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does not resolve with tolerance as most other side effects do Sedation and cognitive slowing: dose-dependent CNS depression that diminishes as tolerance develops over days to weeks of regular use Dizziness and orthostatic hypotension: resulting from opioid-induced vasodilation and blunted baroreceptor reflex responses Pruritus (itching): driven by histamine release from mast cells rather than an IgE-mediated allergic hypersensitivity reaction Miosis (pinpoint pupils): resulting from oculomotor nerve stimulation at the Edinger-Westphal nucleus

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Suppression of nitrative damage by metallothionein in diabetic heart contributes to the prevention of cardiomyopathy