Dr.
Anadil Fidaa Anver
Dept of Pharmacology
INTRODUCTION
❑ Also called non-narcotic/ non- opioid/aspirin
like analgesics
❑ NSAIDs have :-
• Analgesic action
• Antipyretic action
• Anti-inflammatory action
❑ They act by inhibiting prostaglandin synthesis
CLASSIFICATION
A. Nonselective COX inhibitors
1. Salicylates
Aspirin
2. Para-aminophenol derivatives
Paracetamol
3. Propionic acid derivatives
Ibuprofen, naproxen, ketoprofen, Flurbiprofen
4. Acetic acid derivatives
Indomethacin, Ketorolac
CLASSIFICATION
5. Fenamates (anthranilic acids)
Mefenamic acid
6. Pyrazolone derivatives
Phenylbutazone, azapropazone
7. Oxicams (Enolic acid derivatives)
Piroxicam, tenoxicam
CLASSIFICATION
B. Preferential COX-2 inhibitors
Diclofenac, aceclofenac, meloxicam, nimesulide
C. Selective COX-2 inhibitors
Celecoxib, parecoxib, etoricoxib
MOA
• During inflammation, arachidonic acid liberated from
membrane phospholipids is converted to prostaglandins
(PGs), catalysed by the enzyme cyclo-oxygenase (COX)
• These prostaglandins produce hyperalgesia—they sensitize
the nerve endings to pain
• NSAIDs inhibit the PG synthesis by inhibiting the enzyme
cyclo-oxygenase
Aspirin is the prototype drug
1. Analgesic effect:
Prevent PG mediated sensitisation of peripheral nerve
endings
Increase pain threshold
Mainly used for relieving musculoskeletal pain,
dysmenorrhoea and pain associated with
inflammation or tissue damage
2. Antipyretic effect:
Reset the hypothalamic thermostat by inhibiting
synthesis of PGs in the hypothalamus and reduce the
elevated body temperature during fever
Promote heat loss by enhanced sweating & cutaneous
vasodilatation
3. Anti-inflammatory effect:
Anti-inflammatory effect seen at high doses
(4-6 g/day)
Signs of inflammation like tenderness, swelling,
erythema and pain reduced
But, the progression of the disease is not affected
The anti-inflammatory action of NSAIDs is mainly due
to inhibition of PG synthesis at the site of injury
(PGs present in inflammatory tissues responsible for
oedema, erythema & pain)
4. Antiplatelet (antithrombotic) effect:
Aspirin in low doses irreversibly inhibits platelet TXA2
synthesis and produces antiplatelet effect, which lasts
for 8–10 days, i.e. the life time of the platelets.
Aspirin in high doses inhibits both PGI2 and TXA2
synthesis, hence antiplatelet effect is lost
5. Acid–base and electrolyte balance:
In therapeutic doses, salicylates produce significant
respiratory stimulation → more CO2 is washed out
resulting in respiratory alkalosis which is compensated
by excretion of bicarbonate
In toxic doses, the respiratory centre is depressed →
CO2 accumulates → can lead to respiratory acidosis.
Later, there is uncompensated metabolic acidosis
6. GIT:
Aspirin irritates the gastric mucosa and produces
nausea, vomiting and dyspepsia.
Aspirin also stimulates CTZ and produces vomiting
Erosive gastritis, gastric ulceration and GI bleeding
can occur at higher doses
Mechanism:
PGs are cytoprotective to gastric mucosa because they
reduce acid secretion & increase mucus production.
Salicylates increase gastric acid secretion & suppress
the protective effect of prostaglandins by inhibiting
their synthesis
7. CVS:
Prolonged use may cause salt and water retention →
worsen CCF & hypertension
8. Urate excretion:
Salicylates, in therapeutic doses, inhibit urate secretion
into the renal tubules and increase the plasma urate levels.
In high doses, salicylates inhibit the reabsorption of uric
acid in the renal tubules and produce uricosuric effect.
Pharmacokinetics
Absorption : stomach & small intestine
Rapidly deacetylated salicylic acid
80-90% plasma protein bound
Enters brain and crosses placenta
Uses
1. As Analgesic
Headache
Myalgia
Neuralgia
Joint pain
Tooth ache
Dysmenorrhea
2. Fever
3. Inflammatory conditions
Arthritis
Fibromyositis etc
4. A/c rheumatic fever:
4-6 g/day
5. Rheumatoid arthritis:
Pain, swelling, morning stiffness reduced
Do not alter the progress of the disease
6. Osteoarthritis:
Symptomatic relief
7. Post myocardial infarction & stroke:
Aspirin in low dose - Inhibit platelet aggregation
Reduces reinfarction in post MI patients
Reduces TIA & stroke
8. Other uses
Delay labour
PIH & pre eclampsia
P D A closure in new born
Prevent colon cancer
Adverse effects
1. GI tract
Nausea, vomiting
Peptic ulcer
Occult blood loss in stools
2. Allergic reactions
Rashes, urticaria, angio-oedema & asthma
3. Haemolysis in G6PD deficient patients
4. Nephrotoxicity on long term use
5. Hepatotoxicity
6. Salicylism
High doses given for long term causes salicylism
Charecterised by
➢ Headache, vertigo, dizziness, tinnitus,
➢ Mental confusion, sweating,
➢ Difficulty in hearing,
➢ Vomiting, diarrhoea, thirst & dehydration
7. Reye’s syndrome:
Hepatic dysfunction seen in children
Develops a few days after a viral infection like influenza
& varicella
Increased incidence when aspirin used to treat fever
8. Pregnancy & infancy
Aspirin given at term delays labor (due to inhibitionof
PG synthesis)
Increases postpartum bleeding (due tom inhibition of
platelet aggregation)
Premature closure of ductus arteriosus → portal
hypertension in baby
PARACETAMOL
Acetaminophen
Relatively safe and effective analgesic
❑ACTIONS
Good antipyretic
Analgesic action
Weak anti inflammatory action
Advantages of Paracetamol over
Aspirin
Do not stimulate respiration
Do not affect acid base balance
No gastric irritation
Do not affect platelet function
Safe and well tolerated in antipyretic doses
No risk of Reye’ s syndrome in children
ADVERSE EFFECTS
Antipyretic dose – safe and well tolerated
Nausea & rashes may occur
Higher doses - Hepatotoxic
USES
Analgesic – painful conditions like toothache,
headache, myalgia
Antipyretic - fever
SELECTIVE COX-2 INHIBITORS
COXIBS – Celecoxib, parecoxib, etoricoxib
MERITS
Inhibit COX -2 without affecting COX-1
Do not inhibit platelet aggregation
Less gastric mucosal damage
DEMERITS
Prothrombotic - increased cardiovascular &
cerebrovascular complications → increase risk of
myocardial infection & stroke
USES
In patients who cannot tolerate other NSAIDs & are at high
risk of developing peptic ulcer
TOPICAL NSAIDs
Systemic toxicity is minimal.
Diclofenac, ibuprofen, naproxen, etc. - useful topically
for musculoskeletal pain.
Used in backache, osteoarthritis, sprain, etc.
Flurbiprofen and diclofenac eye drops used in
ophthalmic practice.