Analgesic antipyretics/ NSAIDs/Non narcotic analgesics

1. Miss. Rani S. Dhole
Asst. Professor
Annasaheb Dange College of D. Pharmacy, Ashta, Sangli

3. Peripheral mechanisms of pain

4. The mechanisms of NSAIDs

5. - PGs, mostly by COX-1, are constitutively expressed in almost all
tissues; COX-2 appears to only be constitutively expressed in the brain,
kidney, bones, reproductive organs, and some neoplasms
- Under normal physiologic conditions, PGs play an essential homeostatic
role in cytoprotection of gastric mucosa, hemostasis, renal physiology,
gestation, and parturition
- In platelets there is only COX-1exist (converts arachidonic acid to TxA2)
- COX-1 predominant in gastric mucosa (source of cytoprotective PGs)
- The production of PGs, (inducible COX-2 activity >> COX-1) at sites
of inflammation propagate pain, fever

6.  Analgesic
Analgesics are the agents which relive or suppress the sensation of
pain by acting on CNS but without producing loss of consciousness
 Antipyretics
Antipyretics are agents which reduce elevated body temperature
 Anti inflammatory agents
Used to produce symptomatic relief from inflammation

7. Classification of Non-narcotic Analgesic
(1) Nonselective COX inhibitors
A. Salicylates Eg. Aspirin
B. Propionic acid derivatives Eg. Ibuprofen, ketoprofen
C. Acetic acid derivatives Eg. Ketorolac, indomethacin
D. Pyrazolone derivatives Eg. Phenylbutazone
E. Enolic acid derivatives Eg. Piroxicam
F. Fenamates Eg. Mephenamic acid
(2) Preferential COX-2 inhibitors
Eg. Nimesulide, Diclofenac
(3) Selective COX-2 inhibitors
Eg. Celecoxib, eterocoxib
(4) Analgesic antipyretics with poor anti- inflammatory action
Para amino phenol derivative Eg. Paracetamol
Benzoxazocine derivative Eg. Nefopam

8. 3. Pharmacological actions of NSAIDs
Analgesia –
 Relieves dull pain of low intensity that related to joints, muscles, headache, etc.
by acting on hypothalamus
 It reduces PG synthesis & release. Also blocks the effect of bradykinin on pain
producing receptor
Antipyretic –
Pyrexia means rise in body temperature
Due to high prostaglandin level
Salicylates resets the mechanism of heat regulation to normal & promote heat
loss by vasodilation of small blood vessels as well as increased sweating
anti-inflammatory
By variety of stimuli in the body bradykinin & prostaglandin like substances
are released which leads to inflammation.
Salicylates reduce the capillary permeability & exudation of fluid
It inhibit the release of these substances & thus cause anti- inflammatory effect

9. Antiplatelet – At low dose it inhibit platelet aggregation, prolong bleeding time;
have anticoagulant effects
On respiration-
 Stimulates respiration by acting on medullary respiratory centre
 It increases the consumption of O2 by skeletal muscle that is increases CO2
concentration
 These may results into hyperventilation and causes respiratory alkalosis
On blood system-
Reduces platelet aggregation, prolongs bleeding time
On GIT-
It causes dyspepsia, nausea, vomitting, epigastric distress, ulcers, etc.
Metabolic effect-
Salicylates enhances the use of glucose by the tissues, which lowers the blood sugar
level (large dose)
They are also effective in dermatological disorders
It has keratolytic effect hence used in tretment of corns
Also useful in fungal infections

10. Uricosuric effect-
Increases plasma uric acid level by interfering uric acid secretion by distal tubule
In dose less than 3 gm/day blocks tubular secretion of uric acid & raise the blood
Uric acid level.
But when dose is increased upto 5 gm or more it prevents reabsorption of uric acid &
increase its excretion
Therefore in small dose uric acid retention & in large dose shows uricosuric effect
Hepatic & renal effect-
Salicylates increases the secretion of bile by stimulation of hepatic parenchyma
In large doses it causes hepatic necrosis
ADME of salicylates
Absorption: Well absorbed in stomach, small intestine & intact skin
(Always given on food to prevent gastric irritation)
Distribution: Bounds to plasma proteins
Metabolism: in liver by conjugation
Excretion: in urine (pH dependant ie increase in pH increases the elimination)

11. Aspirin-Mechanism of Action: Covalent Binding to COX
Aspirin covalently and irreversibly modifies both COX-1 and COX-2 by
acetylating serine-530 in the active site
Acetylation results in a steric block, preventing arachidonic acid from binding

12. Aspirin Dose: 0.3- 1 g/day orally
Salicylism:
Causes due to prolonged administration of salicylates in the
treatment of rheumatic fever or rheumatoid arthritis
Symptoms:
Headache
Dizziness
Vertigo
Tinnitus
Nausea, vomitting
Respiratory depression
Electrolyte imbalance
Overdose:
hepatic damage
Reye’s syndrome(kids) swelling in the liver and brain
severe hepatic damage and
encephalopathy
Treatment:
Rehydration
Gastric lavage
(stomach pumping or gastric irrigation, is
the process of cleaning out the contents of
the stomach)
IV of potassium/ dextrose/ sodium
bicarbonate ( excretion )
Sponging with cold water or alcohol

13.  Local applications: Keratolytic, fungistatic, antiseptic
 Relieve dull pain
 Antipyretic
 Anti inflammatory
 Anti rheumatic
 Antiplatelet

14.  Gastrointestinal symptoms: Dyspepsia, nausea, vomitting,
ulcer
 Allergic reaction (urticaria), edema, aspirin asthma,
occasionally anaphylactic shock)
 Renal/ hepatic damage
 Bleeding
 Respiratory alkalosis

15. - analgesia
- antipyretic
- no significant anti-inflammatory effects
- no gastric irritation
- half life 2 –3 h
- not contraindicated for asthma
- The major concern regarding the use of acetaminophen is the
potential for high doses to cause liver toxicity

16. - Inhibits Prostaglandin synthatase
- analgesia
- Antipyretic
- anti-inflammatory effects
- In treatment of rheumatoid arthritis
- Alternative to aspirin

17. Indomethacin
- analgesic
- Antipyretic
- anti-inflammatory effects
- Its use is not recommended unless aspirin therapy is not effective or
not tolerated

18. Diclofenac
- analgesia
- Antipyretic
- anti-inflammatory effects
- More potent than indomethacin
- Useful in musculoskeletal disorder, dysmenorrhoea
- Choice of dug in Ankylosing spondylitis (An inflammatory arthritis
affecting the spine and large joints.)
-

19. 1. In peptic ulcer, there are lesions in the stomach,
associated bleeding and pain.
2.Aspirin causes irritation to stomach, gastric erosion,
gastritis, gastric ulcer and G.I bleeding.
3.Thus aspirin can worsen the condition of peptic
ulcer and hence should not be given.

20.  If aspirin is taken on empty stomach, it causes gastric
irritation, nausea & vomitting
 Also causes GIT bleeding
 Aspirin can increases secretion of HCl in stomach,
indirectly by decreasing prostaglandin level may results
into ulceration
 Aspirin when administered after meal or with sodium
bicarbonate, secreted acid in stomach gets neutrallised
by sodium bicarbonate
 It may avoids gastric complications mentioned above

21.  Salicylate therapy can causes GI bleeding resulting in
homeostasis & anaemia
 Salicylates in large dses reduces the plasma prothrombin level
causing hypoprothrombinaemia
 In low dosses disturbance in blood clotting due to interference
with PG level
 Hypoprothrombinaemia & hemorrhoegic complications can be
prevented to treated with use of vitK