An Energy comparison between polycarbonate and glass half-gallon milk bottles used in a returnable refillable system

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Investigation of in vitro transdermal absorption of fentanyl from patches placed on skin samples obtained from various anatomic regions of dogs

Objective-To investigate in vitro transdermal absorption of fentanyl from patches through skin samples obtained from various anatomic regions of dogs. Sample Population-Skin samples from 5 Greyhounds. Procedure-Skin samples from the dogs' thoracic, neck, and groin regions were collected postmortem and frozen. After samples were thawed, circular sections were cut and placed in Franz-type diffusion cells in a water bath (32degreesC). A commercial fentanyl patch, attached to an acetate strip with a circular hole, was applied to each skin sample. Cellulose strips were used as control membranes. Samples of receptor fluid in the diffusion cells were collected at intervals for 48 hours, and fentanyl concentrations were analyzed by use of high-performance liquid chromatography. Results-Mean +/- SD release rate of fentanyl from the patch, defined by its absorption rate through the non-rate-limiting cellulose membrane, was linear during the first 8 hours (2.01 +/- 0.05 pg/cm(2) of cellulose membrane/h) and then decreased. Fentanyl passed through skin from the groin region at a faster rate and with a significantly shorter lag time, compared with findings in neck or thoracic skin samples. Conclusions and Clinical Relevance-In vitro, fentanyl from a patch was absorbed more quickly and to a greater extent through skin collected from the groin region of dogs, compared with skin samples from the thoracic and neck regions. Placement of fentanyl patches in the groin region of dogs may decrease the lag time to achieve analgesia perioperatively; however, in vivo studies are necessary to confirm these findings

A History of Drug Discovery for Treatment of Nausea and Vomiting and the Implications for Future Research.

The origins of the major classes of current anti-emetics are examined. Serendipity is a recurrent theme in discovery of their anti-emetic properties and repurposing from one indication to another is a continuing trend. Notably, the discoveries have occurred against a background of company mergers and changing anti-emetic requirements. Major drug classes include: (i) Muscarinic receptor antagonists-originated from historical accounts of plant extracts containing atropine and hyoscine with development stimulated by the need to prevent sea-sickness among soldiers during beach landings; (ii) Histamine receptor antagonists-searching for replacements for the anti-malaria drug quinine, in short supply because of wartime shipping blockade, facilitated the discovery of histamine (H1) antagonists (e.g., dimenhydrinate), followed by serendipitous discovery of anti-emetic activity against motion sickness in a patient undergoing treatment for urticaria; (iii) Phenothiazines and dopamine receptor antagonists-investigations of their pharmacology as "sedatives" (e.g., chlorpromazine) implicated dopamine receptors in emesis, leading to development of selective dopamine (D2) receptor antagonists (e.g., domperidone with poor ability to penetrate the blood-brain barrier) as anti-emetics in chemotherapy and surgery; (iv) Metoclopramide and selective 5-hydroxytryptamine3(5-HT3) receptor antagonists-metoclopramide was initially assumed to act only via D2 receptor antagonism but subsequently its gastric motility stimulant effect (proposed to contribute to the anti-emetic action) was shown to be due to 5-hydroxytryptamine4 receptor agonism. Pre-clinical studies showed that anti-emetic efficacy against the newly-introduced, highly emetic, chemotherapeutic agent cisplatin was due to antagonism at 5-HT3 receptors. The latter led to identification of selective 5-HT3 receptor antagonists (e.g., granisetron), a major breakthrough in treatment of chemotherapy-induced emesis; (v) Neurokinin1receptor antagonists-antagonists of the actions of substance P were developed as analgesics but pre-clinical studies identified broad-spectrum anti-emetic effects; clinical studies showed particular efficacy in the delayed phase of chemotherapy-induced emesis. Finally, the repurposing of different drugs for treatment of nausea and vomiting is examined, particularly during palliative care, and also the challenges in identifying novel anti-emetic drugs, particularly for treatment of nausea as compared to vomiting. We consider the lessons from the past for the future and ask why there has not been a major breakthrough in the last 20 years