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Photo by Wolfgang Sterneck : www. The first flight I ever took to a Muslim country, a passenger behind me started freaking out mid-flight. He was in his mids, he was German, he had done so much cocaine that he thought he was having a heart attack. Such a shame for the young man. He could have just waited to start the party on arrival in Egypt. Our flight was going from Berlin direct to Hurghada, an Egyptian resort on the Red Sea where a young German with some money to spend would have no trouble getting blitzed, blazed, sunburned and laid. But for one local, legitimate discontent, you only need look at the post-colonial resort culture on the Red Sea. Hurghada was an abomination from the moment we stepped off the plane. It was then, and is now, a jumble of trash heaps and new construction and thin dogs and wary touts and all on top of each other on a sunblasted stretch of Red Sea coast, hot and full of hustlers. But it was the cultural collision of the place that was most unsettling. Even the poorest street urchin spoke fluent German, but only for cadging, not communicating. Merchants drank tea in front of their shops, narrowed their eyes at passersby, and occasionally sang out out a lie or two about their wares. In part, that was because there is barely such a thing as a local in Hurghada. The nothingness was, at the beginning, the attraction. In , the New York Times sent foreign correspondent Christopher Wren there overland with jerry cans of extra fuel for the ride across the desert:. There is little but sun, sand and water. The unsullied beach stretches for miles, the sun shines almost every day and the swimming is little short of spectacular. Exquisite coral reefs offer some of the best scuba-diving and snorkeling in the world. Colorful fish abound in the clear salt water and lobsters as heavy as 11 pounds have been taken off the barren offshore islands. The biggest evening entertainment is still the sunset. Fast-foward a dozen years to my visit, and there was plenty to do beyond the sunset. Clubbing and drinking might be part of the European culture , but it is anathema to most Egyptians. So, too, was the sunbathing. Behind the great walls of the resort complexes, Germans and northern Italians bared all, or at least most, in an effort to capture the sunlight that the accident of their birth had denied them. On my visit to Hurghada, this free-body-culture, which is such a virtue in Germany, had an imperial feel. There could be no clearer sign that these planeloads of sunstarved visitors neither knew nor cared where they were. They paid money and so they should get do exactly as they pleased. It also meant that Muslims would not work the beach or much any other place in the Sheraton, where I had a room. And so, all the cabana boys and bartenders and groundskeepers in their Hawaiian shirts had their forearms exposed, and on those forearms you could see the tell-tale cross carved in their flesh when they were boys. I left Hurghada after a week. I would have left sooner, but a package tour is a package tour, and I was a teenager in tow of my German host family. Even twenty years ago, the nearshore reefs were a graveyard of broken coral. You had to take a boat to the offshore islands to see living coral, and even that was beginning to choke on the exhaust of the resort town. Just after my visit, the first terror attack hit the Red Sea coast, and it hit in Hurghada. It was a drive-by shooting that killed two Egyptians and a German tourist in , alleged to have been carried out by the Islamic Group, the main militant organization fighting the Egyptian government. Men hanged for that crime, but the murders marked the beginning of the security regime that now accompanies any visit to Hurghada. The marvels of Luxor, which we visited by a minibus on a day-trip, now can only be seen as part of an armed convoy of tourbuses that tries valiantly to bring it huffing tourists across the desert to the Nile Valley and back again without loss of life. Giant beach resorts like Kemer, in southwest Turkey, might resemble places like Hurghada on the Egyptian Red Sea coast, but they are actually quite different. Whereas visitors to Kemer can easily wander to neighboring towns for a fish dinner with local wine , guests at Hurghada are guarded against Islamic fundamentalists by armed soldiers and strongly discouraged from leaving the resort. Join our newsletter to get exclusives on where our correspondents travel, what they eat, where they stay. Free to sign up. Sep 25 Author: Nathan Thornburgh ,. Featured City Guides. More Guides.

Management of chronic insomnia using hypnotics: a friend or a foe?

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Official websites use. Share sensitive information only on official, secure websites. Untreated insomnia disorders have a number of adverse health consequences in addition to economic burden caused by it. Available guidelines mention that CBT-I should be preferred over hypnotics. However, several patients of chronic insomnia are not candidate for CBT-I and for them, hypnotics are the only answer. This paper reviews the literature to answer following questions: What is the current understanding regarding place of hypnotics for in management of insomnia disorder? How many patients misuse or abuse hypnotics, especially benzodiazepines, as commonly believed? Do we have data from human studies regarding low-dose benzodiazepine dependence? What does hypnotics produce—withdrawal insomnia, rebound insomnia or end of dose phenomenon? Are adverse effects of benzodiazepines worse than other psychotropic medications? Is prescription of hypnotics more troublesome than untreated insomnia disorder? Available literature suggests that there is an unreasonable negative bias attached to the use of hypnotics. Other patients either discontinue it as insomnia remits or change to occasional use since insomnia may be relapsing remitting disorder , or continue using it in low dose since insomnia reappears as hypnotics are discontinued, similar to increase in blood sugar after hypoglycemics are discontinued. Meta-analysis shows that adverse effects of hypnotics are comparable to that of other psychotropic medications. Considering the consequences and risks associated with untreated insomnia disorder, even long-term use of hypnotics is justified, however with the careful watch that patients are not increasing the dose. This approach is especially important in geographical areas where trained CBT-I therapists are not available. Insomnia disorder or chronic insomnia is one of the highly prevalent sleep disorders with significant morbidity. Treatment of insomnia has been one of the highly debated topics, since treatment outcome is often sub-optimal, from the perspectives of the treating doctor as well as that of the patient \[ 39 \]. Several guidelines are available for the management of acute and chronic insomnia among adult patients mentioning different therapeutic approaches \[ 4 , 40 , 42 , 47 , 50 \]. Recommendations are also available that addressing the management of insomnia disorder in specific age groups, i. These documents mention two different approaches for the management of insomnia- pharmacological and non-pharmacological. Non-pharmacological management of insomnia includes use of multi-model cognitive behaviour therapy for insomnia CBT-I, while a number of pharmacological agents are also mentioned \[ 4 , 40 , 42 , 50 \]. During past 20 years, a significant advancement has been achieved in pharmacological approaches to manage insomnia disorder \[ 47 \]. As of today, myriad medications are available for management of insomnia disorder that are categorized to different classes based upon their pharmacodynamic properties, e. Most of the guidelines mentioned above advocate that CBT-I should be the preferred method for addressing insomnia, while pharmacotherapy may be used for short-term treatment only, i. Arguments mentioned to avoid pharmacotherapy for insomnia including development of tolerance, dependence, and other adverse effects that may occur with hypnotics—benzodiazepines BZD and benzodiazepine receptor antagonists BZRA \[ 42 , 50 \]. The current paper was conceptualized because of the apparent reluctance of physicians in prescribing hypnotics. Common apprehensions against the use of hypnotics are abuse potential, fear of inducing dependence and facing disapproval by the peers. In this paper, we intend to review issues viz. This is a narrative review regarding use of hypnotics for the management of insomnia disorder. However, for some specific sections e. For these sections, individual papers were searched with an attempt of include latest available evidence. With the above-mentioned background, following sections will try to find out why hypnotics remain under-used in the management of insomnia disorder. To understand the intricacies of the enigma of hypnotics, familiarization with the common diagnostic entities used in contemporary classificatory systems and the issues arising from them is essential. Abuse, misuse as well as dependence, all three terms have often been used interchangeably in relation to hypnotics. According to standard definition, dependence is characterized by three pharmacological properties—tolerance, withdrawal, and craving \[ 1 \]. On the other hand, misuse pertains to the use of medication for therapeutic purpose which is not conforming to the medical or legal guidelines. Lastly, abuse refers to use of hypnotics for non-therapeutic purpose, primarily for the recreation \[ 54 , 69 \]. Thus, misuse may clinically present as long-term use of medication than intended but to achieve therapeutic effect, but is not synonymous with abuse and dependence. Laboratory as well as epidemiological evidence suggest that benzodiazepines have relatively lower abuse potential. Similar to anxiety disorder, subjects with insomnia symptoms and healthy controls do not prefer hypnotics over placebo \[ 45 \]. Reinforcement is important for continuation of substance for recreational purpose. However, reinforcing effects have been found only among patients having anxiety, insomnia and moderate alcohol consumption, especially among poly substance users \[ 16 \]. Whether the reinforcement was obtained from the relief of symptoms or the recreation could not be addressed in this paper. Most of the times, hypnotics were consumed for relieving anxiety and sleeplessness \[ 66 \]. Hypnotics, for the recreational purpose, were almost always used by persons consuming other substances—particularly opioids \[ 66 \]. Recent data regarding hypnotics suggest that 1 year prevalence of hypnotic abuse is just 1. Abuse of hypnotics was related to illicit use of other drugs such as opioids and stimulants \[ 22 \]. Interestingly, such low prevalence was observed even though, in this population-based study, subjects were prescribed hypnotics for a variety of reasons, including psychiatric disorders \[ 22 \]. Taken together, available evidence suggest that contrary to common belief, even in at-risk population, only a small number use hypnotics for recreational purpose. Moreover, most of the data regarding abuse potential of hypnotics emerges from case reports and animal studies. Data regarding misuse of hypnotics is also available. Takaesu et al. However, in these subjects, hypnotics were required to relive symptoms, not for the recreational purpose. Misuse of hypnotics is also common among subjects with other psychiatric disorders, not only insomnia. A recent study followed subjects for 1 year after their first prescription of hypnotics. These evidence suggest that long-term use of hypnotics among subjects with insomnia disorder is likely to be related to underlying pathophysiology rather than craving. Moreover, it supports the fact that hypnotics were continued for obtaining therapeutic benefit, similar to long-term therapy with anti-hypertensive and hypoglycemics. In either case, symptoms of primary disease are likely to recur when medications are discontinued. Soldatos et al. In this review, tolerance was defined as reduction in total sleep time and increase in sleep onset latency. It was reported that with intermediate and long-term use of triazolam, sleep onset latency was increased from baseline for 0. However, this was not observed with other hypnotics. Whether change in these values are clinically significant and whether they represent progression of disease insomnia disorder are questions that remain to be explored. A systematic review suggested that benzodiazepine doses remain stable over long-term use 6 months to an year , suggesting absence of tolerance in human \[ 27 \]. These data show the absence of tolerance with hypnotics. An 8-month-long zolpidem trial also suggests that tolerance to hypnotic action does not develop even after chronic use among subjects having chronic insomnia, as commonly believed \[ 44 \]. Similar results were shown by Green et al. Thus, the scientific literature does not support evidence of tolerance to hypnotics among human subjects. One of the important components of dependence is withdrawal symptoms. Data regarding withdrawal symptoms arising from the use of therapeutic doses of hypnotics are insufficient to be considered significant. Rebound insomnia has been considered as manifestation of withdrawal though mistakenly in earlier reports \[ 24 \]. Data regarding rebound insomnia are inconsistent and even when it occurs, it is usually short-lasting 1—2 nights \[ 45 \]. However, Hajak et al. Risk of rebound appears to be high with short acting medications like triazolam compared to long-acting medications viz. Thus, there is a need to carefully distinguish these entities. It has been conceptualized as dependence without tolerance. In this regard, it needs to be understood that long-term usage of benzodiazepines is not synonymous with benzodiazepine dependence. The main behavioural correlates are drug seeking behaviour manifested by doctor shopping and obtaining multiple prescriptions \[ 3 \]. Also, it needs to be understood that benzodiazepines cannot be compared to the classic substances of abuse like cocaine and opioids in the different animal models \[ 26 \]. When pretreated with alcohol and other substances, the reinforcing properties of benzodiazepines are greater, but not when they are used in isolation. Benzodiazepines do influence the dopamine secretion in the ventral tegmental area as shown in the classic studies by Tan et al. Research advocating benzodiazepine usage has collimated with that which cautions against it. The scientific views for long-term low-dose use have been synonymous with the term low-dose dependence \[ 8 , 63 \]. It has been disputed since neuro-adaptive changes were never required nor sufficed for the criteria for dependence \[ 5 , 51 \]. There were anecdotal reports stating that discontinuing benzodiazepines was a challenge in clinical practice. Systematic qualitative approach to the problem informed us of the phenomenon of non-cooperation by non-compliance from subjects treated with long-term therapeutic doses \[ 29 \]. It placed the term with an evidence base that disseminated the reference and its usage in later works \[ 56 — 58 \] Table 1. But this information should be seen in perspectives of information presented in Sects. Self-administration experiments in rhesus monkeys indicated that the animals did derive positive effects from receiving benzodiazepines and would actively seek further administration, although to a lesser extent than with barbiturates \[ 12 , 70 \]. When these experiments were continued over several weeks, the monkeys not only failed to increase their self-administration but actually reduce it by an amount not explainable by pharmacokinetic factors alone \[ 71 \]. An animal study on rats, comparing the differences between chronic high- and low-dose chlordiazepoxide demonstrated that there are similar signs of withdrawal between the two groups with statistically significant differences in the intensity of withdrawal symptoms. A conformational change in the receptors or receptor-coupled counter-adaptive changes were proposed as underlying mechanisms Guarino et al. Thus, animal studies failed to show the recreational effect, tolerance and continuation of medication over long period. The dissimilitude of overestimating sleep while being medicated and the awareness of sleep disturbance upon discontinuation was the discernment for inability to discontinue long-term therapeutic doses of benzodiazepines \[ 48 \]. This could easily be explained by hyperarousal occurring in parallel process model of insomnia \[ 43 , 46 \]. This model also shows why most of the patients suffering from chronic insomnia would continue hypnotics in long term. A recent meta-analysis reported increased risk of fractures but not falls among patients taking zolpidem, however, study was not able differentiate whether these events were related to drugs or to the effects of insomnia \[ 62 \]. Interestingly, not only hypnotics, but also antipsychotics as well as antidepressants increase risk of fall among elderly in different settings, although specific pathophysiologic mechanisms are yet to be elucidated. Among the psychotropics, the odds ratio of falls in the elderly was 2. Risk of fracture in the elderly who were prescribed benzodiazepines was 1. At-risk population for fall and fractures are those on high doses of hypnotics and having co-prescribed psychotropic medications \[ 7 \]. These observations contradict the claims of increased falls and fractures just by use of hypnotics. As of now, there is no substantial evidence that hypnotics depress respiration \[ 7 \]. In fact, a Cochrane review showed that benzodiazepines do not have any significant deterioration in the clinical severity of OSA as measured by apnea—hypopnea index AHI \[ 31 \]. On the contrary this review suggested that Z group of drugs like eszopiclone 3 mg significantly decreased AHI compared to placebo. However, studies included in this review had small sample size with short duration \[ 31 \]. A recent population-based retrospective case—control study showed that there was a statistically significant association between recent benzodiazepine use and adverse respiratory effects in patients with OSA which persisted even after multivariate adjustment. Thus, as of now, it appears that benzodiazepines do not worsen OSA in therapeutic doses. A recent longitudinal study spanning 20 years reported that hypnotics increased mortality in short term within 2 years of prescription ; however, results were confounded by inclusion of subjects with cancer and cardiovascular disorders. Another meta-analysis showed that hypnotics in fact reduce the risk of mortality from cardiac diseases, especially in Asian population \[ 25 \]. On the other hand, initial insomnia and non-refreshing sleep have been found to increase odds for all causes mortality and mortality from cardiovascular diseases \[ 13 \]. Both experimental and epidemiological studies show that hypnotics increase risk of accidents. Another controversy is whether the accidents occur due to the effect of the BZD or the effect of the insomnia disorder itself, which if left untreated induces cognitive deficits and psychomotor slowing \[ 67 \]. A number of factors play a role why hypnotics are avoided in the management of insomnia disorder. First, despite having optimal literature regarding neurobiological basis of insomnia disorder and adverse health consequences of untreated insomnia disorder, it is still not considered as a medical disorder \[ 33 \]. Second, addictive potential of hypnotics has been disproportionately highlighted in a number of meta-analysis and guidelines, however, scientific backing for the claim appears dodgy \[ 42 , 53 \]. Reappearance of symptoms after reduction of dose or discontinuation of medication is a common phenomenon in a number of diseases. Many physicians fail to realize that insomnia is a chronic disorder, similar to diabetes mellitus or hypertension and, hence, requires long-term treatment. Discontinuation of antihypertensives and hypoglycemics leads to increase in blood pressure and blood sugar, respectively, similarly, discontinuation of hypnotics would lead to re-appearance of insomnia \[ 10 \]. A paper from Perlis et al. They advocated that considering the night-to-night variability in insomnia, long-term intermittent hypnotic therapy should be explored as an option \[ 35 \]. Such strategy could reduce direct and indirect costs related to insomnia. Third, besides other reasons, hypnotic prescription was considered to be influenced by industry pressure, for which data were not provided \[ 33 \]. Most of the benzodiazepines are cheap and industry has lost interest in promoting them. While discouraging the use of hypnotics for chronic insomnia, especially in developing and third world countries, benefits and risks must be assessed carefully Fig. These factors are important and worthy of scientific investigation in the future. However, as a reaction to it, clinicians should not err on the side of restricting benzodiazepines thereby and allowing the patients to suffer from the consequences of untreated chronic insomnia. CBT-I has many limitations in terms of candidature, adherence, cost of treatment, adverse effects and is mostly not available in most parts of the world especially low- and middle-income countries. Considering these issues, benzodiazepines are the only available option and it should be prescribed to all deserving patients. Here, one needs to perform a balancing act, treating who needs to be treated and at the same time protecting the vulnerable population, e. RG conceived the study. TJ and AP searched literature. AB and RG reviewed it. RG and TJ prepared first draft. AB and AP critically reviewed it and provided scientific content to bring it to final shape. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. As a library, NLM provides access to scientific literature. Sleep Biol Rhythms. Management of chronic insomnia using hypnotics: a friend or a foe? Find articles by Aniruddha Basu. Find articles by Tanmay Joshi. Find articles by Arghya Pal. Find articles by Ravi Gupta. Studies that evaluated low-dose long-term benzodiazepine usage and withdrawal syndrome. Open in a new tab. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Diazepam 10—30 mg Lorazepam 1—7. Lorazepam 4 mg mean dose Diazepam 10 mg mean dose.

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