The NEJM on HFA inhalers
As a followup to my post the other day…
The NEJM concludes — along with the rest of the world — that HFA albuterol formulations are more expensive than their CFC counterparts. The article (subscription required) delves into some of the differences between the various HFA formulations as well as the differences between CFC and HFA albuterol.
The article doesn't talk much about ProAir HFA, which I find a bit strange, especially as it has captured 60% of the HFA albuterol market. Unrelatedly, it seems that concentrations of albuterol are slightly higher with HFA than the CFC versions, despite the smaller plume.
Here're some semi-relevant differences between Ventolin HFA and Proventil HFA, emphasis mine:
The excipients added to the propellant formulation differ according to the brand of HFA inhaler. For instance, each puff of Proventil HFA releases 4 μl of ethanol. This small amount of ethanol will not have a discernible clinical effect, but it may be of concern for patients who for religious or other reasons abstain from alcohol. Breathalcohol levels of up to 35 μg per 100 ml may be detected for up to 5 minutes after two puffs of Proventil HFA. Unlike CFC propellants, HFA propellants may cause false positive readings in anesthetic gas–monitoring systems. The infrared spectrums of HFA overlap with commonly used anesthetic gases in the range of 8 to 12 μm. One albuterol product, Ventolin HFA, contains no excipients other than the propellant, a characteristic that may improve tolerability for some patients. However, Ventolin HFA comes packaged in a moisture-resistant protective pouch containing a dessicant and has a limited shelf life once it has been removed from the pouch. Ventolin HFAs have a greater affinity for moisture than do CFCs, which means that water vapor is more likely to enter the canister around the meteringvalve gaskets. The other approved HFA inhalers are less susceptible to moisture permeation and do not require a protective pouch.
Shelf life for Ventolin HFA is 2 months after opening, so it's a mixed bag.
A breakdown:
[tags]Medicine, pharmacy, albuterol, HFA, CFC[/tags]
Topical anesthetic for premature ejaculation
One of my most popular posts here at OnThePharm (and most commented on) is my "Dapoxetine for premature ejaculation" entry, with many commenters wondering where and when it will be available. (I have no idea — that's up to the FDA, sorry.) When and if dapoxetine becomes available, I can see it being marketed in much the same way that Viagra has been. And initially it'll be treated by the public as "Tee hee, if you need this, you're less than a man." And slowly PE will become a socially-acceptable thing to talk about, and men will be looked down on less because of the increased awareness.
That's probably the only good thing about DTC advertising that I can think of — making socially-taboo topics more discussion-friendly, and allowing people to seek treatment for what otherwise might be embarrassing private afflictions.
In any case, there's another, potentially more promising treatment for premature ejaculation being tested in the Netherlands and the UK.
"The men who were prescribed the TEMPE spray, which delivers a combination of lidocaine and prilocaine, managed to delay ejaculation by just under an extra four minutes after using the product" reports Professor Wallace Dinsmore from the Royal Victoria Hospital, Belfast.
"Meanwhile the control group, who were prescribed a placebo (dummy) spray, increased their penetration to ejaculation time by just over 40 seconds.
"Overall, the TEMPE spray was 2.4 times more effective than the placebo."
It's not the same ratio as EMLA:
The men in the TEMPE group (Topical Eutectic Mixture for Premature Ejaculation) administered three metered sprays of the local anaesthetic preparation to the glans of their penis 15 minutes before intercourse. This delivered a total of 22.5mg of lidocaine and 7.5mg of prilocaine.
Not knowing the weight or volume of the mixture, I can't calculate the concentration, but that seems pretty high to me. It is a spray though, so in theory, it won't last as long as rubbing in a cream. It'll be interesting to see where this goes in terms of treating PE, and possibly for quick in-house topic anesthetic perhaps similar to Gebauer's ethyl chloride.*
*And for anyone out there who suffers from PE thinking about using Gebauer's to achieve a similar effect, don't bother. I know a kid who's nickname is "Frosty" for a reason. You'll have trouble finding your testicles, never mind getting an erection. (Ah, fraternity pranks in pharmacy school…)
[tags]Medicine, pharmacy, premature ejaculation, men's health[/tags]
More on the discovery on an old antibiotic
Thanks to a reader, I've gotten my hands on the actual study of the old antibiotic that I mentioned last week. If you recall, I expressed some doubts about the "newness" of the atun-based compound, wondering if it could be a product of mold growing in the seeds or on the leaves. My doubts have been laid to rest:
We preserved the leaves and kernels of A racemosa collected in the Independent State of Samoa in 70% ethanol and prepared alcohol extracts according to standard protocol. Various concentrations of kernel extract and leaf extract were added to samples of two Gram positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and two Gram negative bacteria (Pseudomonas aeruginosa and Escherichia coli) in a minimal inhibitory concentration assay. This assay was performed in cation adjusted Mueller-Hinton broth according to the standard protocol.
The assay showed that the extracts from A racemosa (the atun tree described by Rumphius) had antibacterial activity that was specific for the Gram positive bacteria tested (table). The minimal inhibitory concentrations of the leaf extract were significantly different from those of the kernel extract in both of the Gram positive bacteria…
Etc. etc. I might've guessed that they controlled for this sort of think. I guess I just got carried away with my own cleverness… 
[tags]Medicine, pharmacy, antibiotics, drug discovery, MRSA[/tags]
Transdermal Alzheimer's vaccine in the works
Vaccines are becoming the new medical hotness. Cervical cancer, otitis media, shingles, and now a second Alzheimer's effort. (I covered the first one here.)
This time it's a transdermal vaccine that's working in mouse models. Mouse models, of course, don't translate to successful human trials, but it's a good start. This vaccine works by causing the immune system to recognize the toxic amyloid beta proteins and triggering an attack on them.
Why transdermal?
They found that transdermal immunization with Ab does not appear to trigger specific toxicities associated with past immunization strategies.
Specialized immune cells prevalent in the skin, called Langerhans, may direct the body's reaction to the vaccine toward a response that is beneficial instead of overly aggressive and ultimately harmful, Dr. Tan said.
They're hopeful that they can reduce memory loss and reduce the relevant population's senile plaque burden.
"If those studies show clear cognitive benefits," Dr. Tan said, "we believe clinical trials to evaluate a beta amyloid skin patch or topical cream in patients with Alzheimer's would be warranted."
Har har. Emphasis mine.
[tags]Medicine, vaccine, Alzheimer's, geriatrics[/tags]
DCA: activating apoptosis by turning mitochondria back on
I saw this in a couple of places a few days ago, but I'm just getting to it now, what with classes starting this week and many other things going on. In the time that the story was published and now, there has been a huge amount of interest generated in the story, and the University of Alberta has set up a DCA information/donation page, because as Jack points out, there's no money to be made by a pharmaceutical company here as DCA (dichloroacetate) is an unpatentable compound.
DCA shows a huge amount of promise in both in vitro and mouse models of tumor growth, and it doesn't seem to be selective about the specifics of the tumor itself. The reason is because DCA works by activating cell mitochondria which in turn turns on a cell's ability to die naturally (apoptosis). It's thought that cellular mitochondria shut down due to a lack of oxygen, and instead cellular metabolism stops at glycolysis. (Normal metabolism results in pyruvate being transported into the mitochondria for further metabolism netting greater ATP production.)
The phenomenon might also explain how secondary cancers form. Glycolysis generates lactic acid, which can break down the collagen matrix holding cells together. This means abnormal cells can be released and float to other parts of the body, where they seed new tumours.
It does indeed seem to be a good time to get cancer, if any time could be described as such.
[tags]Medicine, pharmacy, DCA, oncology, cancer, cellular metabolism[/tags]
Pancreatic cancer vaccine shows some promise
A vaccine for pancreatic cancer in Phase II trials is showing some promise in extending patient's lives according to Reuter's.
Most of the patients who got the vaccine survived at least two years, Dr. Daniel Laheru of Johns Hopkins University in Baltimore and colleagues told a meeting of gastrointestinal cancer specialists.
In the phase II study of 60 patients, 88 percent were alive a year later and 76 percent lived two years.
In comparison, 63 percent of patients treated with surgery alone survive a year and 42 percent live two years.
Interesting, but as nearly as I can tell, this research is actually from November 2005. It looks like it's making news because it was just presented at the 2007 Gastrointestinal Cancers Symposium. Regardless, this is good news. How long until we have a regular bevy of cancer vaccines in our arsenal?
[tags]Medicine, cancer, pancreatic cancer, vaccines[/tags]
Using propranolol to block malaria
A (relatively) new study in PLoS Medicine indicates that using propranolol can prevent malaria from gaining access to erythrocytes by dampening Gs peptide activity.
Dampening the signaling mechanism also inhibited parasitic growth at the blood-stage. While the study deals with propranolol specifically, other beta-blockers have similar activity. Given how inexpensive this particular class of drug is on the whole, this could open up huge new avenues of treatment in cash-strapped third-world nations.
When used in combination with existing antimalarials in cell culture, propranolol reduced the 50% and 90% inhibitory concentrations for existing drugs against P. falciparum by 5- to 10-fold and was also effective in reducing drug dose in animal models of infection.
The conclusion states:
Together these data establish that, in addition to invasion, erythrocyte G protein signaling is needed for intracellular parasite proliferation and thus may present a novel antimalarial target. The results provide proof of the concept that erythrocyte Gs antagonism offers a novel strategy to fight infection and that it has potential to be used to develop combination therapies with existing antimalarials.
[tags]Medicine, pharmacy, propranolol, malaria, biochemistry[/tags]