Depolarizing paralyzants

However, this specific category of drugs may be further sub-divided into two heads, namely (/) Competitive (or stabilizing) paralyzants, and ii) Depolarizing paralyzants. 

C. Atropine will not directly paralyze the respiratory muscles. However, it can prevent the detection of early signs of an overdose of neostigmine, which can quickly progress to a depolarizing block of skeletal muscle and paralysis of the respiratory muscles. Dry mouth, ocular disturbances, and tachycardia are common side effects of atropine given alone, but these effects are less likely to occur with competition between atropine and the increase in the synaptic ACh produced by inhibition of AChE by neostigmine. 

Low doses of nicotine stimulate respiration through activation of chemoreceptors in the aortic arch and carotid bodies, while high doses directly stimulate the respiratory centers. In toxic doses, nicotine depresses respiration by inhibiting the respiratory centers in the brainstem and by a complex action at the receptors at the neuromuscular junction of the respiratory muscles. At these neuromuscular receptors, nicotine appears to occupy the receptors, and the end plate is depolarized. After this, the muscle accommodates and relaxes. These central and peripheral effects paralyze the respiratory muscles. 

Fenvalerate has low toxicity in mammals due to its rapid metabolic breakdown. It acts directly on nerve axons by prolonging sodium channel opening in cell membranes. Insects exposed to fenvalerate are quickly paralyzed exposure causes quick insect knockdown. In small animals, type II pyrethroids cause salivation, chewing, burrowing, choreoathetosis, and seizures. They also cause lower action potential amplitude, marked membrane depolarization, and eventual total neural activity blockade. Fenvalerate is likely to act both on peripheral and central nervous system. It is also a potent inhibitor of calcineurin (protein phosphatase 2B). 

Certain pyrethroids such as pyrethrins, allethrin and tetramethrin stimulate and then paralyze insects. Various nerves were stimulated to produce repetitive discharges either spontaneously or in response to a single stimulus (1-J>). The depolarizing after-potential was elevated by the pyrethroids and reached the threshold for repetitive after-discharges ( ,Z). At high concentrations of pyrethroids the membrane was gradually depolarized and impulse conduction was eventually blocked (f>,Z) Repetitive responses in the postsynaptic element in the pyrethroid-poisoned preparations were induced at the presynaptic nerve terminals (8.-1Q). Thus the nerve membrane appears to be the major target site of pyrethroids. 

Pyrantel, as pyrvinium, is available as the extremely insoluble and nonabsorbed pamoic acid salt one oral dose cures pinworm and Ascaris infections. It is curious that whipworm and threadworm infections do not respond. The drug acts as a depolarizing neuromuscular blocking agent (Chapter 8) on worms, which are then paralyzed. In Ascaris muscle strips it is 100 times more active than acetylcholine. 

These are also termed as depolarizing neuromuscular blocking drugs. They are nicotinic agonists that essentially interact (just like ACH) with the post s>iiaptic nicotinic receptors to cause a depolarization of the membrane at the motor end-plate specifically. In reality, their temporary stay at the end-plate is a little longer (unlike ACH) and, therefore, the post synaptic membrane virtually remain depolarized. Because, the muscle membrane as well as the resulting contraction can only be excited by a fresh lease of depolarization, the muscle remains paralyzed ultimately. In other words, the virtual initiation for the conducted muscle impulse is due to the short-stayed fall in end-plate membrane potential, and not caused due to the ensued depolarization. 

Not every presynaptic toxin is identical in relation to the release of acetylcholine from the presynaptic site. With P-btx, there is an initial burst of acetylcholine, but eventually the release is stopped. Even though toxins may behave like P-btx, the length of time for acetylcholine release is different for each toxin. Some presynaptic toxins do not release acetylcholine from the beginning and simply stop the release. In such an event, the depolarization wave never reaches the muscle, and the muscle is paralyzed. 

---