This document discusses drugs that act on the musculoskeletal system. It covers NSAIDs like aspirin, ibuprofen, and diclofenac, which reduce inflammation and pain by inhibiting cyclooxygenase enzymes and prostaglandin production. Specific details are provided on the mechanisms of action, uses, dosages, side effects, and toxicity profiles of common NSAIDs like aspirin, ibuprofen, diclofenac, indomethacin, mefenamic acid, celecoxib, and paracetamol. The document explains how these drugs work in the body to provide analgesic, anti-inflammatory, and antipyretic effects.
2. NSAIDs
Drugs used in the treatment of gout
and rheumatic arthritis
Neuromuscular blocking agents
Treatment of myasthenia gravis
3. NSAIDS Drugs
Non steroidal Anti-Inflammatory Drugs
antipyretic,
analgesic, and
anti-inflammatory activities
act primarily by inhibiting the cyclooxygenase
enzymes
Pain Killer( analgesic drugs)
also called as
non opioids analgesics
non narcotic analgesics
aspirin like drugs
5. Prostaglandins
are derived from the fatty acid
arachidonic acid. by membrane
phospholipid
Functions
Platelets aggregation,
vasodilation,
uterine muscle contraction,
decrease acid secretion and
promote mucous membrane in GIT,
maintain ion balance,
maintain hormone release.
Mediators of pain (analgesia) and
inflammation.
Cause fever (pyrexia).
6. Classification of NSAIDs
Based on COX
1. Nonselective COX inhibitors(traditional
NSAIDS)
2. Preferential COX-2 inhibitors
3. Selective COX-2 inhibitors
4. Analgesic-antipyretics with poor anti-
inflammatory action
7. Nonselective COX inhibitors
A. Salicylates
B. Propionic acid derivatives
C. Enolic acid derivatives
D. Fenamates
E. Pyrazolone derivatives
F. Pyrazolone derivatives:
8. A. Non selective COX inhibitors
1. Salicylates:
Aspirin(Acetyl Salicylic
Acid),
Salicylic Acid,
Methyl salicylate.
B. Propionic acid derivatives:
-Ibuprofen,
Naproxen,
Ketoprofen,
Flurbiprofen
C. Enolic acid
derivatives:-
Piroxicam
Tenoxicam
D. Fenamate:-
Mefenamic acid
E. Acetic acid derivative
Ketorolac,
Indomethacin,
F. Pyrazolone
derivatives:
-Phenylbutazone,
Oxyphenbutazone
10. Mechanism of action of NSAIDs
anti-inflammatory effect
decrease PGs and
thromboxane synthesis
inhibit both COX-1 or COX-2
or both
prostaglandins → involved in inflammation
thromboxane →involved in blood clotting
11. pharmacological Action of NSAIDs
They Reduce
inflammation (anti-inflammation)
pain (analgesia) and
fever (antipyretic)
12. Anti-inflammatory action
• inhibits cyclooxygenase activity→ diminishes
prostaglandins --> decrease pain
• suppress production of interleukins
• migration of neutrophils
• inhibit the production of superoxide, peroxides and
radical which are responsible for cell damage
13. Analgesic action
Prostaglandin E2 (PGE2) is thought to sensitize nerve
endings to the action of bradykinin, histamine, and
other chemical mediators released locally by the
inflammatory process.
• Thus, by decreasing PGE2
synthesis, aspirin and other NSAIDs
repress the sensation of pain.
14.
15.
16. Antipyretic action
Hypothalamus control temperature of body
Two Areas
Heat promoting area or posterior hypothalamus
Heat losing center or anterior hypothalamus
Fever occurs when the set-point of the anterior hypothalamic
thermoregulatory center is elevated.
NSAIDs inhibit
PGE2
decrease set
point of
thermoregulator
center
decrease fever
19. Aspirin and other salicylates
non selective COX inhibitor ( inhibits both
COX1 &2)
Mechanism of action
Common as of all NSAIDs
20. Pharmacological Action
Anti inflammatory, analgesic and antipyretic:
Increase acid secretion in GIT By decreasing
mucous protective PG secretion.
Effect on Platelet
thromboxane TXA2 enhances platelet aggregation,
Low doses of aspirin can irreversibly inhibit
thromboxane production in platelets via acetylation
of cyclooxygenase.
21. Aspirin and other salicylates
Uses
Anti-inflammatory, antipyretic, and analgesic
Cardiovascular applications:
Aspirin is used to inhibit platelet aggregation.
Low doses are used prophylactically.
22. Dose:
The salicylates exhibit analgesic activity at low
dose
only at higher dose, these drugs show anti-
inflammatory activity
Dose dependent uses
High Dose
4-5 gm/day→ anti-inflammatory effect
Mod. Dose
300-600 mg every 4-6 hrs → antipyretic action and
analgesic
Low dose
75mg -150 mg → Anti platelet action
23. Adverse Effects
Gastrointestinal:
hyperacidity, epigastric distress, nausea,
and vomiting.
Microscopic GI bleeding is almost
universal in patients treated with
salicylates.
gastrpathy
at high dose stimulates CTZ→ nausea ,
vomiting
24. Blood:
inhibition of platelet aggregation
prolonged bleeding time.
For this reason, aspirin should not be taken for at
least 1 week prior to surgery.
Respiration:
In toxic doses, salicylates cause respiratory
depression
25. Reye’s syndrome:-
Use of salicylates in children with viral
infection may cause hepatic damage with
fatty infiltration and encephalopathy
26. Aspirin and other salicylates
Contraindications
Category C in first and second trimester and D
in third trimester of pregnancy.
Do not use in breastfeeding mothers also.
patients with anticoagulant and valporate
therapy.
27. Aspirin and other salicylates
Toxicity
Salicylate intoxication may be mild or severe.
Mild Salicylate intoxicaton:
by nausea, vomiting, marked hyperventilation,
headache, mental confusion, dizziness, and tinnitus
(ringing or roaring in the ears).
severe salicylate intoxication
Above symptoms
followed by restlessness, hallucinations, convulsions,
coma, respiratory and metabolic acidosis, and death
from respiratory failure.
28. Toxicity cont..
Children are particularly prone to salicylate
intoxication.
Ingestion of as little as 10 g of aspirin (or 5 ml
of methyl salicylate,) can cause death in
children.
29. Salicylate Poisoning Assessment
no specific antidote for salicylate poisoning.
Treatment is symptomatic.
Hospitalization
Gastric lavage follow by activated
charcoal(activated charcoal
Maintain fluid and electrolyte balance.
30. Correct acid-base disturbances.
Intravenous sodium bicarbonate to treat
metabolic acidosis. It also alkalinizes the urine
and enhances renal excretion of salicylates.
Vitamin K1 and blood transfusion If there is
bleeding.
31. Ibuprofen
➢ Non selective COX inhibitor
➢ has moderate anti-inflammatory effect but
potent analgesic effect.
➢ better tolerated than aspirin
➢ can be used in children(does not cause
Reye’s syndrome)
➢ Oral and topical gel
➢ Dose: 400-600mg TDS
32. Adverse Effect
Ringing of ear
bloating
constipation
diarrhea
nausea, vomiting
heart burn
if used for prolonged
chance of renal failure,
33. Diclofenac Sodium
➢ Preferential COX 2 inhibitor
➢ available as potassium or sodium salt
( potassium salt better absorbed)
➢ has potent anti-inflammatory effect.
➢ gets concentrated in synovial fluid, hence
preferred in inflammatory
conditions(arthritis)of joints.
➢ Incidence of hepatotoxicity is more.
34. Oral, i.m, rectal, topical gel and ophthalmic
preparation(eye drops)
Tablet, injection, gels, topical use, eye drops
Dose:
50mg BD or 100mg sustained release
preparation OD
35. Uses
Post Op Pain
Renal colic
RA, acute gout, Ankylosing spondylitis
eyedrops for post op inflammation of eye
36. Indomethacin
➢ a non-selective COX inhibitor
➢ has a potent anti-inflammatory effect.
➢ It inhibits migration of neutrophils to
inflamed area.
➢ It is very effective in ankylosing
spondylitis, acute gout and arthritis.
➢ Oral, eye drops and suppository
➢ Dose:- 25mg,50mg TDS
37. side Effects
➢ has prominent GI side effects.
➢ CNS side effects
➢severe headache, confusion, hallucinations,
etc.
➢ contraindicated in
➢ epileptics, psychiatric patients and drivers.
38. Mefenamic acid
➢ Non selective COX inhibitor
➢ It has analgesic, antipyretic and weak
anti-inflammatory effect
➢ It is used in dysmenorrhoea
,osteoarthritis, rheumatoid arthritis.
➢ Oral Dose:-250-500mg TID
39. Celecoxib
Celecoxib is significantly more selective for
inhibition of COX-2 than COX-1
Used for treatment of RA, osteoarthritis, and
pain.
Do not affect platelet aggregation
Adverse Effect
Edema
Hypertension
Rashes
40. Less gastric effect
High cardiotoxicity, electrolyte
imbalance
Headache, dyspepsia, diarrhea, and
abdominal pain are the most common
adverse effects
Dose 200mg
41. Paracetamol (acetaminophen)
Non selective inhibitor of COX
MOA
inhibits prostaglandin synthesis in the CNS hence
have a potent analgesic and antipyretic effect
but have less effect in tissue PG synthesis so
have poor anti-inflammatory activity.
42. PCM uses
➢ As antipyretic:-
➢To reduce body temperature during fever
➢ As analgesic:
➢To relieve headache, toothache, myalgia,
dysmenorrhoea etc.
➢ is the preferred analgesic and antipyretic in
patients with peptic ulcer, hemophilia,
bronchial asthma and children.
43. Pharmacological action
No effect on respiration
No adverse effect on CVS
Less chance of GIT damage
No effect on uric acid excretion
CNS devoid of salicylism
so its very safe drug
45. PCM ADR
1. Side effects are rare, occasionally causes
skin rashes and nausea.
2. Hepatotoxicity :with acute overdose or
chronic use.
3. Nephrotoxicity is commonly seen on
chronic use.
46. PCM poisoning
20 gm PCM is lethal in Adult
Acute overdosage
causes hepatotoxicity-the symptoms are
nausea, vomiting, diarrhea, abdominal pain,
hypoglycemia, hypotension, coma etc.
Death is usually due to hepatic necrosis.
47. Treatment of toxixity
Antidote N-acetylcystine is given
intravenously.
Gastric lavage should be done
➢ Activated charcoal for decrease
absorption of paracetamol from the gut.
➢ Haemodialysis may be required in cases
with acute renal failure.