Tishk International University

College of Pharmacy

Anti Inflammatory Agents

Prepared by:
Ayub Baiz Abdulla
Abdulmalik Abdulkhaliq
Muhammad Khalid
Ayad Ahmad

Supervised by:
Dr. Mohammad Javed Naim

March 2024
Table of content

Introduction ............................................................................................................................................ 2
Classification and structure of Anti-inflammatory agents: ..................................................................... 3
Classification of Nonsteroidal anti-inflammatory ............................................................................... 3
Mechanism action of nonsteroidal anti-inflammatory ....................................................................... 5
Mechanism action of aspirin ........................................................................................................... 6
Classification of Steroidal anti-inflammatory ..................................................................................... 7
Uses of anti-inflammatory drugs .......................................................................................................... 11
Anti-inflammatory drugs Adverse effects ............................................................................................. 11
Reference .............................................................................................................................................. 12

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Introduction

Inflammation is a defense response of our body to hazardous stimuli such as allergens and/or
injury to the tissues; on the other hand, uncontrolled inflammatory response is the main cause
of a vast continuum of disorders including allergies, cardiovascular dysfunctions, metabolic
syndrome, cancer, and autoimmune diseases imposing a huge economic burden on individuals
and consequently on the society. T here are various medicines for controlling and suppressing
inflammatory crisis; steroids, nonsteroid anti-inflammatory drugs, and immunosuppressant are
the practical examples of these medications which are associated with adverse effects while in
practice our goal is to apply minimum effective dose by the highest efficacy with the least
adverse effects. Thus, we need to apply natural anti-inflammatory factors within medication
therapy to achieve increased pharmacological response and the lowest degree of unwanted side
effects . Herbal medicines are promoting subjects in medicine and, of course, we have to
increase our knowledge about Complementary, alternative, and traditional medicines are the
pivotal source of herbal medication guidance, but surely modern medicine must prove these
guidelines through scientific methods before using them in practice.
Inflammation usually occurs when infectious microorganisms such as bacteria, viruses or fungi
invade the body, reside in particular tissues and/or circulate in the blood . Inflammation. May
also happen in response to processes such as tissue injury, cell death, cancer, ischemia and
degeneration . Mostly, both the innate immune response as well as the adaptive immune
response are involved in the formation of inflammation . The innate immune system is the
foremost defense mechanism against invading microorganisms and cancer cells, involving the
activity of various cells including macrophages, mast cells and dendritic cells. The adaptive
immune systems. Involves the activity of more specialized cells such as B and T cells who are
responsible for eradicating invading pathogens and cancer cells by producing specific receptors
and antibodies.
Reducing pain, inflammation, and fever with salicy- late-containing plant extracts can be traced
through- out written human history. One hundred and fifty years ago, Felix Hoffman acetylated
salicylic acid and created aspirin. Aspirin inhibits the cyclooxyge- nase (COX) enzymes COX-
1 and COX-2, which syn- thesize inflammatory mediators called prostaglandins and
thromboxanes. The ability to block production of prostaglandins and thromboxanes accounts
for as- pirin being the world's most used therapeutic agent. Second to aspirin are nonsteroidal
anti-inflammatory drugs (NSAIDS), which target COX-2 and hence the synthesis of
prostaglandins, particularly PGE2. Synthetic forms of natural cortisol (termed glucocor-
ticoids) are also widely used to treat many inflamma- tory diseases, and despite their side
effects, glucocor- ticoids remain a mainstay for reducing inflammation.
Non-steroidal anti-inflammatory drugs (NSAIDs) are a diverse group of compounds with
similar biological capabilities: all NSAIDs reduce or eliminate the erythema, swelling, elevated
temperature and pain caused by a variety of inflammatory stimuli. The mechanisms of action
of NSAIDs have not yet been fully elucidated, but evidence suggests that their anti-
inflammatory effects are primarily achieved through inhibiting prostaglandin production. This
mode of action is common to all NSAIDs

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Classification and structure of Anti-inflammatory agents:
Classification of Nonsteroidal anti-inflammatory

NSAIDs are a class of medications used to treat pain, fever, and other inflammatory processes.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a drug class FDA-approved for use as
antipyretic, anti-inflammatory, and analgesic agents. These effects make NSAIDs useful for
treating muscle pain, dysmenorrhea, arthritic conditions, pyrexia, gout, migraines, and used as
opioid-sparing agents in certain acute trauma cases.

1. Non selective cox inhibitors: these agents block the entire action of the cyclooxygenase
both 1 and 2, ex:mefenamic acid.
2. Preferential COX-2 inhibitors: Nimesulide, Diclofenac, aceclofenace, Meloxicam,
Etodolac.
3. selective cox 2 inhibitors: these agents that only have cox 2 inhibition effect without
inhibition of cox 1. ex: celecoxib, parecoxib.
4. analgesics-antipyretic with poor anti-inflammatory effect: these agents have more
effect on the body temperature that they reduce the temperature and leads to antipyretic
effect, but they have lower anti-inflammatory effect. ex: para-amino phenol derivatives
like paracetamol.

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4
Mechanism action of nonsteroidal anti-inflammatory

NSAIDs inhibit Cycloxygenase (COX), the enzyme that catalyses the synthesis of cyclic
endoperoxides, from the arachidonic acid to form PGs. The two COX isoenzymes are COX-1
and COX-2.
The function of COX-1 is to produce PGs that are involved in normal cellular activity,
(protection of gastric mucosa, maintenance of kidney function).
COX-2 is responsible for the production of PGs at the inflammation sites.
Most NSAIDs inhibit both COX-1 and COX-2 with varying degree of selectivity. Selective
COX-2 inhibitor may eliminate the side effects associated with NSAIDs due to COX-1
inhibition, such as gastric and renal effect.

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Mechanism action of aspirin

Acetylsalicylic acid (ASA) blocks prostaglandin synthesis. It is non-selective for COX-1 and COX-2
enzymes 9,10,11. Inhibition of COX-1 results in the inhibition of platelet aggregation for about 7-10
days (average platelet lifespan). The acetyl group of acetylsalicylic acid binds with a serine residue of
the cyclooxygenase-1 (COX-1) enzyme, leading to irreversible inhibition. This prevents the
production of pain-causing prostaglandins. This process also stops the conversion of arachidonic acid
to thromboxane A2 (TXA2), which is a potent inducer of platelet aggregation Label. Platelet
aggregation can result in clots and harmful venous and arterial thromboembolism, leading to
conditions such as pulmonary embolism and stroke.

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Classification of Steroidal anti-inflammatory
Corticosteroids are the class of steroid. These are produced in the adrenal cortex. These are the
class of drugs that lower the inflammation in the body. They also reduce the activity of immune
system.
1. Glucocorticoids:
➢ Natural ( Cortisone- Hydrocortisone)
➢Synthetic ( Prednisone- Prednisolone- Triamcinolone- Betamethasone-
Dexamethasone)
2. Mineralocorticoids
➢ Natural ( Aldosterone- Deoxycorticosterone)
➢Synthetic ( Fludrocortisone)
Cortisone:-Cortisone is corticosteroid hormone (glucocorticoid) of pregnane type. It is released
by the adrenal gland.

Hydrocortisone: It is usually referred to as the “stress hormone” as it is involved in response to

stress and anxiety, controlled by corticotropin-releasing hormone (CRH). It increases blood
pressure and blood sugar, and reduces immune responses. It has a role as an anti-inflammatory
drug, an anti-allergic agent, an anti-asthmatic drug, a human metabolite, a mouse metabolite
and a drug allergen.

Prednisone: it is used alone or with other medications to treat the symptoms of low
corticosteroid levels (lack of certain substances that are usually produced by the body and are
needed for normal body functioning).

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Prednisolone: it is a glucocorticoid. It is a medication used to treat certain types of allergies,
inflammatory conditions, autoimmune disorders, and cancers.

Triamcinolone: it belongs to a class of drugs called corticosteroids. It prevents the release of

substances in the body that cause inflammation.Triamcinolone oral (taken by mouth) is used
to treat many different conditions such as allergic disorders, skin conditions, ulcerative colitis,
arthritis, lupus, psoriasis, or breathing disorders.

Betamethasone: it is in a class of corticosteroids. It is a steroid medication. It is used for a

number of diseases such as rheumatoid arthritis, systemic lupus erythematosus and skin
diseases like dermatitis.

Dexamethasone: it is a type of corticosteroid medication. It is used in the treatment of rheumatic

problems, skin diseases, allergies, asthma, chronic obstructive lung disease etc.

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Aldosterone : it is a steroid hormone made by the adrenal cortex (the outer layer of the adrenal
gland). It helps control the balance of water and salts in the kidney by keeping sodium in and
releasing potassium from the body.

Deoxycorticosterone: it is a steroid hormone synthesized in the adrenal gland and is a precursor

for the synthesis of cortisol and aldosterone.

Fludrocortisone: it is a corticosteroid that treats Addison’s disease. This condition occurs when
your adrenal glands don’t produce enough of the hormones cortisol and aldosterone.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used primarily to treat inflammation,

mild-tomoderate pain, and fever. Specific uses include the treatment of headache, arthritis,
sports injuries, and menstrual cramps. Anti-inflammatory agents are used to cure or prevent
inflammation caused by prostaglandin (PGE2).
The terms analgesics and analgetic drugs are often used interchangeably to describe a diverse
group of pain medications such as opioids, nonsteroidal anti-inflammatory drugs (NSAIDs),
and triptans, each with very different mechanisms of action for relieving pains of a wide array
of causes.

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Biosynthesis of Prostaglandins (PGs)

General Structure of Prostaglandins

PG is a naturally occurring 20-carbon cyclo pentano fatty acid derivative, derived from
arachidonic acid.

Functions OF PGs
Blood clots are formed when a blood vessel is damaged. A type of PGs called thromboxane
(TxA2) stimulates constriction and clotting of platelets. Conversely, PGI2 have the opposite
effect on the walls of blood vessels.
Certain PGs are involved in the induction of labour and other reproductive processes. PGE2
causes uterine contractions and has been used to induce labour.

Major Effect of PG synthesis inhibition

Analgesia: Prevention of pain nerve ending sensitization
Antipyresis: Reduction of body temperature in hyperthermia
Anti-inflammatory action: Reduction in signs of inflammation (pain, tenderness, swelling and
vasodilatation)
Antithrombotic action: inhibition of platelets aggregation Closure of ductus arteriosus in New-
born

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Uses of anti-inflammatory drugs
You can use NSAIDs to relieve symptoms associated with a range of conditions, including:
 pain (for example, headache, toothache, period cramps, muscle strains and sprains)
 inflammation
 fever
 arthritis
 some autoimmune conditions

Anti-inflammatory drugs Adverse effects

Gastric adverse effects are likely due to the inhibition of COX-1, preventing the creation of
prostaglandins that protect the gastric mucosa. The damage is more likely in a patient that has
a prior history of peptic ulcers. Since it is COX-1 specific, the use of COX-2 selective NSAIDs
is a lower-risk alternative.
Renal adverse effects are because COX-1 and COX-2 facilitate the production of
prostaglandins that play a role in renal hemodynamics. In a patient with normal renal function,
inhibition of prostaglandin synthesis does not pose a large problem; however, in a patient with
renal dysfunction, these prostaglandins play a greater role and can be the source of problems
when reduced via NSAIDs. Complications that can occur include acute renal dysfunction, fluid
and electrolyte disorders, renal papillary necrosis, and nephrotic syndrome/ interstitial
nephritis.
Cardiovascular adverse effects can also be increased with NSAID use; these include MI,
thromboembolic events, and atrial fibrillation. Diclofenac seems to be the NSAID with the
highest reported increase in adverse cardiovascular events.
Hepatic adverse effects are less common; NSAID-associated risk of hepatotoxicity (raised
aminotransferase levels) is not very common, and liver-related hospitalization is very rare.
Among the various NSAIDs, Diclofenac has a higher rate of hepatotoxic effects.
Hematologic adverse effects are possible, particularly with nonselective NSAIDs due to their
antiplatelet activity. This antiplatelet effect typically only poses a problem if the patient has a
history of GI ulcers, diseases that impair platelet activity (hemophilia, thrombocytopenia, von
Willebrand, etc.), and in some perioperative cases.
Other minor adverse effects include anaphylactoid reactions that involve the skin and
pulmonary systems, like urticaria and aspirin-exacerbated respiratory disease.

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Reference
 A. S. Bagad, J. A. Joseph, N. Bhaskaran, and A. Agarwal, "Com- parative evaluation
of anti-inflammatory activity of curcum- inoids, turmerones, and aqueous extract of
Curcuma longa," Advances in Pharmacological Sciences, vol. 2013.
 M. Ghasemian and M. B. Owlia, "A different look at pulsed glucocorticoid protocols;
is high dose oral prednisolone really necessary just after initiation of pulse therapy?"
Journal of Case Reports in Practice.
 Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal anti-
inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best
Pract Res Clin Gastroenterol.
 Harirforoosh S, Asghar W, Jamali F. Adverse effects of nonsteroidal antiinflammatory drugs:
an update of gastrointestinal, cardiovascular and renal complications. J Pharm Pharm Sci.

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