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.

1. Drugs acting in
Musculoskeletal system
Dr. Saroj K. Suwal

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

4. Why Pain
Cell Damage
COX Activated
Prostaglandins
Produced
Pain

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

9. B. Preferential COX-2
inhibitors
 Nimesulide,
 Diclofenac
 Aceclofenac
 Meloxicam,
 Etodolac
c. Selective COX-2
inhibitors
 Celecoxib,
 Etoricoxib,
 Parecoxib
D. Analgesic-antipyretics
with poor anti-
inflammatory action
 Paraaminophenol
derivative:-
Paracetamol
(Acetaminophen).
 Pyrazolone derivatives:
Metamizol(Dipyrone),
Propiphenazone
 Benzoxazocine derivative:-
Nefopam

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.

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

17. Side effects
GI bleeding
GI Ulcer, heart burn
dose dependent hepatitis
Prolong gestation
liver and kidney injury
pulmonary edema
promotes bleeding( inhibit thromboxane)
Hypersensitivity reaction

18. Some common NSAIDS

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

44. ➢ Pharmacokinetics
➢well absorbed orally
➢metabolism in liver
➢ Dose
➢Tab.PCM 500 mg PO X TDS
➢Inj PCM 1gm IV x TDS

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.

48. thanks