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Tuesday, March 31, 2009

Free Medical ebooks

Free Ebooks download

Hundreds of books for free download on every medical subject arranged by title in alphabetical order.

Some of the Pharmacology books are:
  1. Download Medical Pharmacology at a Glance, 4th Edition.Free ...

    Medical Pharmacology at a Glance is one of the most renowned undergraduate texts in the field of medical pharmacology. Following on from the success of the.
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    Pharmacology: PreTest Self-Assessment and Review (Pretest Series) By Marshal Shlafer * Publisher: McGraw-Hill Medical * Number Of Pages: 430 *
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  3. Download Pharmacology,For the Health Care Professions.Free ...

    Pharmacology for the Health Care Professions is an accessible introduction to the pharmacology necessary for health care professionals training to be.
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    This book is an accessible collection of case study scenarios ideal for physiology and pharmacology revision for pharmacy, medical, biomedical science,
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  5. Download Reviews of Physiology, Biochemistry and Pharmacology free ...

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  6. Download Pharmacology 5th Edition.Free Download Link free ebook ...

    This highly acclaimed textbook is a worldwide bestseller, recognized for its emphasis on the mechanisms by which drugs act at the cellular and molecular ...
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  7. Download Pharmacometrics: The Science of Quantitative Pharmacology ...

    Pharmacometrics is the science of interpreting and describing pharmacology in a quantitative fashion. The pharmaceutical industry is integrating.
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  8. Download Clinical Pharmacology Made Ridiculously Simple (MedMaster ...

    CLINICAL PHARMACOLOGY MADE RIDICULOUSLY SIMPLE (MEDMASTER SERIES, SECOND EDITION). Get it. This entry was posted on Saturday, November 24th, ...
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  9. Download Pharmacology PreTest Self-Assessment and Review free ...

    Pharmacology PreTest Self-Assessment and Review Publisher:McGraw-Hill | Pages: 272 | 2001-08-06 | ISBN: 0071367047 | PDF | 2 MB Gives medical students 500.
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  10. Download The Serotonin Receptors From Molecular Pharmacology to ...

    The Serotonin Receptors From Molecular Pharmacology to Human Therapeutics Publisher:Humana Press | Pages:640 | 2006-06-01 | ISBN:1588295680 | PDF | 7.8 MB ...
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Monday, March 30, 2009

Free Medical Books for download

Here are links to a number of free Medical books. The links point to pharmacology books but you can get books on all Medical subjects by exploring the sites given below.
1. MEDICAL BOOKS FREE http://medicalbooksfree.com/?cat=58
This Website is intended to provide medical ebooks for free download by doctors and medical students. There are 23 pharmacology books like:
2. medical-ebooks.
http://medical-ebooks.blogspot.com/search/label/Pharmacology?max-results=7
Hundreds of Medical Books. And many books on Pharmacology for free download such as:

3. DOWNLOAD Free medical books. http://downloadfreemedicalbooks.blogspot.com/
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Pharmacology books are:

4. Med-download. http://www.med-download.blogspot.com/
Free ebooks on Medical subjects. Aditionally, there are links to a number of Antivirus softwares. Pharmacology books include:
Medical dictionaries are also present:

Friday, March 27, 2009

ACE Inhibitors or ARBs in Hypertension and/or Chronic Kidney Disease?

A pair of articles in the January 1, 2008 Annals of Internal Medicine brings together the existing literature to address issues that have persisted since the introduction of angiotensin-receptor blockers (ARBs): namely, when and how these drugs might be advantageous in conditions long served by angiotensin-converting enzyme (ACE) inhibitors.

A meticulous survey of studies found that the two drug classes are about equally safe and effective at managing high blood pressure and have similar effects on other risk factors and clinical outcomes in patients with essential hypertension. It also confirmed that ARBs are less likely to cause coughing, but suggested that the side effect might be less common with ACE inhibitors than randomized trials indicate.

In the setting of chronic kidney disease (CKD), concludes the other study, which is a meta-analysis, ACE inhibitor and ARB monotherapy are similarly effective at reducing proteinuria, but a combination of the two angiotensin-2-suppressing drugs works better than either agent individually. But a blanket recommendation to combine them would be premature, according to the authors, because there is little evidence that the combination would improve clinical outcomes over monotherapy, and the safety of such combination therapy is largely undefined.

Study Highlights

  • Essential hypertension
    • Included were studies that directly compared ACE inhibitors and ARBs of any design (RCTs, controlled trials, nonrandomized trials, cohort and case control studies) lasting at least 12 weeks and enrolling at least 20 patients, which provided direct comparison of ACE inhibitors and ARBs.
    • Outcomes examined were blood pressure control, adherence, quality of life, intermediate outcomes, and harms.
    • Of 61 studies analyzed, 47 were RCTs, 9 were retrospective cohort studies, 1 cross-sectional, 1 case control cohort, and 1 nonrandomized trial.
    • Rates of use as monotherapy were similar for the 2 classes of drugs.
    • ACE inhibitors and ARBs had similar efficacy for blood pressure control, with no significant differences in benefits or harms (strength of evidence: high).
    • Quality-of-life measures and adherence were similar for ACE inhibitors and ARBs.
    • There were no consistent differential effects seen for death and cardiovascular events.
    • Both classes of medication had similar effects on lipid levels, left ventricular mass, and risk for dysglycemia or renal dysfunction.
    • Adverse effects of headache and dizziness were similar for the 2 classes.
    • Cough as an adverse effect was 3 times more common with ACE inhibitors, with overall rates much higher in randomized trials (9.9% vs 3.2%) vs cohort-based studies (1.7% vs 0.6%).
    • The number needed to treat to cause 1 case of chronic cough for ACE inhibitors was 15.
    • The average duration of follow-up exceeded 6 months in only one third of the head-to-head studies, and there was a lack of long-term studies.
    • There was a lack of adequate studies reporting adverse effect profile of both medication classes.
  • Chronic renal disease
    • Included were RCTs of short-term (1 to 4 months) and longer-term (5 to 12 months) studies involving a total of 6181 patients with microalbuminuria and proteinuria of diabetic origin and other causes and reported changes in proteinuria during follow-up.
    • Trials were at least 4 weeks in duration with parallel group or crossover designs.
    • Excluded were studies of patients who had renal transplantation and those with less than 10 participants.
    • Of 49 RCTs, 12 compared ARBs with placebo, 9 with calcium-channel blockers, 23 with ACE inhibitors, and 16 with the combination of ACE inhibitors and ARBs.
    • 23 trials compared combination ARBs and ACE inhibitors with an ACE inhibitor alone.
    • Monotherapy with ACE inhibitors or ARBs reduced proteinuria to a similar degree but less than combination therapy.
    • Mean reduction in proteinuria with combination vs ARB monotherapy in 5- to 12-month studies was 0.75 vs 0.82 (ratio of means) with ACE inhibitors.
    • Monotherapy with ARBs reduced proteinuria vs placebo, with a ratio of means of 0.57 in 1 to 4 months and 0.69 in 5 to 12 months.
    • Results were similar for ACE inhibitors and ARBs vs calcium-channel blockers.
    • 92% of studies lacked quantitative data on adverse drug reactions.
    • In the absence of safety data on long-term combination therapy with ACE inhibitors and ARBs, therapy should be limited to those with stage 3 or 4 disease with close monitoring of potassium levels.
    • The editorialist concluded that monotherapy with ACE inhibitors or ARBs was sufficient treatment for early-stage renal disease with relatively low albumin exertion, and combination therapy was effective for patients with heavier proteinuria when monotherapy failed to decrease 24-hour urinary protein excretion to less than 0.5 g.

Summary

  • ACE inhibitors and ARBs are equivalent in efficacy for the treatment of essential hypertension, and ACE inhibitors are associated with a 3 times higher rate of chronic cough.
  • ACE inhibitors and ARBs are similar in efficacy for the treatment of proteinuria of chronic renal disease, with the combination being more effective than monotherapy with either drug, but long-term adverse effects are not well documented.
Sources:

Sources

  1. Matchar DB, McCrory DC, Orlando LA, et al. Systematic review: Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for treating essential hypertension. Ann Intern Med. 2008;148:16-29.
  2. Kunz R, Friedrich C, Wolbers M, Mann JFE. Meta-analysis: Effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann Intern Med. 2008;148:30-48.
  3. Steve Stiles, Désirée Lie. ACE Inhibitors or ARBs in Hypertension? In Chronic Kidney Disease? Medscape Medical News, Medscape Internal Medicine. January 17, 2008; Reviewed and Renewed: February 13, 2009

Thursday, March 26, 2009

Vinegar Reduces Post-Prandial Glucose

A mixture of vinegar and olive oil is the traditional salad dressing used in the Mediterranean diet. The consumption of vinegar with meals was used as a home remedy for diabetes before the advent of pharmacologic glucose-lowering therapy. Indeed modern studies indicate that vinegar significantly reduces post-meal glycemia, probably because acetic acid slows gastric emptying and thus delays carbohydrate absorption and improves satiety. Recent studies show that 1 to 2 tablespoons of vinegar, when added to a meal containing high-glycemic-index foods such as white bread or white rice, will both: 1) lower post-prandial glucose by 25% to 35% increase post-meal satiety by more than 2-fold. Thus the addition of vinegar to a standard meal can not only improve the meal-induced oxidant stress by blunting the post-prandial glucose excursion, but also can increase and prolong satiety, which should help to reduce food cravings and lower caloric intake over the subsequent 2 to 4 h. Finally, vinegar with olive oil is generally consumed with green leafy vegetables, which have superior nutrient-to-calorie ratios and very low glycemic indexes.

Sources:

Nuts, Olive Oil, and Fish Oil

Nuts, when consumed with a meal, will significantly reduce the post-prandial glucose excursion by slowing digestion. Recent studies show that almonds, pistachios, or peanuts, when eaten along with high glycemic index carbohydrates such as white bread or mashed potatoes, will reduce the post-prandial glucose area under the curve by approximately 30% to 50%. Importantly, nuts also decrease meal-induced oxidative protein damage because they lower post-prandial oxidative stress and additionally provide antioxidants.
A recent trial randomized 772 subjects at high risk for CAD to a low-fat diet or a Mediterranean-style diet supplemented with either walnuts (30 g/day) or virgin olive oil (1 l/week). This trial found that after 3 months the Mediterranean diets supplemented with either nuts or olive oil produced clinically significant reductions in systolic blood pressure, fasting glucose, and inflammatory biomarkers compared with the low-fat diet.

Epidemiologic studies consistently indicate that consumption of nuts at least 5 times per week will reduce CAD and diabetes risks by 20% to 50%. Tree nuts are comprised predominantly of monounsaturated fats and are a rich source of antioxidants, fiber, phytosterols, magnesium, and folic acid, which might beneficially influence CV risk. Replacing refined carbohydrates with monounsaturated fats (using nuts and/or olive oil) will reduce post-prandial hyperglycemia and hypertriglyceridemia, increase high-density lipoprotein, and decrease oxidative stress . One practical way to accomplish this is to substitute nuts (all of which have very low glycemic indexes) for the sugary and starchy snack foods that are staples in the American diet.

Fish oil (omega-3 fatty acids) lowers post-prandial triglyceride levels by 16% to 40% in a dose-dependent fashion, in part by upregulating lipoprotein lipase activity and accelerating the clearance of chylomicrons. Thus, some of the documented anti-inflammatory and cardioprotective activities of omega-3 fatty acids may be conferred in part by significant improvements in post-meal lipid levels

Source: James H. O’Keefe, MD*, Neil M. Gheewala, MS and Joan O. O’Keefe, RD Dietary Strategies for Improving Post-Prandial Glucose, Lipids, Inflammation, and Cardiovascular Health. J Am Coll Cardiol, 2008; 51:249-255, doi:10.1016/j.jacc.2007.10.016

Nonglycemic Effects of Incretins

In addition to their beneficial effects on blood glucose, particularly postprandial glucose, as well as body weight and pancreatic beta cell function, the glucagon-like peptide-1 (GLP-1) receptor agonists (Exenatide, Liraglutide) and dipeptidyl peptidase-4 (DPP-4) inhibitors (Sitagliptin, Vildagliptin) have other beneficial effects. These effects on blood pressure and blood lipids, although not making incretins suitable as primary therapy, may be important benefits to consider in selecting diabetes therapy, because patients with type 2 diabetes mellitus (T2DM) are at increased risk for cardiovascular disease.

Blood Pressure


GLP-1 receptor agonists and DPP-4 inhibitors produce modest reductions in systolic blood pressure and, in some cases, diastolic blood pressure. The importance of hypertension as a cardiovascular risk factor is well established. As concluded by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, each increment of 20/10 mm Hg above 115/75 mm Hg doubles the risk of cardiovascular disease.

Lipid Profile

the GLP-1 receptor agonists and DPP-4 inhibitors produce significant reductions in the triglyceride level. Exenatide and vildagliptin also produce significant improvements in total, LDL-, and HDL-cholesterol. The benefits on reducing cardiovascular risk by lowering total and LDL-cholesterol and raising HDL-cholesterol are well established. As such, they are important targets for treatment as recommended by the National Cholesterol Education Program Expert Panel - Adult Treatment Panel III

Conclusion

The GLP-1 receptor agonists and DPP-4 inhibitors lower blood pressure and improve the lipid profile, which, although not appropriate as primary therapy, makes them especially valuable treatment options for patients with T2DM. These improvements may help to reduce the risk of cardiovascular events. Various approaches can be taken to initiate and modify GLP-1 receptor agonist and DPP-4 inhibitor therapy to improve efficacy and tolerability based on patient characteristics and concomitant therapies.

References

  1. Boschmann M, Engeli S, Dobberstein K, et al. Dipeptidyl-peptidase-IV inhibition augments postprandial lipid mobilization and oxidation in type 2 diabetic patients. J Clin Endocrinol Metab. 2008. In press.
  2. Viswanathan P, Chaudhuri A, Bhatia R, et al. Exenatide therapy in obese patients with type 2 diabetes mellitus treated with insulin. Endocr Pract. 2007;13:444-450.
  3. Ratner RE, Maggs D, Nielsen LL, et al. Long-term effects of exenatide therapy over 82 weeks on glycaemic control and weight in over-weight metformin-treated patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2006;8:419-428.
  4. Vilsboll T, Zdravkovic M, Le Thi T, et al. Liraglutide, a long-acting human glucagon-like peptide-1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes. Diabetes Care. 2007;30:1608-1610.
  5. Colagiuri S, Frid A, Zdravkovic M, et al. The once-daily human GLP-1 analog liraglutide reduces systolic blood pressure in patients with type 2 diabetes. Paper presented at: American Diabetes Association 68th Scientific Session; June 6-10, 2008; San Francisco, CA.
  6. Mistry GC, Maes AL, Lasseter KC, et al. Effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on blood pressure in nondiabetic patients with mild to moderate hypertension. J Clin Pharmacol. 2008;48:592-598.
  7. Chobanian AV, Bakris GL, Black HR, et al; for the National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003;42:1206-1252.
  8. Blonde L, Rosenstock J, Sesti G, et al. Liraglutide: superior glycemia control vs exenatide when added to metformin and/or SU in type 2 diabetes. Paper presented at: Canadian Diabetes Association/Canadian Society of Endocrinology and Metabolism Annual Meeting; October 15-18, 2008; Montreal, Quebec, Canada.
  9. Scott R, Wu M, Sanchez M, et al. Efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy over 12 weeks in patients with type 2 diabetes. Int J Clin Pract. 2007;61:171-180.
  10. Rosenstock J, Brazg R, Andryuk PJ, Lu K, Stein P; for the Sitagliptin Study 019 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2006;28:1556-1568.
  11. Bolli G, Dotta F, Rochotte E, et al. Efficacy and tolerability of vildagliptin vs. pioglitazone when added to metformin: a 24-week, randomized, double-blind study. Diabetes Obes Metab. 2008;10:82-90.
  12. Rosenstock J, Baron MA, Dejager S, Mills D, Schweizer A. Comparison of vildagliptin and rosiglitazone monotherapy in patients with type 2 diabetes. Diabetes Care. 2007;30:217-223.
  13. Grundy SM, Becker D, Clark LT, et al. Third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). Final report. Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3full.pdf. Accessed January 20, 2009.
  14. Daniel A. Nadeau, MD. Incretin Benefits Beyond Glycemic Control. From Primary Care Education Consortium, Medscape Internal Medicine. Posted 03/19/2009. Available at: http://www.medscape.com/viewarticle/588945?src=mp&spon=18&uac=82830HJ

Increased physical activity in middle age is followed by a reduction in mortality comparable with that associated with smoking cessation.

From British Medical Journal

Total Mortality After Changes in Leisure Time Physical Activity in 50 Year Old Men: 35 Year Follow-up of Population Based Cohort

Objective: To examine how change in level of physical activity after middle age influences mortality and to compare it with the effect of smoking cessation.
Design: Population based cohort study with follow-up over 35 years.
Setting: Municipality of Uppsala, Sweden.
Participants: 2205 men aged 50 in 1970-3 who were re-examined at ages 60, 70, 77, and 82 years.
Main Outcome Measure: Total (all cause) mortality.
Results: The absolute mortality rate was 27.1, 23.6, and 18.4 per 1000 person years in the groups with low, medium, and high physical activity, respectively. The relative rate reduction attributable to high physical activity was 32% for low and 22% for medium physical activity. Men who increased their physical activity level between the ages of 50 and 60 continued to have a higher mortality rate during the first five years of follow-up (adjusted hazard ratio 2.64, 95% confidence interval 1.32 to 5.27, compared with unchanged high physical activity). After 10 years of follow-up their increased physical activity was associated with reduced mortality to the level of men with unchanged high physical activity (1.10, 0.87 to 1.38). The reduction in mortality associated with increased physical activity (0.51, 0.26 to 0.97, compared with unchanged low physical activity) was similar to that associated with smoking cessation (0.64, 0.53 to 0.78, compared with continued smoking).
Conclusions: Increased physical activity in middle age is eventually followed by a reduction in mortality to the same level as seen among men with constantly high physical activity. This reduction is comparable with that associated with smoking cessation.

Physical inactivity is associated with increased incidence rates of obesity, diabetes, cardiovascular diseases, osteoporosis, and cancer. Short term randomised controlled trials in young to middle aged adults have shown a healthier risk profile with exercise. It is therefore recommended that adults engage in at least 30 minutes of moderate physical activity preferably on all days of the week. Adherence to these guidelines is associated with half the risk of mortality seen in sedentary people.

Principal findings of this study
Increased levels of physical activity in middle age have an effect on mortality. After a 10 year period of increased physical activity the excess mortality seen in inactive men was reduced to the same levels of mortality as seen in physically active men. There is, however, a period of at least 5 years before this risk reduction during which the risk is higher. The halved mortality rate after 10 years of follow-up after increased physical activity between the ages of 50 and 60 (compared with continued inactivity) was similar to that seen after smoking cessation (compared with continued smoking).

Full text article at BMJ

Blood pressure lowering efficacy of angiotensin converting enzyme (ACE) inhibitors for primary hypertension

With the popularity of ACE inhibitors in mind, investigators conducted a systematic review of published studies to determine how effective the drugs actually are in reducing blood pressure. They also examined dose effectiveness, adverse effects, and the role of co-occurring conditions.

The Study Findings

Researchers looked for double-blind studies comparing ACE inhibitors and placebo. All included studies were at least 3 weeks in duration and measured blood pressure as an endpoint at 3-12 weeks. Studies that featured a response-dependent titration of medications were included in the review. Only research that focused on patients with a blood pressure above 140/90 mm Hg was reviewed.

The review included 92 trials with a total of 12,954 participants (mean age, 54 years). Mean baseline blood pressure was 157/101 mm Hg and mean pulse pressure was 56 mm Hg. The majority (75%) of included studies was industry-sponsored, and 82% of the trials examined fixed-dose ACE inhibitors. The duration of trials was generally short, which limited data with regard to adverse events and study withdrawals.

The main potential source of bias in the research was a lack of information with regard to how the studies were blinded. In addition, the reviewers suggested that the researchers could have preferentially selected patients more likely to respond to ACE inhibitors. This selection bias could make ACE inhibitors appear more effective than they truly are.

The studies covered 14 ACE inhibitors. The degree of homogeneity with regard to their efficacy in reducing blood pressure was remarkable. No one medication appeared superior to others.

Overall, ACE inhibitors had a modest collective effect in reducing blood pressure. The mean reduction in systolic blood pressure ranged between 6 mm Hg and 9 mm Hg, and the mean reduction in diastolic blood pressure was 4-5 mm Hg. Less data were available with regard to the blood pressure effects of ACE inhibitors at 1-12 hours after dosing, but the average decrease in blood pressure with ACE inhibitors around their peak concentration was greater than their average efficacy (11.4/6.4 mm Hg).

Dose Effectiveness

The study provided some important information about the relationship between the dose of ACE inhibitors and their effect on blood pressure. Doses lower than the manufacturers' maximum recommended dosage had the same blood pressure-lowering effect as the maximum dose. For example, doses of one eighth to one quarter of the maximum achieved the blood pressure-lowering effect of the maximum dose in 60% to 70% of cases. Half of the maximum dose achieved it 90% of the time. There was no blood pressure-lowering effect at or below one sixteenth of the maximum suggested dose. These data suggest that use of the maximum dosage of ACE inhibitors to achieve greater blood pressure control is usually unnecessary.

The research also identified dosing information for individual ACE inhibitors and suggested that the manufacturers' recommended starting doses of benazepril, moexipril, and ramipril are higher than the minimum dose needed to reduce blood pressure. Conversely, captopril did not appear effective in reducing blood pressure at the manufacturers' recommended starting dose. Most of the maximum blood pressure-lowering effect of lisinopril was achieved at only one eighth of the recommended maximum dose.

ACE inhibitor dosing was also one of the biggest deficits in the current review. It was clear to the review authors that not all data in regard to the efficacy of different doses of ACE inhibitors were published. Instead, the data were supplied to regulators privately to determine the appropriate dosing range of ACE inhibitors.

Only half of trials provided data in regard to the rate of withdrawal due to adverse events. Collectively, there was no difference between ACE inhibitors and placebo in this critical outcome. ACE inhibitors did not significantly affect patients' heart rate.

Addressing Other Health Issues

Physicians might choose ACE inhibitors to treat hypertension for other possible health benefits associated with these medications, especially the potential to prevent type 2 diabetes. ACE inhibitors can have a positive effect on glucose metabolism through multiple mechanisms, and previous research suggested that they could prevent incident diabetes compared with other antihypertensive medications. Specifically, the Captopril Prevention Project demonstrated a 14% relative reduction in this outcome among participants receiving captopril vs a diuretic or beta-blocker. This benefit, associated with captopril, was evident regardless of the baseline risk for diabetes, although the incidence of diabetes was not a primary outcome of the study.

The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial directly examined the effect of ramipril vs placebo on the incidence of diabetes. This study examined patients with impaired fasting glucose levels or reduced insulin sensitivity but no history of cardiovascular disease. After a median of 3 years of treatment, ramipril was not associated with a significantly lower incidence of diabetes compared with placebo. Median fasting plasma glucose levels were also similar at the end of the trial. However, ramipril was associated with a higher rate of return to normoglycemia.

Physicians might also consider using ACE inhibitors for hypertension in order to prevent incident heart failure. However, although ACE inhibitors are associated with numerous positive outcomes, including reduced mortality, among patients with known heart failure, little evidence exists that they provide special protection against new heart failure. In a study of quinapril and placebo initiated shortly after myocardial infarction, there was no difference between treatment groups in a composite outcome of cardiovascular death and significant cardiovascular events. Specifically, no difference was found in the risk for heart failure among those patients at high cardiovascular risk. Similarly, in the Antihypertensive and Lipid-Lowering Treatment to Prevent Hearth Attack Trial (ALLHAT), the incidence of heart failure was similar among patients receiving lisinopril and chlorthalidone.

Commentary

Although ACE inhibitors may not provide special protection against diabetes or heart failure among patients with hypertension, physicians should still consider these medications when managing hypertension. In fact, the nature of hypertension management dictates that they have to because most patients require more than 1 medication initially. In a recent study of men receiving care at a Veteran Affairs hospital, 60.4% of subjects with hypertension and significant cardiovascular risk were receiving multiple antihypertensive medications. Nevertheless, only 28% of these same patients had reached their goal blood pressure levels, indicating that they needed titration of their medications, if not the addition of other antihypertensive drugs.

Authors' conclusions

There are no clinically meaningful BP lowering differences between different ACE inhibitors. The BP lowering effect of ACE inhibitors is modest; the magnitude of trough BP lowering at one-half the manufacturers' maximum recommended dose and above is -8/-5 mm Hg. Furthermore, 60 to 70% of this trough BP lowering effect occurs with recommended starting doses. The review did not provide a good estimate of the incidence of harms associated with ACE inhibitors because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.

Clinical Pearls

  • In the current review, ACE inhibitors were associated with an average reduction in systolic blood pressure between 6 mm Hg and 9 mm Hg and in diastolic blood pressure of 4-5 mm Hg;

  • ACE inhibitors achieved most of their power in reducing blood pressure at half of the maximum recommended dose, or less;

  • ARBs provide similar reductions in blood pressure compared with ACE inhibitors; and

  • There is no strong evidence that ACE inhibitors can prevent incident diabetes mellitus or heart failure.

Chronic Pain Linked to Low Vitamin D

Inadequate vitamin D may represent an underrecognized source of nociperception and impaired neuromuscular functioning, say researchers.

"Physicians who care for patients with chronic, diffuse pain that seems musculoskeletal — and involves many areas of tenderness to palpation — should strongly consider checking vitamin-D level," Michael Turner, MD, from the Mayo Clinic in Rochester, Minnesota, said in a news release issued Friday.

"For example," he added, "many patients who have been labeled with fibromyalgia are, in fact, suffering from symptomatic vitamin-D inadequacy. Vigilance is especially required when risk factors are present, such as obesity, darker pigmented skin, or limited exposure to sunlight."

Dr. Turner was lead investigator of a study published in the journal Pain Medicine in November 2008. The work suggests a correlation between inadequate vitamin-D levels and the amount of narcotic medication taken by chronic pain patients.

Required Nearly Twice As Much Pain Medication

The researchers found that patients who had inadequate vitamin-D levels and required narcotic pain medication were taking much higher doses — nearly twice as much — as those with adequate levels. These patients also reported worse physical function and worse overall health perception.

The investigators retrospectively studied 267 patients admitted to the Mayo Comprehensive Pain Rehabilitation Center. They compared serum 25-hydroxyvitamin-D levels at the time of admission with other parameters such as the amount and duration of narcotic pain medication used, self-reported levels of pain, emotional distress, physical functioning, health perception, and demographic information such as sex, age, diagnosis, and body-mass index.

Patients with vitamin-D levels below 20 ng/mL were considered to have inadequate amounts. The prevalence of low vitamin D was 26% (95% CI, 20.6% – 31.1%).

Among patients using opioids, the mean morphine-equivalent dose for the inadequate vitamin-D group was 133.5 mg/day compared with 70.0 mg/day for the adequate group (P = .001). The mean duration of opioid use for the inadequate and adequate groups was 71.1 months and 43.8 months, respectively (P = .023).

The researchers also observed a link between increasing body-mass index and decreasing levels of vitamin D.

Inadequate Vitamin D May Create or Sustain Pain

The preliminary results suggest that inadequate vitamin D may play a role in creating or sustaining chronic pain. During an interview, Dr. Turner suggested that patients with inadequate vitamin D may benefit from cholecalciferol 50,000 international units dosed according to the level of deficiency.

But he urged caution for patients with calcium- or phosphate-processing disorders. "Increasing vitamin-D levels could be problematic in patients with kidney failure or stones or primary hyperparathyroidism or sarcoidosis. This doesn't preclude increasing levels, but it might warrant discussion with an endocrinologist," he said.

For patients with adequate vitamin D looking to maintain levels, he recommends10 to 15 minutes of sun exposure with no sunscreen on the trunk and arms and legs 3 times a week.

Source: Pain Med. 2008;9:979-984. Abstract

Marked Decline in Breast Cancer Risk After Stopping Contraceptive pills

Following the release of the 2002 report of the Women's Health Initiative (WHI) trial of estrogen plus progestin (EPT), the use of menopausal hormone therapy in the United States decreased substantially. Subsequently, the incidence of breast cancer also dropped, suggesting a cause-and-effect relation between hormone treatment and breast cancer.

In a study published in N Engl J Med 2009, Leon Speroff, MD and Wendy Y. Chen, MD, MPH analyzed the results of the WHI randomized clinical trial—in which one study group received 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily and another group received placebo—and examined temporal trends in breast-cancer diagnoses in the WHI observational-study cohort. Risk factors for breast cancer, frequency of mammography, and time-specific incidence of breast cancer were assessed in relation to combined hormone use.

RESULTS: In the clinical trial, there were fewer breast-cancer diagnoses in the group receiving estrogen plus progestin than in the placebo group in the initial 2 years of the study, but the number of diagnoses increased over the course of the 5.6-year intervention period. The elevated risk decreased rapidly after both groups stopped taking the study pills, despite a similar frequency of mammography. In the observational study, the incidence of breast cancer was initially about two times as high in the group receiving menopausal hormones as in the placebo group, but this difference in incidence decreased rapidly in about 2 years, coinciding with year-to-year reductions in combined hormone use. During this period, differences in the frequency of mammography between the two groups were unchanged.

The authors concluded that increased risk of breast cancer associated with the use of estrogen plus progestin declined markedly soon after discontinuation of combined hormone therapy and was unrelated to changes in frequency of mammography.

This report from the WHI is not the first about the change in breast cancer prevalence that occurred after the initial WHI publications in 2002, but it is of value because it documents that the change cannot be attributed solely to a decrease in the use of mammography.

The WHI recently updated results on breast cancer risk after discontinuation of the combination EPT arm. Overall results were published for the post-intervention phase in 2008. With mean follow-up of 2.4 years for this phase, a nonsignificant increased risk of breast cancer was still observed (HR, 1.27; 95% CI, 0.91-1.78), with a possible downward trend in cancer risk with follow-up.

This newest report is a more detailed analysis on breast cancer outcomes and also drew data from the observational cohort of the WHI. HRs for 6-month time intervals were calculated for both the intervention and nonintervention phase of the clinical trial. In an intention-to-treat analysis, there was no difference in the slopes of the HRs over time comparing the intervention and post-intervention phases (P = 0.28). However, after adjusting for adherence by censoring nonadherent subjects, there was a statistically significant difference in the slopes with HRs increasing over time for women using EPT, but declining after discontinuation (P = 0.005). Although breast cancer cases appeared to decline more in the intervention arm compared to placebo, mammography rates were similar in both arms. During the post-intervention phase, both breast biopsies and mammograms with abnormalities were more common in the EPT arm compared to placebo. Similar results for breast cancer incidence rates were seen using the observational data, although mammography rates were higher among women who used HT compared to those who did not.

After the WHI results were released in 2002, there was a large decline in HT use in the United States. Several investigators then reported a decline in US breast cancer rates correlating with reporting of the WHI trial results. Given the temporal association, it was speculated that this decrease in breast cancer incidence may have been due to the widespread discontinuation of HT, although other investigators noted that there was also a concomitant decline in mammography utilization, which may also have explained the changes. However, mammography rates were similar in the intervention arms of the WHI trial and were stable over time for women in the observational study, so it would seem unlikely that changes in mammography utilization alone can explain the recent decline in US breast cancer rates.

Friday, March 20, 2009

Anti-Obesity Drugs and the Neural Connection

Obesity is a curse, one that’s extremely difficult to shake off. It’s not just an aspect that’s socially unacceptable (if you’re fat, chances are that you’re not likely to be liked), it’s also dangerous for your health. Obese and overweight people are more susceptible to diseases like diabetes, strokes and cardiac arrests, illnesses that can cause lifelong disabilities and even death.
While a low calorie diet combined with a good exercise routine is the best way to combat obesity, not many people are willing to put themselves through the hardship that this entails. And some people are too morbidly obese to even attempt the mildest form of exercise. This is when they turn to drastic measures like surgery or anti-obesity drugs. While liposuction and stomach tucks come with their own set of complications, it’s the drugs that are used to lose weight that have the most dangerous side effects.
Anti-obesity drugs like taranabant, rimonabant and orlistat work in any one of the following ways:
· They suppress your appetite
· They increase your body’s metabolism
· They interfere with your body’s ability to absorb and break down fat
· They inhibit digestion
· They lower caloric absorption
The problem with these drugs is that they inhibit certain basic bodily functions in order to work, and it is because of this very fact that they’re dangerous. Drugs that suppress appetite, otherwise known as cannabinoid receptors, have been proven to cause brain damage in juvenile mice. They interfere with neural connectivity, and lead to depression, anxiety and suicidal tendencies. This tendency to inhibit neurological development in mice could be mirrored in human infants; and since infancy is a stage where the brain is plastic and keeps modifying at a rapid pace, these drugs could possible cause brains with stunted growths.
The study, undertaken by the Massachusetts Institute of Technology, cautioned that drugs like rimonabant and tarabant which are responsible for suppressing appetite, are liable to target certain psychological pathways that are extremely important for keeping our bodies and brains at an equilibrium.
Besides affecting your mood, anti-obesity drugs could also give you high blood pressure and increase your pulse rate. All these factors lead us to question the efficacy and value of anti-obesity drugs. While doctors prescribe them only in concert with a diet and exercise regime, there are many cases of abuse where people continue to take them without prescriptions. The danger in this is that they’re unaware of the drugs’ potential side effects.
Yes, obesity is socially unacceptable, but if there’s one thing that’s more taboo than the problem of being overweight, it’s insanity. So if you want to keep your brains intact, it’s best you steer clear of these drugs and try to lose weight the regular way. Yes, it’s hard, but you need to remember that the good things in life don’t come easily.
By-line:
This article is contributed by Sarah Scrafford. She invites your questions, comments and freelancing job inquiries at her email address: sarah.scrafford25@gmail.com.

Thursday, March 19, 2009

Early detection of Alzheimer's disease

Researchers at the University Of Pennsylvania School Of Medicine have done a breakthrough study pioneering a biomarker test that can confirm or rule out Alzheimer's disease. The test measures cerebrospinal fluid (CSF) concentrations of two of the disease's biochemical hallmarks, amyloid beta42 peptide and tau protein.
With this information in hand, the scientists also predict whether a person's mild cognitive impairment would convert to Alzheimer's disease over time. The research team, led by Dr. Leslie M. Shaw, Co-Director of the Penn Alzheimer's Disease Neuroimaging Initiative (ADNI) Biomarker Core, could detect this devastating disease at the earliest stages, before dementia symptoms appeared and widespread irreversible damage occurred.
By improving upon a previously suggested pathological CSF biomarker signature, the researchers found evidence of neuron degeneration, marked by an increase in CSF concentration of tau proteins, and plaque deposition, indicated by a decrease in amyloid beta42 concentration. Also, people with two copies of the genetic risk factor for Alzheimer's disease, APOE e4 , had the lowest concentrations of amyloid beta42, compared to those with one or no copies.
"With this test, we can reliably detect and track the progression of Alzheimer's disease," said Shaw. He added: "Validated biomarker tests will improve the focus of Alzheimer's clinical trials enrolling patients at earlier stages of the disease to find treatments that can at least delay, and perhaps stop- neurodegeneration. In addition, prevention trials can test methods to delay or block mild cognitive impairment from converting to full-blown Alzheimer's."
The study appears in the online edition of the Annals of Neurology.
Source-ANI
ARU/M

3000 Steps In 30 Minutes for a Meaningful Exercise Program

Researchers are now suggesting people to walk 150 minutes a week, which is equivalent to 30 minutes each day 5 times a week, though moderate physical activity is known to be beneficial to health. Researchers at the School of Exercise and Nutrition, San Diego State University, point out that pedometers widely used as a physical activity monitoring tool are unable to measure activity intensity.
They have determined that a rate of at least 100 steps per minute achieves moderate intensity activity. According to them, a simple pedometer-based recommendation of 3000 steps in 30 minutes can get people started on a meaningful exercise program.
The researchers monitored 58 woman and 39 men for oxygen uptake while walking on a treadmill. The subjects completed 46-minute sessions at different treadmill speeds between 65 and 110 meters per minute. All subjects wore pedometers, and their heart rates were recorded.
The research team used 3 METs, or metabolic equivalents, as the minimum level of oxygen demand which approximates moderate exercise, to monitor participants in order to determine whether they had reached the moderate-exercise level at a given treadmill speed. From these data, the researchers found that for men, step counts associated with walking at 3 METs were between 92 and 102 steps per minute. For women, according to them, the range was between 91 and 115 steps per minute.
The study been published in the American Journal of Preventive Medicine.
Source-ANI
ARU/SK

Friday, March 13, 2009

A case report on nimesulide and its relation with angina

Salman, M. T.Rahman, S. Z. and Khan, R. A. (2003A case report on nimesulide and its relation with angina. In: International Workshop on Adverse Drug-Reaction Monitoring & 3rd Annual Conference Society of Pharmacovigilance, India11-13 Dec 2003Agra, India.

Even though there might be several cases of NSAIDs induced angina that are not been reported, we could find a definite case of Nimesulide induced angina in Aligarh. A 65 year old female patient was a known case of diabetes mellitis for 17 years and angina pectoris for 10 years for which she was maintained on drugs. She sustained injury after falling down and was found to have Colle’s fracture for which she was advised POP and Tab Nimesulide twice daily alongwith ongoing treatment. On 3rd day, she felt chest pain (angina) for which she used Tab sorbitrate 3-4 times a day but no improvement was noticed. Then she consulted her family physician. On examination, no abnormality was found except that ECG showed changes of ischemia and extra systoles. She was diagnosed as a case of Unstable Angina and advised to stop the suspected drug Nimesulide but continue to take previous treatment. She then showed improvement in angina. As an alternative Tab Brufen (Ibuprofen) 400 mg thrice daily was advised. The patient afterwards complained no problem. In this case, the unstable angina appears to be due to coronary spasm and not due to clot because on withdrawing the suspected drug there was rapid relief. The spasm seems to be related to inherent properties of Nimesulide and not due to prostaglandin inhibition as Brufen did not cause the same symptoms. Alternatively, it may be due to an imbalance between COX 1 and COX 2 activities due to preferencial COX 2 inhibition. Moreover, the inhibition of prostaglandin synthesis may adversely affect cardiovascular homeostasis.

Thursday, March 12, 2009

Serious hepatic reactions associated with the dietary supplement Fortodol

Herb-based dietary supplement contained active drug substance.
> The Medical Products Agency issues a warning against the herb-based dietary supplement Fortodol. The product has been on sale in Sweden since 2004. Analyses of the product revealed that it contains the drug substance nimesulide which is suspected to have caused serious liver injuries including liver failure and cardiovascular events with fatal outcome. At least 240 000 jars totalling 24 million capsules is reported having been sold in Sweden and Norway since 2004.
> The Medical Products Agency has received information about four cases of liver damage among Swedish patients who have taken Fortodol. In one of the cases, this led to acute liver failure resulting in death of the patient. The Norwegian Medical Products Agency has information about five cases of liver damage, and one case of death, with temporal association with the intake of Fortodol. It is known that the substance nimesulide can cause serious liver injury. Nimesulide is not an approved medicinal product in Sweden.
>  People consuming Fortodol should immediately cease the intake of it. Should you suffer from symptoms such as poor appetite, nausea, vomiting, abdominal pain, fatigue, dark urine or yellow skin, you should contact a medical care facility for a liver check up, says Barbro Gerdén, physician at the Medical Products Agency.
> The dietary supplement Fortodol, which is on sale on the Internet and in health food shops is said to relieve arthritis and muscle pains as well as head aches. The table of contents specifies that the product contains turmeric extract and the amino acid dl-phenylalanine. In two of nine analysed batches, the Medical Products Agency found the drug substance nimesulide.
> In those EU-countries where nimesulide is approved as a medicinal product the recommendations state that the substance should only be used for temporary treatments with prescriptions of not more than 30 doses. Fortodol has been sold in packages of up to 100 capsules.
> This is a product which has been launched as a dietary supplement, not as a medicinal product which implies a risk that people use it for longer periods of time, says Per Claeson, pharmacist at the Medical Products Agency.
> This is not the first time that the Medical Products Agency finds hazardous levels of drug substances in products sold as herbal products. Earlier examples are weight loss products and potency enhancers. This is the first time that an illegal drug substance has been discovered in a product used by people with painful disease states such as joint and muscle ailments. 

New Pharmacological Drug Classes Introduced in 2008

Pharmacologic ClassFirst to be Marketed in the U.S.FDA Approved Indication11th Edition Reference
C1 inhibitor
C1 inhibitor (Cinryze)Routine prophylaxis against angioedema attacks in patients with hereditary angioedemapage 1405
CXCR4 chemokine receptor inhibitorplerixa (Mozobil)Mobilization of granulocyte-colony stimulating factor induced hematopoietic stem cells to the peripheral blood prior to collectionpage 1274
peripherally acting µ-opioid receptor antagonistalvimopan (Entereg)Acceleration of the time to gastrointestinal recovery following bowel surgerypages 561-562
methylnaltrexone (Relistor)Treatment of opioid-induced constipation
thrombopoietin receptor agonisteltrombopag (Promacta)Treatment of thrombocytopenia in patients with chronic immune thrombocytopenic purpurapages 1441-1442
romiplostim (Nplate)

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