Articles: human.
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Journal of anesthesia · Sep 1996
Effects of spinal naloxone and naltrindole on the antinociceptive action of intrathecally administered dexmedetomidine.
Intrathecally administered alpha-2 adrenoceptor and opioid agonists are well known to exert antinociceptive effects in humans and various animals. To examine the interaction of these two groups of agents in the spinal cord, we tested the effect of the opioid antagonists naloxone or naltrindole on the antinociceptive action of an intrathecally administered alpha-2 agonist, dexmedetomidine, using a formalin test in rats. 19 groups of Sprague-Dawley rats (250-300 g) were prepared with chronic intrathecal catheters and examined for the effects of agents on the formalin test. Each group contained 6 animals. 50 μl of 5% formalin was injected subcutaneously in the plantar surface of one hind paw. ⋯ Intrathecal dexmedetomidine (1 μg) maximally depressed the behavioral changes in both phase 1 and phase 2 of the formalin test, which was antagonized by the alpha-2 adrenoceptor selective antagonist atipamezole (0.3 μg). Naloxone (0.1-10 μg) or naltrindole (1-10 μg), when coadministered with dexmedetomidine, showed a dose-dependent antagonism to the effect of dexmedetomidine, whereas naloxone, naltrindole, or atipamezole alone showed no effect on the nocieptive behavior due to formalin injection. These results indicate that the antinociceptive effect of intrathecally administered alpha-2 adrenoceptor agonists may involve opioid receptors in the spinal cord.
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Journal of anesthesia · Sep 1996
Cervical sympathectomy affects adrenocorticotropic hormone and thyroid-stimulating hormone in rats.
To examine the effects of bilateral cervical sympathectomy on the secretion of adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), growth hormone (GH), and prolactin (PRL), 18 male rats were divided into three groups: control (Cont), sham operation (Sham), and bilateral cervical sympathectomy (Symp). All rats were kept under a normal circadian rhythm for 2 weeks. Subsequently, blood was collected and plasma ACTH as well as serum TSH, GH, and PRL levels were measured. ⋯ The present results suggest that cervical sympathectomy in the rat increases ACTH secretion and decreases TSH secretion in the pituitary. These effects seem to be due to a mildly increased secretion of melatonin in the pineal body that probably in turn increases corticotropin-releasing factor (CRF) secretion and decreases thyrotropin-releasing hormone (TRH) secretion in the hypothalamus. Extrapolation of these findings to humans suggests that longterm and repeated stellate ganglion block would affect the pituitary secretions of ACTH and TSH.
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The enantiomerically pure (S-enantiomer) amide local anaesthetic drug ropivacaine blocked nerve fibres responsible for transmission of pain (Aδ and fibres) more completely than those that control motor function (Aβ fibres) in in vitro studies. The drug shares the biphasic vascular effects common to the amide local anaesthetic drug class. In vitro studies indicate that ropivacaine is less cardiotoxic than equimolar concentrations of bupivacaine. Apart from one trial in women undergoing hysterectomy, clinical studies that compared the efficacy of different doses of epidurally administered ropivacaine in patients undergoing various surgical procedures did not reveal any consistent dose-related differences with respect to sensory blockade. However, motor blockade did become more intense as the dose of ropivacaine increased. Overall, direct comparisons show that epidural ropivacaine is less potent than epidural bupivacaine when the 2 drugs are administered at the same concentration. However, this difference is less marked in terms of sensory blockade than motor blockade. The greater degree of separation between motor and sensory blockade seen with ropivacaine relative to bupivacaine is more apparent at the lower end of the dosage scale. Nevertheless, higher doses of ropivacaine than bupivacaine are generally required to elicit equivalent anaesthetic effects. Ropivacaine has been shown to induce successful brachial plexus anaesthesia when given at a concentration of 5 mg/ml, but not 2.5 mg/ml, and was as effective as bupivacaine in comparative studies in this indication. Limited data indicate that continuous epidural infusion of ropivacaine post-operatively reduces postsurgical pain in a dose-related manner. Morphine consumption was also reduced. Higher doses of ropivacaine were significantly more effective than placebo. Similarly, ropivacaine controlled postsurgical pain when infiltrated directly into surgical wound sites (i.e. wound infiltration) and was as effective as bupivacaine, and more effective than placebo, in this regard. Adverse events associated with epidurally administered ropivacaine include hypotension, nausea, bradycardia, transient paraesthesia, back pain, urinary retention and fever. The drug appears to have an adverse event profile similar to that of bupivacaine. In animal studies, overdoses of ropivacaine were better tolerated than overdoses of bupivacaine but not lidocaine (lignocaine). Human volunteers tolerated a higher intravenous dosage of ropivacaine than bupivacaine before developing initial signs of toxicity. Thus, ropivacaine, according to animal data, is less cardiotoxic than bupivacaine. Based on available clinical data, ropivacaine appears to be as effective and well tolerated as bupivacaine when equianalgesic doses are compared. The greater degree of separation between motor and sensory blockade seen with ropivacaine relative to bupivacaine at lower concentrations (≈5 mg/ml) will be advantageous in certain applications. ⋯ Recommended epidural doses of ropivacaine for surgical anaesthesia range between 113 and 200mg. Different doses can be achieved by varying either the concentration or volume of solution injected. Epidural ropivacaine administered to control postsurgical pain can be given as a 20 to 40mg bolus with 20 to 30mg top-up doses at ≥30-minute intervals or as a 2 mg/ml continuous epidural infusion at a rate of 6 to 14 ml/h (lumbar) or 4 to 8 ml/h (thoracic).
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Natl Toxicol Program Tech Rep Ser · Aug 1996
NTP Toxicology and Carcinogenesis Studies of Codeine (CAS No. 76-57-3) in F344 Rats and B6C3F1 Mice (Feed Studies).
Codeine is used in a variety of pharmaceuticals including analgesics, sedatives, hypnotics, antiperistaltics, and antitussive agents. The National Cancer Institute and the Food and Drug Administration nominated codeine for study because it is a widely used drug and it is representative of the morphine class of compounds, for which chronic carcinogenicity studies had not been conducted. The oral route of administration was selected because it is the primary route of human exposure. ⋯ Thyroid gland follicular cell hyperplasia was increased in exposed male and female mice. Decreased incidences of benign pheochromocytomas of the adrenal medulla in male rats and mammary gland fibroadenomas and fibroadenomas or adenocarcinomas (combined) in female rats were related to codeine exposure. Synonyms: 7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol; methylmorphine; 3-0-methylmorphine monohydrate; N-methylnorcodeine; morphine-3-methyl ether; morphine monomethyl ether Trade names: Codeinum, Codicept, Coducept, Metilmorfina
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Two cases of severe postpartum anaemia are presented in Jehovah's witnesses who refused blood transfusion. Despite haemoglobin concentrations of less than 3 g/dl both women survived. ⋯ In the other case, recombinant human erythropoietin was used to encourage red cell production. The recovery of haemoglobin concentration in the two cases is compared.