Excerpt from "Anti-Inflammatory Drugs: How to Sort Out the Choices"
Mark G. Papich, DVM, DAVCP North Carolina State University Raliegh, NC
Central Veterinary Conference Aug. 23-26, 2003:
Renal toxicity
In the kidney, prostaglandins play an important role to modulate the
tone of blood vessels and regulating salt and water balance. Renal
injury caused by NSAIDs has been described in people, and horses, but
has not been well documented in small animals. Reported cases of
toxicity occurred when high doses were used or when there were other
complicating factors. Renal injury occurs as a result of inhibition of
renal prostaglandin synthesis (Brown, 1989). In animals that have
decreased renal perfusion caused by dehydration, anesthesia, shock, or
pre-existing renal disease, this leads to renal ischemia (Mathews,
1996).
Additional information is needed with regard to the safety of currently
available COX-2 inhibitors on the kidney. Some of the prostaglandins
that play an important role in salt and water regulation and
hemodynamics in the kidney are synthesized by COX-2 enzymes (Rossat et
all 1999). Constitutive COX-2 is found in various sections of the
kidney and administration of drugs that are selective for COX-2, do not
spare the kidney during adverse conditions. Administration of a
specific COX-2 inhibitor to salt-depleted people decreased renal blood
flow, glomerular filtration rate, and electrolyte excretion (Rossat et
al 1999). One of the concerns during the perioperative period is the
renal safety of NSAID in anesthetized animals. Studies published on
carprofen administration to anesthetized healthy dogs showed no adverse
effects on renal function (Ko et al 2000).
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Excerpt from "Clinical Problem Solving: Putting Clinical Pharmacology
to Work"
Mark G. Papich, DACVCP North Carolina State University Raleigh, NC
Central Veterinary Conference August 23-26 2003
Adult vs Senior/Geriatic Patients
Pets seem to be living longer, and veterinarians are treating more
age-related problems in pets. Veterinary clinics have developed
specific programs in their hospitals for "Senior Pets". There are diets
designed specifically for senior dogs and cats, and even a medication
for the aged dog with cognitive dysfunction (selegiline, Anipryl).
Unfortunately, there is practically nothing available to guide
veterinarians on drug administration to older animals compared to
younger adults. Recommendations published in clinical reviews are based
on extrapolations from studies in people, or the assumption that drug
disposition probably is different in aged animals. Since organ function
declines with age, we presume that drug clearance is affected.
As one ages, there are age-dependent changes in drug distribution that
are a result in a decrease in body water and an increase in the
percentage of body fat. There may be an increase in the volume of
distribution for lipid-soluble drugs and a decrease in distribution for
water-soluble drugs. Unfortunately, there is no available published
information to confirm that these changes in body composttion occur for
veterinary species. >snip<
Disease-Related Differences
Changes in renal function
Age-dependent changes in renal clearance may affect drug clearance
because both glomerular filtration and tubular secretion of drugs
decrease with age (Rowe et al, 1976). >snip<
Changes in Hepatic Function
Like other functions, there are also age-dependent changes in hepatic
clearance. Liver size decreases with age as well as liver blood flow
and microsomal enzyme activity. >snip<
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According to "Minimizing the Risk Factors Associated With the Veterinary
NSAIDs":
One of the most common factors predisposing patients to injury is
surgical anesthesia. Following surgical procedures is one of the four
most common instances that GI injuries occur in dogs.
http://avma.org/onlnews/javma/apr04/040415g.asp
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GENERAL CONSUMER DRUG CONCERNS
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Drugs Of Choice: Just Because They're Advertised On TV Doesn't Mean New
Prescription Medications Are Safe
May 17, 2002
LOS ANGELES (The Los Angeles Daily News) -- One person's miracle drug is
another person's poison pill.
For Encino resident Elaine Sherman, Lotronex worked. But the medication,
recalled in 2000 after only 10 months on the market, was fatal to some.
Lotronex, which treats irritable bowel syndrome, was pulled when side
effects forced some patients to have portions of their colons removed.
At least five died.
That didn't deter Sherman from seeking the drug, the only one that had
worked for her in 20 years of visiting gastroenterologists, homeopaths
and nutritionists.
"I tried other countries, and nobody had it but us," Sherman said. "I
called pharmacies in Canada. I had friends check the Internet."
Sherman wasn't alone in her quest. The FDA was swamped with calls from
Lotronex users lobbying for limited access to the drug.
The story of Lotronex captures the complexities that surround the issue
of drug safety, a web formed by the FDA, pharmaceutical companies,
doctors and patients. All have a part to play. The FDA must thoroughly
test a pharmaceutical company's drug, doctors must heed warnings before
prescribing a medication and patients must adequately weigh pros and
cons.
Follow each step, experts say, and it's still a gamble. There's no such
thing as the perfect pill. Reactions to drugs are individual and vary
with gender, race and age.
THE ME-TOO PHENOMENON
A recent study published in the May 1 issue of the Journal of the
American Medical Association shows that the risks posed by new drugs
entering the market may be substantial. The study, led by Dr. Karen
Lasser of Cambridge Hospital and Harvard Medical School, found that one
in five new drugs produced significant side effects that were not
discovered until after FDA approval.
Of 548 drugs approved between 1975 and 1999, 56 -- roughly 10 percent --
later received warnings of serious side effects or were recalled. The
figure rose to 20 percent for drugs approved toward the end of the time
period studied. The study recommended doctors avoid prescribing new
drugs in favor of older established drugs, unless the new drug
represented a breakthrough.
A rebuttal piece by Drs. Robert Temple and Martin Himmel of the FDA
argued the study overstated the dangers. Drug trials involving a few
thousand patients might not reveal all adverse effects -- some of them
rare -- that appear when a drug enters the general population, they
wrote. They also saw no need for doctors to wait before prescribing a
newly approved drug. "It is worth observing that existing therapy does
not always prove to be completely safe and fully satisfactory and that
there is value in having alternatives," they wrote.
Local physicians say the study reinforced their belief in proceeding
with caution when considering new drugs. Patients suffering from a
terminal illness have little to lose. But many drugs introduced to the
market are "me-too drugs," one company's version of an existing product.
"If I had a life-threatening disease, I might take the risk," said Carlo
Michelotti, chief executive officer of the California Pharmacists
Association. "If it's a me-too drug, I wouldn't be anxious to jump on
the bandwagon until it had some history."
STAYING VIGILANT
Dr. Kenneth Murray, a family practitioner in North Hollywood, said he
waits six months to a year before prescribing new nonbreakthrough
medications to his patients. At Providence St. Joseph Medical Center in
Burbank, Murray also serves on a committee that determines which drugs
to stock at the hospital.
"Compared to 20 years ago, pharmaceuticals today are much more powerful
drugs," he said. "The potential to cause harm is enhanced. They really
have tremendous effects on the body."
Doctors say they have a responsibility to prescribe medications properly
and monitor the results. Both doctors and pharmacists also must consider
drug interactions. Even a drug as seemingly benign as aspirin or
ibuprofen can have an adverse effect if taken by the wrong person, said
Dr. Michael Hirt, an internist and director of the Center for
Integrative Medicine at Encino Tarzana Regional Medical Center.
With Lotronex, some doctors didn't pay attention to the patient profile,
said Hirt, who treats Sherman. Lotronex was approved for women with
chronic diarrhea caused by irritable bowel syndrome. But some doctors
prescribed the medication to IBS sufferers with constipation -- a factor
in some but not all of the problem cases, according to the FDA.
The FDA and Lotronex maker GlaxoSmithKline continue to discuss a plan
that would allow the medication to be prescribed in specific
circumstances, said FDA spokesman Jason Brodsky.
"There are two sides to every drug withdrawal," Brodsky said. "Lotronex
is a case in point where the benefits of a drug for some meant a
dramatic improvement in the quality of life. But for others, the product
had serious effects."
Dr. Greg Thompson runs the Los Angeles County-USC Drug Information
Center, which advises health professionals on drugs, including dosages
and side effects. He is critical of efforts to revive Lotronex even
under restricted conditions.
"This isn't cancer," Thompson said. "Irritable bowel syndrome isn't
worth losing your colon over."
Thompson said doctors and pharmacists need to be more vigilant in
reporting adverse reactions to the FDA's MedWatch. The JAMA study
estimated that less than 10 percent of adverse effects are reported to
MedWatch.
Thompson also would like to see a formal last phase added to drug trials
in which physicians are required to report adverse effects for at least
a year after approval.
"In theory, doctors are supposed to do that now," he said. "But it's a
passive participation. We need to be active."
AS SEEN ON TV
The impact of direct marketing by pharmaceutical companies is yet
another piece of the drug-safety puzzle. Doctors say patients often
demand the medications they see advertised, with little knowledge of the
risks.
The JAMA study noted that new drugs are heavily marketed to both doctors
and consumers, which means they may be in wide distribution before
adverse effects are known.
"I don't feel pharmaceutical companies should market to patients," said
Dr. David Wong, an internist who serves on the committee that oversees
pharmaceuticals at Kaiser Permanente in Panorama City. "Good marketing
is what sells these days."
In his North Hollywood practice, Murray has seen the effects of this
marketing. For years, he has known birth control pills can also reduce
acne and, like many doctors, has prescribed them for this off-label use.
The makers of one pill took the unusual and costly step of returning to
the FDA to get approval for this added use. After television commercials
aired for Ortho Tri-Cyclen, many of Murray's female patients asked to
switch to that brand.
"It's brilliant marketing," Murray said. "The company can accurately say
it's the only birth control pill so approved. The truth of the matter is
they all do that."
Doctors, too, if they have success with a particular medication, can be
swept up by hype. So what's a patient who wants to make smart decisions
about medications to do?
The main thing patients can control is how educated they are about the
medications they take, experts said. Patients should have detailed
discussions about benefits and risks with their doctors and pharmacists.
Another thing doctors and patients can do is increase the focus on
wellness. Preventive measures such as nutrition and exercise should be
the first line of defense, Wong said.
"People want the magic pill," he said. "The truth is, everything has a
side effect. There's no free gift."
Copyright 2002 The Los Angeles Daily News. All rights reserved.