Analgesics Flashcards
What is included in step 1-3 of the WHO Analgesic ladder?
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What is the paracetamol method of action
Inhibits cyclo-oxygenase (COX) and therefore prostaglandin production
Acts only centrally as it cannot reach inflammation sites due to susceptibility to peroxides
Anti-pyrexial action
Inhibits take up of anandamine (endocannabinoid)
Inhibit CNS Na+ channels → analgesic
How is paracetamol metabolised?
Toxic phase 1 biproduct (N-acetyl-P-Benzoquinonelmine)
Conjugated with Glutathione
When body runs out, toxic product NAPQBI builds up → liver damage
What are the paracetamol OD symptoms and treatment?
After 24 hours:
- N&V
- Anorexia
After 3-5 days:
- Abdominal Pain
- Metabolic Problems etc. - Hyper/hypoglycaemia
Treatment: Activated charcoal; N-acetylcysteine; Methionine
What is perfalgan?
IV form of paracetamol
What is the mode of action of NSAIDs?
Competitively inhibit COX1 and/or COX2 Enzymes
COX converts Arachidonic Acid to Prostaglandins
COX2 - inflammatory prostaglandins
COX1 - protective prostaglandins - gastric repair, renal perfusion
Analgesic and Anti-inflammatory action
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What are the safety concerns of using NSAIDs?
GI damage
Damage to kidneys
Sodium and Water retention
Worsening of asthma
What should be done for GI complications when using NSAIDs
PPIs used when ↑Risk of GI complications
Prostaglandin Analogues (Misoprostol) can also be added to mimic → ↑Healing and HCO3 production
What are some non-selective COX-inhibitors? and what are the side effects?
Ibrupofen, Naproxen, Diclofenac
S/E: GI irritation/Ulceration
Name some COX-2 inhibitors
Celecoxib, Etoricoxib
What are the first and second line NSAIDs and what should they be prescribed with in the case of GI problems?
Ibrupofen - 1st
Naproxen - 2nd (less thrombotic risk)
Add PPI
What is the mode of action of opioids?
Inhibit ascending pathways
Direct inhibition: Bind to 1st order nociceptors in periphery → Induces K+ influx into presynaptic membrane → hyperpolarisation
Indirect inhibition: Activation of descending pathways:
Bind to opioid Rs in Nucleus Raphe Magnus (medulla) → stimulation of serotinergic descending pathway → further release of opioids in dorsal horn → further inhibition
Name some weak opioids
Codeine
Dihydrocodeine
Tramadol
How does codeine work? and what is it normally used in combination with?
Analgesic properties comes from 〜10% of drug being metabolised in liver → morphine
Best used with paracetamol for analgesia: Co-codamol
What is the mode of action of Tramadol?
Has opioid and non-opioid properties
Opioid - weak affinity for μ-receptors
Non-opioid: Serotonin-Noradrenaline Reuptake Inhibitor (and stimulates serotonin release)
Naloxone only partially reverses analgesic properties
When should tramadol be taken with caution?
In those with risk of seizures (due to ↑S/N)
May induce CNS toxicity in those using anti-depressants
Name some strong opioids
Morphine, Fentanyl, Diamorphine, Hydromorphone, Methadone, Oxycodone
What is the most appropriate starting agent for strong opioids? and which is used with kidney impairment?
Morphine most apporpriate starting agent
Diamorphine quicker onset, and shorter duration of action
Fentanyl in kidney impairment
What is the antidote for opioids OD?
Naloxone - competitive antagonist of all opioid Rs
Short half life, so OD patients may need top up
Name and anti-spasmodic and what is it’s mode of action?
Baclofen - GABAB R Agonist - ↑inhibition of motoneurone signals
Relieve pain caused by muscle spasm by reducing spasm
Name some anti-convulsants and what are they used for in pain management?
Gabapentin/Pregabalin, Carbamazepine
Gabapentin: GABA analogue, unknown mechanism - licensed for neuropathic pain
S/E: Drowsiness, confusion, dizziness
Pregabalin: also used as adjunct antiepileptic and anxiety disorders
Name some antidepressants used for neuropathic pain
Amitryptiline - neuropathic analgesic
Tricyclic Antidepressant - works as SNRI
S/E: Drowsiness, Arrhythmias, dry mouth, blurred vision
Name an NMDA-R Antagonist used for analgesia
Ketamine
NMDAR - Induction and maintenance of central sensitisation
Ketamine stops this action
What anaesthetics are used in pain management?
Lidocaine Patch
Emla cream (Lidocaine + Prilocaine)
Nerve blocks
What is Entonox?
50% Oxygen; 50% NO
Breathe in through mouth, 4+ breaths for full effect
Eliminated after 30 mins