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Dr. B. Phukan
ANALGESIC - ANTIPYRATICS
(Non-Steroidal Anti-inflammatory Drugs, NSAIDs)

Drugs which relief pain & lowering body temperature & inflammation.
They do not depress CNS, has weaker analgesic action than opioids. They act
primarily on peripheral pain mechanism by inhibiting prostaglandin synthesis
(PG).
Mechanism of pain & inflammation :- the three action of NSAIDs
(Analgesic, Antipyretics & Anti-inflammatory) are mediated through inhibition
of Prostaglandin(PG) synthesis from phospholipids.
Phospholipids (of cell membrane breakdown)
(Phospholipase - A) inhibited by glucocorticoids

Arachidonic acid Chemotaxin

(Cyclooxygenase,Cox) (inhibited by NSAIDs) (5- lipoxygenase)

Prostacyclines (PGI2) Hydroxyl arachidonic acid

Thromboxane (Tx) Leucoteriene (LT)

Prostaglandins (PG)

Prostacyclines (PGI2) – is a vasodilator, hyperalgesic, inhibit platelat

aggregation
Thromboxane (Tx) – is a thrombotic & vasoconstrictor
Prostaglandins (PG) – they are PGE2, PGD2, PGF2∞. They are
vasodilator, hyperalgesic, bronchoconstrictor
Leucoteriene (LT) – they are LTA4, LTB4, LTC4, LTD4. They produce
bronchoconstriction.
Chemotaxin – a Platelet activating factor(PAF), causing vasodilation,
increase of vascular permeability, broncoconstriction
Explaination :-
1) During pain, fever & inflammation, arachidonic acid is liberated from
cell membrane
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2) The enzyme, Cyclooxygenase(COX) converts arachidonic acid to

Prostaglandins, Prostacyclines & Thromboxanes of which PG & PGI2
responsible for inflammation
3) Two forms of COX like COX-1 & COX-2 of which COX-1 is always
present in blood vessels, stomach & kidney. But, COX-2 is induced during
inflammations.
4) Synthesis of COX is inhibited by NSAIDs, so as conversion of
arachidonic acid is inhibited. Aspirin acetylates COX & cause irreversible
inhibition. Most NSAIDs are nonselective COX-1 & COX-2 inhibitors. But,
newer drugs like celecoxib, rofecoxib are selective for COX-2.
5) Glucocorticoids inhibit the release of arachidonic acid from membrane
lipids by inhibiting phospholipase-A i.e. indirectly reduce the production of PG,
PGI2, Tx & LTs.
Classification of NSAIDs :- into 4 subclasses-
A) Nonselective COX inhibitors (Conventional NSAIDs) –
1) Salicylates – Aspirin
2) Pyrazolone – Phenylbutazone, oxyphenbutazone
3) Indole – Indomithacin, sulindac
4) Propionic acids – Ibuprofen, naproxen, ketoprofen
5) Anthranilic acid – Mephenamic acid
6) Aryl- acetic acid - Diclofenac
7) Oxicam – Piroxicam, tenoxicam
8) Pyrrolo-pyrrole – Ketorolac
B) Preferential COX-2 inhibitors –
Eg. Nimesulide, Meloxicam, Nabumetone
C) Selective COX-2 Inhibitors –
Eg. Celecoxib, Rofecoxib, Valdecoxib
D) Analgesic-Antipyretics with poor Anti-inflammatory actions-
1) Para-aminophenol – Paracetamol (acetaminophen)
2) Pyrazolone – Metamizol
3) Benzoxazocine – Netopam
MOA of NSAIDs :- inhibit COX & thereby inhibit production of PG,
PGI2, TX, & LT. Out of COX-1 & COX-2, COX-1 is expressed in most tissues
& may produces adverse effects like ulcerations. COX-2 is expressed in
inflammatory cells only on cell damage. NSAIDS have scavenging effects on
O2 free radicals thereby ↓ tissues damages.
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Salicylates (ASPIRIN)
Aspirin is an acetylsalicylic acid converted into salicylic acid, which is
responsible for most actions in the physiological system.
Pharmacological actions :-
(1) Analgesic-Antipyretic & Anti-inflammatory actions – weaker
analgesic than morphine, use in dull pain in muscles, joints, dysmenorrhoea,
toothache etc. Acts by preventing integration of pain sensation in the thalamus
(at 600mg dose).
Antipyretic action is due to resets the hypothalamic thermostat & rapidly
reduce fever by promoting heat loss by sweating, coetaneous vasodilatation,
but does not ↓heat production.
At high dose (3.6 g/day) it produces ↓inflammation, pain, tenderness,
sweating, vasodilatation & leukocyte infiltration.
(2) On Respiration :- stimulate respiration by stimulating the respiratory
centre & through CO2 production.
(3) On GIT :- Nausea & vomiting due to irritation, stimulation of CTZ
(chemoreceptor trigger zone), ulceration, haemorrhage.
(4) On immunological action :- inhibit antigen-antibody reactions, so,
prevent the release of histamine.
(5) On uricosuric effects :- ↑excretion of uric acid by inhibiting
reabsorption of uric acid in proximal tubule. So, useful in gout.
(6) On CVS :- No effects on normal dose. But, at high dose causes ↓ BP,
paralysis of vasomotor centre.
(7) On Blood :- ↓ ESR, which is high in rheumatic fever. Also ↓
prothrombin level of plasma.
(8) On endrocrine system :- stimulate the release of adrenaline from
adrenal medulla. ↑Adrenocorticotropic hormone (ACTH), but, ↓TSH.
(9) On Metabolic effects :- Hyperglycemic & glycosuria, ↓synthesis of
fatty acids.
(10) Local actions :- antiseptic, fungistatic & keratolytic effects.
Adverse effects :- aspirin may produce various adverse effects-
1) on GIT – nausea, vomiting & diarrhoea. Also there is ulceration,
perforation & haemorrhage.
2) Intolerance – skin rashes, urticaria, pruritis, asthma, anaphylactic
shock.
3) Bone marrow depression – causing agranulocytosis, throm-
bocytopenia & aplastic anaemia.
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4) Fatty infiltration of Liver & Kidney

5) Salicylaism – headache, tinnitus, ↓hearing, drowsiness, lethargy &
confusion.
Therapeutic Uses of Asprin:-
(1) as analgesic (at 0.3 - 1gm) in dull pain - arthralgia, myalgia, neuralgia,
toothache, headache & dysmenorrhoea.
(2) as antipyretic – in fever due to tissue, muscle injury or infections
(3) in Rheumatic arthritis ( at 1 -10gm/day)
(4) for local Application – Dusting Powder As Keratolytic, Fungistatic &
Anti-Septic.
(5) as antiplatelet agent – to prevent thrombosis formation in coronary
arteries, MI, & post stroke.

PARACETAMOL
Paracetamol also known as acetaminophen, synthesised in 1950, a most
commonly used antipyretic, is a p-aminophenol.
Pharmacological action :-
 It is a potent & promptly acting antipyretic
 It raises pain threshold, but has weak peripheral anti-inflammatory action
 It has poor inhibition of PG synthesis in peripheral tissues, but more
action on COX in brain
 In contrast to aspirin, it does not stimulate respiration or acid base
balance, does not increase cellular metabolism
 It has no effect on CVS, Gastric irritation is insignificant
 Mucosal erosion & bleeding occur rarely in overdose
 It does not affect platelet function or clotting factor as aspirin.
 It has no uricosuric effect
Adverse effects :- Paracetamol is safe & well tolerated. Nausea & rashes
occur occasionally. Analgesic nephropathy occurs after heavy ingestion. There
are papillary necrosis, tubular atrophy followed by renal fibrosis. Urine
concentrating ability is lost & kidney shrinks.
Acute Paracetamol poisoning:- in children (at 150mg/kg) who have low
hepatic glucuronide conjugate ability or in adult (at 10gm) produces nausea,
vomiting, abdominal pain & liver tenderness after 12-18hr. Hepatic necrosis,
renal tubular necrosis, hyperglycemia & jaundice after 2 days. In chronic
alcoholic at 5-6g/day results in hepatotoxicity. Not recommended in premature
infants.
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Treatment of paracetamol poisoning :-

 induced vomiting or gastric lavage with activated charcoal
 Use of antidote like N-acetylcysteine, 150mg/kg, iv.
 Symptomatic treatment
Uses :-
 OTC (over the counter) analgesic for headache, musculoskeletal pain,
dysmenorrhoea.
 1st choice for osteoarthritis
 Best drug as antipyretic
 Can be use in all age group (infant to adults)
 Can be used in pregnant & lactating women also
Dose:- 0.5 -1gm, TDS
Nimesulide
A preferential COX-2 inhibitor. Analgesic, antipyretic & anti-
inflammatory activity has been rated comparable to other NSAIDS.
Adverse affects :- gastric tolerance is better. But, Haematuria (blood in urine) in
few children & hepatic failure for which it is banded in Spain, finland, Turkey,
Portugal . Not recommended in UK, USA Australla, Canada for overall safety
in children.
(Note –Have to go through Phenylbutazone, oxyphenbutazone , Indomithacin,
Ibuprofen, Diclofenac, Piroxicam, Celecoxib) .

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Questions
OPIOID ANALGESICS

Q.1 Choice based/fill up -- 1 mark each

a) NSAIDs act primarily on peripheral pain mechanism by inhibiting

--------------------.
b) Aspirin -------------- the enzyme COX & causes irreversible inhibition.
c) Nonselective COX inhibitors are also termed as --------------------- NSAIDs.
d) Celecoxib is a Nonselective COX inhibitors/ Preferential COX-2 inhibitors/
Selective COX-2 Inhibitors.
e) Glucocorticoids inhibit the release of -------------- from membrane lipids by
inhibiting phospholipase-A
f) The antidote for poisoning of peracetamol is ----------------

Q.2 Short notes - 2 marks each

A) NSAIDs, B) Acute Paracetamol poisoning, C) Conventional NSAIDs,

D) Nimesulide
Q.3 What is the are Mechanism of pain & inflammation ? 5
Q.4 What are the end products of phospholipid responsible for pain &
inflammation ? 3
Q.5 Classify NSAIDs with examples. 5
Q.6 What are the Mechanism of action of NSAIDs ? 3
Q.7 What is Acute Paracetamol poisoning ? how it is treated ? 5
Q.8 Why Nimesulide is banded in most countries ? 3
Q.9 What do you mean by NSAIDs ? How they are classified ? What are the
mechanism of action, pharmacological action, adverse effects and therapeutic
uses of aspirin ? 10

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