ARB's increase cancer

The FDA is reviewing the safety of angiotensin-receptor blockers after a recent meta-analysis suggested a small increase in new cancer diagnoses in patients using the drugs.


The agency will update the public with its conclusions as soon as the review is complete. In the meantime, it says the benefits of ARBs outweigh any potential risks, and it advises that the drugs continue to be used as recommended.


Clinicians should report any ARB-related adverse events to the FDA's MedWatch program.

lorcaserin new weight loss drug

Lorcaserin, a selective serotonin 2C receptor agonist, helps patients both lose weight and maintain their weight loss, according to a phase III study conducted by the drug's manufacturer and published in the New England Journal of Medicine.


Some 3200 overweight or obese adults were randomized to take lorcaserin or placebo twice daily for a year, after which lorcaserin recipients continued the drug or switched to placebo for another year. All participants also received nutrition and exercise counseling.


At 1 year, more patients in the lorcaserin group than placebo group had lost at least 5% of their body weight (48% vs. 20% of patients; mean weight loss: 5.8 kg vs. 2.2 kg). In addition, lorcaserin patients who stayed on the drug for a second year were more likely to maintain their weight loss than those who switched to placebo.


Serious adverse events did not differ between lorcaserin and placebo recipients. Unlike some other serotonergic agents, lorcaserin did not increase risk for valvular heart disease.

vitamin e/beta carotene may increase cvd

A systematic review of antioxidants for primary prevention of cardiovascular disease identified four RCTs of vitamin E; the review found no benefits for vitamin E [1). One of the RCTs identified in the review found that vitamin E may increase death from subarachnoid hemorrhage [2). The review also identified six RCTs of beta-carotene; the review found no benefit for beta-carotene. Pooled analysis of four of these six RCTs found that beta-carotene may increase cv mortality

asa lowers MI but increases stroke

The role of aspirin in primary prevention remains uncertain. In a meta-analysis of five RCTs, Foster and colleagues found that aspirin slightly reduced the risk of a serious vascular event (odds ratio, 0.86; 95% CI: 0.80–0.90) and reduced the relative risk of myocardial infarction by about a third (OR, 0.71; 95% CI: 0.60–0.80], but had an uncertain effect on stroke (OR, 1.05; 95% CI: 0.90–1.20) [1]. The meta-analysis found that there were 0.1 excess intracranial bleeds per 1,000 patients treated per year with aspirin, and 0.7 major extracranial bleeds per 1,000 patients treated per year with aspirin. The authors found “insufficient evidence from RCTs to identify which individuals would benefit overall and which would be harmed by regular treatment with aspirin, although those at high and intermediate rather than low risk would be more likely to gain benefit.” ...More

up regulation and down regulation

down-regulation - A reduction in the number of receptors for a control substance, e.g., a hormone, local hormone, neurotransmitter, or a drug, in response to a prolonged excess of the control substance; this is an internal adjustment which usually helps restore homeostasis in a disease state.

up-regulation - An increase in the number of receptors for a control substance, e.g., a hormone, local hormone, neurotransmitter, or a drug, in response to a prolonged decrease of the control substance; this is an internal adjustment which usually helps restore homeostasis in a disease state.

fibrates may lower coronary events not mortality, stroke or HF

Fibrates appear to lower the risk for coronary events, according to a meta-analysis in the Lancet.


Researchers examined data from 18 placebo-controlled trials of fibrates for primary or secondary prevention; some 45,000 adults were included. Overall, coronary events were significantly less common in patients taking fibrates than in those on placebo (8.7% vs. 11.6%). Fibrates were also associated with significant reductions in coronary revascularization, progression of albuminuria, and retinopathy.


There was no benefit in terms of stroke, mortality, or heart failure. Serious drug-related events, including rhabdomyolysis, were not increased with fibrates.


The authors conclude: "The magnitude of effect is moderate, but in high-risk individuals and in those with combined dyslipidemia, clinically meaningful reductions in risk could be achieved."

confidence intervals of brand vs generics

For example, the ratio of test drug to reference drug AUC (test/reference AUC) for Drug A in six subjects results in the following values:

120%, 120%, 110%, 110%, 90%, 110%

The mean test/reference AUC was 110% with 90% CI of 102 to 117. This means that there is 90% probability that the true mean lies between 102% and 117%. -ME-IT EITHER DOES OR DOES'T LIE IN THIS INTERVAL=> 9 OUT OF TEN TIMES IT WILL-Therefore, the drug passes the bioequivalence test and is considered bioequivalent to the reference drug.

In another example, the test/reference AUC for Drug B in six subjects results in the following values:

110%, 190%, 30%, 130%, 90%, 110%

The mean test/reference AUC was 110% with 90% CI of 75 to 145. Although the average test/AUC ratio of the drug (110%) is the same as drug A, there is a 90% probability that the true mean lies between 75% and 145%. The confidence intervals are too wide and therefore, Drug B fails to establish bioequivalence with the reference drug.

As illustrated above, the confidence interval range of 80% to 125% does not mean that drug levels can vary up to 20% between referenced (brand) drug and the test (generic) drug. If drug levels vary by more than 10%, the range of possible values within the 90% confidence interval will likely become too broad and the drug will fail to establish bioequivalence with the reference drug. 12 In fact, in a study using the FDA bioequivalence criteria, the first 224 post-1962 drugs approved over the two year period after the Waxman Hatch amendments were passed, including some narrow therapeutic index drugs, showed a mean bioavailability variation between the generic and brand products of only 3.5%.

Self-Titration of Drugs and Telemonitoring in Hypertension Help Lower BP

Patients with uncontrolled hypertension attain better control with self-titration of medications and automated telemonitoring by clinicians, according to a Lancet study.


Investigators randomized some 500 patients from 24 general practices to self-titration and telemonitoring or to usual care for 1 year. Patients had blood pressures above 140/90 mm Hg despite taking one or two antihypertensive drugs. Intervention patients took pressure readings each morning during the first week of the month. If readings were above the target of 130 systolic for 2 consecutive months, drug dosages were adjusted according to a pre-agreed titration schedule without seeing the family doctor.


By 12 months, mean systolic pressure had dropped 17.6 mm Hg in the intervention group versus 12.2 among controls. Intervention patients were prescribed more drugs over the course of the year than controls — especially calcium antagonists and thiazides. Side effects were largely similar between groups.


An editorialist concludes that wide use of this strategy "is not far off on the horizon."

Glucosamine Doesn't Lessen Disability Related to Low Back Pain

Glucosamine does not reduce pain-related disability in chronic low back pain, according to a JAMA study.


Investigators studied 250 patients who had low back pain for at least 6 months, along with imaging-based evidence of degenerative lumbar osteoarthritis. Subjects were randomized to treatment with either glucosamine (1500 mg) or placebo daily for 6 months and then were followed for an additional 6 months after treatment ended.


The main outcome measure — patients' scores on pain-related disability — dropped in both groups after treatment, but there was no significant difference between the groups.


An editorialist comments that "the most likely explanation for the outcome is simply that glucosamine probably offers little benefit for chronic [low back pain] with osteoarthritis beyond whatever placebo effect it may provide."

how long til ppi's work?

USPharmacist.com > Continuing Education > Exploring the Role of the Pharmacist in OTC PPI Use for Frequent Heartburn: "Some users do experience complete relief on the first day of PPI treatment, but it may take up to 4 days to obtain the full effect.8"

dopamine and prolactin are inversely related

An increase of dopamine decreases prolactin only in the brain ie hypothalamus. Dopamine cannot cross the blood brain barrier. In the peripheral nervous system, dopamine behaves like a catecholamine drug. Hence the use a domperidone, a dopamine blocker, to not only suppress nausea and vomitting (via peripheral dopamine blocking) but must also lower dopamine in the CNS w/c would up prolactin=> lactation. Bromocriptine, a dopamine agonist is used to stop lactation. Breastfeeding increases prolactin, thus decreasing dopamine, and deductively should ahve something to do with postpartum depression.

Intensive Glucose Control Reduces Some Microvascular Complications — At the Cost of Increased Mortality

Intensive glucose control in high-risk diabetes offers mixed results, according to two new analyses from the ACCORD trial.


In ACCORD, patients with type 2 diabetes and elevated cardiovascular risk were randomized to intensive glucose control or standard therapy. About half were also assigned to intensive or standard blood pressure control, and the other half to combination or standard lipid therapy. Intensive glucose control was stopped early, in 2008, because of increased mortality.


Now, writing in the Lancet, ACCORD researchers report that the glucose-control groups did not differ in composite outcomes measuring kidney function, diabetic eye complications, and peripheral neuropathy. However, several components of the composite outcomes (e.g., microalbuminuria, cataract extraction) were less common with intensive glucose control.


And in the New England Journal of Medicine, ACCORD researchers observe that both intensive glucose control and combination lipid therapy reduced progression of retinopathy, while intensive BP control did not.


Despite the microvascular benefits, the Lancet authors conclude, the increased mortality makes aggressive hemoglobin targets in high-risk diabetes seem "imprudent."

Testosterone Therapy Linked to Adverse Cardiovascular Events in Older Men with Limited Mobility

Use of testosterone gel in older men with mobility problems might increase risk for cardiovascular events, according to a small study in the New England Journal of Medicine.


Some 200 community-dwelling men aged 65 or older with low serum testosterone levels and impaired mobility were randomized to use a testosterone gel (10 mg) or placebo daily for 6 months. The trial was stopped early because of an excess of cardiovascular events with testosterone compared with placebo (in 23 vs. 5 subjects). In addition, testosterone recipients developed more respiratory and dermatologic disorders.


The elevated risks persisted after adjustment for baseline risk factors, including diabetes, hyperlipidemia, and hypertension.


The authors note that their findings may not be generalizable to younger men or to those without impaired mobility.