Pharmacological control of pain

Question 1

Nociception

Answer 1

process by which nociceptive information is detected by the brain

Question 2

Antinociception

Answer 2

blockade of nociception

Question 3

Pain

Answer 3

involves nociception and the response

Question 4

Analgesia

Answer 4

blockade of pain

Question 5

Placebo

Answer 5

administration of an inert substance which causes antinociception or analgesia

Question 6

What does Naloxone partially block?

Answer 6

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.

Question 7

What are the 2 diifferent types of pain?

Answer 7

Acute

Chronic

Question 8

WHat does acute pain respond well to?

Answer 8

All types of Analgesic drugs

Question 9

What is chronic pain?

Answer 9

usually defined as pain of more than 3-6 months duration

2 types:

1. due to chronic nociceptive activation
   * responds well to opioids (same pathway as acute pain)
2. neuropathic pain due to adaptive changes
   * responds poorly to opioids

Question 10

Types of Analgesic drugs

Answer 10

1. Local anaesthetics

• lidocaine

2. Non-steroidal anti-inflammatory drugs (NSAIDs)

• aspirin, ibuprofen, paracetamol

3. Opioids

• morphine, codeine

4. Miscellaneous drugs

Question 11

Miscellaneous drugs

Answer 11

• nitrates
  
  • angina
• triptans
  
  • migraine
• carbamazepine
  
  • trigeminal neuralgia
• tri-cyclic antidepressants (TCA)
  
  • amitriptyline
    
    • neuropathic pain
• anticonvulsants
  
  • pregabalin, gabapentin
    
    • neuropathic pain

Question 12

Local anaesthetics

Answer 12

• 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

Question 13

Ascending pain pathway

Answer 13

• 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

Question 14

Descending Pain Pathway

Answer 14

• 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

Question 15

When is one time you should not use Morphine?

Answer 15

In Biliary Colic as morphine causes constriction of the gall bladder

Question 16

Opiod receptors,

where in the body are they found in high concentrations?

Answer 16

Areas involved in pain control have high levels of receptors and peptides

• periaqueductal gray (PAG) - midbrain
• nucleus raphe magnus (NRM) -medulla
• nucleus reticularis paragigantocellularis (NRPG) - medulla
• dorsal horn of the spinal cord dorsal horn of the spinal cord especially lamina II (substantia gelatinosa) - where C fibres come in and synapse

Question 17

Dorsal Horn Lamina

where are A beta fibres found?

Answer 17

They are mechanoreceptors

Found in Lamina III, IV, V, VI

Question 18

Dorsal Horn Lamina

Where are A Delta fibres found?

Answer 18

Mechancoreceptors

• found in Lamina II and III

Nociceptors

• found in Lamina I and V

Question 19

Dorsal Horn Lamina

Where are C fibres found?

Answer 19

THese fibres are mixed, found in the most superficial layers

contain nociceptors, thermoreceptors and mechancoreceptors

found in Lamina I and II

Question 20

Opiod withdrawal syndrome

Early signs

Answer 20

Yawning

lacrimation

runny nose

perspiration

Question 21

Opiod withdrawal syndrome

intermediate (24-60 hrs)

Answer 21

Mydriasis

Piloerection

Tachycardia

Twitiching

Tremor

Restlessness

Question 22

Opiod Withdrawal syndrome

Late (60hrs +)

Answer 22

Muscle Spasm

Fever

Nausea, vomitting

Abdominal cramps

Diarrhoea

Question 23

Which Strong opiod does not produce pin-point pupils?

Answer 23

Pethidine

Question 24

Morphine

effect on opioid receptors?

Answer 24

selective agonist at mui receptors

Question 25

Effects of morphine

Answer 25

* Analgesia * emesis * constipation * respiratory depression * cough suppression * miosis (pin point pupils) * euphoria * itching/urticaria * hypotension * contraction of gall bladder & constriction of biliary sphincter * tolerance * dependence