Anti-inflammatory Drugs

These are broadly divided into two groups; Corticosteroids and Non-
steroidal anti-inflammatory drugs (NSAIDs).
Non-steroidal anti-inflammatory drugs (NSAIDs): NSAIDs by virtue of
inhibiting cyclooxygenases, are effective in suppressing inflammation,
alleviating pain, and lowering fever. Cyclooxygenases (COX) (localized in
endoplasmic reticulum) are responsible for the formation of a group of local
hormones comprising the prostaglandins, prostacyclin, and thromboxanes
(from arachidonic acid). These enzymes possess an elongated pore into which
the substrate arachidonic acid is inserted and converted to an active product.
NSAIDs penetrate into this pore and thus prevent access for arachidonic acid,
leading to reversible blockade of the enzyme. Two principal types of COX can
be distinguished: COX-1 is constitutive, that is, always present and active; it
contributes to the physiological function of organs. Inhibition inevitably
produces unwanted effects, such as mucosal injury, renal damage,
hemodynamic changes, and disturbances of uterine function. COX-2 is
induced by inflammatory processes and produces prostaglandins that
sensitize nociceptors, evoke fever, and promote inflammation by causing
vasodilation and an increase in vascular permeability. However, in some
organs, COX-2 is also expressed constitutively (kidney, vascular endothelium,
uterus, and CNS).
Non-selective COX-inhibitors: These include Acetylsalicylic acid or Aspirin
(Disprin), Paracetamol or Acetaminophen (Panadol), Ibuprofen (Brufen),
Meclofenamic acid (Ponston), Diclofenac (Voren, Phlogen, Dyclo, Dicloron,
Diclostar, Fenac), Metamizole (Dipyrone, Magnapyrol, Novalgene),
Phenylbutazone (Butadin), Piroxicam (Feldene) and Naproxen (Neoprox).
Selective COX-inhibitors: Meloxicam and Nimusulide (Nims) are included in
this group.
Pharmacological actions of NSAIDs:
(a) Antipyretic effect: The hypothalamus that is responsible for thermo-
regulation, is affected by exogenous pyrogens such as bacterial toxins and
endogenous pyrogens (now considered to be IL -1). Pyrogens promote the
synthesis and subsequent release of prostaglandin E (PGE). PGE can raise the
set-point of body temperature, in order to increase heat production,
dissipate heat production, and to raise the body temperature. NSAIDs being
the inhibitors of prostaglandin synthesis are helpful to restore normal
thermoregulatory control mechanism.
(b) Analgesic effect: Some inflammatory mediators like prostaglandins and
bradykinins are also involved in pain sensation. Therefore the anti-
prostaglandinic action of NSAIDs can provide good analgesia in many
conditions such as neuralgia, myalgia, joint pain, muscle pain, and so on, but
these agents are not effective for the suppression of acute pain and visceral
pain.
(c) Anti-inflammatory effect: Prostaglandins are key mediators in
inflammatory reaction, a large number of them exist in inflammation
organizations. NSAIDs have the ability to subside inflammation by inhibiting
the synthesis of prostaglandins.
Clinical uses: NSAIDs are generally indicated for the symptomatic relief of the
many conditions like rheumatoid arthritis (auto-immune-mediated
inflammatory disorder that may affect many tissues and organs, but
principally attacks synovial joints), osteoarthritis, laminitis, dysmenorrhoea
(menstrual pain), metastatic bone pain, headache and migraine,
postoperative pain, pyrexia (fever), renal colic, myalgia and mild-to-
moderate pain due to inflammation and tissue injury. Aspirin is used (for its
inhibitory effect on platelet aggregation) in dissiminated intravascular
coagulation (DIC), thrombo-embolic disorders and heartworm (Dirrofilaria
immitis) infection in dogs.
Adverse effects: The following side effects are linked with improper
administration of NSAIDs.
1. Some prostaglandins (like PGE) possess beneficial role in terms of
suppression of gastric acid secretion and regulation of renal microperfusion.
Thus prostaglandin inhibitors (NSAIDs) can cause (or aggravate) gastric
hyperacidity and renal disturbances.
2. Inhibition of TXA2 synthesis by NSAIDs results in profused bleeding and
delayed clotting time (via inhibiting platelet aggregation). This property can
be benefited to resolve intravascular thrombi (that can cause embolism and
ischemia) in some cardiac disorders like myocardial infarction.
3. NSAIDs that are acidic in nature (like Aspirin and Paracetamol) undergo
hepatic metabolism through glucoronide conjugation. Species that are
inherently deficient in glucoronide conjugatory mechanism (such as
glucoronyl transferase deficiency) are susceptible to serious toxicosis (the
half life of these drugs is abnormally prolonged due to lack of sufficient
biotransformation). Acetylcysteine (precursor of Glutathione and potent
antioxidant) should be used to suppress free radical induced cellular damage
that occurs during this idiosyncratic condition.
4. Large doses of Aspirin may cause hyperglycemia (by uncoupling
phosphorylation during glycolysis) followed by glycosuria (release of glucose
in urine) and deplete liver and muscle glycogen.
5. In humans the use of Aspirin has been implicated in the causation of
salicylism (a syndrome that is characterized by dizziness, vertigo and
reversible visual and auditory impairment) and Reyes syndrome (occurs in
infants suffering from viral infection and it is manifested by hepatic damage
and encephalopathy).
6. Metamizole is known to cause agranulocytosis (decresed synthesis of
agranulocytes; lymphocytes and monocytes).
7. Diclofenac has been banned in many countries (in Nepal, India and Pakistan
in 2006 and in Bangladesh in 2010) for use in livestock because it causes
kidney necrosis in vultures, leading to reduced excretion of uric acid and the
deposition of uric acid crystals in tissues. Death usually occurs within two
days. Studies conducted in Pakistan showed that diclofenac caused acute
kidney failure in vultures when they ate the carcasses of animals that had
recently been treated with it.
Contraindications: NSAIDs are contraindicated in persons suffering from
gastrointestinal ulceration, bleeding disorders and human infants (having
viral infection). Aspirin therapy should be stopped one week before surgery
(to avoid excessive bleeding), and it should be used cautiously in species with
improper metabolizing potential (cats and fish).
Interactions: Aspirin enhances the action and toxicity of oral anticoagulants
and Heparin by increasing risk of bleeding. The urinary excretion of acidic
NSAIDs is increased and decreased by the concomitant administration of
urinary alkalizers (like sodium bi carbonate) and urinary acidifiers (like
ammonium chloride) respectively.

Flunixin Meglumine
The onset of antiinflammatory action is within 2 hours, peak response occurs
between 12 and 16 hours, and duration of action is 36 hours. Analgesic effects
have a more rapid onset and shorter duration than anti-inflammatory
effects.Only 14% of a dose is excreted in urine, but little else is known about
the metabolism of flunixin.
Indications:
Flunixin is used in horses to treat a variety of inflammatory and
painful conditions, including colic, colitis, laminitis, ocular disease, endotoxic
shock, general surgery, respiratory disease, and exertional rhabdomyolysis.
Flunixin is more effective at preventing the clinical signs of endotoxemia than
phenylbutazone, dipyrone, and ibuprofen and may prevent abortion in
endotoxic mares.
It is good painkiller and anti-inflammatory drug also in bovines. Bovine colic
is severe painfull condition in cattles inthis case flunixin meglumine give good
results.
Although not universally accepted, some veterinarians believe that high
doses of flunixin may mask signs of severe visceral pain and interfere with
the clinicians ability to determine when surgical intervention is
necessary.
Side Effects:
(i) Myonecrosis when administered via the IM route
(ii) Overdose of flunixin in horses may cause multiple ulcers on the
tongue, gingiva, palate, lips, and stomach. CNS depression,
listlessness, and anorexia may also occur. Rare anaphylactic-like
reactions may occur particularly after rapid IV administration.
(iii) Acute renal failure and GI damage have been reported in dogs
treated with flunixin.
(iv) Hematochezia and hematuria can be seen in cattle treated for
longer than 3 days.
Horses: 0.25-1 mg/kg IM Ruminants: 1.1-2.2 mg/kg IM
Trade neme composition Packing company Recommended Pics
dose
Fluximine 50mg/ml 50&100ml Ghazi 2ml/45kg
brothers

Loxin 50mg/ml 10,20&50 Selmore 2ml/45kg

ml

Fluean 50mg/ml 10,20&50 Leads 2ml/45kg

ml pharma
Maxin 50mg/ml 10,20,50& Star lab 2ml/45kg
100ml

Phoenix 50mg/ml 50ml Mylab 2ml/45kg

Alivios 50mg/ml 10,20,50 Fatro 2ml/45kg

I-Flox 50mg/ml 10,20,50m Internati 2ml/45kg

l onal
pharma

Flu-Nix D 50mg/ml 10,20,50m Agrilabs 2ml/45kg

l

Flunimeg 50mg/ml 10&30ml Zydus AH 2ml/45kg

 Tricure 50mg/ml 50,100 ICI Cattle
ml 2ml/45kg
H
1ml/45kg

Pri- 50mg/ml 5,10,20, Prix Cattle

Deflame 5 50,100 2ml/45kg
ml
Fluzak 50mg/ml 10,30,5 zakfas 2ml/45kg
0,100ml

Flunixin Meglumine+Oxytetracycline
Trade Name composition Packing company Dose Pics

Oxy-Flu Oxy 10,50&100ml Leads 1ml/100kg

300mg/ml pharma
Flunixin
20mg/ml

FMO Flu-20mg 50, 100 A&K 2ml/45kg

inj. Oxy Pharma
300mg
 Ketoprofen
Ketoprofen is a propionic-acid derivative. The maximum anti-
inflammatory effects of ketoprofen occur 12 hours after dosing and last
for 24 hours. Ketoprofen is labeled for use in horses for the
alleviation of inflammation and pain associated with
musculoskeletal disorders.
Ketoprofen also appears to have a better safety profile in horses than
flunixin or phenylbutazone, although very high doses can cause
depression, icterus, nephritis, hepatitis, and hemorrhagic necrosis of the
adrenal glands.
Horses: 2.2 mg/kg, IV, sid
Ruminants: 2.2 mg/kg, IV; 3 mg/kg, IM, sid
Trade Composition Packing Company Dose Pics
Name
Ketoject 100mg/ml 10,20,50ml selmore Horses
1ml/45kg
Cattles
1ml/33kg

Keto-P 100mg/ml 10,20&50ml Star lab same

Fenleve 100mg/ml 50ml Fatro same
10

Itofen 100mg/ml 10,20,50,100,500 International same

Profenid 50mg/ml 2ml ampule Rhone- Double

Poulenc dose
Rorer

Methampyron + Aminopyrine + Caffeine + Chlorpheniramine