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Biomedical subjects

F Yanagidate

Publications and source records attributed to F Yanagidate.

9 recordsLinked to original sources

Local anesthetics.

Local anesthetics are used broadly to prevent or reverse acute pain and treat symptoms of chronic pain. This chapter, on the analgesic aspects of local anesthetics, reviews their broad actions that affect many different molecular targets and disrupt their functions in pain processing. Application of local anesthetics to peripheral nerve primarily results in the blockade of propagating action potentials, through their inhibition of voltage-gated sodium channels. Such inhibition results from drug binding at a site in the channel's inner pore, accessible from the cytoplasmic opening. Binding of drug molecules to these channels depends on their conformation, with the drugs generally having a higher affinity for the open and inactivated channel states that are induced by membrane depolarization. As a result, the effective potency of these drugs for blocking impulses increases during high-frequency repetitive firing and also under slow depolarization, such as occurs at a region of nerve injury, which is often the locus for generation of abnormal, pain-related ectopic impulses. At distal and central terminals the inhibition of voltage-gated calcium channels by local anesthetics will suppress neurogenic inflammation and the release of neurotransmitters. Actions on receptors that contribute to nociceptive transduction, such as TRPV1 and the bradykinin B2 receptor, provide an independent mode of analgesia. In the spinal cord, where local anesthetics are present during epidural or intrathecal anesthesia, inhibition of inotropic receptors, such as those for glutamate, by local anesthetics further interferes with neuronal transmission. Activation of spinal cord mitogen-activated protein (MAP) kinases, which are essential for the hyperalgesia following injury or incision and occur in both neurons and glia, is inhibited by spinal local anesthetics. Many G protein-coupled receptors are susceptible to local anesthetics, with particular sensitivity of those coupled via the Gq alpha-subunit. Local anesthetics are also infused intravenously to yield plasma concentrations far below those that block normal action potentials, yet that are frequently effective at reversing neuropathic pain. Thus, local anesthetics modify a variety of neuronal membrane channels and receptors, leading to what is probably a synergistic mixture of analgesic mechanisms to achieve effective clinical analgesia.

Anesthesia, Epidural↗

Modified nasal cannula for simultaneous oxygen delivery and end-tidal CO2 monitoring during spontaneous breathing.

BACKGROUND AND OBJECTIVES: Supplemental oxygen is commonly given via nasal cannulae in spontaneously breathing patients. Our modified nasal cannula with a clamp between the nasal prongs can provide O2 via one nostril and CO2 can be sampled through the other one. We have studied whether this cannula can provide oxygenation similar to a standard cannula without affecting end-tidal CO2 monitoring. METHODS: Eighty-six patients were studied during spinal anaesthesia and sedation. In 15 patients, arterial blood was sampled while O2 was delivered at flow rates of 0, 2 and 4 L min(-1), with or without clamping between the prongs of our modified nasal cannula. In the remaining 71 patients, arterial O2 was measured while using our modified nasal cannula with the clamp applied. End-tidal CO2 was recorded on a capnograph and the correlation between end-tidal and arterial values with our modified nasal cannula was investigated. RESULTS: No end-tidal CO2 waveforms were found with oxygen flow greater than 2L min(-1) without clamping between the prongs. With clamping there was a significant correlation (r = 0.83) between arterial and end-tidal CO2. A Bland-Altman analysis revealed a bias of 0.49 kPa with precision of +/-0.76 kPa. Arterial oxygenation was not affected by our modified nasal prongs with clamp as compared to the standard cannula. CONCLUSION: Our modified nasal cannula can provide continuous monitoring of end-tidal CO2 without affecting oxygen delivery in sedated, spontaneously breathing patients.

Aged↗

Epidural oxycodone or morphine following gynaecological surgery.

BACKGROUND: The analgesic action of oxycodone is of rapid onset, in contrast to morphine, and is mediated by kappa-opioid receptors of the spinal cord. We compared analgesia and side-effects of epidural oxycodone with those of morphine after gynaecological surgery. METHODS: We studied prospectively in 75 women in a double-blind, randomized manner: epidural morphine 6 mg day(-1) (n=25), epidural oxycodone 6 mg day(-1) (n=25) and epidural oxycodone 12 mg day(-1) (n=25). All patients underwent gynaecological surgery under general (isoflurane and nitrous oxide) and epidural anaesthesia. Visual analogue scale (VAS) pain scores at rest and on coughing, verbal descriptive scale (VDS) satisfaction scores, sedation scores, pruritus scores and nausea/vomiting scores were recorded for 3 days after surgery. RESULTS: VAS pain scores at rest in patients who received oxycodone 6 mg day(-1) were higher than in patients who received morphine 6 mg day(-1) at 6 h and on the first postoperative day and were significantly higher than in patients who received oxycodone 12 mg day(-1) on the first postoperative day. Scores for nausea, vomiting and pruritus in patients who received oxycodone 6 mg day(-1) and 12 mg day(-1) were lower than those in patients who received morphine. No significant differences were seen in VAS at cough and VDS satisfaction scores between the three groups. CONCLUSION: Epidural oxycodone was as effective as morphine at the doses investigated, with fewer side-effects.

Adult↗

The antinociceptive and sedative effects of carbachol and oxycodone administered into brainstem pontine reticular formation and spinal subarachnoid space in rats.

UNLABELLED: To clarify the supraspinal and spinal actions of a cholinergic agonist, carbachol, and an opioid, oxycodone, we studied their antinociceptive and behavioral effects when administered into brainstem medial pontine reticular formation (mPRF) or spinal subarachnoid space with or without pretreatment of muscarinic receptor subtype antagonist. Sprague-Dawley rats were implanted with a 24-gauge stainless steel guide cannula into the mPRF and chronically implanted with a lumbar intrathecal catheter. Antinociception was tested using tail flick latency, motor coordination was evaluated by the rotarod test, and overt sedation was assessed using a behavioral checklist. Carbachol (0.5-4.0 microg) administered into the mPRF produced significant dose- and time-dependent antinociception, sedation, and motor dysfunction. These were completely blocked by pretreatment with atropine and the M(2) muscarinic antagonist, methoctramine, and partially blocked by pretreatment with M(1) pirenzepine but not with M(3) p-fHHSID: Oxycodone administered into the mPRF did not produce such effects. Spinal carbachol and oxycodone produced antinociception without any behavioral effects; their antinociceptive effects were completely blocked by pretreatment with atropine and M(2) antagonist. These results suggest that the antinociceptive action of carbachol is mediated by muscarinic cholinergic receptor activation, especially by M(2) receptor subtype in mPRF and spinal cord, and that although oxycodone seems unlikely to affect the cholinergic transmission of mPRF, spinal oxycodone-induced analgesia is at least partly mediated via the activation of M(2) receptor subtype at the spinal cord. IMPLICATIONS: Carbachol-induced antinociception and sedation is mediated with the activation of M(2) muscarinic receptors. Oxycodone administered into brainstem medial pontine reticular formation did not cause any antinociceptive or behavioral effects, but its spinal administration produced a significant antinociception via M(2) muscarinic receptor activation

Analgesics, Non-Narcotic↗

Clonidine premedication reduces maternal requirement for intravenous morphine after cesarean delivery without affecting newborn's outcome.

BACKGROUND AND OBJECTIVES: The alpha(2)-agonist clonidine has several benefits for patients undergoing surgery. During and after elective cesarean delivery (C-section), we assessed the condition of parturient and neonate when one half of the parturients were pretreated with oral clonidine. METHODS: Forty-six consenting parturients were studied in a randomized, double-blinded manner. Preanesthetic medication was atropine and famotidine with or without clonidine 4 microg/kg. After baseline measurements in parturients and fetuses, combined spinal and epidural anesthesia was established (1.6 mL of 0.5% tetracaine diluted with 10% dextrose in water). C-section was performed while breathing oxygen spontaneously (3 L/min) through a facemask. After delivery, neonates were assessed at 1 and 5 minutes, and the condition of mother and neonate was observed for 48 hours. RESULTS: Parturients receiving clonidine showed no hemodynamic instability during and after C-section, and while their visual analog scale (VAS) scores, verbal descriptive scale (VDS) scores, and sedation scores did not differ from those without clonidine, they needed significantly less patient-controlled analgesia (PCA) morphine for postoperative pain for the first 2 days (P < .01). Fetal heart rate, umbilical artery and vein pH and gas tensions, and the Apgar-scores of the newborns showed no intergroup differences. No neonatal depression or bradycardia was observed for 48 hours after delivery. CONCLUSION: The present results indicate that oral clonidine reduces the PCA morphine requirement after C-section without compromising the condition of the fetus or newborn. Further study including larger number of patients would be needed before we conclude that oral clonidine for parturients is safe for their newborns.

Adult↗