Summarize the following text to main points and sub-points and make detailed explain for them:

 
 
STAGE - 4 
PHARMACOLOGY
 
 الفريق الوزاري 
1 
 Anti-inflammatory drugs  
Inflammation is a normal, protective response to tissue injury caused by physical trauma, 
noxious chemicals, or microbiologic agents.  
 
Inflammation is the body’s effort to inactivate or destroy invading organisms, remove 
irritants, and set the stage for tissue repair. When healing is complete, the inflammatory 
process usually subsides.  
 
However, inappropriate activation of the immune system can result in inflammation and 
immune-mediated diseases such as rheumatoid arthritis (RA). In RA, white blood cells (WBCs) 
initiate an inflammatory attack.  
 
WBC activation leads to stimulation of T lymphocytes, which recruit and activate monocytes 
and macrophages.  
 
These cells secrete proinflammatory cytokines, including tumor necrosis factor (TNF)-α and 
interleukin (IL)-1, into the synovial cavity, ultimately leading to joint destruction and other 
systemic abnormalities characteristic of RA.   
 
In addition to T lymphocyte activation, the B lymphocytes are also involved and produce 
rheumatoid factor and other autoantibodies to maintain inflammation.   
 
Pharmacotherapy for RA includes anti-inflammatory and/or immunosuppressive agents that 
modulate/reduce the inflammatory process, with the goals of reducing inflammation and 
pain, and halting or slowing disease progression.   
 
Prostaglandins: Prostaglandins are unsaturated fatty acid derivatives containing 20 carbons 
that include a cyclic ring structure. [Note: These compounds are sometimes referred to as 
eicosanoids].   
 
Thromboxanes,leukotrienes, 
 and 
 the 
 hydroperoxyeicosatetraenoic 
 and 
hydroxyeicosatetraenoic acids (HPETEs and HETEs, respectively) are related lipids, 
synthesized from the same precursors as the prostaglandins, and use interrelated pathways.  
 
 
 Synthesis of prostaglandins  
Arachidonic acid, a 20-carbon fatty acid, is the primary precursor of the prostaglandins and 
related compounds. There are two major pathways in the synthesis of the eicosanoids from 
arachidonic acid.  
 
Cyclooxygenase pathway: All eicosanoids with ring structures that is, the prostaglandins, 
thromboxanes, and prostacyclins are synthesized via the cyclooxygenase pathway.   
 
 
STAGE - 4 
PHARMACOLOGY
 
 الفريق الوزاري 
2 
Two related isoforms of the cyclooxygenase enzymes have been described. Cyclooxygenase-
1 (COX-1) is responsible for the physiologic production of prostanoids, COX-1 is described as 
a housekeeping enzyme that regulates normal cellular processes, such as gastric 
cytoprotection, vascular homeostasis, platelet aggregation, and kidney function whereas  
Cyclooxygenase-2 (COX-2) causes the elevated production of prostanoids that occurs in sites 
of disease and inflammation.  
 
COX-2 is constitutively expressed in tissues such as the brain, kidney, and bone. Its expression 
at other sites is increased during states of inflammation.   
 
Lipoxygenase pathway: Alternatively, several lipoxygenases can act on arachidonic acid to 
form leukotrienes or lipoxins, depending on the tissue.  
 
 
 Functions of prostaglandins in the body  
Prostaglandins and their metabolites produced endogenously in tissues. They control many 
physiological functions, such as acid secretion and mucus production in the gastrointestinal 
(GI) tract, uterine contractions, and renal blood flow.   
 
Prostaglandins are also among the chemical mediators that are released in allergic and 
inflammatory processes. Intradermal, intravenous, or intra-arterial injections of small 
amounts of prostaglandins mimic many components of inflammation. .  
 
 
 Non-steroidal anti-inflammatory drugs (NSAIDs)  
All NSAIDs, including the traditional nonselective drugs and the subclass of selective 
cyclooxygenase-2 (COX-2) inhibitors, have the following actions:  
 
Anti-inflammatory, analgesic, and antipyretic.   
NSAIDs are a chemically heterogeneous group of organic acids that share certain therapeutic 
actions and adverse effects.  
 
All of the NSAIDs act by inhibiting the cyclooxygenase enzymes that catalyze the first step in 
prostanoid biosynthesis. This leads to decreased prostaglandin synthesis with both beneficial 
and unwanted effects.  
 
 
 
 
 
 
 
 
STAGE - 4 
PHARMACOLOGY
 
 الفريق الوزاري 
3 
Aspirin and other NSAIDs  
Aspirin can be thought of as a traditional NSAID, but it exhibits anti-inflammatory activity 
only at relatively high doses that are rarely used.   
 
It is used more frequently at lower doses to prevent cardiovascular events such as stroke and 
myocardial infarction (MI).   
 
Aspirin is often differentiated from other NSAIDs since it is an irreversible inhibitor of 
cyclooxygenase activity.  
 
 
Mechanism of action:  
Aspirin is a weak organic acid that irreversibly acetylates and, thus, inactivates 
cyclooxygenase. The other NSAIDs are reversible inhibitors of cyclooxygenase.  
 
The NSAIDs, including aspirin, have three major 
therapeutic actions:  
 
they reduce inflammation (anti-inflammatory), pain 
(analgesic effect), and fever (antipyretic effect). However, 
not all NSAIDs are equally effective in each of these 
actions.  
  
 
 
 
 
Actions of Aspirin and other NSAIDs:   
1-Anti-inflammatory effect  
Anti-inflammatory actions: Inhibition of cyclooxygenase diminishes the formation of 
prostaglandins since PGE2 induce acute inflammation through mast cell activation via the 
EP3 receptors.  Aspirin inhibits inflammation in arthritis, but it neither arrests the progress of 
the disease nor induces remission.  
 
2-Analgesic action: PGE2 is thought to sensitize nerve endings to the action of bradykinin, 
histamine, and other chemical mediators released locally by the inflammatory process.  Thus, 
by decreasing PGE2 synthesis, the sensation of pain can be decreased.  
 
 
 
 
 
 
STAGE - 4 
PHARMACOLOGY
 
 الفريق الوزاري 
4 
As COX-2 is expressed during times of inflammation and injury, it is thought that inhibition of 
this enzyme is responsible for the analgesic activity of NSAIDs.   
 
Note: No single NSAID has demonstrated superior efficacy over another, and they are 
generally considered to have equivalent analgesic efficacy.   
 
The NSAIDs are used mainly for the 
management of mild to moderate pain arising 
from 
musculoskeletal 
disorders. 
One 
exception is ketorolac, which can be used for 
more severe pain, but for only a short 
duration.  
 
3-Antipyretic action: Fever occurs when the 
set-point 
of 
the 
anterior 
hypothalamic 
thermoregulatory 
center 
is 
elevated. 
Lipoxygenase pathway: Alternatively, several 
lipoxygenases can act on arachidonic acid to 
form leukotrienes or lipoxins, depending on 
the tissue.  
 
This can be caused by PGE2 synthesis, which is stimulated when endogenous fever-producing 
agents (pyrogens), such as cytokines, are released from WBCs that are activated by infection, 
hypersensitivity, malignancy, or inflammation.   
 
The NSAIDs lower body temperature in patients with fever by impeding PGE2 synthesis and 
release, resetting the “thermostat” back toward normal.   
 
This rapidly lowers the body temperature of febrile patients by increasing heat dissipation 
through peripheral vasodilation and sweating. NSAIDs have no effect on normal body 
temperature.  
 
 
 Therapeutic uses of NSAIDs  
-Anti-inflammatory and analgesic uses: NSAIDs are used in the treatment of osteoarthritis, 
gout, RA, and common conditions requiring analgesia (for example, headache, arthralgia, 
myalgia, and dysmenorrhea).  
 
Combinations of opioids and NSAIDs may be effective in treating pain caused by malignancy. 
Furthermore, the addition of NSAIDs may lead to an opioid-sparing effect, allowing for lower 
doses of opioids to be utilized.   
 
 
 
STAGE - 4 
PHARMACOLOGY
 
 الفريق الوزاري 
5 
The salicylates exhibit analgesic activity at lower doses. Only at higher doses do these drugs 
show anti-inflammatory activity. For example, two 325-mg aspirin tablets administered four 
times daily produce analgesia, whereas 12 to 20 tablets per day produce both analgesic and 
anti-inflammatory activity.  
 
-Antipyretic uses: Aspirin, ibuprofen, and naproxen may be used to treat fever. [Note: Aspirin 
should be avoided in patients less than 19 years old with viral infections, such as varicella 
(chickenpox) or influenza, to prevent Reye syndrome—a syndrome that can cause 
fulminating hepatitis with cerebral edema, often leading to death.  
 
• Cardiovascular applications  
Aspirin irreversibly inhibits COX-1–mediated production of TXA2, thereby reducing TXA2-
mediated vasoconstriction and platelet aggregation and the subsequent risk of 
cardiovascular events. The antiplatelet effects persist for the life of the platelet.  
 
Low doses of aspirin (75 to 162 mg—commonly 81 mg) are used prophylactically to reduce 
the risk of recurrent cardiovascular events, transient ischemic attacks (TIAs), stroke, and 
death in patients with a history of previous MI, TIA, or stroke.  
 
C

Summary :