Basic & clinical pharmacology & toxicology
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Basic Clin. Pharmacol. Toxicol. · Feb 2013
General practitioners' and hospital physicians' preference for morphine or oxycodone as first-time choice for a strong opioid: a National Register-based study.
The aim of this study was to characterize first-time oxycodone and morphine prescriptions in outpatients by type of prescriber and naivety in regard to strong opioids. All prescriptions for morphine and oxycodone in Denmark reported to the National Register of Medicinal Product Statistics in 2010 were analysed. If a patient had not had a prescription filled for the same drug within the last 2 years, the prescription was defined as a first-time prescription. ⋯ Hospital physicians had a greater preference for oxycodone over morphine than GPs (OR 1.34, 95% CI 1.29-1.39). However, GPs were responsible for approximately 61% of all first-time prescriptions for both oxycodone and morphine for strong opioid-naive patients. In conclusion, oxycodone is to a great extent prescribed as the first-choice strong opioid, and both GPs and hospital physicians seem to contribute to this prescribing pattern of strong opioids to outpatients.
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Basic Clin. Pharmacol. Toxicol. · Feb 2013
Comparative StudyRegulation of neuropathic hypersensitivity by α(2) -adrenoceptors in the pontine A7 cell group.
Pontine A5, A6 (locus coeruleus) and A7 cell groups provide noradrenergic innervation of the spinal cord. Here, we assessed whether activation of α(2) -adrenoceptors in A7 influences peripheral nerve injury-induced hypersensitivity in the rat, and whether spinal α(2) -adrenoceptors mediate the descending effect. Fadolmidine, an α(2) -adrenoceptor agonist that because of its pharmacokinetic properties has a limited spread from the injection site, was microinjected through a chronic guide cannula into A7 or for comparison into A6 ipsilateral to the nerve injury. ⋯ Fadolmidine in A7 failed to influence mechanical hyperalgesia or heat nociception at doses that produced a tactile antihypersensitivity effect. We propose that tonic noradrenergic drive of A6 by A7 promotes neuropathic hypersensitivity by suppressing descending noradrenergic inhibition originating in A6. Consequently, the activation of inhibitory α(2) -adrenoceptors within the pontine A7 cell group suppresses neuropathic hypersensitivity by disinhibiting A6 and its descending noradrenergic pathways acting on spinal α(2) -adrenoceptors.
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Basic Clin. Pharmacol. Toxicol. · Feb 2013
Review Randomized Controlled TrialThe effect of paracetamol and tropisetron on pain: experimental studies and a review of published data.
Experimental studies suggest that paracetamol-induced analgesia is mediated via central serotonergic pathways and attenuated by 5-HT3-antagonists. However, clinical studies do not support this, and 5-HT3-antagonists are expected to reduce pain by blocking the descending pronociceptive pathway. The current project tested whether tropisetron attenuates analgesia by paracetamol. ⋯ As paracetamol did not have a measurable analgesic effect in these tests, no conclusions can be drawn about the interaction between paracetamol and tropisetron. However, tropisetron may have an analgesic effect of its own. Clinicians should not avoid using these drugs together, unless larger clinical studies indicate otherwise.
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Basic Clin. Pharmacol. Toxicol. · Dec 2012
Randomized Controlled TrialThe absorption profile of pregabalin in chronic pancreatitis.
It was recently shown that pregabalin decreased pain associated with chronic pancreatitis. It is well known that pancreatitis patients suffer from fat malabsorption with accompanying diarrhoea because of loss of exocrine pancreatic enzyme production. This may lead to changes in the mucosal surface in the small intestine and possibly affect the absorption of pregabalin. ⋯ Time to maximum observed plasma concentration (T(max) ) was 1.53 (95% CI 1.09-2.05). The maximum plasma concentration (C(max) ) was 1.98 μg/ml (95% CI 1.69-2.34), and area under the plasma concentration-time profile (area under the curve) was 18.2 μg*hr/ml (95% CI 14.7-26.3). Pregabalin is well absorbed in patients with chronic pancreatitis, and the pharmacokinetic profile of pregabalin is not extensively affected by chronic pancreatitis.
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Basic Clin. Pharmacol. Toxicol. · Dec 2012
Randomized Controlled TrialThe analgesic concentration of oxycodone with co-administration of paracetamol -- a dose-finding study in adult patients undergoing laparoscopic cholecystectomy.
We have previously shown that paracetamol has an opioid-sparing effect in tonsillectomy, and now, we evaluated the analgesic efficacy of paracetamol i.v. in early post-operative pain after laparoscopic cholecystectomy (LCC). Twenty-four patients with LCC were randomized to receive paracetamol i.v. 1 g (group 1) or 2 g (group 2) at the end of surgery. All patients were provided 0.1 mg/kg of oxycodone i.v. 15 min. before the end of surgery. ⋯ At the onset of pain, P-oxycodone (MEC) was similar in both groups, 25 ng/ml (19-32) in group 1 and 24 ng/ml (16-34) in group 2. The pain relief (MEAC) was achieved in group 1 with P-oxycodone 70 ng/ml (30-131) and in group 2 with 62 ng/ml (36-100) (p = 0.48). In conclusion, in the early-phase after LCC, there was no significant difference between the effect of paracetamol doses of 1 g and 2 g i.v. on the need of i.v. oxycodone.