Sodium impulse

Mode of Action. DDT and its analogues specifically affect the peripheral sense organs of insects and produce violent trains of afferent impulses that result in hyperactivity, convulsions, and paralysis. Death results from metaboHc exhaustion and the production of an endogenous neurotoxin. The very high lipophilic nature of these compounds faciUtates absorption through the insect cuticle and penetration to the nerve tissue. The specific site of action is thought to be the sodium channels of the axon, through inhibition of Ca " ATPase. 

Local anesthetics produce anesthesia by blocking nerve impulse conduction in sensory, as well as motor nerve, fibers. Nerve impulses are initiated by membrane depolarization, effected by the opening of a sodium ion channel and an influx of sodium ions. Local anesthetics act by inhibiting the channel s opening they bind to a receptor located in the channel s interior. The degree of blockage on an isolated nerve depends not only on the amount of dmg, but also on the rate of nerve stimulation (153—156). 

Muscle activity is accompanied by cellular pumping of sodium ions. The energy requirements of the sodium pump have been studied on an individual cardiac muscle mounted inside a tiny differential calorimeter and stimulated by electrical impulses. The heat evolved was different in the presence and absence of a known inhibitor of the sodium pump. 

Table 8 5 shows that each of the four common s-block ions is abundant not only in seawater but also in body fluids, where these ions play essential biochemical roles. Sodium is the most abundant cation in fluids that are outside of cells, and proper functioning of body cells requires that sodium concentrations be maintained within a narrow range. One of the main functions of the kidneys is to control the excretion of sodium. Whereas sodium cations are abundant in the fluids outside of cells, potassium cations are the most abundant ions in the fluids inside cells. The difference in ion concentration across cell walls is responsible for the generation of nerve impulses that drive muscle contraction. If the difference in potassium ion concentration across cell walls deteriorates, muscular activity, including the regular muscle contractions of the heart, can be seriously disrupted. 

Fig. 4.1 Hypothetical model of pathogenesis of pain in DSP. (1) Injury of peripheral nerve fibers due to multifocal inflammation and secreted macrophage activation products results in abnormal spontaneous activity of neighboring uninjured nociceptive fibers ( peripheral sensitization ). (2) Furthermore, the aberrant inflammatory response in DRG leads to alterations in neuronal sodium and calcium channel expression and ectopic impulse generation. (3) This results in central remodeling within the dorsal horn due to A-fiber sprouting and synaptic formation with pain fibers in lamina 11, and maintenance of neuropathic pain ( central sensitization ). Reproduced with permission from (Keswani et al. 2002)...

The mechanism of action of these anesthetics involves the blockade of sodium channels in the membrane of the second-order sensory neuron. The binding site for these anesthetics is on a subunit of the sodium channel located near the internal surface of the cell membrane. Therefore, the agent must enter the neuron in order to block the sodium channel effectively. Without the influx of sodium, neurons cannot depolarize and generate an action potential, so the second-order sensory neuron cannot be stimulated by impulses elicited by pain receptors associated with the first-order sensory neuron. In other words, the pain signal is effectively interrupted at the level of the spinal cord and does not travel any higher in the CNS. In this way, the brain does not perceive pain. 

Potassium, like sodium, is involved in ionic equilibria, and the opening and closing of sodium and potassium ion channels create the electrochemical gradients across cell membranes that transmit nerve impulses and other information and regulate cellular function. 

ATP is used not only to power muscle contraction, but also to re-establish the resting state of the cell. At the end of the contraction cycle, calcium must be transported back into the sarcoplasmic reticulum, a process which is ATP driven by an active pump mechanism. Additionally, an active sodium-potassium ATPase pump is required to reset the membrane potential by extruding sodium from the sarcoplasm after each wave of depolarization. When cytoplasmic Ca2- falls, tropomyosin takes up its original position on the actin and prevents myosin binding and the muscle relaxes. Once back in the sarcoplasmic reticulum, calcium binds with a protein called calsequestrin, where it remains until the muscle is again stimulated by a neural impulse leading to calcium release into the cytosol and the cycle repeats. 

Of the greatest importance is the role of these ions in the conduction of signals along neurons. The flow of sodium and potassinm ions across the neuronal membrane is the basis for transmission of neural impulses (chapter 21). 

Mood Stabilizers. Lithium (Eskalith, Lithobid), valproic acid (Depakene), sodium valproate (Depakote), and carbamazepine (Tegretol) are most often used by psychiatrists to treat the bipolar disorders. These so-called mood stabilizers are also used to treat impulsivity and agitation in a variety of psychiatric disorders including dementia, certain personality disorders, and the disruptive behavior disorders of childhood. 

Though the oxidation potentials of potassium nitrate (KN KNO3) and sodium nitrate (SN NaN03) are high, both metal nitrates generate combustion products of high Mg, Thus, the specific impulse becomes low when KN or SN is used in a rocket propellant KN and SN are used as major ingredients of explosives and in pyrotechnics. KN is a weU-known material as a major component of black powder. 

The mechanism of action of hydantoins is not yet conclusive. According to one hypothesis, hydantoins prevent high-frequency activation of the epileptogenic center and also facilitate secretion of sodium ions, which reduces excitation of neurons and prevents then-activation upon contact with impulses from the epileptogenic center. 

This group consists of j3-adrenergic receptor blockers, the antiarrhythmic activity of which is associated with inhibition of adrenergic innervation action of the circulatory adrenaline on the heart. Because all 8-adrenoblockers reduce stimulatory sympathetic nerve impulses of catecholamines on the heart, reduce transmembrane sodium ion transport, and reduce the speed of conduction of excitation, sinoatrial node and contractibility of the myocardium is reduced, and automatism of sinus nodes is suppressed and atrial and ventricular tachyarrhythmia is inhibited. 

Pharmacology Potassium participates in a number of essential physiological processes, such as maintenance of intracellular tonicity and a proper relationship with sodium across cell membranes, cellular metabolism, transmission of nerve impulses, contraction of cardiac, skeletal, and smooth muscle, acid-base balance, and maintenance of normal renal function. Normal potassium serum levels range from 3.5 to 5 mEq/L. 

Recent drug development studies have centered on the capacity of known antiepileptic drugs (AEDs) to interact with ion channels, and it is now established that several agents appear to be exerting their effects primarily by inhibiting ion channels. Modulation of neuronal sodium channels decreases cellular excitability and the propagation of nerve impulses. Inhibition of sodium channels appears to be a major component of the mechanism of action of several anticonvulsant drugs. 

Mectianism of Action An anticonvulsant that blocks sodium channels, resulting in stabilization of hyperexcited neural membranes, inhibition of repef if ive neuronal firing, and diminishing synapfic impulses. Therapeutic Effect Prevenfs seizures. Pharmacokinetics Complefely absorbed from GI tract and extensively metabolized in the liver to active metabolite. Protein binding 40%. Primarily excreted in urine. Half-life 2 hr metabolite, 6-10 hr. 

Mechanism of Action A surface or local anesthetic which is not chemically related to the "caine" types of local anesthetics. Decreases the neuronal membrane permeability to sodium ions, blocking both initiation and conduction of nerve impulses, therefore inhibiting depolarization of the neuron. Therapeutic Effect Temporarily relieves pain and itching associated with anogenital pruritus or irritation. 

It is a keto analog of carbamazepine. It produces blockade of voltage sensitive sodium channels, leading to stabilisation of hyperexcited neural membranes, inhibition of repetitive neuronal firing and diminution of propagation of synaptic impulses. 

Kavoussi RJ, Coccaro EF. Divalproex sodium for impulsive aggressive behavior in patients with personality disorder. J Clin Psychiatry 1998 59 676-680. 

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