Pharmacological controll of pain

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Non-opioid analgesics for inflammatory, rheumatoid and myalgic pain
NSAIDS, paracetamol, nefopam, steroids.
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When would you use nefopam?
For pain that is unresponsive to opioids and NSAIDs
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Non-opioid analgesics for neuropathic pain
anti-convulsants (Na channel blockers), anti-depressant agents (amino uptake inhibitors) and calcium channel blockers.
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Non-opioid analgesics for migraine
5-HT agonists, miscellaneous agents
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What is an important lipid produced from membranes, what enzyme
Arachadonic acid, phospholipase A2
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What happens to arachadonic acid?
Cyclo-oxygenase 1 breaks it down into cyclic endoperoxides PGG2, which is converted into PGH2
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What is PGH2 converted into? Enzymes?
PGE2 > isomerase. PGI2 > prostacyclin synthase
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Do PGE2 and PGI2 cause pain?
No- they sensitise tissues to other stimuli that are painful. Enhancers rather than producers.
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Why is there a local increase in prosoglandin production?
More phospholipase A2 and cyclo-oxygenase 2 upregulated by cytokines, growth factors, endotoxins.
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What do prostoglandins do?
acts directly to increase activity of sensory neuron specific VGnaC. Reduces activity of vgK channels. Much more likely to fire.
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another action of prosoglandins
Sensitise vaniloid polymodal receptors - trpv1.
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How do NSAID's work?
Block the cyclooxygneases, make the neurons less 'twitchy'
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What are prostaglandin receptors?
DP, EP, FP IP, TP. GPCRs linked to adenylate cyclase
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CNS effect of NSAIDs
anti-pyretic, reduce temperature because they inhibit the release of prostoglandins in the hypothalamus
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All NSAIDs have the same side effects, what are they?
- Dyspepsia, nausea, skin reactions, renal insufficience, nephropaty, bronchospasm.
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How does asprin work?
Acetylates the enzyme and permanantly disables it.
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When asprin acetylates COX enzymes, what happens
it can'tmake prostaglandins, it makes lipids called lipoxins that resolve inflammation
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Why can't children have asprin?
Can give rise to reyes syndrome.
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Iboprufens mechanism of action
reversible blocker of COX1 and Cox2, cox1 more.
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Why can't we target cox2?
Role in the protection against thrombosis, so leads to heart attacks.
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Other NSAID approachesS
NO-NSAIDS, LOX COX inhibitors.
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Suggested mechanism for paracetamol action?
Activate TRPA1 receptors, or COX3 sliced variant of COX1
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Examples of neuropathic pain
trigeminal neuralgia, post-herpatic neuralgia - after shingles. diabetic neuropathy. reflex sympathetic dytrophy (bullet).
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The drug of choice in trigemnial neuralgia and it's mechanism
carbamezapine, an anti-convulsant sodium channel blocker.
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Unwanted side effects of carbamazepine
sedation, ataxia, blurred vision, leucopenia
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Drug to treat post-herpetic neuralgia and reflect sympathetic dystropy
amytriptyline, a tri-cyclic antidepressants that prevents amine uptake
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How do VGnaC work without killing us.
they are state dependant. blocks past a certain frequency of firing.
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Gabapentin
Ca2+ channel blocker, binds to a2delta subunit. neurotonin anticonvulsant.
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PregbaLIN
A new improved version of gabapentin
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When would you use nefopam?

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For pain that is unresponsive to opioids and NSAIDs

Card 3

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Non-opioid analgesics for neuropathic pain

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Card 4

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Non-opioid analgesics for migraine

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Card 5

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What is an important lipid produced from membranes, what enzyme

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