24. ANALGESIC AND ANTI-INFLAMMATORY AGENTS

Introduction

Analgesic and anti-inflammatory agents are medicines used mainly to relieve pain, reduce inflammation and control fever. Analgesics reduce pain without affecting the cause, while anti-inflammatory drugs act on mediators of inflammation. Broadly, these drugs are divided into opioid analgesics and non-opioid analgesics (NSAIDs and paracetamol).

Opioid Analgesics

Opioids are strong pain-relieving medicines acting mainly on the central nervous system. They bind to specific opioid receptors called µ (mu), κ (kappa) and δ (delta). These receptors are located in the brain, spinal cord and peripheral nerves. Opioids can be natural (morphine, codeine), semisynthetic (heroin, hydromorphone) or synthetic (pethidine, fentanyl, tramadol).

Mechanism of Action

Opioids produce analgesia by reducing neurotransmitter release in the spinal cord and altering pain perception at the brain level. They also modify emotional response to pain and increase pain threshold.

Pharmacological Actions of Morphine (Prototype)

  • Analgesia: Effective for severe pain of trauma, MI, cancer and postoperative pain.
  • Euphoria: Feeling of well-being; reduces anxiety and fear.
  • Sedation: Causes drowsiness and reduced physical activity.
  • Respiratory depression: Reduces response of respiratory centre to CO₂, major cause of death in overdose.
  • Cough suppression: Direct action on cough centre.
  • Miosis: Pinpoint pupils, characteristic of opioid overdose.
  • GIT effects: Constipation due to reduced bowel motility.
  • CVS: Peripheral vasodilatation may reduce BP.

Adverse Effects of Opioids

  • Nausea, vomiting and constipation
  • Drowsiness and mental clouding
  • Respiratory depression
  • Hypotension
  • Dependence and tolerance
  • Withdrawal symptoms on abrupt stoppage

Contraindications

  • Head injury
  • Bronchial asthma and COPD
  • Hypotension and shock
  • Infants and elderly patients
  • Undiagnosed acute abdomen

Important Opioids

Codeine

Milder analgesic, strongly effective as cough suppressant; less addictive and safer than morphine.

Pethidine (Meperidine)

Synthetic opioid with faster onset; can cause tremors and seizures due to toxic metabolite.

Loperamide, Diphenoxylate

Used for diarrhoea due to strong GI action; do not cross BBB significantly.

Opioid Antagonists

  • Naloxone: Drug of choice for opioid overdose; reverses respiratory depression.
  • Naltrexone: Used in de-addiction therapy and alcoholism.

Non-Opioid Analgesics (NSAIDs)

NSAIDs reduce pain, fever and inflammation mainly by inhibiting cyclooxygenase (COX) enzymes responsible for prostaglandin synthesis.

Classification of NSAIDs

  • Non-selective COX inhibitors: Aspirin, ibuprofen, naproxen, diclofenac, indomethacin, piroxicam
  • Preferential COX-2 inhibitors: Aceclofenac, meloxicam, nimesulide
  • Selective COX-2 inhibitors: Etoricoxib, parecoxib
  • Weak analgesic-antipyretics: Paracetamol

Mechanism of Action

NSAIDs block COX-1 and COX-2 enzymes leading to decreased prostaglandin and thromboxane formation. This reduces pain sensitization, fever and inflammation.

Pharmacological Actions

  • Analgesic: Effective for mild to moderate pain such as headache, toothache, dysmenorrhoea and musculoskeletal pain.
  • Antipyretic: Reduce fever by acting on hypothalamus.
  • Anti-inflammatory: Useful in arthritis, sprains, soft tissue injuries.
  • Antiplatelet: Low-dose aspirin prevents thrombosis (50–325 mg/day).

Adverse Effects of NSAIDs

  • Gastric irritation, ulcer and bleeding
  • Hypersensitivity reactions (aspirin-induced asthma)
  • Renal impairment and fluid retention
  • Prolonged bleeding due to reduced platelet function
  • Reye’s syndrome in children (aspirin)

Important NSAIDs

Aspirin

Prototype NSAID with strong antiplatelet action; used in fever, pain, inflammatory diseases and prevention of MI. Ulcer risk is high.

Ibuprofen and Naproxen

Commonly used for musculoskeletal pain; have good safety profile.

Diclofenac

Effective anti-inflammatory medicine widely used for arthritis and injuries.

Nimesulide

Preferential COX-2 inhibitor; hepatotoxicity reported, contraindicated in children.

Etoricoxib

Selective COX-2 inhibitor with low gastric irritation; used in arthritis and chronic pain.

Paracetamol (Acetaminophen)

Good analgesic and antipyretic with minimal gastric irritation. Preferred in children, asthma patients, ulcer patients and during pregnancy.

Adverse Effects

  • Rare rashes and nausea
  • Hepatotoxicity in overdose due to formation of toxic metabolite (NAPQI)
  • Renal damage on long-term use

Treatment of Paracetamol Poisoning

N-acetylcysteine replenishes glutathione and prevents liver injury. Activated charcoal reduces absorption if given early.

Uses of Analgesic and Anti-Inflammatory Agents

  • Headache, toothache, menstrual pain, musculoskeletal disorders
  • Arthritis, bursitis, tendinitis
  • Fever management
  • Severe pain relief (opioids)
  • Postoperative pain and cancer pain
  • Thromboembolic prevention (low-dose aspirin)

Detailed Notes:

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