Peripheral nerves, effect

BW443C is a novel opioid used for the treatment of cough, but which does not enter the brain and so exerts its effects only on peripheral nerves. It has not been tested as an antitussive in humans due to its rapid metabolism in the lungs but the concqrt of a peripheral opioid is still possible. 

Herzberg U, Sagen J (2001) Peripheral nerve exposure to HIV viral envelope protein gpl20 induces neuropathic pain and spinal gliosis. J Neuroimmunol 116(l) 29-39 Herzmann C, Johnson MA et al (2005) Long-term effect of acetyl-L-carnitine for antiretroviral toxic neuropathy. HIV Clin Trials 6(6) 344-350... 

An intriguing area of research on opioids has been the accumulating evidence for plasticity in opioid controls. The degree of effectiveness of morphine analgesia is snbject to modulation by other transmitter systems in the spinal cord and by pathological changes induced by peripheral nerve injury. Thus in neuropathic states, pain after nerve injury, morphine analgesia can be reduced (but can still be effective) and tactics other than dose-escalation to circumvent this will be briefly discussed in Chapter 21. 

In addition to changes within the nerve, sympathetic afferents become able to activate sensory afferents via as yet poorly characterised a-adrenoceptors. These interactions between adjacent sensory and autonomic nerve axons and between ganglion cells result in excitation spreading between different nerve fibres. These peripheral ectopic impulses can cause spontaneous pain and prime the spinal cord to exhibit enhanced evoked responses to stimuli, which themselves have greater effects due to increased sensitivity of the peripheral nerves. 

Yagihashi, S., Kamijo, M., Yagjhashi, N. and Nagai, K. (1992). Effect of aminoguanidine on functional and structural abnormalities in peripheral nerve of STZ-induced diabetic rats. Diabetes 41, 47-52. 

Local anesthetics interact with peripheral nerve cell membranes and exert a pharmacological effect [34]. Potential oscillation was measured in the presence of 20 mM hydrochlorides of procaine, lidocaine, tetracaine, and dibucaine (structures shown in Fig. 16) [19]. Amplitude and the oscillatory and induction periods changed, the extent depending on the... 

Another very important site for drug delivery is the central nervous system (CNS). The blood-brain barrier presents a formidable barrier to the effective delivery of most agents to the brain. Interesting work is now advancing in such areas as direct convective delivery of macromolecules (and presumably in the future macromolecular drug carriers) to the spinal cord [238] and even to peripheral nerves [239]. For the interested reader, the delivery of therapeutic molecules into the CNS has also been recently comprehensively reviewed... 

NS (occup) Neurological No effect on peripheral nerve function 60-80 (levels measured) Ishida et al. 1996 Spivey et al. 1980... 

Chronic exposure to Pb has been shown to cause anaemia, neurotoxic effects, such as reduced cognitive performance and reduced peripheral nerve conduction velocity, and nephrotoxicity. Children are more sensitive to exposure to Pb than adults, especially during the first 2 years of life [41], For children, exposure to lead can cause growth retardation, affect the neuropsychological development and cause encephalopathy [39]. Adverse reproductive effects due to lead exposure have been observed for both men and women. Exposure of pregnant women to low concentrations of lead is associated with miscarriages and low birth weights [40],... 

Histamine also induces antinociceptive (i.e. pain-relieving) responses in animals after microinjection into several brain regions [73, 74]. H, and H2 mechanisms are significant and both neuronal and humoral mechanisms may be involved. Brain H2 receptors appear to mediate some forms of endogenous analgesic responses, especially those elicited by exposure to stressors [75]. Many of the modulatory actions of histamine discussed above appear to be activated as part of stress responses. For reasons that remain unclear, histamine releasers, such as thioperamide, show only mild, biphasic antinociceptive actions, even though histamine is a potent and effective analgesic substance. Outside the brain, both H and H3 receptors exist on certain types of sensory nerves and activation of these receptors promotes and inhibits, respectively, peripheral nerve transmission related to pain and/or inflammation [76,77]. 

Spinal disinhibition allows more nociceptive signal input. Following peripheral nerve injury there is a reduction in the GABAergic component of postsynaptic inhibitory currents caused by a degeneration of GABAergic interneurons [24] (Fig. 57-6). This loss of inhibition (disinhibition) results in an overall increase in the excitability of dorsal horn neurons. The degeneration of inhibitory interneurons is due to an excitotoxic effect of primary afferent ectopic activity on dorsal horn neurons [26]. 

Vijverberg, H.P.M., G.S.F. Ruigt, and J.V.D. Bercken. 1982. Structure-related effects of pyrethroid insecticides on the lateral-line sense organ and on peripheral nerves of the clawed frog, Xenopus laevis. Pestic. Biochem. Physiol. 18 315-324. 

A number of OPC are capable of rendering a delayed neurotoxic effect (DNE). This effect becomes apparent gradually, after a certain latent period (usually 14 to 21 days, sometimes 1 to 5 years after the acute poisoning survived) and is characterized clinically by the development of ataxia, muscular weakness, paresis and paralysis of the extremities. Morphologically, it is characterized by fiber demyelinization of spinal pathways and peripheral nerves. Till present time, near 40,000 cases have been described, when paresis and paralysis developed in human beings as a result of their exposure to OPC (TOCP, mipaphox, chloropyrophos, trichlorfon, etc.) [1],... 

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