ANALGESICS in anaesthesia to help provide multimodal pain care

Multimodal analgesics

1. ANALGESICS DR IMRAAN AHMED MBChB MMed FCA(ECSA) Senior Registrar Anaesthesia & Critical Care

2. PAIN MEDIATORS Nociceptors – initiate the pathway Neuromediators Prostaglandins Substance P Serotonin Others – leukotrienes, bradykinins, etc

3. ANALGESICS Acute pain Opioids and related drugs NSAIDs Ketamine Local anaesthetics Chronic pain

4. OPIOID ANALGESICS From “opium” Gold standard - morphine Opiate – naturally occurring Opioid – any synthetic with affinity for opioid receptors

5. OPIOID RECEPTORS Brain, spinal cord, mesenteric plexus Various types – but all similar structure and function Leads to inhibition of NT release Inhibition of propagation of pain

6. MORPHINE Naturally occurring Comparison point for all opioids Oral (tablets, suspension), IV, IM IV/IM – 0.1 to 0.2 mg/kg 4-hrly Oral – 0.3 to 0.5 mg/kg 4-hrly

7. MORPHINE - EFFECTS CNS Analgesia Sedation Euphoria Meiosis RS Depression CVS Mild hypotension Mild bradycardia

8. MORPHINE - EFFECTS GIT n/v Constipation Other Histamine pruritus

9. MORPHINE - KINETICS Low lipid solubility – delayed absorption Slow onset – peak 10-20 mins Duration 3-4 hrs Oral bioavailability – 30% - 1 st pass metabolism

10. MORPHINE - KINETICS Hepatic metabolism – 70% morphine 3- glucuronide – antagonist 30% morphine-6 glucuronide (active and more potent) Renal excretion Cautions: hepatic/renal

11. DIAMORPHINE Prodrug – has no effect until metabolized Hydrolysed to 6-monoacetylmorphine More lipid soluble Less resp depression

12. PETHIDINE (MEPERIDINE) Synthetic derivative IV/IM. Also have tablet formulation 0.5 – 1 mg/kg 4-6 hrly

13. PETHIDINE - EFFECTS Similar to morphine, but Less meiosis Anti-cholinergic effects – tachycardia, dry mouth

14. PETHIDINE - KINETICS More lipid soluble – faster act Oral bioavailability – 50% Duration – 150-180 mins Metabolised by liver Pethidinic acid – inactive Norpethidine - epileptogenic

15. FENTANYL Synthetic 100x more potent Similar effects as morphine, but less histamine release 600x more lipid soluble – fast onset 60-90s Shorter duration – 30-40 mins

16. FENTANYL IV – 1 to 2 mcg/kg Transdermal patch Rapidly metabolised in liver Norfentanyl – inactive excreted in urine

17. TRAMADOL Not a true opioid – but has activity at opioid receptors 10-20x less potent IV/IM/PO Effects similar, Less resp depression Less constipation

18. TRAMADOL - KINETICS Well absorbed from gut – 70-90% Metabolised in liver – weakly analgesic metabolites Excreted in urine

19. NALOXONE Opioid receptor antagonist Opioid overdose 1-4 mcg/kg IV Drawback – short action less than 30mins Concern in morphine may need repeat

20. NSAIDs Non-steroidal anti-inflammatory drugs Wide range – mild to moderate pain PO/PR, some IV/IM

21. TYPES OF COX COX-1 constitutive Renal Gastric mucosa Platelets COX-2 inducible Tissue damage COX-3 central Pyrexia/pain

22. ADVERSE EFFECTS Gastric mucosa Renal blood flow Platelet function Bronchospasm – asthmatics Hepatotoxicity Less in selective

23. ASPIRIN Salicylate derivative Analgesic, anti platetlet (low dose – CVA, MI) Well absorbed orally Metabolised in liver Caution <12 yrs – Reyes syndrome – mitochondrial damage/hepatotoxicity

24. PARACETAMOL COX-3 inhibitor – analgesic, anti-pyretic No gastric irritation PO/PR/IV 10-15 mg/kg every 6hrs 80-90% bioavailabilty

25. PARACETAMOL Metabolised in liver N-acetyl-para-amino- benzoquinoneimine – highly toxic in very large amounts

26. DICLOFENAC PO/PR/IV/IM 1mg/kg every 8-12hrs Side effects similar to all, in particular Gastric Renal platelet

27. IBUPROFEN Tablets/syrup 20mg/kg/day usually 3 divided doses Less incidence of adverse effects

28. SPECIFIC COX-2 INHIBITORS Much less adverse effects, because of selectivity However, stroke and MI Withdrawn by FDA

29. OTHER ANALGESIC ADJUNCTS Ketamine NMDA antagonist –spinal cord Sub anaesthetic doses – 0.25 to 0.5 mg/kg Local anaesthetics Steroids Anti-inflammatory