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Part 7: Anti-inflammatory, antipyretic and
antigout drugs
Nonsteroidal anti-inflammatory
drugs (NSAIDs):
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Aspirin
Diclofenac
Etodolac
Meclofenamate
Fenoprofen
Flurbiprofen
Ibuprofen
Indomethacin
Ketorolac
Ketoprofen
Meloxicam
Naproxen
Piroxicam
COX-2 inhibitors:
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Celecoxib
Eterocoxib..
Other analgesics:
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Overview:
Inflammation is defined as a localized protective
response stimulated by injury to tissues, which
serves to destroy, dilute, or wall off both the
injurious agent and injured tissue.
Classic signs and symptoms of inflammation include
pain, fever, loss of function, redness, and swelling.
These symptoms result from arterial, venous, and
capillary dilation; enhanced blood flow and vascular
permeability; exudation of fluids, including plasma
proteins; and leukocyte migration into the inflammatory
focus. The inflammatory response is mediated by a
host of endogenous compounds, including proteins
of the complement system, histamine, serotonin,
bradykinin, Leukotrienes, and prostaglandins, the
latter two begin major contributors to the symptoms of
inflammation.
Paracetamol.
Arachidonic acid is released from phospholipids in cell
membranes in response to triggering event. It is
Antigout:
metabolized in either the prostaglandin pathway or the
 Allopurinol
leukotriene pathway, both of which are branches of the
 Colchicine
arachidonic acid pathway, as shown in figure below.
Both of these pathways lead to inflammation, edema, headache, and other pain characteristic of
the body’s response to injury or inflammatory illness such as arthritis.
DantiRUGS FOR GOUT
In the prostaglandin pathway, arachidonic acid is converted by the enzyme cyclooxygenase into
various prostaglandins. Prostaglandins mediate inflammation by inducing vasodilation and
enhancing vasopermeability. These effects in turn potentiate the action of proinflammatory
substances such as histamine and bradykinin in the production of edema and pain.
The leukotriene pathway utilizes lipooxygenases to metabolize the arachidonic acid and convert
it into various leukotrienes. Although leukotrienes are more newly discovered than prostaglandins
and not as well studied, they are also mediators of inflammation, promoting vasoconstriction,
bronchospasms, and increased vascular permeability with resultant edema.
Nonsteroidal anti-inflammatory drugs (NSAIDs):
NSAIDs comprise a large and chemically diverse group of drugs that possess analgesic, antiinflammatory, and antipyretic activity. They are used for the relief of mild to moderate headaches,
myalgia, neuralgia, and arthralgia; alleviation of postoperative pain; relief of the pain associated
with arthritic disorders, and treatment of gout and hyperuricemia. Aspirin is used for its effect in
inhibiting platelet aggregation, which has been shown to have protective qualities against certain
cardiovascular events.
Steroidal anti-inflammatory drugs (dexamethasone, prednisone) are also used for similar purposes.
NSAIDs have a generally more favorable adverse effect profile than steroidal anti-inflammatory drugs.
Chemical Categories of NSAIDs:
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Salicylates: Aspirin. 
Acetic acid derivatives: Diclofenac sodium, Indomethacin, Mefenamic acid, Ketorolac. 
Cyclooxygenase-2 (COX-2) inhibitors: Celecoxib, etirocoxib. 
Enolic acid derivatives: Meloxicam, Piroxicam, loxicam. 
Propionic acid derivatives: Ibuprofen, Ketoprofen, flurboprofen, Naproxen.
Mechanism of action:
NSAIDs relieve pain, headache, and inflammation by blocking the chemical activity of the
enzyme called cyclooxygenase COX. There are at least two types of cyclooxygenase COX:
- COX-1 is the isoform of the enzyme that promotes the synthesis of prostaglandins, which
have primarily beneficial effects on various body functions. One example is their role in
maintaining an intact gastrointestinal mucosa.
-COX-2 isoform promotes the synthesis of prostaglandins that involved in inflammatory processes.
In 1998, the newest class of NSAIDs, the COX-2 inhibitors, was approved. These drugs work by
specifically inhibiting the COX-2 isoform of cyclooxygenase and theoretically have limited or no
effects on COX-1.
One notable effect of aspirin is its inhibition of platelet aggregation, also known as its antiplatelet
activity. Aspirin has the unique property of being are irreversible inhibitor of COX-1 receptors
within the platelets themselves.
As antipyretic—reduces fever- they inhibits prostaglandin E2 within the area of the brain that
controls temperature
Indications:
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Analgesia (mild to moderate) 
Antigout effects 
Antiinflammatory effects 
Antipyretic effects 
Relief of vascular headache 
Platelet inhibition (aspirin) 
Rheumatoid arthritis 
Contraindications:
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Known drug allergy. 
Conditions that place the patient at risk for bleeding. 
Patients with documented aspirin allergy should not receive NSAIDs. 
Severe renal or hepatic disease. 
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NSAIDs are generally rayed as pregnancy category C drugs for use during the first
two trimesters of pregnancy but are rated as pregnancy category D for use during the
third trimester. 
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These drugs are not recommended for nursing mothers. 
Adverse effects:
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One of the more common and potentially serious adverse effects of the NSAIDs is their
effect on the GIT. Symptoms range from mild symptoms such as heartburn to the most
severe GI complication, GI bleeding. 
Acute renal failure is quite common with NSAIDs use, especially if the patient is dehydrated. 
Cardiovasculr risk. May cause an increase risk of serious cardiovascular thrombotic
events, myocardial infarction, and stroke. This risk increase with duration of use. Patients
with CV disease or risk factors for CV disease may be at greater risk. 
Drug profile:
1- Salicylic acid (aspirin)
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More potent effect on platelet aggregation and thermal regulatory center in the brain
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Analgesic and Antipyretic (325-650 mg) 3 times daily.
Antiinflammatory (325-650 mg) 3 times daily.
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Antithrombotic
effect: used in the treatment of MI and other thromboembolic disorders (81-325
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mg)
Aspirin and other salicylates all have one specific contraindication in children. In children
under 12 years old aspirin has been associated strongly with Rey’s syndrome. Rey’s
syndrome is an acute and potentially life-threatening condition involving
neurologic
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deficits that can lead to coma and may also involve liver damage.
Salicylate toxicity:
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Adults: tinnitus and hearing loss 
Children: hyperventilation and CNS effects 
Metabolic acidosis and respiratory alkalosis may be present 
Treatment:
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Gastric lavage 
If patient hyperthermic: ice packs 
Manage acid-based abnormality 
Insure high urine volume 
Urine alkalinization (sodium bicarbonate infusion) promotes salicylate excretion 
2- Diclofenac acid:
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Diclofenac sodium (Voltaren). 
Diclofenac potassium (Cataflam). 
o Diclofenac deanol (Tratul).
Dosage forms: 
o Orally (tab, SR tab, Cap)
o Rectal supp.
o Injection (IM, IV).
o Topically (emulgel)
o Eye drops.
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Safety in pediatric is not established, so using in children if necessary. 
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Excretion in breast milk is very low, so using during lactating if necessary. 
3- Ibuprofen:
 Dosage forms: oral tablet, oral suspension. 
 Using in pediatric according to weight, in pediatric over 5-7 Kg. 
 Given every 6-8 hours daily. 
 Excreted is low in breast milk. 
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4- Indomethacin:
 Dosage forms: oral cap, rectal Supp (adult). 
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Indomethacin used I.V to promote closure of patent ductus arteriosus, a heart defect
that sometimes occurs in premature infants. 
Safety in pediatric is not established. 
5- Naproxen:
 Dosage form: oral tab, oral cap. 
 Given once or twice daily. 
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Can’t be used in children less than 12 years old. But use in IV form to promote closure
of patent ductus. Can’t be used in nursing mothers. 
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6- Meloxicam, Loxicam
 Used to treat arthritis. 
 Given once or twice daily. 
 Found as oral tab or oral cap (7.5 mg, 15 mg). 
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7- Mefenamic acid:
 Found as oral tab, oral susp. 
 Therapy should not exceed 1 week due to heamatologic adverse effects. 
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8- Celecoxib (Cox-2 inhibitors)
 Found as oral cap. 
 Have a CV risks. 
 Have little effect on platelet function. 
 Should not be used in patients with sulfa allergy. 
Antigout Drugs:
Gout is caused by overproduction of uric acid or decreased uric acid excretion, or both. This
overproduction and/or decreased excretion can often result in hyperuricemia. When the body
contains too much uric acid, deposits of uric acid crystals collect in tissues and joints. This causes
an inflammatory response and extreme pain, because these crystals are like small needles that jab
and stick into sensitive tissues and joints, which is an end product of purine metabolism.
Purines are part of the normal dietary intake and are used to make the essential structural units
of DNA and RNA. During purine metabolism, they are converted from hypoxanthine to xanthine
and eventually to uric acid. This pathway is overactive in patients with gout and is reduced by
antigout drug therapy. The goals of gout treatment are to decrease the symptoms of an acute
attack and tp prevent recurrent attacks.
Drug profiles:
Although specific antigout drugs are available, the NSAIDs are considered first-line therapy for most
patients with gout the specific antigout drugs-allopurinol, colchicines, probencid, and sulfinpyrazoneare targeted at the underlying defect in uric acid metabolism, which causes either overproduction or
underexcretionof uric acid.
1- Allopurinol:
Mechanism of action:
  Inhibit xanthine oxidase enzyme. 
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Indicated for patient with overproduction of uric acid.
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Adverse effects: agranulocytosis, aplastic anemia, and serious skin conditions.
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Is available only as oral preparations.
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The Max dose 800 mg/ day. The usual recommended dose 200-600 mg/ day.
Category C in pregnancy.
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Onset of action is 1-2 weeks.
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2- Colchicine:
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Appears to be effective in the treatment of the gout by reducing the inflammatory response.
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Used for short-term treatment.
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Adverse effects: bleeding to GIT and urinary tract.
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Is contraindicated
in patient sensitive to colchicine and those with hepatic, renal, GI and CV
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diseases.
D category in pregnancy.
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Given orally and onset of action is 12 hours.
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Nursing implications
NSAIDs:
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Before beginning
therapy, assess for conditions that may be contraindications to therapy,
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especially:
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Bleeding disorders
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 Assess for conditions that require cautious use 
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GI lesions or peptic ulcer disease
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Performlab studies as indicated (cardiac, renal, and liver function studies, CBC, platelet
count)
Perform a medication history to assess for potential drug interactions
Several serious drug interactions exist
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Do NOT give salicylates to children and teenagers because of the risk of Reye’s syndrome
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Because these drugs generally cause GI
distress, they are often better tolerated if taken with
food, milk, or an antacid to avoid irritation
Explain to patients that therapeutic effects may not be seen for 3 to 4 weeks
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Educate patients about the various adverse effects of NSAIDs, and inform
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physician if these effects become severe or if bleeding or GI pain occurs
Informpatients to watch closely for the occurrence of any unusual bleeding, such as in the
stool
Advise patients that enteric-coated tablets should not be crushed or chewed
Monitor for therapeutic effects, which vary according to the condition being treated
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