Diabetes is a metabolic disorder characterized by relative or absolute deficiency of insulin, resulting in hyperglycemia. The main treatment of diabetes relies on subcutaneous insulin administration by injection or continuous infusion to control glucose levels, besides oral hypoglycemic agents for type 2 diabetes. Novel routes of insulin administration are an area of research in the diabetes field as insulin injection therapy is burdensome and painful for many patients. Inhalational insulin is a potential alternative to subcutaneous insulin in the management of diabetes. The large surface area, good vascularization, immense capacity for solute exchange and ultra-thinness of the alveolar epithelium facilitates systemic delivery of insulin via pulmonary administration. Inhaled insulin has been recently approved by Food and Drug Administration (FDA). It is a novel, rapid-acting inhaled insulin with a pharmacokinetic profile that is different from all other insulin products and comparatively safer than the previous failed inhaled insulin (Exubera).

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Objectives: To compare anti-inflammatory effect of atorvastatin and rosuvastatin in patients of acute coronary syndrome. Materials and Methods: The study was a prospective, open-labeled, randomized and single-center study conducted on 100 patients of acute coronary syndrome. Patients were assigned to atorvastatin 40 mg daily or rosuvastatin 20 mg daily for 4 weeks. C-reactive protein (CRP) levels, lipid profiles, erythrocyte sedimentation rate (ESR) and adverse effects were measured at beginning and at the end of 4 weeks. Results: Baseline parameters and clinical profile did not differ between the two groups. CRP levels significantly decreased from beginning to the end of 4 weeks in both atorvastatin and rosuvastatin groups (from 35.48 to 23.07 mg/l and from 35.88 to 19.91 mg/l respectively, both P < 0.001). However, there was significant difference between the levels of CRP in patients of the rosuvastatin group as compared to the atorvastatin group (19.91 ± 6.32 vs 23.07 ± 7.47, P < 0.05). In addition, both the drugs were associated with a reduction in total cholesterol, LDL levels and ESR at the end of 4 weeks as compared to the beginning (P < 0.001 for all comparisons). Conclusion: Both atorvastatin (40 mg) and rosuvastatin (20 mg) are effective in decreasing CRP and LDL cholesterol levels even in a short duration of 4 weeks. Rosuvastatin was found to be more effective in decreasing CRP levels.

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Opioid-induced constipation (OIC) is one of the most troublesome and the most common effects of opioid use leading to deterioration in quality of life of the patients and also has potentially deleterious repercussions on adherence and compliance to opioid therapy. With the current guidelines advocating liberal use of opioids by physicians even for non-cancer chronic pain, the situation is further complicated as these individuals are not undergoing palliative care and hence there cannot be any justification to subject these patients to the severe constipation brought on by opioid therapy which is no less debilitating than the chronic pain. The aim in these patients is to prevent the opioid-induced constipation but at the same time allow the analgesic activity of opioids. Many drugs have been used with limited success but the most specific among them were the peripherally acting mu opioid receptor antagonists (PAMORA). Methylnaltrexone and alvimopan were the early drugs in this group but were not approved for oral use in OIC. However naloxegol, the latest PAMORA has been very recently approved as the first oral drug for OIC. This article gives an overview of OIC, its current management and more specifically the development and approval of naloxegol, including pharmacokinetics, details of various clinical trials, adverse effects and its current status for the management of OIC.

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Objective: To assess the pulmonary function and quality of life in asthma patients receiving vitamin D₃ supplementation with inhaled budesonide and formoterol. Materials and Methods: This was a double blinded, randomized, comparative study. Patients were recruited as per the study criteria and randomized into two groups: usual care group (n = 69) patients received budesonide (800 μg) with formoterol (24 μg) and intervention care group (n = 72) patients received vitamin D₃ (1000 IU) supplementation along with budesonide (800 μg) plus formoterol (24 μg) for a period of 6 months. Results: A total of 140 patients completed the study. Significant within-group improvement and non-significant between-group improvement is observed with respect to FEV₁. In terms of health-related quality of life, within-group comparison revealed a significant (P < 0.05) improvement in all the domains of SGRQ. However, between-group comparisons showed statistically significant (P < 0.05) improvement in symptom, impact and total scores. Conclusion: On the basis of our findings, we conclude that supplementation of vitamin D₃ is effective in improving the quality of life rather than pulmonary function in severe asthmatics. However, further studies are warranted to substantiate the present findings.

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Rocuronium is a non-depolarizing neuromuscular blocking agent (NDNMBA), employed in the clinic as an adjunct to general anesthesia to facilitate tracheal intubation rapid sequence, and to provide skeletal muscle relaxation during surgery. Many cases of resistance to neuromuscular blocking agents (NMBAs) have been anecdotally reported. There are specific pathologic states, such as upper motor neuron lesions, severe thermal injuries, liver disease, renal failure, disuse atrophy, all of which show an increased resistance to the effects of nondepolarizing muscle relaxants. Also concurrent drug therapy can alter the efficacy of NMBAs such as some classes of antibiotics, furosemide, β receptor agonists, phosphodiesterase inhibitors, calcium antagonists, respiratory stimulants but also ketamine, propofol and barbiturates at high concentrations. In this scenario we describe an unusual case of 20-years-old man who showed a complete resistance to rocuronium maybe due to a glucocorticoids concomitant therapy.

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Objective: To investigate the ability of sildenafil to inhibit the contractility of isolated non pregnant human myometrium. Materials and Methods: The inhibitory effect of three concentrations (3, 10, and 30 µM) of sildenafil on 55 mM KCl-induced contractility of isolated non-pregnant human myometrium was studied. The ability of the guanylyl cyclase inhibitor ODQ (10 µM), the adenylyl cyclase inhibitor MDL-12,330A (10 µM), the non-specific potassium channel blocker TEA (2 mM), and the calcium-sensitive potassium (BKCa) channel blocker iberiotoxin (100 nM) to reverse the inhibition of 10 µM sildenafil on KCl-induced myometrial contractility was also studied. Results: Sildenafil produced a concentration-dependent inhibition of KCl-induced myometrial contractility that was statistically significant at all three concentrations of sildenafil used. The inhibition by 10 µM sildenafil of KCl-induced myometrial contractility was not reversed by the concurrent administration of ODQ or MDL-12,330A. The inhibition of 10 µM sildenafil of myometrial contractility was partially reversed by concurrent administration of TEA and totally and significantly reversed by the concurrent administration of iberiotoxin. Conclusions: These results suggest that sildenafil inhibits the contractility of isolated non-pregnant human myometrium. The results suggest that sildenafil does so by opening BKCa channels.

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We report a rare case of exercise-induced anaphylaxis (EIA), occurring exclusively with exercise, without any other associated trigger, detected in the prodromal phase, and prevented from additional anaphylaxis episodes by treatment with cetirizine and 10 mg daily of antileukotriene montelukast to date. EIA is a syndrome in which patients experience a spectrum of the symptoms of anaphylaxis ranging from mild cutaneous signs to severe systemic manifestations such as hypotension, syncope, and even death after increased physical activity. Many people have triggers, such as, a variety of foods, various medications, alcohol, cold weather, humidity, and seasonal and hormonal changes along with exercise that cause the symptoms. Typically, either exercise or the specific trigger alone will rarely cause symptoms. It is differentiated from cholinergic urticaria by the absence of response to passive body warming and emotional stress.

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We report a case of a 41-year-old lady, who developed severe hypotension and sinus bradycardia, following oral consumption of 20 g of phenytoin and 500 mg of glibenclamide. She required high dose of inotropes and a temporary transvenous pacer for her hemodynamic instability. This life-threatening cardiotoxicity of phenytoin could have been due to its interaction with sulphonylurea. It is imperative to be aware of drug interactions, due to which, life-threatening cardiovascular manifestations following phenytoin toxicity can occur.

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Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic drugs. They control both fasting and postprandial hyperglycemia by inhibiting degradation of incretin hormones, such as, glucagon-like peptide-1(GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Sitagliptin is the first DPP-4 inhibitor to be marketed in India. In addition to its glucose lowering effect, it also suppresses immunity resulting in various infections in a diabetes patient. Here, we describe the simultaneous development of two infections (acalculous pyelonephritis and cholecystitis) in a postmenopausal female patient, well-controlled on sitagliptin-based anti-diabetic therapy.

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Psoriasis is a common, chronic, disfiguring, inflammatory, and proliferative condition of the skin. It manifests with varying degrees of severity and can be treated with various immune modulators. This is a case report of a 57-year-old male patient of psoriasis on long-term oral methotrexate, who developed methotrexate toxicity when given an injection of methotrexate for unstable psoriasis. After recovery, the patient was started on cyclosporine 100 mg twice a day. After a week, he developed thrombocytosis, which reverted a week after cyclosporine was stopped. The patient is currently being managed with acitretin. The aim of this case report is to emphasize the various unpredictable adverse reactions encountered during treatment of psoriasis, especially when a combination or sequential treatment is used. There is a need for caution, as late sequelae of long-term administration of the systemic agents used in the treatment of psoriasis are still unknown.

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Introduction: To investigate the actions of adenosine A_2B receptor modulators on VEGF and NO levels in CsA nephropathy. Materials and Methods: Nephropathy was induced by administrating 25 mg/kg (s.c) of CsA for 5 weeks. The VEGF and NO levels were measured in kidney tissue. Serum creatinine, creatinine clearance, urinary albumin excretion, blood urea nitrogen, kidney pathology score were measured to assess renal function. The analysis of mRNA expression of A_2B receptor and VEGF was performed. Results: Administration of CsA for 5 weeks induced adverse renal function. The mRNA expression of VEGF was reduced in renal tissue after 5 weeks of CsA treatment. The renal VEGF and NO levels were also reduced in these animals. In vivo administration of A_2B adenosine receptor agonist increased renal VEGF which was inhibited by a selective A_2BAR antagonist (MRS1754) in CsA-treated animals. The increase in VEGF was associated with reversal of adverse renal functions. The effects of A_2BAR modulators were prominent in CsA-treated animals compared with control animals suggesting CsA treatment may upregulate A_2BARs. The mRNA expression of A_2BAR was increased after 5 weeks of CsA. Conclusions: A_2BAR modulators may provide new therapeutic options to retard CsA nephropathy by mediating renal VEGF and NO.

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Baclofen is a gamma- aminobutyric acid B (GABA B) agonist used for the management of spasticity associated with spinal cord injury. Oral baclofen might cause constipation, but intestinal pseudo-obstruction is very rare. We report a 50-year-old male with spasticity following cervical discectomy (C3-4) on oral baclofen for 6 months with intestinal pseudo-obstruction. He had undergone open suprapubic cystostomy for traumatic urethral injury, 45 days prior to the presentation and adhesive intestinal obstruction was also considered a possibility. However, there were no air fluid levels on abdominal radiographs and ultrasound abdomen was non-contributory. Withdrawal of baclofen was therapeutic in this patient. This case is being reported to highlight the rare possibility of oral baclofen induced intestinal pseudo-obstruction.

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Adverse drug reactions play a substantial role in the etiology of gynecomastia. Gynecomastia as an adverse drug reaction, related to some cardiovascular drugs, has been reported in literature. Nebivolol is a third generation beta-blocker, and gynecomastia as an adverse effect on the consumption of this drug has not been reported in any article yet. We herein present the case of a 42-year-old male, who developed bilateral gynecomastia following nebivolol use and complete regression after discontinuation of nebivolol. Other reasons causing gynecomastia were excluded. Discontinuation of the responsible drug is quite sufficient with regard to the treatment of drug-induced gynecomastia, without any pharmacological or surgical treatment.

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