1. Analgesia Sarah Biggs & Francesca Holt

2. Treatment for Pain Nociceptive Pain - NSAIDs and Opioids Neuropathic Pain (e.g. Phantom limb pain and post-stroke pain) –TCAs (Tri-cyclic antidepressants) Eg. Amitriptyline –AEDs (Anti-epileptic drugs) Eg. Carbemazepine Gabapentin

3. WHO Pain Ladder

4. NSAIDs NSAIDs bind COX and so inhibit it -> Prostaglandins not made from arachadonic acid (COX needed for this reaction) ->No stimulation of prostanoid receptors (no prostaglandins)  Less 2 nd messengers  Less Na+ channels open  Less cell depolarisation = NO PAIN Aspirin is the only NSAID that irreversibly binds (this is why it is used as an anti-platelet too)

5. Action Potential (reminder)

6. Commonly used NSAIDs Aspirin Ibuprofen (weak action) Naproxen (strong, low side-effects) Diclofenac (strong, low side-effects) Indomethacin (strong, high side effects) Celecoxib Etoricoxib Parecoxib COX-2 Inhibitors:

7. Side Effects Generally few problems with low dosage, short term usage  GI problems: vomitting, diarrhoea, bleeding/ulceration (COX 1)  CV incidents: thrombosis (increased risk with COX2)  Headache  Renal impairment NSAID Intoxication (Salicylism)  Tinnitus, ototoxicity  Vertigo  Hyperventilation Pulmonary apnoea, respiratory arrest Tachycardia, hypotension, asystole Delirium, hallucinations Renal Failure Coma

8. Opioid Agonist & Antagonists Mimic endogenous opioids Agonist/antagonists derived from basic morphine structure Activity graded: Pure agonists, full agonist activity Strong activity (e.g. morphine, diamorphine, tramadol) Weak activity (e.g. codeine, dihydrocodeine) Partial agonists/mixed agonist- antagonist Nalorphine, pentazocine, buprenorphine Antagonists Naloxone, naltrexone

9. Opioids Bind to G-protein linked receptors -> Inhibit adenylate cyclase -> reduction in cAMP -> increased opening of K+ channels (hyperpolarisation) -> Decrease in Ca2+ channel opening so inhibition of transmitter release

10. Side Effects and Intoxication Nausea and vomiting Constipation Respiratory depression Conscious depression/mood alterations Miosis Anaphylaxis Psychiatric changes Tolerance and dependancy – addiction/withdrawal Treatment of overdose Naloxone or Naltrexone 3 cardinal signs of intoxication

11. Thank You