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PM3B: Autumn > Pain and Analgesia > Flashcards

Pain and Analgesia Flashcards

1
Q

What is the best definition of pain

A

An unpleasant sensory or emotional experience associated with actual or potential tissue damage, or described in terms of such damage

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2
Q

What are the two classes of pain

A

Nociceptive pain

Neuropathic pain

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3
Q

Describe how Nociceptive pain works and give examples of it

A

Peripheral visceral or somatic pain
Directe action of pain sensing receptors in response to noxious stimuli that alerts organic of impending tissue damage

Examples:
Inflammation
Fractures
Burns
Bumps and bruises
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4
Q

Describe how Neuropathic pain works and give examples of it

A

Pain produced by damage to dysfunction of nerves in peripheral or central nervous system

Examples:
Nerve 
Trauma
Peripheral neuropathy
Phantom limb pain
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5
Q

What are the three processes of nociceptive pain

A
  1. Detection of pain in the periphery
  2. Transmission of pain signals from periphery to spinal cord- mainly by C fibres and Adelta fibres
  3. Reception of signals by higher central brain centers- afferent activity generates pain sensation that initates response
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6
Q

What is the function of A beta fibres

A

Touch and pressure (mechanoreceptors)

Target of TENS and acupuncture

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7
Q

What is the function of A delta fibres

A

Sharp pain (NOCICEPTORS)

Touch (Mechanoreceptors)

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8
Q

What is the function of C fibres

A

Dull and burning pain (NOCICEPTORS)

Touch (Mechanoreceptors)

Temperature (Thermoceptors)

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9
Q

What is the gate control pain theory

A

Formed of transmission neurones which supply the thalamus area of brain with sensory information

The neurones are affected by:
Small inhibitory neurones
Nociceptors (C and A delta fibres)
Mechanoreceptor (A Beta fibre) input

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10
Q

Describe the gate control pain theory (4 steps)

A
  1. Small inhibitory neurones (substantial gelantinosa SG interneurones) that inhibit and close the gate to reduce pain
  2. Activation of C and A-delta fibres open the gate and increase pain by direct excitation of the gate and inhibition of SG interneurones
  3. Activation of A beta fibres to close the gate- excitation of SG interneurones
  4. Descending inhibitory pathways from the CNS close the gate by:
    Inhibition of the gate and direct activation of SG interneurones
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11
Q

What are the six inflammatory mediators of peripheral pain

A
  1. Bradykinin
  2. Substance P
  3. Adenosine Triphosphate (ATP)
  4. Protons (H+)
  5. Endogenous activators of TRPV1
  6. Prostanoids
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12
Q

Describe how bradykinin plays a part as an inflammatory mediator of peripheral pain

A

Made from vascular precursors and activates:

Beta 2 receptors: Nociceptive neurones
Beta 1 receptors: Metabolite unregulated via inflammation

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13
Q

Describe how Substance P plays a part as an inflammatory mediator of peripheral pain

A

Activates NKA (neurokinin) receptors in nociceptive pain

  • Enhances NMDA action (hypersensitivity)
  • CGRP peptide is co-released
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14
Q

Describe how Adenosine Triphosphate plays a part as an inflammatory mediator of peripheral pain

A

Activates P2X3 receptors

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15
Q

Describe how Protons (H+) plays a part as an inflammatory mediator of peripheral pain

A

Activates acid sensing ion channels (ASICS)

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16
Q

Describe how Endogenous activators of TPV1 vanillin receptors plays a part as an inflammatory mediator of peripheral pain

A

Heat
Target of capsaicin (API in chilli)

It is unregulated by BK and nerve growth factor

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17
Q

Describe how PROSTANOIDS plays a part as an inflammatory mediator of peripheral pain

A

Formed of prostaglandins and thromboxane

PGE2 and PGF2 are released in inflammation- greatly increased responses to bradykinin and 5-HT

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18
Q

Describe how GLUTAMATE plays a part as an inflammatory mediator of peripheral pain

A

Excitatory amino acid that acts at AMPA to mediate acute pain (fast response, baseline set)

NMDA receptor has delayed response

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19
Q

What are the two types of neuropathic pain and explain them

A

Sodium channel clustering- redistribution of sodium channels to areas of nerve damage can set up ectopic (out of place) firing

Sympathetic NS mediated pain- up regulation of alpha adrenoceptor means that noradrenaline release causes pain

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20
Q

What are the main drugs for nociceptive and neuropathic pain

A

Nociceptive pain:
Non opioid: paracetamol, aspirin, NSAIDS
OPIOID analgesics

Neuropathic pain:
Anti-deppresants
Anti-convulsants
Other CNS related drugs

21
Q

What is the mechanism of action of aspirin and its role

A

Blocks cycloxygenase enzymes
COX-1 (constitutive form)
COX-2 (induced at damage sites) isoforms

Role:
Anti platelet effects (TXA2 effect)
Anti-pyretic (fever reducer)

22
Q

Give examples of non selective NSAIDS

A

Indoles:
DICLOFENAC and Indomethacin

Propionic acid derivatives:
Ibuprofen
Naproxen
Ketoprofen

23
Q

Give examples of COX-2 selective NSAIDS that were withdrawn

A

Rofecoxib and Valdecoxib- cardiovascular side effects

24
Q

Give examples of COX-2 selective NSAIDS and their uses

A

Celecoxib and Etoricoxib

Licensed for Rheumatoid arthritis, osteoarthritis pain and gout

25
Q

What is Nefopam

A

A non opioid drug that is used for persistent pain when NSAIDS are ineffective

26
Q

What is the mechanism of action of paracetamol

A

TRPA1 mediates spinal antinociception and this is induced by acetaminophen

27
Q

What does co-dydramol consist of

A

Paracetamol wit dihydrocodeine tartate

28
Q

What is the main endogenous agonist for mu, delta and kappa receptors in opioid receptor G alpha i/o?

A

Beta endorphins

29
Q

What is the therapeutic agonist for Mu receptors and its clinical uses

A

Morphine
Codeine
Fentanyl
Pethidine

All forms of nociceptive pain: cancer, pre/post operative pain

30
Q

What is the therapeutic agonist for kappa receptors

A

Pentazocine

31
Q

How do you affect spinal action with opioid action

A

Activation of presynaptic receptors with more Mu than Delta to reduce transmitter release

32
Q

How do you affect Supra-spinal action

A

Opioid action at mu (delta and kappa) receptors to enhance descending inhibitory pathway in brain stem/mid brain

Involves noradrenaline and 5-HT release by blocking GABA inhibition

33
Q

Describe the use of morphine as a partial agonist of Mu: role, metabolism, dose, route

A

Reduces affective component pain

Metabolised to morphine-6-glucuronide

Dose: titrated to the amount depending on pain relief

Commonly given via:
IV or oral morphine sulfate (MST)

34
Q

Describe Fentanyl, potency, duration and form

A

Very potent
Short duration
Often used as a transdermal patch

35
Q

Describe where Pethidine is normally used

A

Used during labour

Lack of effect of uterine contraction

36
Q

Describe the use of oxycodone

A

Control of pain in palliative care

37
Q

Describe the use of codeine and dihydrocodeine and its side effects

A

Low efficacy, orally effective

Not too addictive, widely used for mild pain (back, head, toothache)

Side effects:
CONSTIPATION with long term use
Nausea and Vomiting

38
Q

Describe Diamorphine its pharmacodynamic properties and use

A

Heroin metabolised to morphine

High lipid solubility means higher efficacy and rapid action

Used in weak patients in palliative care

39
Q

Describe Tramadol and its role

A

Weak Opioid Analgesic

Inhibitor of noradrenaline uptake and transport system

40
Q

What are the side effects of opioid analgesics and explain how they occur (5)

A

Respiratory Depression:
Reduction of sensitivity of respiratory centre

Euphoria:
Acts on reward pathway to increase dopamine release
(example: kappa agonist Pentazocine)

Cough suppression (anti-tussive)

Nausea- activation of chemoreceptor trigger zone that activates vomiting centre
(antiemetics co prescribed)

Constipation- maintained contraction of smooth muscle

41
Q

What is the treatment option of respiratory depression

A

NALOXONE

42
Q

What are the five drugs used to treat neuropathic pain

A
  1. Anti-epileptic drugs
  2. Tricyclic (antidepressants)
  3. Ketamine
  4. Lidocaine or bupivacaine
  5. Ziconotide
  6. Cannabinoid agonists
43
Q

Give examples of the anti-epilpetic drugs used in neuropathic pain and what they do

A
  1. Carbmazepine and Phenytoin (Na channel blocker)

2. Gabapentin and pregabalin (calcium channel effect)

44
Q

Give examples of Tricyclic anti-depressant drugs used in neuropathic pain and what they do

A

Duloxetine- selective serotonin and norepinephrine reuptake inhibitor

Imipramine/Amitriptyline

45
Q

What does ketamine do in neuropathic pain

A

Analgesic block of NMDA receptor

46
Q

What does lidocaine or bupivacaine do in neuropathic pain

A

Local anaesthetics that block Na Channel (nerve block) when injected close to sensory nerve

47
Q

What does Ziconotide do in neuropathic pain

A

Acts as a calcium channel blocker and injected intrathecally to spine

48
Q

Give an example of a cannabinoid agonist and what its used to treat

A

Used to treat pain in multiple sclerosis patients

SATIVEX- mixture of THC and CBD

PM3B: Autumn (19 decks)

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