COX 2 inhibitor

1. NUR HAJRIYA BRAHMI

2. An enzyme that catalyzes the synthesis of
prostaglandins from arachnoid acid
It’s activity associated with 2 iso-enzymes
expressed as COX-1 and COX-2
COX -1 essential in homeostatic process such
as platelet aggregation, gastrointestinal
mucosal integrity and renal fuction
COX 2 is inducible, expressed in mainly at
sites of injury (brain and kidneys),mediates
inflammation, fever, pain , and
carcinogenesis

4. A varied group of drugs processing analgesic,
antiinflammatory, and antipyretic effects.
Inhibited both COX-1 and COX-2 enzymes.

5. Characteristic Potensial Adverse Effect
Decrease activation and sensitization of
peripheral nociceptors
Inhibition of platelet aggregation
Attenuate the inflammatory response Gastric ulceration
Absence of dependence or addictional potential Renal dysfunction
Synergistic effect with opioids Hepatocellular injury
Preemptive Analgesia (decrease neuronal
sesitization)
Asthma Exacerbation
Absence of depression of breathing Allergic reaction
Less nausea and vomiting compared with opioids Tinnitus
Long duration of action Urticaria
Less dose variability compared with opioids
No pupillary changes
Absence of cognitive effects

6. Examples of Drugs Characteristic Dosage
Celecoxib Pain and inflammation
related to Osteorthritis
and Rheumatoid Arthritis
OA : 1x 200 mg daily
RA : 2 x 100 – 200 mg daily
Rofecoxib
Withdrawn since double
the risk of myocardial
infarction and CVA
Acute surgical pain
Acute menstrual pain
Loading 50 mg then 25 mg
daily
Valdecoxib Relief post operative pain 40 mg : 1 hour before
surgery , and additional 40
mg after surgery if needed
Parecoxib The only available with
parenteral form
Post operative pain relief 40 mg : 1 hour before
surgery , and additional 40
mg after surgery if needed

7. Clinical Use Description
Analgesic efficacy Suitable for : pain due to osteoarthritis,
rheumtoid arthritis, acute gout, dental pain,
dysmenorrhea, musculoskeletal conditon.
Acute post operative pain : orthopaedic
surgery and arthroscopy
Post operative Pain Management Reduce post operative pain by suppressing
COX mediated production of prostaglandin E
 minimize sensitivity of peripheral
nociceptor of pain.
Lack of effect on platelet function and
bleeding
Tolerable for patient with gastritis or gastric
ulcer, asthma
Protection Against Colorectal Cancer Inhibit colon tumor growth, adenomatous
polyps
Protection Against Dementia Decrease inflammatory process of neural
destruction

8. Side Effect Description
Gastrointestinal Toxicity Nonselective NSAID  inhibition of COX-1  minimize PG
that protect gastrointestinal mucose by maintaining
mucosal blood flow and increase secretion mucous and
bicarbonate
50% decrease inCOX-2 spesific inhibitor
Coagulation Effects Platelet aggregitation and homeostasis depend on the
ability of platelets to generate thromboxane mediated by
COX-1.
COX-2 inhibitor have no effect on platelet aggregation,
bleeding time or post operative blood loss.
Cardiac effect COX-2 inhibitor selective suppression of PG I2
(vasoprotective) without affecting thromboxane A2
(procoagulant), increasing the risk of myocrdial infarction.
Hypertensive effect PG modulate systemic blood pressure by virtue effect on
vascular tone arterial smooth muscle and control of
extracellular fluid volume (natriuretic effect).

9. Side Effect Description
Renal Effect PG participate autoregulation on renal blood flow and
glomerular filtration. Nephrotoxic potential increase in
elderly that had NSAID. Prerenal azotemia reflecting decrease
renal perfusion is the most frequent pattern of renal injury,
hipercloremic metabolic acidosis in association hyperkalemia
mostly occur with patient with preexisting renal disease.
Hepatic Effect Increase in plasma concentration of liver transaminase
Allergy Contraindication to treatment with celecoxib and valdecoxib
is sulfonamide hypersensitivity.
Should not be administer to patient who have asthma,
urticaria or allergic type reaction to aspirin.
Asthma May trigger bronchoconstriction by blocking COX mediated
conversion of arachdonic acid to prostaglandin esp PG E2 (a
poten antiinflammatory substance).

11. Chemical Classification Example of drugs
Carboxylic Acid
Acetylated
Nonacetylated
Aspirin
Salicylamide
Acetic Acid Indometacin, tolmetin
Propionic Acid Ibuprofen, Naproxen, Ketoprofen
Enolic acid Phenylbutazone, piroxicam
Pyrrolopyrrole Ketorolac

12. Drugs Description
Aspirin
Acetylsalicylic Acid
Produce analgesia through irreversible acetylate COX enzyme
 decrease synthesis and release of PG. Leukotrients
pathway remain intake, does not interact with opioid
receptor, little effect on release histamin/serotonin.
Rapidly absorb from small intestine , the rate of absorption
influenced by administer tablet and gastric emptying time :
more acid the rate is increased, food delay absorption.
Metabolism in hepar, excreted in the urine .
Clinical Use : analgesic symptomatic relief of low intensity
pain associated with headache and musculoskeletal disorders
; antipyretic, antiplatelet drugs for myocardial infarct.
Major side effects of aspirin teraphy related to gastrointestinal
tract dysfunction (gastric irritation and ulceration) and
inhibition of platelet function (prolongation of bleeding time).
The other side effect will be CNS Simulation (hyperventilation
– direct effect to medullary ventilatory centre), tinnitus,
hepatic dysfunction, aspirin induced asthma.

13. Drugs Description
Acetaminophen Widely used as analgesic and antipyretic , an over the counter drug
Alternate to aspirin if given 325 to 650 mg every 4 – 6 hours, esp for
pediatric patient and patients whom salicylates not recommended.
Unlike aspirin, acetaminophen does not gastric irritation, alter
aggregation of platelet.
Weak antiinflammatory effect.
Oral route administration
It’s metabolit (p-aminophenol) concentrated in the hypertonic
renal papillae (nephrotoxic : it’s oxidize and binds convalently to
sulfhidryl containing tissue-macromolecule and deplete stores of
reduce gluthation, leading to cell necrosis.

14. Drugs Description
Ketorolac Exhibit potent analgesic (for post op analesia : less painful
ambulatory procedur or for supplement to opioids, moderate anti
inflamatory effect).
Exhibit a ceiling effect to post operative analgesia
30 mg ketorolac IM similar potency of analgesia as 10 mg morphin
or 100 mg meperidine.
Absence of ventilatory or cardiovascular depression
Little or no effect on biliary tract : useful analgesic when spasm of
the biliry tract is undesirable.
IM : max plasma concentration achieved 45 – 60 mins elimination
time is 5 hours.
Clearance is decrease in elderly , the dose should be less
Inhibit platelet aggregation by reversible inhibition of prostaglandin
synthetase
Life threatening bronchospasm may follow in nasal polyp patient,
asthma, and aspirin sensitiviy.
Gastro intestinal irritation and perforation, nausea may accompany