Pain & Analgesia Manpreet & Olivia

Outline 1.Pain Receptors 2.WHO Pain Ladder 3.Pain Treatment -> Types of Analgesics - NSAIDs - Opioids

What are the 2 main types of pain? Neuropathic pain Nociceptive pain arises from stimulation of specific pain receptors – free nerve endings ‘groan’ pain from C fibres and ‘ouch’ pain from A-delta fibres Tx: NSAIDS & Opioids E.g. phantom limb pain, trigeminal neuralgia, post-stroke pain arises from PNS and CNS Tx: Tricyclic antidepressants (TCAs) & Antiepileptic drugs (AEDs)

WHO Pain Ladder Step 1 - Mild To Moderate non-opioids = NSAIDs (e.g. aspirin) and paracetamol Step 2 - Moderate To Severe mild opioids like codeine +/- non-opioids Step 3 - Severe strong opioids like morphine with or without non-opioids

NSAIDs Main Uses 1.Anti-inflammation 2.Anti-pyretic 3.Analgesic 4.Anti-coagulant Mechanism Of Action block prostaglandin (PG) production by inhibiting COX enzymes COX enzymes normally breakdown arachidonic acid to produce PGs

NSAIDs - Examples aspirin ibuprofen = considered to have quite weak action naproxen = strong, low side effects diclofenac indomethacin = strong, high side effects COX 2 inhibitors: - Celecoxib - Parecoxib

NSAIDs - Side Effects can delay healing so not used post-operatively or post-partum GI = vomiting, nausea, diarrhoea, bleeding/ulceration CV = thrombosis reye’s syndrome is specific to aspirin and is why not recommended <16 use aspirin Intoxication salicylism = acute or chronic digestion of NSAIDs auditory, pulmonary, CV, CNS, GI, renal failure, coma treatment = fluid replacement, haemodialysis, activated charcoal, lorazepam/diazepam for seizures

Opioids Main Uses 1.Analgesic 2.Anaesthesia 3.Cough suppressant 4.Anti-diarrhoeal Routes Of Administration IV = rapid effect IM Rectal = decreases N&V but slow Oral = easy to administer but slow Sublingual Epidural PCA = need a catheter (invasive) Patches = can cause local irritation

Opioids - Types Pure Agonists strong activity = morphine, diamorphine and tramadol weak activity = codeine and dihydrocodeine Partial Agonists buprenorphine pentazocine Antagonists naloxene (1/2 hours half-life) naltrexone (10 hour half-life)

Opioids – Mechanism Of Action decrease neuronal transmissions by: ●decrease opening of voltage dependent calcium channels (VDCC) ●which decreases calcium release from intracellular stores ●increase potassium outflow of cells ●decrease exocyotosis metabolism:  primarily in the liver  the metabolites are highly water soluble and excreted in urine

Opioid Side Effects & Overdose ●Miosis ●Respiratory depression ●Decreased consciousness 3 cardinal signs of intoxication: ●Nausea/Vomiting ●Decreased gastric motility = constipation ●Anaphylaxis ●Psychiatric changes, especially tramadol (often have hallucinations) ●Tolerance & dependence - addiction/withdrawal ●AND the major 3…. Treatment for OD: ●opioid antagonists = naloxone & naltrexone (whichever is appropriate re: half-life) ●coma cocktail = naloxone, oxygen, glucose and thiamine

Thank you! Any Questions?