A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfillment of the requirements for the degree of Master of Science in Medicine in Pharmaceutical Affairs Johannesburg, South Africa 2017 / In the Republic of South Africa codeine containing medicines are either sold as prescription only medicines or over the counter depending on the strength of codeine contained in the medicine. The analgesic properties of codeine are thought to be derived from the conversion of codeine to morphine. Codeine is often combined with nonsteroidal anti-inflammatory drugs (NSAIDs).Codeine is a relatively weak opioid analgesic that has seemingly addictive properties; the misuse of codeine-containing-medicines can cause morbidity in patients with known codeine addiction. The Regulation of codeine has been reviewed in a number of countries to try and curb the misuse of the product. This involves the reduction in the strength of codeine, reduction in the package size and duration of treatment of over-the-counter (OTC) codeine containing products and in some countries the OTC codeine containing products have been rescheduled into prescription only medicines. The study aims to monitor and describe trends in the sales of OTC codeine-containing medicines from Pick n Pay retail pharmacies in Gauteng, Western Cape and KwaZulu Natal provinces of South Africa from July 2011 to June 2014. Secondary data on the sales of OTC codeine-containing medicines from Pick n Pay Pharmacies database was obtained, which described the(1) pharmacy name, (2) the trade name of the medicine items sold, (3) the quantities of the medicines sold, (4) the purchase date of medicine, (5) the cost of the medicine, (6) the age of the purchaser, (7) the gender of the purchaser and (8) the mode of payment used when purchasing for the study period. A statistical software system, SPSS® version 20 was used to analyse the data. The study findings indicate a steady increase in the sales of the OTC codeine containing medicine over the years. Females were found to be the main purchasers of these products and the age group which purchased most of the products is the 40 to 45 years age group. The top three selling brands of the OTC codeine containing medicines were found to be Genpayne Capsules (30%), Myprodol Capsules (27%) and Mybuline Tablets (14%) of all the sales of these products in the three provinces combined. The mode of payment used for these purchases was mainly cash payment which accounted for sixty-five percent of the payments. There is a need to review the Codeine Car Initiative to monitor and audit the sales of these products so as to make an informed decision on their appropriate regulation. / MT2017

Codeine-containing medication is commonly used for pain after c-section. In most people, 10% of codeine is biotransformed into morphine by the Cytochrome P450 enzyme 2D6 (CYP2D6). Individuals who convert up to 50 fold more codeine into morphine, ultrarapid metaboizers, are at a greater risk for adverse effects. Conversely poor metabolizers, individuals who convert almost no codeine into morphine, are at risk for untreated pain. The pharmacodynamic relationship between codeine-analgesia and CYP2D6 genotype is studied for possible development of a titration model. To minimize these treatment risks, alternatives to opioids are sought. Reiki, an ancient Japanese form of healing used to treat pain and depression, has not been systematically reviewed for its efficacy in treating pain. My systematic review of Reiki literature (n=12) showed that while most trials yielded a positive result on primary outcomes, all existing Reiki studies lacked in one of the three key areas of proper patient allocation concealment, randomization or blinding which can lead to the introduction of bias. We designed a randomized controlled trial using distant Reiki for postpartum pain, taking careful steps to control for each of those three key areas. Eighty pregnant women scheduled for an elective c-section where recruited and randomly allocated to one of the two arms (n=40 Reiki and n=40 control). Women were monitored in hospital for up to three days. Visual Analogue Scores (VAS) for pain were recorded 4 times per day; and all pain medication, adverse effects and milestone recovery rates after c-section were recorded. Blood samples were taken to determine CYP2D6 genotype. We determined that distant Reiki did not reduce women’s pain; neither the measured pain nor the cumulative dose of pain medication differed between groups. Moreover, rates of recovery after c-section were also not different between the two groups. This led to the conclusion that distant Reiki was not suitable as a primary method of controlling pain after c-section. Our second study (n=45) looked for correlation between CYP2D6 genotype and effectiveness of codeine analgesia. Only a small sample of the women were genetic extremes (n=2 poor metabolizers and n=3 ultrarapid metabolizers), while most were, as expected, extensive or intermediate metabolizers. An individual examination of each of these cases provided valuable insight into patients where CYP2D6 polymorphism is clinically relevant. Two of the three ultrarapid metabolizers stopped opioid analgesia due to adverse effects, while both poor metabolizers complained that the codeine-containing medication was not providing analgesia (i.e. ineffective pain treatment). Healthcare providers need to be aware of patient response to pharmacotherapy and use this information to individualize postpartum opioid analgesia.

Codeine-containing medication is commonly used for pain after c-section. In most people, 10% of codeine is biotransformed into morphine by the Cytochrome P450 enzyme 2D6 (CYP2D6). Individuals who convert up to 50 fold more codeine into morphine, ultrarapid metaboizers, are at a greater risk for adverse effects. Conversely poor metabolizers, individuals who convert almost no codeine into morphine, are at risk for untreated pain. The pharmacodynamic relationship between codeine-analgesia and CYP2D6 genotype is studied for possible development of a titration model. To minimize these treatment risks, alternatives to opioids are sought. Reiki, an ancient Japanese form of healing used to treat pain and depression, has not been systematically reviewed for its efficacy in treating pain. My systematic review of Reiki literature (n=12) showed that while most trials yielded a positive result on primary outcomes, all existing Reiki studies lacked in one of the three key areas of proper patient allocation concealment, randomization or blinding which can lead to the introduction of bias. We designed a randomized controlled trial using distant Reiki for postpartum pain, taking careful steps to control for each of those three key areas. Eighty pregnant women scheduled for an elective c-section where recruited and randomly allocated to one of the two arms (n=40 Reiki and n=40 control). Women were monitored in hospital for up to three days. Visual Analogue Scores (VAS) for pain were recorded 4 times per day; and all pain medication, adverse effects and milestone recovery rates after c-section were recorded. Blood samples were taken to determine CYP2D6 genotype. We determined that distant Reiki did not reduce women’s pain; neither the measured pain nor the cumulative dose of pain medication differed between groups. Moreover, rates of recovery after c-section were also not different between the two groups. This led to the conclusion that distant Reiki was not suitable as a primary method of controlling pain after c-section. Our second study (n=45) looked for correlation between CYP2D6 genotype and effectiveness of codeine analgesia. Only a small sample of the women were genetic extremes (n=2 poor metabolizers and n=3 ultrarapid metabolizers), while most were, as expected, extensive or intermediate metabolizers. An individual examination of each of these cases provided valuable insight into patients where CYP2D6 polymorphism is clinically relevant. Two of the three ultrarapid metabolizers stopped opioid analgesia due to adverse effects, while both poor metabolizers complained that the codeine-containing medication was not providing analgesia (i.e. ineffective pain treatment). Healthcare providers need to be aware of patient response to pharmacotherapy and use this information to individualize postpartum opioid analgesia.

No description available.

Thesis (M.S.)--University of Wisconsin--Madison, 1940. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 24-27).

No description available.

Graduation date: 1999

Diss. (sammanfattning) Linköping : Univ., 2001. / Härtill 5 uppsatser.

The opiate alkaloid (-)-morphine and the Amaryllidaceae alkaloid (-)-galanthamine are well known for their analgesic and anticholinergic properties, respectively. The chemical feature that connects these two molecules is that they are both biosynthesized from an ortho-para phenolic oxidative coupling. Attempts to mimic this aesthetic chemistry in the laboratory for the practical production of these alkaloids have not resulted in good yields of these compounds and there is a lot of scope for improvement. Despite the enormous amount of work devoted to this area, the simple para-alkylation of an appropriately substituted phenol derivative to generate a cross conjugated 2, 5-cyclohexadienone has not been reported. This strategy would avoid the low-yielding phenolic oxidation reaction and the product would merely require a double reductive amination of the aromatic aldehyde and the latent aldehyde (in the acetal) to produce narwedine, the synthetic precursor to (-)-galanthamine. On the other hand, the same intermediate can be elaborated to (±)-morphine via a Henry reaction, followed by reduction and reductive amination. Following the aforementioned methodology, we have successfully completed the synthesis of both these alkaloids via the common intermediate, a 2, 5-cross-conjugated cyclohexadienone. A demonstration of the use of this methodology towards achieving an enantioselective synthesis of these compounds has also been made. The overall yield of the 8 step procedure for galanthamine proceeds in 65% yield, which is approximately five times the yield of the current manufacturing process for this molecule. The synthesis of (±)-morphine, for the first time, allows access to codeine without having to reduce codeinone and, with an overall yield of 20% for the 14 step process, makes this the shortest synthesis of morphine. / text

Currently, there is a growing body of research characterizing the blood-brain barrier (BBB) under normal physiological conditions; however, little is known about BBB regulation under pathophysiological conditions, such as inflammatory pain. This dissertation elucidates peripheral inflammatory pain effects on the BBB both functionally in terms of permeability and structurally via tight junction (TJ) protein expression and regulation.Inflammation was produced by subcutaneous injection of formalin, lambda-carrageenan, or complete Freund's adjuvant (CFA) into the right hind paw of rats. In situ perfusion and Western blot analyses were performed to assess BBB integrity after inflammatory insult. In situ brain perfusion determined that peripheral inflammation significantly increased the uptake of a membrane impermeant marker, sucrose into the cerebral hemispheres in all inflammatory models. Subsequently, a 0-168h time course study of lambda-carrageenan-induced inflammatory pain elicited a biphasic increase in BBB permeability of sucrose with the first phase occurring from 1-6h and the second phase occuring at 48h. Lambda-carrageenan-induced inflammatory pain also increased brain uptake of a commonly used analgesic, codeine at the same time-points. This is the first known observation that peripheral inflammation results in greater analgesic drug uptake to the brain. This uptake also correlated with its antinociceptive profile over a 168h time course. This suggests the presence of inflammatory pain may be an important consideration in therapeutic drug dosing, potential adverse effects and/or neurotoxicity.Western blot analyses showed altered TJ protein expression during peripheral inflammation. Occludin significantly decreased in the lambda-carrageenan- and CFA-treated groups. ZO-1 expression was significantly increased in all pain models. Claudin-1 protein expression was present at the BBB and remained unchanged during inflammation. Actin expression was significantly increased in the lambda-carrageenan- and CFA-treated groups. Over a 72h time period with lambda-carrageenan-induced inflammatory pain, altered TJ protein expression of occludin and ZO-1 correlated with permeability changes in BBB function. This is the first report of peripheral inflammation inducing alterations in TJs and increasing permeability of the BBB. This dissertation demonstrates that changes in the structure of TJs leading to alterations in the BBB may have important clinical ramifications concerning central nervous system homeostasis and therapeutic drug delivery.