed in the therapeutic use of Rauwolfia alkaloids is nasal congestion and stuffiness, which may be so severe as to necessitate discontinuing of therapy. Increased motility of the bowel, diarrhea, and increased gastric secretion resulting from its action on the autonomic nervous system are frequently observed. Skin eruptions, epistaxis, and peptic ulceration are rare complications. 

Causes neurotoxicity, autonomic and central nervous system toxicity, alopecia, mild leukopenia, mild anemia, and mild thrombocytopenia, as well as nausea, vomiting, diarrhea, constipation, stomatitis, and oral ulceration.3... 

This classic in the field of pharmacology provides detailed information on anatomy and functions of the autonomic nervous system. Although primarily concerned with drugs and how they act upon the body, there are also excellent sections on the toxicity of gases and vapors and heavy metals. Goodman and Gilman thoroughly evaluate many of the more widely used compounds utilized by the pharmaceutical industry. 

Due to its effect on microtubule assembly, this drug has the ability to arrest mitotic cells in metaphase. Particularly affected are rapidly dividing cells, such as those in skin, hair and bone marrow. In addition, the activity of secretory cells is diminished, as movement of secretory substances out of a secretory cell is inhibited. This could potentially affect all systems in the body (e.g., endocrine systems and systems heavily regulated by the autonomic nervous system). In short, this drug is extremely toxic if administered improperly, and could result in fatality. 

A few central nervous system stimulants exhibit predominant central stimulant action, e.g., strychnine, nikethamide, leptazol, picrotoxine, etc. others possess multiple side-effects,. e.g., ephedrine and atropine act on the autonomic nervous system and finally a number of drugs do exert temporary stimulation of CNS in toxic doses, e.g., local anaesthetics, santonin, salicylates. In usual praetiee, the eentral nervous system stimulants find their use in emergencies for prompt and short-term exeitation of CNS, because a prolonged stimulation may be followed by depression. 

I. Mechanism of toxicity. The scorpion grasps its prey with its anterior pincers, arches its pseudoabdomen, and stabs with the stinger. Stings also result from stepping on the stinger. The venom of C exilicauda contains numerous digestive enzymes (eg, hyaluronidase and phospholipase) and several neurotoxins. Alteration in sodium channel flow results in excessive stimulation at neuromuscular junctions and the autonomic nervous system. 

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