The nonsteroidal anti-inflammatory drugs (NSAIDs) Celebrex and Vioxx
have recently come under fire when it was admitted that these drugs
could significantly increase the risk of heart attack and stroke. Are
these the only NSAIDs capable of increasing this risk though?
Many heart disturbances, including
heart attack, result from decreased blood flow to the heart. Common
causes of decreased blood flow include arterial plaque formation, blood
clots, and narrowing of the arteries from muscular contraction of the
Arterial plaque formation starts
with damage to the blood vessel walls. This leads to depositing of cholesterol
and calcium on the arterial walls. One of the most common causes of
the arterial damage is high blood pressure caused from constriction
of blood vessels. Various factors may lead to blood vessel constriction.
These include elevated serum calcium, elevated insulin levels in type
2 diabetes, and epinephrine (adrenaline) induced constriction. NSAIDs
constrict blood vessels as well, which leads to an elevation of blood
pressure. Increased blood pressure may result in narrowing of the arteries
from plaque due to resulting arterial damage. This narrowing of the
arteries not only increases the risk of heart attack, but also of thrombic
and embolytic stroke.
Because NSAIDs constrict blood
vessels, these drugs increase the risk of angina, heart arrhythmias,
and heart attack in people with already impaired perfusion to the heart.
These include individuals with previous angina, or heart attacks, history
of congestive heart failure, diabetics, and individuals who tend to
put out too much epinephrine, etc.
Further risk comes from the fact
that NSAIDs inhibit prostaglandins, including prostacyclin, also known
as prostaglandin I2 (PGI2). PGI2 is produced by healthy endothelial
cells of blood vessels. The roles of PGI2 are to dilate blood vessels,
to increase blood flow, and to inhibit platelet formation and blood
clot formation. By dilating blood vessels, blood pressure is reduced,
and more blood reaches critical areas, such as the brain and heart.
This also lowers the risk of heart disease by reducing arterial damage,
which would otherwise lead to plaque formation. By reducing blood clot
formation, the risk of heart attack and thrombic stroke are reduced.
Both damage to endothelial cells and the use of NSAIDs inhibit PGI2
production, which increases blood clot formation and reduces blood flow.
Production of blood clots and reduction of blood flow increase the risk
of angina, arrhythmias, and heart attack, as well as transient ishemic
attacks, and thrombic stroke.
As we can see, the increased
risk of heart attack and stroke are not limited to certain NSAIDs, but
rather can occur with all pharmaceutical NSAIDs. And the problem is
not a new finding. The blood vessel constricting effects of NSAIDs have
been known for decades. Part of the drug approval process includes knowing
how the drug works. NSAIDs are known, and have been known, to work by
consticting blood vessels. When blood vessels are overdilated by inflamamtory
prostaglandins, they become permeable, which leads to leakage of fluids
in to the surounding tissues, and resulting inflammation. By consticting
blood vessels, NSAIDs prevent blood vessels from leaking. It is well
known that the adverse effects of liver and kidney failure by NSAIDs
is due to impeded blood flow to these organs due to this constiction
of the blood vessels. Other organs, such as the heart, as well as glands
are adversely affected by the impeded blood flow in the same manner.
Therefore, the only explanation for the increased risk of heart attack
and stroke being "discovered" recently would be that the drug
companies and FDA knew about the problem all along and just recently
decided to make this known fact public.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are
commonly used as pain relievers for inflammatory conditions. These drugs
include ibuprofen (Advil, Motrin, Nuprin), naproxen, (Aleve), aspirin,
rofecoxib (Vioxx), and celecoxib (Celebrex). Although, the pain relieving
effects come with some potentially dangerous, and possibly deadly side
NSAIDs work by inhibiting hormones, known as prostaglandins. Prostaglandins
serve numerous functions within the body including regulating blood
pressure, antidepressant, protecting the stomach from acid, etc. Inflammatory
prostaglandins are essential for increasing blood flow to injured areas,
which promotes healing by increasing oxygen and nutrient levels to the
injured site. Prostaglandins do this by dilating the blood vessels.
The inflammation occurs when the blood vessels are dilated, which causes
the blood vessels to become permeable. This permeability causes the
small blood vessels to leak fluid in to the surrounding tissues, which
leads to the swelling. NSAIDs decrease the pain and swelling by countering
these inflammatory prostaglandins. This causes the blood vessels to
constrict, thereby reducing leakage of capillaries.
By reducing blood flow, NSAIDs actually inhibit the
healing process. Although this is one of the more mild side effects
of these drugs. Other side effects of NSAIDs include, but are not limited
to, liver failure, kidney failure, aseptic meningitis, loss of vision,
tinnitus (ringing in the ears), high blood pressure, depression, and
The most common side effect is bleeding ulcers, which
leads to the majority of the over 16,000 deaths annually from these
drugs. These ulcerations occur from the inhibition of another prostaglandin
required to form the protective mucous lining of the stomach. This mucous
coating protects the stomach wall from stomach acid. By inhibiting the
formation of the protective stomach lining, the stomach wall is prone
to direct attack from the stomach acid, leading to ulceration of the
stomach wall and internal bleeding.
Constriction of blood flow leads to elevation of blood
pressure. Loss of vision and tinnitus occur from reduced blood flow
to the eye and in the area of the neck, due to the blood vessel constriction.
Prostaglandins play a major role in mood. By countering
prostaglandins, the use of NSAIDs will cause depression.
Kidney and liver failure occur from a lack of blood
flow to these organs. In fact, 2 dozen people died from ibuprofen induced
hepatitis during clinical trials. People with poor perfusion to the
organs, such as those with congestive heart failure, diabetes, Raynaud's,
etc. are at a higher risk for the damage or organ failure since blood
flow is already reduced in these individuals. Further constriction of
the blood vessels by NSAIDs may completely cut off the blood supply
to organs and glands leading to damage or complete failure.
Contrary to popular belief, it does not take long
term use or overdose to cause organ failure. In fact a single, recommended,
dose can cause sufficient constriction of the blood vessels to cause
damage. I know of 4 people that developed kidney failure after taking
a single recommended dose of ibuprofen. And the number of cases is most
likely heavily underreported since adverse effects of drugs are commonly
attributed to other disorders.
The NSAID Bextra, manufactured by the pharmaceutical
company Pfizer, was approved by the FDA in November of 2001. Bextra
was later recalled after it was revealed that the drug could cause potentially
deadly allergic reactions, and the disorders Steven's-Johnson syndrome,
and toxic epidermal necrolysis.
The new proposals for warning labels on these drugs
need to include the risk of adverse effects from recommended use as
well. Not only long term use and overdose as is currently being recommended.
A few other recommendations that I feel should
be implemented include:
- Pulling NSAIDs off the market as was done
with Bextra since the safety studies were either never done, or were
suppressed by the drug companies, or ignored by the FDA, to get approval.
- Requiring more evidence of safety before approving
- Charging pharmaceutical drug company executives,
and FDA officials, with manslaughter when it is shown that side effects
were hidden to gain approval, and it has resulted in deaths. Right
now only pharmaceutical companies are held liable. Although only by
civil liability, not criminal. Fines are sometimes imposed against
pharmaceutical companies, although they are hardly punishment. Fines
are generally around a million dollars, or slightly higher when the
drug companies have made hundreds of millions or even billons of dollars
in profits. This is hardly punishment, and encourages the drug companies
to hide adverse effects since profits will far outweigh any liabilities.
- Heavier civil penalties against the drug companies
to actually punish them for deliberately hiding known side effects,
and for manipulating research to make their drugs appear safe and
- Civil lawsuits should not only include the
drug companies, but also the FDA officials who receive gifts, payoffs,
and jobs to push the drugs through the approval process.
- Cracking down on illegal investments by FDA
officials in to the drug companies they regulate. This is a violation
of insider trading laws. Despite this, nothing has been done to correct
this illegal activity within the FDA despite the illegal investments
being reported for nearly 3 decades.
- Faster action on pulling drugs from the market
suspected of causing harm until safety of the drugs can be established.
- Testing of drugs by independent testing agencies.
Currently the FDA requires the drug companies to provide their own
safety data to obtain approval. If the drug company has already invested
millions of dollars in to the drug, and a safety issue appears the
drug company is not going to reveal the safety issue and risk approval
being denied. This is a major reason drugs are being approved, then
being pulled several years later, after the drug companies have not
only paid for the cost of approval, but have also paid stockholders
and made millions of dollars or more in profits.
- Drugs requiring a prescription when they are
originally approved should remain only available by prescription.
They should not be made available over the counter when the drug's
patent expires. The chemistry, or dangers, of the drug do not change
just because the patent has expired on the drug.