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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(1) The standard treatment for type 1 diabetes is intensive insulin therapy, with at least 3 daily subcutaneous injections. Insulin is sometimes useful in type 2 diabetes, in which case the first-line treatment is an injection of isophane insulin at bedtime, in addition to ongoing oral antidiabetic therapy. (2) Pfizer has been granted marketing authorization in the EU for a powdered insulin product for pulmonary inhalation, for the treatment of adults with type 1 or type 2 diabetes. Two dose strengths are available (1 and 3 mg). (3) When inhaled, the insulin powder acts as rapidly as subcutaneous lispro insulin and lasts as long as a standard insulin injection. (4) Inhalation of 1 mg of insulin powder has similar glucose-lowering effects as 3 units of subcutaneous insulin, but inhalation of 3 mg is comparable to 8 units rather than 9 units of injected insulin. Three inhalations of 1 mg each have more glucose-lowering potency than a single inhalation of 3 mg. (5) None of the clinical trials published thus far have assessed the effects of inhaled insulin on clinical complications of diabetes. (6) In patients with type 1 diabetes, 7 randomised trials have compared inhaled insulin plus 1 or 2 subcutaneous injections of long-acting insulin with standard or intensive insulin therapy. They failed to show that intensive insulin therapy consisting of 3 insulin inhalations plus 1 or 2 injections of long-acting insulin reduced the HbA1c concentration or the frequency of hypoglycaemia more effectively than standard insulin therapy consisting of 2 daily subcutaneous insulin injections. (7) In type 2 diabetes, the addition of inhaled insulin has not been compared with the addition of injected insulin in patients whose glycaemia is not controlled by oral antidiabetic therapy. (8) In type 2 diabetes, 3 randomised trials have compared intensive insulin therapy based on inhaled insulin to subcutaneous insulin (2 to 4 daily injections), without oral antidiabetic drugs. The results suggest that glycaemic control is similar with both treatments. (9) The adverse effects of inhaled insulin have been assessed in fewer than 4000 patients participating in clinical trials, fewer than 600 of whom were treated for more than a year. During treatment lasting a few months, the most frequent short-term adverse effects (other than hypoglycaemia) seem to be mild respiratory adverse effects (cough, upper airway infections, etc.). (10) Treatment with inhaled insulin causes a gradual reduction in the peak expiratory flow rate (not convincingly shown to be reversible after the end of treatment) as well as a high incidence of anti-insulin antibodies. The possible long-term clinical consequences of these changes are unknown. The results of planned, long-term comparative trials should be available in 2014-2016. (11) The assessment of inhaled insulin in patients with respiratory disorders is inadequate. The effect of acute respiratory tract infections on the efficacy of inhaled insulin has not been adequately assessed. (12) Smoking (active or passive) and salbutamol, to a lesser extent, have important effects on the efficacy of inhaled insulin. (13) The insulin powder is very sensitive to high humidity, which can occur under normal conditions, leading to a risk of under-dosing. (14) The inhalation device is much larger than an injector pen. It does not permit precise insulin dose adjustment and delivers a maximum of 8 units per inhalation. (15) In practice, the many unknowns concerning the adverse effects of long-term treatment with inhaled insulin powder will probably not be resolved before 2016. In the meantime, subcutaneous injection remains the standard method of insulin delivery.
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PMID:Inhaled human insulin: new drug. No short-term advantages, too many unknowns in the long term. 1716 35

Syncope is a transient, self-limiting loss of consciousness usually leading to a fall. The onset of syncope is relatively rapid and the subsequent recovery is spontaneous, complete and usually prompt. As syncope is a symptom, the aim of the diagnostic work-up is to assess whether there is a syncope or another "nonsyncopal" condition, whether there are clinical features suggesting the diagnosis, whether the patient has an increased risk for mortality or recurrent episodes, and whether the patient must be admitted to hospital. The diagnostic work-up is given for two cases: a 68-year-old male with insulin-dependent diabetes experienced his first syncope after lunch. The clinical judgment suggested a neurocardiogenic syncope. The initial evaluation consisting of history, physical examination and twelve-lead ECG evidenced that the patient received several drugs for arterial hypertension so that an orthostatic hypotension had to be ruled out. The twelve-lead ECG showed a left bundle branch block suggesting an arrhythmic syncope and the need for additional diagnostics: an echocardiography mainly to assess the left ventricular function which was normal, and a 24-h long-term ECG to rule out arrhythmias which were not observed. The patient gets an explanation of his risk and the reassurance about his excellent prognosis and some preventive lifestyle modifications such as sufficient volume intake. The second case is a sick 58-year-old male with tracheal cough und aggravating breathing who had a syncope on his way to the toilette. The cause of the syncope was related to a bronchitis with high fever. The patient received a causative treatment and recovered completely.
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PMID:[Syncope]. 1718 Jun 54

Inhaled human insulin (Exubera) is a rapid-acting regular human insulin administered by oral inhalation before meals. It provides a non-invasive alternative to multiple subcutaneous injections for the treatment of hyperglycemia in adult patients with type 1 and type 2 diabetes. Compared with subcutaneous rapid-acting insulin analogs, Exubera provides equivalent HbA1c control. As a monotherapy or in combination with oral agents, Exubera also provides greater glycemic control than oral agents alone, at least in patients with high levels of HbA1c. Exubera demonstrates improved patient satisfaction compared with subcutaneous insulin or oral agents alone. When offered as a treatment option together with standard treatments in uncontrolled patients naive to insulin, Exubera increases acceptance of insulin therapy three-fold compared with patients offered standard regimens only. Exubera is well tolerated in comparison to subcutaneous insulin, with a similar incidence of mild to moderate hypoglycemia. Although cough is a common adverse effect early in therapy, this leads to treatment discontinuations in less than 1% of patients. Despite an increased incidence of insulin antibodies compared with subcutaneous administration, and a consistent but minor impact on pulmonary function, long-term safety data of up to 4 years continue to support the safety profile of Exubera.
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PMID:Inhaled human insulin (Exubera): clinical profile and patient considerations. 1758 78

In the article some merits and some limitations of inhaled insulin (Exubera produced by Pfizer) in the treatment of adult patients with type 1 or 2 diabetes were presented. Up till now about 3500 volunteers usually in short-term study periods (6 months) were examined. Some patients were observed in the course of treatment even 4-7 years. Inhaled insulin was well tolerated by patients and they accepted with satisfaction this new form of drug. Main adverse events were a small decrease in the forced expiratory volume at 1 s (FEV1) and a small decline in carbon monoxide diffusion capacity with no clinical significance a well as a mild or moderate cough occurring temporally. Inhaled insulin is contraindicated in smokers and patients with bronchial asthma, bronchitis and pulmonary emphysema. Despite the approval of inhaled insulin for use in adult patients with type 1 or 2 diabetes in the United States and European Union in January 2006, Pfizer designed Real World Trial to estimate the costleffectiveness of this drug and the effect of the availability of Exubera as a treatment options for glycemic control.
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PMID:[Perspectives of inhaled insulin treatment]. 1772 16

Angiotensin converting enzyme (ACE) inhibitors usually cause severe coughing and intolerance while antagonists for angiotensin AT(1) receptor do not stimulate the production of nitric oxide (NO). NO has been shown to regulate arterial hypertension and insulin resistance. Hence, new hybrids of antagonist for angiotensin AT(1) receptor and a NO donor may have potent anti-hypertensive effect and regulate glucose metabolism and insulin resistance. Herein, the effects of [6-(nitrooxymethyl)pyridin-2-yl] methyl 4'-[1-(1,7'-dimethyl-2'-propyl-1H,3'H-2,5'-bibenzo[d]imidazol-3'-yl)ethyl] biphenyl-2-carboxylate (WB1106), a novel NO-releasing derivative of telmisartan newly synthesized, on the vasocontraction, hypertension and diet-induced insulin resistance were examined in vitro using rat aortic strips and in normotensive and spontaneous hypertension rats (SHR rats). Apparently, WB1106 induced the vasorelaxation of contracted rat aortic strips in a dose- and time-dependent manner, which depended on the activity of guanylate cyclase, a characteristic of NO-related function. Furthermore, WB1106 reduced the contractile and blood pressure responses to angiotensin II, which relied on the release of telmisartan. Moreover, treatment with WB1106 significantly reduced the blood pressure with similar potency to telmitarsan and increased the contents of cGMP in SHR rats. Therefore, WB1106 possesses both the angiotensin AT(1) receptor antagonist activity of telmisartan and the NO-releasing property of a 'slow NO donor'. Importantly, in contrast to equimolar telmisartan, treatment with WB1106 significantly attenuated body weight gains and improved glucose tolerance in high-fat and carbohydrate-fed rats, reflecting a synergistic effect of NO and telmisartan. Potentially, WB1106 may be a potent anti-hypertensive drug for treatment of hypertension and diabetes-related cardiovascular diseases in the clinic.
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PMID:WB1106, a novel nitric oxide-releasing derivative of telmisartan, inhibits hypertension and improves glucose metabolism in rats. 1782 96

Cortex Lycii Radicis (CLR) has been used as a traditional Oriental medicine as an antipyretic and to treat pneumonia, night-sweats, cough, hematemesis, inflammation, and diabetes mellitus for centuries. This study aimed to determine the effects of CLR on alloxan-induced diabetic mice and its mechanisms. Based on thin-layer chromatography (TLC) assay, the main compounds of CLR include an organic acid, flavone, alkaloid, polysaccharide, anthraquinone, and saponin. The mice were divided into four groups: normal control (NC), diabetes control (DC), diabetes+high-dose CLR (200 mg kg(-1)), and diabetes+low-dose CLR (100 mg kg(-1)). The diabetic mice were administered CLR daily for 28 days. The CLR treatment resulted in significant decreases in fasting blood glucose, total cholesterol, and triglycerides. CLR also showed a tendency to improve body weight gain in diabetic mice. Furthermore, the serum insulin level of each group was assayed, and the DC group had a lower serum insulin level than the NC group. Insulin levels were dose dependently raised in the CLR-treated groups compared with the DC group. According to single-cell gel electrophoresis and LD(50) analysis, CLR was nontoxic to the animals. The results indicate that CLR alleviates the blood glucose and lipid increases associated with diabetes and improves the abnormal glucose metabolism and increases insulin secretion by restoring impaired pancrease beta-cells in alloxan-induced diabetic mice. The results suggest that CLR has hypoglycemic potential and could be useful in diabetes therapy.
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PMID:Hypoglycemic effects and mechanisms of action of Cortex Lycii Radicis on alloxan-induced diabetic mice. 1791 29

European Union has recently approved a form of insulin intended to be inhaled. This innovative presentation has the potential to partially or completely replace the injections and thus facilitate starting insulin therapy which is considered with apprehension and too often differed. On this occasion, we reviewed the issues raised by this pulmonary route for systemic absorption (anatomical and cytological limits, cellular mechanisms, relevant physical parameters, facilitating chemical cofactors, role of tobacco smoking and of common respiratory diseases). The pharmacokinetics of inhaled and injectable insulins are comparable, apart from an appreciably faster absorption of the former and both show the same intra-individual variability. The total biodisponibility is definitely lower with the inhaled way but it is notably increased in smokers. These characteristics can vary according to the inhalation system used. A frequent induced cough, the increase in circulating anti-insulin antibodies and a potentially higher cost are not really determining obstacles. The indications will have to be clearly specified and the long-term inocuity of long term inhalation of such a mitogene especially in children and former smokers remains to be formally proven.
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PMID:[Inhaled insulin: a model for pulmonary systemic absorption?]. 1844 82

Over the past few years significant steps forward have been made towards the development of insulin formulations suitable for inhalation via several delivery systems. This innovative route of insulin delivery offers the potential of administering pre-meal insulin in a non-invasive way to patients currently receiving multiple daily injections. This article describes the pharmacodynamic and pharmacokinetic profiles and the efficacy and safety data of inhaled insulin preparations. Particular emphasis is placed on Exubera, which currently has the largest pool of efficacy and safety data. In patients with type 1 diabetes 24-week trials have demonstrated that inhaled insulin was equally efficacious to short acting insulin (2-4 daily injections). Results of trials conducted in type 2 diabetes showed inhaled insulin efficacy too, and a potential role for inhaled insulin in patients failing oral medications. Safety data have shown that the most common reported adverse event is mild cough, which appears to be decreasing in frequency during the course of therapy. Higher antibody titers have been observed in patients treated with inhaled insulin compared to subjects treated with sub-cutaneous insulin. However, the titers do not present any association with clinical correlates. The safety area in need of higher scrutiny is naturally the area of pulmonary function tests (PFTs). A brief synopsis of PFTs is followed by the review of PFTs data following short and long term treatment with inhaled insulin. Two-year data in type 2 diabetes showed a significant change in Forced Expiratory Volume in 1 second (FEV1) after 6 months of treatment, but not after 9, 12,18,24 months of treatment and 6 and 12 months of wash-out. In type 1 diabetes a significant change in Diffusing Lung Capacity of Carbon Monoxide (DLCO) was observed after 24 weeks of inhaled insulin therapy. Long-term data in type 1 diabetes are only available as part of a pooled sample composed of patients with both type 1 and type 2 diabetes. In these patients, who had received inhaled insulin for at least 4 years, annualized changes of FEV1 and DLCO were similar in the group treated with inhaled insulin compared to the group treated with sub-cutaneous insulin.
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PMID:Inhaled insulin: a novel and non-invasive way for insulin administration? 1869 Sep 26

After more than 80 years of history the American and European Drug Agencies (FDA and EMEA) approved the first pulmonary delivered version of insulin (Exubera) from Pfizer/Nektar early 2006. However, in October 2007, Pfizer announced it would be taking Exubera off the market, citing that the drug had failed to gain market acceptance. Since 1924 various attempts have been made to get away from injectable insulin. Three alternative delivery methods where always discussed: Delivery to the upper nasal airways or the deep lungs, and through the stomach. From these, the delivery through the deep lungs is the most promising, because the physiological barriers for the uptake are the smallest, the inspired aerosol is deposited on a large area and the absorption into the blood happens through the extremely thin alveolar membrane. However, there is concern about the long-term effects of inhaling a growth protein into the lungs. It was assumed that the large surface area over which the insulin is spread out would minimize negative effects. But recent news indicates that, at least in smokers, the bronchial tumour rate under inhaled insulin seems to be increased. These findings, despite the fact that they are not yet statistical significant and in no case found in a non-smoker, give additional arguments to stop marketing this approach. Several companies worked on providing inhalable insulin and the insulin powder inhalation system Exubera was the most advanced technology. Treatment has been approved for adults only and patients with pulmonary diseases (e.g., asthma, emphysema, COPD) and smokers (current smokers and individuals who recently quitted smoking) were excluded from this therapy. Pharmacokinetics and pharmacodynamics of Exubera are similar to those found with short-acting subcutaneous human insulin or insulin analogs. It is thus possible to use Exubera as a substitute for short-acting human insulin or insulin analogs. Typical side effects of inhaled insulin were coughing, shortness of breath, sore throat and dry mouth. Physical exercise increases the transport of inhaled insulin into the circulation and in consequence the likelihood of hypoglycemia. Other problems were the inability to deliver precise insulin doses, because the smallest blister pack available contained the equivalent of 3 U of regular insulin and this dose would make it difficult for many people using insulin to achieve accurate control, which is the real goal of any insulin therapy. For example, someone on 60 U of insulin per day would lower the blood glucose about 90 mg/dl (5 mmol) per 3 U pack, while someone on 30 U a day would drop 180 mg/dl (10 mmol) per pack. Precise control was not possible, especially compared with an insulin pump that can deliver one twentieth of a unit with precision. Another disadvantage was the size of the device. The Exubera inhaler, when closed, was about the size of a 200 ml water glass. It opened to about twice the size for delivery. To our information also other companies (Eli Lilly in cooperation with ALKERMES, Novo Nordisk (AERx, Liquid), Andaris (Powder)) stopped further development and it is unclear whether an inhaled form of insulin will ever be marketed, because of the problems that have occurred. Only Mannkind (Technosphere, Powder) is still working on a Phase III trial. However, our review will briefly summarize the experience regarding inhalant administration of insulin and will describe potential future developments for this type of therapy focussing on the lung.
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PMID:Inhaled insulin--does it become reality? 1921 34

Elevated blood pressure levels are highly prevalent and are a major reason for cardiovascular events and thus place a significant financial burden on healthcare systems worldwide. Guidelines recommend five first-line anti-hypertensive drug classes, but compelling indications may indicate favoring one drug class over another. Angiotensin receptor blockers (ARBs) have demonstrated a blood pressure lowering efficacy which is at least comparable with other drug classes, including ACE inhibitors (ACE-I), beta-blockers, calcium channel blockers and diuretics. They have, in addition, a lower side effect profile than other drug classes and patients on ARBs are more persistent with therapy. Compelling indications for the use of ARBs are heart failure, post-myocardial infarction, diabetic nephropathy, proteinuria/microalbuminuria, left ventricular hypertrophy, atrial fibrillation, metabolic syndrome and ACE-I induced cough. The ARB irbesartan has demonstrated a high efficacy in lowering blood pressure, which has been shown to be at least comparable with ACE-Is and superior to other ARBs such as losartan and valsartan. This translated into a better cost-effectiveness for irbesartan than for valsartan and losartan in the treatment of hypertension. In addition, irbesartan has been shown to be effective in both early and late stage diabetic nephropathy. It has further demonstrated considerable cost savings over standard therapy including beta-blockers, diuretics and non-dihydropyridine calcium channel blockers at all stages of kidney disease. Based on efficacy data from the Irbesartan Diabetic Nephropathy Trial and Reduction of Endpoints in NIDDM (non insulin dependant diabetes melitis) with the Angiotensin II Antagonist Losartan Study, it has also demonstrated cost savings over losartan in late stage renal disease. While both losartan and irbesartan are registered for the treatment of late stage diabetic nephropathy, irbesartan is also registered for early stage diabetic nephropathy in the EU. In summary, the data from randomized clinical trials on the efficacy of antihypertensive drugs provides an indication of their real value to patients. In addition observational data from clinical practice and proven end-organ protection in diabetic nephropathy provides further evidence of the true value of irbesartan compared to other ARBs in the treatment of hypertension.
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PMID:The value of irbesartan in the management of hypertension. 1960


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