Pain Flashcards
Paracetamol
MOA and Side effects
Anti-pyretic (anti-fever) and analgesic but little anti-inflammatory effects.
• Prevents pain: stopping prostaglandin synthesis in the CNS = through decreasing prostaglandin E2-induced reduction of glycine inhibition of spinal cord cells - endogenous spinal inhibitory mechanisms: normal.
o Decreased glycine.
• Inhibit reuptake of endogenous cannabinoids from synaptic cleft = increases effect on antinociception
Ineffective as Anti-Inflammatory:
• Reduces the active oxidised form of COX-2, preventing it from forming pro-inflammatory stimuli (e.g. prostaglandins/thromboxanes).
• BUT: in the presence of peroxides (exist at sites of inflammation) mechanisms becomes inefficient (COX-2 oxidisation by peroxides).
Side effects: Nausea and GI Bleeding
NSAIDs - ibuprofen
MOA and side effects
Mild to moderate pain.
Both analgesic and anti-inflammatory.
• Inhibits the activity of COX-1 and COX-2 enzymes.
• Decreases prostaglandin formation, recruitment of leucocytes.
• Reduces sensitisation by these inflammatory mediators.
• (!) Also travel across the BBB to have effects on the prostaglandin synthesis in the CNS.
Side effects: Related to inhibition of COX-1.
• COX-1 regulates production of prostaglandins in the GI tract (protect the mucosa).
• Long-term use of NSAIDs can lead to peptic ulcers.
NSAIDs: Diclofenac
MOA and side effects
Moderate to Severe Pain
Inhibit the formation of prostaglandins.
(!) Longer acting vs ibuprofen.
• Analgesic efficacy comparable to low-dose opioids.
Due to additional activity of inhibiting phospholipase A2 and reductions in arachidonic acid (needed for synthesis of prostaglandins and leukotrienes).
Side effects:
• Lower COX-1 selectivity: reduces the risk of GI complications.
• Higher risk of CV complications due to inhibition of endothelial prostacyclin but not thromboxane.
• Therefore, contraindicated in people with IHD and strokes.
NSAIDs: Rofecoxib
MOA and side effects
Selective for COX-2 Inhibitors.
Side effects: Nausea and GI bleeding
Anticonvulsants
MOA and side effects
Pregabalin - from Pain PBL
Beneficial after 1 week of treatment.
• Binding to alpha2 delta 1 subunit of N-type voltage gated calcium channels.
• Reduction in Ca2+ entry = decreased release of neurotransmitters (glutamate, noradrenaline etc…).
(!) Alpha 2 delta 1 subunits increased in some neuropathic conditions.
Side effects: More Common - • Drowsiness, dizziness and headaches Less Common - • Peripheral oedema, visual problems, weight gain, confusion
Carbamazepine and sodium valproate act on sodium
channe
All can be given for neuropathic pain and trigeminal neuralgia.
NSAIDs - aspirin
MOA
COX-1 and COX-2 inhibitor - analgesic, antipyretic, anti-inflammatory
Tricyclic antidepressants
MOA and side effects
Amitryptiline - in pain PBL
Often described for neuropathic pain as depression and insomnia are common complications.
• Inhibit reuptake of amines.
• Mainly 5-HT vs noradrenaline (SNRI).
• Inhibits sodium channels, L-type Ca2+ channels and subtypes of K+ channels and acts on NMDA receptors.
• Has affinity for various other receptors e.g. H1, muscarinic alpha-1 and alpha-2 adrenoceptors (cause of side effects)
Side effects: • Weight gain • Appetite changes. • Muscle stiffness, constipation, urinary retention, dry mouth (muscarinic effects). • Postural Hypotension (adrenergic) • Nausea nervousness, dizziness.
Side effects due to anticholinergic activity (inhibition of acetylcholine muscarinic receptors, acetylcholine adrenergic receptors etc…).
Acupuncture
MOA
Acupuncture is a form of diffuse noxious inhibitory control (DNIC), whereby pain in one part of
the body may reduce pain in all other parts of the body. Nociceptors are activated when pins
are pushed into the superficial musculature. Nociceptive input then activates the descending
inhibitory neurons in the brainstem reticular formation (periaqueductal gray, raphe nuclei and
locus coeruleus). This may be effective for some forms of acute or on-going pain, but the
clinical evidence for acupuncture in chronic pain is strongly debated. In neuropathic
conditions, where the functions of the descending analgesic control systems may change, it is
largely ineffective.
Opioid
Examples, MOA, Side effects
Act on opioid receptors
Examples:
Morphine:
Stimulate Mu Opioid Receptors
• Decreased neuronal excitability (by increasing K+ conductance) and decreased release of neurotransmitters (decreases Ca2+ influx).
Descending Inhibitory pathways
• Stimulate the periaqueductal gray (decreases pain efferent pathways)
• Inhibit the substantia gelatinosa of the SC. (Lamina II: where interneurons are.
Limbic System
• Reduces the anxiety of pain.
Side effects:
• Paradoxically increased sensitivity to pain.
• Constipation, nausea, respiratory, depression and sleepiness.
Other examples:
Fentanyl
Neuropathic Pain treatment strategy
- Offer anticonvulsant (pregabalin) or tricyclic antidepressant (amitriptyline).
a. Also: duloxetine (SNRI), gabapeptin (calcium channel ligands.). - Try switching if initial drug is not tolerance.
- Consider tramadol (opioid agonist) only if acute rescue theraphy is needed.
- If oral treatment not tolerated: consider capsaicin cream.
Local anaesthetic
Types, MOA, Risk
Examples: lignocaine, prilocaine
- Blockage of sodium channels
- Administered through surface, infiltration, epidural.
o (!) Risk of systemic toxicity: hypotension, respiratory depression.
General anaesthetics
MOA, risk
• Activation of inhibitory receptors/inhibition of excitatory receptors.
o Induce CV depression (why it is monitored in surgery)
