OPIOIDS AND NSAIDS (PAIN AND INFLAMMATION) Flashcards
(28 cards)
What are the 5 components of the pain pathway?
Transduction → Conduction → Transmission → Modulation → Perception
What fibres are involved in pain conduction and what sensations do they carry?
Aδ fibres: sharp, well-localised pain
C fibres: dull, aching, poorly localised pain
What is the mechanism of action of paracetamol?
Weak COX inhibitor; binds at the peroxide site
Antipyretic and analgesic, not anti-inflammatory
Inhibits central prostaglandin synthesis
Why does paracetamol have no anti-inflammatory effect?
In inflammatory states, peroxide levels are high and displace paracetamol at its binding site
Outline paracetamol pharmacokinetics.
High oral bioavailability (85–98%)
Widely distributed, crosses BBB
Metabolised in liver:
Phase 1 (CYP2E1) → toxic NAPQI
Phase 2: glucuronidation & sulfation
5% excreted unchanged in urine
What are the clinical signs and risks of paracetamol toxicity?
Liver damage (↑ALT/AST), nephrotoxicity
Accumulation of NAPQI if glutathione depleted
Treatment: Activated charcoal (<1h), NAC as antidote
Classify opioids based on receptor activity.
Full agonists: Morphine, Fentanyl, Alfentanyl, Ramifentanil, Sufentanyl, Oxycodone, Methadone, Codeine, Pethidine, Hydromorphone
Partial agonists: Buprenorphine, Pentazocine
Atypical opioids: Tramadol, Tapentadol
What receptor do most opioids act on and what is its pathway?
μ-opioid receptor (MOR), a GPCR
Inhibits ascending (glutamate) and disinhibits descending (↓GABA) pain pathways
What is the mechanism of MOR (Mu opioid receptor) agonists?
Presynaptic: ↓ Ca²⁺ influx → ↓ neurotransmitter (e.g., glutamate, GABA)
Postsynaptic: ↑ K⁺ efflux → hyperpolarisation
What are the additional mechanisms of atypical opioids like tramadol and tapentadol?
Inhibit reuptake of NE and 5HT
Enhance descending inhibition of pain
What are common side effects of opioids?
Respiratory depression, sedation, constipation, dependence, nausea, hypotension, pruritis
Which opioid has the lowest risk of respiratory depression?
Buprenorphine—due to partial agonism at MOR
How is opioid tolerance developed?
Due to receptor desensitisation and internalisation; cross-tolerance may occur between agents
How are opioids metabolised?
Phase 1: via CYP2D6, 3A4
Morphine → active morphine-6-glucuronide
Codeine → morphine (CYP2D6 dependent)
What are the pharmacogenetic considerations with codeine?
Poor CYP2D6 metabolisers: ↓ efficacy
Ultra-rapid metabolisers: ↑ risk of toxicity
What is the antidote for opioid overdose?
Naloxone (MOR antagonist), reverses respiratory depression
What is the mechanism of action of NSAIDs?
Inhibit COX enzymes → ↓ prostaglandin synthesis
Anti-inflammatory, analgesic, antipyretic
Differentiate between COX-1 and COX-2.
COX-1: Constitutive → gastric protection, platelet function
COX-2: Inducible → inflammation and pain
Name non-selective vs COX-2 selective NSAIDs.
Non-selective: Ibuprofen, Diclofenac, Naproxen
COX-2 selective: Celecoxib, Parecoxib, Etoricoxib
What are NSAID-induced renal adverse effects?
↓PGE2/PGI2 → ↓ renal perfusion
Risk of acute kidney injury (esp. in elderly, CHF, dehydration)
List GI adverse effects of NSAIDs.
Gastric irritation and ulceration
Systemic effect (not prevented by food)
Contraindicated in active peptic ulcer
Avoid in pregnancy 3rd trimester
How does aspirin differ from other NSAIDs?
Irreversible COX inhibition
Low-dose: antiplatelet; High-dose: analgesic, anti-inflammatory
When is aspirin contraindicated?
Children <16 yrs (Reye’s Syndrome risk)
Aspirin-sensitive asthma
What is the pathophysiology of migraines?
Trigeminal activation → ↑ CGRP, SP, Neurokinin A → vasodilation + inflammation
