WEB ASSIGNMENT 11
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There are two VERY common NSAIDS used in animal species, phenylbutazone (trade name for human version is Butazolidine) and flunixin meglumine (Banamine). How do these NSAIDS differ from the NSAIDS commonly used in humans? Do they work differently? Have different side effects? Why aren’t they prescribed for human use? [Note: phenylbutazone is on occasion]. Why are they acceptable for animal use?
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7 comments:
Phenylbutazone is an NSAID commonly used in horses for the following purposes:
Analgesia: Pain relief from infections and musculoskeletal disorders including sprains, overuse injuries, tendonitis, arthralgias, arthritis, and laminitis. Like other NSAIDs, acts directly on musculoskeletal tissue to control inflammation, thereby reducing secondary inflammatory damage, alleviating pain, and restoring range of motion. Does not cure musculoskeletal ailments or work well on colic pain.
Antipyresis: Reduction of fevers. Antipyretic qualities may mask other symptoms; therefore, should not be administered for this purpose unless a veterinarian has concluded that the horse would not be able to eat or drink without its use or that the fever might hinder the horse's recovery. http://en.wikipedia.org/wiki/Phenylbutazone
Flunixin meglumine also had oral activity and differs from indomethacin in having more analgesic activity per unit of anti-inflammatory activity. In mice, flunixin meglumine is equipotent to pentazocine and more potent than meperidine and codeine in the abdominal constriction test. In primates, flunixin meglumine at 10 mg/kg i.m., produced a degree of analgesic efficacy comparable to that of a clinically effective dose of morphine (0.3 mg/kg). In contrast to codeine, tolerance to the analgesic action of flunixin meglumine was not observed. Furthermore, flunixin meglumine retained its activity in rats made tolerant to codeine. Unlike narcotics, the analgesic effect of flunixin meglumine is not antagonized by naloxone after acute administration in rats. These results indicate that flunixin meglumine is a parenterally and orally effective analgesic in animals and is unlikely to have narcotic or drug dependence liability. http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=850126&dopt=Abstract
Flunixin meglumine and phenylbutazone were selective inhibitors of COX-1. Carprofen and flunixin meglumine, but not phenylbutazone, inhibited LPS-induction of iNOS. Carprofen and, to a lesser degree, flunixin meglumine had inhibitory effects on NFκB activation.
http://avmajournals.avma.org/doi/abs/10.2460/ajvr.2003.64.211
The only differences that I can see that these drugs have compared to other NSAID’s is that they have extreme analgesic activity. Other than that they do not appear to have a mechanism of action that different than other NSAID’s.
They have the same types of side effects that consist mainly of gastrointestinal upset and toxicity.
Phenylbutazone became available for use in humans for the treatment of rheumatoid arthritis and gout in 1949. However, it is no longer approved, and thus not marketed, for any human use in the United States. This is because some patients treated with phenylbutazone have experienced severe toxic reactions, and other effective, less toxic drugs are available to treat the same conditions.
http://lawrence.osu.edu/ag/butazone.htm
Obviously is these drug are acceptible for horse and cattle use because of the dosage per body weight. Human weigh much less than these animals.
Phenylbutazone used for horses and dogs is a potent pain reliever, antipyretic and anti-inflammatory drug. It’s used in animals usually for lameness that it caused by soft tissue injury, muscle soreness, bone and joint problems.
The drug Butazolidine is used in humans for treating fever, pain, and inflammation. A severe side effect of this drug is that it can cause severe bone marrow toxicity which would cause a dangerous decrease in the patient’s white blood cell count. Because of this effect it is most desirable to receive the lowest effective dose.
Bone marrow depression is seen among both types of drugs for humans and animals, but it seems to affect humans more readily. The other side effects between the two drugs are similar.
The drug Banamine is used in horses for colic and pain relief. With every drug there is a caution on seeking the lowest effective dosage. I’m guessing that since horses weigh much more than humans that it is safer for horses than for humans. Phenylbutazone is given to horses and dogs, but there is a very narrow safety margin for dogs. Usually GI protectant drugs (misprostal, cimetidine, omeprazole, rantidine or sucralfate) are used along with this NSAID in dogs.
http://www.wedgewoodpharmacy.com/monographs/flunixin.asp
http://www.wedgewoodpharmacy.com/monographs/phenylbutazone.asp
http://www.horse-previews.com/1196articles/1196vetcorner.html
http://www.medicinenet.com/phenylbutazone/article.htm
Phenylbutazone has analgesic, anti-inflammatory, antipyrexic, and mild uricosuric properties. The proposed mechanism of action is by the inhibition of cyclooxy¬genase, thereby reducing prostaglandin synthesis. Other pharmacologic actions phenylbu¬tazone may induce include reduced renal blood flow and decreased glomerular filtration rate, decreased platelet aggregation, and gastric mucosal damage.
One manufacturer lists the following as the indications for phenylbuta¬zone: “For the relief of inflammatory conditions associated with the musculoskeletal sys¬tem in dogs and horses.” It has been used pri¬marily for the treatment of lameness in horses and occasionally as an analgesic/anti-in¬flammatory, antipyrexic in dogs, cattle, and swine.
Flunixin meglumine is a non-steroidal anti-inflammatory drug (NSAID) and cyclo-oxygenase inhibitor. It is a potent analgesic, antipyretic, and anti-inflammatory. NSAIDs work by inhibiting the body's production of prostaglandins and other chemicals that stimulate the body's inflammatory response. Some of these actions may be dose dependent. NSAIDs are quickly absorbed into the blood stream; pain relief and fever reduction usually starts within one to two hours.
Flunixin has been indicated in various species, including: Horses: foal diarrheas, shock, colitis, respiratory disease, post-race treatment, and pre- and post ophthalmic and general surgery; Dogs: disk problems, arthritis, heat stroke, diarrhea, shock, ophthalmic inflammatory conditions, pre- and post ophthalmic and general surgery, and treatment of parvovirus infection; Cattle: acute respiratory disease, acute coliform mastitis with endotoxic shock, pain (downer cow), and calf diarrheas; Swine: agalactia/hypogalactia, lameness, and piglet diarrhea.
These NSAIDs have the same mechanism of action however they are much stronger. This makes the drugs very dangerous to use in humans because it can cause severe bone marrow toxicity which would cause a dangerous decrease in the patient’s white blood cell count. With the larger animals the safe dosages cover a larger range. As with most other NSADS sides effects include GI bleeding.
http://www.wedgewoodpharmacy.com/monographs/phenylbutazone.asp
http://www.elephantcare.org/Drugs/phenylbu.htm
www.wedgewoodpharmacy.com/monographs/flunixin.asp
http://www.elephantcare.org/Drugs/flunixin.htm
Phenylbutazone: Butazolidine-
-Humans: Phenylbutazone is a nonsteroidal anti-inflammatory drug (NSAID) effective in treating fever, pain, and inflammation in the body. As a group, NSAIDs are non-narcotic relievers of mild to moderate pain of many causes, including injury, menstrual cramps, arthritis and other musculoskeletal conditions. Since the response to different NSAIDs varies from patient to patient, it is not unusual for a doctor to try a variety NSAIDs for any given condition. However, because of an unique risk of bone marrow suppression (causing dangerously low white blood counts), phenylbutazone is generally reserved only for short-term use in selected patients. It can also cause ulcerations, abdominal burning, pain, cramping, nausea, gastritis, and even serious gastrointestinal bleeding and liver toxicity. Sometimes, stomach ulceration and bleeding can occur without any abdominal pain. Black tarry stools, weakness, and dizziness upon standing may be the only signs of internal bleeding. Rash, kidney impairment, ringing in the ears, and lightheadedness are also seen.
http://www.medicinenet.com/phenylbutazone/article.htm
-Horses: As with many of the NSAIDS, phenylbutazone should not be used in horses with a history of, or pre-existing hematologic or bone marrow abnormalities (bleeding disorders), or in animals with pre-existing gastrointestinal ulcers. Both phenylbutazone and its active ingredient, oxyphenbutazone, are highly bound to plasma proteins and, therefore, caution is advised when using this medication in horses with hypoproteinemia (low blood protein) and gastrointestinal ulceration. Foals are at greatest risk, especially if they have a heavy parasite burden or are undernourished. Phenylbutazone may cause decreased blood flow to the kidneys and result in sodium and water retention. Therefore, be cautious with its use in animals with pre-existing renal disease associated with congestive heart failure.
http://www.omafra.gov.on.ca/english/livestock/horses/facts/info_pheny.htm
Flunixin meglumine: Banamine-
-Horse: Flunixin Meglumine is a NSAID (Non-steroidal anti-inflammatory drug) used in horses. Because it targets the inflamed tissue, Flunixin Meglumine is mainly used for colic pain, muscle pain, and joint disease, as well as to alleviate fevers and pain. It is also effective in injuries of the eye.
Flunixin Meglumine should not be given for more than five days. Like most NSAIDs it can produce gastrointestinal side effects if the drug is given in high doses or over several days. Flunixin Meglumine may be given orally as a paste or as granules in feed. It can also be used intramuscularly or intravenously, although because it is very irritating to tissue, the IV route is preferred, and in cattle it is the labeled route of administration.
In the USA the trade names are Banamine and Flunixamine.
In the UK a common trade name is Finadyne.
http://www.answers.com/topic/flunixin-meglumine
Phenylbutazone belongs to the family of medicines known as nonsteroidal anti-inflammatory drugs or NSAIDs. Non-steroidal anti-inflammatory drugs reduce pain and inflammation by limiting the action of a substance known as prostaglandin that promotes these effects. Phenylbutazone is used for the treatment of ankylosing spondylitis, a type of rheumatoid arthritis that involves inflammation of the joints between the vertebrae of the spine. Ankylosing spondylitis results in stiffening of the spinal joints and ligaments, making movement increasingly painful and difficult. Phenylbutazone is also used for acute cases (flare-ups) of gout. Because of a high incidence of serious adverse effects compared with other medications, phenylbutazone is recommended only when other NSAIDs and options have been tried and found unsatisfactory. Treatment should not exceed one week unless absolutely necessary.
Side Effects:
diarrhea, dizziness, drowsiness, lightheadedness, headache,
heartburn, indigestion, nausea, vomiting, mild to moderate abdominal or stomach cramps, pain, discomfort, bitter taste, constipation, flushing
increased sensitivity of eyes to light, increased sensitivity of skin to sunlight, increased sweating, loss of appetite
sleeping problems, unusual tiredness or weakness, skin rash, bleeding from cuts or scratches that lasts longer than usual,
bloody or cloudy urine,
blurred vision or change in vision, burning feeling in throat, chest, or stomach, difficult or painful urination, frequent urge to urinate, hives, itching, blisters, redness of skin tenderness, burning, peeling, thickening, or scaling of skin, increase in blood pressure,
ringing in ears, swallowing difficulties, swelling in legs or around ankles, unusual or unexpected heavy vaginal bleeding,
swelling of face, hands, feet, or lower legs, rapid weight gain,
bloody or black tarry stools or dark urine, bloody vomit with material that looks like coffee grounds, fainting, fast or irregular breathing, fast irregular heartbeat or pulse,
large hive-like swellings on face, eyelids, mouth, lips or tongue
puffiness or swelling around the eyes, lips, or tongue, severe stomach pain shortness of breath
sores, ulcers, or white spots on lips or in mouth, spitting up blood.
flunixin meglumine:
Horse: Flunixin Meglumine Injection is recommended for the alleviation of inflammation and pain associated with musculoskeletal disorders in the horse. It is also recommended for the alleviation of visceral pain associated with colic in the horse.
Cattle: Flunixin Meglumine Injection is indicated for the control of pyrexia associated with bovine respiratory disease and endotoxemia. Flunixin Meglumine Injection is also indicated for the control of inflammation in endotoxemia.
The side effects are very similar to other NSAIDS.
These medicines are used in animals primarily due to their larger mass. In humans, there is a narrow therapeutic range. In animals, the mass is much larger, and allows a more safe administration. It is very easy to give a toxic dose to a human by a small miscalculation. The mechanisms are very similar thus the same category (NSAIDS). The therapeutic range is the major difference.
http://www.medbroadcast.com/drug_info_details.asp?brand_name_id=152
http://www.fda.gov/cvm/FOI/200-308s030106.pdf
Phenylbutazone is used as a non-steroidal anti-inflammatory drug for the treatment of chronic pain. Its use is limited by such severe side effects as suppression of white blood cell production and aplastic anemia.It provides pain relief of common aches and pains.It also reduces fever. It acts directly on the musculce tissue to decreae inflammation in the musce and reducing pain. Antipyresis qualities mask other symptoms therefor should not be administered unless and veterinarian has been contacted.
Flunixin Meglumine is an anti-inflammatory drug that targets the inflammed tissue and is primarily used for colic pain, muscle pain, and joint disease.It should not be given for more than 5 continuous days due to the high increase of gastrointestinal side effects.
NSAIDS in humans are able to inhibit COX-1 which is also an indication of platelet aggregation. This is an indication useful for the management of arterial thrombosis and the prevention of adverse cardiovascular events. It inhibits platelt aggregation because it inhibits the action of thromboxane.
Phenylbutazone use to be prescribed to humans but due to its chirality it proofed to be toxic for some people. Horses are probably capable of handling NSAIDS that humans find toxic because of their bigger overall mass and size.
Phenylbutazone (Butazolidine): Is an NSAID used primarily in horses; although, it's also used in other animals as well as humans. For horses, Phenylbutazone is mainly used for lameness, soft tissue injury, muscle soreness, bone and joint problems, and laminitis. For dogs Phenylbutazone is used for chronic pain caused from osteoarthritis. Side effects include ulcers, bone marrow depletion, rash, slower renal blood flow, and loss of protein as well as local pain and irritation at injection site. For dogs and horses Phenylbutazone is generally injected although sometimes it will be mixed with grain, or dog food, while in humans it is given PO in tablet or capsule form in a 100mg dose. The side effects are the same for animals as they are for humans; but, the dose is generally a lot smaller.
Flunixin Meglumine (Banamine): Is an NSAID for large animals. I found dosage information for the drug listed for horses, cattle, and elephants. The drug may be administered either PO, IM, or IV. It is recommended to discontinue Flunixin after five days of use to reduce the chance of gastrointestinal side effects from taking the drug. It is used to treat inflamed tissue, colic pain, muscle pain, joint disease, reduce fever, and in eye injuries.
A big reason why these drugs are safe for large animals is simply because they are BIG. Average weight of a man from the US is 190 pounds (so says wikipedia), average weight of a bull elephant is up to 15,000 pounds!
References: http://tinyurl.com/2cpqxp
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http://tinyurl.com/yqpx24
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