Analgesics

Introduction Analgesics are drugs that relieve pain due to multiple causes without affecting its cause. Relieve pain by selective action in CNS or peripheral pain mechanism without producing unconciousness. 2 types – NSAID Opioids

NSAID

Classification Non selective COX inhibitors Salicylic acid: Aspirin Propionic acid derivative: Ibuprofen, Ketoprofen Anthranilic acid derivative: Mefenemic acid Aryl acetic acid derivative: Diclofenac Oxicam derivatives: Piroxicam, Tenoxicam Pyrrolo-pyrrole derivatives: Ketorolac Indole derivative: Indomethacin Pyrrazolone derivative: Phenylbutazone Preferential COX2 inhibitors: Nimesulide, Meloxicam

IV. Analgesic-antipyretic with poor anti- inflammatory action: III. Selective COX2 inhibitors: Celecoxib, Rofecoxib, Valdecoxib IV. Analgesic-antipyretic with poor anti- inflammatory action: Paraamino phenol derivative: Paracetamol Pyrrazolone derivative: Propiphenazone Benzoxazocine derivative: Mefopam

Mechanism of action These drugs inhibit the synthesis of prostaglandins. Phospholipids are converted to arachidonic acid by phospholipase A. Arachidonic acid is then converted to prostaglandin by COX enzyme. NSAID inhibit COX enzyme.

Therapeutic actions Analgesia Anti-pyresis Anti-inflammatory Patency of ductus arteriosus Primary dysmenorrhoea

Side effects Gastrointestinal side effects: Dyspepsia, nausea, vomiting, diarrhoea or constipation Disturbance in platelet function Inhibition of uterine motility leading to prolongation of gestation period Can cause intrauterine closure of ductus arteriosus in infants Increased risk of post partum haemorrhage Analgesic nephropathy

Opioids

Classification Pure agonists: high affinity for mu receptors and varying affinity for delta and kappa receptors; lack appreciable activity at sigma receptors Total opium alkaloids: Omnapon Purified opium alkaloids: Morphine, Codeine Synthetic analogues of morphine: Heroin, Levorphenol Synthetic analogues of codeine: dihydrocodeine, Tramadol Morphine substitutes: Meperidine and its analogues: Meperidine, fentanyl, Sufentanyl, Alfentanyl, Ramifentanyl, Diphenoxylate, Loperamide Methadon and its analogues: Methadon, Levomethadyl acetate, Dextropropoxyphene

II. Partial agonist and mixed agonist- antagonist: Pentazocin, Nalbuphine, Butorphenol, Buprenorphine, Meptazinol, Dezocine III. Pure antagonist: Naloxone, Neltrexone

Mode of action Endogenous opioid peptides (encephalins, dynorphins, endorphins) are attached to specifc opioid receptors. Three opioid receptors are mu, kappa and delta. Opioids act on these receptors to produce effects

Indications As analgesic in MI,biliary cholic, post operative pain, obstetrical analgesia Sedation Diarrhoea As pre-anaesthetic medication and as balance anaesthesia Cough Dyspnoea in acute left ventricular failure

Contraindications Head injury Increased intracranial pressure Hypotension and haemorrhage Bronchial asthma Myxoedema, multiple sclerosis & Addison’s disease Grossly impaired liver and kidney function In presence of convulsive diseases Biliary cholic Benign prostatic hypertrophy

Adverse effects Behavioural: anxiety, confusion, dysphoria, restlessness Nausea, vomiting Increased biliary pressure Urinary retention Hypersensitive reaction: itching around nose and urticaria by i.v. routes Postural hypotension, increased intracranial pressure, respiratory depression