by Shiban Ganju
After a year of worrying about the health reform – that wasn’t, and economic meltdown – that was, a phone call from brother in law (BIL) made me ruminate about sexually dysfunctional people. They are of two types: overachievers and underachievers. The news of our latest overachiever, Tiger Woods had caused considerable jealousy and anguish to BIL. Reason: Tiger ‘wood’ and BIL wouldn’t. Years at the hedge fund desk had sapped his libido into ‘libidon’t’.
I would not have found out about BIL’s problem, had he not fainted and fallen flat on his face. He phoned to tell me that he felt dizzy often and had fainted thrice. I was aware, that years of two-Marlboro-packs-a-day had smoke- grilled the arteries of his heart and legs into spastic narrow channels and now he had to take nitrate pills to relax them. Drugged vessels would dilate and ease the blood flow. But with drugs, bad always accompanies good. As a side effect – especially, if he stood up suddenly –his legs would accumulate all the blood gushing down with gravity; his blood pressure would drop and his blood- less head would swirl. Fainting spells pointed to excessive fall of blood pressure, which would spin him out of his senses.
Just to pick on him, I asked, “What other medicine are you on? Are you taking Cialis?”
“No, I am not.”
“Then it must be Levitra or Viagra.”
“How do you know?” he was surprised. The fact is, I didn’t know – until then.
“BIL, doubling your vessel dilators is a no-no.”
While we have no numbers on Tiger Woods' predilection, BIL is one of many with his affliction. According to NIH, 30 million people in the USA – probably many millions more in the world- are living a happy asexual life. OK, they may not be happy, but they don’t seem be as concerned as the pharmaceutical companies had hoped.
The sales of Viagra-Cialis-Levitra have been less than predicted for the market size. This sexually shattering news even mounted the pages of New York Times on Dec 4, 2005, when Alex Branson reported,
“Seven years after Pfizer made Viagra a cultural touchstone and commercial blockbuster, the market for impotence medicines appears to have fallen well short of what was once predicted.
Heavy advertising to consumers, totaling more than $400 million in 2004, has made Viagra and its newer competitors, Cialis and Levitra, among the best-known drug brands in the United States, and their combined global sales reached about $2.5 billion last year. But the number of new prescriptions for the drugs has fallen steadily this year. Doctors wrote about 10 percent fewer new prescriptions in October than they did in October of 2004.”
Much to the consternation of Viagra-Cialis-Levitra pushers, it seems that people preferentially spend their money on the therapy of some real health issues like high blood pressure, diabetes, high cholesterol, anxiety and depression, which may even be the primary causes of erectile dysfunction (ED) – the politically correct term for impotence.
But such compounds are what intrigue is made of: a mixture of glory, sex, betrayal and money.
The story starts in 1978, when a biochemist, Robert Furchgott, discovered a substance in the lining of blood vessels, which he called “endothelium derived relaxing factor.” Further research revealed that the relaxing factor was Nitric Oxide (NO), which, through a series of chemical steps, increases the levels of a muscle relaxer: cGMP. After its work is done, cGMP disintegrates under the influence of another compound called phosphodiesterase. Twenty years after the initial fundamental discovery, Robert Furchgott won the Nobel Prize in medicine 1998, for analysis and understanding of endothelium derived relaxing factor.
This profound discovery set the research in high gear for developing drugs to relax coronary vessels and reduce blood pressure. The scientists at Pfizer developed one such drug – Sildenafil, which blocks phosphodiesterase, thus preventing the breakdown of cGMP. That prolongs the action of cGMP, making the dilated blood vessels stay engorged with flowing blood for longer time.
The drug developers at Pfizer tried to treat angina with Sildenafil. They not only found it ineffective but it also produced unnecessary side effects. But the clever business developers at Pfizer found Sildenafil’s main virtue in its vice and marketed it for the side effect: to treat erectile dysfunction. The side effect proved profitable beyond belief. The trade name was Viagra.
A new class of drugs was thus born: phosphodiesterase (PDE) inhibitors. The race to find similar drugs began. In 1994, a biotech company, ICOS, started working on a different PDE inhibitor: tadafil. Eyeing potential future profits, Eli Lily pharmaceutical company entered into a joint venture with ICOS to develop and market this drug. After FDA approved tadafil in 2004, Eli Lily bought out ICOS for 2.3 billion dollars in 2007. Then they promptly closed ICOS Corporation and fired most of its employees.
Between high tension acts of glory, profits, discoveries and brutal business, comic relief is always welcome. “The 2007 Ig Nobel Prize in Aviation went to Patricia V. Agostino, Santiago A. Plano and Diego A. Golombek of Universidad Nacional de Quilmes, Argentina, for their discovery that Viagra aids jet lag recovery in hamsters.”
Post market surveillance of the PDE inhibitors has revealed some other effects. It so happens, that there are many types of PDE scattered in various organs and the result of PDE inhibitor action may be good or bad. Inhibition of PDE in lungs dilates its blood vessels, which has a positive therapeutic benefit for high blood pressure in the lungs – pulmonary hypertension, which was a difficult-to-treat disease before the advent of these drugs. But inhibition of PDE in retina causes vision disturbance and that in ear gives hearing problems. Occasionally, irregularity of cardiac rhythm may be a fatal consequence.
These side effects, including fatality, have not dissuaded the hedonists. The popularity of PDE inhibitors has increased with the young recreation seekers, who take it not only to fake their masculine prowess, but also to induce an illusion of enhanced experience in combination with other illegal drugs. A mixture with ‘ecstasy’ and opiates makes “Sextacy”, “trail mix” or “rockin and rolin” and a mixture with amyl nitrite results in death.
Sildenafil and BIL have had a long relationship. As a macho hedge fund trader, he played with the stock options of these dug companies. He knew the drug would strike it big when, in 2006, he found that the United Auto Workers had succeeded in getting GM to pay for Viagra under the labor agreement. GM had become the biggest private buyer – about 17 million dollars worth – of life style drugs, mainly Viagra.
BIL envisioned, speeding hunks of steel made by the masculine hands by Sildenafil-ed auto workers, would bring in the new generation of Viagra power cars. So he bought GM stock too. But Viagra stimulus was not enough to turn GM into an alpha-male of car makers. BIL lost money and later his job.
The collapse, of BIL’s hedge fund company left him with depression, which led to ED. He is trapped in the cycle of ED and depression feeding on each other, making both worse. After the failure of his hedge fund, it has been difficult for him to keep up with the down Jones. Bad economy has taken its toll. He can’t trade options; now he just swallows the ‘blue pill’. But BIL is stoic about it; everyone goes through hard spells. Look at Tiger Woods.