Pain Relief: An Overview of Drug Types and Mechanisms

Pain relief is a crucial aspect of managing various medical conditions. Pain medications are broadly categorized into two main types:

1. Opioid Pain Relief:

• Structure and Action: Opioids are compounds structurally similar to morphine, acting on opioid receptors in the central nervous system, leading to pain relief, sedation, euphoria, and cough suppression.

• Key Functional Groups of Morphine:

• Phenol group at C3:

• Alkylation: Reduces pain-relieving effects, increases addiction potential (e.g., codeine = methyl morphine).

• Esterification: Enhances the effects of morphine (e.g., acetyl morphine).

• Alcohol group at C6:

• Dehydration, esterification, etherification: Enhance pain relief and toxicity, shorten duration of action (e.g., heroin = diacetyl morphine, significantly increases pain relief and addiction).

• Morphine and Opioid Receptors:

• μ (mu) receptor: Miosis (constricted pupils), respiratory depression, bradycardia (slow heart rate), reduced gastrointestinal spasms, spinal pain relief, euphoria.

• κ (kappa) receptor: Miosis (less than μ), respiratory depression, supraspinal pain relief, sedation.

• Effects of Morphine on the Nervous System:

• Central Nervous System: Pain relief (cancer pain, visceral cramps, selective pain relief), sedation, euphoria, respiratory depression, cough suppression, endocrine suppression (hypothalamic suppression, ADH release enhancement), nausea, vomiting, miosis.

• Peripheral Nervous System: Smooth muscle contraction, vasodilation, increased histamine release, decreased metabolism, hypotension.

• Opioid Classification:

• Full agonists: Morphine, Meperidine, Fentanyl.

• Partial agonists: Buprenorphine, Pentazocine, Nalbuphine.

• Antagonists: Naloxone, Naltrexone.

• Effects and Indications:

• Strong opioid agonists: Mepiridin, Fentanyl (rapid onset after 2-3 minutes, potent pain relief 80-100 times morphine).

• Moderate to weak opioid agonists: Codeine, Dextropropoxyphene.

• Opioid antagonists: Naloxone, Naltrexone.

• Naloxone: Antagonist at μ and κ receptors.

• Naltrexone: Prolonged action, non-tolerance, no withdrawal syndrome with long-term use.

• Indications for opioid antagonists: Management of acute opioid overdose, heroin withdrawal.

• Indications for opioid use:

• Post-traumatic pain, cancer pain, post-surgical pain.

• Renal colic, biliary colic: morphine + antispasmodics.

• Adjunctive use during anesthesia and pre-anesthesia: Morphine, Fentanyl.

• Acute pulmonary edema: Morphine suppresses alveolar fluid secretion.

• Opioid Toxicity:

• Acute toxicity: Headache, dizziness, miosis, respiratory depression, vomiting, cyanosis, hypotension, cardiovascular collapse leading to death. Antidote: Naloxone, Naltrexone.

• Chronic toxicity: Constipation, death from infectious diseases (like HIV), addiction, withdrawal syndrome, drug tolerance, drug dependence.

• Withdrawal syndrome: Emotional disturbance, nausea, muscle aches, fever, sweating.

• Tolerance: Need to increase dosage for the same initial effect with prolonged use.

• Dependence: Withdrawal syndrome occurs upon discontinuation of the drug.

2. Non-Opioid Pain Relief (NSAIDs):

• Mechanism: Inhibition of COX (cyclooxygenase), preventing arachidonic acid from forming prostaglandins.

• COX-1: Located in blood vessels, stomach, kidneys.

• COX-2: Influences inflammatory effects.

• Adverse effects of NSAIDs:

• Respiratory: Pseudo-asthma, exacerbation of asthma (due to COX inhibition, leading to increased leukotriene synthesis).

• Gastrointestinal: Gastric ulcers (due to reduced PGE1, PGE2).

• Renal: Decreased glomerular filtration, fluid retention, increased potassium, interstitial nephritis (due to reduced PGE2, PGI2).

• Hematologic: Prolonged clotting time (due to reduced platelet aggregation and prothrombin).

• Circulatory: Fluid retention, hypertension, edema.

• General indications for NSAIDs: Mild to moderate pain, accompanied by inflammation, fever, acute and chronic inflammatory conditions (rheumatoid arthritis, acute gout).

• Contraindications for NSAIDs: Gastric ulcers, NSAID allergy, asthma, first and third trimesters of pregnancy.

• Classification of NSAIDs:

• Non-selective COX inhibitors: Aspirin, Acetaminophen (paracetamol), Idomethaxine, Ibuprofen.

• Selective COX-2 inhibitors: Coxib group: celecoxib, etoricoxib.

• Mechanism of Aspirin: Irreversible COX inhibition leading to PG synthesis inhibition, irreversible platelet aggregation inhibition lasting 8-10 days.

• Indications for Aspirin: Prevention of thrombosis, embolism such as stroke, myocardial infarction (dose 75-100mg).

• Contraindications for Aspirin: Limited in children due to Reye’s syndrome.

• Indications for Acetaminophen (paracetamol): Pain relief, fever reduction, no anti-inflammatory effects, no side effects (bleeding, gastric ulcers, kidney disease), high doses lead to liver cell necrosis, toxic dose 150mg/kg/day, antidote: N-acetylcysteine.

• Strong anti-inflammatory agents in descending order: Indomethaxin > phenylbutazone > aspirin.

• Indications for Indomethaxone: Acute gout, closure of ductus arteriosus in premature infants. High toxicity (not for children).

• Indications for Ibuprofen: Pain relief, anti-inflammatory, fever reduction from mild to moderate.

• Indications for coxib group: Celecoxib, etoricoxib treatment of acute gout.

Appropriate use of pain medications:

• Mild pain: Peripheral analgesics Aspirin, Paracetamol, NSAIDs.

• Moderate pain: Weak central analgesics Codeine, Dextropropoxyphene + peripheral analgesics + adjunctive drugs.

• Severe pain: Strong central analgesics Morphine + adjunctive drugs.

Note: Pain medication use should always be under the guidance of a physician to ensure safety and efficacy.