Peripheral sensory effects

Eye. Adverse effects may be produced by splashes of Hquids or soflds, and by materials dispersed in the atmosphere. The eye is particularly sensitive to peripheral sensory irritants in the atmosphere. Toxic effects that may be induced include transient acute inflammation, persistent damage, and, occasionally, sensitivity reactions. ToxicologicaHy significant amounts of material may be absorbed by the periocular blood vessels in cases of splash contamination of the eye with materials of high acute toxicity (58). 

Hi-receptors in the adrenal medulla stimulates the release of the two catecholamines noradrenaline and adrenaline as well as enkephalins. In the heart, histamine produces negative inotropic effects via Hr receptor stimulation, but these are normally masked by the positive effects of H2-receptor stimulation on heart rate and force of contraction. Histamine Hi-receptors are widely distributed in human brain and highest densities are found in neocortex, hippocampus, nucleus accumbens, thalamus and posterior hypothalamus where they predominantly excite neuronal activity. Histamine Hrreceptor stimulation can also activate peripheral sensory nerve endings leading to itching and a surrounding vasodilatation ( flare ) due to an axonal reflex and the consequent release of peptide neurotransmitters from collateral nerve endings. 

Mechanism of Action An analgesic that depletes and prevents reaccumulation of the chemomediator of pain impulses (substance P) from peripheral sensory neurons to CNS. Therapeutic Effect Relieves pain. 

CR is a potent peripheral sensory Irritant of low toxicity by the usual routes of administration.3 It appears safer than CS, which replaced CN and DM in turn as riot-control agent because of greater effectiveness and lower toxicity. Table 4-20 shows comparative toxi-citles of these compounds in several species.2... 

Opioid agonists produce analgesia by binding to specific G protein-coupled receptors that are located in brain and spinal cord regions involved in the transmission and modulation of pain (Figure 31-1). Some effects may be mediated by opioid receptors on peripheral sensory nerve endings. 

The main dose-limiting toxicity is neurotoxicity, usually expressed as a peripheral sensory neuropathy, although autonomic nervous system dysfunction with orthostatic hypotension, urinary retention, paralytic ileus, or constipation, cranial nerve palsies, ataxia, seizures, and coma have been observed. While myelosuppression occurs, it is generally milder and much less significant than with vinblastine. The other potential adverse effect that can develop is the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). 

Although not a taxane, ixabepilone is a novel microtubule inhibitor that was recently approved for metastatic breast cancer in combination with the oral fluoropyrimidine capecitabine or as monotherapy. It is a semisynthetic analog of epothilone B, and is active in the M phase of the cell cycle. This agent binds directly to 6-tubulin subunits on microtubules, leading to inhibition of normal microtubule dynamics. Of note, this agent continues to have activity in drug-resistant tumors that overexpress P-glycoprotein or tubulin mutations. The main adverse effects include myelosuppression, hypersensitivity reactions, and neurotoxicity in the form of peripheral sensory neuropathy. 

Periphery Opioids also bind to peripheral sensory nerve fibers and their terminals. As in the CNS, they inhibit Ca -dependent release of excitatory, proinflammatory substances (for example, substance P) from these nerve endings. It has been suggested that this may contribute to the antiinflammatory effects of opioids. 

The property of drugs that allows these adaptive differences with conventional reinforcers is a basic one drugs enter the brain and directly activate or disinhibit DA neurons. In contrast, for their effects on DA neurons, conventional reinforcer drugs depend on the stimulation of a long chain of neurons triggered by stimulation of peripheral sensory receptors. 

Estrogens cause abnormalities of tryptophan metabolism that resemble those seen in vitamin Be deficiency, and the vitamin is widely used to treat the side effects of estrogen administration and estrogen-associated symptoms of the premenstrual syndrome, although there is litde evidence of its efficacy. High doses of the vitamin, of the order of 100 times requirements, cause peripheral sensory neuropathy. 

After initial contradictory reports it is now established that arsenic can cross the blood-brain barrier and produces alternations in whole rat brain biogenic amines levels in animals chronically exposed to arsenite (Tripathi et al, 1997). The neurological effects are many and varied. Usually, peripheral neuropathy, sensory neuropathy (Hafeman et al, 2005), and encephalopathy are the initial complaints associated with acute arsenic poisoning. Acute exposure to arsenic in humans has been shown to result in problems of memory, difficulties in concentration, mental confusion, and anxiety (Hall, 2002 Rodriguez et al, 2003). Other neurological symptoms arising due to arsenic are primarily those of a peripheral sensory neuritis, predominantly numbness, severe paresthesia of the distal portion of the extremities, diminished sense of touch, pain, heat and cold, and symmetrically reduced muscle power (Menkes, 1997). 

Riot control agents such as CN are those that cause disabling physiological effects when they come into contact with the eyes or skin, or when inhaled. They have the capacity to cause intense sensory irritation of the skin and mucous membranes of the eye and respiratory tract. They are peripheral sensory irritants that pharmacologically interact with sensory nerve receptors in skin and mucosal surfaces at the site of contamination resulting in local pain and discomfort sensations with associated reflexes. The reflex associated with the inhalation exposure of irritants is the Kratschmer reflex. This reflex causes apnea, bradycardia, and a biphasic fall and rise in aortic blood pressure. 

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