Thursday, January 3, 2008

Innovations in Pharmacology: An Arrested Development?

With the recent controversies surrounding the side - effects of BEXTRA and VIOXX, does this mean that recent advances in pharmacology had reached a dead end?


By: Ringo Bones and Vanessa Uy


The supposedly side – effect free and more effective substitutes for aspirin – BEXTRA and VIOXX- are fast becoming a non-starter for the multi-million dollar pharmaceutical industry. By now, almost all of us are wondering if the “miracles of modern science” has recently abandoned the field of pharmacology. Is this problem truly insurmountable as implied by the latest buzz - words in pharmaceutical / pharmacological publications? Let’s cite some examples.

Before the advent of antibiotics like penicillin, the only cure available for venereal diseases are arsenical compounds (developed during the 19th Century) so toxic that the cure was more likely to kill you than cure you. Now -the problem created by the misuse of our tried-and-true arsenal of antibiotics - are the drug-resistant pathogens engendered by the improper use and administration of antibiotics. That’s why back in the 1990’s arsenicals were re-introduced as a venereal disease cure against multi drug resistant syphilis.

Back in the 1950’s, thalidomide was developed as a much safer substitute for barbiturate-based sleeping pills. It was reported back then that one woman attempted to commit suicide by taking thalidomide based pills and failed to take her own life. Then the teratogenic effects of thalidomide surfaced after the drug was already widely marketed in Europe.

Probably developed during the height of the Cold War i.e. mid to late 1950’s – pyridostigmine bromide – was developed as a substitute for atropine sulfate to counteract the effects of cholinesterase inhibitor based weaponry i.e. nerve gas / nerve agents. Atropine sulfate was known to interfere with the infantry’s physical exertion i.e. dodging bullets upon intramuscular injection. Pyridostigmine bromide was designed to avoid this “inconvenience.” But back in April 1995, pharmacologist Mohamed Abou-Donia, while examining the nature of “Gulf War Syndrome” discovered that pyridostigmine bromide while effective at protecting soldiers against nerve agents by binding to – and shielding – the enzyme that nerve gas attacks. But it also grabs onto enzymes that help break down toxic chemicals thus the probable agent responsible for causing “Gulf War Syndrome.” This is quite the opposite of what atropine sulfate does – by increasing the body’s metabolism so that the nerve agents are flushed out of the body before it can do serious damage.

While a number of pharmaceutical companies choose to wait for unfortunate side – effects to occur before pulling their product off the market. Some – like the ASTRA ZENECA company, choose to voluntarily withdraw their product before a large number of unfortunate side – effects or fatalities could occur. ASTRA ZENECA developed the anticoagulant XIMELAGATRAN as a less toxic replacement for warfarin. XIMELAGATRAN was the first member of direct thrombin inhibitors that can be taken orally. For the benefit of those who do not know what is warfarin, it is the main ingredient in rat poison. Warfarin kills rats by making them bleed to death due to its anti coagulant effects. Also, warfarin makes a good rat poison / rodenticide because in case of accidental poisoning to humans, Vitamin K tablets can be used as a very effective antidote. In 2006, ASTRA ZENECA – the manufacturer of XIMELAGATRAN – announced that it would not attempt to market XIMELAGATRAN after reports of hepatoxicity (liver damage) during trials,and to discontinue it’s distribution in countries where the drug had been approved.

While in the last week of July 2007, the type-2 diabetes maintenance drug AVANDIA – a ROSIGLITAZONE and METFORMINE combination in one convenient pill - has been under scrutiny because recent studies of 7,500 patients have shown that 1 in 50 developed a heart attack. While some, developed fluid retention problems. One-fourth of their test subjects is aged below 50. This report has caused the stock value of GlaxoSmithKlein – AVANDIA’s manufacturer – to fall. Due to lack of a suitable replacement, and since AVANDIA had become ubiquitous with type-2 diabetes sufferers around the world. Majority of the world’s pharmaceutical regulatory bodies has just advised General Practitioners to closely monitor their patients who are presently taking AVANDIA.

This bothersome phenomena where innovations can no longer improve a trusty –but – rusty “workhorse” has finally invaded the world of pharmacology. This “phenomena” had plagued the hi-fi / audio industry for the past 20 –or so – years. It has the effect of rendering the decade –or more- advances in digital recording unable to “out – beauty” the good ol’ analogue sound recording i.e. 30 in/sec magnetic tape recording.

Will the tropanol derivative atropine – despite its negative physiological effects – be the “better” choice in protecting the fighting men and women the world over against cholinesterase inhibitor based weaponry well into the next century for the reason that replacements are proven to do more harm than good? And what about aspirin, are we just fortunate that it was discovered and marketed well before draconian laws to govern the pharmaceutical industry were legislated and enforced? From a pharmacological standpoint, it seems that chemical – based pharmaceuticals are inherently toxic to the human physiology. This is why the major pharmaceutical companies the world over are investing millions in their Research and Development department to develop drugs / agents that work using the principles of the science of genetic engineering like BENITEC’s RNA interference therapy. Presently, it seems the careful management of therapeutic regimens is the only viable option. In retrospect, the progress of the science of pharmacology has always been dependent – or hindered depending your point of view – to the current “politics” that engendered the legislation of draconian laws that regulate the pharmaceutical industry.

3 comments:

Yoav said...

As someone who became familiar with Duke University pharmacologist Dr. Mohamad B. Abou-Donia's work with regard to finding out if Gulf War Syndrome is a real affliction or just something the American "liberal media" created, Dr. Abou-Donia's findings really did show statistically significant correlation with regards to the harmful effects of experimental anti-nerve agents / anti-cholineesterase inhibitor "cures". Dr. Abou-Donia even has findings proving the harmful effects of a long-used mosquito repellent by the US Armed Forces called DEET. You can also try checking out Dr. Asaf Durakovic's work on the harmful health effects of depleted uranium projectiles used in Operation: Desert Storm.

Maribeth said...

From a perspective of the pharmacological industry. Pyridostigmine Bromide or "PB Pills" as they are colloquially known in the movie JARHEADS was approved by the US FDA back in 1955 for use in treating myasthenia gravis, a neuromuscular disease which causes muscle weakness and fatigue. PB pills are only effective against soman and it's related organophsphate nerve agents. PB is next to useless against the cholinesterase inhibitive properties of sarin nerve gas.
The continued work of Dr. Mohamed B. Abou-Donia also revealed that some asthma medications interact negatively with lawn pesticides, sometimes with lethal consequences. Looks like the Gulf War Syndrome is no longer confined to Operation: Desert Storm as the US Government want's us to believe.

Timur said...

Compared to Dr. Asaf Durakovic's findings on the detrimental effects of depleted uranium armor piercing incendiary rounds on US servicemen during Operation Desert Storm, the Duke University pharmacologist Dr. Mohamed Abou-Donia's work on pyridostigmine bromide and its detrimental effects on US soldiers is relatively obscure in comparison. Even though Dr. Abou-Donia's latter findings also include the harmful effects of the mosquito repellant DEET to asthmatics using anti-asthma medication.