They are also called
“Nonnarcotics,Nonopiodids,or Aspirin like
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Definition: NSAIDs are chemically diverse class of drugs
(>70 NSAIDs in use) that have anti-inflammatory,
analgesic, and antipyretic properties.
Among the most frequently prescribed drugs
-worldwide: 70 million people/day prescribed NSAIDs
230 million people/day take OTC NSAIDs
-USA: 80 billion aspirin tablets consumed/year
constitute 4% of all prescriptions
Properties of Prostaglandins
•Physiological Functions of Prostaglandins
Pain: PGI2 and PGE2 sensitize nerve endings to bradykinin,
Histamine and substance P
Inflammation: PGI2, PGD2 and PGE2 are vasodilators
Protection of the gastric mucosa: PGI2
Maintenance of renal blood flow: PGE2
Platelets: PGI2 and PGD2 inhibit platelet aggregation
TXA2 stimulates platelet aggregation
Uterus: PGD2 contracts uterus
PGs---induce hyperalgesia by increasing
sensitivity of afferent nerve endings to chemical
and mechanical stimuli and thus amplify action of
other algesics-bradykinins, histamine, TNF-alpha,
PGs in CNS lowers threshold of central pain
NSAIDS block this pain sensitizing mechanism
therefore effective against inflammation asso. Pain
The opioids are the drugs of choice for the
treatment of moderate-to-severe pain, the NSAIDs are
most frequently used for mild-to-moderate pain.
Prostaglandins by themselves do not cause pain but
lower the threshold of the C fiber nociceptors.
As a result, lower concentrations of bradykinin and
histamine are required to activate the nociceptor.
Fever in infection is produced by pyrogens, TNF,
ILs, interferon-induce production of PGs in
hypothalamus-raise its temp. set point.
NASIDs block the action of pyrogens.(cox-2).
Fever also can occur through non PG mediated
mech.—incomplete explanation ???
Inhibition of PG synthesis at the site of injury.
Anti-inflammatory action of each drug
corresponds with their potency to inhibit COX.
NSAIDs -also inhibit expression/ activity of
adhesion molecules, growth factors like GMCSF,IL-6,and lymphocyte transformation factorsaffected.
NSAIDs-Stabilises leucocytes lysosomal
membrane, and antagonizes certain act.. Of
Increase levels of PGs in menstrual blood
flow, endometrial biopsies, and their
metabolites is seen in dysmennorhic
women.—myometrial ischaemia –menstrual
NSAIDs-lowers uterine PGs--relief
Inhibit synthesis of TXA2 by acetylating
platelet COX irreversibly.
responsible for maintaining
patency in foetal circulation.
Sudden increase in PG synthesis by uterus
triggers labour and facilitate progression.
NSAIDs –delay and retard labour
Gastric mucosal damage
Inhibition of synthesis of gastro protective PGS
(E2,I2)- decrease in mucus,HCO3,increases acid
secretion, may promote mucosal ischemia.
Ion trapping with NSAIDs also play role.
Conditions like hypovoleumia, decrease renal perfusion,
and Na+ loss- induce renal PG synthesis –leading to
vasodilatation, inhibition of cl - reabsorption…
1. Cox dependent impair renal bl.flow.—decrease in gfrrenal insufficiency.
2. JG Cox 2 dependent Na and water retention.
3. Rare ability to cause papillary necrosis on habitual
Renal effects more marked in pts of
CHF, Hypovolemia, hepatic cirrhosis renal disease, pts on
diuretics and antihypertensive----edema
Aspirin is acetyl salicylic acid converted in
body to salicylic acid.
MOA-aspirin inhibits COX irreversibly by
acetylating one of its serine residue.
1.Analgesic- relives pain related to inflammation, tissue
injury, connective tissue etc.
-obtunding peripheral receptors
-prevents PGs mediated nerve ending sensitization.
-raises threshold for pain perception in central sub
2.Antipyretic- resets the hypothalamic thermostat.
3.Antiinflammatorysigns of inflammation like pain, tenderness, swelling,
vasodilatation and leukocyte infiltration are suppressed.
At anti-inflammatory doses: 1.↑ heat loss 2.↓ blood sugar
At anti-inflammatory doses - increased respiratory rate.
In salicylate poisoning- resp.depression
Acid base balance and electrolyte balance
-Initially Increased Co2 production and its washout resp.alkalosis.
-Later Co2 retention –resp. acidosis (high doses)
-Followed by metabolic acidosis.
-dehydration occurs in poisoning.
At toxic doses –depresses VMC, BP falls, CHF may precipitate
Dose related effect….
GITEpigastric distress, nausea and vomiting
Back diffusion of H+ ions
Focal necrosis of mucosal cells
Nausea, vomiting ,gi distress
Gastric mucosal damage, peptic ulceration.
Dizziness, tinnitus, vertigo, reversible impairment in hearing and vision,
excitement ,mental confusion, hyperventilation, electrolyte imbalance.
Reye’s syndrome-hepatic encephalopathy esp. in children
having viral infection.
Acute salicylate poisoningMore common in childrens, fatal dose for adults 15-16g
Children suffering from influenza, chickenpox
Chronic liver diseases
CHF, lower cardiac reserve
Delayed labor, more postpartum bleed, premature
closure of ductus arteiosus
Aspirin displaces warrfarin,
naproxen,sulfonylurese, phenytoin from its
pp binding sites-toxicity of these agents.
Inhibits tubular secretion of uric acid and
antagonizes action of uricosuric agents.
Blunts action of diuretics
Uses of aspirin
Aspirin 300mg-600mg 6-8.hlly
2. As antipyretic- in various infections, PUO
3. Acute rheumatic fever4. Rheumatoid arthritis5. Osteoarthitiis6. Postmyocardial infraction & poststroke patients.
7. Otherpregnancy induced hypertension
to delay labour
to close patent ductus arteriosus
Potent anti-inflammatory, antipyretic, analgesic.
Inhibit neutrophil motility.
High incidences of GIT and CNS side effects.
RA not responding to Aspirin.
Acute exacerbation of destructive orthopathies.
Malignancy asso. refractory fever.
DOC- PDA- dose:0.1-0.2mg/ kg12 hourly
Pharmacokinetics Ibuprofen 400-800mg TDS
Naproxen 250mg BD…(Gout)
Ketoprofen 50-100mg BD
Flubiprofen- ocular anti inflammatory
- Better tolerated orally and the incidences of adverse
reactions are low.
- Highly protein bound drugs like aspirin can displace
warrfarin, sulfonylurese, phenytoin from its pp binding
sites…..toxicity of these agents.
Anthranyllic acid derivatives-
Analgesic, antipyretic, anti-inflammatory.
antagonizes certain actions of PGs.
exerts peripheral as well as central analgesic
skin rash, dizziness
analgesic, effective in dysmenorrhea
Aryl acetic acid derivative-
Similar in efficacy to Naproxen.
Anti inflammatory action- reduces
neutrophil chemotaxis and superoxide
Dose:50mg BDUses-same as Ibuprofen.
Long acting potent NSAIDs similar to
Decreases production of IgM rheumatoid factor.
Reduces leucocytes proliferation and ratio of T
-helper cells to T- suppressor cells.
Meloxicam new congener of Piroxicam is
selective for COX II 10 times more than COX I.
Novel analgesic, modest anti inflammatory drug.
In post operative pain it has equaled efficacy of
Morphine but do not have morphine like side effects.
1. Post operative pains
2. Acute musculoskeletal pain
3. Renal colic
5. Pain due to metastasis.
preferential cox2 inhibitor
Used mainly short lasting painful conditions-
sport injuries, sinusitis, ear nose disorders, dental
surgery, bursitis, low backache, dysmenorrhea,
po. pain, o.a.
S/E - fulminant hepatitis
Cox-1 vs. Cox-2
• GI cytoprotection
• Platelet activity
• Renal function
• Renal function
• Tissue repair
Why do Cox-2 inhibitors increase risk for heart disease?
#1. Because they adversely effect the ratio of thromboxane to prostacyclin
Selective COX2 inhibitors
Rofecoxib 12.5-25mg OD
Valdecoxib 20mg BD
Low ulcerogenic potential
-TXA2 level were not reduced
-Other Side effects are low
Pedal edema & rise in B.P occurs as a result of salt and water
retention due to inhibition of constitutive COX II in JG cells. This
may precipitate CHF.
COX II inhibition –inhibits PGI2 –prothrombotic
influence….increased cardiovascular events. QT changes in ECG
Use- for long term use as analgesic in chronic pain.
Good & promptly acting antipyretic.
Analgesic- central action
Negligible anti-inflammatory action.
Poor inhibitor of PG synthesis in
More active on COX in brain
In contrast to aspirin-
does not stimulate respiration
does not affect acid base balance.
or cellular metabolism.
No effect on
P/K- metabolism by glucuronic acid conjugation.
S/E- safe drug at antipyretic dose.
Analgesic nephropathy (at toxic doses)
Acute paracetmol poisoning- small children
- having low hepatic glucuronide conjugating ability.
- if large doses >250mg/kg
Manifestations• Nausea , vomiting.
• Abdominal pain
• Liver impairment- hepatic necrosis
• Impaired consciousness
• Renal tubular necrosis
RxGastric lavage, activated charcoal
N-acetylcysteine 150mg/kg i.v over 15 mins followed by
same dose over 20 hrs.
Choice of NSAIDs
Mild to moderate pain with inflammationParacetmol, Low dose Ibuprofen
Acute musculosketal, OA, injury associated with
Gastric intolerance –
Pt. with allergy to aspirin & other NSAIDs -
1. A suggested treatment algorithm
(American Journal of Medicine 105, 53S-60S, 1998)
Opioids or Tramadol
NSAIDs or Tramadol
Acetaminophen or Ibuprofen
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