Recently in pharmaceutical research Category

Viagra has a history of unforeseen beneficial side effects and happy accidents - it started off as a heart medication, after all.  Now doctors have discovered another medical application for the drug, in what Dr. Richard Smith, a pediatric otolaryngologist calls an "exciting and serendipitous finding."

According to a small study and preliminary report, sildenafil can shrink disfiguring lymphatic growths in children, know as severe lymphatic malformations. The cause of the growths is unknown, but the masses of fluid and lymphatic vessels can grown as large as a basketball.

Doctors aren't sure how sildenafil works to shrink the growths, but one theory is that it stimulates circulation in the lymphatic system, allowing fluid to drain. The drugs new-found property was discovered while an infant was being given sildenafil for pulmonary hypertension, and doctors observed that a lymphatic growth shrunk during the treatment.

The cost of the treatment is reportedly up to $1,000 a month, but Pfizer has been donating the drugs. That's great - they win some points for that. But my question is, why is it so expensive in the first place? The drug is Revatio, which is essentially the same thing as Viagra, right? Is it just more expensive because it's packaged in a different dosage? That's one of the silly things about the pharma business - they charge you more for a smaller dose.

Anyway, the discovery is good news for kids with this rare condition, and may not be a cure, but at least offers hope for treatment.

Nitric oxide, the catalyst for Viagra's magic, has a number of other important functions in the body. It's been established that NO can stimulate healing (besides sexual healing, wise guy). NO has properties that combat bacteria, stimulate immune response, and promote healing in wounds, and it's ideal for tough-to-treat MRSA (methicillin-resistant S. aureus) infections. The problem is that it's a gas, and so far there hasn't been a good way to deliver it to the site of an infection.

Welcome to the world of nanoparticles. Nanoparticles are - well, the most important thing about them is that they're really, really, really tiny, so they can go places bigger particles can't. Now researchers have developed NO-releasing nanoparticles that can penetrate skin, where they unleash that NO like scrubbing bubbles on infected soft tissue.

Oh, yeah - and the nanoparticles had one other interesting effect in lab tests: they caused rats to get erections. Bonus.

So, how do you think the researchers came up with that bright idea? One of the co-authors of the paper describing the study "notes that, beyond the antimicrobial and wound healing applications, the important role of nitric oxide in maintaining vascular health also lead to the team's testing of the efficacy of NO nanoparticles in addressing conditions associated with endothelial dysfunctions."

Translation: "We know what Viagra does, so we thought we'd give it a shot and see if this worked too."

"NO nanoparticles were shown to increase erectile function when applied topically to the penis of rats...and even more importantly, in a post-radical prostatectomy animal model with cavernous nerve transection - a clinical scenario in which PDE-5 inhibitors (Viagra) are ineffective."

Sorry. Now you all need a little brain bleach to expunge the image of some unfortunate lab assistant tasked with applying this stuff to rat genitalia, but the takeaway is that it may be able to get the job done even when Viagra can't - giving hope to those whose erectile dysfunction is Viagra-resistant.

I could see the development of NO-delivering nanoparticles having a similar trajectory to that of Viagra: a drug developed for one purpose that turns out to be wildly effective at something much more compelling. Oh, sure, saving lives is great and all, but face it, stiff erections trump staph infections.

If you know your Viagra history, you know that the drug sildenafil was originally developed as a medication to treat heart conditions and high blood pressure. At the time, it was considered a flop at that, but more than made up for it with its spectacular sexual side effects.

Viagra's monumental property of countering erectile dysfunction all but eclipsed any other medical applications. There has been some continued research, and sildenafil has proven effective in treating pulmonary hypertension as well as a few other less common conditions.

Now it seems researchers were perhaps a little too hasty in tossing in the towel on using Viagra for cardiac treatments. Some 15 years later, a recently published study shows that sildenafil may have dramatic benefits for patients suffering from diastolic heart failure, working within minutes. This has big implications. "Of all the patients aged over 60 who are in hospital because of a weak heart, half suffer from diastolic heart failure" explains Prof. Dr. Wolfgang Linke, author of the study.

The article indicates the initial experiments were done with dogs having diastolic heart failure. Perhaps that's what was ailing Ingrid the pitbull, who we met in our last post. She was rescued from death's door step by a quick-thinking vet who prescribed Viagra. Maybe the doc was ahead of the curve and had already read the medical literature.

Paradoxically, the drug helps by relaxing heart tissue that has become too stiff. Not what comes to mind when you think Viagra, but the enzyme that the drug inhibits acts differently in different organs of the body.

Just goes to show, the little blue pill truly is a wonder drug: it softens hard hearts and hardens soft...

Condom maker Durex announced last week the launch of a new condom produced in partnership with Futura Pharmaceuticals that could revolutionize the way men look at prophylactics. In fact, it may even give some incentive to slip into one. And  its producer are hoping it may help them gain some ground against Trojan, which rules the U.S. condom market with a 75% share, compared to Durex's 6-8%.

Dubbed "Viagra in a condom", the product is intended to help men who have difficulty staying erect or may feel inhibited by wearing a rubber. The condom tip contains a small amount of Zanifil gel, which will stimulate blood flow to the wearer's penis, resulting in a firmer, larger erection. An additive aids in quick absorption through the skin. The gel is derived from nitroglycerine, which dilates blood vessels (like Viagra, it raises levels of nitric oxide, but by a different mechanism). It acts pretty fast, so your little soldier won't be left dangling there like a deflated balloon animal.

So, is this a Viagra killer? Nah. There isn't any comparison yet of effectiveness, but I'd be willing to bet that a dab of Zanafril doesn't pack the same punch goof ol' Vitamin V. Plus there will be some people who won't be able to use this product. There's not been much mention of side effects, but it's guaranteed that the gel will give someone a rash (in a very uncomfortable spot), and if the condoms are latex, that precludes anyone with latex allergies. However, the product is likely to be popular with younger men who have occasional difficulty, confidence issues, or feel that Viagra is for geriatrics.

The condoms over-the-counter availability has been a selling point, but we could also see where that could be a drawback. When you slide these over to the checker at the drugstore, you're basically broadcasting to the world: I can't stay hard. So we predict there will be big bucks to be had selling these online. No word on a price tag, although the maker has said they will have a "premium" cost. Hmm. What could that mean? Something like $5.00 each?

The makers foresee another possible setback. Women buy about 40% of the condoms sold. Says Futura CEO James Barder: "If the packaging says it will give you a bigger penis, and a woman gives it to a man, it might cause a reaction, like 'What, you're saying my penis is small?'"

Or, "What, you're saying I can't stay hard long enough to satisfy you?"

Apparently without irony, Barder added:
"This area does have sensitivities. Positioning is critical."

Indeed.

Hope springs eternal that a remedy will be found for low female libido, but that search has suffered another setback. BioSante Pharmaceutical's stock plunged on the news that its "female Viagra" drug, LibiGel, was no more effective than a placebo in trials. The topical formula is a testosterone gel for women.

Other studies suggested that their formula worked (and testosterone cream is often prescribed "off label" to treat low sex drive in women), so the company expected safety concerns to be its biggest obstacle.

Although Pfizer gave up several years ago on using sildenafil for women, there were reports last year that the company was looking into another drug - a compound called UK-414,495 - but then that seemed to hit a dead end as well.

Why is the formula for "female Viagra" so elusive? Maybe it's because comparing female and male sexual response is like comparing apples and oranges - or apples and bananas, if you prefer. Viagra works on the hydraulics of the sexual anatomy - the  blood vessels that engorge the genital tissue - not the mechanisms that generate libido or sexual desire. The assumption is that's a given, that guys will have no problem with "wanting" to have sex. The issue is not desire, but ability to perform. Whereas with women, it's often the interest itself that needs to be stimulated.

Maybe that's why the placebo was just as effective as the drug in the trials - they say the most important sexual organ is between your ears.

As we've noted here before, Viagra doesn't work for everyone who suffers from erectile dysfunction. In fact, some ED has proven downright drug resistant - some men who have take Viagra don't get the desired results.

A team of doctors has devised a treatment method that may help with these tough cases. The procedure involves inserting stents - small mesh tubes - into pelvic arteries to keep them open and increase blood flow. Although Viagra's action dilates blood vessels, if the vessels themselves are blocked enough, circulation will still be compromised and the blood won't get to where it needs to go. Implanting stents had a positive effect for 20 out of 30 patients who had the procedure, which is an impressive success rate.

If you're heard of stents being used before, it's most likely been in relation to heart surgery, since stenting is most commonly used to open blocked blood vessels around the heart. The medical company, Medtronic, that is sponsoring the studies, won't comment on the design of the pelvic stents as compared to the heart stents they make.

Doctors involved in the study are quick to point out that this is very preliminary and experimental research, and the stenting procedure is not intended to be a substitute for Viagra or other ED drugs. "We see this as an adjunct to current therapy," said research head Dr. Jason Rogers. "We can't recommend that doctors start doing this."

It doesn't sound like this is an operation that will make Viagra obsolete, especially since there are various causes of ED. But for some people, it might get things moving down there enough for the drugs to do their job. 

It's well established that Viagra can affect some people's eyesight - blurred or bluish tinged vision is a known side effect of the drug. Not a common one, but it happens. But anecdotal evidence and some preliminary medical studies indicates that Viagra may affect hearing as well.

An article published earlier this year in The Laryngoscope cited 47 cases of sudden hearing loss associated with Viagra or other PDE-5 inhibitors such as Cialis or Levitra (with the change in hearing occurring within 24 hours of the patient having taken the drug). Over 200 other cases were reported but not included in the study due to lack of detail. Average age of those experience hearing loss was 57. The majority lost hearing in one ear only. (It was also reported that the ratio of male to female patients reporting hearing loss was 7 to 1, but it's hard to know the significance of that given the fact that not many women take Viagra).

Doctors don't know how these drugs might cause hearing loss, but one theory is that increased blood flow to the inner ear damages tissues. This seems plausible. The same increased circulation and dilation of blood vessels that causes headaches and a sense of pressure in the head is blasting blood into the delicate tissues of the inner ear. Or it could be some other physiological process. And although the reported cases involved sudden and dramatic loss of hearing, it seems it could also be possible that a regular Viagra user might experience less noticeable and cumulative hearing damage over time.

There's no conclusive evidence that Viagra or similar ED meds directly cause hearing loss. The connection between the meds and hearing loss in these cases was temporal - meaning it happened soon after the drug was taken. All doctors can say is that "further research is warranted," and that patients should be warned about this potential side effect. But if you're a regular user of an ED drug and you're over 40, it might be a good idea to get your hearing checked periodically.

The press was buzzing over a new research study which showed that Viagra doesn't appear to negatively affect vision. We've read through the research, so you don't have to. Here's the title:

Retinal Effects of 6 Months of Daily Use of Tadalafil or Sildenafil
Arch Ophthalmol. 2009;127(4):367-373.

"Tadalafil" is the generic name of Cialis; "Sildenafil" is the generic name of Viagra.

What they did:
Took generally healthy men with mild erectile dysfunction. Gave some Viagra (50 mg), some Cialis (5 mg), and some a placebo every day for 6 months. Checked their retinas; everything seemed fine.

Who paid for the study:
Eli Lilly, the makers of Cialis, paid for the study. They wanted to show that Cialis is safe for everyday use. Viagra was included in the study for comparison. Levitra wasn't tested.

What it tells us:
It's pretty safe to take Viagra or Cialis every day, and it doesn't cause any medium-term eye problems. The vast majority of patients were able to tolerate the drugs without any serious problems.

What it doesn't tell us:
The test only went on for 6 months, so it doesn't provide information on long-term effects.

Cool things we found out:
Cialis reaches peak plasma concentrations 2 hours after a single dose
Viagra reaches peak plasma concentrations 30 minutes to two and a half hours (mean 88 minutes; median 60 minutes)

So it seems like Viagra takes full effect very differently for different people, even on an empty stomach. For some people it takes only 30 minutes, others over two hours. Cialis seems to take two hours to take full effect.

If you're tired of popping blue pills, there may be some hope on the way. Scientists have developed nanoparticles loaded with nitric oxide. Rub this onto the appropriate area of the body, and it produces amazing results - at least in rats:

In the study, to be published today at the annual meeting of the American Urological Association, Davies and his colleagues loaded the nanoparticles with nitric oxide, a chemical that occurs naturally in the body where it makes blood vessels expand and fill with blood.

They applied the particles to the skin of rats bred to suffer from impotence. They observed a rapid and strong response.

The advantages of such a technique are obvious. Drugs like Viagra, Cialis, and Levitra affect the entire body, and so produce side effects like headache, stuffy nose, etc. A drug you apply directly to the area needing engorgement is likely to work more quickly and produce fewer side effects.

This is obviously very early research, so don't look for it at your local pharmacy, but this is something to watch.