Pharmacology of Pain Flashcards

1
Q

What are the three main types of pain?

A
  1. Nociceptive (e.g. acute noxious mechanical,
    thermal, electrical stimuli)
  2. Inflammatory (e.g. semi-acute or chronic ischaemia, infection)
  3. Neuropathic (e.g. chronic maladaptive
    plasticity after traumatic injury)
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2
Q

With pain, what happens in the first seconds to minutes?

A

Activation of nociceptive specific/wide dynamic range neurones proportional to the intensity of the stimulus

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3
Q

With pain, what happens in the first minutes to days?

A

Sensitisation of terminals at the injury site and delayed central sensitisation

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4
Q

With pain, what happens in the first days to months?

A

Changes in the supply of trophic factors, sprouting of fibres and abnormal innervation, and trans-synaptic degeneration

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5
Q

What are some of the targets for treating pain? (5)

A
COX-2 (make prostaglandins)
Nitric oxide synthase
Glutamate receptors (NMDA and non-NMDA)
Neurokinin 1 receptors
Opioid receptors (e.g. µ receptors)
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6
Q

How do opioids affect the periaqueductal gray and nucleus reticularis paragigantocellularis? What else do they affect?

A

They stimulate the periaqueductal gray and nucleus reticularis paragigantocellularis.
This stimulates the nucleus raphe magnus which inhibits dorsal horn (using 5-HT and enkephalins).
They also directly inhibit the dorsal horn and the nociceptive afferent neuron to the periphery.

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7
Q

What structures are activated by nociceptive stimuli? (8)

A
Spinal cord
Thalamus
Somatosensory cortex
Anterior cingulate cortex
Insula
Amygdala
Prefrontal cortex
Hippocampus
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8
Q

What factors influence pain perception? (6)

A

Cognition – attention/distraction, etc
Context – beliefs, expectations, placebo
Genetics
Injury – peripheral/central sensitisation
Chemical and structural – atrophy/dysfunction
Mood – depression, anxiety, catastrophizing

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9
Q

What influences your risk of developing chronic pain? (3)

A

Hardware at birth
Environmental influences
Gene x environment interactions

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10
Q

What endogenous opioid peptides are involved in nociception?

A

Enkephalins (derivied from proenkephalin)
Dynorphins (derived from prodynorphin)
Beta endorphin
(+ Pro-opiomelanocortin)

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11
Q

Why are endogenous opioids rapidly inactivated in the circulation?

A

They are targets for peptidases.

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12
Q

Give an example of a pro-nociceptive endogenous system.

A

Cholecystokinin

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13
Q

Why do opioid agonists have a broad spectrum of effects?

A

Due to the wide distribution of opioid receptors.

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14
Q

List the 4 types of endogenous opioid system receptors.

A

Mu (1, 2, 3)
Delta (1, 2)
Kappa (1, 2, 3)
Nociceptin/orphain receptor

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15
Q

What is the effect of morphine on conductance and neurotransmitter release?

A

Activating potassium conductance and decreasing calcium conductance
Decreased excitability and decreased release of neurotransmitter

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16
Q

Give some examples of opiates. (6)

A
Morphine
Methadone
Sufentanil
Fentanyl
Pethidine
Pentazocine
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17
Q

Mu receptor effects:

  • What type of analgesia/where?
  • What are the main side effects? (4)
  • Can it be used as a sedative?
  • Is it addictive?
A

Supraspinal (some spinal and peripheral as well)
Respiratory depression, pupillary constriction, reduced GI motility, euphoria
Yes
Yes

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18
Q

Delta receptor effects:

  • What type of analgesia/where?
  • What are the main side effects? (2)
  • Can it be used as a sedative?
  • Is it addictive?
A

Spinal analgesia
Resp depression (less than Mu) and reduced GI motility
No
No

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19
Q

Kappa receptor effects:

  • What type of analgesia/where?
  • What are the main side effects? (3)
  • Can it be used as a sedative?
  • Is it addictive?
A

Peripheral (and some spinal)
Resp depression (but less than delta and mu), reduced GI motility (less than delta and mu), dysphoria
Yes
No

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20
Q

What other effects do opiates have on the GI system? (3)

A

Urinary urgery
Decreased secretions
Nausea and vomiting

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21
Q

What effect do opiates have on the cardiovascular system? What about on the skin?

A

Hypotension

Itching

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22
Q

What is naloxone?

A

Opiate antagonist

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23
Q

Why is it important to titre morphine?

A

There is an active metabolite M6G. This can accumulate if renal function is impaired.

24
Q

What is heroin the drug of choice for?

A

Cachexia

25
Q

Methadone – why can it accumulate?

A

The half-life increases on repeated dosing

26
Q

What does PCA stand for?

A

Patient-controlled analgesia

27
Q

How many genetic polymorphisms have been identified in the Mu opioid receptor gene?

A

Over 100

28
Q

What is norpethidine?

A

A metabolite of pethidine, which is toxic

29
Q

What is meptazinol?

A

A u1 receptor agonist

30
Q

Analgesic ladder – what is this not appropriate for? What does it use as a reference?

A

Acute or chronic joint pain management

Cancer pain

31
Q

What are the three steps of the analgesic ladder?

A

Non-opioids
Moderate efficacy opioids and non-opioids
High efficacy opioids and non-opioids

32
Q

How does paracetamol work? What does it do?

A

Reduces the active oxidised form of COX-2
Modulates the endogenous cannabinoid system

Analgesic
Antipyretic
Little anti-inflammatory effect

33
Q

How does aspirin work? What does it do?

A

Inhibits COX-1 and COX-2

Analgesic, antipyretic and anti-inflammatory

34
Q

How do ibuprofen, diclofenac and ketoprofen work? What do they do?

A

COX-1 and 2 inhibitor
Analgesic
Anti-inflammatory

35
Q

What class of drug is aspirin, ibuprofen, diclofenac etc…?

A

NSAIDs

36
Q

What is rofecoxib?

A

Selective COX-2 inhibitor

37
Q

What are the major side effects of NSAIDs?

A

Nausea and GI bleeding

38
Q

What are NSAIDs indicated for? (4)

A

Arthritis
Dysmenorrhea
Gout
Muscle spasm

39
Q

What specific types of drugs are given to manage migraines?

A

Triptans

Ergotamine derivatives

40
Q

What is amitriptyline? What pain does it treat? How does it work?

A

Tricyclic anti-depressant
Neuropathic pain and cancer pain
Inhibits the reuptake of amines and blocks sodium and calcium channels

41
Q

What are carbamazepine, sodium valproate, pregabalin? What pain do they treat?

A

Anticonvulsant drugs

Neuropathic pain and trigeminal neuralgia

42
Q

What channels do carbamazepine and sodium valproate act on?

A

Sodium

43
Q

What does pregabalin act on?

A

Alpha-2-delta subunit of calcium channels

44
Q

What type of drug is baclofen?

A

GABA receptor agonist

45
Q

How do channels do local anaesthetics work on?

A

Block sodium channels

46
Q

What channel does gabapentin, pregabalin and verapamil work on?

A

Calcium

47
Q

What type of drug is ketamine and dextromethorphan?

A

NMDA glutamate receptors

48
Q

What are the NICE guidelines for neuropathic pain?

A
  1. Offer amitriptyline, gabapentin or pregabalin as initial treatment
  2. Then offer one of the remaining drugs and try switching
  3. Only consider tramadol if acute rescue therapy is needed
  4. Consider capsaicin cream for localised pain if they don’t want oral treatments.
49
Q

Give 3 examples of local anaesthetics.

A

Lignocaine
Bupivacaine
Prilocaine

50
Q

What risks are associated with local anaesthetics?

A

Hypotension
Respiratory depression
Bradycardia

51
Q

General anaesthetics - how do they work? What do most of them induce?

A

Activate inhibitory receptors or inhibit excitatory receptors
Most induce CV depression

52
Q

How are general anaesthetics administered?

A

Inhalational (e.g. halothane, nitrous oxide, xenon)

IV (propofol, ketamine)

53
Q

What is trigeminal neuralgia?

A

The most common facial pain syndrome
There are sudden, paroxysmal attacks of pain, lasting a few seconds to minutes, felt in the cheeks, nose, upper lip, teeth etc…

54
Q

What is the most common cause of trigeminal neuralgia?

A

Compression, distortion or stretching of the nerve V

root fibres by a branch of the anterior or posterior inferior cerebellar artery

55
Q

How is trigeminal neuralgia treated?

A

Carbamazepine (anticonvulsant, sodium channels) +/- baclofen
Baclofen - GABA receptor agonist
Phenytoin
Valproate (anticonvulsant, sodium channels)
Clonazepam