non-steroidal anti-inflammatory drugs

1. QURATULAIN MUGHAL
BATCH IV
DOCTOR OF PHYSICAL THERAPY
ISRA UNIVERSITY
NONSTEROIDAL ANTI-
INFLAMMATORY DRUG
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2. NSAIDs
These are non-opioid analgesia.
In addition they have anti-inflammatory,
antipyretic and uricosuric properties-without
addiction liability.
NSAIDs inhibit the prostaglandins(PG) synthesis
by inhibiting the enzyme cyclo-oxygenase(COX).
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3. CLASSIFICATION
NSAIDs can be classified based on their mechanism of
action.
A.Nonselective cox-1 inhibitors
B.Selective cox-2 inhibitors
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4. MECHANISM OF ACTION
NSAIDs inhibiting both the cyclooxygenase-1
(COX-1) and cyclooxygenase-2 (COX-2)
isoenzymes.
COX catalyzes the formation of prostaglandins and
thromboxane from arachidonic acid (itself derived
from the cellular phospholipid bilayer by
phospholipase A2)
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6. A. Nonselective cox inhibitors
1.Salicylic acid derivatives
2. Para-aminophenol derivatives
3.Pyrazolone derivatives
4.Indole acetic acid derivatives
5.Arylacetic acid derivatives
6.Propionic acid derivatives
7.Anthranilic acids (fenamates)
8.Oxicams
9.Alkanones
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7. 1.SALICYLIC ACID
DERIVATIVES
Aspirin, sodium salicylate, diflunisal.
Salicytes are salts of salicylic acid.
e.g. methyl salicylate, sodium salicylate,
acetyl salicylate acid (aspirin).
Aspirin is taken as the prototype.
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9. PHARMACOLOGICAL ACTIONS
1. ANALGESIA:
 Good analgesic and relieves pain of inflammatory
origin without euphoric and hypnosis.
 Pain originating from the integumental structures
such as muscles, bones, joints, and pain in
connective tissues is relieved.
 But in vague visceral pain, aspirin is relatively
ineffective.
 No development of tolerance and dependence.
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10. 2.ANTIPYRETIC ACTION
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In fever, salicylates bring down the temperature to
normal level.
But, in normal individuals, there is no change in
temperature.
Inhibits the PG synthesis in hypothalamus and reset
the thermostat at the normal level.
Enhanced sweating and cutaneous vasodilation
promote heat loss and assist in ant.ipyretic action

11. 3.ANTI-INFLAMMATORY ACTION
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At higher doses of 4-6gm/day ,aspirin acts as anti-
inflammatory agent.
Sign of inflammation like tenderness, swelling,
erythema and pain are all reduced or suppressed.
But the progression of disease in RA and RF or OA is
not affected.
PG inhibition which cause inflammation, erythema
and pain.

12. 4.RESPIRATION
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In therapeutic dose of 4-6 g/day salicylates increase
consumption of oxygen by skeletal muscles.
The co2 production increase, which stimulates the
respiratory center.
Also stimulates the medullary respiratory center.
Both these action cause the respiratory depth and
rate increase.
These effects are dose dependent.

13. 5.ACID-BASE AND ELECTROLYTE
BALANCE
In respiratory alkalosis, pH becomes alkaline.
This is compensated by increased excretion of HCO3
in urine.
With respiratory depression the pH decreases and
there is acidosis.
Toxic doses also depress the vasomotor center and
cause the renal dysfunction resulting in
accumulation of strong acids of metabolic origin like
lactic, pyruvic and acetoacetic acids.
With high dose dehydration occurs.
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14. 6.METABOLIC EFFECTS
Salicylates enhance the cellular metabolism.
More O2 is used and more CO2 is produced specially
in skeletal muscles-leading to increased heat
production.
Glucose utilization is increased leading to mild
hypoglycemia.
In toxic dose, hyperpyrexia, protein catabolism,
negative nitrogen balance and hyperglycemia due to
central sympathetic stimulation which adrenaline
levels.
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15. 7.GIT
Aspirin is gastric irritant.
Irritation of gastric mucosa leads to epigastric
distress, nausea and vomiting.
In higher dose gastric erosion, ulceration and GI
bleeding can occur.
MECHANISM: Salicylates increase gastric acid
secretion and suppress the protective effect of
prostaglandins by inhibiting their synthesis (we
know that PGs increase mucous production in the
stomach and protect from ulceration).
It platelet aggregation which the tendency to bleed.
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16. 8.CVS
In therapeutic doses no significant CVS effects are
seen.
In toxic doses it depress the VMC and thus depress
the circulation.
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17. 9.IMMUNOLOGICAL EFFECTS
In higher doses, salicylates suppress several antigen-
antibody reactions.
It inhibits antibody production. Ag-Ab aggregation
and antigen induced release of histamine.
These effects might also help in rheumatic fever.
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18. 10.URIC ACID EXCRETION
Uric acid is excreted by secretion from distal tubules.
In a dose of 1-2g/day, aspirin increase plasma urate
level b/c it inhibit urate secretion by the distal
tubules.
Large dose of >5g/day increase the urate excretion
b/c it inhibit the reabsorption of urate by the
proximal tubules causing uricosuria.
But, its uricosuria effect can’t be used for treatment
of gout b/c high doses are required and such doses
result in many adverse effects.
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19. 11.BLOOD
Even in small doses aspirin inhibits TXA2 synthesis
by platelets.
It therefore interferes with platelet aggregation
and prolongs the bleeding time.
Even a single dose can irreversibly inhibit TXA2
synthesis in the platelets.
b/c platelets have no nuclei, they can’t synthesize
cyclooxygenase and fresh platelets have to be
formed to restore TXA2 activity.
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20. 12.LOCAL EFFECTS
Salicylic acid when applied locally is a keratolytic.
It also has a mild antiseptic and fungistatic
properties.
Salicylic acid is also a irritant for the broken skin.
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21. PHARMACOKINETICS
Salicylates are absorb from the stomach and upper
small intestine.
But aspirin is such as poorly soluble, hence not well-
absorbed.
When administered as microfine particles,
absorption increases.
Thus the particles size, pH of GIT, solubility of
preparation and presence of food in the stomach
influence the absorption.
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22. CONTINUE..
Salicylic acid and methylsalicylates are absorbed
from the intact skin.
They are extensively bound to plasma proteins.
Aspirin is broken down in liver, plasma and other
tissues to release salicylic acid which is the active
form.
Plasma t1/2 of aspirin is 3-5hour.
Salicylates are excreted in urine.
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23. ADVERSE EFFECTS
Nausea, epigastric distress, vomiting, erosive
gastritis, peptic ulcer, increased occult blood loss in
stools are common.
Allergic reactions are manifested as rashes, urticaria,
angio-edema, and asthma.
Nephrotoxicity
Hepatotoxicity
In pregnancy it delays the onset of labor due to
inhibition of PG synthesis.
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24. PRECAUTIONS AND
CONTRAINDICATION
Peptic ulcer
Liver diseases
Bleeding tendencies
Pregnancy
Stop salicylates one week before surgery
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25. USES
Fever
Analgesic
Inflammation
Osteoarthritis
Postmyocardial infraction
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26. DRUG INTERACTION
Salicylates compete for protein binding sites and
displace other drug resulting in toxicity with:
 warfarin
Naproxen
phenytoin and
sulfonylureas.
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27. 2.PARA-AMINOPHENOL
DERIVATIVES
Paracetamol or acetaminophen
ACTION:
Analgesic
Antipyretic
Weak anti-inflammatory
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28. PHARMACOKINETICS
ABSORPTION: orally, 30% protein bound
METABOLISM: by hepatic microsomal enzymes
(glucuronide and glutathione conjugation)
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29. MECHANISM
A small portion of paracetamol is metabolized to a
toxic compound-N-acetyl-benzoquinone-imine
Which destroy generally by conjugation with
glutathione
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30. B.SELECTIVE COX-2 INHIBITORS
CELECOXIB AND ROFECOXIB:
Both diaryl subsituted compounds are highly
selective COX-2 inhibitors.
They have good anti-inflammatory, analgesic
properties but don’t affect platelet aggregation.
Both tolerated b/c of milder gastric irritation.
Both cause hypertension and edema
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32. USES
Acute painful condition like:
Postoperative pain, dysmenorrhea and dental pain
Osteoarthritis
Rheumatoid arthritis
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