Low-dose clonidine and neostigmine prolong the duration of intrathecal bupivacaine-fentanyl for labor analgesia.
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BACKGROUND: Intrathecal (IT) opioid and local anesthetic combinations are popular for labor analgesia because of rapid, effective pain relief, but the duration of analgesia is limited. This study was undertaken to determine whether the addition of clonidine and neostigmine to IT bupivacaine-fentanyl would increase the duration of analgesia without increasing side effects for patients in labor. METHODS: Forty-five healthy parturients in active labor were randomized to receive a 2-ml IT dose of one of the following dextrose-containing solutions using the combined spinal-epidural technique: (1) bupivacaine 2.5 mg and fentanyl 25 microg (BF); (2) BF plus clonidine 30 microg (BFC); or (3) BFC plus neostigmine 10 microg (BFCN). Pain, sensory levels, motor block, side effects, maternal vital signs, and fetal heart rate were systematically assessed. RESULTS: Patients administered BFCN had significantly longer analgesia (165+/-32 min) than those who received BF (90+/-21 min; P<0.001) or BFC (123+/-21 min; P<0.001). Pain scores, block characteristics, maternal vital signs, Apgar scores, maternal satisfaction, and side effects were similar among groups except for nausea, which was significantly greater in the BFCN group (P<0.05 as compared with BFC). CONCLUSIONS: The addition of clonidine and neostigmine significantly increased the duration of analgesia from IT bupivacaine-fentanyl during labor, but neostigmine caused more nausea. Although serious side effects were not observed in this study, safety must be further addressed before the routine use of multiple IT drugs is advocated. (+info)
Inhibitory effect of clonidine on ketamine-induced norepinephrine release from the medial prefrontal cortex in rats.
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We have investigated the effect of clonidine on ketamine-induced norepinephrine release from the medial prefrontal cortex in rats using microdialysis. Twenty-one male Wistar rats weighing 200-300 g were allocated randomly to one of four groups: i.p. injection of ketamine 100 mg kg-1 with clonidine 0 (saline: group C0, n = 6), 3 (group C3, n = 5), 30 (group C30, n = 5) and 300 micrograms kg-1 (group C300, n = 5). As reported previously, ketamine increases norepinephrine release. In groups C0 and C3, marked increases in norepinephrine release were observed with maximum values of mean 483 (SEM 55)% and 412 (53)% compared with basal values, respectively. Although significant increases in norepinephrine release were also observed (276 (43)%) in group C30, they were significantly lower than those in groups C0 and C3 (P < 0.01 and P < 0.05, respectively). In group C300, there was a significant reduction in norepinephrine release (62 (13)%) compared with basal and the three other groups (P < 0.01). This inhibitory effect of clonidine on norepinephrine may be related to reduction in undesirable emergence reactions after ketamine anaesthesia. (+info)
Effects of menstrual cycle and race on peripheral vascular alpha-adrenergic responsiveness.
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Gender differences in the incidence of many cardiovascular diseases may be due to the effects of sex hormones. Both alpha(1)- and alpha(2)-adrenergic receptors produce vasoconstriction in peripheral blood vessels and have demonstrated gender effects in previous studies. In addition, race has been shown to influence the effects of some alpha-adrenergic stimuli. We therefore sought to determine the effects of the menstrual cycle and race on peripheral blood flow responses to the intra-arterial infusion of phenylephrine (alpha(1)-agonist) and clonidine (alpha(2)-agonist). Ten white and 8 black women were studied during the early luteal phase and the follicular phase; these phases were verified in each woman through measurements of plasma estradiol and progesterone. Plasma norepinephrine was measured with HPLC. During phenylephrine infusion, there was significantly greater vasoconstriction in the luteal phase versus the follicular phase (P<0.05). There were no differences (P>0.8) between white and black women. During clonidine infusion, white women showed significantly more vasoconstriction in the follicular phase than during the luteal phase (P<0.006). For black women, the responses for both phases did not differ (P>0.9). Blood pressures were significantly higher in the black women (diastolic P<0.005, systolic P<0.05). The luteal-phase elevation of alpha(1)-adrenergic responses may be due to elevated levels of estradiol, progesterone, or both. The lack of luteal-phase reduction in alpha(2)-adrenergic vasoconstriction in black women may contribute to their increased pressor responses to adrenergic stimuli. (+info)
Harmane produces hypotension following microinjection into the RVLM: possible role of I(1)-imidazoline receptors.
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The beta-carboline, harmane (0.1 - 1.0 nmol) produces dose dependent hypotension when microinjected unilaterally into the rostral ventrolateral medulla (RVLM) of the anaesthetized rat. The potency of harmane on blood pressure is similar to that of the imidazoline, clonidine. The hypotensive effects of both clonidine and harmane are reversed by microinjection of the relatively I(1)-receptor selective antagonist efaroxan (20 nmol). These results are consistent with harmane acting at an I(1)-receptor in the RVLM. This is the first report of an endogenous ligand for I(1)-receptors that has central effects on blood pressure. (+info)
Both alpha(1A)- and alpha(1B)-adrenergic receptor subtypes couple to the transient outward current (I(To)) in rat ventricular myocytes.
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1. Regulation of transient outward current (I(To)) by alpha(1)-adrenergic (alpha(1)AR) plays a key role in cardiac repolarization. alpha(1)ARs comprise a heterogeneous family; two natively expressed subtypes (alpha(1A) and alpha(1B)) and three cloned subtypes (alpha(1a), alpha(1b) and alpha(1d)) can be distinguished. We have examined the electrophysiological role of each alpha(1)AR subtype in regulating I(To) in isolated rat ventricular myocytes. 2. Reverse transcription-PCR study revealed the presence of three subtype mRNAs (alpha(1a), alpha(1b) and alpha(1d)) in rat myocytes. 3. Radioligand binding assay using [(125)I]-HEAT showed that the inhibition curves for alpha(1A)AR-selective antagonists (WB4101, 5-methylurapidil, (+)-niguldipine and KMD-3213) in rat ventricles best fit a two-site model, with 30% high and 70% low affinity binding sites. The high affinity sites were resistant to 100 microM chloroethylclonidine (CEC), while the low affinity sites were highly inactivated by CEC. 4. Whole cell voltage clamp study revealed that methoxamine reduced a 4-aminopyridine(4-AP)-sensitive component of I(To) in the isolated rat ventricle myocytes. Lower concentrations of KMD-3213 (1 nM) or 5-MU (10 nM) did not affect the methoxamine-induced reduction of I(To). On the other hand, CEC treatment (100 microM) of isolated myocytes reduced the methoxamine-induced reduction of I(To) by 46%, and the remaining response was abolished by lower concentrations of KMD-3213 or 5-MU. 5. The results indicate that rat ventricular myocytes express transcripts of the three alpha(1)AR subtypes (alpha(1a), alpha(1b) and alpha(1d)); however, two pharmacologically distinct alpha(1)AR subtypes (alpha(1A) and alpha(1B)) are predominating in receptor populations, with approximately 30% alpha(1A)AR and 70% alpha(1B)AR. Although both alpha(1A) and alpha(1B)AR subtypes are coupled to the cardiac I(To), alpha(1B)ARs predominantly mediate alpha(1)AR-induced effect. (+info)
A comparative study of clonidine versus a combination of diazepam and atropine for premedication in orthopaedic patients.
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Sixty patients in the age group of 18-60 years of A.S.A. Grade I/II risk, scheduled for elective orthopaedic surgeries under general anaesthesia were studied for pre-medication with either oral clonidine or with combination of effects of diazepam & atropine. Patients in Group A (clonidine group) received tablet clonidine 100 mcg (1 tablet) if less than 50 kg in weight and 200 mcg if weighing more than 50 kg two hours before surgery. Patients in Group B (Diazepam-atropine group) received one tablet of Diazepam (10 mg) orally two hours before surgery and injection atropine-sulphate 0.01 mg/kg half an hour preoperatively by intramuscular route. In our study, the sedative and anti-sialogogue effects of clonidine were comparable to those of diazepam-atropine combination, which are commonly used premedicants. The anti-anxiety effect of clonidine was found to be better than that of diazepam-atropine combination. Clonidine also proved to be a better agent for the attenuation of pressor response to laryngoscopy and intubation. Thus, oral clonidine is a better premedicant compared to atropine-diazepam combination. Also, it is a more acceptable agent because of its oral route of administration. (+info)
Antiallodynic effect of intrathecal gabapentin and its interaction with clonidine in a rat model of postoperative pain.
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BACKGROUND: Systemic administration of gabapentin was shown previously to attenuate mechanical allodynia in a rat model of postoperative pain. Because intrathecal administration of gabapentin is effective in other hypersensitivity states, the authors tested its effect in the postoperative model, its interaction with another antiallodynic agent (clonidine), and a possible mechanism of gabapentin action (entry into sites of action via an L-amino acid transporter). METHODS: Male Sprague-Dawley rats were anesthetized with halothane, and an incision of the plantaris muscle of right hind paw induced punctate mechanical allodynia. Withdrawal threshold to von Frey filament application near the incision site was determined before and 2 h after surgery. Then, an intrathecal injection was performed and thresholds were determined every 30 min for 3 h thereafter. RESULTS: Paw incision induced a mechanical hypersensitivity (mechanical threshold > 25 g before incision and < 5 g after). Intrathecal gabapentin dose-dependently (10-100 microg) reduced mechanical allodynia. Intrathecal injection of an inhibitor of L-amino acid transporters or a competitor for this transporter, L-leucine, did not reverse the intrathecal effect of gabapentin. The ED50 of intrathecal gabapentin, clonidine, and their combination were 51, 31, and 9 microg, respectively, and isobolographic analysis showed synergy between gabapentin and clonidine. CONCLUSIONS: Intrathecal gabapentin is effective against tactile allodynia that occurs after paw incision, and interacts synergistically with clonidine. Unlike results in vitro, gabapentin does not obligatorily need to enter cells via the L-amino acid transporter mechanism to achieve its effects in vivo. (+info)
Intrathecal dexmedetomidine attenuates hypercapnic but not hypoxic cerebral vasodilation in anesthetized rabbits.
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BACKGROUND: Systemic dexmedetomidine (DXM) attenuates the cerebral vasodilation induced by hypercapnia and decreases the cerebral blood flow response to hypoxia. We determined whether lumbar intrathecal DXM affected the cerebrovascular reactivity to hypercapnia and hypoxia. METHODS: Rabbits (n = 55) anesthetized with pentobarbital were prepared for measurement of pial vessel diameters using a closed cranial window preparation. The first study evaluated the response to hypercapnia after intrathecal administration of DXM (2 microg/kg; n = 7) or normal saline (n = 8). The second evaluated the response to hypercapnia after intrathecal DXM in the presence of yohimbine (20 microg/kg followed by DXM 2 microg/kg; n = 7). The third evaluated the response to mild or moderate hypoxia after intrathecal DXM (2 microg/kg; n = 7) or normal saline (n = 7). The hypercapnic responses were also examined in the presence of systemic DXM (2, 10 microg/kg; n = 6), topical DXM (10-8 m, 10-6 m; n = 6) and of intrathecal clonidine (2 microg/kg; n = 7). RESULTS: The pial arteriolar dilator response to hypercapnia was significantly attenuated after intrathecal administration of DXM. Pretreatment with yohimbine completely blocked the decreased reactivity to hypercapnia. Intrathecal clonidine, although less than DXM, also attenuate the hypercapnic response. Intrathecal DXM did not affect the vasodilation of pial arterioles induced by mild or moderate hypoxia. The systemic DXM 10 microg/kg and topical DXM 10-6 m, but not systemic 2 microg/kg and topical 10-8 m, attenuated hypercapnic vasodilation of pial arterioles. CONCLUSIONS: The presence of alpha2-adrenoceptor agonist administered intrathecally into the lumbar spinal region attenuates hypercapnic but not hypoxic cerebral vasodilation, probably via a stimulation of central alpha2-adrenergic receptors of the central nervous system. (+info)