EXPERT OPINION ON CODEINE AND CODEINE CONTAINING DRUGS

Kodein (3 metil morfin) bir opiat olup analjezik, antitüssiv, antidiareik ve diğer bazı tıbbi amaçlar için kullanılabilmektedir. Afyonda (Papaver somniferum) bulunan alkoloidler içerisinde morfinden sonraki en baskın opioiddir ve %3 oranında bulunur. Ülkemizde analjezik olarak paracetamol (Aferin kapsül, Geralgine K tablet), asetilsalisilik asit (Dolviran tablet) ve nonsteroidantienflamatuarlarla (Nurofen Plus) birlikte kombine olarak kullanılmaktadır. Birleşmiş Milletler Tek Sözleşmesi'nin eki listelerden II nolu listede (UN 61 Single Convention - Schedule II ) yer almaktadır. Bu nedenle tıbbi kullanımı hariç, sözleşmeye taraf her ülkede üretimi, ithali, ihracı, bulundurulması ve kullanımı yasaklanmıştır. İllegal olarak tablet veya toz formunda, tek başına veya diğer uyuşturucu ve uyarıcı maddelerle birlikte satılmaktadır. Kodein içeren medikal preparatlar da suiistimal edilmektedir. Kodeinli öksürük şurubu, enerji içeceği ve şeker ile hazırlanan ve özellikle hip hop camiası arasında yaygın olan argo kullanımda "Purple Drunk" adlı içecek en önemli suistimal maddelerindendir. Kodein ile ilişkili ölümler konusunda yapılmış 107 olguluk bir çalışmada, vakaların 101 adedinin toksikolojik analizinde kodeine %62 oranında asetaminophen, %20 oranında salisilatın eşlik etmekte olması kodein içeren ilaçların suiistimalini ortaya koymaktadır. Tıbbi müstahzarların içerisinde yer alan kodeinin kö- tüye kullanımında, preparatların içerisindeki kodein miktarının az olması nedeni ile ilaç fazla miktarda içilmektedir. Bu durum bireyi söz konusu müstahzarın içerisinde bulunan parasetamol, asetil salisilik asit gibi diğer ilaç etken maddelerinin toksik etkisi ile karşı karşıya bırakmakta ve gastrointestinal kanama, renal tubüler asidoz ve sensorinöral işitme kaybına neden olmaktadır. Bu yan etkilerden kaçınmayı bilen deneyimli kullanıcılar, sosyal medya aracılığı ile tıbbi müstahzarlarda bulunan diğer maddelerden kodeinin nasıl kolayca ayrılacağını açıklayarak deneyimsiz diğerlerini bilgilendirmektedir. Önerilen metot soğuk su ekstraksiyonu olarak adlandırılmaktadır.Codeine (3-methylmorphine) is an opiate used for analgesic, antitussive, antidiarrheal and some other medical purposes. It is the second-most predominant alkaloid in Papaver somniferum, at up to three percent. Codeine is used as an analgesic in a combinated form with paracetamol (Aferin capsule, Geralgine K tablet), acetylsalicylic acid (Dolviran tablet), and nonsteroidal anti-inflammatory drugs (Nurofen Plus) in Turkey. Codeine is listed at appendix Schedule II under the 1961 United Nations Single Convention on Narcotic Drugs. For this reason it's production, manufacture, export, import, possession or use except for medical purposes is prohibited at all signatory countries. It is illegally sold pure or in combination with other psychotropic substances at the form of tablet or powder. Medical preparations containing codeine are also abused. "Purple Drunk" slang termed drink which is especially popular in hip hop community and prepared with codeine containing cough syrup, energy drink and candy is one of the most important recreational drugs. The fact that codein was detected in toxicological analysis of 101 cases together with acetaminophen (62%) and salicylate (20%) in a research of 107 cases on codeinerelated deaths reveals the abuse of codein containing medical preparations. In the abuse of codeine containing medical drugs, large amounts are ingested due to low codein concentration of preparations. This fact confronts the individual with toxic effects of other active medical substances such as paracetamol or acetylsalicylic acid found in these preparations and causes gastrointestinal bleeding, renal tubular acidosis, and sensorineural hearing loss. The experienced users who know to avoid these side effects inform the less experienced others by means of social media, explaining how to easily separate codeine from other ingredients of medical preparations. The recommended method is called "cold water extraction"

DOSE DEPENDENT EFFECTS OF CAFFEIC ACID PHENETHYL ESTER ON HEART RATE AND BLOOD PRESSURE IN RATS

Aim: Caffeic acid phenethyl ester (CAPE) is one of the major components of honeybee propolis and its structure is similar to flavonoids. The molecular mechanisms of the effects of CAPE on various systems including cardiovascular system have not been known well. The aim of the present study was to investigate the short term dose dependent in vivo cardiovascular effects including heart rate and blood pressure changes induced by CAPE in Sprague Dawley rats. Methods: The rats were anaesthetized and randomly divided into six groups (n:6 rats) as follows: the first two groups of rats were injected 0.9% NaCl or 10% alcohol; the other groups were injected 1 mg kg-1, 5 mg kg-1 10 mg kg-1 or 20 mg kg-1 CAPE i.v. Results: CAPE injection caused decrease in mean blood pressure (MBP) up to 20 sec. for 1 mg CAPE group and up to 2 min for 5 and 10 mg CAPE groups. On the other hand, heart rate (HR) was found to be decreased up to 10 min. for 10 mg CAPE group Conclusion: CAPE causes decrease in both HR and MBP and may affect conduction velocity and contractility in heart due to possible effects on neuronal transmission

The effects of ginkgo biloba extract on plasma glutathion peroxidase, superoxide dismutase, adenosine deaminase and nitric oxide levels in cisplatin-induced nephrotoxicity

Amaç: Sisplatin (CDDP) geniş spekturumlu platin türevi bir antineoplastik ajandır. Kuvvetli nefrotoksisite riskinden dolayı tedavide kullanımı oldukça kısıtlıdır. CDDP’nin böbrek dokusunda yaptığı hasarın altında yatan mekanizma büyük oranda reaktif oksijen ürünleri (ROS)’ne bağlıdır. Ginkgo biloba ekstraktı (GBE)= Egb 761, birçok organ ve dokunun birbirinden farklı ama ortak olarak serbest radikallerin öncelikli rol oynadığı patolojilerinde kullanılmakta olup tedavide faydalı etkisi olduğu görülmüştür. Bu çalışma GBE’nin sisplatin nefrotoksisitesine karşı koruyucu etkisinin olup olmadığını tespit etmek amacıyla planlanmıştır. Gereç ve Yöntemler: Bu çalışmada erkek Sprague Dawley sıçanlar (60 günlük) kullanıldı. Hayvanlar rastgele seçilerek 4 gruba ayrıldı: Kontrol grubu (n= 7), IP 7 mg/kg’dan tek doz CDDP (Cisplatin, Ebewe) uygulanan grup (n= 8), CDDP ile birlikte IP 10 mg/kg E-vit (Evigen-Aksu) verilen grup (n= 9), CDDP ile birlikte oral 100 mg/kg GBE uygulanan grup (n= 7). Deneysel işlemlerden 10 gün sonra hayvanların kanları alınarak uygulanan ajanların plazma oksidan/antioksidan sisteme olan etkileri araştırıldı. Bulgular: Veriler istatistiksel olarak incelendiğinde; CDDP alan sıçanların plazma glutatyon peroksidaz (GSH-Px) aktivitesinde azalma söz konusu iken, adenozin deaminaz (ADA) aktivitesinde ve nitrik oksit (NO) değerlerinde artışa rastlanmıştır. Plazma süperoksit dismutaz (SOD) aktivitesinde, gruplar arasında herhangi bir değişiklik olmamıştır. CDDP + E-vit verilmesi ile GSH-Px ve ADA aktivitelerinde kontrole yakın olmak üzere NO değerlerinde de bir düzelme gözlenmiştir. CDDP + GBE alan grubun GSH-Px aktiviteleri sadece CDDP alan gruba göre anlamlı derecede artmıştır (p< 0.014). GBE aynı zamanda CDDP ile artmış olan ADA ve NO değerlerinde istatistiksel olarak anlamlı olmayan belirgin bir azalma sağlamıştır. Sonuç: Bu sonuçlara göre CDDP ile oluşturulan nefrotoksisitenin temelinde hücre savunma sisteminin bozulması söz kosudur. Antioksidan özelliği olan GBE, burada kısmen koruyucu bir etkinlik göstermiştir. CDDP nefrotoksisitesinde GBE’nin kesin tedavi edici bir ilaç olarak değerlendirilebilmesi için henüz çok erkendir. Bu nedenle farklı doz, farklı süre ve farklı denek sayılarıyla yeni çalışmaların yapılması uygun olacaktır.Objective: Cisplatin (CDDP), derived from platinium, is a broad-spectrum antineoplastic agent. It has not commonly been used as a therapeutic agent because of its nephrotoxicity risk. The underlying mechanism in nephrotoxi-city has been attributed to reactive oxygen species (ROS). Gingko biloba extract (GBE, Egb 761) has been shown to be effective on some organ and tissue pathologies induced by ROS. The aim of this experimental study was to determine whether antioxidant GBE has a preventive effect on nephrotoxi-city induced by CDDP through oxidative damage. Material and Methods: Male Sprague Dawley rats (60 days old) were used in the experiments. Rats were randomly assigned to one of four groups: control or untreated rats (n=7); rats treated with i.p. injection in a single dose of 7 mg/kg body wt CDDP (Cisplatin, Ebewe) (n=8); rats treated with CDDP plus i.p. injection of 10 mg/kg body wt vitamin E (Evigen-Aksu, Turkey) (n=9); and rats treated with CDDP plus oral administration of GBE in a dosage of 100 mg/kg body wt (n=7). After 10 days of experimental procedure, animals were euthanized by bleeding, kidneys were removed and oxidant and antioxidant parameters were examined to determine the effects of agents as applied to the rats. Results: In treated rats, the activity of plasma glutathion peroxidase (GSH-Px) was decreased, but adenosine deaminase (ADA) and nitric oxide (NO) levels were increased with CDDP. The activity of superoxide dismutase (SOD) remained unchanged in all study groups. Upon treating the rats with CDDP + vit E, the activities of GSH-Px and ADA, and the level of NO were improved. In the case of CDDP + GBE application, we determined an increased activity of GSH-Px in comparison with the rats treated with CDDP (p&lt;0.014). GBE also decreased the levels of ADA and NO, which were increased in the CDDP-treated group. Conclusion: In keeping with the results, the main underlying mechanism in CDDP-induced nephrotoxicity appears to be due to renal tubular cell damage. GBE appeared to induce a beneficial therapeutic effect in this study. However, we can not yet consider GBE to be a new therapeutic agent in CDDP nephrotoxicity until further studies with various doses, different time intervals, and more animal numbers have been provided

The efficacy of vitamin E and erdosteine on metabolic enzyme activities of bleomycin-induced lung fibrosis in rats

Amaç: Bu çalışmada deneysel olarak i.t. BLM uygulanması ile sıçan akciğerinde oluşturulan fibrozisde E vitamini (E vit) ve erdosteinin hekzokinaz (HK), glukoz-6-fosfat dehidrogenaz (G6PD), laktat dehidrogenaz (LDH) ve malat dehidrogenaz (MDH) enzim aktiviteleri üzerine etkilerinin araştırılması planlandı. Gereç ve Yöntem: Sıçanlar I. kontrol (n=8), II. BLM (i.t. tek doz, 7.5 ü/kg) (n=9), III. BLM + E vit (intra peritoneal, 10 mg/kg, 16 gün) (n=9), IV. BLM + erdostein (oral, 10 mg/kg, 16 gün) (n=10) şeklinde 4 gruba ayrıldı. Bulgular: Kontrol grubu ile BLM grubu karşılaştırıldığında, akciğer dokusu HK, G6PD, LDH ve MDH aktivitelerinde BLM grubunda önemli artış olduğu bulundu. BLM grubu ile BLM + E vit ve BLM + erdostein grupları karşılaştırıldığında bütün enzim aktivitelerinde kontrol grubuna yakın önemli bir azalma olduğu gözlendi.Sonuç: BLM diğer dokulara kıyasla çok fazla etkilediği akciğer dokusunda, glukozun girdiği ana metabolik yolların enzimlerini olumsuz yönde etkilediği, E vit ve erdosteinin çalışılan enzim aktiviteleri üzerine daha çok koruyucu yönde etki gösterdiği söylenebilir. Bununda muhtemel sebebinin, BLM'nin akciğer dokusu hasarı oluştururken serbest oksijen radikallerini oluşturması, buna karşılık uyguladığımız antioksidan karakterli E vit ve erdostein maddelerinin serbest radikal süpürücü etkileri ile kısmen hücre ve doku bütünlüğünü koruyarak stabilizasyon sağlaması olduğu söylenebilir.Purpose: In this study the effect of vitamin E and erdosteine on the activity of hexokinase (HK), glu-cose-6-phosphate dehydrogenase (G6PD), lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) has been assessed in BLM induced lung fibrosis in rats. Materials and Methods: Rats were divided into fourgroups; I-Control (n=8), II- BLM (i.t. one dose 7,5 u/kg) (n=9), III- BLM + vitamin E (intraperitoneal, 10 mg/kğ, 16 day ) (n=9), IV- Blm + erdostein (oral, 10 mg/kg, 16 day) (n=10). Results: The activities of HK, G6PD, LDH and MDH were measured in lung tissue. There was significant increase in enzyme activities in treated rats compared to controls. All of the enzyme activities significantly decreased nearly to the levels of controls in both of the treatment groups (BLM + vitamin E and BLM + erdosteine). The reduction in enzyme activities were similar between treatment groups (BLM + vitamin E and BLM + erdosteine). Conclusion: BLM alters the enzyme activities of main metabolic pathway (especially on lung tissue). It may be suggested that there were preventive effects of vitamin E and erdosteine on the activities of HK, G6PD, LDH and MDH in lung tissue. These results indicate that erdosteine may be a promising drug for protection against bleomycin-induced lung fibrosis

Protective effect of Nigella sativa oil against thioacetamide-induced liver injury in rats

antioxidant which is known to have liver protective effects, against thioacetamide (TAA)-induced liver injury. Accordingly, we aimed to investigate the toxicity of a hepatotoxic agent, thioacetamide, compared the NSO and NAC liver preventive effects in experimental animal model. Wistar-albino rats were randomly allocated to five groups, each consisting of eight rats, and were subjected to different treatment regimens for 6 days. Alanine aminotransferase (ALT), malondialdehyde (MDA), and protein carbonyl (PC) levels decreased significantly by NSO treatment (P [Med-Science 2017; 6(1.000): 96-103

Melatonin regulation of some important metabolic enzymes during intestinal ischemia/reperfusion injury in rats

Intestinal ischemia/reperfusion (I/R) injury is known to result from both tissue hypoxia and the consequences of reperfusion of ischemic tissues. In addition, ATP stores are depleted during ischemia because of the relatively inefficient production of ATP by glycolysis. In this study, the effect of melatonin on some important metabolic enzymes hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PD), lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) responsible for generation of energy was investigated. Melatonin was determined to cause a distinct regulation of these enzymes. While the activity of the enzyme HK of the first step of glycolysis was significantly higher in pre-melatonin treated I/R group than group I/R animals, the activities of LDH and G6PD were decreased markedly with melatonin application. Although, the MDH levels of pre-melatonin treated I/R group were higher than the sham control group, this might not be a result of melatonin application, since both I/R and I/(Mel/R) groups also showed even higher MDH activity than the control group

The effect of cafeic acid phenethyl ester on the activities of metabolic enzymes after cisplation-induced nephrotoxicity in rats

Amaç: Daha önceden yaptığımız çalışmada sisplatin nefrotoksitesi üzerine kafeik asit fenetil ester'in (CAPE) koruyucu etkisi olduğu gösterilmiştir. Bu çalışmada, daha önceki çalışmamızda kullanılan sıçanların böbrek dokuları yeniden analiz adildi ve sisplatinin böbrek dokusunda hekzokinaz (HK), glukoz-6-fosfat dehidrogenaz (G6PD), laktat dehidrogenaz (LD1I) ve m a la t dehidrogenaz (MDH) enzim aktiviteleri üzerine etkisi ve buna CAPE'nin koruyucu etkisi araştırıldı. Metod: 22 adet sıçan üç gruba ayrıldı. Grup-I (n=6): sadece intraperitoneal izotonik NaCl; Grup-II (n=9): tek dozda 7 mg/kg sisplatin ve Grup-III (n=7): sisplatin uygulamasından 2 gün önce başlamak üzere CAPE lOfimol/kg 1x1 intraperitoneal yolla 7 gün verildi. Yedinci gün anestezi altında dekapite edilerek öldürülen sıçanların böbrek dokuları alındı. Böbrek dokusunda hekzokinaz (HK), glukoz-6-fosfat dehidrogenaz (G6PD), laktat dehidrogenaz (LDH) ve malat dehidrogenaz (MDH) aktiviteleri spektrofotometrik olarak ölçüldü. Bulgular: Sisplatin böbrek dokusunda HK ve G6PD aktivitelerinde kontrol grubuna göre anlamlı bir artmaya neden oldu (p0.05). CAPE verilen sıçanlarda kontrol ve sisplatin grubuna göre LDH aktivitesinde anlamlı bir artma bulundu (Sırasıyla, p0.05). Üç grupta da MDH aktivitesi değişmedi (p>0.05). Sonuç: Sisplatinle hasarlanmış böbrek dokusunda, HK ve G6PD enzimi gibi karbonhidrat metabolizmasında rolü olan enzimlerin aktivitelerinin artabileceği gösterilmiştir.Aim: In a former study, we have showed that CAPE has preventive effect on cisplatin-induced nephrotoxicity. In this study we re-analyzed the renal tissues of the rats used formerly and investigated whether cisplatin has any effects on hexokinase (UK), glucose-6-phosphate dehydrogenase (G6PD), lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) enzyme activities in renal tisssues, and the possible preventive role of CAPE on this effect. Methods: The study was performed with 22 rats in 3 main groups: group I (n=6): 0.9% saline solution was applied to the rats intraperitoneally (i.p.); group II (n=9): 7 mg/kg single dose cisplatin was administered i.p.; and group III (n=7): 10/umol/kg from lOftmol/ml CAPE solution was administered daily 1x1 begining 2 days before cisplatin administration. At the /7th day of treatment, the rats were killed by decapitation under anesthesia, autopsied and their kidney tissues were removed. Spectrophotometric methods were used to determine the activities of above-mentioned enzymes in the kidney tissue. Results: The results of the experiment demonstrated that HK and G6PD activities were increased significantly in the cisplatin group compared with the control group (p&lt;0.05). The most increase of HK was seen in the CAPE group. CAPE prevented the increases of G6PD activities nonsignificantly (p&gt;0.05). LDH activity was increased significantly in the CAPE group compared with cisplatin group or the control group (p&lt;0.05). Cisplatin did not affect solely the LDH activity (p&gt;0.05). There was no significant difference in the LDH activity between cisplatin and control groups, and nor in the MDH activities among cisplatin, CAPE, and control groups (p&gt;0.05). Conclusion: From these results, it can be concluded that the activities of enzymes playing role in carbohydrate metabolism like HK and G6PD may increase in the course of cisplatin-induced nephrotoxicity process

ORIGINAL ARTICLE - COMPARATIVE EFFECTS OF LOSARTAN AND ENALAPRIL ON SERUM DIGOXIN LEVELS IN PATIENTS WITH CONGESTIVE HEART FAILURE

The aim of this study was to investigate the effect of AT1-receptor antagonist, losartan usage in place of angiotensin converting enzyme (ACE) inhibitor, enalapril, in patients with congestive heart failure (CHF) on serum digoxin concentrations. The study was performed in 17 patients (14 men, 3 women) with CHF of New York Heart Association (NYHA) functional class II. Their ages ranged from 42-73 (61.9 ± 2.4) years and they all were being treated with enalapril and digoxin at the time of the study. Serum digoxin levels were measured after 15 days of enalapril treatment just before taking digoxin dose in the morning and 2 and 6 hours after digoxin medication. Then, losartan was added to treatment instead of enalapril and after 15 days, serum digoxin levels were measured again in the same patients. Trough serum digoxin levels were 1.19 ± 0.09 ng/mL after 15 days of enalapril treatment and 1.30 ± 0.13 ng/mL after 15 days of losartan treatment, the digoxin levels at two and six hours after the morning dosage were 1.79 ± 0.18 and 1.43 ± 0.13 ng/mL after enalapril treatment, and 1.88 ± 0.16 and 1.37 ± 0.12 ng/mL after losartan treatment. Losartan treatment did not change the serum digoxin concentrations compared to enalapril treatment. Using losartan instead of enalapril in patients with CHF receiving enalapril together with digoxin did not affect serum digoxin concentrations

Ankaferd Blood Stopper Is More Effective Than Adrenaline Plus Lidocaine And Gelatin Foam In The Treatment Of Epistaxis In Rabbits

BACKGROUND: Epistaxis is an important emergency that can sometimes be life threatening without effective intervention. Persistent and recurrent bleeding can lead to aspiration, hypotension, hypoxia, or even severe and mortal cardiovascular complications. Providing prompt hemostasis is important, and the hemostatic method used must be easily and locally applicable, efficient, and inexpensive. OBJECTIVE: The aim of this study was to assess the hemostatic efficacy of Ankaferd Blood Stopper (ABS) in an experimental epistaxis model and to determine the histopathologic alterations with topical ABS application. METHODS: Twenty-eight New Zealand rabbits were evaluated in 4 study groups. Topical ABS, gelatin foam (GF), adrenalin + lidocaine (AL), and serum physiologic as negative control (C) were applied to the animals for controlling epistaxis. The bleeding was generated with a standard mucosal incision in all groups. Cotton pieces soaked with ABS, AL, C, and GF were applied to the nasal bleeding area. Time of hemostasis was recorded. Tissue samples were obtained after hemostasis for histopathologic examination. The samples were stained with hematoxylin and eosin (HE) and phosphotungstic acid hematoxylin (PTAH) and were examined under a light microscope. In this experimental study, the observers were blind to ABS, AL, and C but not to GF, because of its solid nature. RESULTS: Median durations required for hemostasis in ABS, AL, GF, and C groups were recorded as 30, 90, 90, and 210 seconds, respectively. The time until termination of bleeding in the ABS group was significantly shorter than that in the AL, GF, and C groups (P = 0.002, P = 0.002, and P = 0.001, respectively). On histopathologic evaluation, after staining with HE, minimal fibrin at the incision edges and a few extravasated erythrocytes were observed in the C, AL, and GF groups. In the ABS group, a dark amorphous material surrounded by fibrin, filling the space between the edges of incisions, was noticed. Fibrin was determined in the C, GF, and AL groups with PTAH stain and in the positive control group. In the ABS group, it was observed that the amorphous substance surrounded by fibrin seen in the HE sections was not stained with PTAH. CONCLUSIONS: Topical nasal ABS application controlled epistaxis faster than C, GF, and AL in this animal bleeding model. The bleeding model used here might fail to replicate the type of injury that would be likely to result in life-threatening bleeding in humans, which should be considered a limitation of the present study. The histopathologic findings in the nasal incision area suggest that ABS might affect global hemostasis by inducing a unique protein network formation, potentially representing a different mechanism of action among conventional antihemorrhagic applications. (Curr Ther Res Clin Exp. 2011;72:185-194) (C) 2011 Elsevier HS Journals, Inc. All rights reserved.WoSScopu