NSAIDs

gago hahaha.

COXIBS

* Celecoxib
* Etoricoxib
* Meloxicam
* Valedecoxib

COX 2 Selective Inhibitor Specific Agents

* Diclofenac
* Diflusinal
* Etodolac
* Fenoprofen
* Flurbiprofen
* Ibuprofen
* Indomethacin
* Ketoprofen
* Ketorolac
* Meclofenamate
* Mefenamic Acid
* Nabumetone
* Naproxen
* Oxaprozin
* Phenylbutazone
* Piroxican
* Sulindac
* Tenoxicam
* Tiaprofen
* Tolmetin
* Azapropazone
* Carprofen

Nonselective COX inhibitor (penge lima kasi caloocan kabisaduhin to)

Protein binding, Metabolism, Excretion similar to Aspirin

Pattern of Absorption

Salicylic acid

Active metabolite form of Aspirin

Consumed orally. Aspirin is absorbed in the stomach and small intestine, 80 to 90 is bound to plasma like albumin, 10 to 20 is distributed to the body where it exerts therapeutic effects. It is then hydrolyzed in the bloodstream to salicylic acid, which is further metabolized by oxidation in the liver. It is excreted via kidney. (try to get the gist)

Pharmacokinetic of Aspirin

Absorbed rapidly and completely in the upper GI tract. Plasma protein binding here varies from 20 to 50%. In the liver, acetaminophen is metabolized into toxic N-acetyl-p-benzoQuinone imine (NAPQI). NAPQI is detoxified by conjugation with glutathione (GSH), forming mercapturic acid, which is excreted in the urine. (gist lang)

Pharmacokinetics for Acetaminophen

Celecoxib

* COX 2 Selective (10-20x more selective for COX 2 than COX 1)
* As effective against Rheumatic and Osteoarthritis as other NSAIDs
* Caused fewer stomach ulcers than other NSAIDs
* no platelet aggregation effect
* can cause rashes, maybe cuz its a sulfonamide

Etoricoxib

* COX 2 selective
* Bipyridine derivative
* **2nd gen COX 2 inhibitor w/ high selectivity** ratio for COX 2
* metabolized by hepatic P450 enzymes followed by renal excretion and has an elimination half-life of **22 hours.**
* As effective against Osteoarthritis, Acute gouty arthritis and primary dysmenorrhea as other trad NSAIDs
* Approved by the UK for OA, RA and acute gouty Arthritis

Meloxicam

* Enolcarboxamide related to Piroxicam.
* Not as selective as other coxibs, more so preferential in selectivity.
* Popular in EU for rheumatic diseases and recently in US for OA
* less GIT probs than Piroxicam, Diclofenac and Naproxen

Valdecoxib

* Diaryl substitute isoxazole
* Highly selective COX 2 inhibitor
* Analgesic dose is 20mg bid
* fucks up sulfonamide-sensitive pts.9
* nono in US for risk of CV probs and possible Stevens Johnson syndrome (epidermal necrolysis)

Diclofenac

* A phenylacetic acid derivative
* relatively nonselective
* impairs renal blood flow at 150 mg a day
* In eyes, as a .1% ophthalmic preparation, it is recommended for prevention of postop ophthalmic inflammation can be used after intraocular lens implantation (artificial less implant) and strabismus surgery (surgical treatment sa duling or cross-eye).
* Rectal suppository: for preemptive analgesia and postoperative nausea
* available as mouthwash and IM admin in Europe

Diflunisal

* derived from salicylic acid but is not metabolized back into it or salicylate
* recommended dose for RA is 500 to 1000 mg bid
* claimed to be effective in cancer pain w/ bone metastases and for pain control in 3rd molar surgeries.
* 2% oral ointment of this is clinically useful for painful oral lesions.
* limited for renally impaired patients.

Etodolac

* Racemic actic acid derivative and slightly more COX 2 selective than most other NSAIDs with a COX2:COX1 activity ratio of about 10
* 200 to 400 mg tid or qid
* good postop pain relief for coronary bypass op but has transient renal impairment issues
* Claimed to cause less gastric toxicity in terms of ulcer than other non selectives

Fenoprofen

* Propionic acid derivative
* NSAID most closely assoc with interstitial nephritis and is rarely used tbh.

Flurbiprofen

* Propionic acid derivative w/ a more complex MOA than other NSAIDs
* Effective at 200 to 400 mg od, comparable to aspirin and other NSAIDs in clinical trials for RA, ankylosing spondylitis, gout and OA
* Also available in a topical ophthalmic formulation for inhibition of intraoperative miosis
* IV given has been found to be effective for periop analgesia in minor ear, neck or nose surgery and in lozenge form for sore throat
* LOZENGE FOR SORE THROAT

Ibuprofen

* Derivative of phenylpropionic acid


* 4g aspirin = 2.4g of this for the same anti-inflammatory effect
* if dose is lower, is analgesic but not anti-inflammatory.
* Topical cream version is absorbed by fascia and muscle
* 400mg Liquid gel variation of this prompts relief in post op dental pain
* Better than indomethacin by having you pee more, less fluid retention, and is as effective in closing patient ductus arteriosus in preterm infants
* also gives GIT irritation and bleeding but less than aspirin

Indomethacin

* Derived from indole.
* potent nonselective COX inhibitor (hater ng lahat)
* inhibits phospholipase A (precursor of arachidonic) and C, reduce neutrophil migration and dec. T cell and B cell proliferation.
* Indicated for Rheumatic condition, popular in gout and ankylosing spondylitis.
* Used to patent ductus arteriosus.
* Ophthalmic Preparation: Conjunctival Inflammation and pain reduction after traumatic corneal abrasion.
* Oral Rinse: Gingival inflammation

Ketoprofen

* Propionic acid derivative that inhibits both **COX and lipoxygenase**
* Equal with other NSAIDS in terms of treating RA, OA, gout, dysmenorrhea and other painful at dosages of 100-300 mg/d
* not superior than other NSAIDs

Ketorolac

* promoted for systemic use as an analgesic, not as anti inflam
* Used to replace morphine in some mild to mod postsurgical pain
* Often IM or IV, Oral also avail.
* if used decreases opioid requirement by 25 to 50%

Meclofenamate and Mefenamic acid

* Inhibits both COX and phospholipase A2 (fat that is precursor for phospholipase)
* Rarely used today, do be toxic, more than aspirin even

NABUMETONE

* non-acid NSAID in current use
* converted to active acetic acid derivative within body
* 24 hour half-life
* Similar properties with other NSAIDs, less damaging if 1000mg/d but 1500-2000mg/d is more often needed

Naproxen

* Napththylpropionic acid derivative
* only NSAID presently marketed as a single enatiomer and is a nonselective COX inhibitor.
* Effective against rheumatologic function
* Available in slow-release formulation and as an oral suspension

Oxaprozin

* Propionic acid derivative
* long af half-life, 50-60 hrs
* more useful in gout than some other NSAIDs

Phenylbutazone

* Pyrazolone derivative but rarely used today because of its toxicity

Piroxicam

* Nonselective COX inhibitor
* at high concentration also inhibits polymorphonuclear leukocyte migration, decreases oxygen radial production and inhibits lymphocyte function.
* Used for the usual rheumatic indications

Sulindac

* Used in rheumatic conditions, suppresses familial intestinal polyposis.
* May inhibit the development of colon, breast and prostate cancer

Tenoxicam

* Oxicam similar to piroxicam
* Long half-life, efficacy and toxicity profile

Tiaprofen

* Racemic propionic acid derivative, 1-2 hour shortlife
* Inhibit renal uric acid reabsorption, thus decreasing serum uric acid slightly.
* Available oral and IM admin.

Tolmentin

* Not used often, short half-life + ineffective in gout.

Azapropazone and Carprofen

* Pyrazolone derivative
* Related to phenylbutazone structurally but is less likely to cause agranulocytosis.
* 2nd one has a propionic acid derivative with a half-life of 10-16 hours