Clin Pharmacokinet
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Tramadol, a centrally acting analgesic structurally related to codeine and morphine, consists of two enantiomers, both of which contribute to analgesic activity via different mechanisms. (+)-Tramadol and the metabolite (+)-O-desmethyl-tramadol (M1) are agonists of the mu opioid receptor. (+)-Tramadol inhibits serotonin reuptake and (-)-tramadol inhibits norepinephrine reuptake, enhancing inhibitory effects on pain transmission in the spinal cord. The complementary and synergistic actions of the two enantiomers improve the analgesic efficacy and tolerability profile of the racemate. Tramadol is available as drops, capsules and sustained-release formulations for oral use, suppositories for rectal use and solution for intramuscular, intravenous and subcutaneous injection. ⋯ Tramadol may prove particularly useful in patients with a risk of poor cardiopulmonary function, after surgery of the thorax or upper abdomen and when non-opioid analgesics are contraindicated. Tramadol is an effective and well tolerated agent to reduce pain resulting from trauma, renal or biliary colic and labour, and also for the management of chronic pain of malignant or nonmalignant origin, particularly neuropathic pain. Tramadol appears to produce less constipation and dependence than equianalgesic doses of strong opioids.
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Spacer devices are attachments to the mouthpieces of pressurised metered dose inhalers (pMDIs), and range from tube spacers with a volume of <50 mL to holding chambers with a volume of 750 mL. Compared with a pMDI alone, spacers minimise coordination difficulties, reduce oropharyngeal deposition and often increase lung deposition. ⋯ In patients with severe acute asthma or severe chronic obstructive pulmonary disease, a pMDI plus large volume spacer may be a viable alternative to a nebuliser for delivering large bronchodilator doses. Although the addition of a spacer to every pMDI would not be justified, the use of large volume spacers has been recommended for any inhaled asthma drug in young children, and as a means of reducing systemic bioavailability of inhaled corticosteroids in adults and children alike.
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Review
Antiepileptic-induced resistance to neuromuscular blockers: mechanisms and clinical significance.
Prolonged administration of antiepileptic drugs is associated with several drug interactions. In the field of anaesthesia and critical care, patients exhibit both sensitivity and resistance to non-depolarising neuromuscular blockers (NDNMBs) after acute and long-term administration of antiepileptic drugs, respectively. Although antiepileptic therapy alone has only mild neuromuscular effects, acutely administered antiepileptic drugs can potentiate the neuromuscular effects of NDNMBs as a result of direct pre- and post-junctional effects. Resistance to NDNMBs during long-term antiepileptic therapy is due to multiple factors operating alone or in combination, including induction of hepatic drug metabolism, increased protein binding of the NDNMBs and/or upregulation of acetylcholine receptors.
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This review uses a candidate gene approach to identify possible pharmacogenetic modulators of opioid therapy, and discusses these modulators together with demonstrated genetic causes for the variability in clinical effects of opioids. Genetically caused inactivity of cytochrome P450 (CYP) 2D6 renders codeine ineffective (lack of morphine formation), slightly decreases the efficacy of tramadol (lack of formation of the active O-desmethyl-tramadol) and slightly decreases the clearance of methadone. MDR1 mutations often demonstrate pharmacogenetic consequences, and since opioids are among the P-glycoprotein substrates, opioid pharmacology may be affected by MDR1 mutations. ⋯ Genetically precipitated drug interactions might render a standard opioid dose toxic and should, therefore, be taken into consideration. Mutations affecting opioid receptors and pain perception/processing are of interest for the study of opioid actions, but with modern practice of on-demand administration of opioids their utility may be limited to explaining why some patients need higher opioid doses; however, the adverse effects profile may be modified by these mutations. Nonetheless, at a limited level, pharmacogenetics can be expected to facilitate individualised opioid therapy.
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Comparative Study Clinical Trial Controlled Clinical Trial
Pharmacokinetics of oxycodone after intravenous, buccal, intramuscular and gastric administration in children.
To evaluate the pharmacokinetics of four administration routes of oxycodone parenteral liquid (10 mg/mL), single intravenous and intramuscular injections and buccal and gastric administration, in children. ⋯ The pharmacokinetics of intravenous oxycodone in children aged 6-93 months are fairly similar to those reported in adults. Intramuscular administration provides relatively constant drug absorption, but after buccal and gastric administration the interindividual variation in the rate and extent of absorption is large.