NSAIDs are commonly used analgesic, antipyretic and anti-inflammatory drugs. They work by inhibiting cyclooxygenase (COX) enzymes, decreasing synthesis of prostaglandins. There are two main COX isoforms, COX-1 and COX-2. NSAIDs can be nonselective inhibitors of both isoforms or selective inhibitors of COX-2. The main pharmacological effects of NSAIDs are analgesia, antipyresis and reduction of inflammation by decreasing prostaglandin levels. However, they also carry risks of adverse gastrointestinal, renal and platelet effects due to inhibition of the constitutive COX-1 isoform.

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PHARMACOLOGY
OF
NONSTEROIDAL ANTINFLAMMATORY
DRUGS (NSAIDS)
ANALGESICS
• Newer drugs being introduced and the
development of new modalities of pain
control particularly in companion animal
species
• Analgesic therapy is best initiated before
surgery or as soon as possible in the case of
trauma or postoperatively.
Analgesics: Pharmacological agents
• OPIOIDS
• NON STEROIDAL ANTI-INFLAMMATORY DRUGS
(NSAIDS)
• CORTICOSTEROIDS( STEROIDAL ANTIINFLAMMATORY)
• LOCAL ANAESTHETICS
• Αlpha 2-AGONISTS
• KETAMINE, GABAPENTIN ETC.
Pharmacological agents
Different sites of action
Combined therapy
Dose of each individual drug to be
reduced.
The most commonly used class of
analgesics in domestic animals are
opioids (narcotic analgesics) and NSAIDs
(non narcotic analgesics)
NSAIDS INTRODUCTION
 Over The Counter (OTC) Analgesics/ Pain Killers
 Aspirin-like drugs/ Non narcotic analgesics
 provide symptomatic relief from pain and swelling in
chronic joint disease such as occurs in osteo- and
rheumatoid arthritis, and in more acute inflammatory
conditions such as sports injuries, fractures, sprains and
other soft tissue injuries
 Virtually all NSAIDs, particularly the 'classic' NSAIDs, can
have significant unwanted effects
 Newer agents have fewer adverse actions ???
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)
• Most widely prescribed /OTC drugs in the treatment of pain and
inflammation in many conditions(musculoskeletal).
THE ADVANTAGES OVER OPIOIDS/DIFFERENCES
 OTC Drugs
 No immunosuppressive and metabolic side effects
associated with corticosteroids.
 Devoid of sedation, hypotension, bradycardia and
respiratory depression
 Long acting analgesia for mild to moderately painful
conditions,
 Analgesic, Antipyretic and Antiinflammatory actions
 Not controlled substances / schedule drugs
DRAWBACKS
 Potencywise : lesser than opioids .with their effect on visceral pain
considered to be poor.
 Other potential adverse effcets: gastric, hepatic and renal

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MECHANISM OF ACTION
• Inhibition of cyclo-oxygenase (COX) enzyme(s) which
leads to a decrease in the synthesis of various
prostaglandins and thromboxanes (COX inhibitor- Non
Selective and Selective/Preferential COX2 inhibitor)
• May also inhibit phospholipase A enzyme; major
mechanism for effects of glucocorticoids on
prostaglandin production.
• Few agents like ketoprofen, tepoxalin, licofelone inhibit
lipooxygenase enzyme involved in leukotrienes synthesis,
in addition to cyclooxygenase inhibition (DUAL COX-LOX
inhibitor)
NSAIDS.. contd Tissue membrane injury Pathway
COX-3 Arachadonic Acid
COX-1 COX-2
Prostaglandins
PGE2,PGI2,TXA2
GI Protection
Renal Blood Flow
Platelet Function
Prostaglandins
PGD2,E2,F2
Inflammation & Pain
Renal Blood Flow
GI Protection
LOX
Leukotrienes
LTB4,C4,D4
Inflammation
GI Ulceration
Prostacyclin
s
Vasodilation
Platelet Autonomy
Membrane Phospholipid
Phospholipase A2
GLUCOCORTICODS
NSAIDS
MOA
• The principal therapeutic effects of NSAIDs derive
from their ability to inhibit prostaglandin production.
• The first enzyme in the prostaglandin synthetic
pathway is prostaglandin G/H synthase, also known as
cyclooxygenase or COX.
• This enzyme converts arachidonic acid (AA) to the
unstable intermediates PGG2 and PGH2 and leads to the
production of thromboxane A2 (TXA2) and a variety of
prostaglandins
• There are two forms of cyclooxygenase,
cyclooxygenase-1 (COX-1) and cyclooxygenase-2
(COX-2).
• "COX-3.“ is a Splice variants of COX 1
• COX-1 is a primarily constitutive isoform found in
most normal cells and tissues
• Cytokines and inflammatory mediators that accompany
inflammation induce COX-2 production
• However, COX-2 also is constitutively expressed in
certain areas of kidney and brain and is induced in
endothelial cells by laminar shear forces

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MOA
• Importantly, COX-1, is expressed as the dominant,
constitutive isoform in gastric epithelial cells and is the
major source of cytoprotective prostaglandin formation
• Inhibition of COX-1 at this site is thought to account
largely for the gastric adverse events that complicate
therapy with NSAIDs
• Aspirin and NSAIDs inhibit the COX enzymes and
prostaglandin production; they do not inhibit the
lipoxygenase pathways of AA metabolism and hence do
not suppress LT formation
COX-1 (Constitutive)
 Virtually all tissues of the body
 Catalyzes the formation of constitutive PG, which mediate
a variety of normal physiologic effects including hemostasis,
GI mucosal protection, and protection of the kidney from
hypotensive insult.
COX-2 (Inducible)
 Activated in damaged and inflamed tissues and catalyzes
the formation of inducible PG, including PGE2, associated
with intensifying the inflammatory response
 Involved in thermoregulation and the pain response to
injury.
COX-3
 In brain, involved with central pain relief and
thermoregulation
NSAIDS.. contd
Classification
• NONSELECTIVE COX INHIBITORS
• inhibit both COX isoforms- COX 1 and COX 2
• SELECTIVE (COXIBS) /PREFERENTIAL COX 2
inhibitors
– inhibit COX 2 selectively/preferantially
• COX 3 INHIBITOR
– inhibit COX 3 isoform in brain
COX-2
inhibitors
• Selective (coxibs)
• Preferential
COX-3
inhibitors
•Antipyretic
analgesics
Nonselective
COX-1/COX-2
inhibitors
NSAIDs
COX inhibitors
Salicylic acid derivaties
o Aspirin ( Acetyl salicylic acid)-
Prototype
o Sodium salicylate
oCholine megnesium trisalicylate
 Diflunisal
 Sulfasalazine
 Olsalazine
 Choline
Indole and indene acetic acid
Sulindac, indomethacin, etodolac
Arylpropionic acid derivatives/
Propionates
Ibuprofen, Naproxen
Flurbiprofen, Ketoprofenn,
Fenoprofen, Oxaprofen
Vedaprofen (COX 2)
Heteroaryl acetic acids
Tolmetin, Diclofenac
Ketorolac, eltenac
Anthranilic acids(fenamates)
.Mefenamic acid. Tolfenamic acid
.Meclofenamic acid, flufenamic
Enolicacid / Enolates (Oxicams)
Piroxicam, Piroxicam beta-cyclodextrin
(prodrug), Lornoxicam, Tenoxicam
Meloxicam (COX 2 inhibitor)
Alkanones
Nabumetone (COX 2 inhibtr)
Phenylacetates: Acelcofenac, Diclofenac
Pyrazolones: Phenazone, metamizole
(Analgin) Propyphenazone, etc.
Pyrazolidinediones: Oxyphenbutazone,
Phenylbutazone
NONSELECTIVE COX INHIBITORS

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Structurally
Diaryl-substitited furonones
 Rofecoxib (COX 2 inhibitor)
Diaryl-substituted pyrazoles
 Celecoxib (COX 2 inhibitor)
Indole acetic acids
 Etodolac (COX 2 inhibitor)
Sulfonalides
Nimesulide (COX 2 inhibitor)
SELECTIVE COX-2 inhibitors
Selective COX-2 inhibitors (COXIBS)
• Celecoxib, firacoxib
• Etoricoxib, deracoxib, lumiracoxib
• Parecoxib, rofecoxib, valdecoxib
PREFERENTIAL COX-2 INHIBITORS
• Meloxicam, vedaprofen
• Nimesulide, Aceclofenac
• Nabumetone, Etodolac
COX 3 INHIBITOR
• Paracetamol, phenacetin
• Acetanilid
DUAL COX-LOX inhibitor
• ketoprofen, tepoxalin, licofelone
Agents with poor Anti inflammatory activity
(Primarily only Antipyretic and Analgesic)
• Paracetamol
• Phenacetin
• Acetanilid
• Metamizole(analgin)
• Nefopam
• Most are nonselective COX inhibitors, with COX 1
inhibition ratio being highest
• Meloxicam, nimesulide, etodolac and aceclofenac are
considered as preferential COX-2 inhibitors.
• The newer ‘Coxib’ class of selective COX-2 inhibitors
includes rofecoxib, celecoxib, valdecoxib, parecoxib,
deracoxicb, etoricoxib, firocoxib, lumiracoxib
• Paracetamol (acetaminophen) is a selective COX-3
inhibitor with only analgesic and antipyretic actions,
devoid of anti-inflammatory action
NSAIDS.. contd

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General characteristics of NSAIDS
• weak organic acids
• AI, AP, Analgesic primarily + antiplatelet, uricosuric-
difference in activities
• Symptomatic relief only
• effective in pain of low to moderate intensity -
musculoskeletal
• interspecies differences in dosage and effects
• Except salicylates, many show PPB – drug interactions
• Metablism in liver
• Penetrate BBB
• No tolereance, dependance, respiratory, CNS depression
unlike opioids
PHARMACOLOGICAL EFFECTS
• All the NSAIDs have actions very similar to those of ASPIRIN
• Three main therapeutic effects are:
• AN ANTI-INFLAMMATORY EFFECT: modification of the inflammatory reaction ;
• AN ANALGESIC EFFECT: reduction of certain types of (especially inflammatory)
pain and
• AN ANTIPYRETIC effect: lowering of body temperature when this is raised in
disease (i.e. fever).
• Antiplatelet and uricosuric action
All the NSAIDs share, to a greater or lesser degree, the same types of
mechanism-based SIDE EFFECTS.
• GASTRIC IRRITATION, which may range from simple discomfort to ulcer
formation
• An effect on RENAL BLOOD FLOW in the compromised kidney
• A tendency TO PROLONG BLEEDING through inhibition of platelet function
• Controversially, it is argued that they may also all-but especially COX-2
selective drugs-increase the likelihood of thrombotic events such as
myocardial infarction by inhibiting prostaglandin (PG) I2 synthesis.
PAIN
• NSAIDs are particularly effective when inflammation has caused sensitization of
pain receptors to normally painless mechanical or chemical stimuli
• Pain that accompanies inflammation and tissue injury probably results from local
stimulation of pain fibers and enhanced pain sensitivity (hyperalgesia), in part a
consequence of increased excitability of central neurons in the spinal cord
• Bradykinin, released from plasma kininogen, and cytokines, such as TNF-a, IL-1,
and IL-8, appear to be particularly important in eliciting the pain of inflammation
• These agents liberate prostaglandins and probably other mediators that promote
hyperalgesia
• Neuropeptides, such as substance P and calcitonin gene-related peptide (CGRP),
also may be involved in eliciting pain
Analgesic..
• these drugs usually are effective only against pain of low-to-
moderate intensity
• Although their maximal efficacy is generally much less than the
opioids, NSAIDs lack the unwanted adverse effects of opiates in the
CNS, including respiratory depression and the development of
physical dependence
• NSAIDs do not change the perception of sensory modalities other
than pain
• Chronic postoperative pain or pain arising from inflammation is
controlled particularly well by NSAIDs, whereas pain arising from
the hollow viscera usually is not relieved
• Regulation of body temperature requires a delicate balance
between the production and loss of heat
• Hypothalamus – Thermoregulatory Centre- regulates the set point
at which body temperature is maintained
• This set point is elevated in fever, and NSAIDs promote its return
to normal
• These drugs do not influence body temperature when it is
elevated by factors such as exercise or in response to ambient
temperature
FEVER
• Fever may reflect infection or result from tissue damage,
inflammation, graft rejection, or malignancy
 These conditions all enhance formation of cytokines such as IL-
1b, IL-6, interferons, and TNF-a(Pyrogens)
 The cytokines increase synthesis of PGE2 in circumventricular
organs in and adjacent to the preoptic hypothalamic area
 PGE2, in turn, increases cyclic AMP and triggers the
hypothalamus to elevate body temperature by promoting an
increase in heat generation and a decrease in heat loss
 NSAIDS inhibit fever caused by agents that enhance the
synthesis of IL-1 and other cytokines, which presumably cause
fever, at least in part, by inducing the endogenous synthesis of
prostaglandins
FEVER

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Antipyretic..
• NSAIDs reduce fever in most situations, but not the circadian
variation in temperature or the rise in response to exercise or
increased ambient temperature
• Comparative analysis of the impact of NSAIDs and selective
COX-2 inhibitors suggests that COX-2 is the dominant source
of prostaglandins that mediate the rise in temperature
evoked by bacterial LPS administration
• This is consistent with the antipyretic clinical efficacy of both
subclasses of NSAIDs
Anti-inflammatory..
 Mainly in the treatment of musculoskeletal disorders, such as
rheumatoid arthritis and osteoarthritis
• The NSAIDs reduce mainly those components of the inflammatory
and immune response in which prostaglandins, mainly derived
from COX-2, play a significant part.
• These include: vasodilatation, oedema (by an indirect action: the
vasodilatation facilitates and potentiates the action of mediators
such as histamine that increase the permeability of postcapillary
venules, pain , again potentiating other mediators, such as
bradykinin.
Antiinflammatory …
• The NSAIDs suppress the pain, swelling and increased blood flow
associated with inflammation but have little or no action on the
actual progress of the underlying chronic disease itself
• As a class, they are generally without effect on other aspects of
inflammation, such as leucocyte migration, lysosomal enzyme
release and toxic oxygen radical production, that contribute to
tissue damage in chronic inflammatory conditions such as
rheumatoid arthritis, vasculitis and nephritis.
– Anti-inflammatory effects may inhibit antibody production.
– potential to cause gastric ulceration.
 In general, NSAIDs provide only symptomatic relief from pain and
inflammation associated with the disease, do not arrest the
progression of pathological injury to tissue
Pharmacological Effects
– Antipyretic, analgesic, and anti-inflammatory properties.
( acetaminophen: no antiinflammatory)
– Less potent analgesics than opioids
– Potent antithrombotic / antiplatelet( by TXA2 inhibition) and
antiendotoxic poroprties (few)
– Reduce the effect of endotoxaemia by inhibiting the
production of eicosanoids and thromboxanes, which are
responsible for many of the clinical manifestations of
endotoxaemia such as changes in cardiovascular output
(vasoconstriction, followed by vasodilation), and renal blood
flow, fever, ileus, leucopenia and a tendency to develop
coagulaopathies.
– It is most common secondary to ischemic gastrointestinal
injury or metritis.
– Flunixin, phenyl butazone, ketoprofen and meloxicam are the
most effective in endotoxaemia
NSAIDS.. contd
– inhibits platelet aggregation by inhibiting thromboxanes
synthesis
– Has been prophylactically used for prevention or reoccurrence
of heart attack (leading to myocardial infarction) or stroke in
humans resulting from thrombosis.
– Chondrotoxic as they inhibit the synthesis of cartilage
proteoglycans (aspirin, naproxen, and ibuprofen)
– Carprofen and meloxicam, are considered chondroneutral, or
depending on dose, actually stimulate the production of
cartilage matrix
NSAIDS.. contd
Haematological - ANTIPLATELET EFFECTS (WITH ASPIRIN)
• Aspirin irreversibly inhibits platelet COX, so that aspirin's
antiplatelet effect lasts 8–10 days (the life of the platelet)
• prolonged clotting time, increased tendency for bleeding
• Aspirin decreases the incidence of transient ischemic attacks,
unstable angina, coronary artery thrombosis with myocardial
infarction, and thrombosis after coronary artery bypass
grafting
Effect on Respiration: triphasic
1. Low doses: uncoupling phosphorylation → ↑ CO2 →
stimulates respiration.
2. Direct stimulation of respiratory center → Hyperventilation
→ resp. alkalosis → renal compensation
3. Depression of respiratory center and cardiovascular center
→ ↓ BP, respiratory acidosis, no compensation + metabolic
acidosis also

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Metabolic (Mostly with Aspirin)
1. Uncoupling of Oxid. Phosphorylation
2. Hyperglycemia, glycosuria, and depletion of muscle and
hepatic glycogen
3. enhanced protein catabolism
4. increase urate excretion at normal doses, butt reduce at
lower doses
5. reduces plasma free fattya cid and cholesterol levels
• Renal effects
• PGE2 and PGI2- involved in maintaining renal blood flow
• Inhibition of synthesis leads to- sodium and water
retention, oedema, hyperkalemia
Endocrine:
• Release epinephrine from adr. Medulla
• stimulate ACTH secretion from ant. pituitary
COX-2 SELECTIVE INHIBITORS (COXIBS) EFFECTS
• Developed in an attempt to inhibit prostaglandin synthesis by
the COX-2 isoenzyme induced at sites of inflammation
without affecting the action of the constitutively active
"housekeeping" COX-1 isoenzyme found in the
gastrointestinal tract, kidneys, and platelets.
• COXibs selectively bind to and block the active site of the COX-
2 enzyme much more effectively than that of COX-1.
• COX-2 inhibitors have analgesic, antipyretic, and anti-
inflammatory effects similar to those of nonselective NSAIDs
but with an approximate halving of gastrointestinal adverse
effects.
COX 2 inhibitors(COXIBS)
• COX-2 inhibitors at usual doses have been shown to have no
impact on platelet aggregation, which is mediated by the
COX-1 isoenzyme.
• As a result, COX-2 inhibitors do not offer the cardioprotective
effects of traditional nonselective NSAIDs, which has resulted
in some patients taking low-dose aspirin in addition to a coxib
regimen to maintain this effect.
• COX-2 is constitutively active within the kidney, recommended
doses of COX-2 inhibitors cause renal toxicities similar to
those associated with traditional NSAIDs.
• Clinical data have suggested a higher incidence of
cardiovascular thrombotic events associated with COX-2
inhibitors such as rofecoxib and valdecoxib, resulting in their
withdrawal from the market
PHARMACOKINETICS
• Food impair the oral absorption of NSAID in horses and ruminants.
• Formulations cause tissue necrosis if injected perivascularly.
• Biotransformed in the liver to inactive metabolites that are excreted by
the kidney
• Half-lives vary significantly by species (and in some cases by breed)
• Cats tend to be deficient in certain families of glucuronyl transferases
that are important for glucuronidation.
• As a result, drugs that are excreted as glucuronide conjugates such as
aspirin, paracetamol (acetaminophen) may have a prolonged half-
life in cats, increasing the risk of toxicity due to drug accumulation
Pharmacokinetics and Pharmacodynamics
• Most of the NSAIDs are rapidly and completely absorbed
from the gastrointestinal tract
• peak concentrations occurring within 1 to 4 hours.
• Aspirin begins to acetylate platelets within minutes of reaching
the presystemic circulation
• The presence of food tends to delay absorption without
affecting peak concentration
• Most NSAIDs are extensively protein-bound (95% to 99%)
• Undergo hepatic metabolism and renal excretion
• In general, NSAIDs are not recommended in the setting of
advanced hepatic or renal disease due to their adverse
pharmacodynamic effects
Comparative action between
COX inhibitors
COX-1/COX-2
inhibitors
COX-2
Inhibitors
1. Analgesic action + + +
2. Antipyretic action + +
3. Antiinflammatory action + + +
4. Antiplatelet aggregatory + ----
5. Gastric mucosal damage + + + +
6. Renal salt / water retention + +
7. Delay/prolongation of labor
8. Infertility
+ +
----
+
+ +
9. Ductus arteriosus closure + ?
10. Aspirin-like asthma
11. Cardiotoxicity
+
----
?
+ +

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Indications
• Pain resulting from musculoskeletal injury
either due to trauma or surgery
• As adjunctive therapy to antimicrobial
treatment in acute respiratory diseases in
cattle.
• Antiendotoxic to reduce endotoxaemia( eg:
flunixin, phenyl butazone)
• Antithrombotic (eg: aspirin) to prevent
thrombosis.
NSAIDS.. contd
Effective and well- tolerated analgesics in cats
 Meloxicam, ketoprofen, carprofen, flunixin,
piroxicam and tepoxalin for short-term
treatment (five days)
Drug Interactions
• Combination therapy- either tNSAIDs or COX-2 inhibitors with
"cardioprotective" low-dose aspirin- increases significantly the
gastrointestinal adverse events over either class of NSAID alone
• NSAIDs might attenuate the effectiveness of ACE inhibitors
• NSAIDs may increase the frequency or severity of gastrointestinal
ulceration when combined with corticosteroids
• Augment the risk of bleeding in patients receiving warfarin
• Many NSAIDs are highly bound to plasma proteins and thus may
displace other drugs from their binding sites
Drugs Result
Diuretics Decrease diuresis
Beta-blockers Decrease antihypertensive effect
ACE inhibitors Decrease antihypertensive effect
Anticoagulants Increase of GI bleeding
Sulfonylurea Increase hypoglycemic risk
Cyclosporine Increase nephrotoxicity
GCS Increase of GI bleeding
Alcohol Increase of GI bleeding
Drug interactions with NSAIDs
SIDE /ADVERSE EFFECTS
• Injections- Cellulitis, thrombophlebitis and tissue
necrosis
• Gastric irritation, ulceration, erosion, perforation and
bleeding
• Renal toxicity – ARF and CRF
• Haematological effects : Bleeding, thrombocytopenia,
haemolytic anaemia and agranulocytosis
• Hepatotoxicity- Liver damage
• CNS (behavioural disturbances, seizure precipitaion)
• Skin (rashes, pruritus) manifestations
NSAIDS.. contd
Mechanisms by which NSAIDs may induce mucosal injury

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Cardiovascular
• Selective inhibitors of COX-2 depress PGI2 formation by
endothelial cells without concomitant inhibition of platelet
thromboxane
• PGI2 restrains the cardiovascular effects of TXA2, affording a
mechanism by which selective inhibitors might increase the
risk of thrombosis
• Placebo-controlled trials have now revealed an increased
incidence of myocardial infarction and stroke in patients
treated with rofecoxib, valdecoxib and celecoxib consistent
with a mechanism-based cardiovascular hazard for the class
• Patients at increased risk of cardiovascular disease or
thrombosis are particularly prone to cardiovascular adverse
events on these agents
Blood Pressure, Renal, and Renovascular
Adverse Events
• NSAIDs have little effect on renal function or blood pressure
in normal human subjects
• However, in patients with congestive heart failure, hepatic
cirrhosis, chronic kidney disease, hypovolemia, and other
states of activation of the sympathoadrenal or renin-
angiotensin systems, prostaglandin formation becomes crucial
in model systems and in humans
• NSAIDs are associated with loss of the prostaglandin-induced
inhibition of both the reabsorption of Cl- and the action of
antidiuretic hormone, leading to the retention of salt and water
•CONTD..
•NSAIDs promote reabsorption of K+ as a result of decreased
availability of Na+ at distal tubular sites and suppression of the
prostaglandin-induced secretion of renin
•Deletion of receptors for both PGI2 and PGE2 elevate blood
pressure , mechanistically integrating hypertension with a
predisposition to thrombosis
•Although this hypothesis has never been addressed directly,
epidemiological studies suggest hypertensive complications
occur more commonly in patients treated with coxibs than with
tNSAIDs
 Analgesic Nephropathy
 Analgesic nephropathy is a condition of slowly
progressive renal failure, decreased concentrating
capacity of the renal tubule, and sterile pyuria
 Risk factors are the chronic use of high doses of
combinations of NSAIDs and frequent urinary tract
infections
 If recognized early, discontinuation of NSAIDs permits
recovery of renal function

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Pregnancy and Lactation
•In the hours before parturition, there is induction of
myometrial COX-2 expression, and levels of prostaglandin E2
and F2a increase markedly in the myometrium during labor
•Prolongation of gestation by NSAIDs has been demonstrated
in model systems and in humans
•Some NSAIDs, particularly indomethacin, have been used off-
label to terminate preterm labor
•However, this use is associated with closure of the ductus
arteriosus and impaired fetal circulation in utero, particularly in
fetuses older than 32 weeks' gestation
• COX-2-selective inhibitors have been used as tocolytic agents;
this use has been associated with stenosis of the ductus
arteriosus and oligohydramnios
• Finally, the use of NSAIDs and aspirin late in pregnancy may
increase the risk of postpartum hemorrhage
• Therefore pregnancy, especially close to term, is a relative
contraindication to the use of all NSAIDs, and their use must
be weighed against potential fetal risk, even in cases of
premature labor, and especially in cases of pregnancy-induced
hypertension, where they have been used with questionable
effect
Hypersensitivity.
• vasomotor rhinitis
• angioedema
• generalized urticaria
• bronchial asthma
• laryngeal edema
• bronchoconstriction
• flushing
• hypotension
• shock
Treatment of aspirin hypersensitivity is similar to that of other
severe hypersensitivity reactions, with support of vital organ
function and administration of epinephrine
Aspirin Resistance
• All forms of treatment failure with aspirin have been
collectively called "aspirin resistance"
• Although this has attracted much attention, there is little
information concerning the prevalence of a stable, aspirin-
specific resistance or the precise mechanisms that might
convey this "resistance"
• Genetic variants of COX-1 that cosegregate with
resistance have been described, but the relation to clinical
outcome is not clear
PREDISPOSING FACTORS FOR ADVERSE EFFECTS
• Concurrent corticosteroid treatment
• Dehydration
• Hypovolaemic/post traumatic shock
• Disruption to normal gut blood flow
• Empty stomch
• Pre-existing renal insufficiency
• Aged animals pose additional risk
NSAIDS.. contd
Discontinue NSAID therapy if
• Decrease or increase in appetite or thirst
• Vomiting
• diarrhea or black, tarry or bloody stools
• Lethargy
• Seizure
• Aggression or confusion
• Jaundice (yellowing of skin, gums or eyes)
• Change in urinary habits (frequency, color or
smell), red, itchy skin
NSAIDS.. contd

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11
CONTRAINDICATIONS
• In animals suffering from gastrointestinal ulceration or
bleeding
• Blood dyscrasia.
• Cardiac, hepatic or renal impairment (insufficiency)
• Dehydraion,, hypovolaemia or hypotension
• Concurrent use of potentially nephrotoxic drugs (eg:
aminoglycosides, diuretics, )
• Not advisable in in pregnant animals and animals nearing the
oestrus as COX-2 induction is necessary for ovulation and
implanation of the embryo.
• Found to delay the parturition, if used nearing term.
• The dose or the duration not to be exceeded longer
NSAIDS.. contd
Agents used for preventing/healing the gastric
ulceration effects due to NSAID use(chronic/high
dose)
• H2 receptor antagonists (eg: ranitidine)
• Proton pump inhibitors (eg: omeprazole)
• Cytoprotective drugs (eg: PGE1 anlog-
misoprostol)
• Ulcer healing drug- suclralfate
NSAIDS.. contd
Pathophysiologic events in a gouty joint
Synoviocytes phagocytose urate crystals and then secrete
inflammatory mediators, which attract and activate polymor-
phonuclear leukocytes (PMN) and mononuclear phagocytes
(MNP) (macrophages). Drugs active in gout inhibit crystal
phagocytosis and polymorphonuclear leukocyte and macro-
phage release of inflammatory mediators.
(PG – prostaglandin; IL-1 – interleukin-1; LTB4 – leukotriene B4)
GOUT
DRUGS IN GOUT
(1) Acute goat
Colchicine
Diclofenac, Indometacin,
Naproxen, Phenylbutazone, Piroxiam
(2) Chronic gout
Uricostatics (xantine oxidase inhibitors)
Allopurinol, Febuxostat
Uricosurics
Benzbromarone, Probenecide
Sulfinpyrazone
Uricolytics: Uricase, Rasburicase
Drug combinations
(allopurinol & benzbromarone)
INDIVIDUAL NSAIDS
NONSELECTIVE COX-INHIBITORS
AGENTS WITH ANALGESIC AND MARKED ANTI-
INFLAMMATORY ACTIVITY
1.Salicylic Acid Derivatives/Salicylates
 Aspirin(Acetylsalicylic acid; ASA)
 one of the most extensively used over-the-counter drugs
 first developed in 1899
 occurs as a white crystalline substance
 stable in dry air but hydrolyses to salicylic acid and acetic acid in
moist air.
 slightly soluble in water and freely soluble in alcohol
 Salicylism- overdose/toxicity

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ASPIRIN (Acetyl Salicylic acid )
• Relief of mild to moderate pain associated with
musculoskeletal inflammation or osteoarthritis.
• No definitive efficacy studies in animals
• In cats, used for its anti-platelet effects in
thromboembolic disease, every 48 hr, to allow for
prolonged metabolism.
• May induce mucosal erosion and ulceration in dogs
• Vomiting and melena may be seen at higher doses
• Overdose can result in salicylate poisoning, characterized
by severe acid-base abnormalities, hemorrhage, seizures,
coma, and death
TREATMENT:
• Treatment of aspirin over dosage is symptomatic and
supportive
• Acidosis,! treatment and forced alkaline diuresis with sodium
bicarbonate should be performed for serious ingestion.
• Most important part of treatment is external cooling and IV
fluids with Na+, K+, HC03" and glucose
• Treatment of aspirin induced GI lesions includes the H2-
receptor antagonists (e.g., ranitidine), the PGE1 analogues
(e.g., misoprostol) or the proton Bump inhibitor omeprazole
Sodium Salicylate
• Used mainly as analgesic, antipyretic and antirheumatic drug
• Occasionally, it is used as a uricosuric drug.
• Dose
• Dogs: 10 mg/kg, IV, 2 times daily.
• Horses: 35 mg/kg, iv; 4 times daily
Salicylic Acid
• It is used externally mainly in combination with benzoic acid
in ointments and alcoholic solutions for their antifungal action
Other Salicylic Acid Derivatives
•Sodium thiosalicylate
•Choline salicylate
•Magnesium salicylate
•Methyl salicylate (oil of wintergreen)
•Calcium carbaspirin
•Salsalate (salicylsalicylic acid)
•Salol (phenyl salicylate)
•Benorylate (ester of aspirin and paracetamol)
•Salicylamide
Metabolism of Aspirin
ACETANILIDE AND PHENACETIN
• (acetophenetidin) are aniline (a dye) derivatives and
chemically related to paracetamol
• Acetanilide in addition forms aniline as a metabolite, which
is highly toxic and readily converts haemoglobin into
methaemoglobin
• Phenacetin, once incorporated in the well-known APC
(aspirin, phenacetin and caffeine) tablet, has been associated
with high incidence of necrosis of renal papilla in man and is,
therefore, not freely available
• Both acetanilide and phenacetin are now banned in many
countries including India and are not used in therapeutics

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Paracetamol (ACETAMINOPHEN)
• Little ulcerogenic potential
• No effect on platelets or bleeding time.
• More effective in inhibiting COX-3, in the
brain rather than in the periphery.
• Dose-dependent adverse effects include
depression, vomiting, and
methemoglobinemia
• Use in cats is contraindicated due to a lack of
glucuronosyl transferase and the potential for
hemolytic anemia and centrilobular hepatic
necrosis.
• N-acetyl cysteine- antidote
Paracetamol (ACETAMINOPHEN)
• Present in many OTC pain and cold remedies
• Although equivalent to Aspirin as an effective analgesic and
antipyretic agent, paracetamol differs in that it lacks
antiinflam- matory properties.
• It does not affect uric acid levels and lacks platelet-
inhibiting properties.
• Useful in mild to moderate pain: headache, myalgia,
postpartum pain.
• Alone is inadequate therapy for inflammatory conditions
such as rheumatoid arthritis, although it may be used as an
analgesic adjunct to antiinflammatory therapy.
• For mild analgesia, paracetamol is the preferred drug in
patients allergic to Aspirin or when salicylates are poorly
tolerated.
• It is preferable to Aspirin in patients with hemophilia or a
history of peptic ulcer and bronchospasm.
• Preferred to Aspirin in children with viral infections.
Paracetamol (ACETAMINOPHEN)
Acute paracetamol poisoning
• in small children and felines- who have low
hepatic glucuronide conjugating ability.
• N-acetyl-p-benzoquinoneimine (NABQI) is a
highly reactive arylating metabolite of paracetamol
which detoxicated by conjugation with glutathione.
• When a very large doses of paracetamol are taken,
the glucuroconjugation capacity is saturated, more
NABQI is formed, hepatic glutathione is depleted
and NABQI binds covalently to proteins in liver
cells (and renal tubules) causing necrosis.
NABQI
Heinz Body Anemia vs. Methemoglobinemia
Reactive Chemical + Oxyhemoglobin
Iron Oxidation
Methemoglobinemia
Cyanosis
Reaction with Globin
Globin Precipitation
Heinz Body Formation
Hemolysis

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Cats and Hemoglobin
• The major form of hemoglobin in the cat has
more reactive –SH groups (8) than any other
animal; makes it prone to denaturing
• The cat spleen does not effectively remove
abnormal red cells
• Moist cat food contains propylene glycol; cats
on this food are more susceptible to Heinz
Body formation
Signs of Toxicity
• Methemoglobinemia, Heinz body formation in
cats
• Cyanosis, dyspnea
• Facial and paw edema
• Anorexia, vomiting
• Delayed liver injury
• Humans and dogs develop hepatic necrosis in
overdoses
Facial Edema
Treatment of Toxicity
• GI decontamination, Activated charcoal, given orally or
through the tube to prevent GI absorption,
• N-acetylcysteine to replenish and substitute for
GSH (140 mg/kg loading dose; 70 mg/kg 6 x 6 hrs
maintenance dose)
– When given orally don’t mix w/ act. Charcoal
• Sodium sulfate is alternative to NAC (50 mg/kg q 4
hrs)
• Ascorbic acid (200 mg/kg q 8 hrs) used to treat
methemoglobinemia in cats, methylene blue (4
mg/kg in dogs; 15 mg/kg in cattle; 1.5 mg/kg in cats)
in other animals
Pyrazolone Derivatives
PHENYLBUTAZONE
• for the treatment of rheumatoid arthritis and other
musculoskeletal disorders
• for use in horses and dogs
• affinity for plasma proteins can displace other highly bound
drugs like warfarin
• Phenylbutazone is biotransformed primarily in liver to active
metabolites oxyphenbutazone and y-hydroxyphenylbutazone
OXYPHENBUTAZONE
• one of the active metabolites of phenylbutazone
• a lesser gastric irritant action than phenylbutazone but is
not superior to the parent drug
AZAPROPAZONE
• a weak inhibitor of cyclooxygenase
• potent uricosuric agent, particularly useful for the
treatment of acute gout
• also for the treatment of rheumatic arthritis and
osteoarthritis

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Indole and Indene Acetic Acid Derivatives
ETODOLAC
• In dogs for the management of pain and inflammation
associated with osteoarthritis
• Mechanism of action
• Like other NSAIDs, etodolac is an inhibitor of cyclooxygenase
enzyme
• Also thought to inhibit macrophage chemotaxis, which may
explain some of the antiinflammatory activity
• Wide safety margin, preferred eye drops for conjuctivitis
• Dose
• Dogs: 10 - 15 mg/kg, PO, once daily. For long-term therapy,
the dose should be reduced to minimum effective level
INDOMETHACIN
• Indomethacin is a methylated indole derivative
• not used in dogs because it is more ulcerogenic than other
NSAIDs in this species
• It is mainly used in human medicine and has limited use in
veterinary practice
SULINDAC
•Sulindac is closely related to indomethacin
•pro-drug that metabolises to its active sulphide metabolite
•for treatment of rheumatoid arthritis, osteoarthritis and
ankylosing spondylitis in man
•Not approved for use in animals
DICLOFENAC
• sodium and potassium (more safer) salts
• GI bleeding(>2 -3days), nephro, hepatotoxic
• Short lasting antiplatelet action
• reduces also neutrophil chemotaxis and superoxide production at
the inflammatory site
• Toxic in elephants
• highly toxic to vultures- which feed on carcasses, tretaed with
diclofenac
• veterinary use banned due to drastic reduction in vulture
population due to kidney damage- Gout
• Vulture death-???? Diclofenac or else??? Debatable now
• Meloxicam , tolfenamic acid, ketoprofen nimesulide have
replaced this largely
PIROXICAM
• Treatment of some cancers in dogs and cats
• Pain due to osteoarthritis.
• Many types of tumors, including nasal epithelial
tumors, mammary tumors, colorectal tumors, oral
squamous cell carcinoma, oral melanoma, prostatic
carcinoma, transitional cell carcinoma (TCC) of the
urinary bladder , osteosarcoma. and some rectal
neoplasms.
• Methotrexate should not be combined with
piroxicam due to potential severe toxicity
MELOXICAM
recently developed congener of piroxicam
• the anti-inflammatory efficacy similar to piroxicam
• GI and renal side effects are significantly less in dogs for
relieving pain and inflammation associated with osteoarthritis
and synovitis
• It is given by oral, sc, im,IV routes
• Antiexudative action- in respiratory conditions- pneumonia,
endotoxaemia
• Antisecretory actions- in secertory diarrhoea
• Dose
• Dogs: 0.2 mg/kg, PO, as a single dose for 1 day, then 0.1
mg/kg, once daily
• Cats: 0.2 - 0.3 mg/kg, SC or PO as a single dose for 1 day,
then 0.1 mg/kg, PO, 2 times weekly

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FLUNIXIN
• Flunixin meglumine is a nicotinic acid used mainly in horses
and also other species like cattle and swine
• alleviates pain arising from spasms (colic) of the GI tract and
is particularly useful for control of severe visceral pain
• does not appreciably alter GI motility in horses and may
improve haemodynamic in animals with septic shock
• Flunixin should not be used in animals with a history of
hypersensitivity reaction to it or aspirin
• Flunixin is usually considered to be contraindicated in cats
Dose
• For anti-inflammatory and analgesic effects
(muscuio-skeletal disorders)
• Dogs: 1 mg/kg, PO, once daily for up to 3 days. Three-days
course may be repeated once weekly for chronic conditions
• Cats: 0.25 mg/kg, SC or IM, once only. May be repeated in
12-24 hours, if needed
• Horses: 1.1 mg/kg, PO, IM or IV, once daily for up to 5 days
• Cattle: 2.2 mg/kg, slow IV, once daily for up to 5 days
• Swine: 1.1-2.2 mg/kg, IV, IM, PO, 1 to 2 times daily or as
needed based on clinical response
• Birds: 1-10 mg/kg, IM
AGENTS WITH ANALGESIC AND MILD TO
MODERATE ANTIINFLAMMATORY ACTIVITY
 Propionic Acid Derivatives/Aryl Propionic Acid Derivatives
• NAPROXEN
• suppression of prostaglandins synthesis. Additionally, naproxen inhibits
leucocytes migration
• Bioavailability after oral administration is about 50% in horses and 70-
100% in dogs
• long half-life is likely due to enterohepatic cycling in the dogs
• naproxen is used primarily in horses
• Dose
• Horses: 10 mg/kg, PO, 2 times daily for up to 14 days
• : 5 mg/kg, slow IV, followed by 10 mg/ kg, PO 2 times daily for up to 14
days
• Dogs: 1.1 mg/kg, PO, 2 times daily
Anthranilic Acid Derivatives/ Fenamates
• MECLOFENAMICACID
• In high concentrations, it may have, antagonistic effects on
histamine and kinins
• In horses, meclofenamic acid can be detected in urine for at
least 4 days following the final dose
• should be avoided during the last stages of pregnancy
• Dose
• Horses: 2.2 mg/kg, PO, once daily for 5 to 7 days best in feed
If treatment is required past 7 days, dosage may be reduced
and interval may be increased to lowest effective level
• Dogs: 1.1 mg/kg, PO, once daily for 5 to 7 days. Dosage may
be reduced, if required past 7 days
• MEFENAMICACID
• Mefenamic acid is another anthranilic acid derivative that
possesses analgesic, antipyretic and anti-inflammatory
activities
• Has lower efficacy
• TOLFENAMIC ACID
• Tolfenamic acid is similar in activity to meclofenamic acid and
is used mainly in veterinary medicine
• Dose
• Dogs & cats: 4 mg/kg, PO, once daily for 3 days given with
food. May be repeated after 4 days
• : 4 mg/kg, SC or IM. May be repeated once after 24 hours, if
required
• Cattle: 2 mg/kg, IM, once daily
NIMESULIDE
 relatively weak inhibitor of COX-1, but has significant
inhibitory effect on the COX-2
 exert its effects by inhibition of histamine release, reduced
generation of superoxide by neutrophils, inhibition of
platelet activating factor and free radical scavenging
 There is evidence that nimesulide inhibits also release of
tumour necrosis factor-alpha(TNF a) and, thus, reduces the
formation of cytokines
 It also blocks the metalloproteinase activity of articular
chondrocytes
 Useful for patients that have allergic hypersensitivity to aspirin
and other NSAIDs
Sulphonanilide Derivatives

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Nimesulide
Contraindications
• Animals suffering from gastrointestinal ulceration or
bleeding.
• Hypersensitivity to the product.
• Animals suffering from cardiac, hepatic or renal impairment.
• Evidence of a blood dyscrasia.
• Puppies younger than 4 months and in dogs under 3,5 kg.
• Not for use in cats, pregnant animals
NABUMETONE
• Recently developed prodrug
• Nabumetone itself is a weak inhibitor of cyclooxygenase
enzyme
• main active metabolite 6-methoxy-2-naphthylacetic acid (6-
MNA) which is a potent inhibitor of cyclooxygenase, in
particular COX-2
Alkalones
METAMIZOLE (DIPYRONE, ANALGIN)
• is a pyrazoline derivative that continues to be used as an
analgesic and antipyretic agent in spite of its ban in some
countries
Analgin can be given orally, i.m. as well as i.v. (very slowly).
• Pain at the i.m. injection site and rarely abscess
can occur. Occasionally an i.v. injection produces
fall in BP.
• Long-term use of metamizole should be avoided as it may
result in agranulocytosis and neutropenia
It also has a tendency to increase bleeding as a result Of
suppression of formation of prothrombin
• Dose Horses: 5 -10 g (total dose) IV, SC or IM. Dose may be
repeated 1 or 2 times at 8 hour intervals
Pyrazolone Derivatives
Benzoxazocine Derivatives
NEFOPAM
• Nefopam is a recently introduced NSAID for use in
human medicine, which does not inhibit prostaglandins
synthesis
• It acts rapidly with an efficacy approaching morphine,
yet it has no opioid actions
• Favourable results hare been obtained in short lasting
musculo-skeletal pain not responding to other NSAIDs
CARPROFEN
• Approved to manage pain and inflammation
associated with osteoarthritis and acute pain
associated with soft-tissue and orthopedic
surgery in dogs.
• The exact mechanism unclear. has greater
selectivity for COX-2 over COX-1
• Labrador Retrievers more prone for toxicity
PHENYLBUTAZONE
• Generally a safe and effective drug in the horse
• Lameness, resulting from from soft tissue injury,
muscle soreness, bone and joint problems, and
laminitis
• Avoided or used with caution in pregnant or nursing
animals.
• May affect blood levels and duration of action of
phentoin, valproic acid, sulfonamides, sulfonylurea
antidiabetic agents, barbiturates, promethazine,
rifampin, chlorpheniramine, diphenhydramine,
penicillin G.

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NIMESULIDE
• In dogs for relief of pain associated with
musculo-skeletal inflammation
• Not indicated for use in puppies younger than
4 months/ dogs under 5kg. and in cats
• Contraindicated in pregnant and lactating
bitches.
• No studies with regard to use in cattle.
KETOPROFEN
• Most commonly prescribed for musculoskeletal pain
from soft tissue injury, osteoarthritis or other bone
and joint problems.
• Potent inhibitor of COX and bradykinin and may also
inhibit some lipoxygenases.
• Efficacy is comparable to that of opioids in the
management of pain following orthopedic and soft-
tissue surgery in dogs.
• Used to reduce or control fevers due to viral or
bacterial infections.
• Used in the management of colic for protection from
bacterial toxins (endotoxemia).
ACECLOFENAC
• Faster, more potent analgesic, antipyretic and anti-
inflammatory activities
• Superior form other NSAIDs as it has selectivity for COX-
2, and is well tolerated, with better GI tolerability and
improved cardiovascular safety when compared to other
selective COX-2 inhibitors.
• It also shows Increased matrix component synthesis and
protection of chondrocytes against apoptosis.
• Efficiently interferes with neutrophils adhesion to
endothelium and this effect may represent an additional
relevant mechanism in its anti-inflammatory activity DOSAGE
10 mg/kg (4.5 mg/lb) on initial day of treatment followed by a daily maintenance dose of
10 mg/kg. Dogs with severe arthritic pain may be given an initial dose of 20 mg/kg
(9.1 mg/lb) to increase the likelihood of reaching minimum effective concentration after
the first dose.
Guidelines for minimising the damage from NSAID
therapy
• Combining analgesic drugs allows for reduction in the
dose of any one analgesic????
• Aggressive analgesic therapy of several days’ duration
should be tapered rather than stopped abruptly.
• Many animals benefit from combined or multimodal
therapy (eg, combining an α2-agonist and an opioid, also
administering an NSAID).
• Many of the commercially available NSAIDs in
combination with other suitable agents for their
synergestic action in pain relieving:
• muscle relaxants like chlorzoxazone, carisoprodol,
chlomezanone, methocarbamol, tizanidine and anti-
inflammatory enzymes like serratiopeptidase.

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NSAID Doses in Small Animals
NSAID Canine
(mg/kg)
Feline
(mg/kg)
Etodolac 10-15 PO QD Not Recommended
Carprofen 4.4 PO, IV, SQ
QD
1-3 SQ ONCE
Deracoxib 1-2 PO QD Not Recommended
NSAID Doses in Dogs and Cats
NSAID Canine
(mg/kg)
Feline
(mg/kg)
Tepoxalin 10 PO QD 5 PO BID
Meloxicam 0.1 SQ ONCE
0.1 PO QD
0.3 SQ ONCE,
0.1 SC then
0.05 PO QD x
5 days
Firocoxib 5 PO QD Not Recommended
NSAID Doses in Small Animals
NSAID Canine
(mg/kg)
Feline
(mg/kg)
Ketoprofen 2 IV, IM, SC
q12-24h
1-2 IV, IM, SC
q12-24h
Phenylbutazone 10-15 PO
q8-12h max
4 days
Not Recommended
NSAID Doses in Small Animals
NSAID Canine
(mg/kg)
Feline
(mg/kg)
Flunixin 1.0 IV, SC
ONCE
1.0 POMax 3
days
Not Recommended
Aspirin 10-25 PO q8-
12h
10 q2-3 days
NSAID Doses in Horses & Cattle
NSAID Horses
(mg/kg)
Cattle (mg/kg)
Ketoprofen 1-2.2 IV, SC
q12-24h
1-2 IM, SQ
q12-24h
Phenylbutazone 2-4 IV, PO
q12-24h
Unclear
Flunixin 1.1 IV, IM
QD
1.1 - 2.2 IV QD
NSAID Doses in Swine & Small
Ruminants
NSAID Swine
(mg/kg)
Sheep
(mg/kg)
Goats
(mg/kg)
Ketoprofen 1-3 IV,
IM, SC
PO QD
3 IV,IM QD 3 IV,IM QD
Phenylbutazone 4-8 PO
BID
2-8 IV
QD
2-4 IV,PO
QD
2-4 IV,PO
QD

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NSAID Doses in Swine & Small
Ruminants
NSAID Swine
(mg/kg)
Sheep
(mg/kg)
Goats
(mg/kg)
Flunixin 0.5-2.2
IV,SQ QD
Max 3
days
0.5 - 2.2
IV, IM,PO
QD- TID
Max 3
days
0.5 - 2.2
IV, IM,PO
QD- TID
Max 3
days
Carprofen 2-4 IV, SC,
PO BID
4 SQ QD 4 SQ QD
Adjuvant analgesic drugs
• Generally not considered to be primary first
choice analgesics
• Used in combination with other analgesic
drugs in acute pain states to manage severe
pain, so as to reduce the dose of the primary
analgesic
Adjuvant analgesic drugs…contd
Methocarbamol
– Muscle relaxant that exerts its effect by acting on the
CNS ,relieve muscle tension associated with arthritis in
pets.
– Weak sedative properties and may make the urine
appear darker.
Alpha-2 agonists
Xylazine and Medetomidine hydrochloride
NMDA Receptor Antagonists
Ketamine, dextromethorphan, memantine, and
amantadine
Adjuvant analgesic drugs…contd
Gabapentin
– A newer anticonvulsant
– Used in dogs and cats for the treatment of chronic pain,
particularly of neuropathic origin and also used in chronic
arthritic pain and pain associated with malignancy.
– Most effective when combined with other types of analgesic
agents, NSAIDs, permitting the use of lower doses.
– Side effects are mild sedation and ataxia.
– Care to be taken in animals with decreased liver or renal
function.
– It should not be discontinued abruptly because withdrawal may
precipitate seizures or rebound pain.
– The dosage should be decreased over the course of two to three
weeks.
– The commercially available human liquid-product contains
xylitol, which can be hepatotoxic in dogs.
Adjuvant analgesic drugs…contd
Local anaesthetics
 Long acting agent bupiavcaine is used along with lidocaine for
long acting pain relief.
A single dose of bupivacaine injected at a local site will provide
local analgesia for 6-10 hours.
Lidocaine is administetred as an intravenous constant rate
infusion(50-70µg/kg/minute in dogs, 10µg/kg/min in cats) is
effective in the treatment of neuropathic pain, periosteal and
peritoneal pain.
It may also reduce the opioid requirement after surgery when
administered as constant rate infusion.
Corticosteroids
– Major side effects when given over extended periods of time.
– Given in the minimal amount that will control and inflammation
and should not be given more than two or three times a week.
Adjuvant analgesic drugs…contd
Other adjunctive drugs
 chondroprotectives, anxiolytics and sedatives like
benzodiazepines (eg: diazepam, midozolam), tricyclic
antidepressants( eg: amitryptilline, imipramine),doxycycline,
omega-3 fatty acids, magnesium, immunonutritional modifiers
and bioflavinoids.
 Non-pharmacologic therapies include acupuncture,
electroacupuncture and various electrical nerve stimulation
procedures, laser therapy and pulsed magnetic field therapy.

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Other Antiinflammatories
CHRONDROPROTECTIVE COMPOUNDS
• Heparinoids: Polysulfated glycosaminoglycan and Pentosan
polysulfate sodium
• improve clinical outcome in animals with osteoarthritis.
• Heparin-like’ in structure and high dosages may inhibit
clotting mechanisms.
• Indicated in Non-infectious and non-immune arthritis
• Contraindicated in advanced hepatic or renal
impairment,uncontrolled bleeding, trauma, infection,
neoplasia,concurrent treatment or within 24 hours of Cstds
SODIUM HYALURONATE:
• is the sodium salt of hyaluronic acid
• a constituent of the high molecular weight
cartilage matrix molecules, aggregated
proteoglycans, and is also present in synovial
fluid.
• Administered by intra-articular or IV route for
joint diseases in the horse
• Arthritis associated with synovitis; navicular
disease
CHONDROITIN AND GLUCOSAMINE
• Assist the repair of cartilage by providing the
‘building blocks’ for new proteoglycan
formation.
• A proportion of these ingested
macromolecules may be absorbed intact, and
some components penetrate the joint.
• dogs with osteoarthritis
DIMETHYL SULFOXIDE (DIMETHYL SULPHOXIDE, DMSO):
• is a solvent that readily dissolves both water-
soluble and lipid-soluble drugs
• used to transport drugs through skin.
• It also possesses some anti-inflammatory
activity and causes dissolution of collagen