Buying coke online in Munster

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Buying coke online in Munster

Former Galway hurler Justin Campbell, who is now an addiction counsellor. The numbers of people being treated for cocaine addiction has tripled in six years. Picture: Ray Ryan. Cocaine use in rural Ireland is growing so much that users are now claiming it is easier to get the drugs online than pizza. As part of a new Irish Examiner focus on drug use in rural Ireland, interviewees have told this newspaper about using apps such as WhatsApp, Tiktok, and Snapchat to order cocaine and that, in some cases, the drugs are being delivered by taxi. Users and garda sources also say money is also being exchanged for deals through online payment options such as Revolut. Experts in the field say the country's current drug policy is clearly not working given the increasing number of people recreationally using. One garda source told the Irish Examiner that nothing surprises him anymore about cocaine use in Ireland. He highlighted how drug dealing has evolved from the traditional meet-ups where drugs were exchanged for cash, to social media transactions with online payment options. The GAA is now considering a motion, brought before its Congress in recent weeks, which would see all players who wish to participate in an adult championship match having to have completed courses, approved by GAA Central Council, on alcohol, gambling, and substance abuse AGSA and anti-doping education in that Championship year or the preceding one. Failure to do so would lead to a one-match suspension. As a client said to me the other day, it is easier to get cocaine online than it is a pizza. They are using social media to get it. In January, the Medical Bureau of Road Safety published its report, which highlighted that the number of tests of motorists detecting cocaine in drug driving cases almost trebled — from in to 1, in A total of 2, people were treated for problem cocaine use in Ireland in — more than three times the number of cases reported in cases , according to a report published by the Health Research Board last July. Ms Lambert says:. The increase in recreational use does indicate that current policies are not working in terms of reducing the volume of substances circulating in communities. Read More. Lunchtime News. Sign up to the best reads of the week from irishexaminer. Please click here for our privacy statement. Sign in My Account Sign out. Homepage news Cocaine 'easier to order online than pizza' in rural Ireland says hurler turned counsellor Former Galway hurler Justin Campbell, who is now an addiction counsellor. Much dereliction in our towns and villages, but also glimmers of hope. More than 2, pubs shut down since the peak of the Celtic Tiger, report finds. More in this section. RTB wants new powers to inspect properties to crack down on unregistered landlords. Subscribe Now. Sign Up. Latest Cork to host relics of St Bernadette of Lourdes for two days at the end of the month What to look out for as jumps racing proper clicks into gear Cuts to Cork City's bus service 'could be reversed', says Ryan Asylum seekers stay another night in temporary accommodation after storm damages tents. Most Read. Man, 20s, killed in West Cork after vehicle plunges over ditch. Watch: Michael Healy-Rae comes to blows with Taoiseach in bizarre animated video. Cork man who repeatedly raped his teenage sister-in-law is jailed.

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Buying coke online in Munster

Official websites use. Share sensitive information only on official, secure websites. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. In the past, interactions between drugs and vitamin D have received only little or no attention in the health care practices. However, since more and more drugs are used for the treatment of patients, this topic is increasingly relevant. Several drugs can interfere with the vitamin D and bone metabolism. Drugs that activate the pregnane X receptor can disrupt vitamin D metabolism and vitamin D function. Beside this, the medication oriented supplementation of vitamin D can ameliorate the pharmacologic action of some drugs, such as bisphosphonates, cytostatics and statins. Vitamin D has long been known for its effects on calcium and bone metabolism. Vitamin D deficiency causes a lack of bone mineralization, which manifests as rickets in children and osteomalacia in adults. Its physiological effects are not only limited to bone. Interactions between drugs and vitamin D have received only little or no attention in the medical and pharmaceutical world in the past. Since more and more drugs are used for the treatment of patients, this topic is increasingly relevant. As such interactions impact the health of the patient and the action and side effects of the drug, physicians and pharmacists should pay more attention to this fact in the future. As vitamin D deficiency leads to bone damage, it is particularly important to ensure an adequate vitamin D supply in cases of pre-existing osteoporosis or during long-term intake of drugs that promote the development of bone damage. Even after bone damage has already occurred, therapeutic use of vitamin D is often not considered. A number of drugs are known to interfere with the vitamin D metabolism through activation of the pregnane X receptor and thereby causing vitamin D deficiency. The following article discusses the mechanisms of an interaction between vitamin D and the relevant drug groups. The resultant metabolites are physiologically inactive and are excreted as acids following further metabolic stages. Expression of the hydroxylases is partially dependent on the calcium and parathyroid hormone levels in the blood and partially regulated by 1,25 OH 2 D itself. In this way, the concentration of circulating 1,25 OH 2 D and thus both calcium and phosphate homeostasis in the blood is strictly regulated. Various drugs can interfere in this balance through activation of the pregnane X receptor PXR. In the pregnane X receptor PXR of mouse was first identified as a member of the nuclear receptor NR superfamily on the basis of its sequence homology with other NRs. The pregnane X receptor can thereby bind to vitamin D-responsive elements VDRE at the DNA and, as a transcription factor, affect the expression of genes whose expression is normally regulated by vitamin D. PXR-ligands are structurally diverse and include a wide variety of pharmaceutical agents, such as antiepileptics, anti-inflammatory agents or antiretroviral drugs Table 1. Through activation of the pregnane X receptor, expression of the hydroxylases is upregulated, leading to increased degradation of 25 OH D and 1,25 OH 2 D Fig. In addition to the hydroxylases, the ligands of the pregnane X receptor induce other cytochrome P enzymes, which are involved in the biotransformation of numerous active substances e. Figure 1. PXR-mediated drug-induced degradation of vitamin D proposed model according to Pascussi, and Holick, It was documented more than 40 y ago that institutionalized children who were on multiple anti-seizure medications developed rickets that was resistant to normal vitamin D therapy. The risk of bone fractures is two to six times higher in patients with epilepsy than in the average population and comparable to that seen in patients undergoing long-term glucocorticoid therapy. AED-induced disturbances of bone integrity are mainly influenced by the type, dosage and duration of the antiepileptic therapy. A dose-dependent increase in the risk of fractures was particularly observed during therapy with carbamazepine, oxcarbazepine, clonazepam, Phenobarbital, phenytoin, primidone, and valproic acid. AED-induced disturbances of bone metabolism are usually accompanied by a fall in the 25 OH D level, hypocalcemia, secondary hyperparathyroidism, and increased bone turnover with a decrease in bone density. In the pathogenesis of AED-induced bone disease, a central role is played by the pharmacokinetic interaction between the AEDs and vitamin D: the enzyme inducers carbamazepine, phenobarbital, phenytoin, and primidone can activate the pregnane X receptor, which then upregulates expression of the hydroxylases, which can cause vitamin D deficiency. AED-induced bone disease can also occur even with more modern AEDs, such as gabapentin, lamotrigine and levetiracetam, which have little or no effect on the activity of the cytochrome enzyme, as other mechanisms are probably also involved in the development of this bone damage Table 2. Valproic acid-induced osteopathy, for example, cannot be explained by an induction of hydroxylases, as valproic acid inhibits cytochrome P enzymes and is not a ligand of the pregnane X receptor. Prophylaxis with vitamin D is recommended for all subjects using AEDs. Any deficiency should be treated as required with targeted supplementation in order to prevent osteopathy. Glucocorticoid-induced osteoporosis is one of the most significant forms of drug-induced osteopathy. Disturbances of bone mineralization are therefore always likely during long-term glucocorticoid therapy, irrespective of the route of administration oral, parenteral, inhalation ; children, adolescents and postmenopausal women are particularly at risk. Impaired bone metabolism is also possible during treatment with low-dose or intermittently administered glucocorticoids. The fracture risk depends on the daily glucocorticoid dose administered. A retrospective data evaluation of a British patient collective showed that the risk of spinal fractures in patients who took less than 2. In patients on doses of between 2. If more than 7. Furthermore, glucocorticoids reduce the production of sex hormones, thereby reducing their positive effect on the bones. Glucocorticoids also reduce intestinal calcium absorption and concurrently increase renal calcium excretion; this can lead to a fall in serum calcium levels. Some glucocorticoids e. In patients with multiple sclerosis high-dose and short-term intravenous glucocorticoid regimens can cause a decrease in bone formation. Multiple sclerosis MS is generally associated with reduced bone mass and higher frequency of osteoporosis. During long- and short-term glucocorticoid therapy, the vitamin D status should always be monitored, especially in patients with multiple sclerosis and bronchial asthma, by means of laboratory tests and any deficiency corrected by means of targeted supplementation, in order to reduce the risk of glucocorticoid-induced disturbances of bone metabolism. Beyond that, clinical evidence suggests an important role of vitamin D deficiency as a modifiable risk factor in MS. Low circulating levels of 25 OH D have been found in MS patients, especially during relapses, suggesting that vitamin D could be involved in the regulation of the clinical disease activity. Patients undergoing glucocorticoid treatment of bronchial asthma could derive a further benefit from vitamin D supplementation. Patients with low 25 OH D levels suffered considerably more often from respiratory infections than patients with normal 25 OH D levels. The lower the 25 OH D levels, the poorer the lung function values of the children and the higher the glucocorticoid doses with which the children were treated. Corticosteroid use and worsening airflow limitation were associated with lower 25 OH D serum levels in asthmatic patients. A possible explanation for this is that 1,25 OH 2 D modulates the expression of cytokines with marked anti-inflammatory and anti-allergic properties e. In vitro studies also showed that vitamin D can enhance the immunosuppressive function of dexamethasone. Further studies are required, however, to investigate whether vitamin D supplementation in patients with bronchial asthma actually reduces the frequency of respiratory infections and improves the anti-inflammatory effect of inhaled glucocorticoids. Bisphosphonates are among the most frequently prescribed drugs in osteoporosis therapy. In addition, they are used successfully in the treatment of Paget disease of bone, bone metastases of solid tumors, multiple myelomas and hypercalcemia of malignancy. Based on their structure, bisphosphonates can be divided into two groups: the amino-substituted bisphosphonates, alendronic acid, ibandronic acid, risedronic acid, zoledronic acid and pamidronic acid and the non-nitrogen-containing bisphosphonates, etidronic acid and clodronic acid. Bisphosphonates accumulate at the bone surface and are particularly absorbed in regions with increased bone turnover from osteoclasts. Through the action of various mechanisms, they subsequently lead to apoptosis of the osteoclasts and thus inhibit bone resorption. In patients with vitamin D deficiency and an insufficient calcium intake, bisphosphonate therapy without concurrent vitamin D supplementation can lead to hypomagnesemia and hypocalcemia, sometimes resulting in tetany and severe disturbance of bone mineralization. Hypocalcemia was mainly observed after intravenous administration of bisphosphonates such as zoledronic acid. On the one hand, increased parathyroid hormone levels can impair the efficacy of the bisphosphonates on bone, as parathyroid hormone is a potent stimulator of osteoclast activity. On the other hand, in the bone micromilieu, parathyroid hormone increases the production of cytokines and growth factors, which can promote tumor growth. The effect of vitamin D status on parathyroid hormone levels and the efficacy of bisphosphonate therapy on bone density was investigated in a study with postmenopausal women. The bone density in the lumbar spine was not affected by either the parathyroid hormone or the 25 OH D level. These data suggest that optimal 25 OH D serum levels may lead to further reduction in bone loss at the hip in patients on bisphosphonates. Women with vitamin D deficiency had a significantly higher risk of bone fractures than women with normal vitamin D status adjusted odds ratio 1. Optimal vitamin D repletion seems to be necessary to maximize the response to anti-resorbers in terms of both BMD changes and anti-fracture efficacy. This threshold level of 25 OH D is higher than that considered adequate by the Institute of Medicine, arguing that higher levels may be required for specific therapeutic outcomes. In persons infected with the human immunodeficiency virus HIV , the osteoporosis risk is more than three times higher than in persons not infected with HIV. It has been shown that glycoproteins of HIV-1 pgag, gp impair bone calcium utilization and reduce osteoblast activity. Upregulation of proinflammatory cytokines \[e. The risk of osteopathy is additionally increased by antiretroviral therapy. Disturbances of vitamin D metabolism, particularly an increased vitamin degradation due to induction of CYP3A4, appear to play a major role. In this study, the risk of severe vitamin D deficiency was significantly increased by intake of the non-nucleoside reverse transcriptase inhibitor efavirenz. Against this background, vitamin D administration in individuals infected with HIV appears appropriate, in order to reduce the risk of drug-induced osteopathy. Vitamin D may also reduce the mitochondrial toxicity of antiretroviral virostatic drugs, whose effects include muscle pain and lipid metabolism disorders. All these active substances are used in the treatment of estrogen receptor-positive breast cancer. As aromatase inhibitors block estrogen synthesis and thus markedly reduce estrogen levels, treatment with these active substances also results in a severe reduction of the effect of estrogens on bone. Estrogens promote intestinal calcium absorption and bone mineralization; above all, however, they inhibit osteoclast activity. Intake of aromatase inhibitors reduces bone density and increases the risk of bone fractures. Similar effects are likely following administration of a pure estrogen receptor antagonist; no data are yet available, however, on the long-term effect of fulvestrant on bones. Selective estrogen receptor modulators have estrogenic or anti-estrogenic effects, depending on the tissue. Whereas tamoxifen reduces the effects of estrogens in the breast, its effect on bone more closely resembles that of an estrogen receptor agonist and it shows a certain antiresorptive effect. Nevertheless, a decrease in bone density was observed in various studies during tamoxifen therapy, particularly in pre-menopausal women. Further side effects occurring in association with tamoxifen are bone and muscle pain and a rise in serum triglyceride levels. Aromatase inhibitor associated arthralgia limits adherence to therapy in breast cancer. The pathophysiology may involve vitamin D status. Vitamin D deficiency is associated with a syndrome of musculoskeletal symptoms with generalized nonspecific musculoskeletal pain and stiffness, as well as impaired muscle strength and function that is similar to that induced by aromatase inhibitors therapy. A prospective study with women investigated the effect of vitamin D status on the occurrence of arthralgia during treatment with aromatase inhibitors, such as anastrozole, letrozole and exemestane. Despite vitamin D supplementation with IU daily and, depending on the baseline value, sometimes with an additional 16, IU every two weeks, adequate 25 OH D levels were only achieved in half the women within a three-month period. During the course of the study, there was an increase in joint pain mean 1. In a pilot study the prevalence of suboptimal vitamin D status in 60 women initiating adjuvant therapy with letrozole for breast cancer was assessed, and determined, whether the supplementation of 50, IU vitamin D per week could reduce musculoskeletal symptoms and fatigue associated with aromatase inhibitors therapy. Baseline 25 OH D levels were obtained, and women were started on letrozole. At week 16, after 12 weeks on high-dose vitamin D, 25 OH D levels were measured. Santini and colleagues observed that 25 OH D levels fell considerably further in breast cancer patients on anti-tumor treatment with anthracyclines and taxanes, so that it can be assumed that almost all breast cancer patients have a vitamin D deficiency. According to case studies, mucocutaneous side effects e. If one considers that some cytostatic agents e. Vitamin D deficiency is an independent risk factor for hypertension. Epidemiological and clinical studies have long shown an association between inadequate exposure to sunlight, vitamin D deficiency and hypertension or increased plasma-renin activity. This is additionally underlined by the fact that mean blood pressure values are lower in summer than in winter. Animal studies have shown that vitamin D deficiency increases blood pressure through an interaction with the renin-angiotensin system. In genetically altered mice so-called vitamin D receptor null mice , which cannot synthesize vitamin D, it was observed that renin expression, the activity of the renin-angiotensin system, and the production of angiotensin II were drastically increased. The mice developed hypertension, cardiac hypertrophy, and edema. These observations correlate with those made in normal mice, in which inhibition of vitamin D biosynthesis led to a rise in renin expression, whereas the injection of 1,25 OH 2 D suppressed renin expression. Other mechanisms contributing to the antihypertensive effect of vitamin D are the direct effects of 1,25 OH 2 D on endothelial function, parathyroid hormone secretion and insulin sensitivity Fig. Vitamin D and magnesium have a mutually enhancing effect on endothelial function and vascular reactivity and on many metabolic processes e. The antihypertensive effect of magnesium has been demonstrated in numerous interventional studies. Although administration of vitamin D and magnesium alone to patients with hypertension severity II or III is not likely to normalize blood pressure according to the WHO criteria, supplementation of vitamin D and magnesium monitored by laboratory-diagnostic tests may nevertheless allow attempts to reduce the dosage of other antihypertensive substances e. This could certainly reduce many side effects of the antihypertensive drugs used e. Figure 2. Vitamin D-deficiency and development of hypertension and insulin resistance possible mechanisms. The enzyme, 3-hydromethylglutaryl coenzyme A HMG-CoA reductase, plays a key role regulating the synthesis of cholesterol. A vitamin D deficiency therefore appears to be associated with increased activity of these enzymes. A pilot study with 63 patients investigated the effect of the serum 25 OH D level on the lipid-modulating effect of atorvastatin. The informative value of this study is, however, limited by the small number of participants. As vitamin D also influences cardiovascular risk through other mechanisms e. He was inspired to write this work while his wife, Katia, was staying in a lung sanatorium in Davos in Prior to the discovery of antibiotics, periods spent in sun sanatoriums in high alpine regions were considered the standard therapy of tuberculosis. In addition to other effects on the immune system, 1,25 OH 2 D induces the synthesis of antimicrobial peptides, the so-called cathelicidins, which in turn kills the Mycobacterium tuberculosis. In a recent, multicenter, double-blind, randomized study, in addition to a standard therapy with antituberculotic drugs, patients with newly diagnosed open tuberculosis of the lung received either , IU vitamin D 3 four times at d intervals or placebo. The primary endpoint was the time from the beginning of the tuberculostatic therapy to the time when no further bacteria were detectable in the sputum. In patients in the vitamin D group, this took on average In addition, the patients were genotyped with regard to certain variants of the vitamin D receptor TaqI-variants tt, Tt, TT and the effect of the vitamin D receptor genotype on the success of the vitamin D administration was investigated. After 56 d, the mean serum calcidiol level in the drug group was The efficacy and side effect rate of several drugs can be improved by vitamin D. With regard to pharmacokinetic interactions, mediated by the pregnane X receptor, it can be assumed that the active substances described in this paper are not the only ones that interact with the PXR-VDR system and can lead to vitamin D deficiency. During long-term medication, therefore, vitamin D status \[serum 25 OH D level\] should generally be monitored and any deficiency corrected. Previously published online: www. As a library, NLM provides access to scientific literature. Find articles by Klaus Kisters. John's wort Hyperforin. Open in a new tab. 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. Carbamazepine, phenobarbital, phenytoin, primidone. Carbamazepine, phenytoin Valproic acid, carbamazepine Phenytoin. Increased bone turnover irrespective of vitamin D and parathyroid hormone levels. Vitamin K deficiency due to increased vitamin K metabolism with influence on the vitamin K-dependent modification of matrix proteins.

Buying coke online in Munster