Neuromuscular

C14H30CI2N2O4. White powder prepared from dimethylaminoethanol and succinyl chloride, followed by methylation. Neuromuscular blocking agent used to relax skeletal muscles during certain types of surgical operation. 

Mode of Action. All of the insecticidal carbamates are cholinergic, and poisoned insects and mammals exhibit violent convulsions and other neuromuscular disturbances. The insecticides are strong carbamylating inhibitors of acetylcholinesterase and may also have a direct action on the acetylcholine receptors because of their pronounced stmctural resemblance to acetylcholine. The overall mechanism for carbamate interaction with acetylcholinesterase is analogous to the normal three-step hydrolysis of acetylcholine however, is much slower than with the acetylated enzyme. 

The alimentary symptoms may be overshadowed by neuromuscular dysfunction, accompanied by signs of motor weakness that may progress to paralysis of the exterior muscles or the wrist (wrist drop), and less often, of the ankles (foot drop). Encephalopathy, the most serious result of lead poisoning, frequendy occurs in children as a result of pica, ie, ingestion of inorganic lead compounds in paint chips this rarely occurs in adults. Nephropathy has also been associated with chronic lead poisoning (147). The toxic effects of lead may be most pronounced on the developing fetus. Consequendy, women must be particulady cautious of lead exposure (148). The U.S. Center for Disease Control recommends a blood level of less than 10 p.m per 100 mL for children. 

The calcium ion, necessary for blood-clot formation, stimulates release of bloodclotting factors from platelets (see Blood, coagulants and anticoagulants) (25). Neuromuscular excitabihty also depends on the relative concentrations of Na", Ca ", Mg ", and (26). Upon a decrease in... 

OtherMa.gnesium Disorders. Neuromuscular irritabHity, convulsions, muscle tremors, mental changes such as confusion, disorientation, and haHucinations, heart disease, and kidney stones have aH been attributed to magnesium deficiency. Excess Mg " can lead to intoxication exemplified by drowsiness, stupor, and eventuaHy coma. 

Two specialties of the nervous system are speed and localization, accompHshed using highly developed electrical signaling and close cellular apposition. At specialized points of communication, such as the synapse and the neuromuscular junction, the cells are separated by a nanometer or less. 

Autoantibodies are directed against nicotinic acetylcholine receptors in myasthenia gravis, resulting in receptor loss, skeletal muscle paralysis, and dysfunction (100). In addition, antibodies directed against voltage-gated Ca " channels produce similar neuromuscular dysfunction of Lambert-Eaton... 

Isoflurane is a respiratory depressant (71). At concentrations which are associated with surgical levels of anesthesia, there is Htde or no depression of myocardial function. In experimental animals, isoflurane is the safest of the oral clinical agents (72). Cardiac output is maintained despite a decrease in stroke volume. This is usually because of an increase in heart rate. The decrease in blood pressure can be used to produce "deHberate hypotension" necessary for some intracranial procedures (73). This agent produces less sensitization of the human heart to epinephrine relative to the other inhaled anesthetics. Isoflurane potentiates the action of neuromuscular blockers and when used alone can produce sufficient muscle relaxation (74). Of all the inhaled agents currently in use, isoflurane is metabolized to the least extent (75). Unlike halothane, isoflurane does not appear to produce Hver injury and unlike methoxyflurane, isoflurane is not associated with renal toxicity. 

R = / -C H ), in low doses, exhibits the former behavior and is used primarily as an extradural agent in obstetrics. The lowest effective extradural concentration of etidocaine (21, X = CH, R = R = 2H, R = / -C H ), however, shows both adequate sensory and profound motor blockade so that it is useful in surgical situations where maximum neuromuscular blockade is necessary. In an isolated nerve preparation, bupivacaine blocks unmyelinated C fibers which are mainly responsible for pain perception at a much greater extent than the myelinated A fibers which carry motor impulses. It is postulated that absorption of bupivacaine by the vasculature at the site of injection, combined with the slow diffusion of this agent, results in an insufficient amount of the drug penetrating the large A fibers to cause motor conduction blockade. Clinically, motor block can be observed in some procedures. 

The principal arninoglycoside toxicides are neuromuscular paralysis, ototoxicity, and nephrotoxicity. Neuromuscular paralysis is a relatively rare complication resulting from high aminoglycoside concentrations at the neuromuscular junctions following, for example, rapid bolus intravenous injection or peritoneal instillation, rather than the normal intravenous infusion. The mechanism apparentiy involves an inhibition of both the presynaptic release of acetylcholine and the acetylcholine postsynaptic receptors (51). 

The human body has more than 600 muscles. The body s movement is performed by muscle contractions, which are stimulated by the nervous system. This system links muscle tissue to the spinal cord and brain. The network of nerve cells which carries the brain s signals directs the flow of muscular energy. Most muscular activity occurs beyond the range of the conscious mind. The body, working through the neuromuscular network, manages... 

Enzyme Inhibition. Some materials produce toxic effects by inhibition of biologically vital enzyme systems, leading to an impairment of normal biochemical pathways. The toxic organophosphates, for example, inhibit the cholinesterase group of enzymes. An important factor in thek acute toxicity is the inhibition of acetylocholinesterase at neuromuscular junctions, resulting in an accumulation of the neurotransmitter material acetylcholine and causing muscle paralysis (29) (see Neuroregulators). 

The symptoms of vitamin E deficiency in animals are numerous and vary from species to species (13). Although the deficiency of the vitamin can affect different tissue types such as reproductive, gastrointestinal, vascular, neural, hepatic, and optic in a variety of species such as pigs, rats, mice, dogs, cats, chickens, turkeys, monkeys, and sheep, it is generally found that necrotizing myopathy is relatively common to most species. In humans, vitamin E deficiency can result from poor fat absorption in adults and children. Infants, especially those with low birth weights, typically have a vitamin E deficiency which can easily be corrected by supplements. This deficiency can lead to symptoms such as hemolytic anemia, reduction in red blood cell lifetimes, retinopathy, and neuromuscular disorders. 

Bithionol interferes with the neuromuscular physiology of helminths, impairs egg formation, and may cause defects in the protective cuticle covering the worm. At the biochemical level, the oxidative phosphorylation of the worm is inhibited. 

Acetylcholine is a neurotransmitter at the neuromuscular junction in autonomic ganglia and at postgangHonic parasympathetic nerve endings (see Neuroregulators). In the CNS, the motor-neuron collaterals to the Renshaw cells are cholinergic (43). In the rat brain, acetylcholine occurs in high concentrations in the interpeduncular and caudate nuclei (44). The LD q (subcutaneous) of the chloride in rats is 250 mg/kg. 

Acetylcholine serves as a neurotransmitter. Removal of acetylcholine within the time limits of the synaptic transmission is accomplished by acetylcholinesterase (AChE). The time required for hydrolysis of acetylcholine at the neuromuscular junction is less than a millisecond (turnover time is 150 ps) such that one molecule of AChE can hydrolyze 6 105 acetylcholine molecules per minute. The Km of AChE for acetylcholine is approximately 50-100 pM. AChE is one of the most efficient enzymes known. It works at a rate close to catalytic perfection where substrate diffusion becomes rate limiting. AChE is expressed in cholinergic neurons and muscle cells where it is found attached to the outer surface of the cell membrane. 

Cholinesterases (ChEs), polymorphic carboxyles-terases of broad substrate specificity, terminate neurotransmission at cholinergic synapses and neuromuscular junctions (NMJs). Being sensitive to inhibition by organophosphate (OP) poisons, ChEs belong to the serine hydrolases (B type). ChEs share 65% amino acid sequence homology and have similar molecular forms and active centre structures [1]. Substrate and inhibitor specificities classify ChEs into two subtypes ... 

Curare is a generic term for various South American arrow poisons. Curare has been used for centuries by the Indians along the Amazon and Orinoco rivers for immobilizing and paralyzing wild animals used for food. Preparations of curare are derived from Strychnos species, which contain quaternary neuromuscular alkaloids like tubocurarine. Tubocurarine is a potent antagonist at the nicotinic acetylcholine receptor. 

Neuromuscular junction (NMJ) is the synapse or junction of the axon terminal of motoneurons with the highly excitable region of the muscle fibre s plasma membrane. Neuronal signals pass through the NMJ via the neurotransmitter ACh. Consequent initiation of action potentials across the muscle s cell surface ultimately causes the muscle contraction. 

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