Additionally, morphine undergoes significant first-pass metabolism thus, oral doses must be six-fold greater than parenteral doses to achieve the same degree of analgesia ( 2 2. The onset of morphine-induced analgesia after intravenous administration is relatively slow (6-30 min), partly because of its limited lipid solubility and its slow rate of penetration through the blood-brain barrier. With increasing doses, the degree of analgesia increases until an anesthetic level is reached. Morphine blocks the transmission of nociceptive signals, activates signaling by pain-modulating neurons to the spinal cord, and inhibits transmission from primary afferent nociceptors to dorsal horn sensory projection cells ( 1 1. Morphine-like agonists mediate their effects via the µ opioid receptors to cause pain relief, sedation, euphoria and respiratory depression. Morphine is an agonist of both the µ and the k receptors, and activation of these receptors results in analgesia. Metabolism Morphine Neonate Pharmacokinetics Although much is known about morphine in neonates, further research will be required to ensure that recommended therapeutic doses for analgesia in neonates are evidence based. The results indicate that morphine is extensively glucuronidated and sulfated at positions 3 and 6, and that the glucuronidation rate is lower in younger neonates compared with older infants. The initial and final cutoff points were January 1990 and September 2015, respectively. A bibliographic search was performed using the PubMed database and the keywords “morphine metabolism neonate” and “morphine pharmacokinetics neonate”. Neonatal pain relief may require a blood level of approximately 120 ng/ml, whereas lower levels (20-40 ng/ml) seem adequate for children. Ordinary doses cause constipation, urinary retention and respiratory depression. The morphine-3-glucuronide metabolite has lower clearance, a shorter half-life and a smaller distribution volume compared with the morphine-6 metabolite, which is the most active morphine-like agonist. Steady-state morphine plasma concentrations are achieved after 24-48 hours of infusion, but the glucuronide metabolite plasma concentrations do not reach steady state before 60 hours. Moreover, morphine clearance correlates positively with gestational age and birth weight.
Morphine is glucuronidated and sulfated at positions 3 and 6 the plasma concentration ratios correlate positively with birth weight, which probably reflects increased liver weight with increasing birth weight.
Morphine-like agonists act through the µ opioid receptors to cause pain relief, sedation, euphoria and respiratory depression. Morphine is an agonist of the µ and k receptors, whose activation results in analgesia.
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