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The New Zealand Medical Journal

 Journal of the New Zealand Medical Association, 29-April-2011, Vol 124 No 1333

Unusual adverse effects of well-known drugs

Lipitor (atorvastatin) and Viagra (sildenafil), coming off patent in the United States in 2012 is a significant problem for Pfizer, the world’s biggest selling drug company. The reason for concern arises from the fact that these two drugs are big earners for the company. Lipitor alone is responsible for nearly a fifth of Pfizer’s revenues. This report indicates that a retrenchment to counterbalance includes closing down Pfizer’s Research & Development plant in Sandwich, Kent, UK which will result in the loss of 2400 jobs. A very sad down the track “adverse drug effect”, particularly as the Sandwich lab was where Viagra was developed.
BMJ 2011;342:d771.

Gender empowerment and cigarette smoking

This paper explores the hypothesis that in countries with high gender empowerment the female-to-male smoking prevalence ratio is also higher. Gender empowerment is not an expression that your scribe had met before but it relates to one gender being more powerful than the other.
In the more prosperous countries women have acquired increased economic resources, greater social equality and often greater political clout. Along with these they have unfortunately taken to the weed in greater numbers and these researchers attempt to quantify this by comparing the gender empowerment measure (GEM) with the female/male cigarette smoking prevalence or gender smoking ratio (GSR).
As you would expect the Nordic countries (Denmark, Norway, Sweden, Finland and Iceland) top the list for GEM and most are also top of the GSR. Whereas the Middle East trails at the bottom with their females underpowered and minimal smoking. And I am pleased to report that the GEM figure for New Zealand is approximately 4th place. Unfortunately, however, Kiwi females are in the top 10 of the GSR.
Bull WHO 2011;89:195–202.

Management of osteoporosis – intravenous zoledronic acid or oral alendronate?

Osteoporosis-related low trauma fractures are associated with increased morbidity and mortality, and diminished quality of life. Oral bisphosphonate therapy has been shown to reduce the risk of subsequent fractures and alendronate (ALN) is frequently used in a dose of 70mg orally once per week.
The authors of this study note that adherence to weekly alendronate is often poor and has been reported as low as 50%. They speculate that an annual dose of 4mg of intravenous zoledronate (ZOL) would be as efficacious and safe. Their retrospective cohort study compared these regimens. Lumbar spine bone mineral density (BMD) improved 5.6% in the ZOL patients and 5.5% in the ALN group.
The figures for hip BMD were 2% in the ZOL patients and 2.5% in the ALN group. However, there were significantly more new fractures (p < 0.001) in the ZOL group (7.2%) than the ALN group (1%). The ZOL group were significantly older (p< 0.01) and had a significantly higher proportion of males (p< 0.05) at baseline. There were no serious adverse reactions in either group so probably equally good, except for older men. I note that in NZ a year of ALN would cost $467 and 5mg (not 4) of ZOL would cost $600.
Int Med J 2011;41:186–90.

Loop diuretic tactics in patients with acute decompensated heart failure

This paper concerns the various tactics possible for the patient who develops worsening failure on high dose oral frusemide. They randomised 308 such patients to treatment with frusemide administered intravenously by means of either a bolus every 12 hours or continuous infusion and at either a low dose (equivalent to the patient’s previous oral dose) or a high dose (2.5 times the previous oral dose). Their endpoints were the patient’s global assessment of symptoms and the mean changes in the serum creatinine.
The researchers found no significant difference in either end point between bolus and infusion techniques. There was also no difference in end points between the high and low dose groups. So they would recommend bolus IV frusemide at the same dose as was given orally? However, they also report that the higher IV bolus group had a greater diuresis but a transient worsening of renal function. Methinks, bolus at somewhat higher dose might be best.
N Engl Med 2011;364:797–805.

Paracetamol overdose induced acute severe hepatotoxicity

Paracetamol (acetaminophen) hepatotoxicity is the commonest cause of acute liver failure (ALF) in the UK and I would venture to say that this is also the case in NZ. This report looks at data from 663 such patients admitted to the Scottish Liver Transplant Unit. The overdose was intentional in 75.4% and accidental in 16.6% whilst the pattern was unclear in 8%. Unintentional overdose patients were significantly older, more likely to abuse alcohol, and more commonly overdosed on compound narcotic/paracetamol analgesics compared with intentional overdose patients.
The paracetamol blood concentration and liver function tests were significantly lower in the unintentional patients. However their mortality rate, 38.2% was significantly higher than that of those with an intentional overdose (25.6%) and this was attributed to greater organ dysfunction at admission. As expected. Perhaps the accidental overdose subjects should have a lower threshold for N-acetyl cysteine and early referral to liver transplant units?
Br J Clin Pharmacol 2011;71:272–82.
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