MOA of Aceclofenac

Mechanism of Action of Aceclofenac

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Introduction

Aceclofenac is a widely used nonsteroidal anti-inflammatory drug (NSAID) indicated for pain relief and reduction of inflammation in musculoskeletal and joint disorders. Mechanism of Action of Aceclofenac primarily involves inhibition of cyclooxygenase (COX) enzymes, leading to reduced prostaglandin synthesis. It is often preferred for its relatively better gastrointestinal tolerability compared to some older NSAIDs. Clinically, aceclofenac is used in osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, offering effective pain management and anti-inflammatory benefits.

Mechanism of action of Aceclofenac
Aceclofenac pharmacology
Aceclofenac pharmacology
Aceclofenac clinical pharmacology

Mechanism of Action (Step-wise)

  1. Inhibition of Cyclooxygenase (COX) Enzymes
    • Aceclofenac inhibits cyclooxygenase-2 (COX-2) more selectively than cyclooxygenase-1 (COX-1).
    • This reduces production of pro-inflammatory prostaglandins at sites of inflammation.
  2. Reduced Prostaglandin Synthesis
    • Prostaglandins are mediators responsible for pain, swelling, and fever.
    • Lower prostaglandin levels result in reduced inflammation and analgesia.
  3. Stabilization of Inflammatory Cells
    • Aceclofenac reduces the release of inflammatory cytokines such as TNF-α and IL-1β.
    • Helps control joint inflammation in rheumatoid arthritis and other inflammatory disorders.
  4. Chondroprotective Action
    • Unlike some NSAIDs, aceclofenac may slow down cartilage degeneration.
    • Evidence suggests it stimulates synthesis of extracellular matrix components in cartilage.
  5. Overall Effect
    • Analgesic (pain relief).
    • Anti-inflammatory (reduces swelling and redness).
    • Antipyretic (lowers fever).
Aceclofenac clinical pharmacology flowchart
Aceclofenac MOA Flowchart

Pharmacokinetics

  • Absorption: Well absorbed orally; peak plasma concentration within 1–3 hours.
  • Distribution: Highly plasma protein bound (~99%).
  • Metabolism: Extensively metabolized in the liver to diclofenac (active metabolite).
  • Excretion: Excreted mainly in urine as metabolites.
  • Half-life: 4–4.5 hours.

Clinical Uses

  • Osteoarthritis (pain and stiffness).
  • Rheumatoid arthritis.
  • Ankylosing spondylitis.
  • Musculoskeletal pain and inflammatory conditions.
  • Dental pain, postoperative pain, and soft tissue injuries.

Adverse Effects

  • Common: Dyspepsia, abdominal pain, nausea, diarrhea.
  • Less common: Dizziness, skin rash, edema.
  • Serious: Gastrointestinal bleeding, peptic ulcers, hepatotoxicity, nephrotoxicity, cardiovascular risk (hypertension, stroke).
  • Contraindications: Peptic ulcer disease, severe hepatic/renal impairment, history of NSAID allergy, pregnancy (especially third trimester).

Comparative Analysis

FeatureAceclofenacDiclofenacIbuprofen
COX selectivityMore COX-2 selectiveModerate COX-1/COX-2Non-selective
GI safety profileBetter than diclofenacHigher risk of GI irritationModerate risk
Half-life4–4.5 hours1–2 hours2 hours
Chondroprotective effectYes (supports cartilage)LimitedNo
Common usesArthritis, musculoskeletal painArthritis, inflammationPain, fever, inflammation

MCQs

1. Aceclofenac belongs to which class of drugs?
a) Corticosteroid
b) NSAID
c) DMARD
d) Opioid

Answer: b) NSAID

2. The primary mechanism of action of aceclofenac is:
a) Blocking TNF-α receptors
b) Inhibiting cyclooxygenase enzymes
c) Activating serotonin receptors
d) Enhancing opioid receptors

Answer: b) Inhibiting cyclooxygenase enzymes

3. Aceclofenac is metabolized mainly to:
a) Paracetamol
b) Diclofenac
c) Ibuprofen
d) Naproxen

Answer: b) Diclofenac

4. Which condition is aceclofenac most commonly prescribed for?
a) Hypertension
b) Osteoarthritis
c) Diabetes
d) Tuberculosis

Answer: b) Osteoarthritis

5. Which is a serious side effect of aceclofenac?
a) Constipation
b) Gastrointestinal bleeding
c) Drowsiness
d) Weight gain

Answer: b) Gastrointestinal bleeding

6. Aceclofenac shows partial selectivity for which COX isoform?
a) COX-1
b) COX-2
c) Both equally
d) Neither

Answer: b) COX-2

7. What is the elimination half-life of aceclofenac?
a) 1–2 hours
b) 4–4.5 hours
c) 10 hours
d) 24 hours

Answer: b) 4–4.5 hours

8. Which cytokine is reduced by aceclofenac?
a) IL-6
b) TNF-α
c) Interferon-γ
d) IL-12

Answer: b) TNF-α

9. Aceclofenac is contraindicated in:
a) Diabetes mellitus
b) Peptic ulcer disease
c) Hypothyroidism
d) Asthma (always)

Answer: b) Peptic ulcer disease

10. Which feature makes aceclofenac different from many NSAIDs?
a) It is opioid-sparing
b) It has chondroprotective effects
c) It is not protein-bound
d) It acts on opioid receptors

Answer: b) It has chondroprotective effects

FAQs

Q1. Is aceclofenac safer than diclofenac?
Yes, aceclofenac has better gastrointestinal tolerability than diclofenac.

Q2. Can aceclofenac be taken with food?
Yes, it is usually recommended with food to reduce gastric irritation.

Q3. Is aceclofenac safe in pregnancy?
No, especially contraindicated in the third trimester.

Q4. Does aceclofenac affect cartilage?
Yes, it has mild chondroprotective effects compared to other NSAIDs.

Q5. Can aceclofenac cause kidney damage?
Yes, long-term or high-dose use may impair renal function.

Q6. What is the typical dose of aceclofenac?
Usually 100 mg twice daily (oral).

References

  • Goodman & Gilman’s The Pharmacological Basis of Therapeutics
  • Katzung Basic and Clinical Pharmacology
  • Harrison’s Principles of Internal Medicine
  • Clinical NSAID safety guidelines

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