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 compositi Packing compan Recommend Pics
neme
on y ed dose
Fluximin 50mg/ml 50&100 Ghazi 2ml/45kg
e ml brother
s
Loxin 50mg/ml 10,20&5 Selmor 2ml/45kg
0ml e

Fluean 50mg/ml 10,20&5 Leads 2ml/45kg

0ml 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 10,20,50 Internat 2ml/45kg

ml ional
pharma

Flu-Nix 50mg/ml 10,20,50 Agrilab 2ml/45kg

D ml s

Flunime 50mg/ml 10&30m Zydus 2ml/45kg

g l AH

Flunixin Meglumine+Oxytetracycline
Trade compositi Packing company Dose Pics
Name on
Oxy-Flu Oxy 10,50&100 Leads 1ml/100k
300mg/ml ml pharma g
Flunixin
20mg/ml
 Ketoprofen
Ketoprofen is a propionic-acid derivative. The maximum anti-
inflammatory effectsof 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 Compositio Packing Company Dose Pics
Name n
Ketoject 100mg/ml 10,20,50ml selmore Horses
1ml/45k
g
Cattles
1ml/33k
g
Keto-P 100mg/ml 10,20&50ml Star lab same
Fenleve 100mg/ml 50ml Fatro same
10

Itofen 100mg/ml 10,20,50,100,50 Internationa same

0 l

Profeni 50mg/ml 2ml ampule Rhone- Double

d Poulenc dose
Rorer

Methampyron + Aminopyrine + Caffeine + Chlorpheniramine