University of duhokUniversity of duhokcollege of veterinary medicinecollege of veterinary medicine

Non-steroidal anti-inflammatory drugsNon-steroidal anti-inflammatory drugs

ByBy Jivan Q AhmadJivan Q AhmadE-mail,jivan1425@hotmail.comE-mail,jivan1425@hotmail.com

Non-steroidal anti-inflammatory drugsNon-steroidal anti-inflammatory drugs

Non-steroidal anti-inflammatory drugs, usually abbreviated Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, are drugs with analgesic, to NSAIDs or NAIDs, are drugs with analgesic, antipyretic and, in higher doses, with anti-inflammatory antipyretic and, in higher doses, with anti-inflammatory effects . The term "non-steroidal" is used to distinguish effects . The term "non-steroidal" is used to distinguish these drugs from steroids, which (among a broad range these drugs from steroids, which (among a broad range of other effects) have a similar eicosanoid-depressing, of other effects) have a similar eicosanoid-depressing, anti-inflammatory action. As analgesics, NSAIDs are anti-inflammatory action. As analgesics, NSAIDs are unusual in that they are non-narcoticunusual in that they are non-narcotic..

NSAIDs are among the oldest and most widely used drugs in NSAIDs are among the oldest and most widely used drugs in human history. human history. The ancient GreeksThe ancient Greeks chewed the bark of willow chewed the bark of willow trees to alleviate pain and fever, but it was not until the trees to alleviate pain and fever, but it was not until the 1800s1800s that the active ingredient in willow bark, salicin (which is that the active ingredient in willow bark, salicin (which is metabolized to salicylate), was isolated. At the end of the metabolized to salicylate), was isolated. At the end of the nineteenth centurynineteenth century, acetylsalicylic acid or aspirin was , acetylsalicylic acid or aspirin was synthesized and marketed for its anti-pyretic, anti-synthesized and marketed for its anti-pyretic, anti-inflammatory and analgesic properties. Soon after, compounds inflammatory and analgesic properties. Soon after, compounds with similar properties to aspirin were discovered and with similar properties to aspirin were discovered and collectively named non-steroidal anti-inflammatory drugs collectively named non-steroidal anti-inflammatory drugs (NSAIDs) to distinguish them from the anti-inflammatory (NSAIDs) to distinguish them from the anti-inflammatory activity of glucocorticoids. The connection between NSAIDs activity of glucocorticoids. The connection between NSAIDs and the COX pathway was made in the early and the COX pathway was made in the early 1970s1970s, when , when John VaneJohn Vane proposed that NSAIDs mediate their anti- proposed that NSAIDs mediate their anti-inflammatory effects by inhibiting the enzymatic activity of inflammatory effects by inhibiting the enzymatic activity of COX work for which he was subsequently awarded the Nobel COX work for which he was subsequently awarded the Nobel Prize for physiology or medicinePrize for physiology or medicine..

Mode of ActionMode of Action : :

Generally, the classification NSAID is applied to drugs that Generally, the classification NSAID is applied to drugs that inhibit one or more steps in the metabolism of arachidonic inhibit one or more steps in the metabolism of arachidonic acid (AA). acid (AA). NSAID act primarily to reduce the biosynthesis of NSAID act primarily to reduce the biosynthesis of prostaglandins (PG) by inhibiting cyclooxygenase (COX).prostaglandins (PG) by inhibiting cyclooxygenase (COX). In In general, NSAID do not inhibit lipoxygenase (and hence general, NSAID do not inhibit lipoxygenase (and hence leukotriene) formation, or the formation of other inflammatory leukotriene) formation, or the formation of other inflammatory mediators, although tepoxalin, a recently introduced NSAID mediators, although tepoxalin, a recently introduced NSAID does inhibit lipoxygenase.does inhibit lipoxygenase.

Traditional NSAIDs can be grouped into three classes Traditional NSAIDs can be grouped into three classes based on their inhibition of cox:based on their inhibition of cox:

Class 1: simple, competitive reversible inhibitors that compete Class 1: simple, competitive reversible inhibitors that compete with arachidonic acid for binding to the cox active with arachidonic acid for binding to the cox active site.included in this class are ibuprofen, piroxican, sulindac site.included in this class are ibuprofen, piroxican, sulindac sulfide, flufenamate, mefenamic acid and naproxen.sulfide, flufenamate, mefenamic acid and naproxen.

Class 2: competitive, time dependent, reversible inhibitor that Class 2: competitive, time dependent, reversible inhibitor that bind to the cox active site in a first phase to form reversible bind to the cox active site in a first phase to form reversible enzyme inhibitor complexthat if retained for sufficient time, enzyme inhibitor complexthat if retained for sufficient time, cause non covalent conformational changes in protein. This cause non covalent conformational changes in protein. This class includes indumethacin, flubiprofen, meclofenamic acid class includes indumethacin, flubiprofen, meclofenamic acid and diclofenac.and diclofenac.

Class 3: competitive, time dependent, irreversible inhibitors Class 3: competitive, time dependent, irreversible inhibitors that form an enzyme inhibitor complex after a covalent that form an enzyme inhibitor complex after a covalent conformational change in the protein. Included in this class is conformational change in the protein. Included in this class is aspirin aspirin

Kinetics of NSAID (ADME)Kinetics of NSAID (ADME)Absorption:Absorption: Since all NSAIDs are highly lipophilic substances, Since all NSAIDs are highly lipophilic substances,

Drug absorption after oral administration is generally rapid Drug absorption after oral administration is generally rapid and complete. and complete.

Distribution:Distribution: The most significant aspect of NSAID distribution is The most significant aspect of NSAID distribution is

plasma protein binding.plasma protein binding. Metabolism:Metabolism: Knowledge of the mechanism of action of NSAIDs, as Knowledge of the mechanism of action of NSAIDs, as

competitive inhibitors for arachidonic acid binding to COX, provides a competitive inhibitors for arachidonic acid binding to COX, provides a good tool to predict whether NSAID metabolites are active or not. good tool to predict whether NSAID metabolites are active or not.

Metabolism and elimination is via hepatic conjugation with Metabolism and elimination is via hepatic conjugation with glucoronic acid.glucoronic acid.

Excretion:Excretion: small percentages of NSAIDs are excreted unchanged in urine. If small percentages of NSAIDs are excreted unchanged in urine. If the drug is excreted unchanged, its rate of excretion is expected to increase the drug is excreted unchanged, its rate of excretion is expected to increase if the drug iscoadministered with agents that render the urine pH alkaline if the drug iscoadministered with agents that render the urine pH alkaline such as the antacids aluminum hydroxide and milk of magnesia.such as the antacids aluminum hydroxide and milk of magnesia.

formsforms By mouth,By mouth, they come in tablets, capsules or medicines. This is they come in tablets, capsules or medicines. This is

the most widely used form. the most widely used form. Some NSAIDs are available as Some NSAIDs are available as injectionsinjections. This form is used . This form is used

for the pain after surgical operations and also is very effective for the pain after surgical operations and also is very effective for the treatment of pain produced by kidney stones (renal for the treatment of pain produced by kidney stones (renal colic). colic).

SuppositoriesSuppositories are available. These are often used for post are available. These are often used for post operative pain and sometimes in chronic pain when the patient operative pain and sometimes in chronic pain when the patient is unable to take medication by mouth. is unable to take medication by mouth.

Creams, gelsCreams, gels and and foamsfoams to apply to the skin. These are not felt to apply to the skin. These are not felt to be as effective, but some people do get considerable relief to be as effective, but some people do get considerable relief from their use. from their use.

Common typesCommon types

Aspirin Aspirin carprofencarprofen Diclofenac Diclofenac Ketoprofen Ketoprofen NaproxenNaproxen ValdecoxibValdecoxib Indomethacin Indomethacin Ibuprofen Ibuprofen

AspirinAspirin

Acetylsalicylic Acid, Aspirin is a non-selective, irreversible COX Acetylsalicylic Acid, Aspirin is a non-selective, irreversible COX inhibitor.Aspirin was the first discovered member of the inhibitor.Aspirin was the first discovered member of the non-steroidal anti-inflammatory drugsnon-steroidal anti-inflammatory drugs (NSAIDs) Often used as an (NSAIDs) Often used as an analgesicanalgesic to relieve minor aches and pains, as an to relieve minor aches and pains, as an antipyreticantipyretic to reduce to reduce feverfever, and as an , and as an anti-inflammatoryanti-inflammatory medication. medication.

Mechanism of action/Effect:Mechanism of action/Effect:

The effectiveness of aspirin is largely due to its ability to inhibit The effectiveness of aspirin is largely due to its ability to inhibit prostaglandin synthesis. This is done by irreversibly blocking prostaglandin synthesis. This is done by irreversibly blocking cyclooxygenase (prostaglandin synthase), which catalyzes the cyclooxygenase (prostaglandin synthase), which catalyzes the conversion of arachidonic acid to endoperoxide compounds; at conversion of arachidonic acid to endoperoxide compounds; at appropriate doses, the drug decreases the formation of both the appropriate doses, the drug decreases the formation of both the prostaglandins and thromboxane A2 but not the leukotrienes.prostaglandins and thromboxane A2 but not the leukotrienes.

IndicationsIndicationsThere are three main indications:There are three main indications: Inflammation (treatmentInflammation (treatment)1—Dogs and cats: Aspirin )1—Dogs and cats: Aspirin

is used for the relief of inflammation associated with is used for the relief of inflammation associated with arthritis and joint problems. arthritis and joint problems.

Pain (treatmentPain (treatment)—Cattle, dogs, pigs, and cats: )—Cattle, dogs, pigs, and cats: Aspirin is used for relief from mild to moderate Aspirin is used for relief from mild to moderate somatic pain, such as incisional pain following somatic pain, such as incisional pain following surgery, pain following dental procedures, and surgery, pain following dental procedures, and discomfort associated with cystitis. discomfort associated with cystitis.

Fever (treatment)Fever (treatment)—Cattle, dogs, pigs, and cats: —Cattle, dogs, pigs, and cats: Aspirin is used to reduce fever; however, the Aspirin is used to reduce fever; however, the treatment of fever with antipyretic medications is treatment of fever with antipyretic medications is controversial and specific therapy for the underlying controversial and specific therapy for the underlying disease should be sought.disease should be sought.

Drug InteractionsDrug Interactions

Drugs that alkalinize the urine (e.g., Drugs that alkalinize the urine (e.g., acetazolamide, sodium acetazolamide, sodium bicarbonate)bicarbonate) significantly increase the renal excretion of significantly increase the renal excretion of salicylates. Because carbonic anhydrase inhibitors (e.g., salicylates. Because carbonic anhydrase inhibitors (e.g., acetazolamide, dichlorphenamideacetazolamide, dichlorphenamide) may cause systemic ) may cause systemic acidosis and increase CNS levels of salicylates, toxicity may acidosis and increase CNS levels of salicylates, toxicity may occur. Urinary acidifying drugs (occur. Urinary acidifying drugs (methionine, ammonium methionine, ammonium chloride, ascorbic acidchloride, ascorbic acid) will decrease the urinary excretion of ) will decrease the urinary excretion of salicylates. salicylates. FurosemideFurosemide may compete with the renal excretion may compete with the renal excretion of aspirin and delay its excretion. This may cause symptoms of aspirin and delay its excretion. This may cause symptoms of toxicity in animals receiving high aspirin doses. of toxicity in animals receiving high aspirin doses.

Side/Adverse EffectsSide/Adverse EffectsThe most common side effect of aspirin at therapeutic doses is The most common side effect of aspirin at therapeutic doses is

gastric or intestinal irritation with varying degrees of occult GI gastric or intestinal irritation with varying degrees of occult GI blood loss occurring. The resultant irritation may lead to blood loss occurring. The resultant irritation may lead to vomiting and/or anorexia. Sever blood loss may result in vomiting and/or anorexia. Sever blood loss may result in secondary anemia or hypoprotienemia.In dogs , plain un secondary anemia or hypoprotienemia.In dogs , plain un coated aspirin may be more irritant to the gastric mucosa than coated aspirin may be more irritant to the gastric mucosa than either enteric coated tablets or buffered aspirin. either enteric coated tablets or buffered aspirin. hypersensitivity reaction have been reported in dogs, although hypersensitivity reaction have been reported in dogs, although they are thought to occur rarely.they are thought to occur rarely.

Salicylates are possible teratogenes and their use should be Salicylates are possible teratogenes and their use should be avoided during pregnancy, particularly during later stages. avoided during pregnancy, particularly during later stages.

Vomiting and melena may be seen at higher doses. The PGE1 Vomiting and melena may be seen at higher doses. The PGE1 analog misoprostol may be effective in decreasing GI analog misoprostol may be effective in decreasing GI ulceration associated with aspirin and other NSAID. ulceration associated with aspirin and other NSAID.

Aspirin overdose in any species can result in salicylate poisoning, Aspirin overdose in any species can result in salicylate poisoning, characterized by severe acid-base abnormalities, hemorrhage, characterized by severe acid-base abnormalities, hemorrhage, seizures, coma, and death.seizures, coma, and death.

DosageDosage Recommended dosages Recommended dosages Dogs Dogs For analgesia: 10-25 mg/kg PO Q8-12hFor analgesia: 10-25 mg/kg PO Q8-12h As anti-inflammatory/antirheumatic: 25 mg /kg PO q8hAs anti-inflammatory/antirheumatic: 25 mg /kg PO q8h For antipyrexia: 10 mg/kg PO bidFor antipyrexia: 10 mg/kg PO bid CatsCats For analgesia and anti pyrexia: 10 mg/kg po q48hFor analgesia and anti pyrexia: 10 mg/kg po q48h For treatment of arthritis/antirheumatic/anti-inflammatory: 10-20 mg/kg po For treatment of arthritis/antirheumatic/anti-inflammatory: 10-20 mg/kg po

q48hq48h CattleCattle For analgesia/antipyrexia: 50-100 mg/kg po q12hFor analgesia/antipyrexia: 50-100 mg/kg po q12h horseshorses For analgesia: 25 mg/kg po q12h initially then 10 mg/kg once dailyFor analgesia: 25 mg/kg po q12h initially then 10 mg/kg once daily For laminitis: 5-10 mg/kg, PO q24-48hFor laminitis: 5-10 mg/kg, PO q24-48h

22 . .CARPROFENCARPROFEN

This NSAID of the arylpropionic acid class ,Carprofen This NSAID of the arylpropionic acid class ,Carprofen is approved to manage pain and inflammation is approved to manage pain and inflammation associated with osteoarthritis and acute pain associated with osteoarthritis and acute pain associated with soft-tissue and orthopedic surgery in associated with soft-tissue and orthopedic surgery in dogs. dogs.

In Europe and other countries, carprofen is also In Europe and other countries, carprofen is also registered for use in cattle and for short-term therapy registered for use in cattle and for short-term therapy in cats. In dogs, oral bioavailability is high (90%) and in cats. In dogs, oral bioavailability is high (90%) and plasma concentrations peak ~2-3 hr after dosing. The plasma concentrations peak ~2-3 hr after dosing. The elimination half-life is ~8 hr. As with other NSAID,elimination half-life is ~8 hr. As with other NSAID,

mechanism of actionmechanism of action

The exact mechanism of action of carprofen is unclear. Although The exact mechanism of action of carprofen is unclear. Although it has greater selectivity for COX-2 over COX-1, carprofen is it has greater selectivity for COX-2 over COX-1, carprofen is considered a weak COX inhibitor. In vitro canine cell line considered a weak COX inhibitor. In vitro canine cell line assays indicate that it is 129-fold selective for COX-2, assays indicate that it is 129-fold selective for COX-2, whereas in vitro canine whole blood assays indicate it is 7- to whereas in vitro canine whole blood assays indicate it is 7- to 17-fold selective for COX-2, equine whole blood assays 17-fold selective for COX-2, equine whole blood assays indicate it is 1.6-fold selective for COX-2, and feline whole indicate it is 1.6-fold selective for COX-2, and feline whole blood assays indicate it is 5.5-fold selective for COX-2. Other blood assays indicate it is 5.5-fold selective for COX-2. Other mechanisms of action, including inhibition of PA2 may be mechanisms of action, including inhibition of PA2 may be responsible for its anti-inflammatory effects.responsible for its anti-inflammatory effects.

IndicationsIndications

Carprofen has been used extensively in dogs since its introduction Carprofen has been used extensively in dogs since its introduction nflammation (treatment); or Pain (treatment)nflammation (treatment); or Pain (treatment)— — Dogs: Dogs:

Carprofen caplets, chewable tablets, andCarprofen caplets, chewable tablets, and ELCANinjectionEL ELCANinjectionEL are indicated in the control of inflammation and pain associated are indicated in the control of inflammation and pain associated with osteoarthritis.with osteoarthritis.

Pain, postoperative (treatmentPain, postoperative (treatment)—)—Dogs:Dogs:chewable tabletsEL, and chewable tabletsEL, and injection are indicated in the control of postoperative pain injection are indicated in the control of postoperative pain associated with soft tissue or orthopedic surgery.Preoperative associated with soft tissue or orthopedic surgery.Preoperative administration is recommended because it can be more administration is recommended because it can be more effective than postoperative administration alone in theeffective than postoperative administration alone in the

control of postoperative pain.control of postoperative pain.Inflammation (treatmentInflammation (treatment); or Pain (treatment)— ); or Pain (treatment)— HorsesHorses: :

Although the safety and efficacy have not been established, Although the safety and efficacy have not been established, there is evidence to suggest that oral or parenteral carprofen there is evidence to suggest that oral or parenteral carprofen can be effective in the treatment of pain and inflammation in can be effective in the treatment of pain and inflammation in horses.horses.

Side effectsSide effects Gastrointestinal effects (vomiting, diarrhea, constipation, inappetence, Gastrointestinal effects (vomiting, diarrhea, constipation, inappetence,

melena, hematemesis, gastrointestinal ulceration, gastrointestinal bleeding, melena, hematemesis, gastrointestinal ulceration, gastrointestinal bleeding, pancreatitis); pancreatitis);

hepatic effects(inappetence, vomiting, jaundice, acute hepatic toxicity, hepatic effects(inappetence, vomiting, jaundice, acute hepatic toxicity, hepaticenzyme elevation, abnormal liver function tests,hyperbilirubinemia, hepaticenzyme elevation, abnormal liver function tests,hyperbilirubinemia,

bilirubinuria, hypoalbuminemia); bilirubinuria, hypoalbuminemia); neurologic effects(ataxia, paresis, paralysis, seizures, vestibular signs,neurologic effects(ataxia, paresis, paralysis, seizures, vestibular signs,disorientation); disorientation); urinary effects (hematuria, polyuria, polydipsia, urinary incontinence, urinary effects (hematuria, polyuria, polydipsia, urinary incontinence,

urinary tract infection, azotemia, acute renal failure, tubular abnormalities, urinary tract infection, azotemia, acute renal failure, tubular abnormalities, including acute tubular necrosis, renal tubular necrosis, glucosuria, including acute tubular necrosis, renal tubular necrosis, glucosuria, glomerular disease, including glomerulonephritis); glomerular disease, including glomerulonephritis);

behavioral effects(Sedation, lethargy, hyperactivity, restlessness, behavioral effects(Sedation, lethargy, hyperactivity, restlessness, aggressiveness);aggressiveness);

hematologic effects(immune-mediated hemolytic anemia, immune-hematologic effects(immune-mediated hemolytic anemia, immune-mediated Thrombocytopenia, blood loss anemia, epistaxis);mediated Thrombocytopenia, blood loss anemia, epistaxis);

dermatologic effects(pruritis, increased shedding, alopecia, pyotraumatic dermatologic effects(pruritis, increased shedding, alopecia, pyotraumatic moist dermatitis, necrotizing panniculitis/vasculitis, ventral ecchymosis); moist dermatitis, necrotizing panniculitis/vasculitis, ventral ecchymosis);

immunologic effects or hypersensitivity (facial swelling, hives, erythemaimmunologic effects or hypersensitivity (facial swelling, hives, erythema

DosageDosageDogs:Dogs: As anti-inflammatory/analgesic: 2.2mg/kg po twice As anti-inflammatory/analgesic: 2.2mg/kg po twice

dailydaily For surgical pain: 4mg/kg iv once For surgical pain: 4mg/kg iv once Cats:Cats: For surgical pain: 4mg/kg iv once For surgical pain: 4mg/kg iv once Horses:Horses: As anti-inflammatory/analgesic: 0.7mg/kg iiv one As anti-inflammatory/analgesic: 0.7mg/kg iiv one

timetime

33 . .DiclofenacDiclofenac

Diclofenac(voltaren)(2[(2,6-diclorophenyl)amino]phenylacetate) Diclofenac(voltaren)(2[(2,6-diclorophenyl)amino]phenylacetate) is relatively non selective cox inhibitor. used to reduce is relatively non selective cox inhibitor. used to reduce inflammationinflammation and as an and as an analgesicanalgesic reducing pain in conditions reducing pain in conditions such as such as arthritisarthritis or acute or acute injuryinjury. It can also be used to reduce . It can also be used to reduce

menstrualmenstrual painpain, , dysmenorrheadysmenorrhea.. Mechanism of actionMechanism of action

The exact mechanism of action is not entirely known, but it is The exact mechanism of action is not entirely known, but it is thought that the primary mechanism responsible for its thought that the primary mechanism responsible for its anti-inflammatoryanti-inflammatory / / antipyreticantipyretic / / analgesicanalgesic action is inhibition action is inhibition of of prostaglandinprostaglandin synthesis by inhibition of synthesis by inhibition of cyclooxygenasecyclooxygenase (COX).(COX).

IndicationsIndications musculoskeletal complaints, especially musculoskeletal complaints, especially arthritisarthritis goutgout attacks attacks pain managementpain management in case of in case of kidney stoneskidney stones and and gallstonesgallstones. . acute migraines acute migraines menstrual pain menstrual pain post-operative or post-traumatic pain post-operative or post-traumatic pain Dc liposomal cream is used safely and effectively for Dc liposomal cream is used safely and effectively for

symptomatic treatment of joint-associated lameness in horses symptomatic treatment of joint-associated lameness in horses It's also found very effectively in the treatment of clinical It's also found very effectively in the treatment of clinical

cases of myositis and arthritis in cattle and buffaloes.cases of myositis and arthritis in cattle and buffaloes. Dc in rectal suppository form is a drug of choice for Dc in rectal suppository form is a drug of choice for

preemptive analgesia.preemptive analgesia. Ophthalmic preparation of Dc is used for prevention of Ophthalmic preparation of Dc is used for prevention of

postoperative ophthalmic inflammation postoperative ophthalmic inflammation

Side effectsSide effects in human include gastrointestinal distress, occult in human include gastrointestinal distress, occult

gastrointestinal bleeding, and gastric ulceration. Dc at dosage gastrointestinal bleeding, and gastric ulceration. Dc at dosage of l50mg\day appears to impair renal blood flow and of l50mg\day appears to impair renal blood flow and glomerular filtration rate.glomerular filtration rate.

In veterinary practice, Dc is reported to produce gastric ulcer In veterinary practice, Dc is reported to produce gastric ulcer and mild nephropathy. Hypersensitivity to Dc was also and mild nephropathy. Hypersensitivity to Dc was also

reported in calvesreported in calves . .

DipyroneDipyrone Dipyrone (metamizole). The mechanism of action of dipyrone Dipyrone (metamizole). The mechanism of action of dipyrone

is thought to be similar to that of other NSAIDs: inhibition is thought to be similar to that of other NSAIDs: inhibition of the production of prostaglandins. It is commonly used in of the production of prostaglandins. It is commonly used in the horse as an antipyretic, analgesic, and anti-the horse as an antipyretic, analgesic, and anti-inflammatory.inflammatory.

Dipyrone is a very mild NSAID. Because of its very mild Dipyrone is a very mild NSAID. Because of its very mild analgesic properties it is unlikely to mask abdominal pain due to analgesic properties it is unlikely to mask abdominal pain due to a surgical problem. Traditionally, dipyrone has been thought to a surgical problem. Traditionally, dipyrone has been thought to also have anti-spasmodic properties on the smooth muscle of the also have anti-spasmodic properties on the smooth muscle of the gastro-intestinal tract, which has been the basis for its common gastro-intestinal tract, which has been the basis for its common use in cases of mild colic. Although research evidence does not use in cases of mild colic. Although research evidence does not support any claim of anti-spasmodic activity, many clinicians support any claim of anti-spasmodic activity, many clinicians consider it a very useful drug precisely for this reason. Flunixin consider it a very useful drug precisely for this reason. Flunixin meglumine is a NSAID with stronger analgesic properties that is meglumine is a NSAID with stronger analgesic properties that is also used to treat GI pain.also used to treat GI pain.

Dipyrone may be used in foals and in adult horses to reduce fevers. Dipyrone may be used in foals and in adult horses to reduce fevers. It is not commonly used for the treatment of musculoskeletal It is not commonly used for the treatment of musculoskeletal pain. Dipyrone may be given IM, IV, or subcutaneously.pain. Dipyrone may be given IM, IV, or subcutaneously.

Side EffectsSide Effects

• • The most common side effect for dipyrone is injection site The most common side effect for dipyrone is injection site reactions. These reactions usually respond to hot compresses reactions. These reactions usually respond to hot compresses and NSAIDs. and NSAIDs.

• • Prolonged use of dipyrone may cause bone marrow suppression Prolonged use of dipyrone may cause bone marrow suppression (leukopenia, agranulocytosis). Animals receiving prolonged (leukopenia, agranulocytosis). Animals receiving prolonged courses of dipyrone should be followed with regular CBCs.courses of dipyrone should be followed with regular CBCs.

KetoprofenKetoprofen

Ketoprofen is propionic acid derivative available as a 10% Ketoprofen is propionic acid derivative available as a 10% injectable solution for horses, and as tablets and a 1% injectable solution for horses, and as tablets and a 1% injectable solution for dogs and cats.injectable solution for dogs and cats.

Ketoprofen is a potent inhibitor of COX and bradykinin and may Ketoprofen is a potent inhibitor of COX and bradykinin and may also inhibit some lipoxygenases. Its efficacy is comparable to also inhibit some lipoxygenases. Its efficacy is comparable to that of opioids in the management of pain following that of opioids in the management of pain following orthopedic and soft-tissue surgery in dogs. Following orthopedic and soft-tissue surgery in dogs. Following administration PO, ketoprofen is rapidly absorbed and has a administration PO, ketoprofen is rapidly absorbed and has a terminal half-life in cats and dogs of 2-3 hr. As with other terminal half-life in cats and dogs of 2-3 hr. As with other NSAID, ketoprofen is metabolized in the liver to inactive NSAID, ketoprofen is metabolized in the liver to inactive metabolites that are eliminated by renal excretion.metabolites that are eliminated by renal excretion.

Ketoprofen is recommended for acute pain (up to 5 days) in both Ketoprofen is recommended for acute pain (up to 5 days) in both dogs and cats. In horses, it is used for pain and inflammation dogs and cats. In horses, it is used for pain and inflammation associated with osteoarthritis and for visceral pain associated associated with osteoarthritis and for visceral pain associated with colic. with colic.

Adverse effectsAdverse effects

Adverse effects, including GI upset, are similar to those of other Adverse effects, including GI upset, are similar to those of other NSAID. Other side effects, including hepatopathies and renal NSAID. Other side effects, including hepatopathies and renal disease, have been reported in animals. Due to potential disease, have been reported in animals. Due to potential antiplatelet effects, care should be exercised when using antiplatelet effects, care should be exercised when using

ketoprofen perioperativelyketoprofen perioperatively

ReferencesReferences Dr. Miriam I. YasinDr. Miriam I. Yasin , , The effectiveness of antibiotic, nsaids and glycerol The effectiveness of antibiotic, nsaids and glycerol

in reducing post operative complications of rumonatomy in sheep's, in reducing post operative complications of rumonatomy in sheep's, Susan E. AieloSusan E. Aielo, B.S.,E.l.S ,The Merck Veterinary Manual ., B.S.,E.l.S ,The Merck Veterinary Manual . Donald C. PlumbDonald C. Plumb, Veterinary drug hand book, , Veterinary drug hand book, Forth edition, 2002 Forth edition, 2002 Charles E.OPhardtCharles E.OPhardt ,Virtual chembook, Elmhurst college,, c.2003 ,Virtual chembook, Elmhurst college,, c.2003

(Veterinary—Systemic), The United States Pharmacopeial Convention(Veterinary—Systemic), The United States Pharmacopeial Convention Wedge wood Pharmacy Wedge wood Pharmacy

http://www.wedgewoodpharmacy.com/monographs/dipyrone.asphttp://www.wedgewoodpharmacy.com/monographs/dipyrone.asp Wikipedia, the free encyclopedia.Wikipedia, the free encyclopedia. http://www.drugs.com/vet/dipyrone-50-can.htmlhttp://www.drugs.com/vet/dipyrone-50-can.html