Paralysis irreversible

Phosphonothioate Esters of Phenols. Phosphonates with a single P—C bond are highly toxic and persistent iasecticides but have not been used extensively because some compounds produce delayed neuropathy leading to irreversible paralysis ia higher animals, including humans. Such compounds specifically inhibit an enzyme, neurotoxic esterase, that is responsible for the growth and maintenance of long nerve axons (31,32). 

Administration of the aminoglycosides with the cephalosporins may increase the risks of nephrotoxicity. When the aminoglycosides are administered with loop diuretics there is an increased risk of ototoxicity (irreversible hearing loss). There is an increased risk of neuromuscular blockage (paralysis of the respiratory muscles) if the aminoglycosides are given shortly after general anesthetics (neuromuscular junction blockers). 

Once neurologic deficits appear, progression to irreversible paralysis may occur within hours to days. 

Bronchoconstriction and secretion, muscular weakness or paralysis, CNS depression, including respiratory centers Inhibition of acetylcholinesterase (reversible or irreversible)... 

Stypandra imbricata R. Br. (Liliaceae), is known in Western Australia as blind grass , since ingestion of the plant by goats and sheep often causes initial weakness, incoordination, and paralysis of hind limb, which may progress to prostration and death. Blindness, due to irreversible retinal degeneration and optic nerve atrophy, could persist following recovery from acute intoxication [297-300]. 

A few other organophosphates cause this effect, notably tri-orthocresyl phosphate, as described in Chapter 10. It seems to be due to the interaction between the organophosphate and a protein, which may be an enzyme, in the peripheral nerves. The protein seems to have a critical function and the binding to it is irreversible, causing the nerve to degenerate. The result is paralysis in the legs. The cause of this effect does not seem to be related to the interaction with acetylcholinesterase. The effect appears one or two weeks after exposure to the organophosphate. 

The primary action is to bind irreversibly to the presyn-aptic nerve terminals of peripheral cholinergic nerve fibers. Because the drug does not penetrate the blood-brain barrier, it has no effect on the central nervous system. The binding of botulinum to the nerve terminals blocks the release of acetylcholine at the neuromuscular junction, resulting in a temporary paralysis of the muscle. 

Unlike the nonspecific effects and uncommon occurrence of direct mortality observed in wildlife exposed to chlorinated hydrocarbon pesticides, several studies have documented direct mortality from exposure to OP and carbamate insecticides. The method by which the OPs and carbamate insecticides affect wildlife is quite different from the method by which the chlorinated hydrocarbon insecticides effect wildlife. The OPs and carbamates inhibit cholinesterase, primarily acetylcholinesterase (AChE), which is an enzyme that functions in the breakdown of the neurotransmitter acetylcholine. Acetylcholine functions in the transmission of nerve impulses. Therefore, when AChE is inhibited by an OP or carbamate insecticide, it can no longer breakdown acetylcholine and there is continued transmission of nerve impulses that eventually leads to nerve and muscle exhaustion. The respiratory muscles are a critical muscle group that is affected, often leading to respiratory paralysis as the immediate cause of death. A major difference in the mode of action between OPs and carbamates is that the inhibition of AChE by OPs is, from a biological standpoint, irreversible, while the inhibition from exposure to carbamates is reversible in a biologically relevant time frame. There... 

Hillman et al. [108,109] have suggested that hycanthone may act by binding irreversibly to the ACh receptor in schistosomes resulting in neuromuscular incoordination and paralysis of the digestive tract of the fluke. The worm later dies of starvation. 

Answer D. The symptoms of cholinergic excess seen in this child are indicative of exposure to insecticides such as the organophosphate parathion, which cause irreversible inhibition of acetylcholinesterase. Other symptoms may include CNS excitation and stimulation of the skeletal NMJ, ultimately leading to paralysis of respiratory musdes— DUMB-BELSS. In addition to symptomatic support, management of AChE inhibitor poisoning involves the use of atropine and 2-PAM. 

Most toxic of the steroidal alkaloids present in the skin of dart-poison frogs, Phyllobates. Used as an arrow poison in western Colombia. Opens Na+ channels and depolarizes nerve fibres irreversible depolarization leading to paralysis ventricular fibrillation, cardiac and respiratory failure and death. Effect abolished by tetrodotoxin. Only toxic via damaged skin or digestive tract. Mice lethal at 2-3 pg/kg SC and 0.1 pg/kg IV. 

Protein components of the venom of the banded krait (Bungarus multicinctus). Two major components a- and (3-bungarotoxins. ct-Bungarotoxin binds irreversibly to ACh receptor causing neuromuscular blockade and muscle paralysis similar to effects of curare, p-Bungarotoxin contains several components prevents ACh release at skeletal neuromuscular junction. Crude venom LD50 SC mouse, 0.16 mg/kg bw. 

The previous discussion of amino acid catabolic disorders indicates that catabolic processes are just as important for the proper functioning of cells and organisms as are anabolic processes. This is no less true for molecules that act as neurotransmitters. To maintain precise information transfer, neurotransmitters are usually quickly degraded or removed from the synaptic cleft. An extreme example of enzyme inhibition illustrates the importance of neurotransmitter degradation. Recall that acetylcholine is the neurotransmitter that initiates muscle contraction. Shortly afterwards, the action of acetylcholine is terminated by the enzyme acetylcholinesterase. (Acetylcholine must be destroyed rapidly so that muscle can relax before the next contraction.) Acetylcholinesterase is a serine esterase that hydrolyzes acetylcholine to acetate and choline. Serine esterases have catalytic mechanisms similar to those of the serine proteases (Section 6.4). Both types of enzymes are irreversibly inhibited by DFP (diisopropylfluorophosphate). Exposure to DFP causes muscle paralysis because acetylcholinesterase is irreversibly inhibited. With each nerve impulse, more acetylcholine molecules enter the neuromuscular synaptic cleft. The accumulating acetylcholine molecules repetitively bind to acetylcholine receptors. The overstimulated muscle cells soon become paralyzed (nonfunctional). Affected individuals suffocate because of paralyzed respiratory muscles. 

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