Pharmacological control of pain Flashcards
Nociception
process by which nociceptive information is detected by the brain
Antinociception
blockade of nociception
Pain
involves nociception and the response
Analgesia
blockade of pain
Placebo
administration of an inert substance which causes antinociception or analgesia
What does Naloxone partially block?
Antinociception that is produced by endogenous opiods that are involved in pain control
Naloxone counters the effects of an opiod i.e used in overdoses
electrical stimulation of the periaqueductal gray o r several medullary sites can produce antinociception.
What are the 2 diifferent types of pain?
Acute
Chronic
WHat does acute pain respond well to?
All types of Analgesic drugs
What is chronic pain?
usually defined as pain of more than 3-6 months duration
2 types:
- due to chronic nociceptive activation
* responds well to opioids (same pathway as acute pain) - neuropathic pain due to adaptive changes
* responds poorly to opioids
Types of Analgesic drugs
1. Local anaesthetics
- lidocaine
2. Non-steroidal anti-inflammatory drugs (NSAIDs)
- aspirin, ibuprofen, paracetamol
3. Opioids
- morphine, codeine
4. Miscellaneous drugs
Miscellaneous drugs
-
nitrates
- angina
-
triptans
- migraine
-
carbamazepine
- trigeminal neuralgia
-
tri-cyclic antidepressants (TCA)
- amitriptyline
- neuropathic pain
- amitriptyline
-
anticonvulsants
- pregabalin, gabapentin
- neuropathic pain
- pregabalin, gabapentin
Local anaesthetics
- Na channel blockers
- Weak bases
- At pH 7.4, fairly lipid soluble drugs and the non-ionised form can cross the neuronal membrane
- Inside the neuron, dissociates and the free base binds to Na channel
- highest affinity for inactivated or closed state of the Na channel, they slow the rate at which channels revertto resting state
- block action potential generation by decreasing the number of Na channels available to open
- Greatest effect in rapidly firing neurons
Ascending pain pathway
- Activation of nociceptive primary afferents ( A o r C fibres) which enter dorsal horn and synapse onto interneurons or projection neurons
- Activation of projection neurones in the dorsal horn which travel to the brain in the spinothalamic tract
- If one records firing of dorsal horn neurones, opioids inhibit firing and stop transduction of the signal to the brain.
- Inhibit release of glutamate and substance P from primary afferents
Descending Pain Pathway
- Activation of PAG and NRM by morphine causes
- increase firing of descending pathway to dorsal horn.
- involves mainly serotonergic neurons and depletion of 5HT o r 5HT antagonists decrease anti-nocice ptive effect of morphine.
- Effect in PAG an d NRM is due to inhibition of release of GABA from local interneurons.
- This leads to disinhibition inhibition of the descending descending serotonergic serotonergic pathway pathway which decreases transmission of nociceptive information through the dorsal horn.
Opiod receptors on GABA terminals -> decrease GABA release therefore disinhibition
When is one time you should not use Morphine?
In Biliary Colic as morphine causes constriction of the gall bladder
