Nerve conduction block

Clinical use Because of its long duration of action, bupivacaine is indicated for long surgical anesthesia where a considerable amount of postoperative pain is expected such as dental and oral surgeries. Infiltration using a 0.25 % solution of bupivacaine produces sensory anesthesia with an onset of 2 to 5 min and a duration of 2 to 4 h or greater (Tetzlaff, 2000). A nerve conduction block with a duration of between 4 to 8 h and occasionally up to 24 h is achieved with injection of 0.5 to 0.75 %... 

Clinical use The indications for levobupivacaine include wound infiltration (0.25 % solution), nerve conduction block (0.25 - 0.5 %), spinal analgesia (0.5 %) and epidural anesthesia (0.5 to 0.75 %). For labour analgesia, lower concentrations of levobupivacaine are recommended when administered as epidural injection (0.125 to 0.25 % up to 25 mg) or infusion (0.25 %). The maximum dose for ilioinguinal or iliohypogastric block in children is 1.25 mg/kg/side (0.25 to 0.5 % solutions). For postoperative pain management, levobupivacaine can be applied epidurally in combination with the opioids fentanyl or morphine or with the a2-agonist clonidine. 

Local application of concentrated sodium channel blockers can provide complete pain relief through nerve conduction block (local anesthetics). This approach to pain relief is limited to a few applications involving short-term treatment of acute pain, since sodium channels are also vital to conduction in the heart, CNS, skeletal muscle, and non-nociceptive sensory neurons. However, some types of chronic pain signaling appear to be sensitive to sodium channel blockers at concentrations that do not cause conduction block. In particular, neuropathic pain, defined as chronic pain resulting from a primary lesion or dysfunction of the peripheral nervous system by the International Association for the Study of Pain (IASP) [58], is thought to originate from aberrant signaling in the nervous system and can be ameliorated by sodium channel blockers. 

J. J. Kendig and E. N. Cohen, Pressure Antagonism to Nerve Conduction Block by Anesthetic Agents, Anesthesiology 41, 6-10 (1977). 

Toman, J.E., Woodbury, J.W, Woodbury, L.A., 1947. Nerve conduction block by disopropylfluorophosphate (DFP) and eserine without change in demarcation potential. Fed. Proc. 6 (1 Pt 2), 216. 

Thousands of compounds have been tested which exhibit some kind of nerve conduction blocking activity. Indeed, many compounds which are known for other types of pharmacological activity such as antihistamines, compounds with activity at adrenergic receptors and tranquillisers block nerves to some extent. Hie wide range of compounds which have been used over the years has been narrowed down to a few effective agents. The earlier used esters such as procaine have been largely superseded by amides. The utility of these agents has been refined by development of advanced procedures for their administration, such as the use of epidural and spinal injection. 

A conduction block is a type of regional anesthesia produced by injection of a local anesthetic drug into or near a nerve trunk. Examples of a conduction block include an epidural block (injection of a local anesthetic into the space surrounding the dura of the spinal cord) a trails sacral (caudal) block (injection of a local anesthetic into the epidural space at the level of the sacrococcygeal notch) and brachial plexus block (injection of a local anesdietic into the brachial plexus). Epidural, especially, and trailssacral blocks are often used in obstetrics. A brachial plexus block may be used for surgery of the arm or hand. 

General anesthetics are usually small solutes with relatively simple molecular structure. As overviewed before, Meyer and Overton have proposed that the potency of general anesthetics correlates with their solubility in organic solvents (the Meyer-Overton theory) almost a century ago. On the other hand, local anesthetics widely used are positively charged amphiphiles in solution and reversibly block the nerve conduction. We expect that the partition of both general and local anesthetics into lipid bilayer membranes plays a key role in controlling the anesthetic potency. Bilayer interfaces are crucial for the delivery of the anesthetics. 

In a study where both peripheral and central nervous system effects were measured in rats co-exposed to u-hexane and toluene (Pryor and Rebert 1992), toluene exposure at 1,400 ppm for 14 hours a day for 9 weeks prevented the peripheral neurotoxicity (decreased grip strength and nerve conduction velocities) caused by exposure to 4,000 ppm 77-hcxanc alone. There was no reciprocal action of 77-hexane on the motor syndrome (shortened and widened gait and widened landing foot splay) and hearing loss caused by toluene. Brainstem auditory response amplitudes were decreased by 77-hcxanc, co-exposure to toluene did not block this effect. 

Local anesthesia involves the blockade of nerve conduction in order to stop sensation. Because local anesthetics act on all nerve fibers they may also temporarily create motor paralysis. The usefulness of local anesthetics is their ability to completely block axonal transduction, which is reversible and without any apparent lasting effects. 

Substances that block the serine residue in the active center of acetylcholinesterase [2j—e.g., the neurotoxin E605 and other organophosphates—prevent ACh degradation and thus cause prolonged stimulation of the postsynaptic cell. This impairs nerve conduction and muscle contraction. Curare, a paralyzing arrow-poison used by South American Indians, competitively inhibits binding of ACh to its receptor. 

Procaine and the other local anaesthetic drugs prevent the generation and the conduction of the nerve impulses. Their main site of action is the cell membrane, since conduction block can be demonstrated in giant axons from which the axoplasm has been removed [25]. 

Raising the concentration of Ca in the medium pathing, a nerve may relieve conduction block produced by local anesthetics. Relief occurs because Ca alters the surface potential on the membrane, and hence the transmembrane electrical field. This, in turn, reduces the degree of inactivation of the Na channels and the affinity of the latter for the local anaesthetic molecule [25, 27]. 

Mechanism of Action A local anesthetic that blocks nerve conduction in the autonomic, sensory, and motor nerve fibers. Competes with calcium ions for membrane... 

Is directly related chemically to opioid analgesics Is metabolized by the microsomal metabolizing system Blocks nerve conduction effectively Blocks norepinephrine receptors directly... 

Local anaesthetics slow the rate of rise of the action potential and reduce its height. They also slow impulse conduction and lengthen the refractory period (Figure 5.7). They may elevate the threshold potential but do not affect the RMP. As more and more Na+ channels are blocked by local anaesthetic the value of each successive spike potential gradually decreases to the point where it fails to achieve the value of the threshold potential (Figure 5.7). At this point nerve conduction ceases. 

Action potential propagation Local anesthetics, tetrodotoxin,1 saxitoxin2 Nerve axons Block sodium channels block conduction... 

Local anesthetics preferentially block small fibers because the distance over which such fibers can passively propagate an electrical impulse is shorter. During the onset of local anesthesia, when short sections of a nerve are blocked, the small-diameter fibers are the first to fail to conduct electrical impulses. For myelinated nerves, at least two and preferably three successive nodes of Ranvier must be blocked by the local anesthetic to halt impulse propagation. Therefore, myelinated nerves tend to become blocked before unmyelinated nerves of the same diameter. For this reason, the preganglionic fibers are blocked before the smaller unmyelinated C fibers involved in pain transmission. 

In a concentration range higher than those exhibiting repetitive responses, this class of compounds blocks the nerve conduction. We have also determined neuro-blocking activity in terms of the minimum effective concentration (MBC in M) in the saline solution 76). In contrast to effect on excitatory activity, substituent effects... 

LAs block nerve conduction when applied locally to nervous tissue by a voltage- and frequency-dependent inhibition of sodium currents (see Voltage-gated Sodium Channels Structure and Function1). Due to this mechanism, they preferentially block hyperexcitable cells and interfere comparatively less with normal physiological sensory and motor function. However, they are not selective for pain-relevant sodium channel subtypes so that they have a relatively high risk of adverse effects associated with the central nervous and cardiovascular systems when administered systemically. Known LAs are not active when administered orally. 

When applied locally to nerve tissue in appropriate concentrations, local anesthetics (Figure 23.2) reversibly block the action potentials responsible for nerve conduction. They act on any part of the nervous system and on every type of nerve fiber. Thus, a local anesthetic in contact with a nerve trank can cause both sensory and motor paralysis in the area innervated. The necessary practical advantage of the local anesthetics is that their action is reversible at clinically relevant concentra-... 

Cocaine, which blocks the uptake of catecholamines, produces dose-dependent effects, initially causing euphoria, vasoconstriction, and tachycardia, and in toxic doses, convulsions, myocardial depression, ventricular fibrillation, medullary depression, and death. Cocaine is able to block nerve conduction and currently is used only for topical anesthesia. 

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