Non Steroidal Anti inflammatory drugs ( NSAIDS )

: Prepared by
Hadel mostafa talha
Marwa ali abo alkhairat
Ola abdulnasser Ellfi
Supervised by :
Dr. abdulraof alkosby
 Non Steroidal Anti inflammatory drugs ( NSAIDS )

Introduction
When your back hurts, head aches, arthritis acts up or you’re feeling feverish,
chances are you’ll be reaching for an NSAID (non-steroidal anti-inflammatory
.drug) for relief
You take an NSAID every time you consume an aspirin, or an Advil, or an Aleve.
These drugs are common pain and fever relievers. Every day millions of people
choose an NSAID to help them relieve headache, body aches, swelling, stiffness
.and fever
NSAIDs block the production of certain body chemicals that cause inflammation. NSAIDs are good
at treating pain caused by slow tissue damage, such as arthritis pain. NSAIDs also work well fighting
back pain, menstrual cramps and headaches.
NSAIDs work like corticosteroids (also called steroids), without many of the side effects of steroids.
Steroids are man-made drugs that are similar to cortisone, a naturally-occurring hormone. Like
cortisone, NSAIDs reduce pain and inflammation that often come with joint and muscle diseases
and injuries.
Pharmacokinetics
Most non steroidal anti-inflammatory drugs are weak acids, with a pKa of 3-5. They are absorbed well from
the stomach and intestinal mucosa. They are highly protein-bound in plasma (typically >95%), usually to
albumin, so that their volume of distribution typically approximates to plasma volume.
Most NSAIDs are metabolized in the liver by oxidation and conjugation to inactive metabolites that typically
are excreted in the urine, though some drugs are partially excreted in bile. Metabolism may be abnormal in
certain disease states, and accumulation may occur even with normal dosage. Ibuprofen and diclofenac have
short half-lives (2-3 hours).
Some NSAIDs (typically oxicams) have very long half-lives (e.g. 20-60 hours).The pharmacokinetics profile
of NSAIDs is illustrated , and as indicated for oral administration of NSAIDs most NSAIDs are weak acids
and absorbs well in the stomach and intestinal mucosa. They are also metabolized in the liver by oxidation
and conjugation, and 95%.bound to plasma protein, with high bioavailability.
Pharmacokinetic
NSAIDs are well absorbed following oral administration Once absorbed they are typically highly bound to serum
albumin because they are weak organic acids Most NSAIDs are metabolized predominantly in the liver and are
subsequently excreted in the urine. This has important implications in patients with hepatic and/or renal
dysfunction. Some NSAIDs (indomethacin, sulindac, and piroxicam) have prominent enterohepatic circulation.
This may result in a prolonged half-life. NSAIDs with short half-lives achieve maximum plasma
concentrations quickly whereas those with longer half-lives achieve this more slowly.
Sulindac and nabumetone require conversion to an active compound after first-pass metabolism through the
liver. Once steady-state pharmacokinetics have been achieved, tissue concentrations of NSAIDs do not vary
greatly. Highly lipid-soluble NSAIDs can penetrate the central nervous system and may cause adverse effects
such as headache; this is most frequently noted with indomethacin.
excretion effect: The administration of Aspirin in high doses may reduce renal tubular excretion of urate can are
trans-ported by the same mechanism.
The widespread use of NSAIDs has shown the adverse effect of the drug becoming increasingly common. An
estimated 10–20% of NSAID patients experience dyspepsia and in the 1990s high doses of prescription of NSAIDs
were associated with serious upper gastrointestinal adverse events, including bleeding. There are issues of debate
over the benefits and risks of the use of NSAIDs for the treatment of chronic musculoskeletal pain.
Each drug has a benefit-risk profile and balancing the risk of no treatment with the competing potential risks of
various therapies is the responsibility of the clinician. In the last decade most deaths associated with gastric
bleeding have declined. NSAIDs like most drugs, has the potential to interact with other medications. The case of
concurrent use of NSAIDs and the antibiotics such as quinolone may increase the risk of quinolones' adverse central
nervous system effects, including seizure.
Excretion

NSAIDs are mostly excreted as phase-II glucouronides and in a few cases as sulfate conjugates. In

addition, small percentages of NSAIDs are excreted unchanged in urine. If the drug is excreted

unchanged, its rate of excretion is expected to increase if the drug is coadministered with agents

that render the urine pH alkaline such as the antacids aluminum hydroxide and milk of magnesia

(5&6).
Absorption

The NSAIDs share similar absorption properties as all NSAIDs are highly lipophilic

substances. Absorption occurs throughout the gastrointestinal tract, but particularly in the

stomach of monogastric animals, the pH is normally more acidic than plasma pH. An acidic

environment promotes the absorption of NSAIDs which, as weak acids, are less ionized in

gastric juice and therefore absorbed by the mechanism of ionic or diffusion trapping. Most

NSAIDs are given as oral tablets or capsules; others are given by injection to avoid gastric

irritation (4&5).
ASA is absorbed primarily intact, and then is hydrolyzed by plasma and tissue (liver) esterases

to salicylic acid. ASA and salicylic acid is extensively bound to plasma albumin – the ionized

carboxyl and aromatic functionalities both contribute to plasma protein binding.

This may result in drug-drug interactions with other anionic drugs that are administered

concurrently and are also highly bound by plasma protein.

Drug absorption is determined by the drug’s physicochemical properties, formulation, and route of
administration. Dosage forms (eg, tablets, capsules, solutions), consisting of the drug plus other ingredients, are
formulated to be given by various routes (eg, oral, buccal, sublingual, rectal, parenteral, topical, inhalational).
Regardless of the route of administration, drugs must be in solution to be absorbed. Thus, solid forms (eg,
tablets) must be able to disintegrate and deaggregate.
Unless given IV, a drug must cross several semipermeable cell membranes before it reaches the systemic
circulation. Cell membranes are biologic barriers that selectively inhibit passage of drug molecules. The
membranes are composed primarily of a bimolecular lipid matrix, which determines membrane permeability
characteristics. Drugs may cross cell membranes by
Passive diffusion
Facilitated passive diffusion
Active transport
Pinocytosis
Sometimes various globular proteins embedded in the matrix function as receptors and help transport molecules
across the membrane.
Metabolism: Salicylic acid and drugs like ASA that are converted to salicylic acid undergo a variety of
secondary metabolic transformations including: glycine conjugation to yield salicyluric acid, ring
hydroxylation and carboxyl and phenol glucuronide conjugation. The salicylates and their metabolites are
eliminated by renal mechanism.
The action of Aspirin and other NSAIDs are significant only at anti-inflammatory doses. The cellular

metabolism is increased, particularly at the skeletal muscles, due to the uncoupling of oxidative

phosphorylation resulting from the increase in heat production. There is increased utilization of glucose and

blood sugar may decrease particularly in diabetics and liver glycogen is depleted. However, hyperglycemia is

often seen at toxic doses: this is due to central sympathetic stimulation and release of adrenaline and GCS.

Chronic use of large doses cause negative nitrogen balance by increased conversion of protein to carbohydrate

Plasma free fatty and cholesterol are reduced.

Distribution
The most significant aspect of NSAIDs distribution is plasma-protein binding which is high (>95%)
for most NSAIDs, although salicylate is an exception, with binding of ~50%. The major plasma
protein component is albumin. The high degree of protein binding limits renal excretion of most
NSAIDs. High plasma-protein binding may also limit the distribution of NSAIDs from plasma to
body fluids and tissues. However, this does not necessarily limit and may even enhance therapeutic
efficacy in acute inflammation because protein leaks from the vascular comparent into inflamed
tissues and because drug concentrations in inflammatory exudates commonly exceed those in
plasma (4&5). Protein binding does limit penetration into fluids such as milk. Flunixin and
phenylbutazone have concentrations in milk that are ~1% of the plasma levels, corresponding
approximately to the nonbound plasma concentration.
Currently available NSAIDs are indicated for the treatment of mild to moderately severe, acute and chronic

pain, inflammation and pyrexia. Non-steroidal anti-inflammatory drugs differ widely in potency and

therapeutic efficacy. Differences in efficacy can be explained by varying degrees of COX and cytokine

inhibition, non-COX mechanisms, differing analgesia versus anti-inflammatory effects, and wide individual

variation in response, within and between species.

A large number of non-steroidal anti-inflammatory drugs, of different chemical groups are available for

veterinary use. For the Livestock sector Montajat Pharmaceuticals is providing safe and cost effective NSAIDs

for the better management of diseases to ensure optimal production. Some of the known brands are discussed

below. For more details, please visit www.montajat.biz.