Pharmacol Rep
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Statins are considered to be safe, well tolerated and the most efficient drugs for the treatment of hypercholesterolemia, one of the main risk factor for atherosclerosis, and therefore they are frequently prescribed medications. The most severe adverse effect of statins is myotoxicity, in the form of myopathy, myalgia, myositis or rhabdomyolysis. Clinical trials commonly define statin toxicity as myalgia or muscle weakness with creatine kinase (CK) levels greater than 10 times the normal upper limit. ⋯ This review focuses on a number of them. The prevention of statin-related myopathy involves using the lowest statin dose required to achieve therapeutic goals and avoiding polytherapy with drugs known to increase systemic exposure and myopathy risk. Currently, the only effective treatment of statin-induced myopathy is the discontinuation of statin use in patients affected by muscle aches, pains and elevated CK levels.
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The kynurenine aminotransferases (KATs) KAT I and KAT II are pivotal to the synthesis of kynurenic acid (KYNA), the only known endogenous glutamate receptor antagonist and neuroprotectant. KAT I and II have been found in avian, rodent, and human retina. Expression of KAT I in Müller cell endfeet and KAT II in retinal ganglion cells has been documented. ⋯ In DBA/2J mice, a model of ocular hypertension, an age-dependent decrease of retinal KYNA and KATs was found. In the corpora amylacea in the human retina intensive KAT I and II immunoreactivity was demonstrated. In summary, these findings point to the potential involvement of KYNA in the mechanisms of retinal aging and neurodegeneration.
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Oxycodone is a valued opioid analgesic, which may be administered either as the first strong opioid or when other strong opioids are ineffective. In case of insufficient analgesia and/or intense adverse effects such as sedation, hallucinations and nausea/vomiting a switch from another opioid to oxycodone might be beneficial. Oxycodone is administered to opioid-naive patients with severe pain and to patients who were unsuccessfully treated with weak opioids, namely tramadol, codeine and dihydrocodeine. ⋯ Another new product that was launched recently is a combination of prolonged-release oxycodone with prolonged-release naloxone (oxycodone/naloxone tablets). The aim of this review is to outline the pharmacodynamic and pharmacokinetic properties, drug interactions, dosing rules, adverse effects, equianalgesic dose ratio with other opioids and clinical studies of oxycodone in patients with cancer pain. The potential role of oxycodone/naloxone in chronic pain management and its impact on the bowel function is also discussed.
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In most cancer patients, pain is successfully treated with pharmacological measures such as opioid analgesics alone or opioid analgesics combined with adjuvant analgesics (co-analgesics). Opioids for mild-to-moderate pain (formerly called weak opioids) are usually recommended in the treatment of cancer pain of moderate intensity. ⋯ Its unique mechanism of action, analgesic efficacy and profile of adverse effects are responsible for its successful use in patients with different types of acute and chronic pain, including neuropathic pain. The aim of this article is to summarize the data regarding pharmacodynamics, pharmacokinetics, possible drug interactions, adverse effects, dosing guidelines, equipotency with other opioid analgesics and clinical studies comparing efficacy, adverse reactions and safety of tramadol to other opioids in cancer pain treatment.
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The risk of cardiotoxicity is the most serious drawback to the clinical usefulness of anthracycline antineoplastic antibiotics, which include doxorubicin (adriamycin), daunorubicin or epirubicin. Nevertheless, these compounds remain among the most widely used anticancer drugs. The molecular pathogenesis of anthracycline cardiotoxicity remains highly controversial, although the oxidative stress-based hypothesis involving intramyocardial production of reactive oxygen species (ROS) has gained the widest acceptance. ⋯ Numerous antioxidants, although efficient in cellular or acute animal experiments, have failed to alleviate anthracycline cardiotoxicity in clinically relevant chronic animal models or clinical trials. In addition, studies with chelators that are stronger and more selective for iron than ADR-925 have also yielded negative or, at best, mixed outcomes. Hence, several lines of evidence suggest that mechanisms other than the traditionally emphasized "ROS and iron" hypothesis are involved in anthracycline-induced cardiotoxicity and that these alternative mechanisms may be better bases for designing approaches to achieve efficient and safe cardioprotection.